text:
Bevacizumab

Bevacizumab, sold under the brand name Avastin among others, is a monoclonal antibody medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, ovarian cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

Common side effects when used for cancer include nose bleeds, headache, high blood pressure, and rash. Other severe side effects include gastrointestinal perforation, bleeding, allergic reactions, blood clots, and an increased risk of infection. When used for eye disease side effects can include vision loss and retinal detachment. Bevacizumab is a monoclonal antibody that functions as an angiogenesis inhibitor. It works by slowing the growth of new blood vessels by inhibiting vascular endothelial growth factor A (VEGF-A), in other words anti–VEGF therapy.

Bevacizumab was approved for medical use in the United States in 2004. It is on the World Health Organization's List of Essential Medicines  It is listed for its use in treating eye disease.

Colorectal cancer
Bevacizumab was approved in the United States in February 2004, for use in metastatic colorectal cancer when used with standard chemotherapy treatment (as first-line treatment). In June 2006, it was approved with 5-fluorouracil-based therapy for second-line metastatic colorectal cancer.

It was approved by the European Medicines Agency (EMA) in January 2005, for use in colorectal cancer.

Bevacizumab has also been examined as an add on to other chemotherapy drugs in people with non-metastatic colon cancer. The data from two large randomized studies showed no benefit in preventing the cancer from returning and a potential to cause harm in this setting.

In the EU, bevacizumab in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of adults with metastatic carcinoma of the colon or rectum.

Lung cancer
In 2006, the US Food and Drug Administration (FDA) approved bevacizumab for use in first-line advanced nonsquamous non-small cell lung cancer in combination with carboplatin/paclitaxel chemotherapy. The approval was based on the pivotal study E4599 (conducted by the Eastern Cooperative Oncology Group), which demonstrated a two-month improvement in overall survival in patients treated with bevacizumab (Sandler, et al. NEJM 2004). A preplanned analysis of histology in E4599 demonstrated a four-month median survival benefit with bevacizumab for people with adenocarcinoma (Sandler, et al. JTO 2010); adenocarcinoma represents approximately 85% of all non-squamous cell carcinomas of the lung.

A subsequent European clinical trial, AVAiL, was first reported in 2009 and confirmed the significant improvement in progression-free survival shown in E4599 (Reck, et al. Ann. Oncol. 2010). An overall survival benefit was not demonstrated in patients treated with bevacizumab; however, this may be due to the more limited use of bevacizumab as maintenance treatment in AVAiL versus E4599 (this differential effect is also apparent in the European vs US trials of bevacizumab in colorectal cancer: Tyagi and Grothey, Clin Colorectal Cancer, 2006). As an anti-angiogenic agent, there is no mechanistic rationale for stopping bevacizumab before disease progression. Stated another way, the survival benefits achieved with bevacizumab can only be expected when used in accordance with the clinical evidence: continued until disease progression or treatment-limiting side effects.

Another large European-based clinical trial with bevacizumab in lung cancer, AVAPERL, was reported in October 2011 (Barlesi, et al. ECCM 2011). First-line patients were treated with bevacizumab plus cisplatin/pemetrexed for four cycles, and then randomized to receive maintenance treatment with either bevacizumab/pemetrexed or bevacizumab alone until disease progression. Maintenance treatment with bevacizumab/pemetrexed demonstrated a 50% reduction in risk of progression vs bevacizumab alone (median PFS: 10.2 vs 6.6 months). Maintenance treatment with bevacizumab/pemetrexed did not confer a significant increase in overall survival vs bevacizumab alone on follow up analysis.

The National Comprehensive Cancer Network recommends bevacizumab as standard first-line treatment in combination with any platinum-based chemotherapy, followed by maintenance bevacizumab until disease progression. Higher doses are usually given with carboplatin-based chemotherapy, whereas the lower dose is usually given with cisplatin-based chemotherapy.

In the EU, bevacizumab, in addition to platinum-based chemotherapy, is indicated for first-line treatment of adults with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology. Bevacizumab, in combination with erlotinib, is indicated for first-line treatment of adults with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations.

Breast cancer
In December 2010, the US Food and Drug Administration (FDA) notified its intention to remove the breast cancer indication from bevacizumab, saying that it had not been shown to be safe and effective in breast cancer patients. The combined data from four different clinical trials showed that bevacizumab neither prolonged overall survival nor slowed disease progression sufficiently to outweigh the risk it presents to patients. This only prevented Genentech from marketing bevacizumab for breast cancer. Doctors are free to prescribe bevacizumab off label, although insurance companies are less likely to approve off-label treatments. In June 2011, an FDA panel unanimously rejected an appeal by Roche. A panel of cancer experts ruled for a second time that Avastin should no longer be used in breast cancer patients, clearing the way for the US government to remove its endorsement from the drug. The June 2011 meeting of the FDA's oncologic drug advisory committee was the last step in an appeal by the drug's maker. The committee concluded that breast cancer clinical studies of patients taking Avastin have shown no advantage in survival rates, no improvement in quality of life, and significant side effects.

On 11 October 2011, the FDA announced that the agency was revoking the agency's approval of the breast cancer indication for bevacizumab after concluding that the drug had not been shown to be safe and effective for that use.

In the EU, bevacizumab in combination with paclitaxel is indicated for first-line treatment of adults with metastatic breast cancer. Bevacizumab in combination with capecitabine is indicated for first-line treatment of adults with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate.

Renal cancers
In certain renal (kidney) cancers, bevacizumab improves the progression free survival time but not survival time. In 2009, the FDA approved bevacizumab for use in metastatic renal cell cancer (a form of kidney cancer). following earlier reports of activity EU approval was granted in 2007.

In the EU, bevacizumab in combination with interferon alfa-2a is indicated for first-line treatment of adults with advanced and/or metastatic renal cell cancer.

Brain cancers
Bevacizumab slows tumor growth but does not affect overall survival in people with glioblastoma. The FDA granted accelerated approval for the treatment of recurrent glioblastoma multiforme in May 2009. A 2018 Cochrane review deemed there to not be good evidence for its use in recurrences either.

Macular degeneration
In the EU, bevacizumab gamma (Lytenava) is indicated for the treatment of neovascular (wet) age-related macular degeneration (nAMD).

Ovarian cancer
In 2018, the US Food and Drug Administration (FDA) approved bevacizumab in combination with chemotherapy for stage III or IV of ovarian cancer after initial surgical operation, followed by single-agent bevacizumab. The approval was based on a study of the addition of bevacizumab to carboplatin and paclitaxel. Progression-free survival was increased to 18 months from 13 months.

In the EU, bevacizumab, in combination with carboplatin and paclitaxel is indicated for the front-line treatment of adults with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. Bevacizumab, in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel, is indicated for treatment of adults with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.

In May 2020, the FDA expanded the indication of olaparib to include its combination with bevacizumab for first-line maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.

Cervical cancer
In the EU, bevacizumab, in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in people who cannot receive platinum therapy, is indicated for the treatment of adults with persistent, recurrent, or metastatic carcinoma of the cervix.

Adverse effects
Bevacizumab inhibits the growth of blood vessels, which is part of the body's normal healing and maintenance. The body grows new blood vessels in wound healing, and as collateral circulation around blocked or atherosclerotic blood vessels. One concern is that bevacizumab will interfere with these normal processes, and worsen conditions like coronary artery disease or peripheral artery disease.

The main side effects are hypertension and heightened risk of bleeding. Bowel perforation has been reported. Fatigue and infection are also common.

In advanced lung cancer, less than half of patients qualify for treatment. Nasal septum perforation and renal thrombotic microangiopathy have been reported. In December 2010, the FDA warned of the risk of developing perforations in the body, including in the nose, stomach, and intestines.

In 2013, Hoffmann-La Roche announced that the drug was associated with 52 cases of necrotizing fasciitis from 1997 to 2012, of which 17 patients died. About 2/3 of cases involved patients with colorectal cancer, or patients with gastrointestinal perforations or fistulas.

These effects are largely avoided in ophthalmological use since the drug is introduced directly into the eye thus minimizing any effects on the rest of the body.

Neurological adverse events include reversible posterior encephalopathy syndrome. Ischemic and hemorrhagic strokes are also possible.

Protein in the urine occurs in approximately 20% of people. This does not require permanent discontinuation of the drug. Nonetheless, the presence of nephrotic syndrome necessitates permanent discontinuation of bevacizumab.

Mechanism of action
Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A). VEGF-A is a growth factor protein that stimulates angiogenesis in a variety of diseases, especially in cancer. By binding VEGF-A, bevacizumab should act outside the cell, but in some cases (cervical and breast cancer) it is taken up by cells through constitutive endocytosis. It also is taken up by retinal photoreceptor cells after intravitreal injection.

Chemistry
Bevacizumab was originally derived from a mouse monoclonal antibody generated from mice immunized with the 165-residue form of recombinant human vascular endothelial growth factor. It was humanized by retaining the binding region and replacing the rest with a human full light chain and a human truncated IgG1 heavy chain, with some other substitutions. The resulting plasmid was transfected into Chinese hamster ovary cells which are grown in industrial fermentation systems.

History
Bevacizumab is a recombinant humanized monoclonal antibody and in 2004, it became the first clinically used angiogenesis inhibitor. Its development was based on the discovery of human vascular endothelial growth factor (VEGF), a protein that stimulated blood vessel growth, in the laboratory of Genentech scientist Napoleone Ferrara. Ferrara later demonstrated that antibodies against VEGF inhibit tumor growth in mice. His work validated the hypothesis of Judah Folkman, proposed in 1971, that stopping angiogenesis might be useful in controlling cancer growth.

Approval
It received its first approval in the United States in 2004, for combination use with standard chemotherapy for metastatic colon cancer. It has since been approved for use in certain lung cancers, renal cancers, ovarian cancers, and glioblastoma multiforme of the brain.

In 2008, bevacizumab was approved for breast cancer by the FDA, but the approval was revoked on 18 November 2011  because, although there was evidence that it slowed progression of metastatic breast cancer, there was no evidence that it extended life or improved quality of life, and it caused adverse effects including severe high blood pressure and hemorrhaging.

In 2008, the FDA gave bevacizumab provisional approval for metastatic breast cancer, subject to further studies. The FDA's advisory panel had recommended against approval. In July 2010, after new studies failed to show a significant benefit, the FDA's advisory panel recommended against the indication for advanced breast cancer. Genentech requested a hearing, which was granted in June 2011. The FDA ruled to withdraw the breast cancer indication in November 2011. FDA approval is required for Genentech to market a drug for that indication. Doctors may sometimes prescribe it for that indication, although insurance companies are less likely to pay for it.

