Miracle-dz/UniFAR-FTUs huggingface dataset:
Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion

Despite the immune-privileged status of the male genital tract, infection and inflammation of the male genital tract are important etiological factors in male infertility. A common observation in clinical and experimental orchitis as well as in systemic infection and inflammation are decreased levels of testosterone. Emerging data point to an immunosuppressive role of testosterone. In our study, we substituted testosterone levels in experimental autoimmune orchitis (EAO) in rat by s.c. testosterone implants. EAO development was reduced to 17% when animals were treated with low-dose testosterone implants (3 cm long, EAO+T3) and to 33% when rats were supplied with high-dose testosterone implants (24 cm, EAO+T24) compared with 80% of animals developing disease in the EAO control group. In the testis, testosterone replacement in EAO animals prevented the accumulation of macrophages and significantly reduced the number of CD4+ T cells with a strong concomitant increase in the number of regulatory T cells (CD4+CD25+Foxp3+) compared with EAO control. In vitro testosterone treatment of naive T cells led to an expansion of the regulatory T cell subset with suppressive activity and ameliorated MCP-1–stimulated chemotaxis of T lymphocytes in a Transwell assay. Moreover, expression of proinflammatory mediators such as MCP-1, TNF-α, and IL-6 in the testis and secretion of Th1 cytokines such as IFN-γ and IL-2 by mononuclear cells isolated from testicular draining lymph nodes were decreased in the EAO+T3 and EAO+T24 groups. Thus, our study shows an immunomodulatory and protective effect of testosterone substitution in the pathogenesis of EAO and suggests androgens as a new factor in the differentiation of regulatory T cells.
Accuracy of Scanning Laser Polarimetry, Scanning Laser Tomography, and Their Combination in a Glaucoma Screening Trial

PurposeTo compare the usefulness in glaucoma screening of scanning laser polarimetry (GDx-VCC), scanning laser tomography [Heidelberg retina tomograph II (HRT II)], and their combined evaluation. MethodsIn a nonpopulation-based prepublicized trial, self-recruited white participants were screened for glaucoma with GDx-VCC, HRT II, and by independent clinical examination. Cases with possible glaucoma as found with any of the screening methods underwent a detailed clinical investigation to verify or exclude glaucoma. ResultsOf the 136 attendees 118 participants (218 eyes) successfully underwent the GDx-VCC and HRT II measurements. Twenty-three eyes (11%) of 13 participants had glaucoma. Seventeen of these glaucomatous eyes (74%) had early damage. Evaluated separately, the GDx-VCC screening test (borderline cases grouped with the normal cases) performed best with 96.8% specificity, 89.5% accuracy, 7.5 positive likelihood ratio (PLR), but with only 23.8% sensitivity. Accuracy and PLR for all HRT parameters were <86.4% and <3.7, respectively. Combining different threshold criteria, for GDx-VCC accuracy increased to 90.3% to 90.8% and PLR to 14.0 to 17.7; but for HRT no useful increase was seen (accuracy <86.4% and PLR<4.7 for all combinations). Combination of the best HRT and GDx-VCC criteria resulted in a PLR which was increased compared with the HRT combinations, but decreased compared with the GDx-VCC combinations (PLR<12.7 for all combinations). ConclusionsIn this white screening population with relatively high risk for mild glaucomatous damage, a combination of different GDx-VCC criteria was useful for glaucoma screening; but combinations of HRT criteria or combinations of GDx-VCC criteria with HRT criteria were less good for this purpose.
The multiple roles of the CD8 coreceptor in T cell biology: opportunities for the selective modulation of self‐reactive cytotoxic T cells

Short peptide fragments generated by intracellular protein cleavage are presented on the surface of most nucleated cells bound to highly polymorphic MHCI molecules. These pMHCI complexes constitute an interface that allows the immune system to identify and eradicate anomalous cells, such as those that harbor infectious agents, through the activation of CTLs. Molecular recognition of pMHCI complexes is mediated primarily by clonally distributed TCRs expressed on the surface of CTLs. The coreceptor CD8 contributes to this antigen‐recognition process by binding to a largely invariant region of the MHCI molecule and by promoting intracellular signaling, the effects of which serve to enhance TCR stimuli triggered by cognate ligands. Recent investigations have shed light on the role of CD8 in the activation of MHCI‐restricted, antigen‐experienced T cells and in the processes of T cell selection and lineage commitment in the thymus. Here, we review these data and discuss their implications for the development of potential therapeutic strategies that selectively target pathogenic CTL responses erroneously directed against self‐derived antigens.
The influence of desipramine on thyroid hormone metabolism in rat brain.

