On this basis these excitation energy budgets were compared and c

On this basis these excitation energy budgets were compared and contrasted in the context of the three complementary deactivation processes. The results of these calculations will now be analysed. We present the results of our model calculations for June (the northern hemisphere summer) and January (the northern hemisphere winter), divided

into three climatic zones, in this section and in Annex 3. By way of example Figure 3, Figure 4 and Figure 5 in subsection 3.1 show plots of the vertical distributions of quantum yields Φ (in the general, broader this website sense according to definitions (2), (4) and (6) respectively) of all three processes deactivating pigment molecule excitation energy in sea waters of different trophic PLX4032 order types. Subsection 3.2, on the other hand, gives the ranges of seasonal variability of the components of the phytoplankton pigment excitation energy budget on the basis of the same quantum yields Φ averaged for the euphotic zone (Figure 6). The graphics and description cover the main features of the quantum yields, but the details of the calculations of selected characteristics of all four yields/efficiencies of the three processes are given in tabular form in Annex 3. The differentiation in the vertical distributions of the three elements of

the phytoplankton pigment excitation energy budget is due, directly or indirectly, to the variability in irradiance conditions at different depths in the sea. This is illustrated in Figure 3, Figure 4 and Figure 5, which show depth profiles of the quantum yields Φ of all three processes in waters of different trophic types. We can see from these plots that the quantum yield of the conversion

of pigment molecule activation energy into heat ΦH, (see plots b1, b2, b3 and b4 in Figure 3, Figure 4 and Figure 5) is much or very much greater than the quantum yields of fluorescence Φfl (plots a1, a2, a3 and a4 on these figures) and photosynthesis Φph (plots c1, c2, c3 and c4 on these figures) in every possible configuration of environmental factors in different geographical regions and seasons DOCK10 of the year. Values of ΦH begin at ca 0.61 in the lower layers of eutrophic waters and increase with decreasing trophic index Ca(0) and also with decreasing depth (i.e. with irradiance increasing towards the surface), especially in eutrophic waters though less so in mesotrophic ones, rising in some cases to 0.9 and even more. Most of the light energy absorbed by pigments is converted into heat. Quantum yields of heat production ΦH are from ca 2 to 10 times greater than those of photosynthesis Φph in the same waters and from as much as ca 20 to 150 times greater than those of fluorescence Φfl. Φfl and Φph vary with depth in a slightly different way than ΦH.

A smaller study (N = 39) by the same group reported no difference

A smaller study (N = 39) by the same group reported no differences in patient survival, graft survival, or BPAR incidence between patients receiving SRL/standard TAC and those receiving SRL/reduced TAC (Table 1) [49]. However, 38% and 6% of patients on standard TAC were discontinued due to TAC nephrotoxicity and thrombotic microangiopathy, respectively. Several factors may have contributed to the apparent increased nephrotoxicity, including the study population (79% black), use of kidneys from deceased

donors, and high incidence of delayed graft function (59%). Two-year data compared similar regimens in 132 live donor renal allotransplant patients [50]. The efficacy outcomes were patient survival and graft

survival, BPAR incidence, and graft function. At 2 years, renal function BAY 80-6946 was significantly improved with the TAC-free regimen (SRL/MMF), compared with EX527 the SRL/TAC-sparing regimen, as measured by serum creatinine level and calculated GFR (both p < 0.05; Table 1). In addition, the rate of acute rejection was numerically lower in the TAC-free group (13.5% vs 18.5%; p = ns). Three-year results from a long-term study (N = 150) comparing SRL/TAC, MMF/TAC, and SRL/CsA are also available [51]. At 3 years, patient survival, graft survival, and BPAR incidence did not differ significantly among the 3 groups (Table 1), although the latter showed a trend in favor of MMF/TAC (p = 0.07). Although renal function (as measured by creatinine) was acceptable in each of the 3 groups, the MMF/TAC group was statistically more favorable when compared with SRL/CsA at 12, 24, and 36 months

