In the research of Hoenig,62, 63 and 65 Reker,65 and colleagues v

In the research of Hoenig,62, 63 and 65 Reker,65 and colleagues variables such as the availability of an adaptive kitchen, the number of disciplines present at chart rounds, and the physical therapist caseload were included. In Donabedian’s scheme,66 process is defined as what is actually done to or with the patient within the overall structure. It includes processes typically considered “clinical” and indirect care, “guest services,” and administrative

procedures. In the short term, structure dictates process, whereas both structure and process affect outcomes. To date, Hoenig,62, 63 and 65 Reker,65 and colleagues have not addressed process, at least not in the meaning of that term considered here. The long-standing interest of Strasser et al67, 68 and 69 in delineating characteristics of the rehabilitation CAL-101 molecular weight team and establishing their impact on patient outcomes is also focused on classifying the structure of rehabilitation. Other attempts to characterize rehabilitation services using a combination of characteristics such as location, Epacadostat molecular weight general thrust of activities, and program type have been published.70

Most of these are ad hoc efforts to impose order on the unruliness of existing services, without the benefit of (explicit) relevant theories.71, 72, 73 and 74 Structure elements and process elements other than direct care, such as chart rounds and other coordinative structures/processes, can explain changes in patient outcome only because they are necessary but not sufficient conditions for the delivery of treatments.75 One could imagine a state-of-the-art

rehabilitation facility with a well-trained staff meeting 24 hours a day busy coordinating care, with no one ever seeing a patient.75 Thus, to explain what is going on in the black box and use the information to explain outcomes, we need to do more than classify structure and the indirect categories of process. Even more recent than the work of these authors is research that has inductively (or “bottom up,” in the terminology of DeJong et al2) created classifications of the therapy process (what is actually done with, to, and for patients) as part of practice-based evidence (PBE) studies of inpatient rehabilitation. Relevant articles have been published of tuclazepam rehabilitation for stroke,76, 77 and 78 knee or hip replacement,79 and 80 spinal cord injury (SCI),81 and 82 and traumatic brain injury (TBI).83 and 84 In all of these projects, clinicians developed lists of “active ingredients” used in their practice: treatments (“activities”) that they presumed to have a significant impact on outcome, with subcategories and modifiers (“interventions”) added as appropriate. Data collection forms allowed them to characterize each treatment session in terms of the “activities” delivered, and the quantity of each, mostly in terms of minutes.

61, t(20) = 3 60, p =  0020] and Inhibition [β =  35, t(20) = 2 1

61, t(20) = 3.60, p = .0020] and Inhibition [β = .35, t(20) = 2.18, p = .0421] were individually

significant predictors. Subitizing slope remained a non-significant predictor when it was entered into the regression with only the Inhibition ability measure [R2 = .368, F(21,2) = 6.13, p = .0080; Subitizing: β = −.19, p = .34; Inhibition: β = .48, p = .0297]. We have contrasted five theories of DD using several measures of the MR theory and alternatives. We found robust evidence for impaired visuo-spatial WM and STM in DD and also found evidence for impaired inhibition function in DD. Data did not support the MR theory of DD. In contrast, verbal STM/WM were intact including both digit and word span. Several studies reported

similar dissociation between ATM/ATR assay spatial and verbal STM/WM in DD (McLean and Hitch, 1999, Andersson and Ostergren, 2013, Schuchardt et al., 2008, Ashkenazi et al., 2012 and Passolunghi and Mammarella, 2010). Other studies reported impaired verbal STM/WM in DD (e.g., Geary et al., 1991 and Geary et al., 2012). A potential dissociating feature seems to be that studies not reporting verbal WM differences noted that they attempted to match DD and control groups on reading and/or verbal performance (McLean and Hitch, 1999, van der Sluis et al., 2005, Schuchardt et al., 2008, Andersson and Ostergren, NVP-BGJ398 order 2013, Ashkenazi et al., 2012 and Passolunghi and Mammarella, 2010). Our DD group also only included children with pure DD with no dyslexia and with normal reading/verbal IQ. This probably explains the lack of verbal memory differences. In fact, Schuchardt et al. (2008) tested both visual and spatial STM in DD, dyslexic, DD + dyslexic and normal populations and found only visual STM impairment in DD and only verbal STM impairment in dyslexics. Hence, it seems that when reading and verbal