The effect of the antidepressant desipramine (DMI) on the activities of the three iodothyronine deiodinase isoenzymes involved in the central metabolism of thyroid hormones were investigated in 11 brain regions and 3 peripheral tissues in the rat. The investigations were carried out at three different times during the light/dark cycle: 5 A.M., 1 P.M. and 11 P.M. Interest is focused on changes in the two enzymes that catalyze: i) the 5'deiodination of T4 to the biologically active T3, i.e., type II 5'deiodinase (5'D-II), and ii) the 5 (or inner-ring) deiodination of T3 to the biologically inactive 3,3'T2, i.e., type III 5 deiodinase (5D-III). Fourteen days' treatment with 20 mg/kg DMI, but not with 5 mg/kg DMI, induced significant increases in 5'D-II in eight different areas of the CNS. The regions affected were identical to those that receive noradrenergic input from the locus coeruleus. Even control animals showed a circadian rhythm of 5'D-II activity in some brain regions, and the effects of DMI also depended on the time of death within the 24-hr rhythm. 5D-III was not affected. Serum T4 were lower after administration of DMI, most probably because of enhanced tissue uptake of T4. This is in line with the corresponding finding in depressed patients, indicating that similar changes in both central and peripheral thyroid hormone metabolism may occur after antidepressant pharmacotherapy in both humans and rats. These data support the hypothesis that interactions with the CNS metabolism of the thyroid hormones may be involved in the mechanisms of action of DMI.
Advanced Vertebral Fracture Among Newly Diagnosed Children With Acute Lymphoblastic Leukemia: Results of the Canadian Steroid‐Associated Osteoporosis in the Pediatric Population (STOPP) Research Program

Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to BMD and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age, 5.3 yr; 108 boys) with ALL (precursor B cell: N = 167; T cell: N = 19) who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco‐lumbar spine radiograph, bone age (also used for metacarpal morphometry), and BMD. Vertebral morphometry was carried out by the Genant semiquantitative method. Twenty‐nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bimodal, with most occurring in the midthoracic and thoraco‐lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z‐scores compared with those without (mean ± SD, −2.1 ± 1.5 versus −1.1 ± 1.2; p < 0.001). LS BMD Z‐score, second metacarpal percent cortical area Z‐score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z‐score, the odds for fracture increased by 80% (95% CI: 10–193%); the presence of back pain had an OR of 4.7 (95% CI: 1.5–14.5). These results show that vertebral compression is an under‐recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined.
IPACT With Grant Estimation (IPACT-GE) Scheme for Ethernet Passive Optical Networks

Dynamic bandwidth allocation (DBA) is an open and hot topic in the Ethernet passive optical network (EPON), which is regarded as one of the best choices for next-generation access networks. This paper proposes an estimation-based scheme, interleaved polling with adaptive cycle time with grant estimation (IPACT-GE), for effective upstream channel sharing among multiple optical network units (ONUs) in EPONs. By estimating the amount of new packets arriving between two consecutive pollings and granting ONUs with extra estimated amount, the proposed IPACT-GE scheme can achieve shorter waiting delay and less buffer occupancy at the light load than IPACT, a significant DBA scheme in EPONs. Moreover, when combined with the strict priority queue (SPQ) mechanism to provide differentiated services, IPACT-GE can greatly mitigate the light load penalty that is obvious in the IPACT solution combined with SPQ.
A correct, zero-overhead protocol for network updates