The drug remains approved for breast cancer use in other countries, including Australia. It has been funded by the English NHS Cancer Drugs Fund, but in January 2015 it was proposed to remove it from the approved list. It remains on the Cancer Drugs Fund as of March 2023.

Use for macular degeneration
In 2015, there was a fierce debate in the UK and other European countries concerning the choice of prescribing bevacizumab or ranibizumab (Lucentis) for wet AMD. In the UK, part of the tension was between on the one hand, both the European Medicines Agency and the Medicines and Healthcare products Regulatory Agency which had approved Lucentis but not Avastin for wet AMD, and their interest in ensuring that doctors do not use medicines off-label when there are other, approved medications for the same indication, and on the other hand, NICE in the UK, which sets treatment guidelines, and has been unable so far to appraise Avastin as a first-line treatment, in order to save money for the National Health Service. Novartis and Roche (which respectively have marketing rights and ownership rights for Avastin) had not conducted clinical trials to get approval for Avastin for wet AMD and had no intention of doing so. Further, both companies lobbied against treatment guidelines that would make Avastin a first-line treatment, and when government-funded studies comparing the two drugs were published, they published papers emphasizing the risks of using Avastin for wet AMD.

In March 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Lytenava (bevacizumab gamma), intended for treatment of neovascular (wet) age-related macular degeneration (nAMD). The applicant for this medicinal product is Outlook Therapeutics Limited. Lytenava was approved for medical use in the European Union in May 2024.

Breast cancer approval
In March 2007, the European Commission approved bevacizumab in combination with paclitaxel for the first-line treatment of metastatic breast cancer.

In 2008, the FDA approved bevacizumab for use in breast cancer. A panel of outside advisers voted 5 to 4 against approval, but their recommendations were overruled. The panel expressed concern that data from the clinical trial did not show any increase in quality of life or prolonging of life for patients—two important benchmarks for late-stage cancer treatments. The clinical trial did show that bevacizumab reduced tumor volumes and showed an increase in progression free survival time. It was based on this data that the FDA chose to overrule the recommendation of the panel of advisers. This decision was lauded by patient advocacy groups and some oncologists. Other oncologists felt that granting approval for late-stage cancer therapies that did not prolong or increase the quality of life for patients would give license to pharmaceutical companies to ignore these important benchmarks when developing new late-stage cancer therapies.

In 2010, before the FDA announcement, The National Comprehensive Cancer Network (NCCN) updated the NCCN Clinical Practice Guidelines for Oncology (NCCN Guidelines) for Breast Cancer to affirm the recommendation regarding the use of bevacizumab in the treatment of metastatic breast cancer.

In 2011, the US Food and Drug Administration removed bevacizumab indication for metastatic breast cancer after concluding that the drug has not been shown to be safe and effective. The specific indication that was withdrawn was for the use of bevacizumab in metastatic breast cancer, with paclitaxel for the treatment of people who have not received chemotherapy for metastatic HER2-negative breast cancer.

Counterfeit
In February 2012, Roche and its US biotech unit Genentech announced that counterfeit Avastin had been distributed in the United States. The investigation is ongoing, but differences in the outer packaging make identification of the bogus drugs simple for medical providers. Roche analyzed three bogus vials of Avastin and found they contained salt, starch, citrate, isopropanol, propanediol, t-butanol, benzoic acid, di-fluorinated benzene ring, acetone and phthalate moiety, but no active ingredients of the cancer drug. According to Roche, the levels of the chemicals were not consistent; whether the chemicals were at harmful concentrations could not therefore be determined. The counterfeit Avastin has been traced back to Egypt, and it entered legitimate supply chains via Europe to the United States.

Biosimilars
In July 2014, two pharming companies, PlantForm and PharmaPraxis, announced plans to commercialize a biosimilar version of bevacizumab made using a tobacco expression system in collaboration with the Fraunhofer Center for Molecular Biology.

In September 2017, the US FDA approved Amgen's biosimilar (generic name bevacizumab-awwb, product name Mvasi) for six cancer indications.

In January 2018, Mvasi was approved for use in the European Union.

In February 2019, Zirabev was approved for use in the European Union. Zirabev was approved for medical use in the United States in June 2019, and in Australia in November 2019.

In June 2020, Mvasi was approved for medical use in Australia.

In August 2020, Aybintio was approved for use in the European Union.

In September 2020, Equidacent was approved for use in the European Union.

In January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Alymsys, intended for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer, and carcinoma of the cervix. Alymsys was approved for medical use in the European Union in March 2021.

In January 2021, Onbevzi was approved for medical use in the European Union.

In June 2019, and June 2021, Zirabev was approved for medical use in Canada.

Oyavas was approved for medical use in the European Union in March 2021.

Abevmy was approved for medical use in the European Union in April 2021, and in Australia in September 2021.

In September 2021, Bambevi was approved for medical use in Canada.

Bevacip and Bevaciptin were approved for medical use in Australia in November 2021.

In November 2021, Abevmy and Aybintio were approved for medical use in Canada.

In April 2022, bevacizumab-maly (Alymsys) was approved for medical use in the United States.

In August 2022, Vegzelma was approved for medical use in the European Union.

In September 2022, bevacizumab-adcd (Vegzelma) was approved for medical use in the United States.

In June 2023, Enzene Biosciences launched its bevacizumab biosimilar in India.

Bevacizumab-tnjn (Avzivi) was approved for medical use in the United States in December 2023.

In May 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Avzivi, intended for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer and carcinoma of the cervix. The applicant for this medicinal product is FGK Representative Service GmbH.

Research
A study released in April 2009, found that bevacizumab is not effective at preventing recurrences of non-metastatic colon cancer following surgery.

Bevacizumab has been tested in ovarian cancer where it has shown improvement in progression-free survival but not in overall survival. and glioblastoma multiforme where it failed to improve overall survival.

Bevacizumab has been investigated as a possible treatment of pancreatic cancer, as an addition to chemotherapy, but studies have shown no improvement in survival. It may also cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.

The drug has also undergone trials as an addition to established chemotherapy protocols and surgery in the treatment of pediatric osteosarcoma, and other sarcomas, such as leiomyosarcoma.

Bevacizumab has been studied as a treatment for cancers that grow from the nerve connecting the ear and the brain.

title: Bevacizumab


text:
BMW X3

The BMW X3 is an SUV manufactured by BMW since 2003, based on the BMW 3 Series platform. Now in its third generation, BMW markets the car as a Sports Activity Vehicle, the company's proprietary descriptor for its X-line luxury vehicles.

The first-generation X3 was designed by BMW in conjunction with Magna Steyr of Graz, Austria—who also manufactured all X3s under contract to BMW. BMW manufactured the second-generation X3 at their Spartanburg plant in South Carolina, United States. Starting with the third generation, BMW South Africa's Rosslyn plant began production of the X3, alongside the Spartanburg plant, after the facility underwent a major upgrade to prepare for the X3 production, replacing the long-running 3 Series production in the plant. About 76,000 units will be manufactured there annually.

The car was the first mid-size, premium SUV on the market. In 2008, BMW started competing with the Mercedes-Benz GLK-Class (renamed GLC-Class since 2016), and numerous other SUVs in this segment. The X3 is smaller than the X5 and X6, and bigger than the X1 and the X2.

An all-electric variant is sold as the BMW iX3.

First generation (E83; 2003)
The first-generation BMW X3, internally designated as the E83, was produced from 2003 to 2010 and based on the BMW 3 Series platform. The E83 was designed by BMW in conjunction with Magna Steyr of Graz, Austria who also manufactured all first-generation X3s under contract to BMW.

As a precursor to the X3, in 2003 BMW presented the xActivity concept vehicle at the Detroit Auto Show featuring the 3 Series platform and a fixed-profile convertible body style with reinforced longitudinal rails connect the A-pillars to the rear of the car on both sides, eliminating B- or C-pillars.

The X3 premiered in September 2003 at the Frankfurt Auto Show (Internationale Automobil-Ausstellung), sharing its rear suspension with the E46 330xi and using an automatic four-wheel drive system marketed as xDrive. All X3 models feature BMW's all-wheel drive system, with a default 40:60 torque split between the front and rear axles and the ability to direct all torque to either axle. The system used an electronically controlled multiple-plate clutch to enable infinitely adjustable, fully variable distribution of torque from front to rear with the capability of up to 100 per cent of engine torque going to either axle. BMW markets the crossover as a Sports Activity Vehicle, the company's descriptor for its X-line of vehicles.

The X3 was conceived to combine the agility of a compact model with the driving experience of the company's X5. The X3 featured an upright, high H-point seating configuration, marketed as "command seating". Styling exhibited interacting concave and convex surfacing, characteristic for the company at the time along with a reinterpreted Hofmeister kink.

BMW upgraded the model in 2005 and facelifted the model in 2007, with revised body bumpers, engine, interior trim, and suspension.

The X3 3.0i won the Canadian Car of the Year Best Sports Utility Vehicle award for 2005. The X3 was initially criticised for its harsh ride, austere interior, lack of off-road capability and high price.

U.S-spec X3 models were well-equipped, with standard equipment such as: the BMW Business A/M-F/M-CD radio (with optional dealer-activated Bluetooth functionality for wireless phones), an eight-speaker premium audio system, leatherette-trimmed seating surfaces, dual power front bucket seats, aluminium interior trim accents, keyless entry, and seventeen-inch (17") aluminium-alloy wheels. Optional equipment included a ten-speaker premium audio system with Digital Sound Processing (DSP), Sirius Satellite Radio, a dashboard-mounted colour GPS navigational system that replaced the upper dashboard storage compartment and contained a modified version of BMW's "iDrive" multimedia system, eighteen-inch (and later nineteen-inch) aluminium-alloy wheels, Nevada leather-trimmed seating surfaces, heated front and rear seats, a heated steering wheel, a security system, BMW Assist, a panoramic dual-pane moonroof, Xenon front headlamps with adaptive front headlamps, and sport front bucket seats.

2003–2006

 * Bluetooth could actually be ordered straight from the factory (part of the Premium Package) and functioned without dealer intervention. (Although the BMW X3 was originally offered and promised with Bluetooth support in 2004, none of the cars that shipped from the factory actually had it installed. Few were able to get it to work with servicing from their dealer.)
 * The interior was upgraded with more consistent plastic panels. Also instead of having grey carpeting which was present on all 2004 X3s, the 2005 X3 came with carpeting that matched the leather ordered (with the exception of the Terracotta interior with black carpeting).
 * Slightly softer suspension.
 * Front fenders are one-piece, as opposed to the two-piece found on 2004 models.
 * A 2.0d engine became available in 2005 for some markets – joining the 2.5i and 3.0i engines (found stateside) as well as the 3.0d engine sold elsewhere in the world.
 * An 'Open-Door' indicator was added on the 2004 models.

