Miracle-dz/UniFAR-FTUs huggingface dataset:
Anabolic androgenic steroid abuse and mood disorder: a case report.

Current data suggest that the use of anabolic androgenic steroids (AAS) has become quite common among athletes, bodybuilders, as well as adolescents and young adults who want to increase their muscle mass for aesthetic or athletic reasons. Commonly used anabolic steroids are the oral 17α alkyl derivatives of testosterone (methyl testosterone, oxymetholone, oxandrolone, stanozolol) and the intramuscular 17β-esterified agents such as nandrolone decaonate, nandrolone phenpropionate, testosterone cypionate and testosterone propionate (Blue and Lombardo, 1999). The abuse of AAS has been associated with various psychiatric manifestations: sleep disorders, anxiety, labile mood, mania, depression, irritability, aggression, violence, suicidal and homicidal ideation and behaviour, psychosis, confusion and delirium. Long-term abuse may lead to the development of a dependence syndrome and associated withdrawal symptoms on attempted discontinuation (Hall et al., 2005; NIDA, 2006).
Sex-dependent genetic markers of CYP3A4 expression and activity in human liver microsomes.

OBJECTIVE To find genetic markers of the individual cytochrome P450 (CYP)3A expression. METHODS A large collection of liver samples phenotyped for CYP3A expression and activity was genotyped for CYP3A variants. Data were analyzed for associations between CYP3A phenotypes and genotypes, and for evidence of recent selection. RESULTS We report associations between the hepatic CYP3A4 protein expression level, as well as its enzymatic activity, measured as verapamil N-dealkylation, and genetic polymorphisms from two regions within the CYP3A gene cluster. One region is defined by several variants, mostly located within CYP3A7, the other by a single nucleotide polymorphism in intron 7 of CYP3A4. The effects of these single nucleotide polymorphisms are sex-dependent. For example, female carriers of T alleles of the single nucleotide polymorphism rs4646437C>T in CYP3A4 intron 7 have, respectively, 5.1-fold and 2.7-fold higher expression and activity compared with male T-carriers, but only 2.2-fold and 1.4-fold higher expression and activity compared with males of genotype CC. A regression analysis indicates that the impact of these single nucleotide polymorphisms in men goes beyond the previously reported sex effect. The rs4646437C undergoes positive selection in Caucasians, as evidenced by its relative extended haplotype homozygosity value located within the uppermost percentile of a genome-wide test set of haplotypes in the same 5% frequency bin. CONCLUSIONS Our findings reconcile the apparent contradiction between the evidence for the influence of the individual genetic makeup on CYP3A4 expression and activity suggested by clinical studies, and the failure to identify the responsible gene variants.
Algorithms for Finding Magic Labelings of Triangles

We present a new algorithm for finding vertexmagic total labelings of disjoint unions of triangles. Since exaustive searches are infeasible for large graphs, we use a specialized algorithm designed to find labelings with very restrictive properties, and then attempt to generate other labelings from these. We show constructively that there exists a vertex-magic total labeling, VMTL, for each of the feasible values of 7C3, 9C3 and 11C3.
Exotic becomes erotic: A developmental theory of sexual orientation.

A developmental theory of erotic/romantic attraction is presented that provides the same basic account for opposite-sex and same-sex desire in both men and women. It proposes that biological variables, such as genes, prenatal hormones, and brain neuroanatomy, do not code for sexual orientation per se but for childhood temperaments that influence a child's preferences for sex-typical or sex-atypical activities and peers. These preferences lead children to feel different from oppositeor same-sex peers—to perceive them as dissimilar, unfamiliar, and exotic. This, in turn, produces heightened nonspecific autonomic arousal that subsequently gets eroticized to that same class of dissimilar peers: Exotic becomes erotic. Specific mechanisms for effecting this transformation are proposed. The theory claims to accommodate both the empirical evidence of the biological essentialists and the cultural relativism of the social constructionists.
Nonparametric Change Detection in Multitemporal SAR Images Based on Mean-Shift Clustering

