Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV patients on antiretroviral therapy have high frequencies of CD8 T cells specific for Immediate Early protein-1 of cytomegalovirus

Objective: To assess the frequency and phenotype of cytomegalovirus (CMV)-specific CD8 T cells in previously immunocompromised HIV patients with stable undetectable HIV viremia due to highly active antiretroviral therapy (HAART). Methods: Twenty-one CMV-seropositive HIV patients with nadir CD4 T-cell counts < 50 × 106 cells/l, at least 4 years on HAART and 6 months of complete viral suppression (< 50 HIV RNA copies/ml) and 12 CMV-seropositive, HIV-seronegative age/sex-matched controls were studied. CD4 and CD8 T-cell responses to whole CMV and two HLA-A*02 restricted CMV peptides [NLV from pp65 and VLE from Immediate Early 1 (IE1)] were measured by interferon (IFN)γ ELISpot. Phenotypes of peptide-specific CD8 T cells were determined by tetramer staining. Results: In the ELISpot assay, HIV patients had significantly more CD8 T cells producing IFNγ in response to VLE than controls, whereas numbers of NLV-specific and CMV-specific IFNγ spots were similar. Four HIV patients and one control had large VLE and/or NLV-specific CD8 T-cell populations despite the absence of CMV-specific CD4 T cells. The majority of peptide-specific CD8 T cells from HIV patients and controls were CD28−, CD45RO+ and CD45RA−. However, a significantly higher proportion of VLE-specific CD8 T cells expressed perforin compared to NLV-specific CD8 T cells in HIV patients. Conclusions: HIV patients had elevated numbers of IE1-specific, IFNγ-producing perforin-positive CD8 T cells compared to controls. As IE1 is expressed early during CMV reactivation, these cells may be important for preventing CMV replication to pathogenic levels. In addition, CMV-specific CD4 T cells are not essential for maintenance of large populations of CMV-specific CD8 T cells in aviremic HIV patients on HAART.
Nogo-66 Receptor Antagonist Peptide (NEP1-40) Administration Promotes Functional Recovery and Axonal Growth After Lateral Funiculus Injury in the Adult Rat

Objective. The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST). Methods. Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry. Results. Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group. Conclusions. NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons.
Mast Cell-Induced Lung Injury in Mice Infected with H5N1 Influenza Virus

ABSTRACT Although an important role for mast cells in several viral infections has been demonstrated, its role in the invasion of highly pathogenic H5N1 influenza virus is unknown. In the present study, we demonstrate that mast cells were activated significantly by H5N1 virus (A/chicken/Henan/1/2004) infection both in vivo and in vitro. Mast cells could possibly intensify the lung injury that results from H5N1 infection by releasing proinflammatory mediators, including histamine, tryptase, and gamma interferon (IFN-γ). Lung lesions and apoptosis induced by H5N1 infection were reduced dramatically by treatment with ketotifen, which is a mast cell degranulation inhibitor. A combination of ketotifen and the neuraminidase inhibitor oseltamivir protected 100% of the mice from death postinfection. In conclusion, our data suggest that mast cells play a crucial role in the early stages of H5N1 influenza virus infection and provide a new approach to combat highly pathogenic influenza virus infection.
Structural basis of Flavivirus NS1 assembly and antibody recognition

