Miracle-dz/UniFAR-FTUs huggingface dataset:
Affecting the Homing of Islet-Specific T Cellsby Regulates Development of Type 1 Diabetes Idd9 The Autoimmune Diabetes Locus

Several genetic insulin-dependent diabetes ( Idd ) intervals that confer resistance to autoimmune diabetes have been identiﬁed in mice and humans, but the mechanisms by which they protect against development of diabetes have not been elucidated. To determine the effect of Idd9 on the function of islet-speciﬁc T cells, we established novel BDC-Idd9 mice that harbor BDC2.5 TCR transgenic T cells containing the Idd9 of diabetes-resistant B10 mice. We show that the development and functional responses of islet-speciﬁc T cells from BDC-Idd9 mice are not defective compared with those from BDC mice, which contain the Idd9 of diabetes-susceptible NOD mice. Upon transfer, BDC T cells rapidly induced severe insulitis and diabetes in NOD.scid mice, whereas those from BDC-Idd9 mice mediated a milder insulitis and induced diabetes with a signiﬁcantly delayed onset. BDC and BDC-Idd9 T cells expanded comparably in recipient mice. However, BDC-Idd9 T cells accumulated in splenic periarteriolar lymphatic sheaths, whereas BDC T cells were mainly found in pancreatic lymph nodes and pancreata of recipients, indicating that the transferred T cells differed in their homing. We provide evidence that the migration pattern of transferred BDC and BDC-Idd9 T cells at least partly depends on their differential chemotaxis toward the CCR7 ligand CCL19. Taken together, our data show that the Idd9 locus regulates development of type 1 diabetes by affecting the homing of islet-speciﬁc T cells. The Journal of Immunology, 2006, 176: 5455–5462. BDC2.5 T cells. Therefore, they provide a tool for dissect-ing the effects of Idd9 on the function of islet-speciﬁc CD4 (cid:1) T cells.Inthis study, we report that the Idd9 did not affect the development and activation status of islet-speciﬁc T cells in the BDC-Idd9 mice. BDC-Idd9 T cells were not defective in their responses to a BDC2.5 mimic peptide in vitro or to (cid:1) cell Ag in recipient mice. We demonstrate that islet-speciﬁc T cells containing the B10-derived Idd9 signiﬁcantly delayed the onset of diabetes in NOD.scid mice when compared with onset in mice that received cells from BDC mice. Finally, in adoptive transfer experiments, we show that BDC-Idd9 T cells transferred into recipients had impaired capacities to home in to PLN and inﬁltrate the pancreas but accumulated in splenic periarteriolar lymphatic sheaths (PALS) in comparison to BDC T cells. This different homing pattern was associated with a differential chemotactic reactivity of BDC and BDC-Idd9 T cells toward the CCR7 ligand CCL19. Taken to-gether, these results indicate that Idd9 affects the homing of islet-speciﬁc T cells and thereby regulates the inﬁltration of pancreatic islets and induction of diabetes.
Resolving Ireland’s Banking Crisis

The Irish banking system has been, in effect, on a life-support system since September 2008. Complacency resulted in the banks fuelling the late stage of an obvious construction bubble with massive foreign borrowing, leaving them exposed to solvency and liquidity risks which in past times would have been inconceivable. The Government’s steps to put the system back on a sound basis must have regard both to protecting taxpayers’ interests and to ensuring that credit flows to the economy are not hampered by inadequate capital or liquidity.
PDE10A inhibitors stimulate or suppress motor behavior dependent on the relative activation state of the direct and indirect striatal output pathways