function is preserved, that is, in pure DD, a crucial impairment concerns visuo-spatial WM and/or STM. At least three neuro-imaging studies provide supporting evidence to our findings. Rotzer et al. (2009) demonstrated weaker IPS activation in a spatial WM task in DD than in controls. Rykhlevskaia et al. (2009) reported reduced Olopatadine gray matter density in DD not only in the IPS but also in the fusiform, lingual, parahippocampal gyri and in the hippocampus, areas which may be related to encoding complex visual stimuli. Davis et al. (2009) did not find any IPS differences between DD and controls in an approximate calculation task but reported differences in various brain regions associated with WM and cognitive control functions. Visuo-spatial memory probably provides a mental workspace for various transformations and operations crucial for mathematics. Visuo-spatial strategies and heuristics can be used even in seemingly non-visual tasks, e.g., when adding or subtracting numbers, operations and operands can be imagined/conceptualized along a number line.

Particulate matters critically prevented ARB from generating curr

Particulate matters critically prevented ARB from generating current in anode biofilm, showing 76% reduction of current density. Direct utilization of raw sewage improved current density up to 20%, indicating the significance of fermenters and their syntrophy with ARB. This work was financially supported by Natural Sciences and Engineering AZD0530 Research Council of Canada (NSERC) entitled “Development of energy-efficient wastewater treatment technology using principles of microbial fuel/electrolysis cells” (NSERC DG #402045-2011) and NSERC CRD entitled “Energy recovery from food industry wastewater using microbial electrochemical cells and anaerobic membrane

bioreactor. “
“First time, ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) was isolated from Ferula foetida for its structure determination, and its name was based on the botanical name of plant [27]. In 1925, FA was chemically synthesized and structurally confirmed by spectroscopic techniques, depicted the presence of an unsaturated side chain in FA, and also existence of both cis and trans

isomeric forms [14] and [56]. The double bond present in the side chain is subjected to cis–trans isomerization ( Fig. 1), and the resonance stabilized phenoxy radical accounts for its effective antioxidant activity. It catalyzes the stable phenoxy radical formation upon absorption of ultra-violet light, which gives the strength to FA for terminating buy Dapagliflozin free radical chain reactions. FA is an enormously copious and almost ubiquitous phytochemical phenolic derivative of cinnamic acid, present in plant cell wall components as covalent side chains [66]. Collectively with dihydroferulic acid, it is the component of lignocelluloses, where it confers rigidity to the cell wall by making the crosslink between polysaccharides and lignin. It has been found that FA is linked with a variety of carbohydrates as glycosidic conjugates, different esters and amides with a broad range of natural products [73]. It makes esters by binding with oxyclozanide a variety of molecules such as polysaccharides,

long chain alcohols, various sterols of plant, tetra-hydroisoquinoline-monoterpene glucoside, a cyanogenetic glycoside and an amino-hydroxy-cyclopentenone, flavonoids and different types of hydroxycarboxylic acids including gluconic, tartaric, malic, hydroxycitric, tartronic, quinic, and hydroxy fatty acids [9], [17], [24] and [25]. The aim of this review is to provide the organized outline about natural sources, metabolism, and different applications of FA in biomedical, pharmaceutical, food, cosmetic and other industries, which will provide vast information to a wide range of researchers, working on the different applications of natural products. FA is commonly found in commelinid plants (rice, wheat, oats, and pineapple), grasses, grains, vegetables, flowers, fruits, leaves, beans, seeds of coffee, artichoke, peanut and nuts [8], [47], [48], [49], [72] and [85].

4B) The treatment with OA at 300 μM decreased the lipids content

4B). The treatment with OA at 300 μM decreased the lipids content by 56% compared to vehicle. The association of OA with PUFA (ω-3 and ω-6) increased the NL content compared to OA at 300 μM by: 30% and 25% for EPA and γA, respectively, selleck inhibitor both at 50 μM and 37% for LA at 100 μM (Fig. 4C). OA associated with ω-3 and ω-6 PUFA did not alter the ROS production compared

