Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Roles for MyD88 and Toll-Like Receptor 2 during Leishmania braziliensis Infection in Mice

ABSTRACT We have previously reported that Leishmania braziliensis infection can activate murine dendritic cells (DCs) and upregulate signaling pathways that are essential for the initiation of innate immunity. However, it remains unclear whether Toll-like receptors (TLRs) are involved in L. braziliensis-mediated DC activation. To address this issue, we generated bone marrow-derived DCs from MyD88−/− and TLR2−/− mice and examined their responsiveness to parasite infection. While wild-type DCs were efficiently activated to produce cytokines and prime naïve CD4+ T cells, L. braziliensis-infected MyD88−/− DCs exhibited less activation and decreased production of interleukin-12 (IL-12) p40. Furthermore, MyD88−/− mice were more susceptible to infection in that they developed larger and prolonged lesions compared to those in control mice. In sharp contrast, the lack of TLR2 resulted in an enhanced DC activation and increased IL-12 p40 production after infection. As such, L. braziliensis-infected TLR2−/− DCs were more competent in priming naïve CD4+ T cells in vitro than were their controls, findings which correlated with an increased gamma interferon production in vivo and enhanced resistance to infection. Our results suggest that while MyD88 is indispensable for the generation of protective immunity to L. braziliensis, TLR2 seems to have a regulatory role during infection.
Reconstitution of the human cytoplasmic dynein complex

Cytoplasmic dynein is the major motor protein responsible for microtubule minus-end–directed movements in most eukaryotic cells. It transports a variety of cargoes and has numerous functions during spindle assembly and chromosome segregation. It is a large complex of about 1.4 MDa composed of six different subunits, interacting with a multitude of different partners. Most biochemical studies have been performed either with the native mammalian cytoplasmic dynein complex purified from tissue or, more recently, with recombinant dynein fragments from budding yeast and Dictyostelium. Hardly any information exists about the properties of human dynein. Moreover, experiments with an entire human dynein complex prepared from recombinant subunits with a well-defined composition are lacking. Here, we reconstitute a complete cytoplasmic dynein complex using recombinant human subunits and characterize its biochemical and motile properties. Using analytical gel filtration, sedimentation-velocity ultracentrifugation, and negative-stain electron microscopy, we demonstrate that the smaller subunits of the complex have an important structural function for complex integrity. Fluorescence microscopy experiments reveal that while engaged in collective microtubule transport, the recombinant human cytoplasmic dynein complex is an active, microtubule minus-end–directed motor, as expected. However, in contrast to recombinant dynein of nonmetazoans, individual reconstituted human dynein complexes did not show robust processive motility, suggesting a more intricate mechanism of processivity regulation for the human dynein complex. In the future, the comparison of reconstituted dynein complexes from different species promises to provide molecular insight into the mechanisms regulating the various functions of these large molecular machines.
Counting networks and multi-processor coordination

Many fundamental multi-processor coordination problems can be expressed aa counting problems: processes must, cooperate to assign successive values from a given range, such as addresses in memory or destinations on an interconnection network. Conventional solutions to these problems perform poorly because of synchronization bottlenecks and high memory contention. Motivated by observations on the behavior of sorting networks, we offer a completely new approach to solving such problems. We introduce a new class of networks called counting networks, i.e., networks that can be used to count. We give a counting network construction of depth Iogz n using n log2 n “gates, ” Based on this construction, we provide coordination algorithms that avoid the sequential bottlenecks inherent to former solutions, and have subst ant i all y lower contention. Finally, to show that counting networks are *Carnegie Mellon University. t D&taf Equipment Corporation, Cambridge Research Lab. i MIT Lab. for Computer Science. Supported by ONR contract NOOO14-91-J-1O46, NSF grant CCR-S915206, DARPA contract NOO014-89-J-198S, and by a Rothschild postdoctoral fellowship. A large part of this work was performed while the author was at IBM’s Almaden Research Center. not merely mathematical creatures, we provide experimental evidence that they outperform conventional synchronization techniques under a variety of circumstances.
Effect of Smoking and Caffeine Consumption on Polybrominated Diphenyl Ethers (PBDE) and Polybrominated Biphenyls (PBB)