The enzyme phosphodiesterase 10A (PDE10A) regulates the activity of striatal, medium spiny neurons (MSNs), which are divided into a behaviorally stimulating, Gs‐coupled D1 receptor‐expressing “direct” pathway and a behaviorally suppressant, Gi‐coupled D2 receptor‐expressing “indirect” pathway. Activating both pathways, PDE10A inhibitors (PDE10AIs) combine functional characteristics of D2 antagonists and D1 agonists. While the effects of PDE10AIs on spontaneous and stimulated behavior have been extensively reported, the present study investigates their effects on suppressed behavior under various conditions of reduced dopaminergic neurotransmission: blockade of D1 receptors with SCH‐23390, blockade of D2 receptors with haloperidol, or depletion of dopamine with RO‐4‐1284 or reserpine. In rats, PDE10AIs displayed relatively low cataleptic activity per se. After blocking D1 receptors, however, they induced pronounced catalepsy at low doses close to those required for inhibition of apomorphine‐induced behavior; slightly higher doses resulted in behavioral stimulant effects, counteracting the catalepsy. PDE10AIs also counteracted catalepsy and related behaviors induced by D2 receptor blockade or dopamine depletion; catalepsy was replaced by behavioral stimulant effects under the latter but not the former condition. Similar interactions were observed at the level of locomotion in mice. At doses close to those inhibiting d‐amphetamine‐induced hyperlocomotion, PDE10AIs reversed hypolocomotion induced by D1 receptor blockade or dopamine depletion but not hypolocomotion induced by D2 receptor blockade. It is concluded that PDE10AIs stimulate or inhibit motor behavior dependent on the relative activation state of the direct and indirect striatal output pathways.
Regulation of the Yersinia type III secretion system: traffic control

Yersinia species, as well as many other Gram-negative pathogens, use a type III secretion system (T3SS) to translocate effector proteins from the bacterial cytoplasm to the host cytosol. This T3SS resembles a molecular syringe, with a needle-like shaft connected to a basal body structure, which spans the inner and outer bacterial membranes. The basal body of the injectisome shares a high degree of homology with the bacterial flagellum. Extending from the T3SS basal body is the needle, which is a polymer of a single protein, YscF. The distal end of the needle serves as a platform for the assembly of a tip complex composed of LcrV. Though never directly observed, prevailing models assume that LcrV assists in the insertion of the pore-forming proteins YopB and YopD into the host cell membrane. This completes a bridge between the bacterium and host cell to provide a continuous channel through which effectors are delivered. Significant effort has gone into understanding how the T3SS is assembled, how its substrates are recognized and how substrate delivery is controlled. Arguably the latter topic is the least understood; however, recent advances have provided new insight, and therefore, this review will focus primarily on summarizing the current state of knowledge regarding the control of substrate delivery by the T3SS. Specifically, we will discuss the roles of YopK, as well as YopN and YopE, which have long been linked to regulation of translocation. We also propose models whereby the YopK regulator communicates with the basal body of the T3SS to control translocation.
Cyborg geographies: towards hybrid epistemologies

As a mode of critique, the cyborg is often separated from its role as a figuration. This article reviews Donna Haraway's cyborg theory to restate the importance of the cyborg as a figuration in critical methodology. Figuration is about opening knowledge-making practices to interrogation. I argue that the cyborg enables this inquiry through epistemological hybridization. To do so, cyborg figurations not only adopt a language of being or becoming, but narrate this language in the production of knowledges, to know hybridly. The epistemological hybridization of the cyborg includes four strategies: witnessing, situating, diffracting and acquiring. These are modes of knowing in cyborg geographies. To underline the importance of this use of cyborg theory, I review selected geographic literatures in naturecultures and technosciences, to demonstrate how geographers cite the cyborg. My analysis suggests these literatures emphasize an ontological hybridity that leaves underconsidered the epistemological hybridization at work in cyborg figuration. To take up the cyborg in this way is to place at risk our narrations, to re-make these geographies as hybrid, political work.
Gender congruence and body satisfaction in nonbinary transgender people: A case control study

