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Plant Sciences/Arabidopsis root development

This Article is a draft, you can participate to expand it and clean it up.

To do:
 * summarize interest of Arabidopsis root for biology
 * fill the sections more consistently

Here is a temporary plan about what this review will talk about:
 * Overview of the Arabidopsis seedling
 * Overview of the root
 * Tissues
 * Developmental zones
 * Structure of the root meristem
 * Cell initials
 * Primary vs lateral roots (embryonic vs post-embryonic origin)
 * Hormones in the Arabidopsis seedling root
 * Biotic and abiotic factors affecting root development

Intro
Plant roots are responsible for nutrient and water uptake and provide physical support to the plant. Most of the root system is made of lateral roots that originate postembryonically. Lateral root development is controlled by different factors including nutrient concentration in the plant and the soil (Lopez-Bucio et al., 2003; Malamy, 2005, for a review). This plasticity allows adaptation of the root system to the soil, a very heterogeneous and changing environment, and is consequently very important for the survival of the plant (Grime et al., 1986; Hodge, 2004). The root of the model plant ../Arabidopsis_thaliana/ is a very useful tool for investigating the basis of plant development.The Arabidopsis root has a simple structure and the root meristem is an excellent system in which to study stem cell biology.

The Root Apical Meristem (RAM)
Primary root growth occurs at the root apical meristem (RAM). Unlike the SAM, the RAM produces cells in two directions. The RAM produces a cap of tissue called the root cap, which covers the distal tip of roots. The root cap protects the root tip as it grows through the soil. 1999). The RC perceives and processes many environmental stimuli, and mediates the direction of root growth accordingly. Gravity (gravitropism), light (phototropism), obstacles (thigmotropism), gradients of temperature (thermotropism), humidity (hydrotropism), ions and other chemicals (chemotropism) are all examples of environmental stimuli that are perceived and processed by the cap (Hasenstein & Evans 1988; Ishikawa & Evans 1990; Okada & Shimura 1990; Fortin & Poff 1991; Takahashi 1997;Eapenet al. 2003).

Cells are continuously sloughed off the outer surface of the root cap. The RAM also produces cells proximally that contribute to the root proper, but unlike the SAM, the RAM produces no lateral appendages.

The root meristem is a largely invariant structure made up of few tissue types that undergo predictable divisions and do not produce lateral structures (Dolan et al., 1993). Primary root tissues are organized in concentric cylinders of epidermis, ground tissue (cortex and endodermis), and stele (pericycle and vasculature) from outside to in. These, in turn, are made up of longitudinal cell files that originate from single cells termed initials Scheres et al., 1994). Initials fulfill the minimal definition of a stem cell by producing two cells in every division: the regenerated initial, and a daughter cell that differentiates progressively upon displacement by further rounds of division. Two terminal tissues, the columella (central) and lateral root cap, are also produced by the activity of initials. Together, initials for all tissue types surround a group of four to seven mitotically less active cells in Arabidopsis thaliana known as the quiescent center (QC). Nearly every animal system relies on local signaling to form a stem cell niche, or microenvironment, that promotes stem cell status (reviewed in Spradling et al., 2001; Fuchs et al., 2004). Laser ablation experiments have shown that this is also the case for the plant root and have identified the QC as the source of a signal that inhibits differentiation of the contacting initials (van den Berg et al., 1997). QC cells position the stem cell niche but also behave as stem cells in their own right. Occasional QC divisions are self-renewing and replenish initials that have been displaced from their position (Kidner et al., 2000). Little is known about the molecular mechanisms that determine the properties of the QC or initial cells. Stem cell fate has been correlated with the position of a local maximum of auxin phytohormone perception in the QC and columella root cap initials (Sabatini et al., 1999). Auxin signaling is necessary for QC initiation in the embryo (Hardtke and Berleth, 1998;Hamann et al., 2002)

RAM structure
In many root meristems, cell files can be traced back to a small group of initials. Often these initials are organized in a tiered arrangement, with each tier giving rise to particular tissues. In radish, tier 1 produces root cap and epidermis, tier 2 cortex and tier 3 vasculature. In maize, tier 1 produces only root cap, tier 2 epidermis and cortex, tier 3 vasculature. Other plants show no tiered arrangement or only a single initial layer. Many lower plants such as ferns have a single large pyramidal cell called the apical cell. The apical cell alternates cleavages along its four faces and is the ultimate source of all cells in the meristem.

The center of the RAM is occupied by a quiescent center which has low mitotic activity. The quiescent center is most apparent in actively growing roots and is lost during dormancy, carbohydrate starvation or root cap removal. This is the same region of the meristem to which cell files trace and was postulated to contain the root initials. Evidence suggests the quiescent center does function as the zone of initials. Colchicine induces polyploidy in any cells undergoing mitosis at the time of treatment. In actively growing roots treated with colchicine, sectors of polyploid cells were transient indicating that no initial cells were dividing at the time of treatment. If the quiescent center is eliminated by removal of the root cap, prior to colchicine treatment, then stable sectors of polyploid cells are produced and persist after re-establishment of the quiescent center. Thus infrequent division of initial cells in the quiescent center is the source of cells for the RAM. More recent cell lineage experiments have used transposon activation of a GUS reporter to mark root cell lineages, leading to the same conclusions.

Surgical manipulations have provided information about RAM organization. Quiescent centers surgically explanted to sterile culture regenerated a meristem and grew as a root. Bisected RAMs formed 2 meristems and roots. These experiments demonstrate the organizing capacity for RAMs. Experiments with maize which has a highly tiered meristem suggest the layered structure is not required for normal function. Portions of the maize RAM were removed by glancing incisions and when the RAM regenerated, the layered arrangement was no longer present on the cut side, but was still apparent on the undamaged side. Although the structural arrangement of cells differed from one side to the other, the meristem still produced a normal root. The layered structure may therefore reflect “status quo” patterns of cell division but not have functional significance in the normal production of root tissues.

Embryonic origin of the RAM
The RAM contains the only cells in the plant embryo that are derived from the suspensor rather than the embryo proper. Part of the RAM is derived from the embryo proper but the quiescent center and columella initials (see below) are derived from the very last cell of the suspensor, called the hypophesis.

Arabidopsis root
The Arabidopsis root has a simple structure. There are an unusually small number of tissue and cell types in the Arabidopsis root. It possesses a single layer of cells within its epidermal, cortical, endodermal, and pericycle tissues, as well as a simple set of cells in its vascular tissue. In addition, the number of cells within each layer is fairly constant. For example, the Arabidopsis primary root always possesses eight files of cortex cells, eight files of root-hair cells, and approximately 10-14 files of non-hair cells in the epidermis. Furthermore, the developmental origin of each of the tissue types within the root meristem has been defined.

The Arabidopsis root is a highly ordered affair, consisting of concentric cylinders of cells, with new cells being added at the distal root tip [4]. This radial pattern emanates, by a series of stereotyped divisions, from a small group of stem cells which surround four ‘quiescent centre’ cells at the heart of the root meristem (Figure 1). The quiescent centre has very little mitotic activity itself but functions to maintain the stem cell status of adjacent cells. Cells laid down in front of the advancing tip differentiate to form the root cap which protects the quiescent centre and stem cell niche as they push through the soil. In the cells left behind by the growing tip, division eventually gives way to a phase of rapid cell expansion without division which marks the end of the meristematic zone and the beginning of the elongation zone (Figure 1). Elongated cells then begin to differentiate, marked most clearly by the appearence of root hairs [4]. Thus, as well as its radial organisation, the root has a more general proximo-distal pattern of activities.

Arabidopsis roots are extremely small and simple: the radial pattern consists of concentric arrangements of 6 different tissues, each a single cell layer thick. This allows every cell to be traced back to a specific progenitor in the meristem. All cells trace back to a small group of cells called the promeristem (see handout) and the pattern of cell divisions in the promeristem is invariant. Fate mapping showed that the central cells and columnella root cap cells of the embryonic RAM are derived from the basal cell formed by the first zygotic division, while the remainder of the promeristem is derived from the apical cell.

Cell signaling and RAM organization
Although cell divisions in the arabidopsis RAM typically follow a set pattern, generating relatively invariant cell lineages, laser ablation studies indicate that position rather than lineage is the important factor for determining cell fate (identity). For example, if a cortical initial is ablated, a pericycle cell will invade the voided space, assume the pattern of cell division characteristic of a cortical initial and give rise to cortical and endodermal derivatives. Thus the cell changes fate from pericycle to cortical initial when it’s position is altered.

These studies also demonstrated that the differentiated cells proximal to the RAM influence the fate of cells in the RAM. The cortical/endodermal initial undergoes a transverse division after which the daughter undergoes a periclinal division to give rise to the endodermis and cortex. If three adjacent cortical initial daughter cells were ablated, such that a cortical initial was no longer in contact with any daughter cell, the initial still divided to produce a daughter but now the daughter did not undergo the typical asymmetric periclinal division to generate the cortical and endodermal cell files. Therefore, the more mature, differentiated cells direct the pattern of division and differentiation of the initial cells (van den Berg, 1995).

Two mutants show the same phenotype: endodermis and cortex are replaced by a single cell layer. In the short root mutant the single layer has characteristics of cortex thus shr is required to specify endodermal identity. In contrast, scarecrow has both endodermal and cortical characteristics in the single layer and thus appears to be involved in specifying the cell division that generates the two layers.

The quiescent center regulates the differentiation of neighboring cells. If one or 2 QC cells were ablated, the columnella initials that were no longer in direct contact with a QC cell ceased dividing and underwent differentiation as a columnella cell. Similarly, cortical initial cells that were no longer in direct contact with the a QC cell behaved as cortical daughter cells and underwent an asymmetric division to generate cortical and endodermal cell files. Therefore, direct contact with the QC inhibits the differentiation of initial cells in the RAM (van den Berg, 1997).

Developmental Zones
A developmental gradient is apparent at the growing tip of roots. This gradient can be subdivided into 3 zones. The apical tip is the meristem or zone of cell division. The next zone proximal to the meristem is the zone of elongation where cell division ceases and there is rapid cell growth by elongation. Then comes the zone of differentiation or specialization, where cells assume their final fate. The zone of differentiation is made obvious by the appearance of root hairs in the epidermis and lignification of the xylem that can be visualised by autofluorescence. The remaining part of the root called mature zone is able to produce lateral roots.

Radial Organization of the Root
The outer layer of cells is the epidermis, next layer is the cortex, followed by the endodermis, pericycle and vasculature. Near the root tip, there is also a layer of lateral root cap cells outside the epidermis. In arabidopsis, each of these tissues corresponds to a single layer of cells.

