Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Adrenomedullin in Patients with Rheumatoid Arthritis

The mechanism of arthritis including rheumatoid arthritis (RA) has not been clarified enough in terms of its molecular biology. However, owing to advances in techniques to produce monoclonal antibodies and genetic engineering techniques to produce recombinant proteins, targeted therapies have progressed. Tumor necrosis factor-alpha (TNF-), interleukin-1 (IL-1), interleukin-6 (IL-6), and T-cells (CD28) are representative targets, and therapies targeting them have produced epoch-making results in the treatment of RA. In this text, we report the role and effects of therapy with adrenomedullin as a novel, promising targeted therapy. Adrenomedullin (ADM) is a peptide that was discovered by the assay-based monitoring of platelet cAMP activity (Kitamura et al., 1993). This protein shows not only marked vasodilatory but also in vivo and in vitro anti-inflammatory activities (Isumi et al., 1998). To determine the efficacy of ADM in patients with RA, we researched the plasma level of ADM and its correlation with the plasma CRP level. The result showed that the plasma ADM level in patients with RA was twice that in healthy controls and strongly correlated with the blood CRP level, and the ADM level in synovial tissue in patients with RA was 3 times that in patients with osteoarthritis (Chosa et al., 2003). Then, thorough research is needed to examine whether the cultured RA synoviocytes are related to the ADM in vitro. The result showed that ADM was produced from RA synoviocytes and reduced the IL-6 level in cultured media (Fig. 5). These results suggest the close involvement of ADM in arthritis in RA. Therefore, to examine the therapeutic efficacy of intra-articular ADM injection, we injected ADM into the joint of a rabbit model of adjuvant arthritis, and confirmed the inhibition of arthritis at an early stage. These findings suggest the potentiality of ADM as a novel drug for the treatment of arthritis in RA (Okura et al., 2008).
Retargeting of Human Regulatory T Cells by Single-Chain Bispecific Antibodies

Bispecific Abs hold great potential for immunotherapy of malignant diseases. Because the first components of this new drug class are now entering clinical trials, all aspects of their mode of action should be well understood. Several studies proved that CD8+ and CD4+ effector T cells can be successfully redirected and activated against tumor cells by bispecific Abs both in vitro and in vivo. To our knowledge, this study provides the first evidence that bispecific Abs can also redirect and activate regulatory T cells against a surface Ag, independently of their TCR specificity. After cross-linking, via a bispecific Ab, redirected regulatory T cells upregulate the activation markers CD69 and CD25, as well as regulatory T cell-associated markers, like CTLA-4 and FOXP3. The activated regulatory T cells secrete the immunosuppressive cytokine IL-10, but, in contrast to CD8+ and CD4+ effector T cells, almost no inflammatory cytokines. In addition, the redirected regulatory T cells are able to suppress effector functions of activated autologous CD4+ T cells both in vitro and in vivo. Therefore, the potential risk for activation of regulatory T cells should be taken into consideration when bispecific Abs are applied for the treatment of malignant diseases. In contrast, an Ag/tissue-specific redirection of regulatory T cells with bispecific Abs holds great potential for the treatment of autoimmune diseases and graft rejection.
Quarter wavelength resonators for use in wireless capacitive power transfer

Wireless capacitive power transfer is a growing research area that mainly focuses on non-radiating techniques. It has the potential to be highly efficient, low cost, and less susceptible to alignment issues. One major challenge hindering its widespread use is the high voltages found between the capacitive electrodes. Due to this, bipolar (dual, plus/minus electrode) techniques are predominant in literature, as unipolar (one electrode) techniques generally require even higher voltages for operation. Here we present the use of quarter wave resonators as one method to reduce electrode voltages while maintaining efficient energy transfer in a unipolar capacitive geometry. An accurate theoretical model is given based on standard circuit theory. Experimental verification of power transfer over a 5 m by 0.3 m surface is presented where various loads are placed on the system and changing phase parameters are measured.
Quantitative assessment of AMPA receptor mRNA in human spinal motor neurons isolated by laser capture microdissection