2006–2010
For 2006, the U.S.-spec X3 lost its 2.5L M54 inline 6-cylinder engine for the 2.5i model. The only model available from 2006 onwards for the U.S.-spec X3 was the 3.0L M54 inline 6-cylinder engine (later, the N52 inline 6-cylinder engine) and the 3.0i model (later, 3.0Si or xDrive30i). This further increased the X3's base price.

In September 2006, the E83 received a facelift with revised headlights, grille, front bumper, tail lights, rear bumper, and interior.

For the 2007 model year, the US market X3 was powered by the N52 inline 6-cylinder engine that debuted on the 2006 E90 3 Series. Internationally, the X3 received smaller engines including the 4-cylinder petrol and diesel options. In Europe, the range started with a 2.0-litre 4-cylinder petrol, a 4cyl. turbo diesel and continues with 6-cylinder turbo & bi-turbo diesels. The largest diesel offered was the sport diesel with 210 kW.

U.S. market 2006 X3's were equipped with a version of the 'M' technik body kit with unpainted door sills and wheel arches. U.S. spec Sport Package 2006 X3's received the full 'M' body kit (with painted front, side and rear plastic) available internationally as a factory accessory. 2.5i was removed for sale from the U.S. and Adaptive headlamps and a panoramic sunroof were made available, as well as upgraded dashboard components and leather seating.

Since September 2008, the Edition Exclusive and Edition lifestyle were available. The M-Sport Package was replaced in March 2009 by the Sport Limited Edition.

Pre-facelift styling

Cross Country

The X3 Cross Country, also known as the X3 CC is an X3 prepared for rally raid competition. It features a 2.9-litre inline-6 (debore and destroked M57TU2D30 engine from 3.0 litre to 2.9-litre), twin turbocharged diesel engine.

Second generation (F25; 2010)

The F25 is the second generation of BMW X3. The vehicle was unveiled in 2010 at the 2010 Paris Motor Show. For this generation, production moved from Magna Steyr in Austria to at BMW's United States plant in Greer, South Carolina. Production started on 1 September 2010, and ended in August 2017.

Dimensions-wise, the F25-based X3 is almost as large as the original E53 series X5. At launch, all models use all-wheel drive, badged as xDrive. Transmission choices are a six-speed manual or eight-speed ZF 8HP automatic transmission. The emission standard for all engines was Euro 5, until the June 2014 LCI facelift when all diesels became Euro 6. A rear-wheel drive only model called sDrive was added to the range in some markets in 2012.

M Performance Parts were released in the facelift and can be installed to all models. These include carbon fibre mirrors, a sport steering wheel, M rims, black kidney grilles and Aluminium pedals. 30d models also get a power boost kit making 27 hp more (286 hp) and 18d and 20d models can be fitted with a dual exhaust.

Europe

UK models went on sale on 18 November 2010. Early UK models included the xDrive20d. xDrive30d was added in April 2011. xDrive35d was added from September 2011. sDrive18d was added on 20 August 2012. From Spring 2013, the latest generation of BMW Professional Navigation System became available.

North America

US models arrived in US BMW Centers by the end of 2010 as 2011 model year vehicles. Early US models included xDrive28i, xDrive35i. In 2013 model year (produced in April 2012 and delivered in May 2012), a turbo four cylinder xDrive28i was introduced as replacement for the inline six xDrive28i, with new features such as standard Auto Start/Stop, Driving Dynamics Control with ECO PRO, New Driver Assistance Package (includes Lane Departure Warning). All US market vehicles come with an 8-speed automatic transmission.

For 2011, the F25 X3 is available in the US, only with a 3.0-liter inline six-cylinder gasoline engine either normally aspirated or with a twin-scroll turbocharger.

In 2012, the F25 X3 xDrive28i model's 3.0L naturally-aspired inline six-cylinder gasoline engine was replaced by the 2.0L TwinPower twin-scroll, single-turbo inline four-cylinder gasoline engine that was first introduced on the BMW 3 Series (F30), the BMW N20, more specifically coded N20B20O0. A rear-wheel-drive sDrive28i model joined the X3 model line-up, marking the first non-xDrive BMW SAV to ever be sold in the United States.

In 2013, the F25 X3 xDrive28d model joined the X3 line-up, powered by a 2.0L turbocharged inline four-cylinder diesel engine, again first introduced on the BMW 3 Series (F30). As of 2017, the xDrive28d model of the F25 X3 is no longer available for sale in the United States.

2014 update
In 2014 for the 2015 model year, the F25 received an LCI (Life Cycle Impulse) facelift. Changes include new modified twin circular headlights (optional LED headlights), redesigned kidney grille, new front, and rear bumpers, and exterior mirrors with integrated turn signal indicators; a centre console with the optional automatic climate control system in high-gloss black-panel look, new cup holders with a sliding cover for the centre console, new exterior colours, upholstery designs, interior trim strips, and light-alloy wheels; new xLine equipment package, optional Smart Opener for the automatic tailgate and storage packages.

The vehicle was unveiled in 84th Geneva International Motor Show 2014, followed by 114th New York International Auto Show 2014 (xDrive28d).

Emission violations reported
BMW X3 20d diesel was reported to exceed EU Limit Euro 6 by over 11 times. On 24 September 2015, BMW denied this report in a statement.

Pre-facelift styling

Engines
* United States only. The xDrive28d used the four-cylinder engine from the European-specification xDrive20d models. Vehicles with Diesel engine sold in the United States were since end of 2008 equipped with selective catalysator using Diesel exhaust fluid (DEF) to reduce NOx emissions, while vehicles sold in Europe had a bypass exhaust pipe only.

Third generation (G01; 2017)
The third generation is codenamed G01 and was unveiled in June 2017. Designed by Calvin Luk, BMW's Australian designer, drivetrains include two 2.0-litre diesel units known as B47, a next-generation 3.0-litre diesel engine (B57), and a petrol variant (B58): a gasoline-powered, turbo-charged straight-six with a displacement of 2,998 cc and a plug-in hybrid.

Technology is shared with the BMW 5 Series (G30), such as gesture control (optional), LED exterior and interior lighting, and the BMW iDrive 6.0 system with a 12.5-inch touch-screen monitor for navigation systems. Depending on the model, the new X3 is as much as 55 kg lighter than a comparably equipped corresponding model from the previous X3 generation.

In July 2018, BMW introduced the ability to option the X3 with the sDrive intelligent rear-wheel drive system.

In 2019, the X3 xDrive 30e (which shares its powertrain and platform with the G20 330e xDrive) iPerformance model was introduced, sharing its engine with the X3 sDrive20i/xDrive20i and a 50 kW electric motor, it has a maximum electric range of 27-30 mi. It has a 12 kWh battery (9.6 kWh usable) along with a newly developed system called "XtraBoost" allowing a temporary power increase from the electric motor of up to 30 kW.

All 18–40 and iX3 models can be fitted with M Performance Parts. These include carbon fibre mirrors.

X3 M
In 2019, BMW introduced the X3 M and X3 M Competition (F97), being the first time an X3 had a full M version. The X3 M is fitted with a 3.0 L S58 straight-six that produced 473 horsepower with the Competition models producing 503 horsepower.

Full M models can be fitted with full M specific M Performance Parts. These include a spoiler, sport steering wheel, carbon fibre vents and kidney grilles.

Engines
* 30e has a power output of 210 kW when Electric Boost is engaged.

* iX3 data is calculated by the WLTP measurement procedure (unofficial reported range between 275 - 560 km).

2021 facelift
In June 2021, the mid-life facelift for the X3 was revealed, with production beginning the following month in July. Headlights receive slight tinting, and the taillights are completely redone. The bumper is redone, and a 12.3-inch infotainment system is available for all trims in the United Kingdom.

Alpina XD3
The Alpina XD3 made its debut at the 2018 Geneva Motor Show. The XD3 is fitted with an Alpina-modified version of BMW's B57 diesel inline-six engine. In the quad-turbo left-hand drive version, the engine outputs 285 kW and 770 Nm, giving a 0–100 km/h time of 4.6 s and a top speed of 266 km/h. In the bi-turbo right-hand drive version, the engine outputs 245 kW and 700 Nm, giving it a 0–100 km/h time of 4.9 s and a top speed of 254 km/h.

BMW iX3 (G08; 2020)
The BMW iX3 (model code G08) is a battery electric version of the BMW X3 (G01). It was presented at the 2018 Beijing Motor Show in April as a concept vehicle, it is the third car of the electric-focused BMW i family and the first battery electric BMW SUV. Production began in September 2020 at BMW's factory in Dadong, Shenyang, China. It will not be available in Taiwan, United States, and Canada, reportedly due to the vehicle's limited range and sole rear-wheel-drive configuration for the North American market.

The production version of the BMW iX3 was unveiled in July 2020. It has an 80 kWh battery pack with 73.83 kWh usable capacity, which delivers up to 460 km of range based on the WLTP. The iX3 is powered by a single electric motor on the rear axle that produces 210 kW and accelerates from 0–100 km/h in 6.8 seconds. It has an electronically limited top speed of 180 km/h.

The electric powertrain is BMW's fifth-generation scalable electric drivetrain that is distinguished by a more compact design than that used by the BMW i3 with the electric motor, transmission, and power electrics grouped together in a single component. It does not feature rare-earth materials in its construction and allows BMW to significantly reduce production costs over the old model. The batteries consists of 188 prismatic cells and are positioned on the floor, lowering the centre of gravity by 75 mm. Supported for 150 kW DC fast charging, the iX3 can be charged from 0 to 80 per cent in 34 minutes or 100 km in 10 minutes. It has 510 L of boot space, 40 L smaller than in a conventional X3.

It features adaptive flat LED headlights, 19-inch bi-colour wheels, three-dimensional LED taillights, it also features a BMW Live Cockpit Professional along with a 12-inch digital display and a 12-inch central touch screen and leather seats.

Fourth generation (G45; 2024)
The fourth generation of the X3 was officially unveiled on 19 June 2024 and set to commence production later in 2024, with a planned market launch in North America in the final quarter of 2024.