Sites and regulation of auxin biosynthesis in Arabidopsis roots
Auxin has been shown to be important for many aspects of root development, including initiation and emergence of lateral roots, patterning of the root apical meristem, gravitropism, and root elongation. Auxin biosynthesis occurs in both aerial portions of the plant and in roots; thus, the auxin required for root development could come from either source, or both. To monitor putative internal sites of auxin synthesis in the root, a method for measuring indole-3-acetic acid (IAA) biosynthesis with tissue resolution was developed. We monitored IAA synthesis in 0.5- to 2-mm sections of Arabidopsis thaliana roots and were able to identify an important auxin source in the meristematic region of the primary root tip as well as in the tips of emerged lateral roots. Lower but significant synthesis capacity was observed in tissues upward from the tip, showing that the root contains multiple auxin sources. Root-localized IAA synthesis was diminished in a cyp79B2 cyp79B3 double knockout, suggesting an important role for Trp-dependent IAA synthesis pathways in the root. We present a model for how the primary root is supplied with auxin during early seedling development.

Auxin and RAM organization
Previous work from the Scheres lab [3] showed a high level of induction of auxin responsive genes in a tightly focused region just below the quiescent centre, suggesting a point source of auxin. Various experimental manipulations to increase, reduce or move this point were found to bring about concomitant changes in cell fate, consistent with a morphogen-like role for auxin in root tip patterning [3,5].

A GUS reporter for auxin concentration shows a concentration of auxin just at the distal end of the vasculature, just proximal to the RAM. Disruption of this localized accumulation by auxin transport inhibitors, exogenous auxin application or mutations in genes involved with auxin response, disrupts the organization of cell types in the root apex, as visualized by promoter trap cell markers. Thus the proper localization and perception of this auxin maximum are important for organizing the RAM (Sabatini, 1999).

In maize it has been reported that cells of the QC are characterized by their highly oxidized status. Glutathione and ascorbic acid occur predominately in the oxidized forms in the QC. This is contrasted with the status of these redox intermediates in adjacent, rapidly dividing cells in the root meristem, in which the reduced forms of these two species are favored. Using a redox sensitive fluorescent dye it is possible to visualize an overall oxidizing environment in the QC, and make comparisons with the adjacent, rapidly dividing cells in the root meristem. Altering the distribution of auxin and the location of the auxin maximum in the root tip activates the QC, and cells leave G1 and enter mitosis. Commencement of relatively more rapid cell division in the QC is preceded by changes in the overall redox status of the QC, which becomes less oxidizing. (Jiang, et al, 2003)

the PIN network in root development
Auxin provide positional information. Cell polarity in the meristem disrupted by Auxin transport inhibitors (TIBA, NPA), vesicular traficking inhibitors such as brefeldin A, or actin inhibitors (cytochelasine ...) See mainly Blilou et al (2005), Friml et al (2002, 2003), Benkova et al (2004)

Local accumulation of the plant growth regulator auxin mediates pattern formation in Arabidopsis roots and influences outgrowth and development of lateral root- and shoot-derived primordia. However, it has remained unclear how auxin can simultaneously regulate patterning and organ outgrowth and how its distribution is stabilized in a primordium-specific manner. Blilou et al (2005) have shown that five PIN genes collectively control auxin distribution to regulate cell division and cell expansion in the primary root. Furthermore, the joint action of these genes has an important role in pattern formation by focusing the auxin maximum and restricting the expression domain of PLETHORA (PLT) genes, major determinants for root stem cell specification. In turn, PLT genes are required for PIN gene transcription to stabilize the auxin maximum at the distal root tip. Their data reveal an interaction network of auxin transport facilitators and root fate determinants that control patterning and growth of the root primordium.

The auxin gradients are established, maintained, modified or even completely reversed by a complex interacting network of auxin transporters distributed throughout the region. Evidence for the dynamic nature of auxin gradients has come from a series of seminal papers, the most recent of which [Blilou et al 2005] demonstrates the existence of a network of active auxin transport that recycles auxin around the root

Auxin and ethylene interaction
Ponce et al (2005) found Auxin and ethylene interactions control mitotic activity of the quiescent centre, root cap size, and pattern of cap cell differentiation in maize.

Cytokinins and root development
Gravitropism (Aloni et al 2004), development (Miyawaki et al 2003, Takei et al 2004) nitrate response, control of root meristem activity (Werner et al 2003)

Regulation of the root meristem activity by cytokinins
Cytokinin are essential for cell division, therefore very important for root meristem activity. Produced in root tip (Aloni et al 2004, Miyawaki et al 2004) and vasculature of root mainly. Altough essential for cell proliferation, cytokinin negatively regulate root meristem activity (exogenously supplied cytokinin inhibits root growth, and plant with a lower cytokinin content grow faster as shown by Werner et al (2003) in plant overexpressing cytokinin oxidase (CKX) genes (The CKX proteins degrade irreversibly cytokinin).

Role of cytokinin in the regulation of root gravitropism
The models explaining root gravitropism propose that the growth response of plants to gravity is regulated by asymmetric distribution of auxin (indole-3-acetic acid, IAA). Since cytokinin has a negative regulatory role in root growth, Aloni et al (2004) suspected that it might function as an inhibitor of tropic root elongation during gravity response. Therefore, they examined the free-bioactive-cytokinin-dependent ARR5::GUS expression pattern in root tips of transformants of Arabidopsis thaliana (L.) Heynh., visualized high cytokinin concentrations in the root cap with specific monoclonal antibodies, and complemented the analyses by external application of cytokinin. Their findings show that mainly the statocytes of the cap produce cytokinin, which may contribute to the regulation of root gravitropism. The homogenous symmetric expression of the cytokinin-responsive promoter in vertical root caps rapidly changed within less than 30 min of gravistimulation into an asymmetrical activation pattern, visualized as a lateral, distinctly stained, concentrated spot on the new lower root side of the cap cells. This asymmetric cytokinin distribution obviously caused initiation of a downward curvature near the root apex during the early rapid phase of gravity response, by inhibiting elongation at the lower side and promoting growth at the upper side of the distal elongation zone closely behind the root cap. Exogenous cytokinin applied to vertical roots induced root bending towards the application site, confirming the suspected inhibitory effect of cytokinin in root gravitropism. Our results suggest that the early root graviresponse is controlled by cytokinin. They conclude that both cytokinin and auxin are key hormones that regulate root gravitropism.

Cytokinin and root response to nutrients
Cytokinin and nitrate, phosphate nutrition. Regulation of a set of phosphate starvation genes by cytokinins. Increase in cytokinin content in presence of nitrate. Regulation of Some AtIPT genes by nitrate (Miyawaki et al 2004; Takei et al 2004).

From Franco-Zorilla 2005. Cytokinins control key processes during plant growth and development, and cytokinin receptors CYTOKININ RESPONSE 1/WOODEN LEG/ARABIDOPSIS HISTIDINE KINASE 4 (CRE1/WOL/AHK4), AHK2, and AHK3 have been shown to play a crucial role in this control. The involvement of cytokinins in signaling the status of several nutrients, such as sugar, nitrogen, sulfur, and phosphate (Pi), has also been highlighted, although the full physiological relevance of this role remains unclear. To gain further insights into this aspect of cytokinin action, we characterized a mutant with reduced sensitivity to cytokinin repression of a Pi starvation-responsive reporter gene and show it corresponds to AHK3. As expected, ahk3 displayed reduced responsiveness to cytokinin in callus proliferation and plant growth assays. In addition, ahk3 showed reduced cytokinin repression of several Pi starvation-responsive genes and increased sucrose sensitivity. These effects of the ahk3 mutation were especially evident in combination with the cre1 mutation, indicating partial functional redundancy between these receptors.We examined the effect of these mutations on Pi-starvation responses and found that the double mutant is not significantly affected in long-distance systemic repression of these responses. Remarkably, we found that expression of many Pi-responsive genes is stimulated by sucrose in shoots and to a lesser extent in roots, and the sugar effect in shoots of Pi-starved plants was particularly enhanced in the cre1 ahk3 double mutant. Altogether, these results indicate the existence of multidirectional cross regulation between cytokinin, sugar, and Pi-starvation signaling, thus underlining the role of cytokinin signaling in nutrient sensing and the relative importance of Pi-starvation signaling in the control of plant metabolism and development.

Auxin and cytokinin have overlapping patterns in the Arabidopsis root
Both have maximum concentrations in stele of mature root, columella and vascular initials, both relocalised in the lateral rootcap upon gravi-stimulation.

Cell division control in the RAM
Role of the quiescent center and the  root cap in the maintenance of cell division and meristem size (Werner et al, 2003; Ponce et al, 2005) The mitotic cells can be visualized using genetic markers such as cyclin B1-GUS or GFP fusion reporters genes. The cyclin B is mostly expressed during the G2/M phase of the cell cycle.

Auxin dependent maintenance of an oxidative state of the quiescent center in maize.

Role of Argonaute in meristem formation. The ARGONAUTE gene family is involved in the regulation of gene expression via the RNAi Silencing Complex (RISC). microRNA (miRNA) are 20-22bp RNAs that direct RISC to target genes (Kidner and Martienssen, 2005).

Transcriptional framework for root patterning
http://www.bio.uu.nl/mg/pd/research/transcrframe.html

Root hairs
Root hairs are filamentous structures produced by a subset of cells on the root epidermis. The cells producing root hairs are called trichoblast cells whereas cells which don't are called atrichoblast cells They function to increase the surface area of the root, allowing more efficient water and nutrient uptake. The root epidermis consists of elongated cells of 2 cell types: hair cells and hairless cells. Positional cues specify the pattern of root hair development. Arabidopsis roots are particularly well suited for studying cell patterning. The root is small, with a 1 cell layered cortex, and a very regular pattern of cell division in the RAM that allows the lineage of each cell to be known. The cortex consists of an invariant ring of 8 cells. The epidermis consists of a variable number of cells but there is invariably 8 files of root hair cells. Root hairs always form on epidermal cells positioned over the radial cell wall between cortical cells. The control of cell pattern will be considered in more detail in a later lecture.

Root hair cells can be cytologically distinguished by their dense cytoplasms (delayed vacuolation) early in development, near the onset of elongation; thus cell fate has been specified prior to elongation. The root hair first becomes visible as a swelling at the apical end of the elongate epidermal cell. The protuberance then grows into a root hair by tip growth, similar to pollen tubes. It requires a Ca2+ gradient, golgi vesicle transport and vesicle fusion with the plasma membrane.