Abstract Background: Binary transgender people access gender affirming medical interventions to alleviate gender incongruence and increase body satisfaction. Despite the increase in nonbinary transgender people, this population are less likely to access transgender health services compared to binary transgender people. No research has yet understood why by exploring levels of gender congruence and body satisfaction in nonbinary transgender people. Objective: The aim of this study was to compare levels of gender congruence and body satisfaction in nonbinary transgender people to controls [binary transgender people and cisgender (nontrans) people]. Method: In total, 526 people from a community sample in the UK took part in the study (97 nonbinary, 91 binary, and 338 cisgender identifying people). Participants were asked to complete an online survey about gender congruence and body satisfaction. Results: There were differences in gender congruence and body satisfaction between nonbinary and binary transgender people. On sex-specific parts of the body (i.e., chest, genitalia, and secondary sex characteristics), nonbinary transgender people reported significantly higher levels of gender and body satisfaction compared to binary transgender people. However, there was no difference in congruence and satisfaction with social gender role between the two transgender groups (nonbinary and binary). Cisgender people reported significantly higher levels of gender congruence and body satisfaction compared to transgender people (nonbinary and binary). Conclusions: There are differences in gender congruence and body satisfaction between nonbinary and binary transgender people. Nonbinary individuals may be less likely to access transgender health services due to experiencing less gender incongruence and more body satisfaction compared to binary transgender people. Transgender health services need to be more inclusive of nonbinary transgender people and their support and treatment needs, which may differ from those who identify within the binary gender system.
Heating and cooling of the thermosphere by internal gravity waves

For the first time, estimates of heating and cooling in the upper thermosphere due to dissipating and breaking gravity waves (GWs) of tropospheric origin have been obtained with a comprehensive general circulation model (GCM). A GW parameterization specifically designed for thermospheric heights has been implemented in the CMAT2 GCM covering altitudes from the tropopause to the F2 region, and simulations for the June solstice have been performed. They reveal that the net thermal effect of GWs above the turbopause is cooling. The largest (up to −170 K d−1 in a zonally and temporally averaged sense) cooling takes place in the high latitudes of both hemispheres near 210 km. The instantaneous values of heating and cooling rates are highly variable, and reach up to 500 and −3000 K d−1 in the F2 region, respectively. Inclusion of the GW thermal effects reduces the simulated model temperatures by up to 200 K over the summer pole and by 100 to 170 K at other latitudes near 210 km.
Philosophies of Adult Education as Practiced by Agricultural Education Teachers

Power semiconductor device structures and assemblies with improved heat dissipation characteristics and low impedance interconnections include a thermally-conductive dielectric layer, such as diamondlike carbon (DLC) overlying at least portions of the active major surface of a semiconductor chip, with vias formed in the dielectric layer in alignment with contact pads on the active major surface. A patterned metallization layer is formed over the thermally-conductive dielectric layer, with portions of the metallization layer extending through the vias into electrical contact with the chip contact pads. A metal structure is electrically and thermally coupled to selected areas of the patterned metallization, such as by solder bonding or by a eutectic bonding process. In different embodiments, the metal structure may comprise a metal conductor bonded to the opposite major surface of another power semiconductor device structure, a heat-dissipating device-mounting structure, or simply a low-impedance lead.
Immunometabolic Status during the Peripartum Period Is Enhanced with Supplemental Zn, Mn, and Cu from Amino Acid Complexes and Co from Co Glucoheptonate

The peripartum (or transition) period is the most-critical phase in the productive life of lactating dairy cows and optimal supply of trace minerals through more bioavailable forms could minimize the negative effects associated with this phase. Twenty Holstein cows received a common prepartal diet and postpartal diet. Both diets were partially supplemented with an inorganic (INO) mix of Zn, Mn, and Cu to supply 35, 45, and 6 ppm, respectively, of the diet dry matter (DM). Cows were assigned to treatments in a randomized completed block design, receiving an daily oral bolus with INO or organic trace minerals (AAC) Zn, Mn, Cu, and Co to achieve 75, 65, 11, and 1 ppm supplemental, respectively, in the diet DM. Liver tissue and blood samples were collected throughout the experiment. The lower glutamic-oxaloacetic transaminase concentration after 15 days in milk in AAC cows indicate lower hepatic cell damage. The concentration of cholesterol and albumin increased, while IL-6 decreased over time in AAC cows compared with INO indicating a lower degree of inflammation and better liver function. Although the acute-phase protein ceruloplasmin tended to be lower in AAC cows and corresponded with the reduction in the inflammatory status, the tendency for greater serum amyloid A concentration in AAC indicated an inconsistent response on acute-phase proteins. Oxygen radical absorbance capacity increased over time in AAC cows. Furthermore, the concentrations of nitric oxide, nitrite, nitrate, and the ferric reducing ability of plasma decreased with AAC indicating a lower oxidative stress status. The expression of IL10 and ALB in liver tissue was greater overall in AAC cows reinforcing the anti-inflammatory response detected in plasma. The greater overall expression of PCK1 in AAC cows indicated a greater gluconeogenic capacity, and partly explained the greater milk production response over time. Overall, feeding organic trace minerals as complexed with amino acids during the transition period improved liver function and decreased inflammation and oxidative stress.
Recapitulation in Saccharomyces cerevisiae of Cytochrome b Mutations Conferring Resistance to Atovaquone in Pneumocystis jiroveci

