Miracle-dz/UniFAR-FTUs huggingface dataset:
Mantel statistics to correlate gene expression levels from microarrays with clinical covariates

Mantel statistics provide an additional step to standard approaches in the analysis of gene expression and covariate data, allow the calculation of standard statistics such as correlation, partial correlation, and regression coefficients, and, with permutation tests, provide P values for these statistics to relate the sample covariates to the expression levels. In this article we describe the Mantel statistics and illustrate their use and interpretation with data from a study of seven human oligodendrogliomas (brain tumors) where expression levels of 1,013 genes and five covariates were previously analyzed using standard approaches. In the previous analysis of these data, qualitative relationships were found between gene expressions and two of the clinical covariates. We show in this article how the Mantel statistics are able to formally quantify and provide P values to determine statistical significance of these relationships. We also show how the Mantel statistics can be used to rank subsets of genes, found using standard clustering methods, in terms of differential expression across samples. Genet. Epidemiol. 23:87–96, 2002. © 2002 Wiley‐Liss, Inc.
Upper and Lower Extremity Muscle Fatigue after a Baseball Pitching Performance

Background Previous studies have estimated joint torques and electromyogram activity associated with the pitching motion. Although previous studies have investigated the influence of extended pitching (fatigue) on kinematic and kinetic parameters, no attempts have been made to quantify the fatigue associated with a pitching performance. Purpose Considering previous investigations on muscle activity during pitching, this study investigated muscle fatigue in upper and lower extremity muscle groups after a pitching performance. Study Design Descriptive laboratory study. Methods Thirteen baseball pitchers from 4 universities and 1 independent minor league team were tested before and after 19 games. Pitchers threw an average of 99 pitches during an average of 7 innings. Shoulder, scapular, and lower extremity muscle strengths were assessed using a handheld dynamometer before and after the pitching performances. Results Baseline strength tests revealed that the pitching arm was 12% weaker (P =. 02) in the empty can test (supraspinatus) compared to the contralateral side. Postgame shoulder strength tests revealed selective fatigue of 15% in shoulder flexion (P =. 02), 18% fatigue in internal rotation (P =. 03), and 11% fatigue in shoulder adduction (P =. 01). Minimal fatigue was noted in the empty can test, scapular stabilizers, and hip musculature. Conclusions A trend toward significant baseline strength in internal rotation together with significant selective postgame fatigue on internal rotation of the dominant upper extremity indicate that the internal rotators experience a high performance demand during pitching. Weakness in the empty can test on the dominant arm combined with minimal postgame fatigue was surprising given that studies and injury patterns have indicated a high performance demand on the supraspinatus during pitching.
Comparative Evaluation of HERG Currents and QT Intervals following Challenge with Suspected Torsadogenic and Nontorsadogenic Drugs

The purpose of the present study was to comparatively evaluate human HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. Various concentrations of 14 different drugs were initially evaluated in terms of their relative potency to block IHERG in stably transfected human embryonic kidney cells. Four general categories of drugs were identified: high-potency blockers (IC50 < 0.1 μM) included lidoflazine, terfenadine, and haloperidol; moderate-potency blockers (0.1 μM < IC50 < 1 μM) included sertindole, thioridazine, and prenylamine; low-potency blockers (IC50 > 1 μM) included propafenone, loratadine, pyrilamine, lovastatin, and chlorpheniramine; and ineffective blockers (IC50 > 300 μM) included cimetidine, pentamidine, and arsenic trioxide. All measurements were performed using similar conditions and tested acute drug effects only (<30 min of drug exposure per measurement). Since two of the drugs that were ineffective IHERG blockers, arsenic trioxide and pentamidine, have been associated with cardiac repolarization delays (QT interval lengthening) and torsades de pointes ventricular arrhythmias in patients, we chose to evaluate them further using the isolated perfused rabbit heart model. Neither arsenic trioxide nor pentamidine had any significant effect on QT intervals in this model, even at relatively high (micromolar) concentrations. Similar results were obtained for loratadine in this model. When the hearts were challenged with a known torsadogenic drug such as cisapride, significant QT lengthening was rapidly induced. These results demonstrate that arsenic trioxide and pentamidine are essentially devoid of direct acute effects on cardiac repolarization or inhibition of IHERG.
Differential regulation of gelatinases by transforming growth factor beta-1 in normal equine chondrocytes.