Root branching
Root hairs are responsible for nutrient and water uptake and provide physical support to the plant. Most of the root system is made of lateral roots that originate postembryonically. Lateral root development is controlled by different factors including nutrient concentration in the plant and the soil (Lopez-Bucio et al., 2003; Malamy, 2005, for a review). This plasticity allows adaptation of the root system to the soil, a very heterogeneous and changing environment, and is consequently very important for the survival of the plant (Grime et al., 1986; Hodge, 2004).

Like shoot branching, root branching can be either terminal or lateral, with the terminal mode being more common in lower plants and lateral much more common in angiosperms. Terminal branching involves the division of the RAM into 2 with the subsequent production of 2 roots. Lateral branching is different in roots than in shoots. Lateral roots initiate from internal cells of the pericycle. Initiation occurs in the late cell elongation/early cell differentiation zone, in pericycle cells that are partially to fully differentiated. Thus there is no detached meristem. A small group of pericycle cells reorient their axis of polarity to the radial dimension and begin growing and dividing to form a mound of cells. With continued growth and division, the mound of cells becomes organized into a RAM with root cap, while still within the tissues of the main root. Continued growth allows the lateral root to penetrate the endodermis, cortex and epidermis, finally reaching the exterior of the parent root.

Auxin and cytokinins are key factors in determining lateral root initiation. Exogenous auxin induces a extra lateral roots in a dose dependent manner (ie. more auxin, more lateral roots). Conversely, many auxin mutants show a paucity of lateral roots. Environment also influences lateral root development. Lateral roots in nitrogen deficient environments will respond to applied NO3- by elongating. This requires the function of a myb transcription factor called ANR1. Lateral roots of antisense ANR1 plants do not respond to nitrate. This also demonstrates that this is a specific response to the nitrate stimulus and not simply a nutritional response because the antisense plants are otherwise healthy.

/Lateral root development/
In Arabidopsis thaliana, lateral roots originate postembryonically from a small number of differentiated cells situated in the root pericycle in front of xylem poles called pericycle founder cells (Casimiro et al., 2001; Dubrovsky et al., 2001). As they exit from the root meristem area, pericycle cells in front of xylem poles undergo a round of cell cycle but stop in the G2 phase and remain in this state (Beeckman et al., 2001). Later in the development of the root, these cells can undergo a defined program of oriented cell divisions and expansion to form a lateral root primordium (Malamy and Benfey, 1997; Dubrovsky et al., 2001; Casimiro et al., 2003). Unlike primary root formation that occurs during embryogenesis, lateral root formation is easily accessible to observation and experimentation. Moreover, lateral root formation can be initiated by the application of the plant hormone auxin. Nevertheless, molecular mechanisms of root branching are still poorly understood.

Himanen et al (2002) have shown cyclin-dependent kinase inhibitor KRP2 plays a significant role in the regulation of lateral root initiation. KRP2 appears to regulate early lateral root initiation by blocking the G1-to-S transition and to be regulated transcriptionally by auxin.

Pericycle cell-cycle marking studies (Beeckman et al., 2001; Himanen et al., 2002) and cell type specific marking (Malamy and Benfey, 1997), each utilizing GUS staining, showed the earliest indications of lateral root initiation. In addition, Malamy and Benfey (1997) produced a cell lineage map of the median longitudinal view of the emerging lateral root primordium (LRP). The relative contribution of different pericycle cell files to the LRP is not clear, however various studies placed the number of LRP founder cells at 6–11 (Casimiro et al., 2003; Dubrovsky et al., 2000; Laskowski et al., 1995). Pericycle cells in longitudinal files in contact with the xylem differentiate as LRP founder cells. Generally, two files of pericycle cells are in direct contact with a xylem file but a minimum of three files of the pericycle are usually involved in LRP formation (Casimiro et al., 2003). Xylem-contacting pericycle cells show the first signs of differentiation as LRP founders but adjacent files also contribute to the LRP. Kurup et al (2005) used a lineage marking system combined with a live-cell outlining marker to demonstrate uneven contribution of the LRP pericycle founder files to the emerging lateral root.

Nodule development is thought to be a modified lateral root development

Nutrient Availability Influences Root Development
Several soil nutrients can alter root hair development (Reviewed in López-Bucio et al, 2003). Fe or P deficiencies both induce more epidermal cells to differentiate as root hairs, and both induce root hairs to elongate more than normal. These two pathways appear independent. The Fe pathway appears to function through the ethylene and auxin pathways because ethylene and auxin mutants show altered responses to Fe deficiency. P appears to be ethylene and auxin independent. The increased root hairs increases the surface area of roots, increasing their capacity to absorb limited nutrients.

Several nutrients can also alter root architecture by altering lateral root formation or growth, or by altering primary root growth. High nitrate inhibits lateral root elongation if the root system is uniformly exposed. However if only a portion of the root system experiences high nitrate while the rest experiences deficiency, the section with high nitrate will show elongated lateral roots. A MADS box transcription factor, ANR1 is induced by local high nitrate and is required for the root architecture response.

Nitrate supply increase cytokinin content in the root. Takei et al (2004) have shown the adenosine phosphates-isopentenyltransferase AtIPT3 is a key determinant of nitrate-dependent cytokinin biosynthesis in Arabidopsis.

Phosphate deficiency induces the formation of lateral roots and inhibits root elongation. The result is a dense, highly branched root system. This is compounded by the effect on root hairs. In addition, expression of phosphate transporter genes and other physiological changes result in a root system highly adapted for efficient uptake of P. The effects on root growth are brought on by inhibition of the cell cycle and by low auxin concentrations in the root apical meristems.

Sulfate deficiency also increases lateral root density. The NIT3 (nitrilase3) gene is induced and thought to increase auxin synthesis.

Moreover the cytokinin receptor CRE1/WOL/AHK4 has been shown to be involved in the interaction between phosphate-starvation, sugar, and cytokinin signaling in arabidopsis (Franco-Zorilla et al., 2005)

Several lines of evidence suggest the nutrient ions may act directly as signaling molecules. Mutants in nitrate metabolism still show the normal response to Nitrate. Root systems on plants with adequate phosphate show the classic P starvation phenotype in localized areas of deficiency. Thus the changes in root architecture are not secondary effects of altered metabolism, but appear to be primary effects regulated by the ions themselves.

Related articles
López-Bucio, J., Cruz-Ramirez, A. and Herrera-Estrella, L. (2003) The role of nutrient availability in regulating root architecture. Curr Opin Plant Biol 6: 280-287

Sabatini S, Beis D, Wolkenfelt H, Murfett J, Guilfoyle T, Malamy J, Benfey P, Leyser O, Bechtold N, Weisbeek P, Scheres B (1999) An auxin-dependent distal organizer of pattern and polarity in the Arabidopsis root. Cell 99: 463-72

van den Berg C, Willemsen V, Hage W, Weisbeek P, Scheres B (1995) Cell fate in the Arabidopsis root meristem determined by directional signalling. Nature 378: 62-5.

van den Berg C, Willemsen V, Hendriks G, Weisbeek P, Scheres B (1997) Short-range control of cell differentiation in the Arabidopsis root meristem. Nature 390: 287-9.


text:
Talk:Making an Island/Motivations

A man's home is his castle. Yet a man's island is his santuary. His hiding place, there are no walls more subtle than the sea. No peaks more treacherous than her waves. It is complete solitude, silent like a hand resting in sleep. The Mayans fell quietly and returned to a scattered people, the Aztects rose and fell, their city of Gold to ashes; and here Anthony Marlon would wait. He would wait here on this sub tropical island; perched proud on a vegatative outcrop, where he builds his palm palace. Red parrots, and bats, voices of the spirit world, they gather. He sees them not, he sees them. He knows now... He must wait till the tyranny of the western civilisations make their errors also. He will wait while all their arrogant alliances crumble here into the sea and are lost. Like Atlantis below the vulga waves; How rude that voice, how it calls in the night to him. Mosquito, bites and sweat; dead memories; here are the voices of the lost. And how long? how long till the sea gives up her dead? And the only sound to remain the dark hiss of water on the rocks.

How can you create an island if you don’t have enough money?
“ If you have limited funds, cannot earn enough money to survive, or simply cannot find a job, building an island may be right for you. Provided you live near a body of water, you can build an island which has shelter, food from fishing, and a possible income generating potential in the tourists that would come to visit your island. “There are also many ways an island can be utilized to generate both raw materials and energy. The sea can be farmed just like ordinary land, only the products are different.” Those sentences should be deleted and replaced with something more sensible. There should be a chapter telling about financial motivation, but if you have limited funds and can’t even feed yourself, how would you have enough money to build an island? I agree that an island can be utilised yo generate both raw maters d energy, but in order to have an island, you need money. Dino Bronto Rex (discuss • contribs) 16:18, 25 November 2019 (UTC)
 * Done --Mbrickn (discuss • contribs) 05:36, 26 September 2021 (UTC)

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

title: Talk:Making an Island/Motivations


text:
Plant Sciences/Arabidopsis root development/Pericycle

../Pericycle/ is located between the vascular tissues and the endodermis. It is involved in loading/unloading of vasculature (ref ??).

This tissue has two subpopulation of cells:
 * cells in front of xylem poles (also called Pericycle Founder Cells, PFCs) are blocked in G2 phase and are able to reenter the cell cycle to initiate lateral roots (Beeckman et al 2001). This tissue is therefore considered as an "extended meristem".
 * cells in front of phloem poles are not able to initiate lateral roots.


text:
Radiation Oncology/Primary CNS Lymphoma

Epidemiology

 * Median age of presentation for non-HIV related primary CNS lymphoma is 6th decade. HIV related presentation is related to stage of HIV.
 * Incidence has increased 10-fold in past 30 years, and the increase cannot be totally explained by the advent of HIV.
 * Has traditionally accounted for 1% of intracranial neoplasms in immunocompetent patients. The fraction now is estimated at 4%.
 * Impacts two distinct populations:
 * Immunocompromised (HIV, organ transplantation, immunodeficiency syndromes) - arise from EBV infection of B-cell lymphocytes
 * Immunocompetent - no known etiology. B-cells have no normal role in the brain
 * if HIV+ & surviving longer than 4 years, the frequency may be as high as 10% to 20% - though decreasing with HAART (Perez 2007)
 * PCNSL frequently CSF+ (16% to 47% reported)
 * Ocular involvement in 15% to 20% (vs Primary intraocular lymphoma spreads to the brain in 80%)

Pathology

 * Usually B-cell histology
 * T-cell variants account for <5% of PCNSL in developed countries; their behavior is very similar to B-cells
 * 85% are either aggressive or highly aggressive variants of NHL

