Miracle-dz/UniFAR-FTUs huggingface dataset:
Granzyme A in the Pathogenesis of Type 1 Diabetes: The Yes and the No

Two major unanswered questions related to the pathogenesis of type 1 diabetes (T1D) prevent progress in our ability to intervene in disease development: What breaks immune tolerance to the pancreatic β-cells? And what kills the β-cells? By the surprising demonstration that knockout of the tryptase granzyme A (GrzmA), conventionally considered to be a key proapoptotic mediator of immune killer cell cytotoxicity, does not protect but markedly accelerates and increases incidence of T1D in the nonobese diabetic (NOD) mouse, Mollah et al. (1) add to answering both of these questions. On one hand, they show that GrzmA does not contribute to β-cell killing. On the other hand, their striking finding that diabetes resistance in the proinsulin II transgenic mouse is broken by GrzmA knockout provides evidence of an important role of GrzmA for maintenance of peripheral tolerance. By answering “No” to the question as to whether GrzmA is important in β-cell killing, this study adds to reports showing that granzyme B (GrzmB) (2), Fas (3,4), and perforin (5,6) are dispensable in β-cell killing in the NOD mouse. These observations challenge the view that β-cell destruction in T1D is caused by classic effector T-cell mechanisms and support the notion that these cells do ensure antigen-specific homing and reactivity but then interact with innate immune cells to orchestrate an intraislet inflammatory reaction leading to β-cell killing, the selectivity of which is in part determined by differentiation-dependent sensitivity of β-cells to cytotoxic inflammatory mediators (7). The “Yes” to the question as to whether GrzmA contributes to maintain peripheral tolerance is perhaps …
Precipitation Fluctuations over Northern Hemisphere Land Areas Since the Mid-19th Century

An extensive array of measurements extending back to the mid-19th century was used to investigate large-scale changes in precipitation over Northern Hemisphere land areas. Significant increases in mid-latitude precipitation and concurrent decreases in low-latitude precipitation have occurred over the last 30 to 40 years. Although these large-scale trends are consistent with general circulation model projections of precipitation changes associated with doubled concentrations of atmospheric carbon dioxide, they should be viewed as defining large-scale natural climatic variability. Additional work to refine regional variations and address potential network inhomogeneitics is needed. This study attempts to show secular precipitation fluctuations over hemispheric and continental-scale areas of the Northern Hemisphere.
Discourse, identity and change in mid-to-late life: interdisciplinary perspectives on language and ageing

ABSTRACT The papers in this special issue contribute to the growing body of research on sociolinguistic and discursive interpretations of mid and later life by investigating some of the identity affordances and constraints associated with ‘being middle-aged’ or ‘being old’. The papers here offer qualitative, contextually based analyses of a broad range of data and use various methodological and theoretical perspectives: narrative theory, critical pragmatics, social theory and discursive psychology. The main focus is on the ways in which change impacts on the ageing individual, and how this change is discursively interpreted and negotiated both by and for or about individuals in diverse social frames. We examine age and change as they interact with personal and social identity in personal diary accounts, in print, on the television and web media, in conversations amongst friends and acquaintances, in interviews and during storytelling. Language and communication are examined as resources for making and interpreting the meanings of ageing, at both the macro (societal) and micro (individual and inter-personal) levels.
Support for Buy American Campaigns

The emergence of global markets now ensures consumers the opportunity to purchase products from around the world. The success of imported products in the United States attests to their growing popularity among American consumers. While imports often lead to increased consumer satisfaction, the resulting global competition has also brought the loss of jobs for many American workers. Consequently, labor unions and other industry groups have urged American consumers to "Buy American. " This study uses constructs taken from prosocial literature to provide an explanation for consumers' willingness to purchase domestically produced items as a way to support threatened American workers. Data correlation and regression analysis and also cluster and discriminant analysis. Results showed willingness to buy Amerian is explained by the consumers' perceived salience of the problem, social concern, perceived deservingness of the workers, ethno-national tendencies, pereived inequity of the situation, sense of similarity .
The effect of supplementation of clove and agrimony or clove and lemon balm on growth performance, antioxidant status and selected indices of lipid profile of broiler chickens.

