Miracle-dz/UniFAR-FTUs huggingface dataset:
B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma

Purpose: Multiple myeloma is a usually incurable malignancy of plasma cells. New therapies are urgently needed for multiple myeloma. Adoptive transfer of chimeric antigen receptor (CAR)–expressing T cells is a promising new therapy for hematologic malignancies, but an ideal target antigen for CAR-expressing T-cell therapies for multiple myeloma has not been identified. B-cell maturation antigen (BCMA) is a protein that has been reported to be selectively expressed by B-lineage cells including multiple myeloma cells. Our goal was to determine if BCMA is a suitable target for CAR-expressing T cells. Experimental Design: We conducted an assessment of BCMA expression in normal human tissues and multiple myeloma cells by flow cytometry, quantitative PCR, and immunohistochemistry. We designed and tested novel anti-BCMA CARs. Results: BCMA had a restricted RNA expression pattern. Except for expression in plasma cells, BCMA protein was not detected in normal human tissues. BCMA was not detected on primary human CD34+ hematopoietic cells. We detected uniform BCMA cell-surface expression on primary multiple myeloma cells from five of five patients. We designed the first anti-BCMA CARs to be reported and we transduced T cells with lentiviral vectors encoding these CARs. The CARs gave T cells the ability to specifically recognize BCMA. The anti-BCMA-CAR–transduced T cells exhibited BCMA-specific functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication. Importantly, anti-BCMA-CAR–transduced T cells recognized and killed primary multiple myeloma cells. Conclusions: BCMA is a suitable target for CAR-expressing T cells, and adoptive transfer of anti-BCMA-CAR–expressing T cells is a promising new strategy for treating multiple myeloma. Clin Cancer Res; 19(8); 2048–60. ©2013 AACR.
Biofilm mediates Enterococcus faecalis adhesion, invasion and survival into bovine mammary epithelial cells

We proposed in this study that during intramammary infection, biofilm formation may facilitate adherence and colonization of Enterococcus faecalis to mammary gland epithelium. This was established by comparing six different Ent. faecalis isolates with different biofilm‐forming profiles for their adhesive, invasive and survival capabilities to bovine mammary epithelial cell line (MAC‐T). Our results showed increased ability of the biofilm‐producer Ent. faecalis strains to adhere, invade and survive inside MAC‐T cells rather than nonbiofilm‐producer strains. We showed that growth of bacteria in bovine milk significantly augmented the adherence and invasion of all tested strains, and this feature was abolished again when strains were subcultured in brain heart infusion broth. Moreover, growth in bovine milk significantly increased biofilm formation by all tested strains. These results indicated that biofilm formation by Ent. faecalis, especially after expressing milk‐dependent induction, may have special relevance in the pathogenesis of Ent. faecalis mastitis during intramammary infection by enhancing bovine mammary epithelial adhesion and colonization.
Frequent hepatitis B virus rebound among HIV–hepatitis B virus-coinfected patients following antiretroviral therapy interruption

Background:The impact of antiretroviral therapy (ART) interruption in HIV–hepatitis B virus (HBV)-coinfected patients was examined in the Strategic Management of AntiRetroviral Therapy (SMART) study. Methods:Plasma HBV DNA was measured in all hepatitis B surface antigen-positive (HBV-positive) participants at baseline, and at months 1, 2, 4, 6, 8, 10, and 12. Results:Among HBV-positive participants in the ART interruption (drug conservation) (n = 72) and ART continuation (virological suppression) (n = 62) arms, HBV DNA rebound of more than 1 log from baseline at months 1–4 was seen in 31–33% (P = 0.003) and 3–4% (P = 0.017), respectively. Thirteen HBV-positive participants had HBV DNA rebound of more than 3 log, including 12 in the drug conservation arm, of which eight were on tenofovir-containing regimens. Factors independently associated with a HBV DNA rebound were drug conservation arm (P = 0.0002), nondetectable HBV DNA at baseline (P = 0.007), and black race (P = 0.03). Time to ART reinitiation was shorter (7.5, 15.6, and 17.8 months; P < 0.0001) and proportion reinitiating greater (62.5, 46.5, and 39.7%; P = 0.0002) among HBV-positive participants as compared with hepatitis C virus-positive and non-HBV/hepatitis C virus participants in the drug conservation arm. No hepatic decompensation events occurred among HBV-positive participants in either arm. Conclusion:HBV DNA rebound following ART interruption is common and may be associated with accelerated immune deficiency in HIV–HBV-coinfected patients.
Hepatitis C treatment in “difficult‐to‐treat” psychiatric patients with pegylated interferon‐alpha and ribavirin: Response and psychiatric side effects