Significance Flavivirus nonstructural protein 1 (NS1) is a versatile nonstructural glycoprotein that is expressed on the cell surface and secreted into the extracellular space, where it has immune evasion functions. To date, the structural biology of NS1 is limited, which has hampered a complete understanding of its functions. We describe the previously unidentified high-resolution structure of the C-terminal half of West Nile virus (WNV) and Dengue virus-1 (NS1172–352) NS1 proteins and a separate structure of WNV NS1172–352 with a protective antibody Fab. NS1172–352 forms a head-to-head dimer and adopts a unique fold with an extended β-sheet platform and opposing loop face. These structures have allowed us to develop an architectural model for NS1 assembly and function. The Flavivirus nonstructural protein 1 (NS1) is a conserved, membrane-associated and secreted glycoprotein with replication and immune evasion functions. Secreted NS1 is a hexameric, barrel-shaped lipoprotein that can bind back to the plasma membrane of cells. Antibodies targeting cell surface-associated NS1 can be protective in vivo in a manner dependent on Fc effector functions. We describe here the crystal structure of a C-terminal fragment (residues 172–352) of West Nile (WNV) and Dengue virus NS1 proteins at 1.85 and 2.7 Å resolution, respectively. NS1172–352 assembles as a unique rod-shaped dimer composed of a 16-stranded β-platform flanked on one face by protruding connecting loops. We also determined the 3.0 Å resolution structure of WNV NS1172–352 with the protective 22NS1 antibody Fab, which engages the loop-face of the rod. The head-to-head NS1172–352 dimer we observe in crystal lattices is supported by multiangle light and small-angle X-ray scattering studies. We used the available cryo-electron microscopy reconstruction to develop a pseudoatomic model of the NS1 hexamer. The model was constructed with the NS1172–352 dimeric rod aligned with the long axis of the barrel, and with the loop-face oriented away from the core. Difference densities suggest that the N-terminal region of NS1 forms globular lobes that mediate lateral contacts between dimers in the hexamer. Our model also suggests that the N-terminal lobe forms the surface of the central cavity where lipid binding may occur.
Automatic Effects of Alcohol and Aggressive Cues on Aggressive Thoughts and Behaviors

Numerous studies have shown that alcohol increases aggression. In this article it is proposed that the link between alcohol and aggression is so strong that mere exposure to alcohol-related cues will automatically activate aggressive thoughts and behaviors. Two experiments tested this automaticity theory of alcohol-related aggression. In Experiment 1, participants exposed to alcohol- or weapon-related primes made faster lexical decisions about aggression-related words than did participants exposed to neutral primes. In Experiment 2, participants exposed to alcohol- or aggression-related subliminal primes were more aggressive toward the experimenter than were participants exposed to neutral subliminal primes. In both experiments, the effects of alcohol-related cues were as strong as the effect of aggression-related cues on aggressive thoughts and behaviors. People do not need to drink a drop of alcohol to become aggressive; exposure to alcohol cues is enough to automatically increase aggression.
An Adaptive ARQ Technology for Fast Fading Channel

This paper investigates the adaptive ARQ method for turbo coded communication systems in the fast deep fading environment. Different from the traditional ARQ method, this approach provides various throughput for different quality of service (QoS) in the transportation communications. Based on the typical phenomena observed in the turbo coded communication systems under fast deep fading channels, we defined a new parameter to control the ARQ protocol. We also computed the threshold for the new parameter, similar to the BER prediction in EXIT chart. Simulation results demonstrated that the modified ARQ method reduces the bit error rate with less system cost and lower-complexity
Influence of helminth infections on childhood nutritional status in lowland Bolivia

Infectious disease, such as diarrheal disease, respiratory infections, and parasitic infections, are an important source of nutritional and energetic stress in many populations. Inspired by the research and methodological innovations of A. Roberto Frisancho, this work considers the impact of childhood environment and local disease ecology on child health and nutritional patterns among an indigenous group in lowland Bolivia. Specifically, we examine the association between soil‐transmitted helminth infection, especially hookworm species, and anthropometric markers of short‐ and long‐term nutritional status. Fecal samples, anthropometric dimensions, and health interviews were collected for 92 children ranging in age from 2.0 to 10.9 years. Microscopic examination revealed high levels of parasitic infection, with 76% of children positive for hookworm species infections (77% of girls and 74% of boys). Less common infections included Ascaris lumbricoides, Trichurius trichiura, and Strongyloides stercoralis with only 15% of children positive for multiple‐species infections. After adjusting for sex and age, no statistically significant associations were observed between helminth infections and the frequency of reported illness or anthropometric measures of nutritional status. These data demonstrate the difficulty of assessing nutritional impacts of endemic infections. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.
COX-2 Elevates Oncogenic miR-526b in Breast Cancer by EP4 Activation