Production and sales
On 18 June 2008, the 500,000th X3 was produced in Graz.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: BMW X3


text:
Kia Spectra

The Kia Spectra is a compact car produced by Kia Motors between 2000 and 2009. It took many design components from its predecessor, the Kia Sephia, which ceased production in the year 2000 in most countries. It succeeded the Kia Sephia and it was replaced by the Kia Forte (also known as Kia Cerato in some markets).

First generation
The Kia Spectra was introduced as a front-engine, front-wheel-drive subcompact sedan. It was designed for affordability and versatility to make the most of the rather small amount of space it had to offer.

It was equipped with a 125 horsepower 1.8l DOHC four cylinder engine paired to either a 5-speed manual or 4-speed automatic transmission.

This generation came in three variants: G, GX, and GX-S. It offered a quiet interior, smoooth ride quality, and high-end materials for its price. Despite having good sales, this generation only lasted for two years before undergoing a redesign.

In 2001 the Spectra received a slight facelift regarding the aesthetics of the vehicle.

Second generation
The second generation Kia Spectra, introduced in 2005, expanded upon its predecessor by updating the body styling, adding more power, and improving on functionality.

The engine used during this generation was Hyundai's 2.0l DOHC four cylinder engine dual CVVT(Beta II), producing 138 horsepower and 136 lb-ft of torque, up from the previous 125 horsepower and 108 lb-ft of torque. The transmission options remained the same.

Like the previous years, it offered three trim levels but with different lettering: EX, LX, and SX. The EX was the most basic, the LX added several luxury options, and the SX contributed to more sporty styling.

Russian edition
Years of production: 2000 - 2011 More

title: Kia Spectra


text:
Talk:List of WWF Light Heavyweight Champions

Deletion
This page was voted on for deletion at Votes for deletion/List of WWE Light Heavyweight Champions. The consensus was to keep it. dbenbenn | talk 03:07, 20 Feb 2005 (UTC)

WWE doesn't recongize pre-Michinoku champions
Why was my statement about WWE's refusal to recongize any champions prior to TAKA Michinoku removed? Jeff Silvers 13:25, 30 June 2006 (UTC)
 * It hasnt it has been moved withing the title history. --- Paulley 21:10, 30 June 2006 (UTC)
 * ...Whoops. Didn't see that. Jeff Silvers 09:58, 1 July 2006 (UTC)

Too much information
Is the following passage really necessary on a page describing the list of champions for one specific title?

"Title reigns were determined by professional wrestling matches that involved wrestlers in pre-existing scripted feuds, plots, and storylines or were awarded the title due to scripted circumstances. Wrestlers were portrayed as either villains or heroes as they followed a series of tension-building events, which culminated in a match or series of matches for the championship."

That is a general description of pro-wrestling, which may possibly be relevant on a general page but surely not in this context. - Jarno V 17:28 (CET) 27 February 2009 —Preceding unsigned comment added by 62.163.57.234 (talk) 16:28, 27 February 2009 (UTC)
 * Per WP:IN-U its required.-- TRU  CO   21:04, 27 February 2009 (UTC)

UWA
The article claims that the UWA promoted the WWF light Heavyweight championship until 1997 - but the UWA went out of business in 1995. MPJ-DK (talk) 13:23, 9 March 2009 (UTC)
 * Thanks for pointing that out, I misread the Wrestling Title Histories page for this title, I must have skipped over about the NJPW being lent the title after 1995.-- ₮ RU  C Ө   22:32, 9 March 2009 (UTC)

Move history of title section to main "WWF Light Heavyweight Championship" article?
It seems more sensible to me if the entire history section of this "list" instead be moved to the main "WWF Light Heavyweight Championship" article. This "list" article has more information on the championship than the main article does. Doomtown412 (talk) 23:52, 18 December 2009 (UTC) —Preceding unsigned comment added by Doomtown412 (talk • contribs) 06:20, 1 November 2009 (UTC)

Gillberg championship date?
Raw is War was on 11/16/98, not 11/17/98 so there should be a mention if that was the taping date or something because that day is a Tuesday. Also, Gillberg didn't win the title; Duane Gill did and he later changed his persona to Gillberg. That's like saying Isaac Yankem won the WWF title instead of Kane in 1998. — Preceding unsigned comment added by 98.251.169.178 (talk) 17:36, 18 December 2011 (UTC)

Weight column
I would like to add a weight column to the table where we can list their billed weights. I figure we can default to whatever is displayed on the main page and then if someone learns a different weight at the time they won the title it can be substituted. Ranze (talk) 03:59, 9 February 2015 (UTC)

External links modified
Hello fellow Wikipedians,

I have just modified 2 external links on List of WWF Light Heavyweight Champions. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
 * Added archive https://web.archive.org/web/20050408044957/http://corporate.wwe.com/news/2001/2001_03_23.jsp to http://corporate.wwe.com/news/2001/2001_03_23.jsp
 * Added archive http://www.webcitation.org/6LDla2zy5?url=http://entertainment.howstuffworks.com/pro-wrestling.htm to http://entertainment.howstuffworks.com/pro-wrestling.htm

When you have finished reviewing my changes, you may follow the instructions on the template below to fix any issues with the URLs.

Cheers.— InternetArchiveBot  (Report bug) 17:09, 19 May 2017 (UTC)

Pro Wrestling is scripted?
You mean to tell me that pro wrestling is pre determined and scripted? What a revelation! The entire second paragraph is superfluous and should be removed. — Preceding unsigned comment added by Spman (talk • contribs) 14:01, 20 January 2021 (UTC)


text:
Doug Dohring

Doug Dohring (1957 - September 14, 2023) was the founder, CEO, and Executive Chairman of Age of Learning, Inc., the edtech company that created and runs ABCmouse.com Early Learning Academy, ReadingIQ, Adventure Academy, and My Math Academy and My Reading Academy for schools and districts. Age of Learning was named “Most Innovative Ed Tech Company” by SIIA in the 2023 CODiE Awards. Dohring was also the Chairman of the philanthropic Age of Learning Foundation, a member of the UNESCO Global Education Coalition. Prior to Age of Learning, Dohring was the first CEO of Neopets, Inc.. Doug Dohring died on September 14, 2023.

The Dohring Company
Dohring founded market research firm The Dohring Company in 1986, where he served as Chairman and CEO. Customers for the company's market research services included retail chains including Baskin-Robbins and House of Fabrics, and entertainment firms including Capitol Records, as well as automotive, financial services, and health care companies. Automotive surveys comprised up to 80% of the firm's business in 1995. At that time, the company was ranked 55th on the Advertising Age list of the nation's largest market research firms. It was 92nd on the Los Angeles Business Journal 1995 list of fastest growing private companies in Los Angeles County.

Neopets
Dohring founded Neopets, Inc. after being introduced to the Neopets.com site by a mutual friend upon its December, 1999 launch by two British college students, Adam Powell and Donna Williams. According to BusinessWeek, Dohring bought the site immediately thereafter. In April, 2000, he brought in his first advertising partners for a concept that he trademarked as immersive advertising.

According to a Harvard Business School case study, Neopets, Inc. had reached profitability four months after launching operations, "largely due to the fact that it spends nothing for customer acquisition, relying strictly on word-of-mouth".

Two years after its creation, in December 2001, Neopets had attracted more than 20 million accounts, more than 80% of them under the age of 17. While the "tech bubble" was bursting and large percentages of new websites were folding, Neopets was signing up 50,000 new accounts per day, with members spending an average of four hours or more per month on the site.

Dohring sold the Neopets site to Viacom's MTV Network in June 2005 for $160 million. At the time, approximately 140 million Neopets had been created, with advertising making up about 60% of the company's revenues and a line of plush toys sold through Target Corporation and other stores.

Age of Learning, Inc. and ABCmouse.com
After the sale of Neopets to Viacom in 2005, Dohring founded Age of Learning, Inc., in 2007, and launched the ABCmouse.com Early Learning Academy, website in 2010. The Wall Street Journal said that ABCmouse was "designed to teach basic reading, math, science and other subjects to children between the ages of two and six." Unlike Neopets, which relied on advertising, ABCmouse.com charges a subscription of $12.99 per month or $59.99 per year, and is free to individual teachers, libraries, Head Start programs, and other community organizations.

In 2016, Age of Learning launched ABCmouse for Schools, a service marketed to school districts and groups rather than families or individual teachers.

Age of Learning, a privately held company, was reported to have reached a $1 billion valuation based on $150 million in funding from ICONIQ Capital in May 2016. A subsequent round of funding in June, 2021, led by TPG, raised another $300 million,  which valued the company at $3 billion.

In September 2019, the company appointed former Disney executive Paul Candland as CEO with Dohring being named the Executive Chairman. Candland served as CEO until April, 2022, at which time Dohring resumed his position as CEO.

In January 2020, Dohring announced the formation of the Age of Learning Foundation, which offers free access to Age of Learning digital education programs, at the Education World Forum.

Other business ventures
Dohring was also a principal shareholder in Speedyclick.com circa 1999-2001, which according to a December 2005 Wired Magazine article, "he later sold for $50 million." The $50 million deal included $3 million in cash and $47 million in ShopNow stock, (later renamed as "Network Commerce", and deemed worthless in 2001).

Personal life
A California native, Dohring was the youngest son of a car dealer and a homemaker. He and his wife Laurie, both Scientologists, were married in 1979. They had five children including two sets of identical twins and actor Jason Dohring, best known for his roles in the series Veronica Mars and Moonlight.

Doug Dohring died on September 14, 2023, due to an illness diagnosed four months prior.

title: Doug Dohring


text:
Leila and the Snakes

Leila and the Snakes was an American rock group based out of San Francisco in the 1970s and 1980s.

The group was led by Jane Dornacker (alias "Leila"), who had previously toured with The Tubes. Other members of the group were Pamela Wood on bass and Scott Free on drums, who were later replaced by the brothers Hilary and John Hanes (who billed themselves with the surname "Stench"). Also featured was guitarist Miles Corbin, who went on to form the surf instrumental band the Aqua Velvets.

The band only produced one official release, a single on the ADP label in 1978. Produced by Roger Clark (of Little Roger and the Goosebumps) and arranged by Dick Bright, the record features "Rock and Roll Weirdos" (written by Dornacker), with "Pyramid Power" (written by Dornacker and Clark) on the flip side. Also featured on the record (which cheekily showed the group's bare buttocks on the back of the sleeve) was Pearl E. Gates, who was also part of the Snakes' live act. Eventually, Pearl would quit the group, taking with her the Stench brothers, in order to front her own band, Pearl Harbor and the Explosions. (Pearl would later marry Paul Simonon of The Clash, and sing backup on that group's LP Sandinista!).

