Miracle-dz/UniFAR-FTUs huggingface dataset:
T Cell Development Critically Depends on Prethymic Stromal Patched Expression

We recently described that T cell specification in mice deficient in the Hedgehog (Hh) receptor Patched (Ptch) is blocked at the level of the common lymphoid progenitor in the bone marrow (BM). Adoptive transfer of wild-type BM in Ptch-deficient mice provides evidence that T cell development strictly depends on Ptch expression in the nonhematopoietic compartment. Transplantation experiments using BM deficient in the glucocorticoid receptor exclude any involvement of the stress hormone corticosterone in our model. Using cell-type–specific knockout mice, we show that T cell development is independent of T cell-intrinsic Ptch expression. Furthermore, Ptch expression by the thymus stroma is dispensable, as revealed by fetal thymus organ culture and thymus transplantation. In contrast, analysis of the earliest thymic progenitors in Ptch-deficient mice indicated that Ptch is required for the development or supply of thymic homing progenitors that give rise to earliest thymic progenitors. Collectively, our findings identified Ptch as an exclusive T cell-extrinsic factor necessary for proper development of T cells at their prethymic stage. This observation may be important for current considerations using Hh inhibitors upstream of Ptch in diseases accompanied by aberrant Hh signaling.
The critical role of information sharing to the value proposition of a food systems network

ABSTRACT With goal-directed networks being used so extensively as a strategy to achieve ‘collective impact,’ increased attention is being paid to the investment of participating member organizations’ time, and informational, financial, and human capital in these efforts. Authors draw on the concept of ‘value proposition’ from the business and public administration literature and use extensive network data from a food systems planning network to test hypotheses focusing on the positionality of member organizations within specific operational subnetworks by correlating positionality with multiple assessments of value. Results indicate that embeddedness in the information sharing subnetwork most strongly correlates with member value proposition.
Five-year corneal graft survival. A large, single-center patient cohort.

OBJECTIVE To determine the survival rates and causes of secondary graft failure in a large, consecutive series of penetrating keratoplasties. DESIGN All eyes undergoing penetrating keratoplasty at a single center were evaluated for factors relating to penetrating keratoplasty preoperatively, surgically, and postoperatively at 1, 3, 6, 9, 12, 18, and 24 months and then at yearly intervals. Since 1986, data analysis has been prospective. SETTING A large, private practice, tertiary center for corneal disorders and surgery. PATIENTS A consecutive series of 1819 penetrating keratoplasties performed from August 1982 through August 1990; 13 eyes with primary graft failure were excluded. MAIN OUTCOME MEASURE Graft failure and causes of failure. Follow-up ranged from 1 to 96 months, with a mean of 26.6 months. RESULTS Pseudophakic bullous keratopathy was the most common diagnosis necessitating keratoplasty (38.6%). Secondary failures occurred 111 times (6.1%). The 2- and 5-year survival rates for all grafts in the study were 95% and 91%, respectively. While endothelial failure as a result of immunologic allograft reactions was the most common cause of graft failure (27%), problems with the external surface of the graft caused nearly as many failures (25%). The risk of failure from surface-related problems was highest at 3 months after surgery. There were significantly decreased survival rates for grafts in eyes with regrafts (P < .0001), in eyes left aphakic at keratoplasty (P < .0001), and in eyes with deep stromal vascularization (P < .0001). CONCLUSION Penetrating keratoplasty is a successful form of transplantation, and survival rates are gradually increasing. The risk of graft failure appears highest within the first year after transplantation.
Lactation characteristics of nine breeds of cattle fed various quantities of dietary energy.

Milk yield data were collected by weigh-suckle-weigh procedures at approximately 14, 28, 56, 84, 112, 138, 156, 184, and 212 d postpartum for mature Angus, Braunvieh, Charolais, Gelbvieh, Hereford, Limousin, Red Poll, Pinzgauer, and Simmental cows over a 4-yr period. Individual cows were fed at one of four energy intake levels. Parameters characterizing lactation curves for 431 lactations from 179 cows were estimated by nonlinear regression. Differences due to breed, level of energy intake, and the two-factor interaction between breed and level of ME allowance for scale and shape parameters of lactation curves and derived estimates for time of peak lactation, yield at time of peak lactation, and for total yield for a 210-d lactation period were evaluated. Breed and energy intake level were significant sources of variation for all traits. Pooled over energy levels, daily yields at time of peak lactation of Braunvieh, Gelbvieh, and Pinzgauer were greater (P less than .05) than those of Angus, Charolais, Hereford, and Limousin. Simmental and Red Poll were intermediate. Total lactation yield of the Braunvieh exceeded (P less than .05) that of all other breeds with the exception of Gelbvieh. Hereford produced less milk than (P less than .05) the other breeds. The response in yields at time of peak lactation as energy allowances increased for Braunvieh, Charolis, Gelbvieh, Limousin, and Pinzgauer cows were linear and resulted in higher yields at this time. Linear increases in total 210-d yield and times of peak lactation were observed for all breeds with the exception of Hereford.
Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: a magnetic resonance spectroscopy study.