(p = 0.02, p = 0.05, Fenbendazole and p = 0.04, respectively) and SRL/TAC at 24 months (p = 0.05). Rates of NODM by year 3 were lowest with MMF/TAC (11% vs 27–31% in other groups). Longer-term follow-up of the same study (median of 8 years) showed significant differences or trends with respect to the above endpoints that consistently favored MMF/TAC over the other regimens [52]. Viral infections and need for antilipid therapy were significantly lower with MMF/TAC versus the other regimens combined (p < 0.05), and the incidence of NODM was numerically lower with MMF/TAC (Table 1). Similar long-term findings were reported by Chhabra and colleagues [53]. In their study, 82 renal transplant recipients were followed for up to a mean of 8.5 years. MMF/TAC provided better efficacy and safety than SRL/TAC, with significant differences seen for graft survival and GFR (Table 1). In summary, results to date are derived mainly from single-center studies, and thus more robust data are needed to confirm the preliminary findings. Two small-scale studies compared reduced-dose TAC versus standard-dose TAC, when used in combination with SRL [47] and [49].

Msi is expressed in neural tissues in both the central nervous sy

Msi is expressed in neural tissues in both the central nervous system (CNS) and PNS ( Okano et al., 2002 and Okano et al., 2005). Members of the Msi family include Drosophila Msi, and ascidian MUSASHI from Halocynthia roretzi and Ciona intestinalis ( Kawashima et al., 2000) in invertebrates. Vertebrate Msi family members include the frog (Xenopus laevis) nervous system-specific RNP protein-1 (Nrp-1) ( Richter et al., 1990 and Sharma Ixazomib mouse and Cline, 2010), torafugu (Fugu rubripes) Msi-1 ( Aparicio et al., 2002), chicken (Gallus gallus) Msi1 ( Asai et al., 2005 and Wilson

et al., 2007), mouse (Mus musculus) Msi1 ( Sakakibara et al., 1996), and human (Homo sapiens) MSI1 ( Good et al., 1998). The mouse Musashi2 (Msi2) exhibits high similarity to Msi1 in primary structure, RNA-binding specificity and CNS expression pattern. Msi2 acts cooperatively with Msi1 in the proliferation and maintenance

of NS/PCs (Sakakibara et al., 2001). Human MSI2 was identified during the course of research examining disease progression in chronic myeloid leukemia (Barbouti et al., 2003, Ito et al., 2010 and Kharas et al., 2010). Among Msi family 5-FU mw members, mouse Msi1 is highly enriched in developing NS/PCs (Sakakibara et al., 1996) and is thought to contribute to the maintenance of the NS/PCs by regulating the translation of particular downstream target genes (Imai et al., 2001 and Sakakibara et al., 2002), such that Msi1 competes with eIF4G for binding to PABP, both of which are general translation factors (Kawahara et al., 2008). In this study, we report the sequence and characterize the function of the zebrafish (Danio rerio) Msi family member. One experiment essential for revealing the function of a protein is a loss-of-function study using an animal model. However, the postnatal survival rate of msi1 knockout mice is very low and determination of the adult

phenotype has not been possible. Thus, we used zebrafish as a new animal model for this Msi analysis because of Cyclin-dependent kinase 3 their transparent body, which enables detailed observations of development. Furthermore, manipulation of zebrafish, for example, by zmsi1 knock down (KD) by morpholino oligonucleotides (MOs), is relatively easy compared to mice. This zebrafish model will be an excellent tool with which to study the in vivo functions of Msi. Our present results illustrate the use of this animal model to reveal the roles of zebrafish Msi1 (zMsi1) in CNS development and its potential use as a neurological disease model. The database of zebrafish cDNA sequences contains several fragmented and incomplete sequences of Msi1. Full-length cloning primers were designed using the deposited sequences. To clone zebrafish Msi1, RT-PCR was performed using total RNA obtained from the brain of 5-week-old wild-type zebrafish (RIKEN WT), and identified a 2.3-kb cDNA clone that contained the putative full-length coding sequence of zMsi1.