The band also recorded an album produced by Hugh Cornwell of The Stranglers. No final mix was done, however, and tracks remained unreleased until 2006, when Corbin self-released them as a 12-track album, "Leila and the Snakes".

Later years
Post-Leila, Dornacker became a prominent radio personality in San Francisco as well as played Nurse Murch in the 1983 motion picture The Right Stuff. In 1985, she moved to New York to become a traffic reporter on WNBC radio; tragically, she died the following year when the helicopter she was reporting from crashed into the Hudson River, live on-air. It was the second time her traffic helicopter crashed. She negotiated a very large life insurance policy before going back to her job.

title: Leila and the Snakes


text:
Missy Giove

Melissa 'The Missile' Giove (born 1972) is an American professional downhill mountain biker. Throughout her career she won 14 NORBA downhill titles and 11 world cups. Giove's other accomplishments include three overall NORBA downhill crowns, two World Cup overalls, and the 1994 World Championship title.

Career
Giove was born in Manhattan, NY. She raced for Yeti Cycles, along with other racers: Myles Rockwell, Jimmy Deaton, John Tomac and Johnny O'Mara, managed by former owner of Yeti Cycles, John Parker, the Volvo-Cannondale USA cycling team.

Giove raced wearing the desiccated body of her deceased pet piranha, Gonzo, around her neck, which would become a marketing campaign for Cannondale.

2015, Giove qualified 17th at the World Cup Downhill race at Windham, New York +36.558 seconds off the pace of Rachael Atherton's 3:05.135.

2016, Giove was inducted into the Mountain Bike Hall of Fame.

2022, Giove is a main character in the book, Pressure: A Memoir by Eric Canori.

Legal troubles
1999, May. Giove, along with Amazon Inc. filed a lawsuit against Cannondale (AMAZON, INC. v. CANNONDALE CORP. DIRT CAMP, INC., Civil Action Nos. 99-cv-00571-EWN-PAC, 00-cv-02063-EWN-PAC (D. Colo. March 10, 2006) and Dirt Camp, Inc. for a 1999 Cannondale Product Catolog and sought $2 million dollars in damages. During the summer and early fall of 1998, while Giove was still a member of the team, Cannondale designed, published, and distributed its 1999 products catalog. The catalog included several photographs of Giove. Subsequently, Giove and Team Sports Mountain Inc.(TMSI) failed to renegotiate a contract, and the TSMI/Amazon contract expired on December 31, 1998. Cannondale continued to distribute the 1999 catalog containing Giove's photographs after the TSMI/Amazon contract expired.

2009, June. Giove was arrested in Wilton, New York on charges of conspiring to possess and distribute 174 kilograms (384 pounds) of marijuana found hidden in a car trailer during a routine traffic stop. The case netted over $12,515,738 assets seized in the conspiracy.

2012, November. Giove, pleaded guilty in the case and was sentenced to 5 years on probation and 6 months under house arrest.

title: Missy Giove


text:
Talk:Iolanda Balaș

External links modified
Hello fellow Wikipedians,

I have just modified 2 external links on Iolanda Balaș. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
 * Added archive https://web.archive.org/web/20160304082559/http://www.sports-reference.com/olympics/athletes/ba/iolanda-balas-1.html to http://www.sports-reference.com/olympics/athletes/ba/iolanda-balas-1.html
 * Added archive https://web.archive.org/web/20160304082559/http://www.sports-reference.com/olympics/athletes/ba/iolanda-balas-1.html to http://www.sports-reference.com/olympics/athletes/ba/iolanda-balas-1.html

When you have finished reviewing my changes, you may follow the instructions on the template below to fix any issues with the URLs.

Cheers.— InternetArchiveBot  (Report bug) 13:11, 12 April 2017 (UTC)

Gpintea : Really ? Yoli expressed "regret for not having represented Hungary ?" I really doubt that. I knew her personally, my mother, God bless her soul, was a friend of Yoli and not once has she even hinted on such silly nationalism allegations. Romania offered her advantages impossible to get in Hungary : a leading position in Romanian atletism. a treatment equivalent of that of an army general when she represented Steaua Club, dozens of trips abroad as an atlete and later as a trainer and sports official, approval to get a Fiat 2300 car back in 1966, a rarity even in the West at the time, atlet's training camps in beautiful resorts in the Carpathian Mountains or the Black Sea, all year long if she so wished for herself and her husband (her coach). Now it's true that after the Romanian Revolution, the sponsoring of atletism  took a dive, but whenever she asked, she did obtained funds for the real talents. Besides, she could visit Hungary for unlimited time whenever she wanted, her and her family, and given her status, "family repression" is downright ludicrous. Nono, this is a poor attempt from a probable Hungarian writer to politicize sports and atletism in Hungary's favor. I call this pathetic ! And I really think Wikipedia should clearly state the name of article's authors. Otherwise they look like anonymous denunciations GPintea (talk) 11:00, 1 January 2021 (UTC)

title: Talk:Iolanda Balaș


text:
User:Yosofun

Yosofun is a student of physics taking a year off from grad school. Here are some yosofun-applicable userboxes:

title: User:Yosofun


text:
Conformational isomerism

In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted just by rotations about formally single bonds (refer to figure on single bond rotation). While any two arrangements of atoms in a molecule that differ by rotation about single bonds can be referred to as different conformations, conformations that correspond to local minima on the potential energy surface are specifically called conformational isomers or conformers. Conformations that correspond to local maxima on the energy surface are the transition states between the local-minimum conformational isomers. Rotations about single bonds involve overcoming a rotational energy barrier to interconvert one conformer to another. If the energy barrier is low, there is free rotation and a sample of the compound exists as a rapidly equilibrating mixture of multiple conformers; if the energy barrier is high enough then there is restricted rotation, a molecule may exist for a relatively long time period as a stable rotational isomer or rotamer (an isomer arising from hindered single-bond rotation). When the time scale for interconversion is long enough for isolation of individual rotamers (usually arbitrarily defined as a half-life of interconversion of 1000 seconds or longer), the isomers are termed atropisomers (see: atropisomerism). The ring-flip of substituted cyclohexanes constitutes another common form of conformational isomerism.

Conformational isomers are thus distinct from the other classes of stereoisomers (i. e. configurational isomers) where interconversion necessarily involves breaking and reforming of chemical bonds. For example, L / D - and R/S- configurations of organic molecules have different handedness and optical activities, and can only be interconverted by breaking one or more bonds connected to the chiral atom and reforming a similar bond in a different direction or spatial orientation. They also differ from geometric (cis/trans) isomers, another class of stereoisomers, which require the π-component of double bonds to break for interconversion. (Although the distinction is not always clear-cut, since certain bonds that are formally single bonds actually have double bond character that becomes apparent only when secondary resonance contributors are considered, like the C–N bonds of amides, for instance.) Due to rapid interconversion, conformers are usually not isolable at room temperature.

The study of the energetics between different conformations is referred to as conformational analysis. It is useful for understanding the stability of different isomers, for example, by taking into account the spatial orientation and through-space interactions of substituents. In addition, conformational analysis can be used to predict and explain product selectivity, mechanisms, and rates of reactions. Conformational analysis also plays an important role in rational, structure-based drug design.

Types
Rotating their carbon–carbon bonds, the molecules ethane and propane have three local energy minima. They are structurally and energetically equivalent, and are called the staggered conformers. For each molecule, the three substituents emanating from each carbon–carbon bond are staggered, with each H–C–C–H dihedral angle (and H–C–C–CH3 dihedral angle in the case of propane) equal to 60° (or approximately equal to 60° in the case of propane). The three eclipsed conformations, in which the dihedral angles are zero, are transition states (energy maxima) connecting two equivalent energy minima, the staggered conformers.

The butane molecule is the simplest molecule for which single bond rotations result in two types of nonequivalent structures, known as the anti- and gauche-conformers (see figure).

For example, butane has three conformers relating to its two methyl (CH3) groups: two gauche conformers, which have the methyls ±60° apart and are enantiomeric, and an anti conformer, where the four carbon centres are coplanar and the substituents are 180° apart (refer to free energy diagram of butane). The energy difference between gauche and anti is 0.9 kcal/mol associated with the strain energy of the gauche conformer. The anti conformer is, therefore, the most stable (≈ 0 kcal/mol). The three eclipsed conformations with dihedral angles of 0°, 120°, and 240° are transition states between conformers. Note that the two eclipsed conformations have different energies: at 0° the two methyl groups are eclipsed, resulting in higher energy (≈ 5 kcal/mol) than at 120°, where the methyl groups are eclipsed with hydrogens (≈ 3.5 kcal/mol).

While simple molecules can be described by these types of conformations, more complex molecules require the use of the Klyne–Prelog system to describe the different conformers.

More specific examples of conformational isomerism are detailed elsewhere:
 * Ring conformation
 * Cyclohexane conformations, including with chair and boat conformations among others.
 * Cycloalkane conformations, including medium rings and macrocycles
 * Carbohydrate conformation, which includes cyclohexane conformations as well as other details.
 * Allylic strain – energetics related to rotation about the single bond between an sp2 carbon and an sp3 carbon.
 * Atropisomerism – due to restricted rotation about a bond.
 * Folding, including the secondary and tertiary structure of biopolymers (nucleic acids and proteins).
 * Akamptisomerism – due to restricted inversion of a bond angle.

Equilibrium of conformers
Conformational isomers exist in a dynamic equilibrium, where the relative free energies of isomers determines the population of each isomer and the energy barrier of rotation determines the rate of interconversion between isomers:
 * $$ K = e^{-\Delta G^\circ/RT},$$

where K is the equilibrium constant, ΔG° is the difference in standard free energy between the two conformers in kcal/mol, R is the universal gas constant (1.987×10−3 kcal/mol K), and T is the system's temperature in kelvins. In units of kcal/mol at 298 K,

 * $$ K \approx 10^{-\Delta G^\circ/(1.36\text{ kcal}/\mathrm{mol})}. $$

Thus, every 1.36 kcal/mol corresponds to a factor of about 10 in term of equilibrium constant at temperatures around room temperature. (The "1.36 rule" is useful in general for estimation of equilibrium constants at room temperature from free energy differences. At lower temperatures, a smaller energy difference is needed to obtain a given equilibrium constant.)