The study investigated the effects of diet supplementation with 1% clove flower buds powder combined with either 0.2% lemon balm extract or 0.2% agrimony extract (each of the two pulverized extracts supplied through drinking water) on body weight of broilers, total feed intake, feed conversion ratio and the carcass yield, activity of superoxide dismutase (SOD, EC 1.15.1.1) and glutathione peroxidase (GSH-Px, EC 1.11.1.9) in blood, concentration of sulfhydryl (-SH) groups, malondialdehyde (MDA), vitamin A and E, low-density lipoproteins in the blood plasma, serum cholesterol, total lipids, triglycerides and high-density lipoproteins in broiler chickens at 42 days of age. On the day of hatching, 120 male and female broilers of Cobb 500 were randomly divided into three groups. The control group (1st group) of broilers received a basal diet (BD) without any feed and water additive. Both experimental groups of chicks were fed BD enriched with clove (Syzygium aromaticum L.) powder at a dose of 10 g/kg DM for 42 days. Moreover, either lemon balm (Mellisa officinalis L.) extract or agrimony (Agrimonia eupatoria L.) extract diluted with drinking water (2:1000) was given to broilers in the 2nd and 3rd group respectively. The results indicated that feeding the diets enriched with selected herbal supplements failed to affect the growth performance of broiler chickens at 42 days of age. In addition, this supplementation had no influence on the activities of SOD and GSH-Px, concentration of vitamin A and selected lipid metabolism indices. On the other hand, we observed beneficial effects on some indices of the antioxidant status (increased concentration of -SH groups and vitamin E, decreased concentration of MDA) in the blood of broilers in both experimental groups in comparison with the control group of chickens (p < 0.05). Furthermore, a slightly better antioxidant capacity was found in the blood of broilers supplied the combination of clove and lemon balm compared to clove and agrimony (vitamin E, 11.26 ± 0.73 vs. 9.73 ± 0.64 μmol/L, p < 0.05 respectively). It could be concluded that supplementation of the diet with clove flower buds powder combined with lemon balm extract or agrimony extract dissolved in drinking water has a potential to increase the antioxidant status but fails to influence either the growth performance or the selected lipid metabolism indices of broilers at the age of 42 days.
Children of Alcoholics: A School-Based Comparative Study

This study investigates children of alcoholics (COAs) and their cohorts who are not affected by parental alcoholism (non-COAs). Participants include fourth through sixth grade students who are identified as COAs and non-COAs. The study examines differences between COAs and non-COAs on measures of internalized shame, self-esteem, perceived support, and teacher behavior ratings. Results indicate that COAs and non-COAs demonstrate no significant differences on measures of social support and shame. In contrast, self-esteem and teacher ratings for COAs are significantly lower in comparison to ratings for non-COAs. In addition, teacher ratings of male COAs are significantly negatively affected by their COA status, whereas female COA and non-COA teacher ratings do not differ significantly.
THE NUMBER OF SECRETORY VESICLES REMAINS UNCHANGED FOLLOWING EXOCYTOSIS

Earlier studies using electron microscopy demonstrate that there is no loss of secretory vesicles following exocytosis. Depletion however, of vesicular contents resulting in the formation of empty or partially empty vesicles is seen in electron micrographs, post exocytosis, in a variety of cells. Our studies using atomic force microscopy (AFM) reveal that following stimulation of secretion, live pancreatic acinar cells having 100–180nm in diameter fusion pores located at the apical plasma membrane, dilate only 25–35% during exocytosis. Since secretory vesicles in pancreatic acinar cells range in size from 200nm to 1200nm in diameter, their total incorporation at the fusion pore, would distend the structure much more then what is observed. These earlier results prompted the current study to determine secretory vesicle dynamics in live pancreatic acinar cells following exocytosis. AFM studies on live acinar cells reveal no loss of secretory vesicle number following exocytosis. Parallel studies using electron microscopy, further confirmed our AFM results. These studies demonstrate that following stimulation of secretion, membrane‐bound secretory vesicles transiently dock and fuse to release vesicular contents.
Differential expression of γ‐aminobutyric acid type B receptor subunit mRNAs in the developing nervous system and receptor coupling to adenylyl cyclase in embryonic neurons