5 km north-south and up to 10 km east-west, with an aerial extent

5 km north-south and up to 10 km east-west, with an aerial extent

of approximately 160 km2. There is no indication of temporal overlap in the activity of the three major volcanic complexes on Montserrat (Cassidy et al., 2012). Consistency between the type of deposits present across the island suggests that the andesitic dome forming style of eruption is common to SH, CH and SHV. The only exception is SSH which possesses basaltic and basaltic–andesite lava flows (Zellmer et al., 2003) and is likely to have some temporal overlap with the early activity of SHV. The apparent consistency in eruptive style means that the island’s volcanic centres provide a unique insight into the temporal evolution of a system, from the building of a complex volcanic edifice (SHV) to the eventual TSA HDAC ic50 erosion back to the central core and most proximal deposits of an extinct volcano (SH). The last 15 years of eruption at SHV have been characterised by periods of dome growth and subsequent collapse. The domes selleck grow by extrusion of highly viscous andesitic spines that break off to form blocky, often unstable, talus slopes. Between 1995 and 2009 SHV erupted an estimated 1 km3 dense rock equivalent (DRE) of andesite magma (Wadge

et al., 2010). As the domes grow they can become gravitationally unstable or undermined by slope weakening associated with hydrothermal activity (Sparks et al., 2002). Dome collapses generate volcaniclastic deposits, including clay-rich debris avalanches, pyroclastic flows, surges and lahars (Cole et al., 1998). Collapses have also been triggered by violent vulcanian explosions that produce pumice-rich

flows, surges and lahars, as well as significant volumes of ash (Druitt et al., 2002). The resultant geology is characterised by variably fractured, though relatively competent, cores of andesitic dome rock and talus breccia, surrounded by volcaniclastic aprons. These flanking deposits are often referred to as andesite tuffs (Rea, 1974), though they vary in the proportions of andesite lava blocks, pumice and ash. Such geological framework is not uncommon at dome building composite volcanoes (Fisher et al., 2006) and is observed throughout the Lesser Antilles, for example, Guadeloupe, Martinique, Dominica and St Lucia (Sigurdsson et al., 1980). During periods of repose, erosional forces Methane monooxygenase dominate, expedited by high rainfall, tropical storms and the humid climate (see Section 3). Frequent heavy rain cuts deeply incised radial valleys (locally termed ghauts) and reworks channel fill deposits. Periods of low or no volcanic activity also allow the development of weathered surfaces and soils. Rad et al. (2007) described conglomerate and sand pyroclastic soils, with thicknesses up to 70 m, on the Lesser Antilles islands of Guadeloupe and Martinique. Their study suggests subsurface weathering is considerable, owing to the high permeability and porosity of young pyroclastic deposits.

Participants performed three practice sessions at a self-selected

Participants performed three practice sessions at a self-selected speed and data were captured for three subsequent repetitions of each activity. Three trials were performed and the average of the three was taken. The trials were labeled

manually and processed using a purpose written program in Vicon Body builder software. The data were output as ASCII files and imported into Excel for further analysis. A purpose written program in Excel was used to amalgamate the data on the knee and hip angles and moments produced during the above functional BYL719 order activities. The muscle strength data were combined with the biomechanical moment and angle data to determine the “FD” placed on the muscles during stair negotiation. FD for a muscle group was defined as the muscle moment required at a particular joint angle, divided by the maximum isometric muscle strength available at that joint angle (expressed as a percentage). In other words the functional moment

occurring at a particular position in the joint range was compared with the muscle strength obtained from muscle tests performed at the same position within the joint range. FD was therefore calculated on an instant-to-instant basis for the joint and using the relevant muscle strength for that SGI-1776 datasheet joint at that angle. A linear interpolation was used to estimate joint strength between the muscle test angles as a first approximation. Ideally, it would have been helpful to have measured isometric strength at a greater number of joint positions in order to have a more continuous strength curve. However, we were limited to three positions in order to minimize the effect of fatigue. FD was calculated throughout the movement as the ratio of the moment produced during a functional activity (the moment required to carry out the movement, the demand) to the actual available isometric muscle strength for the respective muscle group at that angle (the participant’s maximum moment generating capacity). For example, if the knee required to produce a moment (estimated from the biomechanical analysis) of 50 Nm at an angle of 45° and our muscle cAMP strength data indicated their maximum

isometric strength at this angle was 100 Nm then the FD would be 50%. If the demand and capacity were equal then the FD would be 100% and if the demand outstripped the capacity then the FD would exceed 100% of the maximal isometric strength at that angle. This is possible during eccentric and concentric contractions where the literature indicates that these may exceed isometric strength by 15–25%. Descriptive statistics were computed and analysis was carried out using SPSS version 16. Data were examined for normality using the Shapiro–Wilks test and were found to be normally distributed. Comparisons between groups were made using analysis of variance. Statistical significance was set at p < 0.05. Data were expressed as means and standard deviations (SD) in the text and tables.