MicroRNAs (miRs) are small regulatory molecules emerging as potential biomarkers in cancer. Previously, it was shown that COX-2 expression promotes breast cancer progression via multiple mechanisms, including induction of stem-like cells (SLC), owing to activation of the prostaglandin E2 receptor EP4 (PTGER4). COX-2 overexpression also upregulated microRNA-526b (miR-526b), in association with aggressive phenotype. Here, the functional roles of miR-526b in breast cancer and the mechanistic role of EP4 signaling in miR-526b upregulation were examined. A positive correlation was noted between miR-526b and COX-2 mRNA expression in COX-2 disparate breast cancer cell lines. Stable overexpression of miR-526b in poorly metastatic MCF7 and SKBR3 cell lines resulted in increased cellular migration, invasion, EMT phenotype and enhanced tumorsphere formation in vitro, and lung colony formation in vivo in immunodeficient mice. Conversely, knockdown of miR-526b in aggressive MCF7-COX-2 and SKBR3-COX-2 cells reduced oncogenic functions and reversed the EMT phenotype, in vitro. Furthermore, it was determined that miR-526b expression is dependent on EP4 receptor activity and downstream PI3K–AKT and cyclic AMP (cAMP) signaling pathways. PI3K–AKT inhibitors blocked EP4 agonist–mediated miR-526b upregulation and tumorsphere formation in MCF7 and SKBR3 cells. NF-κB inhibitor abrogates EP agonist–stimulated miRNA expression in MCF7 and T47D cells, indicating that the NF-κB pathway is also involved in miR-526b regulation. In addition, inhibition of COX-2, EP4, PI3K, and PKA in COX-2–overexpressing cells downregulated miR-526b and its functions in vitro. Finally, miR-526b expression was significantly higher in cancerous than in noncancerous breast tissues and associated with reduced patient survival. In conclusion, miR-526b promotes breast cancer progression, SLC-phenotype through EP4-mediated signaling, and correlates with breast cancer patient survival. Implications: This study presents novel findings that miRNA 526b is a COX-2 upregulated, oncogenic miRNA promoting SLCs, the expression of which follows EP4 receptor-mediated signaling, and is a promising biomarker for monitoring and personalizing breast cancer therapy. Mol Cancer Res; 13(6); 1022–33. ©2015 AACR.
Uterine leiomyoma after embolization by means of gelatin sponge particles alone: report of a case with histopathologic features.

We describe the histopathologic features of uterine leiomyoma after uterine artery embolization (UAE) in a 42-year-old woman. This patient, who was taking antiplatelet drugs for the treatment of cerebral disease, successfully underwent UAE using only gelatin sponge particles for a symptomatic uterine leiomyoma. Although menorrhagia improved moderately after the procedure, she underwent abdominal hysterectomy 11 months later because of recurrent uterine bleeding. Histopathology revealed that most of the area of the uterine leiomyoma was characterized by extensive coagulation necrosis, which support the positive result of the procedure. No significant abnormalities were noted in either the myometrium or endometrium, which also suggested that UAE using only gelatin sponge particles is an appropriate procedure to preserve the uterus. The histologic and radiologic features of this case are discussed. To the best of our knowledge, this is the first reported case of uterine leiomyoma after UAE using only gelatin sponge particles as a primary embolic agent.
Supporting Co-Design using Design Thinking Business Networks