to OA (Fig. 4D). FFA are important mediators of endothelial dysfunction, atherosclerosis and cardiovascular disease (Azekoshi et al., 2010). In this study, SA increased the EC death and ROS production, without affecting NL content. ω-3 PUFA did not protect EC from death induced by SA but increased the lipids content and decreased the ROS production. In contrast, ω-6 PUFA reduced cell death induced by SA, increased lipids accumulation and decreased ROS content. SA-induced cell death confirms the results obtained in previous studies (Artwohl et al., 2004 and Rioux and Legrand, 2007. Artwohl et al., 2008 showed that SA causes apoptosis of various EC lines selleck (HUVECs, HAECs, and EPCs HRECs). Saturated FA (stearic and palmitic acid) are the most abundant FFA in plasma (Hagenfeldt et al., 1972) and the major components of parenteral and enteral nutritional formulations, so the potential for adverse vascular effects initiated by saturated FA are cause for clinical concern. EC apoptosis plays an important role in endothelium

dysfunction and directly affects blood thrombogenicity through

the release of apoptotic microparticles into the bloodstream (Blann et al., 2009). ω-3 PUFA have important anti-inflammatory and anti-apoptotic properties (Massaro et al., 2008 and Suphioglu et al., 2010). Artwohl et al. (2008) showed that low EPA levels (5–20 μM) inhibits SA-induced apoptosis in HUVEC, HAEC, EPC and HREC. In our study, EPA increased the percentage of viable cells without affecting DNA fragmentation Endonuclease induced by SA. However a marked decrease in the proportion of cells with death signs was found in the treatment with ω-6 PUFA and SA. No significant association between LA (ω-6 PUFA) intake (or tissues levels) and CHD risk (Esrey et al., 1996 and Pietinen et al., 1997) and no consistent relations between stroke and LA intake (He et al., 2002 and Sauvaget et al., 2004) have been found. Herein, ω-6 PUFA protected EC from death induced by SA. SA did not affect EC NL content, but it does so in association of SA with ω-3 or ω-6 PUFA. Thus, PUFA, specially ω-6, may protect from SA-induced EC death by incorporating FA into NL (Cnop et al., 2001). ROS have been implicated in the initiation and progression of atherosclerosis. ROS can oxidize lipoproteins, limit the vascular availability of antiatherosclerotic NO, and promote vascular expression of cytokines and adhesion molecules. Treatment of ECV-304 cells with SA for 30 min led to an increase of ROS.

Aspartate

kinase in an allosteric enzyme has a wide appli

Aspartate

kinase in an allosteric enzyme has a wide applications in biotechnological industry and mainly responsible for the biosynthesis of amino acids. The efficiency of biosynthesis is largely depends AG-014699 concentration upon quality of strains used in microbial fermentation. The understanding of the metabolic pathways of lysine biosynthesis and regulation through metabolic engineering helps to the effective strain development. The enzymatic action and mechanism of inhibition of aspartate kinase is well understood through large number of crystallographic and biochemical analysis. However, continued efforts have been made to understand the mechanism and regulation of aspartate kinase from suitable organism to define the successful construction of industrially producing strains. In the aspartate kinase, the binding of lysine to the regulatory domain triggers the structural rearrangements for formation of tetrameriztion of the biological homodimers (Fig. 5). Concurrently, the allosteric transition of the catalytic domain leads to blocking of the nucleotide binding site and eventually loss of enzymatic activity. Cetuximab concentration In CaAK, the mechanism of inhibition follows the similar

fashion when compare to the other class I AK enzymes. Mainly, most of the structural elements which are implicated in probing the catalytic, substrate-binding and allosteric mechanisms are conserved. Secondly, the way of binding of lysine molecules at the interface of the two ACT1 domains from different monomers provides to identify the residues which are implicated

in lysine interactions. This structural observation can be tested by studying inhibition profile of lysine in CaAK. Further, site-directed mutational analysis of these residues makes it possible to engineer the lysine binding site. This eventually helps to manipulating Histone demethylase the biosynthesis of amino acid to increase the amino acid content and nutritive value in crops. Recently, much work has been done to metabolically engineered crops and grains with enhanced amino acid levels [42] and [43]. Thirdly, the mechanism of structural transition to tetramer assembly is similar way to the other three different crystallographic environments. However, the tetramer configuration of CaAK is totally different than the other known AK structures. The improved understanding plant amino acid biosynthesis pathways potentially helps to design strategies employed for metabolic engineering. Finally, most of the residues which are implicated in probing the catalytic, substrate-binding and allosteric mechanisms are also conserved in pathogenic CtAK and CpAK. Therefore, the structure we reported here will provide useful information for drug design targeting on pathogenic AKs. AK is a key enzyme controlling the biosynthesis of lysine. The allosteric regulation of AK represents a typical mechanism of metabolic control of strong rigid node, i.e.