We investigated and compared the results of treating the chronic hepatitis C (HCV) infection of different groups of psychiatric‐risk patients and controls with pegylated interferon alpha (pegIFN‐α) plus ribavirin. Seventy patients were prospectively screened for psychiatric disorders. Seventeen patients without psychiatric diseases or drug addiction (controls), 22 patients with psychiatric disorders, 18 patients who had received methadone substitution treatment and 13 patients who were former drug users were treated with pegIFN‐α plus ribavirin. Sustained virological response (SVR), adherence, and psychiatric side effects (using the Montgomery‐Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale) in the groups were compared. An SVR was found in 58.6% of all patients: 58.8% of the controls, 50% of psychiatric patients, 72.2% of methadone patients, and 53.8% of former drug users. Methadone‐substituted patients and former drug users had significantly higher dropout rates. Scores for neither depressive nor psychotic symptoms differed significantly between groups during treatment. However, the controls had lower pretreatment scores, followed by a significant higher increase to maximum scores. A stepwise logistic regression model showed that only genotype, not group (control, psychiatric, methadone, or former drug abuse), type of psychiatric diagnosis (affective disorder, personality disorder, or schizophrenic disorder), depression scores before and during treatment, change in depression score, antidepressive treatment, sex, or liver enzymes before treatment, was associated with SVR. Conclusion: In an interdisciplinary treatment setting psychiatric diseases and/or drug addiction did not negatively influence psychiatric tolerability of and antiviral response rate to HCV treatment with pegIFN‐α and ribavirin. (HEPATOLOGY 2007.)
Integrating off-the-shelf 3GPP access networks in the OpenEPC software toolkit: Realizing cost-efficient and complete small-scale operator testbeds

With the gradual deployment of LTE in addition to the other 2G and 3G access networks standardized by the 3rd Generation Partnership Project (3GPP) together with the adoption of the 3GPP Evolved Packet Core (EPC) as the all-IP core network architecture, a new level of communication is achieved in the operator wireless environment. The increased network capacity enables a higher number of devices to be connected and to communicate with extended data rates, bringing new opportunities to develop wireless tailored services and to evolve the network functional features like QoS, charging, mobility, security, management and monitoring. This paper describes the Fraunhofer FOKUS OpenEPC testbed extension related to the integration of off-the-shelf cost efficient 3GPP access networks addressing especially the 2G technologies. Through the functionality here presented, the OpenEPC testbed users are able to connect and to exchange data over a 3GPP access, enabling accurate measurements and evaluation of their novel features similar to the real deployed networks, relying on the OpenEPC core network functionality for application delivery support and subscriber, mobility and resources management. The initiative of integrating 3GPP access networks in OpenEPC provides to both the academic and industry researchers the means to rapidly and cost-efficient realize complete small-scale operator networks systems and application support testbeds.
Drug-induced RAF dimerization is independent of RAS mutation status and does not lead to universal MEK dependence for cell survival in head and neck cancers