OBJECTIVE Cartilage destruction in osteoarthritis (OA) is associated with increased levels of several matrix metalloproteinases (MMPs), including the gelatinases MMP-2 and MMP-9. While increases in some MMPs may be destructive, up-regulation of others may result from increases in normal tissue turnover. The production of MMP-2 and MMP-9 by the anabolic transforming growth factor beta-1 (TGF-beta1) in normal equine chondrocytes was investigated. DESIGN Equine chondrocytes from clinically normal femoropatellar joints were maintained in alginate beads. After serum deprivation, cells were exposed to TGF-beta1 at several concentrations for varying times. Activities of MMP-2 and MMP-9 were estimated by gelatin zymography, while mRNA for MMP-2, MMP-9 and collagen type II were detected using reverse transcription-polymerase chain reaction. RESULTS Stimulation with TGF-beta1 differentially regulated MMP-2 and MMP-9, with strong up-regulation of both MMP-9 mRNA and enzyme. Increases in MMP-9 enzyme were dose-dependent (0-49 h). There is some evidence suggesting a slight reduction in MMP-2 release following stimulation. Collagen type II mRNA was transiently increased following stimulation. CONCLUSIONS The different effects of TGF-beta1 on MMP-2 and MMP-9 production by normal chondrocytes suggests different roles for these enzymes. The increases in both MMP-9 and collagen type II mRNA following stimulation may suggest a role for MMP-9 in tissue maintenance. Therefore, increased MMP-9 may be secondary to, as distinct from a cause of, cartilage damage.
Serially connected monolayer MoS2 FETs with channel patterned by a 7.5 nm resolution directed self-assembly lithography

We demonstrate sub-10 nm transistor channel lengths by directed self-assembly patterning of monolayer MoS<sub>2</sub> in a periodic chain of homojunction semiconducting-(2H) and metallic-phase (1T') MoS<sub>2</sub> regions with half-pitch of 7.5 nm. The MoS<sub>2</sub> composite transistor possesses an off-state current of 100 pA/μm and an I<sub>on</sub>/I<sub>off</sub> ratio in excess of 10<sup>5</sup>. Modeling of the resulting current-voltage characteristics reveals that the 2H/1T' MoS<sub>2</sub> homojunction has a resistance of 75 Ω. μm while the 2H-MoS<sub>2</sub> exhibits low-field mobility of ~8 cm<sup>2</sup>/V.s and carrier injection velocity of ~10<sup>6</sup> cm/s.
Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation

In Huntington's Disease and related expanded CAG repeat diseases, a polyglutamine [poly(Gln)] sequence containing 36 repeats in the corresponding disease protein is benign, whereas a sequence with only 2–3 additional glutamines is associated with disease risk. Above this threshold range, longer repeat lengths are associated with earlier ages-of-onset. To investigate the biophysical basis of these effects, we studied the in vitro aggregation kinetics of a series of poly(Gln) peptides. We find that poly(Gln) peptides in solution at 37°C undergo a random coil to β-sheet transition with kinetics superimposable on their aggregation kinetics, suggesting the absence of soluble, β-sheet-rich intermediates in the aggregation process. Details of the time course of aggregate growth confirm that poly(Gln) aggregation occurs by nucleated growth polymerization. Surprisingly, however, and in contrast to conventional models of nucleated growth polymerization of proteins, we find that the aggregation nucleus is a monomer. That is, nucleation of poly(Gln) aggregation corresponds to an unfavorable protein folding reaction. Using parameters derived from the kinetic analysis, we estimate the difference in the free energy of nucleus formation between benign and pathological length poly(Gln)s to be less than 1 kcal/mol. We also use the kinetic parameters to calculate predicted aggregation curves for very low concentrations of poly(Gln) that might obtain in the cell. The repeat-length-dependent differences in predicted aggregation lag times are in the same range as the length-dependent age-of-onset differences in Huntington's disease, suggesting that the biophysics of poly(Gln) aggregation nucleation may play a major role in determining disease onset.
Usage and Exposures at Default of Corporate Credit Lines: An Empirical Study