 * PCNSL Collaborative Group; 2005 PMID 15800313 -- "Primary CNS lymphoma of T-cell origin: a descriptive analysis from the international primary CNS lymphoma collaborative group." (Shenkier TN, J Clin Oncol. 2005 Apr 1;23(10):2233-9.)
 * Retrospective. 12 centers in 7 countries. 45 patients. Median age 60 years, 44% ECOG 0-1, 58% cerebral hemispheres, 26% deep lesions. LDH elevated in 32%, CSF elevated in 79%
 * Outcome: DSS 2-year 51%, 5-year 17%
 * Positive predictors: ECOG 0-1, MTX use
 * Conclusion: Presentation and outcome similar to B-cell PCNSL

Anatomy

 * Restricted to brain, CSF, eyes, or rarely spinal cord
 * Clinicopathologic variants include intracranial lesions, diffuse leptomeningeal or periventricular, vitreous, and spinal lesions.
 * Intracranial primary CNS lymphoma are generally 75% supratentorial and 25% infratentorial.
 * Primary CNS lymphoma is multifocal in 50% of AIDS-related variants, and multifocal in 25% of immunocompetent variants.
 * MRI significantly underestimates extent of involvement; May appear focal on CT or MRI but parenchyma is typically diffusely involved.
 * Intensely enhancing on MRI; may have a diffuse or “cotton wool” appearance on imaging.
 * Classified as Stage IE NHL, because they are typically restricted to a single extranodal site

Prognostic Factors

 * Multiple factors for poor prognosis: Age >60, ECOG PS >1, elevated LDH, elevated CSF protein, deep regions of the brain
 * European Stratification: 5 variables above. Risk groups: 0-1 factors, 2-3 factors, 4-5 factors
 * MSKCC Stratification: 2 variables, age and KPS

 * MSKCC; 2006 (1983-2003) PMID 17116938 -- "Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model." (Abrey LE, J Clin Oncol. 2006 Dec 20;24(36):5711-5.)
 * 338 patients analyzed. RPA analysis. External validation from 3 RTOG prospective trials
 * RPA: Class I (patients <=50), Class II (patients >=50 and KPS >=70), Class III (>50 and KPS <70)
 * MSKCC data: median OS 8.5 years vs. 3.2 years vs. 1.1 years
 * Validation with RTOG data: median OS 5.2 years vs. 2.1 years vs. 0.8 years
 * Conclusion: Simple, universally applicable

 * International Extranodal Lymphoma Study Group; 2003 PMID 12525518 -- "Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience." (Ferreri AJ, J Clin Oncol. 2003 Jan 15;21(2):266-72.)
 * 378 patients analyzed. Five variables developed for prognostic score: 1) age >60, ECOG >1, elevated LDH, high CSF protein, deep regions of the brain.
 * 2-year OS: Score 0-1: 80%; Score 2-3: 48%; Score 4-5: 15%
 * Conclusion: Prognostic score developed

 * France; 1993 (1982-1991) PMID 8494713 -- "Multivariate analysis of prognostic factors in patients with non HIV-related primary cerebral lymphoma. A proposal for a prognostic scoring." (Blay JY, Br J Cancer. 1993 May;67(5):1136-41.)
 * Retrospective. 41 patients with non-HIV PCNSL.
 * Multivariate predictors: CSF protein >0.6 g/l, ECOG >2, Age >60
 * Prognostic risk groups: median OS: good 54 months, intermediate 20 months, poor 4 months
 * Conclusion: heterogenous disease, can be stratified

Overview

 * Debulking surgery typically does not play a role, unless patients have masses that threaten impending herniation
 * Steroids should not be given, unless necessary to prevent herniation, since they can induce significant tumor regression and mask pathology. However, if steroids are given, immunostaining may still be possible even on dead cells
 * Treatment for CNS lymphoma traditionally consisted of whole brain radiation therapy. The results were generally dismal. Although there is a high initial response rate to radiation, the vast majority of patients relapsed within the brain, and died of their disease. Median survival was 1 - 1.5 years, with 5-year OS ~5%
 * Due to rarity of this disease, most studies are Phase II trials
 * RTOG 8315 attempted to dose escalate brain treatment, but ultimately found unacceptably high rates of late side effects without significant improvement in overall survival. Ideal dose appears to be somewhere between 40 and 50 Gy; less than 40 Gy leads to worse survival, more than 50 Gy to worse neurotoxicity
 * Even though CHOP is very effective in systemic NHL, its results in PCNSL have been disappointing
 * Phase II single arm RTOG 9310 showed that chemo followed by RT consolidation had better outcomes than RT alone compared to historical controls. However, there was high neurotoxicity in patients >60 with combined modality therapy
 * High dose methotrexate (HD-MTX) based chemo has become the backbone of primary treatment. Consolidative WBRT is too toxic for older patients (>60) and should be deferred. The role of consolidative WBRT in young patients (<60) is unclear, but appears to improve outcome. Median survival with sequential chemo-RT, as well as high dose chemo alone is now ~4 years
 * Going forward, attempts are to optimize chemo regimens to defer neurotoxicity from consolidative WBRT

Current NCCN guidelines for treatment:
 * For patient with KPS >40 and creatinine clearance >50, high dose MTX based chemotherapy is considered the standard treatment.
 * If CSF cytology is positive, consider intrathecal chemotherapy.
 * For patient with KPS <40 or creatinine clearance <50, WBRT to 45 Gy.

Current indications for radiation therapy:
 * Consider as post-chemotherapy treatment in initial management of select younger patients (see RTOG 9310).
 * Recurrent disease resistant to MTX based chemotherapy.
 * Radiation should be avoided in patients >60 when possible.

Chemo+/-WBRT

 * G-PCNSL-SG-1
 * Multicenter, phase III noninferiority trial, 551 patients Non-AIDS randomized to received HD-MTX +/- WBRT. 318 pts treated per protocol included in analysis.
 * WBRT : 45Gy/30F, 1.5Gy daily fraction
 * Chemo: Initially MTX 4g/m2, but protocol amended in 2006 to give MTX 4g/m2 on day 1 and ifosfamide 1.5g/m2 on day 3-5
 * Primary endpoint: overall survival, defined non-inferior as lower 95% CI not below 0.9. Designed to have 60% power.
 * 2010 PMID 20970380 -- "High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial." (Thiel E, Lancet Oncol. 2010 Nov;11(11):1036-47.)
 * Results: Median f/u: 4.2 years, included only 318/551 treated per protocol
 * Per protocol analysis: median overall survival was 32.4mo(WBRT) vs 37.1mo, HR 1.06 (95% CI= 0.80-1.40, P=0.71). Median PFS was 18.3 mo(WBRT) vs 11·9 mo (P=0.15).
 * Intent to treat analysis: no difference in OS, but WBRT improved PFS (HR=0.79, P=0.041). On subgroup analysis, WBRT improved PFS in patients without CR (HR=0.69, P=0.011), but not with CR (HR=0.79, P=0.21) after chemo.
 * Toxicity: In 79 pt with sustained CR, more radiologic neurotoxicity 76% vs 46%, clinical neurotoxicity 49% vs 26%, in WBRT group
 * 66 patients died after chemotherapy alone (all excluded from results analysis).
 * Conclusion: No significant difference in OS. The PFS benefit of WBRT has to be weighed against the increased toxicity.
 * Criticism: Ferrari Lancet Oncol 2011: PMID 21277546
 * Did NOT meet preset primary endpoint that omitting WBRT had not inferior OS to giving WBRT.
 * Used a per-protocol analysis, rather than intent to treat, which allows for selection biases.
 * Extraordinarily high mortality with HD-MTX alone (12.5%), but all of these patients were excluded from analysis, making the results look better than they are
 * Overall, many major protocol violations, and excluded 42% of the patients originally enrolled
 * 66 pt died during chemo, 49 pt assigned do WBRT who did not get WBRT, 44 pt did not get salvage Ara-C in chemo-only arm with PR, 27 low to f/u, 22 did not have response criteria, 14 pt ineligible
 * Only evaluated neurotoxicity outcomes in 79 patients, and clinical neurotoxicity endpoint not well defined. MMSE planned, but not done for most patients.

Sequential Chemo-WBRT

 * ANOCEF-GOELAMS PRECIS Study; 2019 (2008-2014) PMID 30785830 -- "Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients 60 Years of Age and Younger: Results of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study." (Houillier C, J Clin Oncol. 2019 Apr 1;37(10):823-833. doi: 10.1200/JCO.18.00306. Epub 2019 Feb 20.)
 * Prospective, Phase II. 140 patients, 23 French centers. Untreated primary CNS lymphoma, age <=60. Induction R-MBVP / R-AraC, followed by randomization to Arm 1) Thiotepa / busulfan / cyclophosphamide vs Arm 2) WBRT 40/20.
 * Outcome: 2-year PFS chemo 87% vs WBRT 63%, both exceeded threshold for efficacy, no p-value given
 * Toxicity: Cognitive toxicity worse after WBRT (p = 0.004)
 * Conclusion: Both consolidative chemo and WBRT are effective for patients <=60; efficacy favors chemotherapy. Specific risks should be considered.

 * International Extranodal Lymphoma Study Group (IELSG), 2009 PMID 19767089 — "High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial." (Ferreri AJ, Lancet. 2009 Sep 18. [Epub ahead of print])
 * Multicenter phase 2, randomized. 79 pts, age <=75. Randomized to 4 courses of MTX vs MTX + cytarabine. Following chemo, whole brain RT was given.
 * CR in 18% (MTX) vs 46% (MTX+C); overall response rate 40% and 69%. Increased g3-4 heme toxicity, 15% vs 92%; treatment-related death in 1 pt vs 3 pts.
 * Conclusion: The addition of high-dose cytarabine to high-dose methotrexate improved outcome with acceptable toxicity in pts 75 yrs and younger.