These waters are oligotrophic (Behrenfeld et al , 2005) and seaso

These waters are oligotrophic (Behrenfeld et al., 2005) and seasonal changes in the biological drawdown of CO2 are also expected to be low. Nitrate concentrations vary between 0.15 μmol kg− 1 in the January to May period and 0.6 μmol kg− 1 in the June–December (Garcia et al., 2010). Therefore the seasonal nitrate changes would only produce a decrease of 1 μmol kg− 1 of TCO2 in January–May Target Selective Inhibitor Library price and 4 μmol kg− 1 in June–December, using the Redfield ratio. This would be less than 10% of the change calculated in TCO2. Thus, we do not expect seasonal changes in biologically

drawn down of CO2, sea–air gas exchange, or vertical entrainment alone could explain the decoupling of the TCO2 and TA signals. Transport http://www.selleckchem.com/products/XL184.html and evaporation seem to account for much of the variability in TCO2 and TA in the SEC subregion (Fig. 11). The variabilities in TCO2 and TA are coupled, and peak when the southeast trade winds are strongest in August, enhancing net evaporation (Bingham et al., 2010) and the westward flow of the SEC (Reverdin et al., 1994), both of which would increase SAL, TCO2 and TA. The change in salinity through evaporation affects both TCO2 and TA the same way and NTA is constant over time and space. The TCO2/TA ratio in surface waters is greater in the eastern Pacific and greater transport of waters from the east from

August to February could cause a net decrease in Ωar. This suggests that seasonal changes in the zonal transport of the SEC waters could account for a significant component of the seasonal change in Ωar. The goal of this study was to investigate the variability in the aragonite saturation

state (Ωar) at seasonal and basin scales for the Western Pacific (120°E:140°W and 35°S:30°N). We developed a new relationship between measured values of total alkalinity very and salinity (Eq. (2)) to provide one of the key CO2 system parameters needed to reconstruct and quantify the seasonal cycle of the aragonite saturation state. The TA–SAL relationship was found to be valid under all ENSO conditions and applicable across the entire study region. This relationship is an improvement of previous studies and provides a way to estimate high-resolution surface TA fields with salinity data from observational programs like ARGO (Gould et al., 2004). This updated relationship and the seasonal climatology of surface pCO2 were used to calculate TCO2 and Ωar. The seasonal variability in Ωar is small in the Western Pacific Warm Pool and the North Equatorial Counter Current subregions because TA changes tend to offset the effect of TCO2. Net precipitation changes in these two subregions drive the seasonal variabilities in TA and TCO2. Vertical mixing is inhibited by the quasi-permanence of a barrier layer and the sea–air exchange of CO2 and biological production were found to have only a small influence on the Ωar variability in the WPWP and NECC subregions.

, 2009) Many studies have investigated the strategies/traits by

, 2009). Many studies have investigated the strategies/traits by which specific growth forms of nurse plants modify in very particular ways their microenvironment to cope with the strong microclimatic specificities in TAE (e.g. Young and van Arden Robe, 1986 and Rundel et al., 1994). However, our selleck chemicals survey reported only five studies examining the effects of these traits on the modulation of plant–plant interactions in TAE. Among them, Anthelme et al. (2012) showed that the surface of cushions of Azorella aretioides (Ecuadorian Andes) experiences a higher wind speed than adjacent vegetated areas because they reach a higher size than temperate

cushions (e.g., Reid et al., 2010). This increased wind speed combined with increased isolation from the soil matrix may be responsible for negative effects on air temperature and relative humidity on the surface and the boundary layer of the cushion, and on temperature 5 cm belowground ( Anthelme et al., 2012). However, the authors found that a highly positive impact of A. aretioides on the availability of soil nutrients for colonizing species, a process which probably triggered facilitation on other species. Similarly, Mizuno (1998) selleck screening library found that the pioneer species Senecio keniophytum may facilitate primary succession after

glacier retreat on Mount Kenya slopes by providing humus for seedling establishment MYO10 of other species (long-term foundation effects sensu Badano et al., 2006). Apart from these mechanisms, habitat amelioration by plants through reduction of frost heaving has also been frequently observed in TAE,

