Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-let-7a expression is increased in the mesangial cells of NZB/W mice and increases IL-6 production in vitro

Abstract Recent evidence supports a role for epigenetic alterations in the pathogenesis of systemic lupus erythematosus (SLE). MicroRNAs (miRNAs or miRs) are endogenous epigenetic regulators whose expression is altered in many diseases, including SLE. IL-6 is an inflammatory cytokine produced by mesangial cells during lupus nephritis (LN). IL-6 contains a potential binding site for miRNA-let-7a (let-7a) in its 3′ untranslated region (UTR). We found let-7a expression was significantly increased in the mesangial cells of pre-diseased and actively diseased New Zealand Black/White (NZB/W) mice compared to age-matched New Zealand White (NZW) mice. Overexpression of let-7a in vitro increased IL-6 production in stimulated mesangial cells compared to non-transfected controls. Inhibition of let-7a did not significantly affect immune-stimulated IL-6 production. When stimulated mesangial cells overexpressing let-7a were treated with the transcription inhibitor Actinomycin D (ActD), IL-6 was degraded faster, consistent with the direct targeting of the 3′ UTR of IL-6 by let-7a. Overexpression of let-7a increased the expression of tristetraprolin (TTP), an RNA-binding protein (RBP) that has 5 potential binding regions in the 3′ UTR of IL-6. ActD inhibited the transcription of proteins including TTP that may contribute to the let-7a-mediated increase in immune-stimulated IL-6 production. These data show that NZB/W mice have higher let-7a expression than NZW mice and that increased let-7a expression in vitro increases IL-6 production in stimulated mesangial cells. Further studies examining the role of let-7a expression in inflammation are warranted.
Laws requiring health plans to provide direct access to obstetricians and gynecologists, and use of cancer screening by women.

BACKGROUND Many states have passed legislation mandating that health plans provide direct access to obstetricians/gynecologists (hereinafter "ob/gyns") for women, limiting the ability of plans to require referrals or otherwise restrict access. One benefit of these laws may be improved preventive screening rates, but no literature has examined the relationship between ob/gyn direct access laws and use of breast cancer and cervical cancer screening. DATA AND METHODS We use repeated cross-sections of privately insured women age 18-64 (Pap test) and 40-64 (mammography) from the Behavioral Risk Factor Surveillance System for 1996-2000, linked to data on the presence of ob/gyn direct access laws by state. Outcome measures are receipt of mammography and receipt of a Pap test within the past 2 years. Regression analyses are used to assess the relationship between the presence of ob/gyn direct access laws and screening, adjusting for a range of individual characteristics, fixed state characteristics, and time trends. RESULTS We find no statistically significant relationships between the presence of an ob/gyn direct access law and receipt of either mammography or Pap test screening. We explore a range of alternate specifications and find none that yield clear evidence of a relationship. CONCLUSIONS Laws requiring direct access to ob/gyns are not associated with large or consistent measurable impacts on use of cancer screening.
Giving Australia:Research on Philanthropy in Australia. Summary of Findings

The ‘Giving Australia’ project is an initiative of the Prime Minister’s Community Business Partnership, coordinated by the Australian Council of Social Service (ACOSS) in collaboration with the Centre for Australian Community Organisations and Management (CACOM) at the University of Technology, Sydney, the Australian Centre of Philanthropy and Nonprofit Studies (ACPNS)at the Queensland University of Technology, Roy Morgan Research (RMR),McNair Ingenuity Research and the Fundraising Institute - Australia (FIA).
Central Memory CD4 Cells Are an Early Indicator of Immune Reconstitution in HIV/AIDS Patients with Anti-Retroviral Treatment