Treatments for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) have limited efficacy. One potential therapeutic target for HNSCC is the RAS/RAF/MEK/ERK cascade, which is one of the major signaling pathways for HNSCC cell survival. In HNSCC, RAS can be activated either by HRAS mutation or by upstream signaling. The ABL inhibitor nilotinib acts as a weak RAF inhibitor that induces RAF dimerization and subsequent activation of MEK/ERK in other cancer cell lines with activated RAS, leading to an unexpected dependence on MEK/ERK for cell survival. We hypothesized that nilotinib and the MEK inhibitor MEK162 would be synergistic in HNSCC cell lines owing to the frequent activation of RAS. We treated HNSCC cell lines with nilotinib and performed immunoblotting and cell-viability experiments. We used an orthotopic mouse model to assess synergistic effects in vivo. Nilotinib induced significant BRAF-CRAF heterodimerization and ERK activation irrespective of RAS mutation status. In cell-viability assays, nilotinib synergized with MEK162. MEK162 alone induced G1 arrest that was minimally enhanced by nilotinib. In the mouse model, treatment with MEK162 alone or combined with nilotinib led to tumor growth inhibition. In HNSCC, nilotinib-induced RAF dimerization is independent of RAS mutation status, but this dimerization does not lead to MEK dependence for cell survival in all HNSCC cell lines. MEK inhibition alone leads to decreased proliferation both in vitro and in vivo. Although nilotinib has some synergistic effects with MEK162, other agents may be more effective against HNSCC when combined with MEK162.
dq modeling of five phase synchronous reluctance machines including third harmonic of air-gap MMF

A detailed analysis and development of the d-q equations for a five phase synchronous reluctance machine including the third harmonic of the air-gap are presented. The resulting equations are compared with the equations in the natural (abc) system. Simulation traces are used to confirm the model. The developed equations are compared to the experimental results and the similarities and discrepancies identified. <<ETX>>
Short‐Term Plasticity of Hippocampal Neuropeptides and Neuronal Circuitry in Experimental Status Epilepticus

Summary: Purpose: We used a model of self‐staining status epilepticus (SSSE), induced by brief intermittent stimulation of the perforant path in unanesthetized rats, to study the mechanism of initiation and of maintenance of SSSE and the role of neuropeptides in those processes.
The Modern Grievance Procedure In The United States

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Assessment of Biodosimetry Methods for a Mass-Casualty Radiological Incident: Medical Response and Management Considerations

AbstractFollowing a mass-casualty nuclear disaster, effective medical triage has the potential to save tens of thousands of lives. In order to best use the available scarce resources, there is an urgent need for biodosimetry tools to determine an individual’s radiation dose. Initial triage for radiation exposure will include location during the incident, symptoms, and physical examination. Stepwise triage will include point of care assessment of less than or greater than 2 Gy, followed by secondary assessment, possibly with high throughput screening, to further define an individual’s dose. Given the multisystem nature of radiation injury, it is unlikely that any single biodosimetry assay can be used as a standalone tool to meet the surge in capacity with the timeliness and accuracy needed. As part of the national preparedness and planning for a nuclear or radiological incident, the authors reviewed the primary literature to determine the capabilities and limitations of a number of biodosimetry assays currently available or under development for use in the initial and secondary triage of patients. Understanding the requirements from a response standpoint and the capability and logistics for the various assays will help inform future biodosimetry technology development and acquisition. Factors considered include: type of sample required, dose detection limit, time interval when the assay is feasible biologically, time for sample preparation and analysis, ease of use, logistical requirements, potential throughput, point-of-care capability, and the ability to support patient diagnosis and treatment within a therapeutically relevant time point.
Mechanism of Cell Entry and Transformation by Enzootic Nasal Tumor Virus

ABSTRACT Enzootic nasal tumor virus (ENTV) induces nasal epithelial cancer in infected sheep, but it is a simple retrovirus lacking a known oncogene. ENTV is closely related to jaagsiekte sheep retrovirus (JSRV), which also causes cancer in sheep but in the epithelial cells of the lower airways and alveoli. Here we show that as with JSRV, the envelope (Env) protein of ENTV can transform cultured cells and thus is likely to be responsible for oncogenesis in animals. In addition, the ENTV Env protein mediates virus entry using the same receptor as does JSRV Env, the candidate tumor suppressor Hyal2. However, ENTV Env mediates entry into cells from a more restricted range of species than does JSRV, and based on this finding we have identified amino acid regions in the Env proteins that are important for virus entry. Also, because ENTV does not efficiently use human Hyal2 as a receptor, we cloned the ovine Hyal2 cDNA and show that the encoded protein functions as an efficient receptor for both ENTV and JSRV. In summary, although ENTV and JSRV use the same cell surface receptor for cell entry and apparently transform cells by the same mechanism, they induce cancer in different tissues of infected sheep, indicating that oncogenesis is regulated at some other level. The transcriptional regulatory elements in these viruses are quite different, indicating that tissue-specific oncogenesis is likely regulated at the level of viral gene expression.
CORRELATION OF CLINICAL AND ECHO-CARDIOGRAPHIC SCORES WITH BLOOD "BRAIN NATRIURETIC PEPTIDE" IN PAEDIATRIC PATIENTS WITH HEART FAILURE.