 * RTOG 0227 Protocol -- "Phase I/II Study of Pre-Irradiation Chemotherapy with Methotrexate, Rituximab, and Temozolomide and Post-Irradiation Temozolomide for Primary Central Nervous System Lymphoma"
 * Opened protocol: Rituximab + Temozolomide + Methotrexate -> WBRT 36/30 in 1.2 Gy BID -> Temozolomide

 * EORTC 20962 (1997-2002)
 * Phase II. 52 patients. Non-AIDS-related. MBVP (methotrexate (MTX) teniposide carmustine methylprednisolone) x 2 cycles with 2x IT-MTX, ara-C, and HC. Followed by 40 Gy WBRT.
 * 2003 PMID 14597741 — "High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962." Poortmans PM et al. J Clin Oncol. 2003 Dec 15;21(24):4483-8. Median F/U 2.2 years.
 * Outcome: median OS 3.8 years. 3-yr OS 58%.
 * Toxicity: Grade 3-4 neutropenia 78%; 10% deaths treatment-related
 * Conclusion: MBVP followed by WBRT has a high response rate, but is very toxic

 * RTOG 9310 (1994-1997)
 * Phase II prospective single arm trial. 98 patients. HIV-. Pre-radiation chemotherapy included MTX, vincristine, procarbazine and intraventricular MTX. RT was WBRT to 45 Gy; if ocular lymphoma then eyes 36/20. During study, protocol modified such that if CR after chemo, WBRT 36/30 BID. After RT, patients received hi-dose cytarabine.
 * Primary outcome; 2002 PMID 12488408 — "Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10." DeAngelis LM et al. J Clin Oncol. 2002 Dec 15;20(24):4643-8.
 * Outcome: Median OS 50.4 months in patients <60, and 21.8 months in patients >60 (overall 36.9 months); 5-year OS 32%, no difference if CR after chemo or not
 * Toxicity: 15% patients experienced severe delayed neurologic toxicity.
 * Conclusions: HD-MTX based regimen combined with consolidative RT is superior to RT alone when the overall survival data are compared to historical data. However, patients over age 60 had significant risk of late toxicity from the combined treatment.
 * HFX-RT; 2005 PMID 16193393 -- "Secondary analysis of Radiation Therapy Oncology Group study (RTOG) 9310: an intergroup phase II combined modality treatment of primary central nervous system lymphoma." (Fisher B, J Neurooncol. 2005 Sep;74(2):201-5.)
 * Retrospective. 82 patients, 66 standard WBRT (45/25) and 16 HFX (36/30)
 * Neurotoxicity: Grade 5 (fatal): 10%, HFX 13% vs. RT 9% (NS); leukoencephalopathy later in HFX group. None of CR to chemo developed Grade 5 neurotoxicity
 * Outcome: no difference
 * Conclusion: HFX 25% lower BED dose, but no difference on PFS and OS. It delayed but not eliminate severe neurotoxicity

 * MSKCC; 2006 (1992-1998) PMID 17008697 -- "Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma." (Gavrilovic IT, J Clin Oncol. 2006 Oct 1;24(28):4570-4.)
 * Retrospective. 57 patients, average 65 years old, median KPS 70. Treated with HD-MTX x5 cycles + vincristine. Intra-Ommaya MTX, procarbazine. Then WBRT 45 Gy, followed by Ara-C 2 cycles. WBRT deferred for 68% patients >60. Median F/U 9.6 years for surviving patients
 * Outcome: median OS 4.2 years, median PFS 10.7 years. Median OS for age >60 was 2.4 years, regardless of RT. Median OS for age <60 (most chemo-WBRT) not reached yet
 * Conclusion: Excellent survival. For older patients, defer WBRT. For younger patients, deferring WBRT may significantly compromise disease control

 * Trans-Tasman Radiation Oncology Group, TROG, (1991-97)
 * Phase II. 46 pts. IV MTX (1 g/m2; days 1,8) + leucovorin. Pts with positive CSF received intrathecal Ara-C 60 mg twice/wk x 3 weeks, continued weekly x 3 after clearance of CSF. WBRT began on day 15, 45 Gy in 25 fx (180 cGy/d) with a boost to 50.4 Gy if localized involvement or whole brain dose to 50.4 Gy if diffuse.
 * 2000 PMID 10653867, 2000 — "Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma." O'Brien P et al. J Clin Oncol. 2000 Feb;18(3):519-26.
 * 2006 PMID 16198065, 2006 — "Combined-modality therapy for primary central nervous system lymphoma: Long-term data from a Phase II multicenter study." O'Brien PC et al. Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):408-13.
 * 5-yr OS 37%, MS 36m. 30% actuarial risk of neurotoxicity.
 * Conclusion: combined modality treatment results in improved outcome compared to historical controls.

 * CHOD-BVAM I/II (1990-1995)
 * 2 simultaneous phase II prospective trials to evaluate reduced WBRT. 57 patients. Initial chemotherapy CHOD/BVAM. CR after chemo would place the patient into the BVAM II study (WBRT 30.6 Gy). A non-CR after chemo would place the patient into BVAM I (WBRT 45 Gy + 10 Gy boost to single lesion).
 * 2002 PMID 11773174 -- "Importance of radiotherapy in the outcome of patients with primary CNS lymphoma: an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments." (Bessell EM, J Clin Oncol. 2002 Jan 1;20(1):231-6.)
 * Outcome: Reduced WBRT only predictor of relapse: standard WBRT 29% vs. reduced WBRT 70%. Age >60 only predictor for OS (RR 2.1). In young patients (<60), WBRT dose only predictor for OS: standard WBRT 92% vs. reduced WBRT 60% (SS)
 * Toxicity: Incidence of RT-induced dementia rare in patients <60 years
 * Conclusion: Reduction in WBRT dose in young patients after HD-MTX chemo results in increased risk of relapse and lower OS

Sequential WBRT-chemo

 * NCCTG 96-73-51; 2006 (1998-2003) - PMID 16863926 — "Whole-brain radiotherapy and high-dose methylprednisolone for elderly patients with primary central nervous system lymphoma: Results of North Central Cancer Treatment Group (NCCTG) 96-73-51." Laack NN et al. Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1429-39.
 * 19 pts 70 years and older. After WBRT, 1 gram of methylprednisolone (Solu-Medrol) daily x 5 days, 30 days after RT. Then 1 g q28d until progression.
 * 6 month OS of 33% at interim analysis; trial closed. Final results, longer OS 12.1 m and EFS 11.7 m in comparison to previous NCCTG trial of CHOP + high-dose ara-C + WBRT (OS 7.0m, EFS 4.0m).
 * Conclusion: high dose methylprednisolone warrants further study

WBRT +/- CHOP

 * MRC (1988-95)
 * Phase III Closed early due to poor accrual, short of target population of 90 pts. 53 pts, treated with surgery, then randomized 2:1 to RT->CHOP vs RT alone. RT dose 40/20 WBRT + 14 Gy boost to 2cm margin. In RT-CHOP arm, RT was followed by CHOPx6.
 * 2000 PMID 11002232 — "A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy." Mead GM et al. Cancer. 2000 Sep 15;89(6):1359-70. Median F/U 5 yrs.
 * Outcome: No difference in OS adjusted for age/KPS
 * Conclusion: inconclusive study due to poor accrual, but CHOP no clear role

WBRT alone

 * RTOG 8315 (1983-87)
 * Phase II prospective single arm trial; dose escalation. 41 patients. RT 40 Gy WBRT + 20 Gy boost to the tumor bed + 2cm margins
 * 1992 PMID 1572835 — "Non-Hodgkin's lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315." Nelson DF et al. Int J Radiat Oncol Biol Phys. 1992;23(1):9-17.
 * Outcome: median OS 12.2 months from diagnosis, 2-year OS 28%; Disease recurrence in the brain was 61%
 * Prognostic factors: KPS >=70 median OS 23 months vs. 6 months (SS); age <60 23 months vs. 8 months (SS)
 * Conclusion: Unreasonably high loco-regional recurrence, at the cost of significant leukoencephalopathy and cognitive impairment.

Chemotherapy alone

 * German PCNSL-SG; 2005 PMID 15653703 -- "High-dose methotrexate toxicity in elderly patients with primary central nervous system lymphoma." (Jahnke K, Ann Oncol. 2005 Mar;16(3):445-9. Epub 2005 Jan 14.)
 * Phase IV prospective. 154 patients, 619 HD-MTX cycles, 4 g/m2 unless adjusted for decreased GFR, followed by LV rescue
 * Toxicity: Grade >=3 was <10%; no difference if =60
 * Dose reduction: <60 18% vs. >60 44% (SS)
 * Conclusion: HD-MTX safe treatment, regardless of age

 * German deferred WBRT; 2003 (1995-2001) PMID 14597744 -- "Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy." (Pels H, J Clin Oncol. 2003 Dec 15;21(24):4489-95.)
 * Phase II single arm. 65 patients. High dose MTX and Ara-C based chemotherapy (other chemo agents used include dexamethasone, vinca-alkaloids, ifosfamide, CTX). Intraventricular MTX, prednisolone, and Ara-C were also administered. Median F/U 2.2 years
 * Outcome: Median TTF 1.7 years, median OS 4.2 years. If >60 years, median OS 2.8 years; not reached for <60 years
 * Toxicity: 9% died of treatment related complications. 3% had permanent cognitive dysfunction.
 * Conclusion: Primary chemo with HD-MTX and ARA-C is highly efficient, and outcomes comparable to chemo + RT

Intra-Arterial MTX-based chemo
 * Multi-Institutional; 2009 (1982-2005) PMID 19451444 -- "Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy." (Angelov L, J Clin Oncol. 2009 Jul 20;27(21):3503-9. Epub 2009 May 18.)
 * Phase II single arm. 4 institutions. 149 patients treated with Osmotic BBBD and IA infusion of methrotraxate + etoposide and cyclophosphamide or procarbazine. 46% age > 60, KPS < 70 in 42 %, CSF + in 7.4%
 * Outcome: Overall response rate 81.9%, Median PFS was 1.8 years (95% CI, 1.3 to 2.8 years); 5-year PFS was 31%, 7-year PFS was 25%, Median OS was 3.1 years, 41% estimated 5-year survival, 25% estimated 8.5-year survival, Patients < 60 years median OS = 5.2 yrs and a 5-year survival = 52%, Patients > 60 years had median OS of 2.2 years and a 5-year survival = 30%
 * Toxicity: Peri-procedural seizures in ~10%, Clinical strokes in 7.4% (Risk of permanent damage ~0.2%/BBBD-IA), Limited neurocognitive effects (per paper discussion, no data presented)
 * Conclusion: BBBD and IA chemo results in excellent response and OS with minimal toxicity and allows for delay of WBRT. (Caution to use only in centers with experience in this technique)

Rituxan

 * MSKCC; 2007 PMID 17947720 -- "Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma." (Shah GD, J Clin Oncol. 2007 Oct 20;25(30):4730-5.)
 * Prospective. 30 patients (mean age 57, KPS 70). Treated with 5-7 cycles of induction chemo (R-MPV). If CR, dose-reduced WBRT 23.4 Gy; if PR, standard WBRT 45 Gy. Then 2 cycles Ara-C. Median F/U 3 years
 * Outcome: 2-year OS 67%, PFS 57%. CR in 78% after 7 cycles, 44% after <=5 cycles
 * Toxicity: Grade 3-4 neutropenia 43%, thrombocytopenia 36%, leukopenia 23%. Reduced WBRT in ~2/3 patients
 * Conclusion: Immunochemotherapy is a promising approach; dose-reduced WBRT appears to eliminate risk of neurotoxicity without compromising control

 * ASCO 2004: Abstract 1518 (2002-3) — "Combined immunochemotherapy with reduced dose whole brain radiotherapy (WBRT) for newly diagnosed patients with primary CNS lymphoma (PCNSL)." El Kamar FG.
 * Phase II. 14 pts (of planned 30). Rituxan plus Methotrexate, Procarbazine and Vincristine (MPV). 23.4 Gy if CR after 5-7 cycles. 45 Gy if less than CR.