The number of central memory cells among the CD4+ T cells and the of activation of CD8+ T cells is believed to be a better indicator of immune restoration in patients on antiretroviral therapy (ART) than the absolute numbers of CD4+ and CD8+ T cells alone. In the current study, we investigated the changes in the CD4+ T cell subsets and their association with immune reconstitution and immune activation at early stages of ART. A prospective study was performed in 21 asymptomatic treatment-naive HIV-infected patients with CD4+ T cells less than 350 cells/μl. Blood samples were evaluated at base line, and at 2, 4, 8 and 12 weeks’ post antiretroviral therapy (ART). A biphasic increase of CD4+ T cells, central memory CD4 cells (CD4 CM) and CD4 naïve cells were observed after ART, with a rapid increase before week 4. Change in CD4 CM at week 4 positively correlated with the change in CD4+ T cells at weeks 12 post ART, and negatively correlated with the change in CD8+CD38+ T cells at weeks 12 post ART. We conclude that CD4 CM cells are a major contributor to early immune reconstitution in treatment-naive HIV-infected patients with delayed ART, and might be an early indicator for immune reconstitution.
Strategies for inhibitor treatment and costs in the short and long term: a critical evaluation of recent clinical studies

One important complication of patients with severe haemophilia A is the formation of inhibitory antibodies to factor VIII (FVIII). Immune tolerance induction (ITI) is the treatment of choice for patients with inhibitors, but this approach is successful in about 60% of patients. Treatment of acute bleeding in patients with inhibitors is one of the greatest challenges in haemophilia management and is costly. Bypassing agents are the mainstay of treatment in these patients. The aims of this study were to review the most recent publications concerning the costs of inhibitor treatment. We conducted a literature review using PubMed which yielded 63 papers analysing the costs of inhibitor management of which 12 were suitable for our study. Four of eight studies supported the use of activated prothrombin complex concentrate (aPCC) with lower costs, but the remaining four studies showed that recombinant factor VIIa (rFVIIa) had a lower average treatment cost. Of four ITI studies, two supported lifelong cost‐effectiveness of ITI vs. bypassing agents and the remaining two papers showed a high cost of inhibitor treatment. Dosages, time between onset of bleeding and treatment, patient characteristics and the price of drugs are some of the important issues that should be considered for further studies.
The cell surface glycoprotein layer of the extreme halophile Halobacterium salinarum and its relation to Haloferax volcanii: cryo-electron tomography of freeze-substituted cells and projection studies of negatively stained envelopes.

We have studied the surface layer (S-layer) of Halobacterium salinarum (formerly Halobacterium halobium), an extreme halophile requiring high concentrations of sodium, by electron microscopy of (a) isolated, negatively stained, flattened envelopes and (b) cryo-fixation of intact cells in their high-salt growth medium followed by freeze substitution and tomography of thin sections. From the negatively stained isolated envelopes we have calculated a two-dimensional, projection map that is strikingly similar to that of Haloferax volcanii, an extreme halophile requiring high concentrations of magnesium; both projection maps show the hexagonal arrangement of the morphological units with an identical center-to-center spacing of 150 A; each of the morphological units of the two species has six subunits with a similar density distribution and apparent domain organization. In contrast to the two-dimensional map, the tomographic reconstruction of Halob. salinarum does not agree in a straightforward way with the three-dimensional, electron crystallographic map of negatively stained Halof. volcanii envelopes, although the main features of the lattice and the morphological units are evident. The tomographic reconstruction of sections from epoxy-embedded material suffers from directional compression due to sectioning stress and continuous dimensional changes and mass loss due to electron irradiation. This communication consists, therefore, of three parts: (a) a comparison of the projection maps of negatively stained envelopes of Halof. volcanii and Halob. salinarum; (b) a comparison of the three-dimensional maps obtained by electron crystallography (Halof. volcanii) and low-dose cryo-tomography (Halob. salinarum); and (c) a methodological study of mass loss and dimensional changes of plastic-embedded material under low-dose conditions at room and liquid nitrogen temperatures.
Salt-induced Changes in the Plasma Membrane Proteome of the Halotolerant Alga Dunaliella salina as Revealed by Blue Native Gel Electrophoresis and Nano-LC-MS/MS Analysis*S