Using a unique data set pooled from multiple US financial institutions, we empirically study the credit line usage of middle-market corporate borrowers. We find that defaulted borrowers draw down more of their lines than nondefaulted borrowers. They also increase their usage when approaching default. Riskier borrowers tend to utilize a higher percentage of their credit lines. We find that firms rated as “pass” grade by the lender draw down the credit lines more than those rated below “pass” grade. Usage ratios also vary by collateral type, commitment size, loan purpose type and prior quarter’s usage. Further, we find evidence that usage ratios are higher during economic downturns. The evidence is stronger for nondefaulted firms than for defaulted firms. Taken together, these results suggest that credit line usage is a function of both borrowers’ characteristics and banks’ monitoring and control of these lines.
Physical-Statistical Modeling of Dynamic Indoor Power Delay Profiles

This paper presents a physical-statistical radio channel power delay profiles model for room-to-room communication systems combining the room electromagnetic theory for modeling deterministic channel components with a geometry-based stochastic channel model with time-variant statistics for modeling stochastic components. The deterministic channel component, i.e., mean power delay spectrum, is comprised of specularly reflected paths plus diffuse components due to scattering and diffraction. The specular components are modeled with a set Dirac function, whereas the diffuse components modeling approach is a room electromagnetic theory-based model. Dynamic indoor communication channels are characterized by a non-stationary time- and delay-fading process due to changes in the environment. We analyze and model the time-delay variability of channels using $K$ -factor for small-scale variations and the $t$ -location scale distribution parameters for large-scale variations. It turns out that these parameters cannot be assumed to be constant in time and delay. After modeling of time-delay variations of the first order statistics, we generate channel realizations with appropriate second order statistics. As the result, the presented model enables to describe the evolution of the power delay profile in the time domain.
Active frequency multiplier-by-nine MMIC for millimeter-wave signal generation

An active frequency multiplier-by-nine MMIC with integrated buffer amplifier reaching 94 GHz from X-band is presented. The multiplier-by-nine generates an average output power of −6.5 dBm in the frequency range from 87 to 99 GHz. At 94 GHz the measured output power is −5 dBm with an input power of 9 dBm. The suppression of unwanted harmonics is better than 15 dBc. Phase-noise measurements prove the theoretical noise degeneration of 19 dB for the integrated circuit. The MMIC is realized in the Fraunhofer IAF metamorphic HEMT technology with 100 nm gate-length.
Transportation of Multiple Biological Cells Through Saturation-Controlled Optical Tweezers In Crowded Microenvironments

Transportation of biological cells has attracted increased attention in bioscience and nanomedicine. Existing approaches to achieve automated multicell transportation are generally based on numerous overstrict conditions or assumptions, including static and clean environments, complex theoretical convergence conditions, omitting tool kinematics, and off-line calibrations. This paper presents a novel approach for the automated transportation of multiple cells by using robotically controlled holographic optical tweezers. First, a swarming controller is developed with easily satisfied convergence conditions. The offset between centers of the cell and optical tweezers is constrained by saturation control to maintain the cells in the optically trapping area. An artificial first-order kinematic model of the tweezers is considered in the controller design to reduce controller oscillation. Second, a solution to the collision avoidance of random-moving obstacles is developed to remove the assumption of static or clean environments. Finally, an automated method based on the drag force model and gradient descent optimization is presented to calibrate cell dynamics online. Experiments on yeast cells are performed to verify the effectiveness of the proposed approach.
Studies on the Mechanism of Replication of Adenovirus DNA II. The Nature of Single-Stranded DNA in Replicative Intermediates

Replicative intermediates of adenovirus type 5 DNA contain large stretches of single-stranded DNA. We have shown that this single-stranded DNA is mainly of parental origin, whereas all new DNA synthesized during one round of replication has a double-stranded structure. Hybridization experiments of the single-stranded DNA with isolated complementary strands of adenovirus type 5 DNA showed that this DNA hybridized only with the viral L-strand (the strand with the lower equilibrium density in alkaline CsCl) indicating that it represents the viral H-strand. This observation implies that replication always starts from one and the same molecular end. Electron microscopy of partially denatured Y-shaped intermediates confirmed this and showed that replication started from the molecular right end (the end richest in A-T base pairs). In conclusion, we have shown that replication of adenovirus type 5 DNA starts at the molecular right end, displacing the parental H-strand.
Recognition and management of anxiety and depression in elderly patients.