Salvage

 * MGH; 2005 PMID 15735126 -- "Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma." (Nguyen PL, J Clin Oncol. 2005 Mar 1;23(7):1507-13.)
 * Salvage whole brain RT: median 36 Gy (median 2 Gy/fx, most common 1.5 Gy/fx)
 * 74% overall response rate (37% CR, 37% PR). Improved performance status in 44%. MS 10.9 mo.
 * Conclusion: "For patients with PCNSL who experience treatment failure with methotrexate, WBRT provides high response rates (74%) and a median survival of 10.9 months. Age less than 60 years and response to WBRT predict post-WBRT survival. Modest rates of late neurotoxicity (15%) were seen and were associated with a total dose greater than 36 Gy."

Presentations

 * ASCO 2004 - Video De Angelis LM - "Primary CNS Lymphoma: Update 2004"

Reviews

 * MSKCC; 2007 - PMID 17591569 — "Primary central nervous system lymphoma." (Mohile NA, Semin Radiat Oncol. 2007 Jul;17(3):223-9.)
 * MGH; 2006 - PMID 16525183 — "Primary CNS Lymphoma." (Batchelor T et al. J Clin Oncol. 2006 Vol 24, No 8 (March 10), 2006: pp. 1281-1288.)
 * Yale; 2006 - PMID 16613654 — "Primary lymphoma of the nervous system." (Baehring JM et al. Cancer J. 2006 Jan;12(1):1.)

title: Radiation Oncology/Primary CNS Lymphoma


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User:Sarken~enwikibooks

Also consult my Wikipedia User Page.

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title: User:Sarken~enwikibooks


text:
Talk:Advanced Data Structures and Algorithms

Multilanguage projects
I don't think a CS text book is the right place to discuss multilanguage projects. CS is about more abstract programming aspects than language bindings. 192.160.6.253 16:25, 28 July 2005 (UTC)

 * I'll say that that section did seem a little out of place. But perhaps there are specific algorithms behind it that the author wanted to cover? This one book is in such an early stage that we should probably be less conservative than with something closer to being complete. (I'm still waiting for the flood of suggestions and further chapters to be suggested.) MShonle 20:23, 28 July 2005 (UTC)

 * I'd have to agree with the first guy, mutilanguage projects just move the algorithm to a separate language. Rarely (if ever) do algorithms get passed between languages.--Dragontamer 10:22, 11 August 2005 (UTC)

 * OK, seems like it can be removed. MShonle 14:07, 11 August 2005 (UTC)

 * It's been removed. MShonle 03:49, 21 August 2005 (UTC)

Thoughts from a wiki newbie
I am a retired CS professor who taught an advanced algorithms course for many years. I think I would enjoy contributing to this book, but thought I should test the waters before jumping in. My interest is in graph algorithms of all sorts, but with a focus on classic network optimization problems ranging from minimum spanning tree to network flow and graph matching. The simpler algorithms for some of these problems could appear in the Algorithms book, rather than the Advanced book, but there are some more sophisticated algorithms for these problems that would make more sense in the Advanced book. Is this an appropriate direction in which to take this book? Jonturner53 (discuss • contribs) 19:37, 17 June 2021 (UTC)


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Learn Electronics/Capacitors

Materials
See also Dielectrics

Charging

 * Capacitors can be thought of as temporary sources of voltage. Assume that a capacitor is rated at 10 volts, then, to charge it, any voltage up to 10 V can be supplied to its terminals, possibly directly, or via a series resistance. Many capacitors require proper polarity (direction of applied voltage), otherwise damage could be the result. Capacitors need not be, but can be fully charged.
 * At the moment of first connecting the voltage source to the capacitor a large current flows into the capacitor, and, if desired, that amount of current can be limited by a series resistor. The voltage source usually has an internal resistance in addition, but that resistance may be neglected in some calculations. As the capacitor charges, the voltage at its terminals increases, and because it opposes the applied voltage therefore the charging current decreases until it stops. The capacitor is then fully charged, the voltage at its terminals then being equal to the supplied voltage.
 * Usually, if left alone for some time, a charged capacitor loses its charge slowly. Note that a voltmeter connected across the terminals of a capacitor represents a "load" and in some calculations may not be neglected.
 * If AC is connected to a capacitor, then the capacitor will charge and discharge during each cycle, with an alternating current flowing that can be computed from moment to moment by assuming that the AC voltage is actually a changing DC voltage at each moment, and carefully noting whether the existing voltage across the terminals of the partly charged capacitor adds to, or subtracts from, the applied AC voltage at that moment.
 * There are three voltages in the circuit. 1) Vin the supply voltage, 2) VR the "voltage drop", which is lost across the resistor and is proportional to the current flowing, and 3) VC the voltage across the terminals of the capacitor/condenser.

Discharging
Capacitors when charged are equivalent to a DC voltage source, and the circuit components connected across the capacitor's terminals determine the magnitude of the discharge current. Any such current reduces the amount of charge, and therefore also reduces the voltage across the terminals of the capacitor.

Information
The capacitor is another important basic circuit component. They are used as a means of storing energy. They consist of two conducting plates separated by an insulator. Charge will not flow directly through a capacitor. Instead, when a voltage is applied, charge will accumulate on both plates. The accumulation of charges creates an electric field between the two plates, which is the means of energy storage. Eventually, the plates will 'fill up' with charges and no more will accumulate. At this point, the capacitor has an amount of energy stored that is determined by its size and voltage applied across it. The energy can then be discharged into an electrical load via some manner of switch. The size of a capacitor is determined by several factors: physical size, insulator material used, closeness of the plates, etc. Voltage rating is determined similarly. Capacitor size is measured in farads. Typical capacitor sizes used are in the microfarad range, although the lower bound for typical uses can be as low as picofarads, and as high as millifarads.

At low frequencies, capacitors are fairly uninteresting. After they fill up with charge, nothing happens. Thus, at low frequencies (also, after a long time), they act as an open circuit. However, at shorter time spans (higher frequencies), they show more useful behaviors. They can be combined with a resistor in parallel to control the flow of charge into them, which allows them to charge and discharge at a certain rate. These properties are used extensively in timing circuits, such as a 555 timer square wave generator. Capacitors are also used for filtering. By pairing them with resistors in series, capacitors can reduce the amplitude of sin waves. The reduction in amplitude is a function of frequency. By tuning the values of the resistor and capacitor, the frequencies affected and magnitude of reduction can be altered.

title: Learn Electronics/Capacitors


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User:RJHall

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 * Baelnorn → Dungeons & Dragons/Monsters/Baelnorn
 * Banderlog → Dungeons & Dragons/Monsters/Banderlog
 * Bariaur → Dungeons & Dragons/Monsters/Bariaur
 * Bloodhulk → Dungeons & Dragons/Monsters/Bloodhulk
 * Bloodsilk spider → Dungeons & Dragons/Monsters/Bloodsilk spider
 * Bodak → Dungeons & Dragons/Monsters/Bodak
 * Bogun (Dungeons & Dragons) → Dungeons & Dragons/Monsters/Bogun
 * Bronze serpent (Dungeons & Dragons) → Dungeons & Dragons/Monsters/Bronze serpent
 * Boneclaw → Dungeons & Dragons/Monsters/Boneclaw
 * Brain in a jar (Dungeons & Dragons) → Dungeons & Dragons/Monsters/Brain in a jar
 * Fyrefly → Dungeons & Dragons/Monsters/Fyrefly

title: User:RJHall


text:
User talk:RJHall

It sure is quiet in here. (Sounds of a chill wind whistling under the door crack...) Have a better than typical day. — RJHall 19:41, 28 July 2005 (UTC)

Hi Bob. Welcome to Wikibooks.

Here are some tips to help you get started:
 * You can sign your name on Talk and vote pages using four tildes, like this: ~~~~.
 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Templates can save your time
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

You will find more resources in Community Portal. If you want to ask a question, visit the Study help desk, the Staff lounge, or ask me personally on my talk page.

Thank you for your work on UNIX Computing Security and Wikijunior Solar System. --DavidCary 03:24, 22 December 2005 (UTC)

D&D Pages
If you list the pages you want at WB:RFI, they can be imported from Wikipedia - with the revision history - if it is easier. QU TalkQu 20:00, 24 July 2012 (UTC)
 * Thanks QU. Unfortunately these are imports from page histories. Regards, RJHall (discuss • contribs) 20:02, 24 July 2012 (UTC)
 * The import brings in the whole article history, including all the revisions, so once it is imported you can "revert" it to the version you want. Up to you. QU TalkQu 21:49, 24 July 2012 (UTC)

title: User talk:RJHall


text:
Dutch/Lesson 8/Key

 * Deze wielrenner behaalt een overwinning in de Giro d'Italia
 * Deze wielrenner behaalt er een overwinning in.

 * Het is niet eenvoudig in deze wedstrijd een overwinning te behalen.
 * Het is niet eenvoudig hier een overwinning in te behalen.

 * Van welke wedstrijd is hij ook kampioen?
 * Waar is hij ook kampioen van?

 * Zij doet in de keuken koffie in het zakje.
 * Zij doet er in de keuken koffie in.

 * Koekjes zijn onder kinderen altijd een groot succes.
 * Koekjes zijn er altijd een groot succes onder.

 * Het verschil tussen Amerikaanse en Nederlandse koekjes is niet groot.
 * Het verschil ertussen is niet groot.
 * Het verschil is niet groot ertussen.
 * Het verschil is er niet groot tussen.

 * Achter geen enkel werkwoord moet je een uitgang -ing schrijven.
 * Nergens moet je een uitgang -ing achter schrijven.

 * Je schrijft altijd een punt boven een i.
 * Je schrijft er altijd een punt boven.

 * Hij ging met de trein naar London.
 * Hij ging ermee naar London.
 * Hij ging er naar London mee.

 * Remark: please do not worry too much about the word order. As you can see it is quite irregular and sometimes there are various possibilities. It is one of the hardest aspects of West-Germanic languages (other than English). Unfortunately, for English speakers they lost that after 1066 or so.

title: Dutch/Lesson 8/Key


text:
Dutch/Lesson 10

Grammatica 10-1 ~ Separable verbs
A lot of verbs in English have fixed adverbial complements and a comparable association often holds in Dutch. Compare:

 * the bomb went off.
 * de bom ging af.

 * the light went on.
 * het licht ging aan.