Typically, modern WBMs contain fresh or salt water as the base fl

Typically, modern WBMs contain fresh or salt water as the base fluid and barite (BaSO4) or ilmenite (FeTiO3) as weighting agent. Clays or organic polymers are incorporated to create a homogenous fluid. Other chemicals (e.g. potassium formate and various glycols) are added to achieve viscosity control, shale stability, cooling and lubrication (c.f. Hudgins, 1994 and Neff, 2005). There is a vast literature on the acute toxicity of WBM components, the presentation of which goes beyond the scope of this review, but in general the acute toxicity of WBM is low (Neff, 1987). Monitoring in the NS (Daan and Mulder, 1993, Olsgard and Gray, 1995, Park et al., 2001 and Renaud et al.,

2008) has not revealed any in situ effects of WBM cuttings on sediment macrofauna community structure, implying that any selleck screening library such effects, if present, will be confined to bottoms inside the innermost stations in these studies, i.e. nearer than 25–250 m from the discharge point. The effects mechanisms of WBM cuttings after sedimentation have been studied in several laboratory and mesocosm experiments. Dow et al. (1990) reported Selleck Sorafenib that redox values were depressed for 3 months in sediments mixed with WBM cuttings in an onshore tank system. Schaanning et al. (2008) exposed undisturbed fjord sediment core samples to thinly sedimented

layers of ilmenite based WBM cuttings. Iron sulphide precipitated under caps thicker than 10 mm. Sediment oxygen (SOC) and nitrate consumption, and release of silicate increased immediately under a 12–46 mm cap. The SOC peaked after 9 days and, for most treatments, returned to background levels after 3 weeks. The increase was positively correlated with cap thickness. A 3 mm cap on top of undisturbed sediment box cores from 200 m depth gave no increase in

SOC, and macrofauna biomass and community structure did not change during a 3 month experiment. In a repeat experiment a 3 mm layer of WBM cuttings caused elevated SOC for more than 3 months and 6–24 mm layers for more than 6 months ( Trannum et al., 2010). After 6 months the macrofauna species richness, abundance, biomass, and diversity were negatively correlated with layer thickness. Corresponding layers with natural sediment did not affect the fauna. Trannum (2011) concluded that the most plausible reason Axenfeld syndrome for the fauna effects was sediment oxygen deficiency due to degradation of organic WBM compounds, presumably mud glycol, although chemical toxicity may have played a role as well. It is not likely that glycol degradation will cause the same effects around a cuttings discharge since the glycol most probably will dissipate before the cuttings reach the bottom. Trannum et al. (2011) found only slight differences in macrofauna recolonization in defaunated trays with coarse and fine sediments capped with 6 and 24 mm ilmenite based WBM cuttings deployed in situ at 200 m depth in the Oslofjord, Norway.

In some resource-rich countries, the effects of an increasing age

In some resource-rich countries, the effects of an increasing age of the population may increase demand. In resource-limited countries, imbalances in access to (safe) blood components may change as improved access to health care occurs. The need for blood and blood products is growing every year and large numbers of patients who require life-saving support with blood and blood

products still do not have access to them. It is therefore essential that all countries have the national capacity to collect blood, plasma and cellular components of optimal quality and safety from voluntary, non-remunerated donors in order to meet the national needs for blood components for transfusion and PDMPs. For the supply of PDMPs in particular, in the long term it will not be feasible for a small number of countries to collect sufficient plasma to produce enough PDMPs to meet global needs [7]. In most GSK2118436 nmr countries the estimates of the need for red cells are used to set the

target for the collection of blood donations. If there are minor shortfalls, measures are taken to minimize use until demands are met, usually by increased collections. However for plasma, the recovered plasma (the by-product of whole blood collections) is usually sufficient to meet the demand for clinical use of plasma, but insufficient to meet the demand for PDMPs. Depending DAPT in vivo on the country, the response to such a short fall can be to increase the number of plasma collections by plasmapheresis (and in some countries to pay the donors), or to buy plasma to supplement the domestic supply for