by cushions (e.g. Haussmann et al., 2009) and by giant rosettes (e.g. Pérez, 1989), with positive effects on the seedling establishment of other species (Pérez, 1987a; Table 1). This indicates that facilitation mechanisms in TAE may be highly dependent on the type of facilitator. Other particular types of microclimatic amelioration by nurse plants in TAE have been observed, such as the development of a favourable precipitation regime beneath the canopy of a Hawaiian shrub, which allows the establishment of communities that depend on fog drip (Leuschner and Schulte, 1991). Facilitation through protection from herbivores by tussock grasses has also been suggested by spatial association patterns (Patty et al., 2010) but requires additional manipulative experiments to be evidenced thoroughly (see, e.g. Anthelme and Michalet, 2009). All of these data illustrate the highly specific microhabitat amelioration provided by nurse plants in TAE. Currently, the only study that has tested the SGH explicitly in a tropical alpine environment (Anthelme et al., 2012) corroborated the classical pattern of the SGH along a narrow altitudinal gradient, namely, a higher frequency of facilitative interactions occurred among plants at higher elevations.

There are a considerable number of publications and patents on th

There are a considerable number of publications and patents on the application of vitrification for tissue and whole organ preservation including kidney [32], liver slices [29] and blood vessels [55]. learn more Most tissues studied were either vascular or were organ slices, in both cases the CPA equilibration time throughout the tissue could be effectively reduced by the perfusion of the CPA solution or adjusting the tissue slice thickness [56]. The

earliest accounts of vitrification of articular cartilage are from Jomha et al. [45] and [46]. These two studies demonstrated 42% and 33% cell recovery respectively after vitrification using high concentrations of Me2SO. Song et al. achieved ∼80% chondrocyte viability (Alamar Blue and calcein-AM fluorescent functional assays) in vitrified rabbit full thickness femoral head cartilage. Using cryosubstitution, it was shown that vitrification, or in other words ice-free cryopreservation, was truly achieved [96]. In another study, scanning electron microscopy of the cartilage samples immersed and fast-cooled in ⩾6 M DMSO solution showed a

decrease in the size and total volume of GSK2118436 supplier the enlarged pores due to ice formation [48]. Further evidence of the protection of extracellular matrix from ice formation damage was provided by multiphoton fluorescent imaging of cartilage grafts and Raman spectroscopy of heart valve leaflets, concluding that the tissue extracellular matrix received more extensive damage when frozen with a conventional slow-freezing than when vitrified [18] and [105]. Since the concentrations required for vitrification are generally high, a number of studies have investigated CPA toxicity at high concentrations in cartilage and other tissues providing some valuable information although the data is far from complete. It is clear that CPA toxicity is species and tissue specific; therefore, these results cannot be generalized [5], [23], Temsirolimus mouse [85], [88], [104] and [111]. There are few studies investigating the mechanisms

of toxicity and the effects of high concentrations of CPAs [7], [13], [26], [28], [32] and [113]. More recently, a few studies have investigated CPA toxicity specific to articular cartilage with some general trends in CPA toxicity to chondrocytes and CPA interactions developing [6], [26] and [53]. The specifics of cellular toxicity are not clearly defined at this point and methods of mitigating toxicity of specific CPAs are not available; however the general consensus in the field of cryobiology is to expose cells to the CPA at the lowest concentration and temperature for the shortest exposure time possible so the formation of ice is avoided. This method is called liquidus tracking or stepwise loading and cooling.

44 and 49 There are 1000 registered miRNAs which are predicted

44 and 49 There are 1000 registered miRNAs which are predicted INCB018424 cell line in plants and regulate hundreds of genes, many of which are transcription factors that in turn regulate multiple genes (http://miRNA.sanger.ac.uk/). The ancient miRNA miR-396

regulates seven GROWTH-REGULATING FACTOR (GRF), a plant specific family of transcription factors, which regulate cell expansion, cotyledon,44 size of the meristem50 and cell proliferation in Arabidopsis leaves. 51 Additionally, reduced cell proliferation process in developing leaves by the regulation of miR-396 is noted through the suppression of GRF activity and a decrease in the expression of cell cycle genes. Moreover, miR-396 promotes a moderate increase in organ size. 50 Plants deficient of miR-172 regulate floral homeotic gene, APETALA2, have altered patterns of floral organ development through translational inhibition. 44 Similarly, Mallory et al 52 suggested developmental role for miR-164 directed regulation of NAC-domain genes, which encodes a family PLX3397 mouse of transcription factors CUP-SHAPED COTYLEDON1, which regulates normal embryonic, vegetative and floral development. Moreover, in plant biology the miRNA regulates more targets such as ATP sulfurylases, laccases and