OBJECTIVE To describe important aspects of the recognition and management of anxiety and depression in elderly patients. DESIGN We reviewed pertinent recent articles in the medical literature and compiled guidelines for diagnosing and treating anxiety and depression in the geriatric population. RESULTS Depression and anxiety are common in the elderly population. The development of depression in elderly subjects is associated with a higher risk of death from suicide than for any other age-group. Recognition of depression in elderly patients is often hampered by an inability or reluctance on the part of these patients to report depressive symptoms. In addition, anxiety and depression are often attributed to organic illness in this age-group. Pharmacotherapy is effective; however, older patients are probably more likely than young patients to experience adverse effects. Using medications at lower doses, choosing drugs with shorter half-lives, and avoiding drugs with potent anticholinergic side effects are often advisable. CONCLUSION Anxiety and depression are common conditions among the elderly population. Correct recognition, attention to underlying precipitating factors, and compassionate, supportive care can vastly improve the quality of the lives of these patients.
Prediction of total harmonic distortion based on harmonic modeling of nonlinear loads using measured data for parameter estimation

The total harmonic distortion (THD) of current in a feeder cannot be calculated using THD of each load. Each harmonic order of current can range from cancellation to addition depending on its phase angle. In this paper, a method for prediction of current distortions of nonlinear loads operating together is proposed. This method uses a model able to predict the magnitude spectrum and the phase spectrum of current in nonlinear loads. This paper uses experimental data in a simplified practical approach that is carried out in frequency domain. The model is based on harmonically coupled admittance matrix. These matrices are used to analyze harmonics in static converters. Studies in this paper are based on load tests in LED lamps and compact fluorescent lamps operating together. The model prediction results are compared with measured data.
Construction and characterization of a recombinant canine adenovirus expressing GP5 and M proteins of porcine reproductive and respiratory syndrome virus.

The causative agent of porcine reproductive and respiratory syndrome (PRRS) is PRRS virus (PRRSV), which belongs to the family Arteriviridae. GP5/M protein complex of PRRSV binds to sialoadhesion expressed on the cells to infect the cells. In this study, we developed a canine adenovirus type 2 (CAV-2) recombinant, termed rCAV2-GP5/M, expressing GP5 and M proteins. To evaluate the immunogenicity of the recombinant virus, mice were inoculated subcutaneously with rCAV2-GP5/M, and specific antibodies against PRRSV in the sera were measured by enzyme-linked immunosorbent assay and the viral neutralization test. Two weeks post-immunization (w.p.i.), anti-PRRSV antibodies were detected in the sera, slightly increased by booster immunization at four w.p.i. , and then gradually decreased. The viral neutralizing test showed that neutralizing antibodies were present in the sera collected at two w.p.i. , increased by booster immunization, and reached the maximum titer at six w.p.i. Lymphocyte proliferation responding to PRRSV antigens was also observed from two w.p.i. Although further studies are needed to evaluate the usefulness of the recombinant virus to protect pigs from PPRSV, we succeeded in developing a candidate vaccine against PPRSV infection by using CAV-2 vector.
Glutathione peroxidase mimic ebselen improves glucose-stimulated insulin secretion in murine islets.