Knowledge sharing and management is becoming increasingly important in complex environments where business networks work on joint projects or supply chains. Such environments are characterized by continuous change requires knowledge workers to continually propose new solutions and search and develop knowledge to support these solutions. This new knowledge often comes from externally, or from business partners and must be shared in flexible ways. This paper develops a model for gathering and sharing of knowledge using tools that lead to innovative outcomes. It develops a metamodel that allows dynamic reconfiguration of systems, while reassigning knowledge processing functions to meet emerging needs. The paper then illustrates a prototype for implementing the model on the cloud.
Impaired redistribution of aminophospholipids with distinctive cell shape change during Ca2+‐induced activation of platelets from a patient with Scott syndrome

We have investigated phospholipid redistribution, membrane vesicle shedding, shape change, and granule release following A23187 activation of platelets from a patient with Scott syndrome, characterized by impaired transmembrane migration of phosphatidylserine (PS) accompanied by haemorrhagic complications, and two of her children. Electron spin resonance spectroscopy measurement of phospholipids redistribution showed that the internalization of PS was unaffected by the disorder but, after activation, PS exposure was significantly reduced in platelets from the homozygous‐type patient. Vesicle shedding was also reduced in these platelets. However, the slow redistribution of phosphatidylcholine was similar to that observed in normal platelets. When treated with calpeptin, platelets from the homozygous‐type patient, unlike normal or heterozygous Scott syndrome platelets, showed a smoothly rounded shape without filopods after activation. Following A23187 activation of normal platelets, filopod formation was consecutive to the re‐exposition of aminophospholipids on the outer leaflet of the plasma membrane, and the existence of a floppase (outward aminoPLs translocase) has been suggested. In homozygous Scott syndrome platelets the deficiency in PS re‐exposition, the absence of filopod formation, and low vesicle shedding are correlated with each other, and argue in favour of a disruption of the proposed floppase activity.
Composition and fate of gas and oil released to the water column during the Deepwater Horizon oil spill

Quantitative information regarding the endmember composition of the gas and oil that flowed from the Macondo well during the Deepwater Horizon oil spill is essential for determining the oil flow rate, total oil volume released, and trajectories and fates of hydrocarbon components in the marine environment. Using isobaric gas-tight samplers, we collected discrete samples directly above the Macondo well on June 21, 2010, and analyzed the gas and oil. We found that the fluids flowing from the Macondo well had a gas-to-oil ratio of 1,600 standard cubic feet per petroleum barrel. Based on the measured endmember gas-to-oil ratio and the Federally estimated net liquid oil release of 4.1 million barrels, the total amount of C1-C5 hydrocarbons released to the water column was 1.7 × 1011 g. The endmember gas and oil compositions then enabled us to study the fractionation of petroleum hydrocarbons in discrete water samples collected in June 2010 within a southwest trending hydrocarbon-enriched plume of neutrally buoyant water at a water depth of 1,100 m. The most abundant petroleum hydrocarbons larger than C1-C5 were benzene, toluene, ethylbenzene, and total xylenes at concentrations up to 78 μg L-1. Comparison of the endmember gas and oil composition with the composition of water column samples showed that the plume was preferentially enriched with water-soluble components, indicating that aqueous dissolution played a major role in plume formation, whereas the fates of relatively insoluble petroleum components were initially controlled by other processes.
Beyond chemotherapy for advanced disease—the role of EGFR and PD-1 inhibitors

Penile squamous cell carcinoma (SCC) is a rare malignancy with limited treatment options when the tumor is unresectable and/or chemorefractory. Triplet systemic chemotherapy regimens including taxane and cisplatin are recommended, but the response duration can be short and the treatment-related toxicity high. Only a small proportion of patients survive 1 year or longer with the current standard treatment paradigm. Beyond chemotherapy, the use of novel targeted agents, either alone or in combination with traditional chemotherapeutic agents, has appeared to have promising efficacy in patients with platinum-refractory penile cancer. The frequent overexpression of PD-L1 in advanced penile SCC indicates the potential efficacy of PD-1 inhibitors. Upcoming clinical trials using the immune check-point inhibitors may provide exciting landscape and change the paradigm for patients in the future.
Design, analysis and control of a new multi-output flyback CF-ZVS-QRC