OBJECTIVE Fibromyalgia (FM) has been defined as a systemic disorder that is clinically characterized by pain, cognitive deficit, and the presence of associated psychopathology, all of which are suggestive of a primary brain dysfunction. This study was undertaken to identify the nature of this cerebral dysfunction by assessing the brain metabolite patterns in patients with FM through magnetic resonance spectroscopy (MRS) techniques. METHODS A cohort of 28 female patients with FM and a control group of 24 healthy women of the same age were studied. MRS techniques were used to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women. RESULTS In comparison with healthy controls, patients with FM showed higher levels of glutamate/glutamine (Glx) compounds (mean +/- SD 11.9 +/- 1.6 arbitrary units [AU] versus 13.4 +/- 1.7 AU in controls and patients, respectively; t = 2.517, 35 df, corrected P = 0.03) and a higher Glx:creatine ratio (mean +/- SD 2.1 +/- 0.4 versus 2.4 +/- 1.4, respectively; t = 2.373, 35 df, corrected P = 0.04) in the right amygdala. In FM patients with increased levels of pain intensity, greater fatigue, and more symptoms of depression, inositol levels in the right amygdala and right thalamus were significantly higher. CONCLUSION The distinctive metabolic features found in the right amygdala of patients with FM suggest the possible existence of a neural dysfunction in emotional processing. The results appear to extend previous findings regarding the dysfunction in pain processing observed in patients with FM.
Defining accelerometer thresholds for activity intensities in adolescent girls.

PURPOSE To derive a regression equation that estimates metabolic equivalent (MET) from accelerometer counts, and to define thresholds of accelerometer counts that can be used to delineate sedentary, light, moderate, and vigorous activity in adolescent girls. METHODS Seventy-four healthy 8th grade girls, age 13 - 14 yr, were recruited from urban areas of Baltimore, MD, Minneapolis/St. Paul, MN, and Columbia, SC, to participate in the study. Accelerometer and oxygen consumption (.-)VO(2)) data for 10 activities that varied in intensity from sedentary (e.g., TV watching) to vigorous (e.g., running) were collected. While performing these activities, the girls wore two accelerometers, a heart rate monitor and a Cosmed K4b2 portable metabolic unit for measurement of (.-)VO(2). A random-coefficients model was used to estimate the relationship between accelerometer counts and (.-)VO(2). Activity thresholds were defined by minimizing the false positive and false negative classifications. RESULTS The activities provided a wide range in (.-)VO(2) (3 - 36 mL x kg x min) with a correspondingly wide range in accelerometer counts (1- 3928 counts x 30 s). The regression line for MET score versus counts was MET = 2.01 +/- 0.00171 (counts x 30 s) (mixed model R = 0.84, SEE = 1.36). A threshold of 1500 counts x 30 s defined the lower end of the moderate intensity (approximately 4.6 METs) range of physical activity. That cutpoint distinguished between slow and brisk walking, and gave the lowest number of false positive and false negative classifications. The threshold ranges for sedentary, light, moderate, and vigorous physical activity were found to be 0 - 50, 51- 1499, 1500 - 2600, and >2600 counts x 30 s, respectively. CONCLUSION The developed equation and these activity thresholds can be used for prediction of MET score from accelerometer counts and participation in various intensities of physical activity in adolescent girls.
Detection of the human endogenous retrovirus ERV3-encoded Env-protein in human tissues using antibody-based proteomics

Objectives There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Design Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Participants Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. Setting The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. Main Outcome Measures The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. Results We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. Conclusion This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to human evolution, physiology and disease.
Electronic monitoring: Adherence assessment or intervention?

Abstract PURPOSE: Electronic-monitored adherence is often used as the primary outcome measure for evaluating adherence interventions. However, electronic monitoring may not only measure adherence, but may also improve or impede adherence, making it difficult to assess the extent to which the observed effect size is attributed to the intervention versus electronic monitoring. This study examined whether electronic monitoring and patient diaries alter as well as measure adherence. METHOD: A sample of 180 patients on highly active antiretroviral therapy (HAART) were randomized to one of three adherence surveillance methods (electronic monitoring caps, patient medication diaries, no surveillance control group) for 4 weeks, with adherence measured by a structured interview at baseline and study endpoint; 173 (96%) participants completed the study. RESULTS: After controlling for baseline adherence, a univariate analyses of adherence at study endpoint revealed no significant differences across groups, F(2, 169) = 0.32, p = . 73, with mean adherence rates of 91.4, 92.4, and 93.8 for the electronic monitoring, diaries, and control group, respectively. Similarly, the proportion of participants with good adherence (≥95%) did not differ significantly from baseline to week 4 among all three subgroups. CONCLUSION: These results suggest that electronic monitoring caps and medication diaries do not alter adherence and can be used as outcome measures of interventions without the need to adjust the observed effect size.
Cardiovascular Risk Factors and 5-Year Mortality in the Copenhagen Stroke Study