The halotolerant alga Dunaliella salina is a recognized model photosynthetic organism for studying plant adaptation to high salinity. The adaptation mechanisms involve major changes in the proteome composition associated with energy metabolism and carbon and iron acquisition. To clarify the molecular basis for the remarkable resistance to high salt, we performed a comprehensive proteomics analysis of the plasma membrane. Plasma membrane proteins were recognized by tagging intact cells with a membrane-impermeable biotin derivative. Proteins were resolved by two-dimensional blue native/SDS-PAGE and identified by nano-LC-MS/MS. Of 55 identified proteins, about 60% were integral membrane or membrane-associated proteins. We identified novel surface coat proteins, lipid-metabolizing enzymes, a new family of membrane proteins of unknown function, ion transporters, small GTP-binding proteins, and heat shock proteins. The abundance of 20 protein spots increased and that of two protein spots decreased under high salt. The major salt-regulated proteins were implicated in protein and membrane structure stabilization and within signal transduction pathways. The migration profiles of native protein complexes on blue native gels revealed oligomerization or co-migration of major surface-exposed proteins, which may indicate mechanisms of stabilization at high salinity.
Trends of breast cancer incidence in Iran during 2004-2008: a Bayesian space-time model.

BACKGROUND Breast cancer is the most frequently diagnosed cancer in women and estimating its relative risks and trends of incidence at the area-level is helpful for health policy makers. However, traditional methods of estimation which do not take spatial heterogeneity into account suffer from drawbacks and their results may be misleading, as the estimated maps of incidence vary dramatically in neighboring areas. Spatial methods have been proposed to overcome drawbacks of traditional methods by including spatial sources of variation in the model to produce smoother maps. MATERIALS AND METHODS In this study we analyzed the breast cancer data in Iran during 2004-2008. We used a method proposed to cover spatial and temporal effects simultaneously and their interactions to study trends of breast cancer incidence in Iran. RESULTS The results agree with previous studies but provide new information about two main issues regarding the trend of breast cancer in provinces of Iran. First, this model discovered provinces with high relative risks of breast cancer during the 5 years of the study. Second, new information was provided with respect to overall trend trends o. East-Azerbaijan, Golestan, North-Khorasan, and Khorasan-Razavi had the highest increases in rates of breast cancer incidence whilst Tehran, Isfahan, and Yazd had the highest incidence rates during 2004-2008. CONCLUSIONS Using spatial methods can provide more accurate and detailed information about the incidence or prevalence of a disease. These models can specify provinces with different health priorities in terms of needs for therapy and drugs or demands for efficient education, screening, and preventive policy into action.
Simultaneous Phase Regeneration of MDM Signals Utilizing a Multimode Silicon Waveguide

Mode-division multiplexing (MDM) is an effective technique to enlarge the transmission capacity. In order to extend the transmission distance and increase the transparency of the phase-encoded MDM communication system, all optical phase regeneration (PR) for MDM signals is much in demand. However, the PR of the MDM signals has been rarely reported. In this paper, the simultaneous PR of the MDM signals is proposed and theoretically demonstrated. The PR performance relies on the dispersion engineering of a multimode nonlinear waveguide, obtaining strong intramode phase sensitive amplifications (PSAs), where the involved pumps and the MDM signal component are carried on the same mode. On the other hand, the weak PSA/four wave mixing interaction is ensured among different modes, owing to the large phase mismatch or weak nonlinear coupling. Detailed characteristics are investigated to further optimize the PR performance. Results show an effective phase squeezing for the degraded 20 Gbit/s MDM differential phase-shift keying signals, and the error vector magnitudes of the regenerated signals on dual modes are improved from 10.7% and 11.5% to 4.9% and 3.7%, respectively.
A Signature Verification Framework for Digital Pen Applications