Disturbance of glutamate neurotransmission may contribute to the motor neuron injury seen in amyotrophic lateral sclerosis. Previous studies have suggested that human spinal motor neurons express a specific profile of the AMPA subtype of glutamate receptor with low mRNA expression for the GluR2 AMPA receptor subunit but other studies have contested this finding. The present study uses laser capture microdissection to isolate specifically identified neurons coupled with quantitative RT-PCR to demonstrate that the level of expression of the GluR2 subunit is lower in spinal motor neurons than in dorsal horn neurons from the same spinal cord region. Thus, it is likely that human spinal motor neurons express a proportion of Ca2+-permeable AMPA receptors which may contribute to the selective vulnerability of these cells in amyotrophic lateral sclerosis.
Reaction of Partially Hydrolyzed Products of Saligenin Cyclic Phosphorus Esters Toward SH-Compcunds

In order to know the mechanism for the alkylation of mercaptans and for the inhibition of “SH-enzymes” with saligenin cyclic phosphorus esters, a possible intermediate, that is a ring-opened salicyl ester, and related compounds including saligenin cyclic hydrogen phosphate were synthesized and their reactions with cysteine and yeast alcohol dehydrogenase were investigated. Besides neutral saligenin cyclic esters, only salicyl ester was active as alkylating agent and SH-enzyme inhibitor.
A Prospective, Comparative, Radiological, and Clinical Study of the Influence of the “Remplissage” Procedure on Shoulder Range of Motion After Stabilization by Arthroscopic Bankart Repair

Background: Certain failures of arthroscopic Bankart repairs seem to be related to the presence of a Hill-Sachs defect. It has been suggested that Hill-Sachs lesions can be treated by “remplissage” (filling in) of the defect. The effect of this procedure on the mobility of the shoulder is not known. Purpose: To determine if filling in the Hill-Sachs defect with rotator cuff tendon would modify the range of motion of the operated shoulder. Study Design: Cohort study; Level of evidence, 2. Methods: A prospective study of 2 patient populations (arthroscopic Bankart repair alone vs Bankart and remplissage) was undertaken after selecting patients using the Instability Severity Index Score (ISIS). Patients with a Hill-Sachs lesion seen on anteroposterior radiographs had a remplissage procedure if this procedure allowed them to obtain an ISIS lower than 4. The main clinical outcome was the range of motion (external rotation at the side [ER1], external rotation in abduction [ER2], internal rotation [IR], and forward elevation), assessed by the difference between each shoulder at 1 and 2 years’ follow-up. Complications, recurrence, and the Walch-Duplay scores were noted at the same time. Minimum follow-up was 2 years. Results: No significant statistical difference was noted in the range of motion between each group: ER1, difference of 4° (P = .22); ER2, difference of 3° (P = .49); anterior elevation, difference of 5° (P = .35); and internal rotation, 2 vertebrae (P = .22). The rate of recurrence was identical in both groups (6.25%). For patients without redislocation, the Walch-Duplay score was excellent (14/17) or good (3/17) in the first group and excellent (12/15) or good (3/15) in the second group. Posterosuperior pain during forceful movements or when tired was noted in one third of patients having undergone remplissage. Conclusion: The remplissage technique did not alter the range of motion of the shoulder compared with Bankart procedure alone; however, one third of patients did experience posterosuperior pain.
Populations The Emergence of ' ' Us and Them ' ' in 80 Lines of Code : Modeling Group Genesis in Homogeneous

Psychological explanations of group genesis often require population heterogeneity in identity or other characteristics, whether deep (e.g., religion) or superficial (e.g., eye color). We used agent-based models to explore group genesis in homogeneous populations and found robust group formation with just two basic principles: reciprocity and transitivity. These emergent groups demonstrated in-group cooperation and out-group defection, even though agents lacked common identity. Group formation increased individual payoffs, and group number and size were robust to varying levels of reciprocity and transitivity. Increasing population size increased group size more than group number, and manipulating baseline trust in a population had predictable effects on group genesis. An interactive demonstration of the parameter space and source code for implementing the model are available online.
Sexual dysfunctions and suicidality in patients with bipolar disorder and unipolar depression.