Effect of smoking and caffeine consumption (CC) on the levels of polybrominated diphenyl ethers (PBDE) and polybrominated biphenyls (PBB) has not been adequately studied. Data from 2003–2004 National Health and Nutrition Examination Survey (n = 1013) to simultaneously evaluate the effect of smoking and CC on levels of serum 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47), 2,2',4,4',5-pentabromodiphenyl ether (PBDE-99), 2,2',4,4',6-pentabromodiphenyl ether (PBDE-100), 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE-153), and their sum and 2,2',4,4',5,5'-hexabromobiphenyl (PBB-153) were used. Regression models were fitted with logs of PBDE and PBB as dependent variables and age, age2, gender, body mass index (BMI), race/ethnicity, smoking status, fish/shellfish consumption status during the last 30 d, and CC as independent variables. For lipid-adjusted models, age was negatively associated while age2 was positively associated with almost all PBDE models. The reverse was the case for PBB-153. Body mass index was found to be negatively associated with PBDE-153 and PBB-153. Levels of all whole weight PBDE increased with levels of total lipid. Smoking was not markedly associated with concentrations of either PBDE or PBB. Males displayed significantly higher levels of PBDE-153 and ΣPBDE. For the whole weight PBDE congeners 47, 99, and 100 and PBB-153, non-Hispanic black (NHB) males showed significantly higher levels than NHB females.
Hyaluronic Acid Production in Bacillus subtilis

ABSTRACT The hasA gene from Streptococcus equisimilis, which encodes the enzyme hyaluronan synthase, has been expressed in Bacillus subtilis, resulting in the production of hyaluronic acid (HA) in the 1-MDa range. Artificial operons were assembled and tested, all of which contain the hasA gene along with one or more genes encoding enzymes involved in the synthesis of the UDP-precursor sugars that are required for HA synthesis. It was determined that the production of UDP-glucuronic acid is limiting in B. subtilis and that overexpressing the hasA gene along with the endogenous tuaD gene is sufficient for high-level production of HA. In addition, the B. subtilis-derived material was shown to be secreted and of high quality, comparable to commercially available sources of HA.
Evaluation of mitochondrial DNA copy number estimation techniques

Mitochondrial DNA copy number (mtDNA-CN), a measure of the number of mitochondrial genomes per cell, is a minimally invasive proxy measure for mitochondrial function and has been associated with several aging-related diseases. Although quantitative real-time PCR (qPCR) is the current gold standard method for measuring mtDNA-CN, mtDNA-CN can also be measured from genotyping microarray probe intensities and DNA sequencing read counts. To conduct a comprehensive examination on the performance of these methods, we use known mtDNA-CN correlates (age, sex, white blood cell count, Duffy locus genotype, incident cardiovascular disease) to evaluate mtDNA-CN calculated from qPCR, two microarray platforms, as well as whole genome (WGS) and whole exome sequence (WES) data across 1,085 participants from the Atherosclerosis Risk in Communities (ARIC) study and 3,489 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). We observe mtDNA-CN derived from WGS data is significantly more associated with known correlates compared to all other methods (p < 0.001). Additionally, mtDNA-CN measured from WGS is on average more significantly associated with traits by 5.6 orders of magnitude and has effect size estimates 5.8 times more extreme than the current gold standard of qPCR. We further investigated the role of DNA extraction method on mtDNA-CN estimate reproducibility and found mtDNA-CN estimated from cell lysate is significantly less variable than traditional phenol-chloroform-isoamyl alcohol (p = 5.44×10-4) and silica-based column selection (p = 2.82×10-7). In conclusion, we recommend the field moves towards more accurate methods for mtDNA-CN, as well as re-analyze trait associations as more WGS data becomes available from larger initiatives such as TOPMed.
Neurogenin3 Cooperates with Foxa2 to Autoactivate Its Own Expression*

Background: Neurogenin3 is essential for pancreatic endocrine differentiation, but the mechanisms regulating its expression are poorly understood. Results: Neurogenin3 transcriptionally activates its own gene in a direct autoregulatory loop involving Foxa2. Conclusion: Neurogenin3 and Foxa2 cooperate during endocrine differentiation. Significance: Elucidating the mechanisms governing Neurogenin3 expression and function is crucial to understand pancreatic endocrine differentiation and devise cell replacement therapies in diabetes. The transcription factor Neurogenin3 functions as a master regulator of endocrine pancreas formation, and its deficiency leads to the development of diabetes in humans and mice. In the embryonic pancreas, Neurogenin3 is transiently expressed at high levels for a narrow time window to initiate endocrine differentiation in scattered progenitor cells. The mechanisms controlling these rapid and robust changes in Neurogenin3 expression are poorly understood. In this study, we characterize a Neurogenin3 positive autoregulatory loop whereby this factor may rapidly induce its own levels. We show that Neurogenin3 binds to a conserved upstream fragment of its own gene, inducing deposition of active chromatin marks and the activation of Neurog3 transcription. Additionally, we show that the broadly expressed endodermal forkhead factors Foxa1 and Foxa2 can cooperate synergistically to amplify Neurogenin3 autoregulation in vitro. However, only Foxa2 colocalizes with Neurogenin3 in pancreatic progenitors, thus indicating a primary role for this factor in regulating Neurogenin3 expression in vivo. Furthermore, in addition to decreasing Neurog3 autoregulation, inhibition of Foxa2 by RNA interference attenuates Neurogenin3-dependent activation of the endocrine developmental program in cultured duct mPAC cells. Hence, these data uncover the potential functional cooperation between the endocrine lineage-determining factor Neurogenin3 and the widespread endoderm progenitor factor Foxa2 in the implementation of the endocrine developmental program in the pancreas.
WATER/ICY SUPER-EARTHS: GIANT IMPACTS AND MAXIMUM WATER CONTENT