γ‐Aminobutyric acid type B receptors (GABABRs) mediate both slow inhibitory synaptic activity in the adult nervous system and motility signals for migrating embryonic cortical cells. Previous papers have described the expression of GABABRs in the adult brain, but the expression and functional significance of these gene products in the embryo are largely unknown. Here we examine GABABR expression from rat embryonic day 10 (E10) to E18 compared with adult and ask whether embryonic cortical neurons contain functional GABABR. GABABR1 transcript levels greatly exceed GABABR2 levels in the developing neural tube at E11, and olfactory bulb and striatum at E17 but equalize in most regions of adult nervous tissue, except for the glomerular and granule cell layers of the main olfactory bulb and the striatum. Consistent with expression differences, the binding affinity of GABA for GABABRs is significantly lower in adult striatum compared with cerebellum. Multiple lines of evidence from in situ hybridization, RNase protection, and real‐time PCR demonstrate that GABABR1a, GABABR1b, GABABR1h (a subunit subtype, lacking a sushi domain, that we have identified in embryonic rat brain), GABABR2, and GABABL transcript levels are not coordinately regulated. Despite the functional requirement for a heterodimer of GABABR subunits, the expression of each subunit mRNA is under independent control during embryonic development, and, by E18, GABABRs are negatively coupled to adenylyl cyclase in neocortical neurons. The presence of embryonic GABABR transcripts and protein and functional receptor coupling indicates potentially important roles for GABABRs in modulation of synaptic transmission in the developing embryonic nervous system. J. Comp. Neurol. 473:16–29, 2004. © 2004 Wiley‐Liss, Inc.
Polychlorinated Biphenyls and Hexachlorobenzene in Full-Term Neonates

Objective: To determine actual reference values of polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in full-term neonates. Patients and Methods: Cord blood samples were taken from 200 healthy, full-term neonates in 1998. Blood specimens were immediately centrifuged, and serum was stored in glass tubes at –20°C up to analysis. Six PCB congeners (IUPAC No. 28, 52, 101, 138, 153, and 180) and HCB were determined with capillary gas chromatography with electron capture detection. Study groups were tested on mean differences with Wilcoxon’s test of independent samples. The 95th percentiles by rank were calculated as reference values. Results: One sample was excluded from further evaluation because of unusually high PCB concentrations. Personal data of the remaining 199 newborns showed 106 male and 93 female neonates. Mean gestational age was 40 weeks (range 38–43 weeks), mean birth weight was 3,450 g (2,300–5,060 g). The concentrations of the lower-chlorinated PCB congeners 28, 52, and 101 were below the detection limit with exception of two probes. Reference values (95th percentile by rank) of the higher-chlorinated PCB congeners and HCB were as follows: PCB 138, 0.5 µg/l; PCB 153, 0.5 µg/l; PCB 180, 0.4 µg/l; and HCB, 0.5 µg/l. Conclusions: The results of the present study clearly demonstrate a further decline in the prenatal uptake of PCBs and HCB since 1994–1995. During the past 15 years, a 75% decline in the prenatal burden with PCBs and a 90% reduction in the burden with HCB could be demonstrated.
Acellular Cadaveric Dermis (AlloDerm): A New Alternative for Abdominal Hernia Repair

AlloDerm is an intact human tissue matrix with the critical biochemical and structural components of the dermal extracellular scaffold that enable it to recellularize and revascularize. Its biologic nature provides AlloDerm with an improved capacity to reintegrate with surrounding tissues and less inclination toward infection, erosion, extrusion, and rejection compared with synthetic tissue replacement materials. This retrospective review describes the experience with AlloDerm for incisional hernia and transverse rectus abdominis musculocutaneous flap reconstructions at a plastic surgery practice that handles complex, nonprimary repairs. AlloDerm was observed to provide exceptional safety and tolerability, and to become reintegrated and vascularized with surrounding tissue for tolerable and persistent tissue replacement.
MicroRNA-155 Promotes Resolution of Hypoxia-Inducible Factor 1α Activity during Prolonged Hypoxia