INTRODUCTION Impairment in sexual function is frequent and underestimated in patients with mental disorders, particularly in those with mood disorders. Few studies have examined the relationship between sexual dysfunctions and the clinical characteristics of mood disorders. AIM The aim of the present study was to explore the frequency of sexual dysfunctions in patients with bipolar I disorder (BD) and unipolar depression (UD) with respect to control subjects, as well as their relationship with suicidality. MAIN OUTCOME MEASURES Assessments included: the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (SCID-I/P), the 24-item Brief Psychiatric Rating Scale and the Mood Spectrum Self-Report, a questionnaire exploring lifetime mood spectrum symptomatology including symptoms of sexual functioning and suicidality. METHODS A consecutive sample of 142 patients (60 BD and 82 UD) and a comparison group of 101 control subjects were recruited in a multicenter study involving 11 academic departments of psychiatry. RESULTS Lifetime impairment in the sexual response cycle, including desire, excitement, and ability to achieve orgasm, was significantly more common in patients with mood disorders compared with control subjects. Increase in sexual activity and promiscuity were significantly more common in patients with BD vs. the other two groups. Lifetime dysfunctions in all three phases of the sexual response cycle explored were significantly associated with lifetime suicide attempts in patients with BD and with thoughts of death in patients with UD. In BD patients, the lifetime presence of periods with frequent changes of sexual partners was significantly associated with thoughts of death. CONCLUSIONS Our findings suggest the importance of assessing sexual dysfunctions in patients with either BD or UD, as they may be clinically helpful in identifying phenotypes of mood disorders characterized by high suicidality.
ATM regulates Mre11-dependent DNA end-degradation and microhomology-mediated end joining

The human disorder ataxia telangiectasia (AT), which is characterized by genetic instability and neurodegeneration, results from mutation of the ataxia telangiectasia mutated (ATM) kinase. The loss of ATM leads to cell-cycle checkpoint deficiencies and other DNA damage signaling defects that do not fully explain all pathologies associated with A-T including neuronal loss. In addressing this enigma, we find here that ATM suppresses DNA double-strand break (DSB) repair by microhomology-mediated end joining (MMEJ). We show that ATM repression of DNA end-degradation is dependent on its kinase activities and that Mre11 is the major nuclease behind increased DNA end-degradation and MMEJ repair in A-T. Assessment of MMEJ by an in vivo reporter assay system reveals decreased levels of MMEJ repair in Mre11-knockdown cells and in cells treated with Mre11-nuclease inhibitor mirin. Structure-based modeling of Mre11 dimer engaging DNA ends suggests the 5' ends of a bridged DSB are juxtaposed such that DNA unwinding and 3'-5' exonuclease activities may collaborate to facilitate simultaneous pairing of extended 5' termini and exonucleolytic degradation of the 3' ends in MMEJ. Together our results provide an integrated understanding of ATM and Mre11 in MMEJ: ATM has a critical regulatory function in controlling DNA end-stability and error-prone DSB repair and Mre11 nuclease plays a major role in initiating MMEJ in mammalian cells. These functions of ATM and Mre11 could be particularly important in neuronal cells, which are post-mitotic and therefore depend on mechanisms other than homologous recombination between sister chromatids to repair DSBs.
The human false‐negative rate of rescreening Pap tests

Routine quality control rescreening often is used to calculate the false‐negative rate (FNR) of gynecologic cytology. Theoretic analysis suggests that this is not appropriate, due to the high FNR of rescreening and the inability to actually measure it. The authors sought to determine the FNR of manual rescreening in a large, prospective, two‐arm clinical trial using an analytic instrument in the evaluation.
Effect of oral digoxin in high‐risk heart failure patients: a pre‐specified subgroup analysis of the DIG trial

In the Digitalis Investigation Group (DIG) trial, digoxin reduced mortality or hospitalization due to heart failure (HF) in several pre‐specified high‐risk subgroups of HF patients, but data on protocol‐specified 2‐year outcomes were not presented. In the current study, we examined the effect of digoxin on HF death or HF hospitalization and all‐cause death or all‐cause hospitalization in high‐risk subgroups during the protocol‐specified 2 years of post‐randomization follow‐up.
Incorporation of bacterial quorum sensing in synthetic biology