Three isotherms are given in the diagram depicting the equilibrium distribution of two conformers at different temperatures. At a free energy difference of 0 kcal/mol, this gives an equilibrium constant of 1, meaning that two conformers exist in a 1:1 ratio. The two have equal free energy; neither is more stable, so neither predominates compared to the other. A negative difference in free energy means that a conformer interconverts to a thermodynamically more stable conformation, thus the equilibrium constant will always be greater than 1. For example, the ΔG° for the transformation of butane from the gauche conformer to the anti conformer is −0.47 kcal/mol at 298 K. This gives an equilibrium constant is about 2.2 in favor of the anti conformer, or a 31:69 mixture of gauche:anti conformers at equilibrium. Conversely, a positive difference in free energy means the conformer already is the more stable one, so the interconversion is an unfavorable equilibrium (K < 1). Even for highly unfavorable changes (large positive ΔG°), the equilibrium constant between two conformers can be increased by increasing the temperature, so that the amount of the less stable conformer present at equilibrium increases (although it always remains the minor conformer).

Population distribution of conformers
The fractional population distribution of different conformers follows a Boltzmann distribution:
 * $$ \frac{N_i}{N_\text{total}} = \frac {e^{-E_i/RT}} {\sum_{k=1}^M e^{-E_k/RT}}. $$

The left hand side is the proportion of conformer i in an equilibrating mixture of M conformers in thermodynamic equilibrium. On the right side, Ek (k = 1, 2, ..., M) is the energy of conformer k, R is the molar ideal gas constant (approximately equal to 8.314 J/(mol·K) or 1.987 cal/(mol·K)), and T is the absolute temperature. The denominator of the right side is the partition function.

Factors contributing to the free energy of conformers
The effects of electrostatic and steric interactions of the substituents as well as orbital interactions such as hyperconjugation are responsible for the relative stability of conformers and their transition states. The contributions of these factors vary depending on the nature of the substituents and may either contribute positively or negatively to the energy barrier. Computational studies of small molecules such as ethane suggest that electrostatic effects make the greatest contribution to the energy barrier; however, the barrier is traditionally attributed primarily to steric interactions. In the case of cyclic systems, the steric effect and contribution to the free energy can be approximated by A values, which measure the energy difference when a substituent on cyclohexane in the axial as compared to the equatorial position. In large (>14 atom) rings, there are many accessible low-energy conformations which correspond to the strain-free diamond lattice.

Isolation or observation of conformational isomers
The short timescale of interconversion precludes the separation of conformational isomers in most cases. Atropisomers are conformational isomers which can be separated due to restricted rotation. The equilibrium between conformational isomers can be observed using a variety of spectroscopic techniques.

Protein folding also generates stable conformational isomers which can be observed. The Karplus equation relates the dihedral angle of vicinal protons to their J-coupling constants as measured by NMR. The equation aids in the elucidation of protein folding as well as the conformations of other rigid aliphatic molecules. Protein side chains exhibit rotamers, whose distribution is determined by their steric interaction with different conformations of the backbone. This is evident from statistical analysis of the conformations of protein side chains in the Backbone-dependent rotamer library.

In cyclohexane derivatives, the two chair conformers interconvert with rapidly at room temperature, with cyclohexane itself undergoing the ring-flip at a rates of approximately 105 ring-flips/sec, with an overall energy barrier of 10 kcal/mol (42 kJ/mol), which precludes their separation at ambient temperatures. However, at low temperatures below the coalescence point one can directly monitor the equilibrium by NMR spectroscopy and by dynamic, temperature dependent NMR spectroscopy the barrier interconversion.

The dynamics of conformational (and other kinds of) isomerism can be monitored by NMR spectroscopy at varying temperatures. The technique applies to barriers of 8–14 kcal/mol, and species exhibiting such dynamics are often called "fluxional".

Besides NMR spectroscopy, IR spectroscopy is used to measure conformer ratios. For the axial and equatorial conformer of bromocyclohexane, νCBr differs by almost 50 cm−1.

Conformation-dependent reactions
Reaction rates are highly dependent on the conformation of the reactants. In many cases the dominant product arises from the reaction of the less prevalent conformer, by virtue of the Curtin-Hammett principle. This is typical for situations where the conformational equilibration is much faster than reaction to form the product. The dependence of a reaction on the stereochemical orientation is therefore usually only visible in configurational isomers, in which a particular conformation is locked by substituents. Prediction of rates of many reactions involving the transition between sp2 and sp3 states, such as ketone reduction, alcohol oxidation or nucleophilic substitution is possible if all conformers and their relative stability ruled by their strain is taken into account.

One example with configurational isomers is provided by elimination reactions, which involve the simultaneous removal of a proton and a leaving group from vicinal or antiperiplanar positions under the influence of a base.

The mechanism requires that the departing atoms or groups follow antiparallel trajectories. For open chain substrates this geometric prerequisite is met by at least one of the three staggered conformers. For some cyclic substrates such as cyclohexane, however, an antiparallel arrangement may not be attainable depending on the substituents which might set a conformational lock. Adjacent substituents on a cyclohexane ring can achieve antiperiplanarity only when they occupy trans diaxial positions (that is, both are in axial position, one going up and one going down).

One consequence of this analysis is that trans-4-tert-butylcyclohexyl chloride cannot easily eliminate but instead undergoes substitution (see diagram below) because the most stable conformation has the bulky t-Bu group in the equatorial position, therefore the chloride group is not antiperiplanar with any vicinal hydrogen (it is gauche to all four). The thermodynamically unfavored conformation has the t-Bu group in the axial position, which is higher in energy by more than 5 kcal/mol (see A value). As a result, the t-Bu group "locks" the ring in the conformation where it is in the equatorial position and substitution reaction is observed. On the other hand, cis-4-tert-butylcyclohexyl chloride undergoes elimination because antiperiplanarity of Cl and H can be achieved when the t-Bu group is in the favorable equatorial position.

The repulsion between an axial t-butyl group and hydrogen atoms in the 1,3-diaxial position is so strong that the cyclohexane ring will revert to a twisted boat conformation. The strain in cyclic structures is usually characterized by deviations from ideal bond angles (Baeyer strain), ideal torsional angles (Pitzer strain) or transannular (Prelog) interactions.

Alkane stereochemistry

Alkane conformers arise from rotation around sp3 hybridised carbon–carbon sigma bonds. The smallest alkane with such a chemical bond, ethane, exists as an infinite number of conformations with respect to rotation around the C–C bond. Two of these are recognised as energy minimum (staggered conformation) and energy maximum (eclipsed conformation) forms. The existence of specific conformations is due to hindered rotation around sigma bonds, although a role for hyperconjugation is proposed by a competing theory.

The importance of energy minima and energy maxima is seen by extension of these concepts to more complex molecules for which stable conformations may be predicted as minimum-energy forms. The determination of stable conformations has also played a large role in the establishment of the concept of asymmetric induction and the ability to predict the stereochemistry of reactions controlled by steric effects.

In the example of staggered ethane in Newman projection, a hydrogen atom on one carbon atom has a 60° torsional angle or torsion angle with respect to the nearest hydrogen atom on the other carbon so that steric hindrance is minimised. The staggered conformation is more stable by 12.5 kJ/mol than the eclipsed conformation, which is the energy maximum for ethane. In the eclipsed conformation the torsional angle is minimised.

In butane, the two staggered conformations are no longer equivalent and represent two distinct conformers:the anti-conformation (left-most, below) and the gauche conformation (right-most, below).

Both conformations are free of torsional strain, but, in the gauche conformation, the two methyl groups are in closer proximity than the sum of their van der Waals radii. The interaction between the two methyl groups is repulsive (van der Waals strain), and an energy barrier results.

A measure of the potential energy stored in butane conformers with greater steric hindrance than the 'anti'-conformer ground state is given by these values: The eclipsed methyl groups exert a greater steric strain because of their greater electron density compared to lone hydrogen atoms.
 * Gauche, conformer – 3.8 kJ/mol
 * Eclipsed H and CH3 – 16 kJ/mol
 * Eclipsed CH3 and CH3 – 19 kJ/mol.

The textbook explanation for the existence of the energy maximum for an eclipsed conformation in ethane is steric hindrance, but, with a C-C bond length of 154 pm and a Van der Waals radius for hydrogen of 120 pm, the hydrogen atoms in ethane are never in each other's way. The question of whether steric hindrance is responsible for the eclipsed energy maximum is a topic of debate to this day. One alternative to the steric hindrance explanation is based on hyperconjugation as analyzed within the Natural Bond Orbital framework. In the staggered conformation, one C-H sigma bonding orbital donates electron density to the antibonding orbital of the other C-H bond. The energetic stabilization of this effect is maximized when the two orbitals have maximal overlap, occurring in the staggered conformation. There is no overlap in the eclipsed conformation, leading to a disfavored energy maximum. On the other hand, an analysis within quantitative molecular orbital theory shows that 2-orbital-4-electron (steric) repulsions are dominant over hyperconjugation. A valence bond theory study also emphasizes the importance of steric effects.

Nomenclature
Naming alkanes per standards listed in the IUPAC Gold Book is done according to the Klyne–Prelog system for specifying angles (called either torsional or dihedral angles) between substituents around a single bond:

Torsional strain or "Pitzer strain" refers to resistance to twisting about a bond.
 * a torsion angle between 0° and ±90° is called syn (s)
 * a torsion angle between ±90° and 180° is called anti (a)
 * a torsion angle between 30° and 150° or between −30° and −150° is called clinal (c)
 * a torsion angle between 0° and ±30° or ±150° and 180° is called periplanar (p)
 * a torsion angle between 0° and ±30° is called synperiplanar (sp), also called syn- or cis- conformation
 * a torsion angle between 30° to 90° and −30° to −90° is called synclinal (sc), also called gauche or skew
 * a torsion angle between 90° and 150° or −90° and −150° is called anticlinal (ac)
 * a torsion angle between ±150° and 180° is called antiperiplanar (ap), also called anti- or trans- conformation

Special cases
In n-pentane, the terminal methyl groups experience additional pentane interference.

Replacing hydrogen by fluorine in polytetrafluoroethylene changes the stereochemistry from the zigzag geometry to that of a helix due to electrostatic repulsion of the fluorine atoms in the 1,3 positions. Evidence for the helix structure in the crystalline state is derived from X-ray crystallography and from NMR spectroscopy and circular dichroism in solution.

title: Conformational isomerism


text:
Oklahoma School of Science and Mathematics

The Oklahoma School of Science and Mathematics (OSSM) is a two-year, public residential high school located in Oklahoma City, Oklahoma. Established by the Oklahoma state legislature in 1983, the school was designed to educate academically gifted high school juniors and seniors in advanced mathematics and science. OSSM opened doors to its inaugural class in 1990. It is a member of the National Consortium of Secondary STEM Schools (NCSSS).