ABSTRACT The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1α (but not HIF-2α) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxia-inducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1α mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1α in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1α mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1α stabilization and activity. Based on these data and a mathematical model of HIF-1α suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1α activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1α-dependent transcription.
Photodynamic therapy in the management of juxtapapillary capillary haemangiomas

Capillary haemangiomas occurring on or adjacent to the optic disc pose unique therapeutic problems. Their natural history is highly variable, but has a propensity to lead to the development of progressive exudate with marked deterioration in visual acuity, often culminating in retinal detachment and vitreal haemorrhages. On reviewing the literature, no therapeutic modality has demonstrated an efficacy in treating the lesion and providing an acceptable visual acuity result. A case of a 61‐year‐old man with a left‐sided juxtapapillary capillary haemangioma treated with verteporfin photodynamic therapy is described. The patient's visual acuity improved from 6/36 to 6/12 initially, with an appreciable reduction in exudate and lesion size. Subsequent treatments failed to eradicate the lesion, with visual acuity stabilizing at 6/60. With larger cohorts of patients and variable treatment parameters, the true efficacy of photodynamic therapy to treat these lesions may be determined.
Quantitative comparison of OSEM and penalized likelihood image reconstruction using relative difference penalties for clinical PET

Ordered subset expectation maximization (OSEM) is the most widely used algorithm for clinical PET image reconstruction. OSEM is usually stopped early and post-filtered to control image noise and does not necessarily achieve optimal quantitation accuracy. As an alternative to OSEM, we have recently implemented a penalized likelihood (PL) image reconstruction algorithm for clinical PET using the relative difference penalty with the aim of improving quantitation accuracy without compromising visual image quality. Preliminary clinical studies have demonstrated visual image quality including lesion conspicuity in images reconstructed by the PL algorithm is better than or at least as good as that in OSEM images. In this paper we evaluate lesion quantitation accuracy of the PL algorithm with the relative difference penalty compared to OSEM by using various data sets including phantom data acquired with an anthropomorphic torso phantom, an extended oval phantom and the NEMA image quality phantom; clinical data; and hybrid clinical data generated by adding simulated lesion data to clinical data. We focus on mean standardized uptake values and compare them for PL and OSEM using both time-of-flight (TOF) and non-TOF data. The results demonstrate improvements of PL in lesion quantitation accuracy compared to OSEM with a particular improvement in cold background regions such as lungs.
Screening for Diabetic Retinopathy: The wide-angle retinal camera

OBJECTIVE— To define the test characteristics of four methods of screening for diabetic retinopathy. RESEARCH DESIGN AND METHODS— Four screening methods (an exam by an ophthalmologist through dilated pupils using direct and indirect ophthalmoscopy, an exam by a physician's assistant through dilated pupils using direct ophthalmoscopy, a single 45° retinal photograph without pharmacological dilation, and a set of three dilated 45° retinal photographs) were compared with a reference standard of stereoscopic 30° retinal photographs of seven standard fields read by a central reading center. Sensitivity, specificity, and positive and negative likelihood ratios were calculated after dichotomizing the retinopathy levels into none and mild nonproliferative versus moderate to severe nonproliferative and proliferative. Two sites were used. All patients with diabetes in a VA hospital outpatient clinic between June 1988 and May 1989 were asked to participate. Patients with diabetes identified from a laboratory list of elevated serum glucose values were recruited from a DOD medical center. RESULTS— The subjects (352) had complete exams excluding the exam by the physician's assistant that was added later. The sensitivities, specificities, and positive and negative likelihood ratios are as follows: ophthalmologist 0.33, 0.99, 72, 0.67; photographs without pharmacological dilation 0.61, 0.85, 4.1, 0.46; dilated photographs 0.81, 0.97, 24, 0.19; and physician's assistant 0.14, 0.99, 12, 0.87. CONCLUSIONS— Fundus photographs taken by the 45° camera through pharmacologically dilated pupils and read by trained readers perform as well as ophthalmologists for detecting diabetic retinopathy. Physician extenders can effectively perform the photography with minimal training but would require more training to perform adequate eye exams. In this older population, many patients did not obtain adequate nonpharmacological dilation for use of the 45° camera.
Pressure‐aided transfusion of platelets: does it affect the platelets?