Title of Dissertation: INCORPORATION OF BACTERIAL QUORUM SENSING IN SYNTHETIC BIOLOGY Hsuan-Chen Wu, Doctor of Philosophy, 2012 Directed By: Professor William E. Bentley Fischell Department of Bioengineering The global objective of this research is to develop a synthetic biology toolkit consisting of molecules, cells, and devices that provide flexible, yet selective targeting, sensing, and switching capabilities, that in turn guide biological behavior in userspecified manner. We employ bacteria as “smart” programmable devices. We envision creating bacteria that autonomously move to specific areas, synthesize a drug, deliver the drug, and move on to new sites. “Targeting” endows bacterial cells the means to dock onto specific surfaces with antibody-antigen specificity. Sensing and switching capability allows bacteria to sense and, after making a “decision”, respond by synthesizing and delivering cargo to molecular scale features displayed on target surfaces. Relevant surface features may include an overexpressed receptor on a tumor cell, glucagon-like peptide-1 receptor on pancreatic beta cells, or even other bacterial cells resident in a recalcitrant biofilm. Towards the realization of this goal, we employed an antibody-binding protein G display strategy to complex target-binding antibodies with bacteria. We characterized the assembly and efficacy of this complex by binding to well-defined surfaces decorated with specific antigens. For sensing and switching we made use of the genetic circuitry of bacterial quorum sensing (QS) that coordinates multicellular responses. In particular, we hypothesized the creation of a biological “switch” that would take action only after a certain threshold “feature” density had been detected. Specifically, in our most significant demonstration we designed and implemented QS based sensing and actuating based on the surface density of cancer-indicating EGFR receptors displayed on epithelial
Income Smoothing Over the Business Cycle: Changes in Banks Coordinated Management of Provisions for Loan Losses and Loan Charge-Offs from the Pre-1990 Bust to the 1990s Boom

Prior research shows that during the pre‐1990 bust financially weak banks managed income upward by delaying provisions for losses on heterogeneous loans. In contrast, we predict and find that during the 1990s boom profitable banks managed income downward by accelerating provisions for losses on homogeneous loans. Profitable banks obscured their income smoothing by accelerating charge‐offs of homogeneous loans and by recording more gross charge‐offs to offset recoveries of previously charged‐off loans. Over the three years subsequent to the acceleration of charge‐offs, they had higher and more persistent income before provisions for loan losses than other banks, consistent with income smoothing over a prolonged horizon.
Usability Studies In Virtual And Traditional Computer Aided Design Environments For Spatial Awareness

Abstract : A usability study was used to measure user performance and user preferences for a CAVETM immersive stereoscopic virtual environment with wand interfaces compared directly with a workstation non-stereoscopic traditional CAD interface with keyboard and mouse. In both the CAVETM and the adaptable technology environments, crystal eye glasses are used to produce a stereoscopic view. An ascension flock of birds tracking system is used for tracking the user's head and wand pointing device positions in 3D space.
Solving Minimum Energy Structures with Neural Networks

In this paper, we train a neural network on atomic configurations to predict energy as a function of atom position, then use this neural network to perform optimization to solve for minimum energy atomic configuration. This is a problem of interest because it could potentially provide a boost to both accuracy and speed over traditional numeric methods of solving for the structure of molecules. Previous papers have shown that neural networks trained on the results of numerical simulations can reproduce those results to high accuracy. We construct one such neural network and experiment with new methods of optimizing its parameters, then use it as a function to optimize in order to find the minimum energy configuration for a systems of a few homonuclear atoms. The results are promising, with our neural network accuracy beating that of the baseline neural network for the problem, and the minimization results showing an improvement over the data the neural network was trained on.
Electroencephalographic findings in juvenile delinquency.