Water-rich super-Earth exoplanets are expected to be common. We explore the effect of late giant impacts on the final bulk abundance of water in such planets. We present the results from smoothed particle hydrodynamics simulations of impacts between differentiated water(ice)-rock planets with masses between 0.5 and 5 M⊕ and projectile to target mass ratios from 1:1 to 1:4. We find that giant impacts between bodies of similar composition never decrease the bulk density of the target planet. If the commonly assumed maximum water fraction of 75 wt% for bodies forming beyond the snow line is correct, giant impacts between similar composition bodies cannot serve as a mechanism for increasing the water fraction. Target planets either accrete materials in the same proportion, leaving the water fraction unchanged, or lose material from the water mantle, decreasing the water fraction. The criteria for catastrophic disruption of water-rock planets are similar to those found in previous work on super-Earths of terrestrial composition. Changes in bulk composition for giant impacts onto differentiated bodies of any composition (water rock or rock iron) are described by the same equations. These general laws can be incorporated into future N-body calculations of planet formation to track changes in composition from giant impacts.
New data on the morphology of Procamallanus (Procamallanus) annulatus and Procamallanus (Spirocamallanus) monotaxis (Nematoda: Camallanidae) from marine fishes off New Caledonia

SummaryTwo little-known nematode species of the family Camallanidae, intestinal parasites of marine perciform fishes, are reported from off New Caledonia: Procamallanus (Procamallanus) annulatus Yamaguti, 1955 from the goldenlined spinefoot Siganus lineatus (Valenciennes) (Siganidae) and Procamallanus (Spirocamallanus) monotaxis (Olsen, 1952) from the longspine emperor Lethrinus genivittatus Valenciennes and the slender emperor Lethrinus variegatus Valenciennes (both Lethrinidae). Detailed light and electron microscopical studies (the latter used for the first time in these species) revealed some taxonomically important, previously not observed features, such as the presence of deirids, six crescent-shaped elevations surrounding the mouth, three poorly developed protuberances on the female tail tip and circumcloacal papillae and phasmids on the male tail in P. annulatus, and the presence of a circumoral flange, only 12 (instead of 14 reported) cephalic papillae, the shape of deirids and similar numbers (14–17 and 14–15) of spiral ridges in the male and female buccal capsules in P. monotaxis. The fourth-stage larva of P. annulatus is described for the first time. Firststage larvae of both species were found to possess several digital processes at the tail tip. The present findings represent new host and geographical records of these parasite species.
Web site complexity metrics for measuring navigability

In years, navigability has become the pivot of Web site designs. Existing works fall into two categories. The first is to evaluate and assess a Web site's navigability against a set of criteria or check list. The second is to analyse usage data of the Web site, such as the server log files. This work investigates a metric approach to Web site navigability measurement. In comparison with existing assessment and analysis methods, navigability metrics have the advantages of objectiveness and the possibility of using automated tools to evaluate large-scale Web sites. This work proposes a number of metrics for Web site navigability measurement based on measuring Web site structural complexity. We validate these metrics against Weyuker's software complexity axioms, and report the results of empirical studies of the metrics.
Patients who leave the emergency department against medical advice