fractionation, or to buy PDMPs. To achieve self-sufficiency in plasma derivatives requires a plasma-driven collection based on plasmapheresis, which is expensive and results in products that are uncompetitive with commercial product pricing. Data Pembrolizumab from the US, Germany and Japan all showed an ageing trend in the blood donor pool. There could be more difficulties in recruiting and retaining adequate number of blood donors, affecting the supply of blood and blood products. There is concern that as the population ages, the number of donors will decrease. Ageing populations and increasingly stringent donor selection criteria have reduced the pool of eligible donors. Blood, plasma and cellular blood components, and other therapeutic substances derived from the human body should not be considered as mere ‘commodities’. Donated blood that is provided voluntarily by healthy and socially committed people is a precious national resource. Governments should be accountable for ensuring a sufficient supply of products from these special resources which are and will remain limited by nature. The availability and safety of the supply, the safety of both donors and recipients and the appropriate use of blood, plasma and cellular blood donations are and must remain a public affair.

In WHII a set of non-redundant IRS1 SNPs independently associated

In WHII a set of non-redundant IRS1 SNPs independently associated with T2D was determined by variable selection, Pictilisib purchase using stepwise regression based on the Bayesian information criterion [19]. An additive genetic model was assumed. Of the 23 SNPs, 18 with p < 0.25 on univariate analysis were initially selected for possible inclusion in the multivariate model. Statistically significance was taken as p < 0.01. Following the suggestion of Rothman [20], this more conservative p-value was used in preference to correcting for multiple comparisons. Baseline clinical, biochemical,

and the genetic characteristics of the subjects in WHII and NPHSII are presented in Supplementary Table 3. Subjects who went on to develop T2D were more likely to be obese and hypertensive, and in WHII had, as expected, higher baseline fasting glucose and insulin levels, higher percentage of HbA1c and a higher HOMA-IR

index (all p < 0.001). There were no significant genotype differences between T2D cases and controls; however, in WHII the rs2943641T allele was associated with lower fasting insulin (p = 0.04) and HOMA-IR (p = 0.03) in a mixed regression model over all study phases while adjusting for age, gender, BMI and study phase ( Supplementary Table 4). The overall characteristics of the T2D patients in UDACS, EDS and PREDICT by ethnic group and rs2943641 genotype, are presented in Supplementary Tables 5 and 6. In comparison to European whites, patients of Indian Asian origin had an earlier age of onset of the disease, a lower prevalence of obesity E7080 mouse and were less frequently smokers and carriers of the rs2943641T allele (Supplementary Table 5). No differences in any baseline biochemical measures, including fasting glucose and HbA1c, were observed across genotypes in the two ethnic groups (Supplementary Table 6). In EARSII, there was no ‘case’/‘control’ heterogeneity in age, BMI, BP, fasting glucose or rs2943641 genotype distribution

(Supplementary Table 3) and therefore, ‘cases’ and Meloxicam ‘controls’ were combined in subsequent analyses. No significant differences across genotypes for any of the fasting biochemical variables were observed in this cohort of young individuals; however, rs2943641T allele was associated with lower insulin levels after OGTT (Fig. 1). The effect of rs2943641T appeared to be dominant, with T-allele carriers having area under the curve (AUC) for insulin 13.3% lower than CC homozygotes (p = 0.003). The difference among genotypes was significant at 60 and at 90 min after the OGTT (p = 0.004 and p = 0.03, respectively, Fig. 1). There was no evidence for heterogeneity between ‘cases’ and ‘controls’ for AUCinsulin (p = 0.47), nor were any differences between genotype groups for AUCglucose ( Supplementary Table 7).

1) Comparing transcriptomes of whole bodies and larvae of P pol

1). Comparing transcriptomes of whole bodies and larvae of P. pollicipes could Galunisertib in vitro contribute to the understanding of the complexity of their ontogenetic adaptation to a sessile mode of life and the evolution of cement proteins in cirripeds. EST generation and identification of specific genes of P. pollicipes provide a more general understanding of these crustaceans.