One hundred juvenile delinquents were examined electroencephalographically in order to investigate the incidence and importance of obvious or previously unrecognized temporal lobe epilepsy. This correlation was not found to be significant. Twenty-nine patients were found to have 14 and 6 per second positive spikes. Inquiry also revealed that 13 of the 89 teenagers, for whom a good history could be obtained, had had breath-holding spells in earlier years.
Blocking Cold-Inducible RNA-Binding Protein Protects Liver From Ischemia-Reperfusion Injury

ABSTRACT Cold-inducible RNA-binding protein (CIRP) is a nuclear protein that has been recently identified as a novel inflammatory mediator in hemorrhagic shock and sepsis. We hypothesized that CIRP acts as a potent inflammatory mediator in hepatic ischemia-reperfusion (I/R), and thus blocking CIRP protects against I/R-induced liver injury. Male C57BL/6 mice were subjected to 70% hepatic ischemia by microvascular clamping of the hilum of the left and median liver lobes for 60 min, followed by reperfusion. Anti-CIRP antibody (1 mg/kg body weight) or vehicle (normal saline) in 0.2 mL was injected via the internal jugular vein at the beginning of the reperfusion. Blood and liver tissues were collected 24 h after I/R for various measurements, and a 10-day survival study was performed. Cold-inducible RNA-binding protein released into the circulation was significantly increased 24 h after hepatic I/R. Anti-CIRP antibody treatment markedly reduced hepatocellular damage markers and significantly improved the liver microarchitecture. Anti-CIRP also reduced the systemic and local inflammation demonstrated by attenuation in both serum and hepatic levels of interleukin 6. The expression of neutrophil-attracting chemokine as well as liver neutrophil infiltration was reduced by anti-CIRP treatment. Anti-CIRP also dramatically decreased the amount of apoptosis and nitrosative stress, evidenced by decrease in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining and inducible nitric oxide synthase and cyclooxygenase 2 levels, respectively. Finally, the 10-day survival rate was increased from 37.5% in the vehicle group to 75% in the anti-CIRP treatment group. Thus, targeting CIRP offers potential therapeutic implications in the treatment of hepatic I/R injury.
Debt Composition and Lax Screening in the Corporate Bond Market

Corporate bond markets may suffer from investors’ lack of competence in screening out low-quality issuers. We use data from the Israeli capital market in 1999–2009 to investigate the quality of corporate bond issuers and the role of the institutional investors in the screening process in the corporate bond market. The findings suggest that higher quality firms were more likely to issue bonds, but firms of lower quality tended to raise a higher fraction of their debt through bond issuance. Firms with higher proportion of their debt in bonds out had also a higher tendency to default. Institutional investors intensively funded firms with higher share of bonds in their long-term debt despite their lower quality, and therefore were partially responsible for the lax screening in the corporate bond market.
The newborn rabbit sino‐atrial node expresses a neuronal type I‐like Na+ channel.

1. Newborn rabbit sino‐atrial node (SAN) myocytes were recently found to express a tetrodotoxin (TTX)‐sensitive Na+ current. We now report that the dose‐response relation indicates that this SAN Na+ channel has unusually high TTX sensitivity, with half‐maximal inhibition (26 +/‐ 5 nM) which is more typical of neuronal than cardiac tissue. 2. Additional characterization used mu‐conotoxin GIIIA and Cd2+ as relatively selective blockers of the skeletal and cardiac isoforms, respectively. mu‐Conotoxin GIIIA had no effect on the current recorded from SAN myocytes, but the Cd2+ sensitivity was unexpectedly high for a neuronal isoform (half‐maximal inhibition = 185 +/‐ 8 microM). 3. Analysis of the time constant of inactivation did not reveal evidence of multiple inactivation processes, with the data well fitted by a single, relatively rapid exponential (inactivation time constant = 0.58 +/‐ 0.03 ms at 0 mV). 4. In situ hybridization with anti‐sense cDNA probes was used to test for expression of neuronal type I, II and III Na+ channel isoforms. Myocardial cells in newborn SAN tissue exhibited clear hybridization to the type I, but not the type II or III probes. No hybridization was observed in adult SAN tissue with any of the three probes. 5. It is concluded that the newborn SAN expresses a neuronal type I‐like Na+ channel isoform, and that this probably accounts for the unusual characteristic of high sensitivity to both TTX and Cd2+.