A nonparametric method for unsupervised change detection in multipass synthetic aperture radar (SAR) imagery is described. The method relies on a novel feature capturing the structural change between two SAR images and is robust to the statistical change that may be originated by speckle and coregistration inaccuracies. The proposed method starts from the scatterplot of the amplitude levels in the two images and applies the mean-shift (MS) algorithm to find the modes of the underlying bivariate distribution. If we assume that the two images have been preliminarily coregistered and calibrated on one another, then all the modes lying outside the main diagonal correspond to the structural changes across the two observations. The value of the probability density function (PDF) in any of the off-diagonal modes found by the MS algorithm is translated into a value of conditional information. This value is assigned to all image pixels generating the corresponding cluster in the scatterplot. Thus, a feature is obtained on a per-pixel basis. Experimental results on simulated changes and true SAR images acquired by the COSMO-SkyMed satellite constellation show that the proposed feature exhibits significantly better discrimination capability than the classical log-ratio (LR). Advantages over a preliminary version of the method without MS regularization and over another nonparametric method based on Kullback-Leibler divergence are also demonstrated. The method is robust when it is applied to SAR images with different acquisition angles, whose effects are deemphasized compared to the actual scene changes.
The Effect of Age on Inflammatory Responses and Nerve Root Injuries After Lumbar Disc Herniation: An Experimental Study in a Canine Model

Study Design. An experimental investigation on the effect of age on pathologic events surrounding the herniated disc and at the adjacent nerve root. Objectives. To investigate the role of age on the inflammatory responses and nerve root damage surrounding a sequestered lumbar disc fragment using a dog model. Summary of Background Data. Lumbar disc herniation is manifested in patients by variable clinical findings, natural history, and resorption phenomena in which the variability is particularly noted among patients with different ages. There are no previous reports on the effect of age on pathologic events induced by the herniated disc. Methods. Six beagle dogs, including two animals of each age group of 6, 12, and 24 months (human equivalent ages of 10, 15, and 24 years), were used in this study. The dogs underwent L4–L5, L5–L6, and L6–L7 laminotomy and discectomy under general anesthesia. An autologous intervertebral disc from the tail was divided into anulus fibrosus and nucleus pulposus fragments. The anulus fibrosus and nucleus pulposus fragments were placed in the anterolateral epidural space of L5–L6 and L6–L7, respectively. The L4–L5 discectomy site served as a control. Dogs were killed at 12 weeks after surgery. The lumbar spine was removed en bloc, and histologic sections were prepared consecutively and examined. Results. In the nucleus pulposus group at L6–L7, neovascularity, and intensive infiltration of lymphocytes, macrophages, and fibroblasts were observed surrounding the nucleus pulposus fragment in the 24-month-old group only. Degenerative changes of the nerve root fibers were observed in the 24-month-old group only. In the control and anulus fibrosus groups at L4–L5 and L5–L6, there were no marked inflammatory reactions in all age groups. The nerve root fibers around the anulus fibrosus were normal in all age groups. Conclusions. There is an effect of age on the inflammatory response and nerve root injury caused by the herniated disc. The apparent neuroprotective mechanism in the young animal, and the apparent inflammatory and resorption changes of the nucleus pulposus fragment in the older animal are quite intriguing.
Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials.

OBJECTIVE The authors explored the effect of galantamine on behavioral symptoms in Alzheimer disease (AD). METHODS Data were pooled from 2,033 subjects with mild-to-moderate AD who had participated in one of three randomized, double-blind, placebo-controlled trials of 3-, 5-, and 6-month durations. Subjects included in this post hoc analysis had received treatment with either placebo (N=686) or galantamine (N=1347) in total daily doses of 16 mg, 24 mg, or 32 mg. Behavioral symptoms were measured on the 10-item Neuropsychiatric Inventory (NPI). Four symptom clusters were defined a priori: 1) delusions, hallucinations; 2) agitation, depression, anxiety, apathy, irritability; 3) disinhibition, elation, aberrant motor behavior; 4) hallucinations, anxiety, apathy, aberrant motor behavior. RESULTS At endpoint, mean changes from baseline in NPI scores were significantly different between galantamine-treated subjects and placebo-treated subjects, favoring galantamine for several measures: total NPI, individual domains of agitation/aggression, anxiety, disinhibition, and aberrant motor behavior, and Clusters 1, 3, and 4. The magnitude of the effect sizes was small. CONCLUSIONS In this pooled sample of more than 2,000 subjects with mild-to-moderate AD, those who received galantamine therapy experienced modestly better, but statistically significant, outcomes in their behavioral symptoms than placebo-treated subjects. The cluster of hallucinations, anxiety, apathy and aberrant motor behaviors may represent a specific group of cholinergic-responsive behavioral symptoms.
An Extended-Speed Low-Ripple Torque Control of Switched Reluctance Motor Drives