BACKGROUND Recently brain natriuretic peptide (BNP) level has been introduced as a screening test for congestive heart failure (CHF) in children. The current CHF assessment scores are not satisfactory as they use a large number of variables. OBJECTIVE To evaluate two CHF scores: a modified clinical score and an echocardiographic score and compare them to BNP in paediatric patients. DESIGN Prospective, hospital based study. SETTING Two paediatric cardiac referral centres in Khartoum from April to July 2010. SUBJECTS All patients one month to 18 years of age with the clinical diagnosis of CHF were included. RESULTS Sixty seven patients were enrolled, 39 (58%) had congenital heart disease (CHD), 27 (32%) had rheumatic heart disease (RHD), and seven (10%) had dilated cardiomyopathy (DCM). Twenty four younger children (88%) and 29 older children (85%) had a high clinical score (severe CHF). Twenty one out of 23 younger children with high echo score (91%) had a high clinical score as well (p-value 0.001). In patients with RHD (all with a high clinical score), 81% had a high echo score. (p-value 0.001). All younger children with a high clinical score (n = 24) had a high level of BNP (p-value 0.00). In older children with a high clinical score 28 out of 29 (96%) had a high BNP level (p-value 0.00). Of patients with RHD and a high echo score (21), 16 (76.2%) patients had high BNP level and five (23.8%) had low level of BNP. All patients with DCM had high echo score and all of them had high levels of BNP (100%) (p-value.0.00). CONCLUSION We tested clinical and echo scores and proved their value in assessment of CHF in children. The scores correlated well with BNP level. We recommend the use of these scores as well as BNP level in clinical practice.
Biological and Sociocultural Factors During the School Years Predicting Women's Lifetime Educational Attainment.

BACKGROUND Lifetime educational attainment is an important predictor of health and well-being for women in the United States. In this study, we examine the roles of sociocultural factors in youth and an understudied biological life event, pubertal timing, in predicting women's lifetime educational attainment. METHODS Using data from the National Longitudinal Survey of Youth 1997 cohort (N = 3889), we conducted sequential multivariate linear regression analyses to investigate the influences of macro-level and family-level sociocultural contextual factors in youth (region of country, urbanicity, race/ethnicity, year of birth, household composition, mother's education, and mother's age at first birth) and early menarche, a marker of early pubertal development, on women's educational attainment after age 24. RESULTS Pubertal timing and all sociocultural factors in youth, other than year of birth, predicted women's lifetime educational attainment in bivariate models. Family factors had the strongest associations. When family factors were added to multivariate models, geographic region in youth, and pubertal timing were no longer significant. CONCLUSION Our findings provide additional evidence that family factors should be considered when developing comprehensive and inclusive interventions in childhood and adolescence to promote lifetime educational attainment among girls.
Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients.