In this paper we present a framework for real-time online signature verification scenarios. The proposed framework is based on state-of-the-art feature extraction and Gaussian Mixture Model (GMM) classification. While our signature verification library is generally applicable to any input device using digital pens, we have implemented verification scenarios using the Anoto digital pen. As such our automated signature verification framework becomes an interesting commodity for industry, because the Anoto SDK is easy to apply and the GMM-based classification can be seamlessly integrated. The novelty of this work is the application of our framework that takes real-time online signature verification to every scenario where digital pens may potentially be used. In this paper we describe several scenarios where our framework has been applied, including signatures in financial contracts or ordering processes. We also propose a general approach to integrate the GMM-descriptions into electronic ID-cards in order to also store behavioral biometrics on these cards. In experiments we have measured the performance of the signature verification system when skilled forgeries were present. The interest shown by our partner financial institutions and the results of our initial evaluations indicate that our signature verification framework suits exactly the demands of our clients.
Perilipins Are Associated with Cholesteryl Ester Droplets in Steroidogenic Adrenal Cortical and Leydig Cells (*)

Steroidogenic cells store cholesteryl esters, precursors for steroid hormone synthesis, in intracellular lipid droplets. Cholesteryl ester hydrolysis is activated by protein kinase A and catalyzed by cholesteryl esterase. The esterase is similar, if not identical, to hormone-sensitive lipase in adipocytes where an analogous lipolytic mechanism occurs. Perilipins, proteins located exclusively at lipid droplet surfaces in adipocytes, are polyphosphorylated by protein kinase A in response to lipolytic stimuli, suggesting a role for these proteins in mediating lipid metabolism. The present study reveals that perilipins are associated with cholesteryl ester droplets in two steroidogenic cell lines: Y-1 adrenal cortical cells and MA-10 Leydig cells. The relative abundance of perilipin mRNAs and protein is much less in steroidogenic cells than in adipocytes. Like adipocytes, steroidogenic cells express perilipin A; additionally, the latter cells contain relatively abundant amounts of perilipin C, a protein that is not detectable in adipocytes by Western analysis. The data suggest a strong link between perilipins and lipid hydrolysis that is mediated by the hormone-sensitive lipase/cholesteryl esterase class of enzymes.
Signature Design of Sparsely Spread Code Division Multiple Access Based on Superposed Constellation Distance Analysis

Sparsely spread code division multiple access (SCDMA) is a non-orthogonal superposition coding scheme that allows concurrent communications between a base station and multiple users over a common channel. However, the detection performance of an SCDMA system is mainly determined by its signature matrix, which should be sparse to facilitate the belief propagation (BP) detection. On the other hand, to guarantee good maximum likelihood (ML) detection performance, the minimum Euclidean distance for the equivalent signal constellation after multi-user superposition should be maximized. In this paper, a code distance analysis is proposed for SCDMA systems with a finite number of users and spreading lengths. Based on this analysis, good signature matrices whose factor graphs have very few short cycles and possess large superposed signal constellation distances are designed. The proposed signature matrices have both good BP and ML detection performances. Moreover, their BP detection performances exactly converge to their ML detection performances with few iterations. It is worth pointing out that the proposed signature matrix design could be directly applied to the 5G non-orthogonal multiple access systems.
Research in the exercise sciences: where do we go from here?

The goal of this article is to provide a perspective on how research involving the acute and chronic effects of exercise (referred to as "exercise sciences") on the structure and function of organs systems will evolve in the next century. Within the last 30 years, exercise-related research has rapidly transitioned from an organ to a subcellular/molecular focus. Thus future research will continue to be heavily influenced by molecular biology tools, fueled by both emerging technologies (e.g., "gene-chip microarrays") designed to dissect gene function on a macro scale as well as by the completion of the human genome project in which the approximately 80,000 genes comprising humans will be completely sequenced. These successes will drive the emerging fields of functional genomics (the dissecting of a gene's identity and function) and proteomics (the study of the properties of proteins). Funding levels at the National Institutes of Health will likely increase in order to expand these emerging fields as well as provide avenues for translating fundamental knowledge into solving the complexities of a number of degenerative diseases influenced heavily by activity/inactivity factors such as cardiopulmonary disease, diabetes, obesity, and the debilitating disorders associated with aging. Thus there are many challenges facing future exercise scientists who must harness the new technologies and take an aggressive stance in bringing this important field to the forefront.
On the fault diagnosis in the presence of unknown fault models using pass/fail information