In this paper, an extended-speed low-ripple torque control of switched reluctance motor (SRM) drives using torque sharing function (TSF) is proposed. Two operational modes are defined for the online TSF during commutation: In Mode I, absolute value of rate of change of flux linkage (ARCFL) of incoming phase is higher than outgoing phase; in Mode II, ARCFL of outgoing phase is higher than incoming phase. In order to compensate the torque error produced by imperfect tracking of phase current, a proportional and integral compensator with torque error is added to the torque reference of outgoing phase in Mode I and incoming phase in Mode II. Therefore, the total torque is determined by the phase with lower ARCFL rather than the phase with higher ARCFL as in conventional TSFs. The maximum torque-ripple-free speed of the proposed TSF is increased to more than ten times as the best case in conventional TSFs. Finally, the proposed TSF is verified by both simulations and experiments with a 2.3 kW, 6000 rpm, three-phase 12/8 SRM operating in both linear magnetic and saturated magnetic regions. Results show that the proposed TSF has higher average torque, and much lower torque ripples compared to conventional TSFs.
A small multi-function circular slot antenna for reconfigurable UWB communication applications

A multi-function circular wide-slot antenna with small size is proposed and investigated for reconfigurable ultra-wideband (UWB) communication applications. The antenna can be used as a dual band-notched UWB antenna, a single band-notched UWB antenna, a UWB antenna, or even as a multi-band antenna. The band-notched characteristic is achieved by using a stepped impedance resonator (SIR) and an arc-shaped parasitic element (ASPE), while the multi-function design is realized by incorporating four switches into the SIR and ASPE. Simulation results demonstrate that the proposed antenna, with a wide impedance bandwidth and multi-function switchable properties, is suitable for UWB and cognitive radio communication applications.
Priorities for control of malignant melanoma in Europe.

Cutaneous malignant melanoma (CMM) accounts for the large majority of deaths from skin cancer in young and middle-aged adults. CMM is strongly associated with intense and intermittent sun exposure, particularly early in life (IARC, 1992; Armstrong and Kricker, 1993; Elwood and Jopson, 1997; English et al., 1997). It is consequently a potentially preventable neoplasm. CMM is also effectively treated, provided that early diagnosis of thin lesions is available (Austoker, 1994).
Effects of atorvastatin and pravastatin on glucose tolerance in diabetic rats mildly induced by streptozotocin.

Effects of atorvastatin and pravastatin on glucose tolerance in mildly induced diabetic rats by streptozotocin at 24 mg/kg, i.v. were studied. Non-diabetic and diabetic rats were given orally 0.5% carboxymethylcellulose (control), 8 mg/kg atorvastatin or 8 mg/kg pravastatin once a day for 6 weeks. An oral glucose tolerance test (OGTT) was carried out 1, 2, 3, and 6 weeks after the administration. The blood glucose and plasma insulin levels measured before OGTT in the diabetic rats were not different from those in the non-diabetic rats. However, the hyperglycemic response to OGTT in the diabetic rats significantly exceeded that in the non-diabetic rats. The plasma insulin increased by OGTT in the diabetic rats appeared to be lower than that in the non-diabetic rats. Statin treatments for 1 week did not modify the OGTT-induced hyperglycemia appreciably, although there were some significant differences. More than 2 weeks after administration, the blood glucose levels at several time points after a glucose intake in the atorvastatin-treated diabetic rats were significantly higher than the respective levels in the control diabetic rats. Neither atorvastatin nor pravastatin modified the OGTT-induced insulin secretion. Statins, especially atorvastatin, may influence the glucose tolerance in mildly induced diabetic rats without alterations of insulin secretion.
Treatment of agrammatism in long-term Broca's aphasia.