In this paper, we describe a new protocol for the safe up- date of OpenFlow networks. This protocol meets the packet consistency and weak flow consistency conditions, requires neither on-switch resources nor the diversion of packets to refuges during updates, and alls into the family of Trace- based update protocols. The feature of this protocol is a se- quence of per-switch rule updates. We derive a logic circuit for the update sequence, such that there exists a consistency- preserving update for the switch network if and only if the circuit is satisfiable subject to unsatisfiability of invariant violations; further, each satisfying minterm of the circuit yields a consistency-preserving update sequence.
Seasonal and reproductive variation in body condition in captive female Japanese macaques (Macaca fuscata)

The geographic distribution of Japanese macaques includes populations with the most northern range of any primate species. Not surprisingly, females of this species are characterized by physiological adaptations and unique fat deposition mechanisms that facilitate their survival through the sometimes‐harsh seasonal conditions of temperate climates, as well as sustaining the metabolic costs of mating, pregnancy, and lactation. Here, we explore the relationship between nutritional status, seasonality, and reproductive status using anthropometric and leptin measures from 14 captive female Japanese macaques. No seasonal patterns were found in the levels of leptin, but there were differences between seasons in anthropometric measures, specifically between the beginning and the end of the mating season. Females gained weight and accumulated energy reserves in fall to prepare for mating activity, and to survive the severe conditions of winter, which is also the period of gestation if pregnancy occurs. Lactating females had larger total skinfolds relative to nonlactating individuals, and females with older babies at the beginning of the mating season had larger abdominal skinfolds than did those with younger babies. There was a relationship between the likelihood of conception and nutritional status, with females that conceived during one mating season being in better condition at the end of their previous mating season. Together, these results suggest that, even in captive settings, seasonal breeding has a cost on the energetic demands of mating, and that higher condition (i.e. fatter) females could afford the demands of lactation and reproduced more rapidly. Am. J. Primatol. 72:277–286, 2010. © 2009 Wiley‐Liss, Inc.
The MYB96 Transcription Factor Mediates Abscisic Acid Signaling during Drought Stress Response in Arabidopsis1[W]

Plant adaptive responses to drought are coordinated by adjusting growth and developmental processes as well as molecular and cellular activities. The root system is the primary site that perceives drought stress signals, and its development is profoundly affected by soil water content. Various growth hormones, particularly abscisic acid (ABA) and auxin, play a critical role in root growth under drought through complex signaling networks. Here, we report that a R2R3-type MYB transcription factor, MYB96, regulates drought stress response by integrating ABA and auxin signals. The MYB96-mediated ABA signals are integrated into an auxin signaling pathway that involves a subset of GH3 genes encoding auxin-conjugating enzymes. A MYB96-overexpressing Arabidopsis (Arabidopsis thaliana) mutant exhibited enhanced drought resistance with reduced lateral roots. In the mutant, while lateral root primordia were normally developed, meristem activation and lateral root elongation were suppressed. In contrast, a T-DNA insertional knockout mutant was more susceptible to drought. Auxin also induces MYB96 primarily in the roots, which in turn induces the GH3 genes and modulates endogenous auxin levels during lateral root development. We propose that MYB96 is a molecular link that mediates ABA-auxin cross talk in drought stress response and lateral root growth, providing an adaptive strategy under drought stress conditions.
Randomization, matching, and propensity scores in the design and analysis of experimental studies with measured baseline covariates

In many experimental situations, researchers have information on a number of covariates prior to randomization. This information can be used to balance treatment assignment with respect to these covariates as well as in the analysis of the outcome data. In this paper, we investigate the use of propensity scores in both of these roles. We also introduce a randomization procedure in which the balance of all measured covariates is approximately indexed by the variance of the empirical propensity scores and randomization is restricted to those permutations with the least variable propensity scores. This procedure is compared with recently proposed methods in terms of resulting covariate balance and estimation efficiency. Properties of the estimators resulting from each procedure are compared with estimates which incorporate the propensity score in the analysis stage. Simulation results show that analytical adjustment for the propensity score yields results on par with those obtained through restricted randomization procedures and can be used in conjunction with such procedures to further improve inferential efficiency. Copyright © 2014 John Wiley & Sons, Ltd.
BiCMOS vs. CMOS Operational Amplifiers for High-Speed Pipelined A/D Converters