AIMS Glutathione peroxidase (GPX) mimic ebselen and superoxide dismutase (SOD) mimic copper diisopropylsalicylate (CuDIPs) were used to rescue impaired glucose-stimulated insulin secretion (GSIS) in islets of GPX1 and(or) SOD1-knockout mice. RESULTS Ebselen improved GSIS in islets of all four tested genotypes. The rescue in the GPX1 knockout resulted from a coordinated transcriptional regulation of four key GSIS regulators and was mediated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-mediated signaling pathways. In contrast, CuDIPs improved GSIS only in the SOD1 knockout and suppressed gene expression of the PGC-1α pathway. INNOVATION Islets from the GPX1 and(or) SOD1 knockout mice provided metabolically controlled intracellular hydrogen peroxide (H2O2) and superoxide conditions for the present study to avoid confounding effects. Bioinformatics analyses of gene promoters and expression profiles guided the search for upstream signaling pathways to link the ebselen-initiated H2O2 scavenging to downstream key events of GSIS. The RNA interference was applied to prove PGC-1α as the main mediator for that link. CONCLUSION Our study revealed a novel metabolic use and clinical potential of ebselen in rescuing GSIS in the GPX1-deficient islets and mice, along with distinct differences between the GPX and SOD mimics in this regard. These findings highlight the necessities and opportunities of discretional applications of various antioxidant enzyme mimics in treating insulin secretion disorders. REBOUND TRACK: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16: 293-296, 2012) with the following serving as open reviewers: Regina Brigelius-Flohe, Vadim Gladyshev, Dexing Hou, and Holger Steinbrenner.
Calcitonin gene-related peptide and vasodilator nerves in large cerebral arteries of cats.

Calcitonin gene-related peptide's (CGRP) role(s) was examined in the transmural nerve stimulation (TNS)-induced vasodilator response of the large cerebral arteries of the cat in vitro. Numerous CGRP-like immunoreactive nerves were demonstrated to be present in the adventitial layer of the middle cerebral, anterior communicating and basilar arteries of the cat. An electron microscopic study revealed that immunoreactive material was contained in not only nerve axons but also in the button-like structures, i.e., varicosities, which were located close to smooth muscle cells. Exogenously applied CGRP induced a dose-dependent vasodilator response which was independent of the presence of endothelial cells and of nerve components. Nerve stimulation elicited transient hyperpolarization, i.e., inhibitory junction potential, which was of nonadrenergic, noncholinergic origin. Likewise, CGRP produced hyperpolarization of smooth muscle cells. After incubation of the tissue with capsaicin in vitro, the intensity of the CGRP-like immunoreactivity diminished greatly. The TNS-induced vasodilator response and inhibitory junction potentials were also attenuated after the incubation with capsaicin. These results suggest that CGRP is involved in the TNS-induced vasodilator response of the large cerebral arteries of the cat.
Novel Eph‐family receptor tyrosine kinase is widely expressed in the developing zebrafish nervous system

In a search for novel tyrosine kinases involved in vertebrate development, we have isolated cDNAs corresponding to three distinct members of the Eph‐family of receptor tyrosine kinases. Whole mount RNA in situ hybridization analysis showed all three genes were most abundantly expressed in the developing nervous system. zek1 (zebrafish Eph‐like kinase1) encodes a 981 amino acid polypeptide closely related to the murine Sek1 and Bsk receptors. Cos‐1 cells transfected with zek1 produce a 141 kilodalton tyrosine phosphorylated protein which is recognized by antibodies raised against two predicted Zek1 peptides. These antibodies also recognized a protein of the same apparent molecular weight in lysates from zebrafish embryos and adults. Widespread expression of zek1 in the developing brain and neural tube suggested a generalized function of the Zek1 receptor in neuronal cell ontogeny. Dev. Dyn. 209: 166‐181, 1997. © 1997 Wiley‐Liss, Inc.
Fast, cheap requirements prototype, or else!

Managing requirements modeling and prototyping is risky. If things go awry, projects can spiral out of control. Over the years, with the help of colleagues from industry and academia, the author has identified a requirements modeling and prototyping process that is fast, powerful, cost-effective, sane, and objective. The main lesson learnt is that throwaway prototyping (sometimes called exploratory prototyping) is always cost-effective and always improves specifications. The process has nine steps: elicit initial requirements; model requirements; identify constraints; prioritize initial requirements; design; evaluate designs; specification; interactive prototyping; and requirements validation. <<ETX>>