Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of topoisomerase II alpha gene amplification and deletion in breast cancer.

Topoisomerase IIalpha (TOP2A) is a key enzyme in DNA replication and a molecular target for many important anticancer drugs. TOP2A is amplified or deleted together with amplification of the closely located ERBB2/HER-2/neu oncogene in breast cancer. We characterized the copy number aberrations of TOP2A and ERBB2 in 136 primary breast tumors by FISH. Among the 70 primary tumors with ERBB2 amplification, amplification of TOP2A was found in 29 (41%); 30 tumors (43%) showed a physical deletion of TOP2A; and the copy number for TOP2A was not altered in 11 tumors with ERBB2 amplification (16%). No TOP2A gene aberrations were identified in 65 primary tumors without ERBB2 amplification. Fiber FISH revealed that simultaneously amplified ERBB2 and TOP2A were not present in the same amplicon, because repetitive tandem repeat-like signals of ERBB2 and TOP2A were in separate DNA fibers. The deletion of TOP2A (seen in the MDA-361 cell line and in 31 primary tumors) was interstitial, spanning less than two megabases of DNA. Mean copy numbers of TOP2A (2.4 +/- 0.6 for TOP2A vs. 4.9 +/- 1.1 for chromosome 17 centromere) suggest that the deletion of TOP2A occurs before polyploidization of the genome. Eight primary tumors with high-level ERBB2 amplification showed a new type of intratumoral heterogeneity; two different cell clones with either high-level amplification or deletion of TOP2A were found adjacent to each other in the same tumor. These results indicate that amplification of the ERBB2 oncogene is followed by complex secondary genetic aberrations, which lead to amplification or deletion of the TOP2A gene in a majority of tumors. Genes Chromosomes Cancer 26:142-150, 1999.
Nocturnal dipping is reproducible in the long term

ObjectiveTo examine the long-term reproducibility of nocturnal dipping as a dichotomous and continuous variable. MethodsRetrospective review of an ambulatory blood pressure monitor (ABPM) database of approximately 15 000 patients. Reproducibility of ABPM was assessed by repeatability coefficient. Kappa (κ) statistic and intraclass correlation coefficient were used to quantify dipping as a dichotomous and continuous variable, respectively. ResultsThere were 512 never-treated patients with two ABPM assessments, a mean of 29 (±19) months apart. Blood pressure was 2/0 mmHg (awake) and 2/1 mmHg (asleep) higher on the second ABPM. The repeatability coefficient for awake systolic and awake diastolic pressure was 5.9 and 6.2%, respectively. When the dipper/non-dipper (dichotomous) classification was applied to both ABPMs, dipping status was unchanged in 76% of patients, κ = 0.29. When nocturnal dip was expressed as a continuous variable, the mean nocturnal dip was 14% and the median absolute change between assessments was 3.8%, intraclass correlation coefficient = 0.60. The time interval between assessments was subdivided into (i) within 6 months, (ii) 6 months to 1 year, (iii) 1–2 years, (iv) 2–3 years and (v) more than 3 years. There was remarkable consistency independent of time interval for dipping expressed as a continuous variable but not as dipper/non-dipper. ConclusionThese findings show that in the long term, nocturnal dip is more stable when expressed as a continuous variable. As recent evidence show cardiovascular risk to be inversely related to nocturnal blood pressure in a continuous manner, surely it makes more sense to express nocturnal dip in a similar way to aid stratification of overall cardiovascular risk.
Genome sequence of a serotype M3 strain of group A Streptococcus: Phage-encoded toxins, the high-virulence phenotype, and clone emergence