History
Dr. Earl Mitchell is credited as the originator of the idea of starting OSSM. He was reportedly inspired by a letter about the North Carolina School of Science and Mathematics (NCSSM), written by North Carolina governor Jim Hunt. In 1982, Dr. Mitchell travelled to NCSSM to study their practices, and enlisted Speaker Dan Draper, Representative Penny Williams, and Senator Bernice Shedrick to help bring the idea to fruition.

OSSM was established by HB 1286 in 1983, during the 39th Oklahoma Legislature. The bill's principal authors included Representative Penny Williams, Senator Bernice Shedrick, and Senator Rodger Randle. The bill was signed into law by Governor George Nigh on June 23, 1983.

In 1988, Dr. Edna Manning was appointed the first president of OSSM. Manning aided in the building and development of the institution, supervising the selection of faculty and the development of the curriculum.

When OSSM's inaugural class was accepted in 1990, the school did not have its own campus yet. Students were temporarily housed in OU's Cross Center dormitory in Norman, and took daily shuttle buses to the OU Health Sciences Center (OUHSC) campus in Oklahoma City for their classes. In 1992, OSSM moved into the newly-renovated Lincoln Elementary School, across the street from the OUHSC. During Dr. Manning's tenure as president, the school's campus grew to include a dormitory, a gymnasium, a library, and a science building.

In 2006, Chesapeake Energy gifted OSSM $500,000 to fund an endowed faculty chair in geophysics, the first endowed chair at an Oklahoma public high school.

In June 2012, Dr. Manning retired from her position as president, and was succeeded by Dr. Frank Y.H. Wang. During his tenure, Dr. Wang increased contributions to the OSSM Foundation Faculty Endowment from $4.2 million to $10 million.

On May 31, 2013, the 54th Oklahoma Legislature passed SB 1131, authored by Senator Clark Jolley, and signed into law by Governor Mary Fallin. The bill allows OSSM to accept out-of-state students for up to 10 percent of the student population and charge them tuition. It also allows the school to rent out its facilities, and create summer programs & workshops for which tuition and fees could be charged. Dr. Wang helped create the bill in an effort to generate a new revenue stream, to make up for money lost to severe cuts in state funding.

In June 2021, Dr. Wang announced he will retire at the end of the 2021-22 school year.

General
Admittance to OSSM is conducted through a highly selective application process, with acceptance rates varying over time. The application process consists of five short essays, submission of high school transcripts and standardized test scores (such as the ACT), recommendations from teachers and counselors, personal questionnaires of the student, a statement from the student's parents, and an on-campus interview.

Students are accepted from all over the state of Oklahoma, and students from each of Oklahoma's 77 counties have been selected to attend. Because students hail from across the state, all are required to live on campus during the week. Classes are held five days a week, with the earliest classes starting at 8am and the latest ending at 5:30pm. Some classes, such as astronomy lab and special topics classes, are held at night. Most students have breaks throughout the day depending on their individual, college-style schedule. Students are not allowed in the dorm during their breaks in the academic day, but are to stay academically engaged during these periods. Required physical education classes are held in the afternoon with each student participating in 45 minutes of supervised physical activity twice a week. Fine arts classes (two semesters are required for graduation) are also held in the evenings. One Saturday a month, students are required to take a three-hour test in math, physics, literature, history, or a national standardized test (ACT, SAT, or PSAT). Two weekends a month is called an open weekend, with the students allowed to either go home or stay in the dorms, and the other weekend is an extended weekend with all students required to leave campus.

As part of OSSM's academic program, two hours of study are required each weeknight from 8 to 10pm, with students on structured study (resulting from unfortunate grades) required to study for an additional hour each night, beginning at 7pm. Lights out is at 11pm every night of the week, and internet access is shut off in the dormitories at that time. OSSM fulfills its educational mission at no charge to its students: tuition, books and other class materials, as well as room and board, are all provided by the taxpayers of the State of Oklahoma.

One hundred percent of OSSM graduates are college-bound, and approximately 60% of OSSM graduates choose to remain in-state for college. Of the 1,211 (as of May 2011) graduates since the school's inception, 323 students have been named National Merit Scholars, and an additional 167 students have been selected as National Merit Commended Scholars. Graduates also show exemplary performance in other national scholarship programs, with 227 graduates selected as Robert C. Byrd Scholars, and 124 students nominated for the Presidential Scholars Program, of whom thirteen were named semifinalists and five selected as Presidential Scholars. Graduates excel in statewide scholarship programs, with 553 students receiving Oklahoma State Regents for Higher Education Scholarships and 92 students named Academic All-Staters by the Oklahoma Foundation for Excellence. Twice, in 1998 and again in 2000, the school had the highest ACT composite scores of any high school in the nation. OSSM is also listed as one of the best public high schools in the nation by the Washington Post, in a list of top-performing schools with elite students.

Academics
OSSM's graduation requirements include four semesters of History, four semesters of Literature, two years of the same foreign language (unless this was completed at the student's previous high school), one semester of computer science, four semesters of mathematics including math through Calculus II, three semesters of physics including physics through Electricity and Magnetism, two semesters of chemistry, two semesters of biology, four semesters of physical education, two semesters of fine arts, and two semesters of science, math, or computer science electives. OSSM regularly offers the following classes:

• Biology: Zoology, Plant and Soil Science, Genetics, Anatomy and Physiology, Endocrinology, Embryology, Microbiology, Molecular and Cellular Biology, Psychology, and Neuroscience.

• Chemistry: Introduction to Chemistry, General Chemistry I, General Chemistry II, Organic Chemistry I, Organic Chemistry II, Biochemistry, and Physical Chemistry.

• Computer Science: Introduction to Computer Science, Object Oriented Programming with Java, Data Structures I, Data Structures II, Computer Architecture, and Operating Systems.

• Foreign Languages: Chinese, French, German, Japanese, Latin, and Spanish.

• Geoscience: Exploration Geoscience, Geoscience Seminar

• Humanities: American Literature, World Literature, American History, East Asian History, Modern Middle East, American Film, Music, and Society, Foreign Policy, and History of Western Traditions I and II

• Physics: General Physics, Mechanics, Electricity and Magnetism, Thermal Waves and Optics, Astronomy, Modern Physics I, Modern Physics II, Electronic Circuits, and Theoretical Physics.

• Mathematics: Pre-Calculus II, Pre-Calculus III, Calculus I, Calculus II, Multivariate Calculus, Differential Equations, Linear Algebra, and Probability and Statistics.

• Elective Courses: Abstract Algebra (Mathematics), Chemical Thermodynamics (Chemistry), Real Analysis (Mathematics), Foundations of Mathematics (Mathematics), and other classes have also been offered.

• Fine Arts: Jazz Band, Beginning Guitar, Intermediate Guitar, Drawing, Mixed Media, Sculpture, Abstract Painting, Fiber Arts, Photography, Ballroom Dance, Studio Dance, and Mosaics.

Additionally, students may arrange to take directed studies with faculty members. Many OSSM students choose to participate in the mentorship program in their senior year, in which they perform research with a mentor (who may be an OSSM faculty member, or an off campus expert).

Campus
OSSM is located on thirty-two acres at the northwest corner of 10th Avenue and Lincoln Boulevard near downtown Oklahoma City, near the University of Oklahoma Health Sciences Center. Its main academic building, Lincoln School, was built in 1903, and used as an elementary school, then torn down and rebuilt in 1948 Oklahoma City Public Schools and used until the 1980s. This building houses a computer lab, the campus auditorium, nineteen classrooms, six labs, a student lounge, a study area, basement, and faculty and administrative offices. The Dan Little Residence Hall, with a capacity of nearly 300 students and twelve faculty families, was completed in 1998, located at the center of campus, complete with a basement containing billiards, game tables, and a TV for students to use during their nightly free time. The basement is also a reinforced storm shelter and is large enough to house the entire school population. The Gymnasium, opened in March 1999, provides a full-size basketball court, a weight room, and a dance floor, among other amenities. The Samson Science and Discovery Center was completed in 2001 and houses three chemistry labs, four physics labs, one computer lab, and one demonstration/lecture room, as well as many personal research labs. In Fall 2003, the Senator Bernice Shedrick Library opened, with a capacity of 50,000 books and 10 computers for student use.

In 2000 the school was scheduled to open remote centers in Enid and Tahlequah.

Demographics

 * Student Body: 144
 * Average Class Size: 15–18, though many upper-level classes are smaller
 * Male-Female Ratio: 1:1

Notable alumni

 * Rhiju Das, '95
 * Nancy Chen


text:
Critical variable

Critical variables are defined, for example in thermodynamics, in terms of the values of variables at the critical point.

On a PV diagram, the critical point is an inflection point. Thus:

\left(\frac{\partial P}{\partial V}\right)_{C}=0 $$

\left(\frac{\partial^2 P}{\partial V^2}\right)_{C}=0 $$

For the van der Waals equation, the above yields:

P_C=\frac{a}{27b^2} $$

\displaystyle{V_C=3nb} $$

T_C=\frac{8a}{27bR} $$

title: Critical variable


text:
Rib eye steak

The rib eye or ribeye (known as Scotch fillet in Australia and New Zealand) is a boneless rib steak from the rib section.

Description

Ribeye steaks are mostly composed of the longissimus dorsi muscle but also contain the complexus and spinalis muscles. The longissimus dorsi is also referred to as the "eye of the ribeye". The spinalis is also referred to as the "ribeye cap" and the complexus is a small muscle at the front of the ribeye which may be trimmed off by the butcher.

It is both flavoursome and tender, coming from the lightly worked upper rib cage area which spans from the sixth to twelfth ribs of the cattle. Its marbling of fat makes it very good for fast and hot cooking.

Terminology

 * In Australia and New Zealand, "ribeye" refers to a bone-in rib steak, while the boneless ribeye is known as "Scotch fillet" or "whiskey fillet".
 * In French cuisine, the entrecôte corresponds to the rib eye steak, while rib steak is called côte de bœuf (literally: "beef rib").
 * In Argentine cuisine, the rib eye is known as ojo de bife, while the rib steak is known as ancho de bife.
 * In Chilean cuisine, the boneless rib steak is known as lomo vetado.
 * In Spanish cuisine, the rib eye is known by its French name, entrecot.
 * In French Canada, mainly the province of Québec, it is called "Faux filet" (literally: "fake fillet").
 * In Austria the same cut is known as "Rostbraten", it is usually cut thinner at 0,5-1 cm.
 * On the West Coast of the United States, a boneless rib eye steak is sometimes called a "Spencer steak".
 * In Texas, a boneless rib eye steak is sometimes called a "Maudeen Center Cut".

title: Rib eye steak


text:
Gary Ackers

Gary Keith Ackers (1939 - 2011) was Emeritus Professor of Biochemistry and Molecular Biophysics of Washington University in St. Louis, Missouri.