The only small number of genes that could be functionally annotated in this study indicates that our knowledge about goose barnacle physiology and biological processes is insufficient. The analysis of the fraction of identified unigenes already highlights a large number of genes that are of interest for future research concerning protein evolution (with focus on cement gland proteins) and physiology (involving adaptational and ontogenetic processes). We thank Iago F. Meilán for computer

support. This work was funded by a CTM2007-62034 grant from the Spanish government (Ministerio de Educación y Ciencia) and, a 10MMA103008PR grant by Xunta de Galicia. A. Perina was supported by a scholarship from Ministerio de Economía y Competitividad, Subprograma de Formación de Personal Investigador (FPI) (Spain). B.M. von Reumont was funded by the German Science Foundation (DFG grants: RE 3454/1-1 and RE 3454/1-2). “
“Despite the global economic and environmental importance of salmon, genomic Y-27632 mouse resources for the study of these anadromous fishes are limited. Here we use RNA-Seq to characterize the transcriptome of steelhead (ocean-going Oncorhynchus mykiss). The use of next-generation platforms for de novo sequencing of transcriptomes has been repeatedly demonstrated to be suitable for marker and gene discovery, comparative analysis, and gene expression analysis. For example, high throughput sequencing has been used for transcriptome assembly and annotation in several fishes including sea bream, guppy, Atlantic cod, mud loach, and rainbow

trout ( Calduch-Giner et al., 2013, Fraser et al., 2011, Johansen et al., 2011, Long et al., 2013 and Salem et al., 2010). Rainbow trout and steelhead are different life-history forms of the same species (O. mykiss), however, the freshwater-resident rainbow trout and ocean-going steelhead differ behaviorally, Epothilone B (EPO906, Patupilone) phenotypically, and physiologically ( Hale et al., 2013 and Hayes et al., 2012). In 2010, a 454-based transcriptome was published for rainbow trout ( Salem et al., 2010), but no transcriptome data are currently available for steelhead. The aim of this study was to assemble, annotate, and analyze a high quality reference transcriptome that will enable researchers to assess gene expression levels, conduct comparative analyses, and identify and utilize molecular markers in the anadromous O. mykiss steelhead. The steelhead for this study were collected from the Hood River, in Oregon.

These findings indicate that neurons in the SEF, pre-SMA, and SMA

These findings indicate that neurons in the SEF, pre-SMA, and SMA may proactively regulate movement initiation by adjusting the level of excitation and inhibition of the occulomotor

and skeletomotor systems based on prior performance and anticipated task requirements. This proactive activity in medial frontal cortex is particular interesting, because it could also underlie speed-accuracy tradeoffs in general 54 and 55••]. In addition to controlling the overall responsiveness across trials, the activity in medial frontal cortex could also modulate the momentary responsiveness within an individual trial. The latest decision-making models contain a rising urgency signal that slowly lowers the evidence threshold at which a choice is made 56 and 57]. Such a hypothetical signal explains human and monkey behavioral data well, but no neural correlate of the urgency signal

has been found so far. Selleck Ponatinib It seems worthwhile to test if neurons in the medial frontal cortex might be the source of the urgency signal. However, while proactive control might play a role in decision making, the same might not be true for reactive control mechanisms [58•]. Voluntary behavior requires proactive and reactive control mechanisms that ensure our ability to act independently of habitual and innate response tendencies. Electrophysiological experiments using the stop signal task in humans, monkeys, and rats have uncovered Apoptosis inhibitor a core network of brain structures that is essential for response inhibition. This network includes motor and premotor cortex, basal ganglia, and spinal interneurons. It is shared across mammals and seems to be conserved throughout their evolution. However, the exact function of the different neurons and local circuits in this larger network is still unclear. Most importantly, there is still no consensus on the neural mechanism by which motor responses are inhibited. At the same time, there is new

research directed at the interaction between inhibitory control mechanisms with other control mechanisms in the brain. This research will be important to understand how response inhibition is used and controlled itself to achieve the overall goals of an agent in its day-to-day behavior. N-acetylglucosamine-1-phosphate transferase Making progress will require further investigations using the stop signal paradigm. Experiments in behaving monkeys will likely stay at the core of this enterprise. Monkeys have exceptional behavioral flexibility, which makes them ideal models to study complex control processes. They are also the closed model of human behavior and physiology that is available. At the same time, new rodent animal models will allow to investigate and manipulate neural circuits in unprecedented detail. The future is bright for this exiting field of neuroscience. The author thanks E.E. Emeric for helpful comments to this review. This work was supported by the National Eye Institute through grant R01-EY019039 to VS.