ABSTRACT Pneumocystis jiroveci (human-derived P. carinii) is an opportunistic pathogenic fungus which causes pneumonia and is life-threatening in immunocompromised individuals. Spontaneously acquired resistance to atovaquone, a hydroxynaphthoquinone that is used to treat P. jiroveci infections, was linked to mutations in the mitochondrially encoded cytochrome b gene. Because P. jiroveci cannot be easily cultivated, we have developed Saccharomyces cerevisiae as an alternative system to study atovaquone resistance mutations. In this work, we introduced seven mutations linked with atovaquone resistance in P. jiroveci into the S. cerevisiae cytochrome b gene. The effects of the mutations on the respiratory function and on the sensitivity to the inhibitor were then characterized. Six of the reported mutations lowered the sensitivity of the S. cerevisiae bc1 complex to atovaquone, while one mutation had no effect on the drug resistance. These results were confirmed by monitoring the in vivo resistance of S. cerevisiae mutants which carried both the cytochrome b mutations and a deletion of the ABC transporter genes, allowing the drug to bypass the weakened efflux pump system. S. cerevisiae thus provides an easy-to-use system to characterize in vivo and in vitro cytochrome b mutations reported in pathogens and to assess their role in drug resistance.
Thioredoxin Reductase and its Inhibitors

Thioredoxin plays a crucial role in a wide number of physiological processes, which span from reduction of nucleotides to deoxyriboucleotides to the detoxification from xenobiotics, oxidants and radicals. The redox function of Thioredoxin is critically dependent on the enzyme Thioredoxin NADPH Reductase (TrxR). In view of its indirect involvement in the above mentioned physio/pathological processes, inhibition of TrxR is an important clinical goal. As a general rule, the affinities and mechanisms of binding of TrxR inhibitors to the target enzyme are known with scarce precision and conflicting results abound in the literature. A relevant analysis of published results as well as the experimental procedures is therefore needed, also in view of the critical interest of TrxR inhibitors. We review the inhibitors of TrxR and related flavoreductases and the classical treatment of reversible, competitive, non competitive and uncompetitive inhibition with respect to TrxR, and in some cases we are able to reconcile contradictory results generated by oversimplified data analysis.
Concomitant Pulmonary Tuberculosis in Hospitalized Healthcare-Associated Pneumonia in a Tuberculosis Endemic Area: A Multi-center Retrospective Study

Background In tuberculosis (TB) endemic areas, Mycobacterium tuberculosis is an important but easily misdiagnosed pathogen in community-acquired pneumonia (CAP). However, the occurrence of concomitant pulmonary tuberculosis (PTB) in hospitalized healthcare-associated pneumonia (HCAP) has never been investigated. Methods and Findings Seven hundred and one hospitalized HCAP and 934 hospitalized CAP patients from six medical centers in Taiwan were included in this nationwide retrospective study. Concomitant PTB was defined as active PTB diagnosed within 60 days of admission due to HCAP or CAP. The predictors for concomitant PTB and the impact of PTB on the outcomes of pneumonia were investigated. Among the enrolled subjects, 21/701 (3%) of the HCAP patients and 25/934 (2.7%) of the CAP patients were documented to have concomitant PTB. In multivariate analysis, a history of previous anti-TB treatment (OR = 5.84, 95% CI: 2.29–20.37 in HCAP; OR = 3.33, 95% CI: 1.09–10.22 in CAP) and escalated pneumonia severity index (PSI) scores (OR = 1.014, 95% CI: 1.002–1.026, in HCAP; OR = 1.013, 95% CI: 1.001–1.026, in CAP) were independent predictors for concomitant PTB in both CAP and HCAP patients. Regarding treatment outcomes, HCAP patients with concomitant PTB were associated with more acute respiratory failure within 48 hours of admission (47.6% vs. 22.6%, p = 0.008), higher intensive care unit admission rate (61.9% vs. 35.7%, p = 0.014), longer hospitalization (39.6±34.1 vs. 23.7±27 days, p = 0.009), and higher in-hospital mortality (47.6% vs. 26.3%, p = 0.03) than those without concomitant PTB. Exposure to certain groups of antibiotics for the treatment of pneumonia was not associated with the occurrence of concomitant PTB. Conclusions In HCAP patients, the occurrence of concomitant PTB is comparable with that in CAP patients and associated with higher PSI scores, more acute respiratory failure, and higher in-hospital mortality.
SERIES DOES INFLATION TARGETING MAKE A DIFFERENCE ?