His research focused on thermodynamic linkage analysis of biological macromolecules, addressing the molecular mechanism of cooperative O2 binding to human hemoglobin since the early 1970s. He was a Fellow of the Biophysical Society and one of the founders of the annual Gibbs Conference.

Professor Ackers invented agarose gel chromatography when he was a teenager. He went on the develop analytical gel chromatography methods for determinations of many important characteristics of water-soluble proteins; diffusion coefficient, molecular size, thermodynamics of protein-protein interactions including important changes due to single amino acid substitutions.

title: Gary Ackers


text:
Feel Good Lost

Feel Good Lost is the debut studio album by Broken Social Scene. It was written and recorded primarily by founding members Kevin Drew and Brendan Canning. Unlike their better known 2002 outing You Forgot It in People, Feel Good Lost is mostly an instrumental, post-rock, ambient album, closer in style to BSS predecessor band KC Accidental, although it does feature some vocals by Leslie Feist and Kevin Drew.

Track listing
All songs written by Brendan Canning and Kevin Drew.

title: Feel Good Lost


text:
Talk:AirTrain JFK

AirTrain Transfers
If you get on at Howard Beach and get off at Jamaica, do you pay $5 or $10? --SPUI (talk) 03:20, 20 Feb 2005 (UTC)

 * My guess (from the other side of the country) is $10, $5 every time you go thru an AirTrain faregate. Yes they could have an out-of-(subway)-system transfer, but would people use it? ...After  checking your fine rail map, my guess is maybe.--67.160.146.193 04:44, 11 September 2005 (UTC)

 * It's $5. Pay-Per-Ride, and Airtrain combo cards only. Pacific Coast Highway 22:02, Jun 4, 2005 (UTC) (6:04 PM EST)

 * Entering at Howard Beach, traveling on the JFK AirTrain and exiting at Jamaica Station costs $10. Traveling between the individual terminals is free.  There are no free transfers between the AirTrain JFK and NYC Transit.  Also, if going between the two subway lines, you would have to pay another $2.25 at Jamaica because there are no subway to subway transfers. --Cluefinder42 (talk) 00:20, 11 May 2012 (UTC)

Accessibility
Oh, and is AirTrain handicapped accessible? I'd assume it is, given that it was built recently, but I could find nothing at all online about it. --SPUI (talk) 10:58, 20 Feb 2005 (UTC)

 * All AirTrain trains and stations are ADA-compliant. There are also two designated wheelchair locations on each vehicle.--Cluefinder42 (talk) 00:20, 11 May 2012 (UTC)

Page move
This article has been renamed after the result of a move request:

AirTrain (JFK) → AirTrain JFK and AirTrain (Newark) → AirTrain Newark
These are the official names for the lines. --SPUI (talk) 01:30, 20 Feb 2005 (UTC)
 * Go ahead. Who's protesting this? jdb ❋ 01:41, 20 Feb 2005 (UTC)
 * The man is putting me down with page history and "this page cannot be moved". In theory this page should only be for these cases. --SPUI (talk) 09:18, 20 Feb 2005 (UTC)

 * As a repeated AirTrain JFK customer...Support. —ExplorerCDT 05:24, 20 Feb 2005 (UTC)
 * Support. Jonathunder 18:22, 2005 Feb 20 (UTC)
 * Seems reasonable. Support.  Tomtomtomtomtom 04:07, 28 Feb 2005 (UTC)
 * As one of the passengers of the first two trains of this system (JFK)(and the first train to leave Jamaica), support.   — Rickyrab | Talk 05:18, 15 Apr 2005 (UTC)

How-to Guide
It seems some of this information falls more along the lines of advice and transient information. I want to move portions to Wikitravel but I don't know if there is a standard that should be applied. Consider this as an announcement, but if there is any sort of discussion I will defer. Davilla

It turns out content can't be moved to Wikitravel due to licensing. I'd still wonder if some bits of information here meet merits for inclusion. See Wikitravel:New York (city). Davilla 08:02, 24 July 2005 (UTC)

Expansion to LGA
Are there any plans to extend the AirTrain from Jamica/LIRR to LaGuardia with a stop at Flushing Meadows Park for the Tennis Center and baseball stadium? Nyrmetros 19:14, 23 November 2006 (UTC)

 * An extension to Laguardia has been discussed in the past, but i am not aware of any current plans. The JFK Airtrain was paid for by federal airport funds that can only be used for airport related purposes, so an intermediate stop for the stadium and tennis center might be a problem.--agr 20:23, 23 November 2006 (UTC)

Trainset
I would like to know which is the train Model used for the Airtrain!Is it the Metropolis or? and if you know please add it to the article, i think is important!:)EdwinCasadoBaez (talk) 01:58, 17 January 2008 (UTC)

 * It's pretty far down, but the article does mention that Airtrain JFK is a Bombardier Advanced Rapid Transit system. The trainsets in use at JFK are called Mark II by Bombardier. --Jfruh (talk) 02:13, 17 January 2008 (UTC)
 * AirTrain JFK Mark II variant. A variant of what if not of British Railways Mark 2? Peter Horn User talk 22:05, 4 April 2015 (UTC)
 * No mention of a Mark II' on New York City Subway rolling stock, Long Island Rail Road or the Metro-North Railroad Peter Horn User talk 22:25, 4 April 2015 (UTC)
 * Found it, Skytrain rolling stock. Peter Horn User talk 19:39, 6 April 2015 (UTC)
 * Make that Bombardier Innovia Metro. Peter Horn User talk 20:20, 6 April 2015 (UTC)

Snow
Bombardier ART has been very successful in Vancouver's warm climate, but the Mark I system in Toronto seems to have problems with snow. Does anyone know whether New York's Mark II trains have had similar issues? David Arthur (talk) 15:20, 21 July 2009 (UTC)
 * No mention of a Mark I or a Mark II on New York City Subway rolling stock, Long Island Rail Road or the Metro-North Railroad. Peter Horn User talk 19:03, 6 April 2015 (UTC)
 * Found it, Skytrain rolling stock. Peter Horn User talk 19:40, 6 April 2015 (UTC)
 * Make that Bombardier Innovia Metro. Peter Horn User talk 20:21, 6 April 2015 (UTC)

Elevated railway
If it's elevated above grade (as JFK Airtrain is along most of its route) and if it runs on rails (as JFK Airtrain does), then it's an "el". AirTrain opened in late 2003, becoming the first separate "el" in NYC in several decades (the IRT Third Avenue Line closed in 1973, and the Franklin Avenue Shuttle and Flushing Line are both considered part of the NYC subway system, as is the former Long Island Railroad track on Rockaway). 198.151.130.69 (talk) 16:26, 27 May 2011 (UTC)

External links modified
Hello fellow Wikipedians,

I have just added archive links to 1 one external link on AirTrain JFK. Please take a moment to review my edit. You may add after the link to keep me from modifying it, if I keep adding bad data, but formatting bugs should be reported instead. Alternatively, you can add to keep me off the page altogether, but should be used as a last resort. I made the following changes:
 * Attempted to fix sourcing for http://www.rpa.org/pdf/metrolink.pdf

When you have finished reviewing my changes, please set the checked parameter below to true or failed to let others know (documentation at ).

Cheers.—cyberbot II  Talk to my owner :Online 00:49, 29 March 2016 (UTC)

External links modified
Hello fellow Wikipedians,

I have just modified 2 external links on AirTrain JFK. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
 * Added archive https://web.archive.org/web/20170902095002/https://www.dnainfo.com/new-york/20120521/howard-beach/airtrain-shut-down-for-hours-due-power-outage to https://www.dnainfo.com/new-york/20120521/howard-beach/airtrain-shut-down-for-hours-due-power-outage
 * Added archive https://web.archive.org/web/20171106035703/http://gothamist.com/2012/08/01/air_train_jfk.php to http://gothamist.com/2012/08/01/air_train_jfk.php

When you have finished reviewing my changes, you may follow the instructions on the template below to fix any issues with the URLs.

Cheers.— InternetArchiveBot  (Report bug) 15:30, 21 December 2017 (UTC)

Route map inconsistent
In the route map, for connections at Jamaica, up is away from Manhattan, down is toward Manhattan. At Howard Beach, the connection directions are reversed: up is toward Manhattan, down is away. I found that confusing. It should be easy to reverse the two entries at Howard Beach to match Jamaica, which seems more logical.--agr (talk) 20:02, 3 October 2018 (UTC)

Does AirTrain JFK accept cash?
and anyone else: The Fares section says "Passengers entering or leaving the system at the Jamaica or Howard Beach stations must pay a fare using MetroCard." The Fares section is unclear about this. --RoyGoldsmith (talk) 12:20, 9 March 2019 (UTC)
 * 1) Does AirTrain JFK accept cash or credit cards at Jamaica or Howard Beach? The Fares section mentions that $5 is deducted from MetroCard but it doesn't explicitly say anything about other forms of payment.
 * 2) What about Lefferts Boulevard or Federal Circle? Can I just walk in there without a MetroCard and pay cash?
 * (1) You have to pay for a MetroCard before you enter the system. Cash and credit cards, Smartlink, unlimited MetroCards, or LIRR tickets are not accepted (2) No, if you get in at Lefferts Blvd or Federal Circle, you get to ride for free. Fares are only collected at Howard Beach and Jamaica. epicgenius (talk) 16:23, 9 March 2019 (UTC)
 * To elucidate a little bit on this question: you can "walk in [to Jamaica or Howard Beach] without a MetroCard and pay cash" -- but you have to use that cash to buy a MetroCard. There are machines at the stations where you can buy them -- you don't need to have one in advance and (I'm pretty sure) you don't need to go into the subway section of the station to buy a card. If you arrive at Howard Beach or Jamaica from the airport (or from Lefferts/Federal Circle) without a MetroCard, there are machines on the inside of the faregate whree you can also buy a MetroCard with cash. --Jfruh (talk) 01:02, 27 August 2019 (UTC)

title: Talk:AirTrain JFK


text: Category:Broken Social Scene albums

title: Category:Broken Social Scene albums