In this paper, we propose an effective diagnostic method in the presence of an unknown fault model, based on only pass/fail information on the applied tests. The proposed method deduces faulty conditions that are able to explain the behavior of the defect in the circuit and locates faulty sites, based on the number of detections for the single stuck-at fault at each line, by performing single stuck-at fault simulation with both passing and failing tests. As a result, we can derive a fault model from the faulty condition. To improve the ability of fault diagnosis, our method uses the logic values of lines and the condition whether the stuck-at faults at the lines are detected or not by passing and failing tests. Experimental results show that our method can accurately identify the fault models for 93% of faulty circuits and that the faulty sites are located within several candidates except for circuits with multiple stuck-at faults.
Dissecting the Non-human Primate Brain in Stereotaxic Space

The use of non-human primates provides an excellent translational model for our understanding of developmental and aging processes in humans1-6. In addition, the use of non-human primates has recently afforded the opportunity to naturally model complex psychiatric disorders such as alcohol abuse7. Here we describe a technique for blocking the brain in the coronal plane of the vervet monkey (Chlorocebus aethiops sabeus) in the intact skull in stereotaxic space. The method described here provides a standard plane of section between blocks and subjects and minimizes partial sections between blocks. Sectioning a block of tissue in the coronal plane also facilitates the delineation of an area of interest. This method provides manageable sized blocks since a single hemisphere of the vervet monkey yields more than 1200 sections when slicing at 50μm. Furthermore by blocking the brain into 1cm blocks, it facilitates penetration of sucrose for cyroprotection and allows the block to be sliced on a standard cryostat.
FTR83, a Member of the Large Fish-Specific finTRIM Family, Triggers IFN Pathway and Counters Viral Infection

Tripartite motif (TRIM) proteins are involved in various cellular functions and constitute key factors of the antiviral innate immune response. TRIM proteins can bind viral particles directly, sending them to degradation by the proteasome, or ubiquitinate signaling molecules leading to upregulation of innate immunity. TRIM proteins are present in across metazoans but are particularly numerous in vertebrates where genes comprising a B30.2 domain have been often duplicated. In fish, a TRIM subset named finTRIM is highly diversified, with large gene numbers and clear signatures of positive selection in the B30.2 domain suggesting they may be involved in antiviral mechanisms. finTRIM provides a beautiful model to investigate the primordial implication of B30.2 TRIM subsets in the arsenal of vertebrate antiviral defenses. We show here that ftr83, a zebrafish fintrim gene mainly expressed in the gills, skin and pharynx, encodes a protein affording a potent antiviral activity. In vitro, overexpression of FTR83, but not of its close relative FTR82, induced IFN and IFN-stimulated gene expression and afforded protection against different enveloped and non-enveloped RNA viruses. The kinetics of IFN induction paralleled the development of the antiviral activity, which was abolished by a dominant negative IRF3 mutant. In the context of a viral infection, FTR83 potentiated the IFN response. Expression of chimeric proteins in which the B30.2 domain of FTR83 and the non-protective FTR82 had been exchanged, showed that IFN upregulation and antiviral activity requires both the Ring/BBox/Coiled coil domain (supporting E3 ubiquitin ligase) and the B30.2 domain of FTR83. Finally, loss of function experiments in zebrafish embryos confirms that ftr83 mediates antiviral activity in vivo. Our results show that a member of the largest TRIM subset observed in fish upregulates type I IFN response and afford protection against viral infections, supporting that TRIMs are key antiviral factors across vertebrates.