Genome sequences are available for many bacterial strains, but there has been little progress in using these data to understand the molecular basis of pathogen emergence and differences in strain virulence. Serotype M3 strains of group A Streptococcus (GAS) are a common cause of severe invasive infections with unusually high rates of morbidity and mortality. To gain insight into the molecular basis of this high-virulence phenotype, we sequenced the genome of strain MGAS315, an organism isolated from a patient with streptococcal toxic shock syndrome. The genome is composed of 1,900,521 bp, and it shares ≈1.7 Mb of related genetic material with genomes of serotype M1 and M18 strains. Phage-like elements account for the great majority of variation in gene content relative to the sequenced M1 and M18 strains. Recombination produces chimeric phages and strains with previously uncharacterized arrays of virulence factor genes. Strain MGAS315 has phage genes that encode proteins likely to contribute to pathogenesis, such as streptococcal pyrogenic exotoxin A (SpeA) and SpeK, streptococcal superantigen (SSA), and a previously uncharacterized phospholipase A2 (designated Sla). Infected humans had anti-SpeK, -SSA, and -Sla antibodies, indicating that these GAS proteins are made in vivo. SpeK and SSA were pyrogenic and toxic for rabbits. Serotype M3 strains with the phage-encoded speK and sla genes increased dramatically in frequency late in the 20th century, commensurate with the rise in invasive disease caused by M3 organisms. Taken together, the results show that phage-mediated recombination has played a critical role in the emergence of a new, unusually virulent clone of serotype M3 GAS.
Apoptosis induction by a novel anti-prostate cancer compound, BMD188 (a fatty acid-containing hydroxamic acid), requires the mitochondrial respiratory chain.

We recently developed a class of novel anti-prostate cancer compounds, cyclic hydroxamates that elicit a potent apoptotic response in many tumor cells cultured in vitro (D.G. Tang et al., Biochem. Biophys. Res. Commun., 242: 380-384, 1998). The lead compound, termed BMD188, induces programmed cell death in a variety of prostate cancer cells in vitro as well as in vivo (L. Li et al., Anticancer Res., 19: 51-70, 1999). BMD188 kills androgen-independent prostate cancer cells as well as prostate cancer cells with a multidrug-resistance phenotype. The apoptotic effect of BMD188 in prostate cancer cells does not depend on cell cycle, p53 status, or its purported target, arachidonate 12-lipoxygenase, but does require caspase activation and seems to involve mitochondria. To synthesize more specific and effective anti-prostate cancer hydroxamic acid compounds, it is important to understand their mechanism(s) of action. In the present study, we studied the role of mitochondrial respiratory chain (MRC) in BMD188-induced apoptosis in androgen-independent prostate cancer PC3 cells and compared its effect with that of staurosporine (STS), a widely used apoptosis inducer. Several lines of evidence indicate that BMD188-induced cell death depends on MRC: (a) the death could be significantly inhibited by several complex-specific respiration inhibitors; (b) respiration-deficient rho0 cells were more resistant than wild-type parent cells to apoptosis induction by BMD188; and (c) BMD188 induced a rapid increase in reactive oxygen species in mitochondria, an up-regulation of cytochrome c oxidase subunits, a biphasic alteration (i.e., an early hyperpolarization, followed by later hypopolarization) in the mitochondrial membrane potential (delta psi(m)), dramatic changes in mitochondrial morphology and distribution prior to caspase activation, and an abnormal proliferation of mitochondria at the ultrastructural level. By contrast, STS-induced PC3 apoptosis seemed not to depend on MRC. Taken together, the data suggest that the MRC represents a functional target for anti-prostate cancer hydroxamates.
Does Access to Microfinance Improve Farm Production? Evidence from Rice Farmers in San Francisco, Ag

Poverty level remains high (36.7%) in agricultural areas in the Philippines. The second poorest province in the Philippines is Agusan del Sur with incidence reaching as high as 51.2%. One of the approaches to alleviate poverty is to provide access to capital through microfinance. This study draws conclusion on the link between access to microfinance and farm production taking the municipality of San Francisco in Agusan del Sur as a case. A total of 95 rice farmers were interviewed. Data revealed that microfinance client farmers were producing 27% more than non-client farmers. The production data were fitted using five production functions namely; (1) Neoclassical, (2) Neoclassical with interaction, (3) Cobb-Douglas, (4) Transcendental and (5) Transcendental with interaction. Using ordinary least squares method, Neoclassical function best fit the data with access to microfinance significantly improving farm production by 23%. Output was most responsive to land (0.60 elasticity (E)), followed by fertilizer (0.18 E), labor (0.14 E), herbicide (0.12 E), seed (0.02 E) and pesticide use (0.00 E). Irrigated farms were 23% more productive than non-irrigated farms. Despite the positive impact of access to microfinance, only 34% of the farmers had availed agricultural microfinance loan from formal institutions while only 18% took advantage during the 2nd season of 2010 rice production.
Inhibition of STAT3 signaling blocks obesity-induced mammary hyperplasia in a mouse model.