In English one could consider to go off as the infinitive of a distinct verb. In Dutch the association is even stronger, because in some of the forms of such a verb, e.g. the infinitive, the adverb af is actually written as a prefix. This becomes clear in the future tense:

 * the bomb will go off.
 * de bom zal afgaan.

This means that there are two types of prefixes to a Dutch verb: inseparable ones (such as be-) and separable ones (like af-). The first kind we have seen before:

 * bedoelen - to mean
 * hij bedoelde
 * hij heeft bedoeld

The primitive tenses of a separable verb look like:
 * afgaan
 * het ging af
 * het is afgegaan.

Notice that the separable verb does take the ge- marker of the past participle whereas the inseparable ones do not.

There is another difference, at least in the spoken language: the accent of the word lies on the prefix if it is separable, i.e. one says áfgaan, but bedóélen.

Some prefixes can occur both separably and inseparably such as door- (through, by) and voor- (for,before) and in some cases there are two different verbs that look deceptively the same, one separable, the other not, with different meanings. In the spoken language they differ by word accent, but this is not visible in the written one unless accents are deliberately added to avoid confusion. Compare:

 * vóórkomen - kwam vóór - vóórgekomen - to occur
 * voorkómen - voorkwám - voorkómen - to prevent

 * de kluut komt meer in Nederland voor dan in Engeland.
 * wij moeten er het verdwijnen van zien te voorkomen.

 * the Avocet is more numerous in the Netherlands than in England. (lit. ...occurs more in NL than...)
 * we have to prevent its disappearance.

Notice that just like in the case of the pronominal adverb ervan that translates its, the two parts of the separable verb can end up rather far apart in the sentence.

What we have seen earlier about inversion still applies:

 * Komt de kluut hier meer voor? - inversion in question
 * Gelukkig komt de kluut hier nog steeds voor. - gelukkig put in front for reasons of emphasis.

Another example:

 * een school dóórlopen - to walk through a school building (takes 5 minutes)
 * een school doorlópen - to absolve one's education at a school (takes 5 years).

 * Hij liep het gebouw dóór - he traversed the building
 * Hij doorlíép het gymnasium - he graduated from a grammar school

Relationship to the prepositional adverbs
In fact the comparison between pronominal adverbs and separable verbs is rather pertinent. We will revisit that in Les 17 Many prepositional adverbs occur both as part of pronominal adverbs and of separable verbs:

 * meelopen met... => loop mee met ... (to march along with) (verbal separation)
 * met alles => overal mee (with everything) (pronominal replacement)

 * aanzitten aan ... (to partake in an official dinner party)
 * aan alles => overal aan (at everything) (pronominal replacement)

Thus, occasionally the same prepositional adverb appears twice at the end of the phrase:

 * hij liep overal mee mee. (he went along with anything at all)
 * hij zat overal aan aan. (he was a high level social tiger)

The latter should not be confused with:

 * hij zat overal aan. (he could not keep his hands off of anything)

 * zitten aan (to touch, to not being able to keep your hands off something.)

The comedian Toon Hermans exploited this oddity once to great effect in one of his One Man Shows.

Although many of the prefixes of separable verbs are indeed prepositional adverb, this does not hold for all of them. Sometimes a separable verb results from compounding with e.g. a noun such as in koffiedrinken:

 * koffiedrinken - dronk koffie - koffiegedronken

The verb means a bit more than to consume coffee. "Koffiedrinken" means getting together e.g. with your neighbors to have something to drink (and eat), not necessarily coffee.

Subclauses
Recall from lesson 9: Dag meneer, zou u mij kunnen zeggen waar ik mijn paspoort kunnen laten verlengen?
 * Why does the word zou not follow the personal pronoun ik as it would in English? The reason is that the sentence starting with waar is a dependent subclause and in Dutch these subclauses have their own word order.

In a dependent subclause, e.g. a clause that starts with dat ("that") the separated forms of a separable verb also reunite

 * ik doe het licht uit. - I switch the light off.
 * ik zeg "dat" ik het licht uitdoe. - I say "that" I switch off the light.

Notice also the peculiar position of the verb in the subclause: it moves to the end of the phrase in its entirety.

We will look at the word order in subclauses in detail in the next lesson and we will revisit this complication in word order for separable verbs in particular in lesson 18.

Quizlet
The vocabulary of the lesson can be practiced at Quizlet (57 terms)

Progress made
Cumulative term count:
 * Beginner level: 1053 terms
 * Lesson 9: 139 terms
 * Lesson 10: 53 terms

 * Total number of terms: 1245

title: Dutch/Lesson 10


text:
Super NES Programming/Initialization Tutorial/Snes Init

Contributors

 * Written by the ancient Midfit, with the comment: ''; Cool Init routine! use it in your own code!!
 * Bazz: This was a mess in conjunction with the tutorials. Fixed a ton of things.


text:
Talk:Super NES Programming/Initialization Tutorial

The SNES Central development page bonked. Uploading new files. Snargle 21:16, 28 July 2005 (UTC)

it is still black!! :((

How should the file system look like?(where should each and every file go?)

What do all the flags in the status register do?
About this section:

"In the header file, the label "Start" is declared as the reset vector, so that is where the program shall begin executing:"

sep    #$20        ; Set the A register to 8-bit.

It would help me wrap my head around this, If I could look at a list of flags in the status register and a description of what they all do. If there's already a page for this, then maybe we should link it here? 98.212.132.99 (discuss) 01:38, 21 March 2019 (UTC)

assembler link dead
permission denied

Need explanation of code
This code: lda    #%11100000  ; Load the low byte of the green color. sta    $2122 lda    #%00000000  ; Load the high byte of the green color. sta    $2122

It loads something to A, then stores it. Then it does it again. Its exactly the same code (except for the value assigned to A), so how come the first half sets the low byte of $2122 and the other half sets the high byte? Magic? --Profetylen (discuss • contribs) 23:23, 22 March 2011 (UTC)

 * I'm not an expert but apparently the SNES hardware has an automatic address increment function which mean that successive writes to $2122 write to successive memory localtions in the color palette. Recent Runes (discuss • contribs) 00:19, 24 March 2011 (UTC)

 * Okay! Thanks for clearing that up! :D --Profetylen (discuss • contribs) 23:31, 24 March 2011 (UTC)

I'm using Windows 7 and the SNES assemlber doesn't seem to work :(

I open it, and then it closes automatically :( Please send me an E-Mail (felixlukas@hotmail.com) and post the solution here. 88.69.130.203 (discuss) 10:22, 22 June 2011 (UTC)

NEW EDIT: I am also having the issue of trying to run the assembler. It may only be usable on linux, but I'm hoping for a response as well. cerd@rockets.utoledo.edu

Code example doesn't work right in bsnes
i tried this tutorial code, and was able to set the color just fine when loading the rom in zsnes, but in bsnes, the screen just spazzes out with random blocks. I can confirm this Subcogitate (discuss • contribs) 18:44, 8 February 2013 (UTC)

I've never used ZSNES personally, but I know it takes shortcuts. The provided ROM DOES work on power-on in bsnes, but will give a garbage pattern on reset that matches the pattern from a ROM assembled from the source code, except possibly for the color.

It does NOT appear that the provided ROM was assembled using the same assembler as the provided source code, based on where the RESET vector points to in the "given ROM" compared to the "assembled source code ROM". I'm looking at both the provided ROM and my own assembled ROM using a disassembler and seeing if I can't get the assembled source code to work.

Update: Changing "sta    $212C" to "stz     $212C" in the snes initialization code fixes the demo for BSNES. This prevents objects and the background from being initialized, and the PPU reading garbage. The provided ROM demo works on Power-on, but not on reset because I guess bsnes stores '0' in the accumulator on power-on, and retains the value on reset (the accumulator IS given values in the provided ROM before jumping into an infinite loop).

Opening/using the assembler
Is the assembler provided by the referenced website in the wiki page( http//www.villehelin.com/wla.html) only usable in unix/linux and not windows? I'm to the point where I'm trying to compile the code and I'm at a loss.

Something isn't right.
I followed the steps of the guide exactly, and yet the .smc file does not appear to do anything. The "greenspace.asm" contents are as follows:

.include "Header.inc" .include "Snes_Init.asm"

VBlank:   ; Needed to satisfy interrupt definition in "Header.inc" RTI

.bank 0 .section "MainCode" Start: ; Initialize the SNES Snes_Init sep    #$20         ; Set the A register to 8-bit. lda    #%10000000  ; Force VBlank by turning off screen. sta    $2100 lda    #%11100000  ; Load the low byte of the green color. sta    $2122 lda    #%00000000  ; Load the high byte of the green color. lda    #%00001111  ; End VBlank, setting brightness to 15 (100%). sta    $2100 ; Loop forever. Forever: jmp Forever

.ends

The "greenspace.link" file:

[objects] Greenspace.obj

SD2SNES Problem
I tried to test my ROM on a real SD2SNES cart, and the source code was almost the same as the one in the article, only without the , without the, and the initialisation code as well as the header are included within the main file.

When I tested it on SNES9X, it ran perfectly fine, but when I ran it on SD2SNES, there were a few garbage Japanese characters on the bottom left.

Here's the entire source code: https://pastebin.com/eW1LXdZp -Nikku4211

the forever loop
How does the loop work here? I saw some examples about looping but the loop was trapped inside a subroutine unlike here:

Forever: jmp Forever It jumps to forever, does it pass to the code above or something? Lakhdar Lakhdari (discuss • contribs)
 * Loop forever.


text:
Super NES Programming/Initialization Tutorial/header

Bazz wrote almost this entire header. Use it in your own code!


text:
Talk:Raising Chickens/Other information

Facts
Post your facts that don't fit anywhere else here. Klingoncowboy4 22:35, 28 July 2005 (UTC)

Smaller birds (Bantam vs Leghorn)survive bettor if left to roam free usually because they can fly much bettor and do not put on as much weight as they age.

Questions
Post any questions that don't fit anywhere else here. Klingoncowboy4 22:35, 28 July 2005 (UTC)

Just wondering what common injuries to chickens occur with small kids handling them? My chicken is unbalanced and weak?

Feathers could be pulled out. Wings injured. Mentally, it would probably not want to be handed in any way and fear small children.

How to trim chickens
Could someone put a bit in about trimming chicken's wings to stop them from flying over fences, etc.