superoxide dismutases. 44 miRNAs and their important role in interaction with the target genes analysis in biological system, has support a great potential for the development in current diagnostic and therapeutic strategies in the management of human diseases. And, to understand the Verteporfin concentration gene regulation in various biological systems. All authors have none to declare. “
“Radioiodine is an efficient treatment in Graves’ disease. Some centers give patients ablative doses, whereas in others, treatment purpose is to recover euthyroidism. However, even in this second case, hypothyroidim can occur precociously, during the first year after radioiodine. Radioinduced thyroiditis appears to be the main mechanism involved in the pathogenesis of precocious hypothyroidism.


“Des cas groupés de coqueluche impliquant des soignants sont régulièrement signalés dans des collectivités à risque comme les maternités. Les recommandations vaccinales vis-à-vis de la coqueluche étaient mal connues des professionnels de santé, y compris des médecins du travail. “
“La grossesse est une période de bouleversements de l’organisme. Les modifications physiologiques de la grossesse sont polymorphes. “
“Dilated cardiomyopathy (DCMP) is a progressive disease of heart muscle that is characterized by ventricular chamber enlargement with normal left ventricular wall thickness, systolic dysfunction and with or without diastolic dysfunction.1 Dilated cardiomyopathy is the third most common cause of heart failure with a prevalence of 36.5 per 100,000 in a population based study.

, 2004 and Clarke et al , 2013) However, similar changes were no

, 2004 and Clarke et al., 2013). However, similar changes were not observed following restraint of conventionally housed mice suggesting that the absence of the early microbiota influences stress responsivity into adulthood. Further, monoassociation with Bifidobacterium infantis, a bacterium commonly isolated from the neonate gut, partially rescued the HPA stress activation, and gnotobiotic mice reconstituted with normal specific pathogen-free microbiota exhibited decreased anxiety-like behaviors ( Sudo et al., 2004, Clarke et al., 2013 and Nishino et al., 2013). Further evidence

of the role of microbiota in shaping stress pathway regulation comes from the study selleck chemicals of serotonergic dysregulation, a common feature www.selleckchem.com/products/ABT-888.html in sex-specific affective disorders (Ressler and Nemeroff, 2000 and Goel and Bale, 2010). Consistent with previous reports of sex differences in serotonergic neurocircuitry and established sex differences in the HPA axis stress response (Goel and Bale, 2010), hippocampal serotonin and 5-HIAA, the main metabolite of serotonin, concentrations were higher in conventionally colonized (CC) female mice than in males (Clarke et al., 2013). Interestingly, serotonin and 5-HIAA levels remain unchanged in GF females relative to CC females, while concentrations of these monoamines

and metabolites were increased to female-typical levels in GF male mice (Clarke et al., 2013), suggesting potential dysmasculinization of hippocampal serotonergic neurocircuitry in GF males. Consistent with previous work on early life stress and sex-specific dysregulation of neuroplasticity (Mueller and

Bale, 2008), BDNF expression was decreased in the hippocampus of GF male, but not GF female mice (Clarke et al., 2013). While bacterial colonization of GF males during the post-weaning period did not rescue hippocampal serotonergic alterations, this treatment successfully rescued altered anxiety-like behaviors observed in male GF mice (Clarke et al., 2013). This demonstration of the absence of a normal gut microbiota exhibiting consequences on neurodevelopment and adult behavior in males but not females introduces the possibility that the microbiome may also contribute to a larger extent to sex differences in the susceptibility to disease. Of great importance to stress Wilson disease protein pathway regulation, a direct interaction between gonadal hormones and microbial exposure in mediating sex-specific disease risk has been recently illustrated (Markle et al., 2013 and Yurkovetskiy et al., 2013). The incidence of autoimmune disorders such as type 1 diabetes (T1D) displays a strong female bias, with nearly twice as many females affected as males (Pozzilli et al., 1993). Similar sex-specific susceptibility is observed in the non-obese diabetes (NOD) mouse model where female NOD mice exhibit increased incidence of T1D pathogenesis relative to NOD males (Pozzilli et al., 1993).