Objective Discharge against medical advice (DAMA) from the emergency department (ED) accounts for 0.1% to 2.7% of all ED discharges. DAMA carries a risk of increased mortality and readmissions. Our aim was to investigate the general characteristics of DAMA patients and the differences between them and non-DAMA patients. Methods We reviewed data collected by the National Emergency Medical Center between 2010 and 2011. Subjects were categorized into 2 groups, namely, the DAMA group and the non-DAMA group. We compared these groups with respect to age, gender, trauma or non-trauma status, type of hospital, health insurance, level of consciousness on admission, and diagnosis. Results Of 8,000,529 patients, 222,389 (2.78%) left against medical advice. The risk factors for DAMA across all age groups were as follows: no medical insurance (odds ratio [OR], 1.993), initial response to voice (OR, 2.753) or pain (OR, 2.101), trauma admission (OR, 1.126), admission to a local emergency medical center (OR, 1.215), and increased age. A high risk of DAMA was observed among patients with immune, endocrine, psychiatric, neurological, circulatory diseases, and external causes of morbidity and mortality. Conclusion Although DAMA cases account for only a small percentage of hospital discharges, they are important because DAMA patients have high readmission and mortality rates. It is therefore important to understand the general characteristics and predictors of DAMA in order to improve patient outcome and minimize the economic burden on the healthcare system.
Asset Pricing and Sports Betting

I use sports betting markets as a laboratory to test behavioral theories of cross-sectional asset pricing anomalies. Two unique features of these markets provide a distinguishing test of behavioral theories: 1) the bets are completely idiosyncratic and therefore not confounded by rational theories; 2) the contracts have a known and short termination date where uncertainty is resolved that allows any mispricing to be detected. Analyzing more than a hundred thousand contracts spanning two decades across four major professional sports (NBA, NFL, MLB, and NHL), I find momentum and value effects that move betting prices from the open to the close of betting, that are then completely reversed by the game outcome. These findings are consistent with delayed overreaction theories of asset pricing. In addition, a novel implication of overreaction uncovered in sports betting markets is shown to also predict momentum and value returns in financial markets. Finally, momentum and value effects in betting markets appear smaller than in financial markets and are not large enough to overcome trading costs, limiting the ability to arbitrage them away.
Charlson comorbidity index helps predict the risk of mortality for patients with type 2 diabetic nephropathy

Our intent is to examine the predictive role of Charlson comorbidity index (CCI) on mortality of patients with type 2 diabetic nephropathy (DN). Based on the CCI score, the severity of comorbidity was categorized into three grades: mild, with CCI scores of 1–2; moderate, with CCI scores of 3–4; and severe, with CCI scores ≥5. Factors influencing mortality and differences between groups stratified by CCI were determined by logistical regression analysis and one-way analysis of variance (ANOVA). The impact of CCI on mortality was assessed by the Kaplan-Meier analysis. A total of 533 patients with type 2 DN were enrolled in this study, all of them had comorbidity (CCI score >1), and 44.7% (238/533) died. The mortality increased with CCI scores: 21.0% (50/238) patients with CCI scores of 1–2, 56.7% (135/238) patients with CCI scores of 3–4, and 22.3% (53/238) patients with CCI scores ≥5. Logistical regression analysis showed that CCI scores, hemoglobin, and serum albumin were the potential predictors of mortality (P<0.05). One-way ANOVA analysis showed that DN patients with higher CCI scores had lower levels of hemoglobulin, higher levels of serum creatinine, and higher mortality rates than those with lower CCI scores. The Kaplan-Meier curves showed that survival time decreased when the CCI scores and mortality rates went up. In conclusion, CCI provides a simple, readily applicable, and valid method for classifying comorbidities and predicting the mortality of type 2 DN. An increased awareness of the potential comorbidities in type 2 DN patients may provide insights into this complicated disease and improve the outcomes by identifying and treating patients earlier and more effectively.
Airways remodeling is a distinctive feature of asthma and is related to severity of disease.

PURPOSE Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history. SUBJECTS AND METHODS Thirty-four patients with stable asthma (mean age+/-SD: 26.5+/-9.2 years; 10 female) treated with only inhaled beta2-agonists and eight healthy volunteers (mean age+/-SD: 24.6+/-2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease < or = 1 year), nine patients had long asthmatic history (> 1 year and < or = 10 years), and 14 had prolonged asthmatic history (> 10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina. RESULTS In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 14 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. The mean values of subepithelial layer thickness were 12.4+/-3.3 microm (range, 6.8 to 22.1 microm) in asthmatics, and 4.4+/-0.5 microm (range, 3.8 to 5.2 microm) in healthy subjects (p<0.001). Subepithelial layer thickness of those with severe asthma differed significantly from that of patients with moderate and mild asthma (16.7+/-3.1 microm vs 12.1+/-2.7 microm and 10.8+/-2.4 microm, p<0.01 and p<0.003, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient [rs]=0.581; p<0.001), and negatively correlated with baseline FEV1 (rs=-0.553; p<0.001) and PC20 M (rs=-0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer. CONCLUSIONS We confirmed that airways remodeling is a very distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.