A new multi-output flyback constant frequency zero voltage switching quasi resonant converter with low switching and conduction losses for aerospace applications is presented in this paper. The proposed converter is designed for outputs of 5 V/1 A and 12 V/0.5 A with resonant frequency of 165 kHz. A simple control method based on a single chip two pulse resonant controller UC3861 is developed to regulate 5 V output of the proposed converter and the other output voltage is maintained constant at 12 V. A prototype model of this converter is developed and the control method is implemented. The cross correlation effects of the two outputs are studied for different load variations and supply disturbances in experimental set-up. Results reveal the superiority of the proposed method.
Lipoprotein lipase liberates free fatty acids to inhibit HCV infection and prevent hepatic lipid accumulation

Lipoprotein lipase (LPL) has been identified as an anti‐hepatitis C virus (HCV) host factor, but the cellular mechanism remains elusive. Here, we investigated the cellular mechanism of LPL involving in anti‐HCV. The functional activation of peroxisome proliferator‐activated receptor (PPAR) α signal by LPL transducing into hepatocytes was investigated in HCV‐infected cells, primary human hepatocytes, and in HCV‐core transgenic mice. The result showed that the levels of transcriptional transactivity and nuclear translocation of PPARα in Huh7 cells and primary human hepatocytes were elevated by physiologically ranged LPL treatment of either very‐low density lipoprotein or HCV particles. The LPL‐induced hepatic PPARα activation was weakened by blocking the LPL enzymatic activity, and by preventing the cellular uptake of free unsaturated fatty acids with either albumin chelator or silencing of CD36 translocase. The knockdowns of PPARα and CD36 reversed the LPL‐mediated suppression of HCV infection. Furthermore, treatment with LPL, like the direct activation of PPARα, not only reduced the levels of apolipoproteins B, E, and J, which are involved in assembly and release of HCV virions, but also alleviated hepatic lipid accumulation induced by core protein. HCV‐core transgenic mice exhibited more hepatic miR‐27b, which negatively regulates PPARα expression, than did the wild‐type controls. The induction of LPL activity by fasting in the core transgenic mice activated PPARα downstream target genes that are involved in fatty acid β‐oxidation. Taken together, our study reveals dual beneficial outcomes of LPL in anti‐HCV and anti‐steatosis and shed light on the control of chronic hepatitis C in relation to LPL modulators.
Statistical Modeling of Yield and Variance Instability in Conventional and Organic Cropping Systems

Temporal variation in crop yields has considerable impact at farm, regional, and national levels. To gain a better understanding of the factors contributing to this variation, we quantified the cumulative effects of management practices and soil covariates on total yield (TY), temporal yield variance (TYV) and coefficient of variation (CV) of 2-yr (2 Yr) {corn [Zea mays L. ]-soybean [Glycine max (L.) Merr. ]} and 4-yr (4 Yr) [corn-soybean-spring wheat (Triticum aestivum L.)-alfalfa (Medicago sativa L.)] crop rotations in conventional (CNV) and organic (ORG) cropping systems. Soil covariates differed individually or as a group in their impact on TY, TYV, and CV. Spatial variation, quantified by soil covariates, did not fully explain variation in TY or TYV; whereas, TYV explained up to 86% of variation in TY, both of which were less variable in ORG than in CNV. Multivariate relationships among TYV, CV, management factors, and covariates indicated that TYs of 4-Yr crop rotations were likely to be more stable than TYs of 2-Yr rotations. The largest and most stable yields obtained under both cropping systems are characterized by a combination of optimum TYV and minimum CV values. We developed a classification scheme of cropping systems, crop rotation phases, and management practices based on the three-way relationship between TY, TYV, and CV, and deviations from their respective means. In addition to its utility in selecting the largest and most stable yield, the scheme can be used to measure stability in crop production and strategically deploy appropriate management practices for a given cropping system or crop rotation.