Background: The treatment of cardiovascular risk factors has improved over the recent years and may have improved survival. The aim of this study was to investigate the up-to-date prognostic significance of cardiovascular risk factors for 5-year survival in a large unselected ischemic stroke population. Methods: We studied 905 ischemic stroke patients from the community-based Copenhagen Stroke Study. Patients had a CT scan and stroke severity was measured by the Scandinavian Stroke Scale on admission. A comprehensive evaluation was performed by a standardized medical examination and questionnaire for cardiovascular risk factors, age, and sex. Follow-up was performed 5 years after stroke, and data on mortality were obtained for all, except 6, who had left the country. Five-year mortality was calculated by the Kaplan-Meier procedure and the influence of multiple predictors was analyzed by Cox proportional hazards analyses adjusted for age, gender, stroke severity, and risk factor profile. Results: In Kaplan-Meier analyses atrial fibrillation (AF), ischemic heart disease, diabetes, and previous stroke were associated with increased mortality, while smoking and alcohol intake were associated with decreased mortality. No association was found for hypertension or intermittent claudication. In the final Cox proportional hazard model predictors of 5-year mortality were AF (hazard ratio, HR 1.4; 95% CI 1.1–1.7), diabetes (HR 1.3; 95% CI 1.0–1.6), smoking (HR 1.2; 95% CI 1.0–1.4), and previous stroke (HR 1.4; 95% CI 1.1–1.7), after adjustment for age, gender, and stroke severity. Conclusions: AF, diabetes, smoking, and previous stroke significantly affect long-term survival. Although smoking and daily alcohol consumption appeared to be associated with improved survival in the univariate analyses, adjustment for other factors and especially age revealed the lethal effect of smoking, while the positive effect of alcohol disappeared. More focus on secondary preventive measures, such as anticoagulation for AF, smoking cessation, and proper treatment of diabetes may significantly improve long-term survival.
Identification and Functional Analysis of Splice Variants of the Germ Cell Soluble Adenylyl Cyclase*

In mammalian germ cells, cAMP signaling is dependent on two forms of adenylyl cyclase, the conventional membrane-bound ACIII and a soluble form of adenylyl cyclase (sAC). Recent elucidation of the sAC sequence indicates that this enzyme is phylogenetically distinct from the membrane-bound AC, does not interact with G proteins, and its activity is regulated by bicarbonate ions. Here we have investigated the properties and regulation of this enzyme during spermatogenesis. Two different transcripts encoding a full-length and truncated sAC were identified by reverse transcriptase-polymerase chain reaction and RNase protection analysis. The truncated sAC transcript lacks exon 11 with a premature termination of the open reading frame after the catalytic domain. Reverse transcriptase-polymerase chain reaction with testis RNA from adult mouse and rat of different ages, as well as RNase protection, showed that both transcripts are absent at 11 days of age, appear between 20 and 30 days of age, and are retained in the adult testis. The presence of corresponding proteins in testis, germ cells, and spermatozoa was demonstrated by fast protein liquid chromatography and differential immunoprecipitation with full-length sAC-specific antibodies. Bicarbonate ions activated both sAC forms and increased cAMP levels in germ cells isolated from 25- and 50-day-old rats and adult rats in a concentration-dependent manner. These findings provide evidence that full-length and truncated sAC are generated by alternate splicing. Both forms are active in spermatids, and the bicarbonate present in the seminiferous tubule may be a signal that regulates cAMP levels in these cells.
Photophysical Properties of Xanthophylls in Carotenoproteins from Human Retina¶

Abstract The macula of the human retina contains high amounts of the xanthophyll carotenoids lutein and zeaxanthin [a mixture of (3R,3′R)-zeaxanthin and (3R,3′S-meso)-zeaxanthin]. Recently, it was shown that the uptake and the stabilization of zeaxanthin and lutein into the retina are likely to be mediated by specific xanthophyll-binding proteins (XBP). Here, we have used femtosecond pump–probe spectroscopy to study the dynamics of the S1 state of these xanthophylls in xanthophyll-enriched and native XBP. The results from the native XBP and the enriched XBP were then compared with those for carotenoids in organic solvents and in detergent micelles. Steady-state and transient absorption spectra show that the incorporation of xanthophylls into the protein causes a redshift of the spectra, which is stronger for lutein than for zeaxanthin. The transient absorption spectra further indicate that a part of the xanthophylls remains unbound in the xanthophyll-enriched XBP. The transient absorption spectra of the native XBP prove the presence of both xanthophylls in native XBP. Although the S1 lifetime of lutein does not exhibit any changes when measured in solution, micelles or XBP, we have observed the influence of the environment on the S1 lifetime of meso-zeaxanthin, which has a longer (12 ps) lifetime in XBP than in solution (9 ps). The most pronounced effect was found for vibrational relaxation in the S1 state, which is significantly slower for xanthophylls in XBP compared with micelles and solution. This effect is more pronounced for meso-zeaxanthin, suggesting a specific site of binding of this carotenoid to XBP.
Jointly Designed Nonbinary LDPC Convolutional Codes and Memory-Based Decoder Architecture