This study describes the response of six, long-term (mean = 7.9 years) aphasic patients to a treatment programme (HELPSS) for agrammatism. Comparison of dependent test scores obtained before and after treatment showed that significant improvement occurred in verbal expression as measured by the Northwestern Syntax Screening Test (Lee, 1968) and the Boston Diagnostic Aphasia Examination (Goodglass & Kaplan, 1972). These results indicate that differential aphasia therapies designed for specific aphasia syndromes can be effective even when administered many years after onset of aphasia.
High titers of anti‐HBs prevent rituximab‐related viral reactivation in resolved hepatitis B patient with non‐Hodgkin's lymphoma

Rituximab, an anti‐CD20 monoclonal antibody, is associated with an increased risk of hepatitis B virus (HBV) reactivation. This study aimed to determine the predictive factors for rituximab‐related HBV reactivation in resolved hepatitis B patients, defined as HBsAg‐negative, anti‐HBc‐positive, and undetectable HBV DNA. Among 840 consecutive patients with CD20‐positive B‐cell lymphoma who received rituximab‐based chemotherapy from 2003 through 2014 at Seoul National University Hospital, 732 patients were excluded because either anti‐HBc was not assessed or they were HBsAg‐seropositive. This retrospective study included 108 resolved hepatitis B patients. During a median 33.5‐month follow‐up period, eight cases of HBV reactivation occurred only among the patients with low anti‐HBs titers (<100 mIU/ml) at baseline and those who did not receive antiviral prophylaxis. Using multivariate analyses, antiviral prophylaxis and baseline anti‐HBs titers were the protective factors for HBV reactivation (hazard ratio [HR], 0.90 and 0.95, respectively). Among those who did not receive antiviral prophylaxis, patients with high baseline anti‐HBs (≥100 mIU/ml) experienced significantly lower risk of HBV reactivation (HR, 0.49; P = 0.006) than the patients with low baseline anti‐HBs (<100 mIU/ml) whose cumulative HBV reactivation rates at 6 and 24 months after chemotherapy were 8.3% and 17.3%, respectively. High anti‐HBs titer at baseline and antiviral prophylaxis prevented HBV reactivation, suggesting antiviral prophylaxis should be considered according to baseline anti‐HBs titer. Meticulous follow‐up for ALT and HBV DNA without antiviral prophylaxis might be possible for the patients with high baseline anti‐HBs (≥100 mIU/ml). J. Med. Virol. 88:1010–1017, 2016. © 2015 Wiley Periodicals, Inc.
Application of timing option for preventing the opportunity loss in Japan's biotech start-ups

Biotech start-ups are expected as a rapid commercialization method from life science rather than big pharmaceutical companies. There are about 300 public companies in 1500 biotech start-ups in the U.S.A. , but only 22 public companies in about 500 biotech start-ups in Japan. Why is there such a big numerical difference between both countries? As main key word, timing option is defined as the deferring valuable rights also as a call option to timely start a project in real options. It is considered as a useful tool to decide the optimal timing in trade-off between the irreversible investments as sunk costs and the risky but promising biopharmaceutical projects. If all business chances are assumed as perpetual American call options, we can characterize, calculate and forecast the optimal timing of project starting by parameter setting. Objectives of this paper are to seek the characteristics of the optimal start timing, to understand model structures, and to forecast the optimal timing. Implications are to understand the trade-off between the deferring for uncertain reduction and the opportunity cost of not yet deciding, to control the optimal timing, and to improve the development of innovative new drug from life science.
Cascaded H-bridge converter with multiphase isolated DC/DC converter for large-scale PV system

The large-scale grid-connected photovoltaic (PV) systems have continuously increased, reaching hundreds of megawatts level. This trend will continue in the upcoming years, thus rising new challenges to the existing PV system configurations and grid converters design. The cascaded H-bridge (CHB) converter could be a possible solution to these challenges in terms of scalability and modularity. However, the CHB converter topology faces the issue of leakage current which could cause safety issues. Moreover, the inherent power imbalance issue of a PV system using a CHB topology needs to be handled. This paper introduces a multiphase isolated DC/DC converter which eliminates the leakage current issue. Additionally, a control strategy has been implemented to deal with the power imbalance between different H-bridges in one leg and also between the three phases. Simulation results are presented to validate the performance of the proposed PV system configuration.
Nonparametric Testing for DNA Copy Number Induced Differential mRNA Gene Expression