Yes, as inferred from panel evidence for inflation-targeting countries and a control group of high-achieving industrial countries that do not target inflation. Our evidence suggests that inflation targeting helps countries achieve lower inflation in the long run, have smaller inflation response to oil-price and exchange-rate shocks, strengthen monetary policy independence, improve monetary policy efficiency, and obtain inflation outcomes closer to target levels. Some benefits of inflation targeting are larger when inflation targeters have achieved disinflation and are able to make their inflation targets stationary. Despite these favorable results for inflation targeting, our evidence generally does not suggest that countries that adopt inflation targeting have attained better monetary policy performance relative to our control group of highly successful non-inflation targeters. However, inflation targeting does seem to help all country groups to move toward performance of the control group. The performance attained by industrial-country inflation targeters generally dominates performance of emerging-economy inflation targeters and is similar to that of industrial non-inflation targeting countries. Frederic S. Mishkin Governor Frederic Mishkin Board of Governors of the Federal Reserve System 20th Street and Constitution Ave., N.W. Room B-2052 Stop 47 Washington, DC 20551 and NBER fsm3@columbia.edu Klaus Schmidt-Hebbel Central Bank of Chile Agustinas 1180 Santiago, Chile kschmidt@bcentral.cl
Universal and Nonuniversal Properties of Cross Correlations in Financial Time Series

We use methods of random matrix theory to analyze the cross-correlation matrix C of price changes of the largest 1000 US stocks for the 2-year period 1994-95. We find that the statistics of most of the eigenvalues in the spectrum of C agree with the predictions of random matrix theory, but there are deviations for a few of the largest eigenvalues. We find that C has the universal properties of the Gaussian orthogonal ensemble of random matrices. Furthermore, we analyze the eigenvectors of C through their inverse participation ratio and find eigenvectors with large inverse participation ratios at both edges of the eigenvalue spectrum--a situation reminiscent of results in localization theory.
Channel tracking techniques for OFDM systems in wireless access vehicular environments

Current OFDM based wireless LAN systems assume relative static channel response over the entire packet burst length. This paper proposes applying adaptive filtering concepts to channel estimation of current standardized OFDM systems in order to track the rapidly fluctuating channel response of wireless access vehicular environments (WAVE) for 5.9 GHz dedicated short range communications (DSRC). Different possible reference signals are considered for channel tracking, namely, pilots, symbol demapping output, and Viterbi decoder output. Pilot-aided channel tracking is not feasible with the standard current pilot structure since the number of available pilot subcarriers does not suffice in making an accurate channel estimate. Based on simulations, Viterbi-aided channel estimation has a slight advantage over channel estimation aided by the demapping circuit. Overall, applying channel tracking improves the performance of DSRC systems.
Continuity for multi-type branching processes with varying environments

Conditions are derived for the components of the normed limit of a multi-type branching process with varying environments, to be continuous on (0, ? ). The main tool is an inequality for the concentration function of sums of independent random variables, due originally to Petrov. Using this, we show that if there is a discontinuity present, then a particular linear combination of the population types must converge to a non-random constant (Equation (1)). Ensuring this can not happen provides the desired continuity conditions.