In this paper, a design approach for architecture- aware nonbinary low-density parity-check convolutional codes (NB-LDPC-CCs) is presented to jointly optimizes the code performance and decoder complexity for achieving high energy-efficiency decoder. The proposed NB-LDPC-CCs not only feature simple structure and low degree, but also compete with other published NB-LDPC-CCs on error-correction capability. With these codes, we present a memory-based layered decoder architecture, where the computation units and the scheduling of the computations are optimized to increase energy efficiency. To demonstrate the feasibility of proposed techniques, a time-varying (50,2,4) NB-LDPC-CC over GF(256) is constructed, and associated decoder is implemented in 90 nm CMOS. The code can reach BER=10-5 at SNR=0.9 dB, and support multi code rates with puncturing. Comparing with the state-of-the-art designs, the proposed decoder can save 74% power under the same number of iterations, making it suitable for emerging Internet of Things (IoT) applications.
Systemic lupus erythematosus in three ethnic groups: I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset. LUMINA Study Group. Lupus in minority populations, nature versus nurture.

OBJECTIVE To study the relative impact of immunogenetic versus socioeconomic factors on systemic lupus erythematosus (SLE) at disease onset/presentation. METHODS Medical records regarding SLE onset/ presentation were abstracted on 229 SLE patients who were enrolled in a prospective lupus outcome study. Patients were grouped in equivalent proportions of Caucasians, African Americans, and Hispanics. HLA-DRB1, DQA1, and DQB1 oligotyping, as well as C4 and CR1 allotyping, were carried out by standard methods. In addition to these genetic factors, data on ethnicity, age at SLE onset, monthly income, level of education, and home ownership were entered into stepwise logistic or stepwise multiple linear regression models as independent variables, and each specific clinical feature (neurologic, renal, and cardiovascular disease due to SLE), as well as the total Systemic Lupus Activity Measure (SLAM) score and physician's global assessment of disease activity at disease onset, were entered as dependent variables. RESULTS HLA-DRB1*0301 (DR3), DRB1*1503 (DR2), and DRB1*08 (DR8) alleles were more frequently found in Caucasians, African Americans, and Hispanics, respectively. Hispanics were more likely to have cardiac and renal disease, as well as a higher physician's global assessment of disease activity. African Americans were more likely to have neurologic disease, renal disease, and a higher SLAM score. Those with less education had a higher SLAM score. Patients with HLA-DRB1*01 had less renal disease and a lower SLAM score. Those with C4A*3 alleles had a higher SLAM score and a higher physician's global assessment of disease activity. CONCLUSION Both genetic and socioeconomic determinants, as well as other factors associated with Hispanic and African-American ethnicity, affect the presentation of SLE.
Learning-Induced Enduring Changes in Functional Connectivity among Prefrontal Cortical Neurons

Current thinking about how memories are stored in the brain has been profoundly influenced by Donald O. Hebb's cell assembly hypothesis, which posits that (1) learning produces a stable alteration in patterns of connectivity among repeatedly coactivated neurons, and (2) memory retrieval involves reactivation of those altered patterns of connectivity. However, learning-induced changes in connectivity that persist over long periods of time have not been clearly demonstrated. In the present study, two spatial navigation tasks and a long-term ensemble recording technique are used to describe long-lasting modifications in functional connectivity (FC) (defined as changes in synchronous firing) of prefrontal cortical neurons in behaving rats. Animals were initially trained to alternate visiting two spatial locations on a figure-8-shaped maze to obtain a reward (alternating task 1). Afterward, while continuing on task 1, animals were additionally trained to visit only one spatial location on the same maze to obtain a reward (unilateral task 2). Multiple single units were recorded while rats were undergoing acquisition, retention, and performance of both tasks. Our data indicate that correlated firing of prefrontal cortical neurons changed significantly in early phases of training when learning rate was maximal but became progressively smaller in later phases when learning reached asymptote. After animals became proficient, FC remained constant, although neuronal activities varied across two different tasks. The present finding of negatively accelerated changes in FC confirms associative learning theories and provides crucial neurophysiological evidence for Hebb's hypothesis.