Summary The central dogma of molecular biology relates DNA with mRNA. Array CGH measures DNA copy number and gene expression microarrays measure the amount of mRNA. Methods that integrate data from these two platforms may uncover meaningful biological relationships that further our understanding of cancer. We develop nonparametric tests for the detection of copy number induced differential gene expression. The tests incorporate the uncertainty of the calling of genomic aberrations. The test is preceded by a “tuning algorithm” that discards certain genes to improve the overall power of the false discovery rate selection procedure. Moreover, the test statistics are “shrunken” to borrow information across neighboring genes that share the same array CGH signature. For each gene we also estimate its effect, its amount of differential expression due to copy number changes, and calculate the coefficient of determination. The method is illustrated on breast cancer data, in which it confirms previously reported findings, now with a more profound statistical underpinning.
2 Gene Therapy Using RNAi

In the chapter, we hereby provide a brief review about RNA interference (RNAi) and elucidate its therapeutic applications. The enzymatic synthesis of double-stranded RNA in vitro will be discussed. We also describe how to design and select short interfering RNA (siRNA) sequences. In addition, we also introduce a DNA-directed RNAi (ddRNAi) system, which is designed for the generation of small hairpin RNAs in mammalian cells and is an efficient approach to allow fast and easy expression of hairpin oligonucleotides for therapeutic purpose. Moreover, various strategies for delivery of siRNA to target cells are discussed in this chapter. Under the consideration of distinct need of different diseases, use of transient or stable transfection onto living organism will be introduced. Finally, we will discuss the application of RNAi in clinical or preclinical trial. Some ongoing therapeutic models, efficacy or limitation for RNAi will be demonstrated and clarified.
Catastrophic forgetting in neural networks: the role of rehearsal mechanisms

The author examines the problem of catastrophic forgetting-the overwriting of old information-in neural networks. He notes that R. Ratcliff's (1990) experiments with rehearsal regimes are a possible solution to catastrophic forgetting and describes sweep rehearsal-a much more effective regime. The use of sweep rehearsal, however, eventually encounters practical limits as the ability to recognize learned items begins to diminish. The author suggests that sweep rehearsal extends the approach of rehearsal mechanisms as far as is practicable, and exposes their eventual limitations. <<ETX>>
Elucidation of the Molecular Basis for Arabinoxylan-Debranching Activity of a Thermostable Family GH62 α-l-Arabinofuranosidase from Streptomyces thermoviolaceus

ABSTRACT Xylan-debranching enzymes facilitate the complete hydrolysis of xylan and can be used to alter xylan chemistry. Here, the family GH62 α-l-arabinofuranosidase from Streptomyces thermoviolaceus (SthAbf62A) was shown to have a half-life of 60 min at 60°C and the ability to cleave α-1,3 l-arabinofuranose (l-Araf) from singly substituted xylopyranosyl (Xylp) backbone residues in wheat arabinoxylan; low levels of activity on arabinan as well as 4-nitrophenyl α-l-arabinofuranoside were also detected. After selective removal of α-1,3 l-Araf substituents from disubstituted Xylp residues present in wheat arabinoxylan, SthAbf62A could also cleave the remaining α-1,2 l-Araf substituents, confirming the ability of SthAbf62A to remove α-l-Araf residues that are (1→2) and (1→3) linked to monosubstituted β-d-Xylp sugars. Three-dimensional structures of SthAbf62A and its complex with xylotetraose and l-arabinose confirmed a five-bladed β-propeller fold and revealed a molecular Velcro in blade V between the β1 and β21 strands, a disulfide bond between Cys27 and Cys297, and a calcium ion coordinated in the central channel of the fold. The enzyme-arabinose complex structure further revealed a narrow and seemingly rigid l-arabinose binding pocket situated at the center of one side of the β propeller, which stabilized the arabinofuranosyl substituent through several hydrogen-bonding and hydrophobic interactions. The predicted catalytic amino acids were oriented toward this binding pocket, and the catalytic essentiality of Asp53 and Glu213 was confirmed by site-specific mutagenesis. Complex structures with xylotetraose revealed a shallow cleft for xylan backbone binding that is open at both ends and comprises multiple binding subsites above and flanking the l-arabinose binding pocket.