This paper presents a comparison between BiCMOS and CMOS op-amps to be employed in pipelined analog-to-digital converters. Single and two-stage architectures were considered; in addition, a couple of op-amps exploiting bipolar devices in the input stage are proposed. The amplifiers were designed for the first stage of a 12-b high-speed converter; op-amps are constrained by a fixed power budget and are compared in terms of the error due to their finite DC-gain and incomplete settling.
Differential involvement of phosphatidylinositol 3‐kinase‐related protein kinases in hyperphosphorylation of replication protein A2 in response to replication‐mediated DNA double‐strand breaks

Replication protein A2 (RPA2), a component of the RPA heterotrimer, is hyperphosphorylated and forms nuclear foci in response to camptothecin (CPT) that directly induces replication‐mediated DNA double‐strand breaks (DSBs). Ataxia‐telangiectasia mutated and Rad3‐related kinase (ATR) and DNA‐dependent protein kinase (DNA‐PK) are activated by CPT, and RPA2 is hyperphosphorylated in a DNA‐PK‐dependent manner. To distinguish the roles of phosphatidylinositol 3‐kinase‐related protein kinases including DNA‐PK, ataxia‐telangiectasia mutated (ATM), and ATR, in the response to replication‐mediated DSBs, we analyzed RPA2 focus formation and hyperphosphorylation during exposure to CPT. ATR knock‐down with siRNA suppressed CPT‐induced RPA2 hyperphosphorylation and focus formation. CPT‐induced RPA2 focus formation was normally observed in DNA‐PK‐ or ATM‐deficient cells. Comparison between CPT and hydroxyurea (HU) indirectly inducing DSBs showed that RPA2 hyperphosphorylation is DNA‐PK‐dependent in CPT‐treated cells and DNA‐PK‐independent in HU‐treated cells. Although RPA2 foci rapidly formed in response to HU and CPT, the RPA2 hyperphosphorylation in HU‐treated cells occurred later than in the CPT‐treated cells, indicating that the DNA‐PK dependency of RPA2 hyperphosphorylation is likely to be related to the mode of DSB induction. These results suggest that DNA‐PK is responsible for the RPA2 hyperphosphorylation following ATR‐dependent RPA2 focus formation in response to replication‐mediated DSBs directly induced by CPT.
Mutations in two non-canonical Arabidopsis SWI2/SNF2 chromatin remodeling ATPases cause embryogenesis and stem cell maintenance defects.

SWI2/SNF2 chromatin remodeling ATPases play important roles in plant and metazoan development. Whereas metazoans generally encode one or two SWI2/SNF2 ATPase genes, Arabidopsis encodes four such chromatin regulators: the well-studied BRAHMA and SPLAYED ATPases, as well as two closely related non-canonical SWI2/SNF2 ATPases, CHR12 and CHR23. No developmental role has as yet been described for CHR12 and CHR23. Here, we show that although strong single chr12 or chr23 mutants are morphologically indistinguishable from the wild type, chr12 chr23 double mutants cause embryonic lethality. The double mutant embryos fail to initiate root and shoot meristems, and display few and aberrant cell divisions. Weak double mutant embryos give rise to viable seedlings with dramatic defects in the maintenance of both the shoot and the root stem cell populations. Paradoxically, the stem cell defects are correlated with increased expression of the stem cell markers WUSCHEL and WOX5. During subsequent development, the meristem defects are partially overcome to allow for the formation of very small, bushy adult plants. Based on the observed morphological defects, we named the two chromatin remodelers MINUSCULE 1 and 2. Possible links between minu1 minu2 defects and defects in hormone signaling and replication-coupled chromatin assembly are discussed.
Pubertal Development is Normal in Adolescents After Renal Transplantation in Childhood