Chickens don't fly too well generally and usually Cock birds only fly when trying to catch hens for some luuuurve, and hens only fly when trying to get away. We have much worse problems with Guinea Fowl that are good strong flyers. However that said clipping wings should be carried out pretty much the same as for any bird. Its a two person job to be safe. One of you needs to hold the bird securely and gently extend one wing fully. With some good sharp appropriate shears or scissors you need to cut the row of feathers that are furthest away from the leading edge of the wing. These are the long ones that the bird uses to control the flight. Start next to the body and work out cutting around half of the feather away. It doesn't hurt the bird, but it will look pretty p'd off about it. As you work out towards the tip of the wing you can leave the last few feathers in tact and it will then look OK when the wing is folded in. Usually the recommendation is to just clip one wing, the theory being that this destabilises the bird and discourages it from flying more than clipping both wings. We have to clip both wings on guinea fowl, I think they could still fly if you tied one wing behind their backs! You will need to learn from experience, it is a hands on job. If after you have clipped as described above the bird is still flying, try clipping a little more of the feather away. If still escaping try clipping both wings. Start with a little and work up to more, it will build your confidence, and you are less likely to doing anything that will damage your bird.

I wouldn't reccomend this in some areas though because predatory animals can usually catch them easier. I used to have a chicken that could fly from the ground to the top of a six foot cyclone fence. But it was half wild. If you don't want your totally domestic birds to fly off and the chicken run is secure clip away!

title: Talk:Raising Chickens/Other information


text:
Raising Chickens/Other information

In this section you will find information that doesn't fit anywhere else. Feel free to add your own information here or in the Discussion Page for this section. If you have any questions post them in the discussion page.

Rooster Crow Distance
A fully grown rooster's crow can be heard miles away.

How to Hypnotize a Chicken
You can easily put most chickens into a trance. This strange animal behavior is officially called 'tonic immobility', a natural state of semi-paralysis that many animals exhibit when under threat. There are two main chicken hypnotizing techniques:
 * 1) pet the chicken to calm it, then lightly restrain it and gently lower its head down to the ground, holding its beak on a coin or a rock that contrasts with the surrounding ground; hold the chicken's head in place for about 30 seconds, then slowly remove your hand.
 * 2) pick the chicken up and lay it on the ground on its back, stretching out its neck.  With your finger, slowly draw a line in the dirt straight out from the chicken's beak about 1 to 2 feet, then slowly remove your other hand from the chicken.  Once hypnotized, the chicken will typically remain physically frozen until it is touched or startled.

It may seem cruel to toy with a chicken's brain this way. However, if you need the chicken out of your way for some reason (while you service its pen, for instance) and you don't have anywhere else to put it, this is a useful technique.
 * "Note: When I was little I remember my brother and I would use a technique similar to those described above in order to 'hypnotize' our chickens. It was very entertaining for us as children, and was fun to show to our friends, but I seem to recall our father (who was a farmer) being irritated at us for bothering the chickens in this way. If I remember correctly, he claimed it made the chickens uneasy and negatively affected their egg production. However, I have no idea whether or not this is true. In any case, I would guess that if you have to chase your chickens all over the place and pin them down before you can hypnotize them, it probably is more cruel than anything. On the other hand, if they are 'pets' and trust you (if they are handled easily), it may not have any adverse effect. This is, of course, only in theory."
 * -Anonymous

Random Facts
Chickens know an item still exists even when it is out of sight.

When a chicken softly chirps/clucks around you it is happy

When chickens run away from your hand they think they are more superior than you and therefore do not want to be petted (you can easily force pet them of course) ...vice versa if the chicken lets you pet them

Good Entertainment
Keep wild bird feed outside your house and watch your chicken befriend the birds... or chase away the poor bird visitors!

title: Raising Chickens/Other information


text:
Talk:Art History

write an art history paper].
 * Here's an external link that may be useful:
 * [http://www.skidmore.edu/academics/arthistory/paperpg/index.html How to
 * Another:
 * Alexa's top Art History websites by visitor.

Comments about this collaboration:
 * http://www.futureofthebook.org/blog/archives/2005/10/can_we_write_gr.html

title: Talk:Art History


text:
Mambo Open Source/Creating multiple pages per content item

This article explains how to use the multi-page Mambot to create multiple pages with one single content item.

What is it?
You have probably seen the "Mambo License Guidelines" text that comes with the standard mambo installation. There, you have a page with a table of contents, and a "next page" button at the bottom - within one content item.

This is done using the page break Mambot. The process is quite simple.

How to use it
It work like all other Mambots - you insert a tag and the page breaks. To create a simple page break, do this:

This creates a new page from the content post this tag. You can use multiple tags in one content item, to create multiple pages.

By default, the pages is named "Content item title", "page 2", "page 3" and so on. You can create your own title for each pagebreak by doing this:

Insert any title you like here, but be sure to not use quotes (") anywhere in the tag.


text:
Marinette Aluminum Boat Maintenance/Engine and Transmission/Repowering

The original 318 Borg-Warner trans should be compatible with the 350. Many people think you can change your prop rotation by making an adjustment on the trans. You can change the rotation of the trans by backing off the 4 bolts on the front of the trans & spinning the pump 180 degrees. This must be done if the arrow at the top doesn't show the same rotation that the flywheel moves. If the arrow points the opposite direction as the flywheel's rotation, the trans won't work. You can not change the prop rotation by just turning over the trans pump; that move is made only to let that trans work with that engine. You will notice that when you turn the spline on the front of your trans in one direction, the other end turns the same way. If you go to a 1.5 to 1, the back will turn the opposite as the front. That may be the way to get the rotation you want. I'm curious why you want left hand rotation? Why would it matter in a single inboard? The marina made new exhaust manifolds out of 4" stainless tubing. The motor mounts are adjustable, your motor will still sit on the stringers. Drill new holes in the new location and bolt the motor down once the couplers on the shaft & trans have been perfectly aligned. Use hardwood shims under mounts (or the proper rubber) to reduce noise & vibration. VERY important: measure the length of the new motor & compare it to the 318. Because the 350's were a few inches longer than my 318's, the marina put 1 to 1 trannys on my new motors instead of replacing my 1.5 to 1. Their reason was that they would have had to cut the bulkheads in front of the motors to make room. I was not happy with the results and last fall I decided to do something about it. I cut the bulkheads & mounted 1.91 to 1 trannys on after removing the small direct drives. Now my motors are just sitting on the stringers waiting for a warm day when I have the time to line them up, bolt them down & reconnect everything.


text:
Marinette Aluminum Boat Maintenance/Ventilation

 * /Cabin/
 * /Engine/


text:
Marinette Aluminum Boat Maintenance/Ventilation/Engine

There should be six deck vents on a 28 Express. Two face forward, and four face aft. Ducts should be attached to each running to a low point in the bilge. If no where else, a duct should be attached to the bilge blower, and run to a low point to ensure that any gas fumes are drawn out.

While underway, the bilge blower need not be run because the four aft-facing vents will cause suction exhaust while the two forward-facing vents supply intake pressure.


text:
User:Fuzheado

See me on English wikipedia

title: User:Fuzheado


text:
User:D. F. Schmidt

See w:User:D. F. Schmidt for profile.

title: User:D. F. Schmidt


text:
Marinette Aluminum Boat Maintenance/General Mechanical Info/Windows

Here's an idea for window tracks: don't replace the track unless the track itself is shot. I just found teflon tape about 1/8" thick and 1/4" wide at a plastics supplier in my area (Reed Plastics, Rockville, MD). Using a sharp knife I was able to trim the tape to the width of my track and slide the tape under the glass. This is not the teflon tape used for plumbing to wrap pipe threads.. it's thicker, as noted above, 1/8". It cost me about $23 for a roll that weighed about 1 1/2 lbs -- Reed Plastics sold it by the pound -- don't ask why.

However. . . .if you still want track.. About 45 feet (black) costs $2/ft from Sima Marine in Eastlake, OH. I am not using it because I found the teflon tape will work for me and I don't have to replace all the track (my track is aluminum which isn't available any longer).

Window channels: it's a two person job to remove them and three persons to replace. Not that the panels are heavy, you just run out of hands while balancing hefty pieces of expensive glass.

You'll find just a few screws at the tops/bottoms/sides. On top, be on the lookout for a small bumper that prevents the non-moveable piece of glass from sliding around. It is held in place by one small screw.

After the screws are removed, you can fairly easily wiggle out the lower channel. A suction cup of the type sold to hold onto the hull while cleaning your boat from a dinghy (I think one brand is Holdtite) will come in handy to get a firm grip on the glass. You and partner lower the whole thing safely.

You may be able to get the unit back in place with two people -- I found a third person indispensable for just that few seconds where balance is required.

John Althouse of Marinette, Inc. sells the aluminum channels as well as the plastic ones and if you utilize aluminum, do it -- you will never have to replace them. Plastic channels will get killed by the sun after a few years. When things go back in place, use a good amount of caulk and you're done. One other thing you will want to check is that there are drain openings at both ends of the channels. A small 45-degree cut across the very end of the two upright, outer divider pieces will do that easily.

It's about a 15 to 30 minute removal job and allow the same to put things back in place plus a few minutes to cut the channels to the correct length.

One other thing, you may find that one or more screws are stuck in place. Drill them out using a very slow drill speed, or use a screw extractor tool for stuck screws. It is worth the $15 or so for the tool.


text:
User:Magbatz~enwikibooks

Yo.

title: User:Magbatz~enwikibooks


text:
User talk:Magbatz~enwikibooks

Come introduce yourself at the new users page. If you have any questions, you can ask there or contact me personally.

Thanks for helping to fight vandalism on Wikibooks. We need more people like you, your contribution is greatly appreciated.:) (Donovan|Geocachernemesis|Interact) 02:57, 29 July 2005 (UTC)

Your account will be renamed
Hello,

The developer team at Wikimedia is making some changes to how accounts work, as part of our on-going efforts to provide new and better tools for our users like cross-wiki notifications. These changes will mean you have the same account name everywhere. This will let us give you new features that will help you edit and discuss better, and allow more flexible user permissions for tools. One of the side-effects of this is that user accounts will now have to be unique across all 900 Wikimedia wikis. See the announcement for more information.

Unfortunately, your account clashes with another account also called Magbatz. To make sure that both of you can use all Wikimedia projects in future, we have reserved the name Magbatz~enwikibooks that only you will have. If you like it, you don't have to do anything. If you do not like it, you can pick out a different name.

Your account will still work as before, and you will be credited for all your edits made so far, but you will have to use the new account name when you log in.

Sorry for the inconvenience.

Yours, Keegan Peterzell Community Liaison, Wikimedia Foundation 23:24, 17 March 2015 (UTC)

Renamed
 This account has been renamed as part of single-user login finalisation. If you own this account you can |log in using your previous username and password for more information. If you do not like this account's new name, you can choose your own using this form after logging in: . -- Keegan (WMF) (talk) 05:13, 19 April 2015 (UTC)

title: User talk:Magbatz~enwikibooks