BACKGROUND Serum ferritin is a frequently used marker of iron status in dialysis patients. Iron administration is to be withheld for ferritin values >800 ng/ml according to K/DOQI guidelines. We hypothesized that such non-iron-related factors as elements of the malnutrition-inflammation complex syndrome (MICS) may increase serum ferritin concentration independently of iron status. METHODS We studied 82 prevalent maintenance haemodialysis (MHD) patients (including 43 men), aged 55.7 +/- 15.3 years. The inflammatory and nutritional status was evaluated by serum C-reactive protein (CRP), Subjective Global Assessment (SGA) and its newer, fully quantitative versions, i.e. Dialysis Malnutrition Score (DMS) and Malnutrition-Inflammation Score (MIS). RESULTS All but six patients had been on maintenance doses of intravenous iron dextran (between 100 and 200 mg/month) during the 10 weeks prior to the measurements. Serum ferritin levels were increased across SGA categories: (ANOVA P-value 0.03). Both unadjusted and multivariate adjusted correlation coefficients (r) for serum ferritin and CRP vs pertinent values were statistically significant for DMS and MIS and some other measures of nutritional status and iron indices. After deleting 10 MHD patients with either iron deficiency (ferritin <200 ng/ml) or iron overload (ferritin >2000 ng/ml), in the remaining 72 MHD patients both bivariate and multivariate correlations were much stronger and statistically significant (r = -0.33 and -0.29, respectively, P < 0.01). A multivariate model showed simultaneous, significant correlations between serum ferritin and both markers of inflammation and iron status independent of each other. After dividing the 72 MHD patients into two groups of serum ferritin based on a K/DOQI recommended serum ferritin cut-off of 800 ng/ml, the MIS and logarithm of serum CRP were significantly higher in the higher ferritin group. CONCLUSIONS Serum ferritin values in the range of 200-2000 ng/ml may be increased due to non-iron-related factors including elements of MICS.
Abnormal histone modification patterns in lupus CD4+ T cells.

OBJECTIVE To investigate alterations in histone modifications in patients with systemic lupus erythematosus (SLE). METHODS Global histone H3/H4 acetylation and H3K4/H3K9 methylation in CD4+ T cells from 20 SLE patients and 10 healthy control subjects were assayed using the EpiQuik global histone H3/H4 acetylation and H3K4/H3K9 methylation assay kits. mRNA levels of 12 members of 3 classes of chromatin modifier genes were measured by real-time quantitative polymerase chain reaction. RESULTS Global histone H3 and H4 hypoacetylation was observed in active lupus CD4+ T cells compared with controls (p = 0.002 and p = 0.009, respectively). The degree of histone H3 acetylation correlated negatively with increased disease activity in lupus patients as measured by SLEDAI (r = -0.889, p = 0.044). We found global histone H3K9 hypomethylation in both active and inactive lupus CD4+ T cells, compared with controls (p = 0.001, p = 0.003, respectively). However, global levels of H3K4 methylation were not different between patients and controls. SIRT1 mRNA levels were significantly increased in active lupus CD4+ T cells compared with controls (p < 0.001), while mRNA levels of CREBBP, P300, HDAC2, HDAC7, SUV39H2, and EZH2 were significantly downregulated in patients with active lupus (p < 0.001, p < 0.001, p = 0.01, p < 0.001, p = 0.003, p = 0.001, respectively). CONCLUSION Histone modifications appear abnormal in CD4+ T cells in SLE.
Antidepressant and anxiolytic profiles of newly synthesized arginine vasopressin V1B receptor antagonists: TASP0233278 and TASP0390325

Vasopressin V1B receptor antagonists may be effective for the treatment of depression and anxiety and the objective of this study was to characterize the pharmacological profiles of two newly synthesized arginine vasopressin receptor 1B (V1B receptor) antagonists, TASP0233278 and TASP0390325.
Low Frequency Current Ripple Reduction Technique With Active Control in a Fuel Cell Power System With Inverter Load

A fuel cell power system that contains a single-phase dc-ac inverter tends to draw an ac ripple current at twice the output frequency. Such a ripple current may shorten fuel cell life span and worsen the fuel efficiency due to the hystersis effect. The most obvious impact is it tends to reduce the fuel cell output capacity because the fuel cell controller trips under instantaneous over-current condition. In this paper, the ripple current propagation path is analyzed, and its linearized ac model is derived. The equivalent circuit model and ripple current reduction with passive energy storage component are simulated and verified with experiments. An advanced active control technique is then proposed to incorporate a current control loop in the dc-dc converter for ripple reduction. The proposed active ripple reduction method has been verified with computer simulation and hardware experiment with a proton exchange membrane type fuel cell using a multiphase dc-dc converter along with a full-bridge dc-ac inverter. Test results with open loop, single voltage loop, and the proposed active current-loop control are provided for comparison.