BACKGROUND: In massively bleeding patients, pressure infusers are used for transfusion of red blood cells and plasma but not for platelets (PLTs) due to an assumed negative effect on the PLTs. This study examined whether pressure‐aided in vitro transfusion affected the number, activation state, and/or function of the PLTs as measured by flow cytometry and thrombelastography (TEG).
Economic Freedom and Income Inequality: Does Political Regime Matter?

There is a growing literature studying the effects of economic freedom and democracy on income inequality; nevertheless, the inequality-effects of both factors are apparently studied separately. This paper revisits the income inequality-economic freedom nexus and uncovers the role of political regime in explaining the relationship. Using the latest inequality data from Standardized World Income Inequality (SWIID) version 5.0 for a sample of countries up to 115 over 1970–2014 period, and via dynamic panel GMM estimation method, an inequality model that explicitly captures the interaction effect of economic freedom and democracy is estimated. The findings demonstrate that economic freedom has positive effect on income inequality. The estimated size of inequality-increasing effects of economic freedom is substantial, ranging between 0.3% and 0.5% per annum. Nevertheless, the findings show that the freedom-induced inequality is attenuated in the presence of a democratic regime in the countries under study. Furthermore, freedom of international trade and market deregulation are shown to be the two most consistently significant liberalization policies across the baseline estimations and various sensitivity tests. The paper is concluded with some policy implications.
Comparing prenatal and neonatal diagnosis of hemoglobinopathies.

OBJECTIVES To compare the results of prenatal and neonatal hemoglobinopathy screening, a pilot program was developed at the Northern California Kaiser Permanente Health Care Program, a prepaid health maintenance program serving 2.5 million members. METHODS In this program, 54,700 pregnant women were screened for hemoglobinopathies. RESULTS Of the 54,700 women screened, 1019 (1.9%) had a hemoglobinopathy trait, and 81 women with at-risk fetuses were identified. Half the women with fetuses at risk for thalassemia accepted prenatal diagnosis; of those whose fetuses were at risk for sickle-cell disease or other hemoglobinopathies, 30% accepted prenatal diagnosis. Of the 81 at-risk couples, 53 refused amniocentesis for definitive fetal diagnosis; only 28 (35%) accepted; all 4 women who were carrying a fetus with thalassemia major elected to terminate the pregnancy. Only 7 of the 21 cases of hemoglobinopathies were diagnosed prenatally; 14 were discovered neonatally. CONCLUSIONS Prenatal screening was not found to be an ideal method of identifying hemoglobinopathies of the newborn in this large population. With cost-effectiveness a high priority in health care delivery, we believe that testing of newborns for hemoglobinopathies will continue to be the preferred screening method. A combined prenatal and neonatal program would offer the maximum benefit to patients by adding prenatal counseling, parental options, education, and early complete diagnosis to neonatal screening.
Development and characterization of 21 EST-derived microsatellite markers in Vicia faba (fava bean).

PREMISE OF THE STUDY Expressed sequence tag (EST)-derived microsatellite simple sequence repeat (SSR) markers were developed in Vicia faba L. by screening the NCBI database. Markers were validated and explored for size polymorphism among fava bean accessions. METHODS AND RESULTS Twenty-one EST-SSR primer pairs were identified, and the loci characterized were size polymorphic among 32 fava bean genotypes from diverse geographical locations. The number of alleles (N(a)) per locus ranged from 2 to 9, and expected heterozygosity (H(E)) ranged from 0.0476 to 0.8304, respectively. CONCLUSIONS These markers will be useful to study genetic diversity, genetic mapping, and molecular breeding in fava bean.