Background. This study was conducted to evaluate the pubertal development in adolescents after renal transplantation (RTx) in childhood. Methods. We performed a retrospective review of medical records of 109 RTx recipients (72 males) transplanted at the median age of 4.5 years (range: 0.9–15.8 years). Data on the clinical signs of puberty, growth, bone age, medication, and graft function of 98 patients were analyzed. Furthermore, serum levels of reproductive hormones in 87 patients were assessed to evaluate the progression and outcome of pubertal development. Results. The age at the onset of puberty averaged 12.7 years (range: 9.4–16.2 years) in 55 males and 10.7 years (range: 8.9–12.7 years) in 29 females. The mean age at menarche was 12.5 years (range: 10.5–14.5 years). Twenty-two percent of the boys and none of the girls had a moderately delayed onset of puberty. Children who underwent RTx before the age of 5 years reached puberty earlier than those transplanted at later age (boys 12.3±1.2 vs. 13.4±1.5 years, P<0.01; girls 10.3±0.9 vs. 11.0±1.0 years, P>0.05). The mean length of puberty was 3.9 and 4.7 years for boys and girls, respectively. The bone age was delayed in practically all, and final height was reached at the mean age of 18.1 and 16.0 years in boys and girls, respectively. Pubertal maturation resulted in acceptable final height and reproductive hormone status in great majority of the patients. Conclusion. Pubertal development was normal in all female and most male adolescents after RTx in childhood.
A systems biology based integrative framework to enhance the predictivity of in vitro methods for drug-induced liver injury

Background: Liver injury is the most common cause of postmarketing withdrawal of drugs. Traditional animal toxicity testing methods have proved to be imperfect tools for predicting toxicity observed in the clinic. Objective: Predictive methods that integrate data and insights from several in vitro methods to provide a deeper understanding of the impact of a drug on the liver are the need of the hour. Method: A systems approach based on mathematical modelling using the kinetics of biochemical pathways involved in liver homeostasis coupled with in vitro measurements to quantify drug-induced perturbations is described here. Conclusions: Integrating in silico and in vitro methods provides a powerful platform that allows reasonably accurate and mechanistic-level prediction of drug-induced liver injury. The method demonstrates that several physiological situations can be accurately modelled as can the effect of perturbations induced by drugs. It can also be used along with high-throughput ‘omic’ data to generate testable hypotheses leading to informed decision-making.
Effects of Histone Acetylation on the Solubility and Folding of the Chromatin Fiber*

The folding ability of chromatin fractions containing approximately identical nucleosome numbers and the same linker histone composition, but with different extents of core histone acetylation, were analyzed by analytical ultracentrifugation. It was found that the acetylated fractions consistently exhibited a relatively small but significantly lower extent of compaction than that of their native nonacetylated counterparts. This was regardless of the extent of the size distribution heterogeneity of the fractions analyzed. Furthermore the acetylated chromatin fibers exhibited an enhanced solubility in both NaCl and MgCl2, which is neither the result of a differential binding affinity of the linker histones to chromatin nor of an alteration in the relative amounts of the histone H1 variants.
Estimate the height of vegetation using remote sensing in the groundwater-fluctuating belt in the lower reaches of Heihe River, northwest China

The height of vegetation is an important parameter to characterize the canopy evapotranspiration and the sensible heat flux. For studying the ecological water requirement of vegetation in the groundwater-fluctuating belt in lower reaches of Heihe River, northwest China, the empirical evaluation of the landscape-scale height of vegetation prediction technique was derived from Landsat TM image and the height of vegetation map was obtained in the maximum growing season of study area. The conclusions show that the height of vegetation has obvious spatial difference from non-vegetation covered region to the region covered with desert vegetation and riparian vegetation in the study area. This algorithm is effectual to estimate the height of vegetation in the landscape-scale region. This study lays the foundation for characterizing the canopy evapotranspiration and the sensible heat flux, estimating the regional water requirement of ecology, studying many biological and physical processes in the groundwater-fluctuating belt in the lower reaches of Heihe River.