Compelling epidemiologic evidence indicates that obesity is a risk factor for human cancers, including breast. However, molecular mechanisms by which obesity could contribute to the development of breast cancer remain unclear. To understand the impact of obesity on breast cancer development, we used a mutant mouse that expresses a mutated thyroid hormone receptor β (denoted as PV) with haplodeficiency of the Pten gene (ThrbPV/PVPten+/- mice). We previously showed that adult nulliparous female ThrbPV/PVPten+/- mice developed extensive mammary hyperplasia and breast tumors. In this study, we induced obesity in ThrbPV/PVPten+/- mice by feeding them a high fat diet (HFD). We found HFD exacerbated the extent of mammary hyperplasia in ThrbPV/PVPten+/- mice. HFD elevated serum leptin levels but had no effect on the levels of serum thyroid stimulating hormone, thyroid hormones, and estrogens. Molecular analysis showed that the obesity-induced hyperplasia was mediated by the leptin/leptin receptor-JAK1-STAT3 pathway to increase key cell cycle regulators to stimulate mammary epithelial cell proliferation. Activated STAT3 signaling led to altered expression in the key regulators of epithelial-mesenchymal-transition (EMT) to augment invasiveness and migration of mammary proliferating epithelial cells. Moreover, treatment of HFD-ThrbPV/PVPten+/- mice with a STAT3 inhibitor, S3I-201, markedly reversed the obesity-induced mammary hyperplasia and reduced EMT signals to lessen cell invasiveness and migration. Our studies not only elucidated how obesity could contribute to mammary hyperplasia at the molecular level, but also, importantly, demonstrated that inhibition of the STAT3 activity could be a novel treatment strategy for obesity-induced breast cancer progression.
Genome-wide gene expression profiles of the developing mouse hippocampus

We have analyzed the developmental molecular programs of the mouse hippocampus, a cortical structure critical for learning and memory, by means of large-scale DNA microarray techniques. Of 11,000 genes and expressed sequence tags examined, 1,926 showed dynamic changes during hippocampal development from embryonic day 16 to postnatal day 30. Gene-cluster analysis was used to group these genes into 16 distinct clusters with striking patterns that appear to correlate with major developmental hallmarks and cellular events. These include genes involved in neuronal proliferation, differentiation, and synapse formation. A complete list of the transcriptional changes has been compiled into a comprehensive gene profile database (http://BrainGenomics.Princeton.edu), which should prove valuable in advancing our understanding of the molecular and genetic programs underlying both the development and the functions of the mammalian brain.
Increased catecholamines and heart rate in children with low birth weight: perinatal contributions to sympathoadrenal overactivity

Background. Low birth weight is associated with cardiovascular disease. The underlying mechanisms are unknown. We hypothesized that perinatal stress alters autonomic regulation of the cardiovascular system. In this study, catecholamines, heart rate (HR) and blood pressure (BP) were measured in healthy children with low birth weight.
Association of HLA DRB1 alleles with juvenile idiopathic arthritis in Mexicans.

OBJECTIVE The aim of the study was to investigate association between HLA class II alleles and juvenile idiopathic arthritis (JIA) in Mexican patients. PATIENTS AND METHODS We typed 120 patients with JIA and 99 healthy controls for HLA class II alleles were performed by PCR-SSO. Differences between the whole group of JIA and its subtypes and controls were calculated by using the Xi2; p-values were corrected (pc) with Bonferroni's test. RESULTS The alleles HLA-DRB1*01 (pc= 0.00083) and HLA-DRB1*04 (pc=0.0049) were strongly associated with systemic JIA, while HLA-DRB1*11 and HLA-DRB1*14 were found to have decreased frequencies in the patients with systemic JIA compared to the controls. Two alleles were found to have increased frequencies with JIA oligoarthritis subgroup, HLA-DRB1*11 (p=0.01, pc=NS) and HLA-DRB1*13 (p=0.01, pc=NS). The HLA-DRB1*04 was found increased frequencies with susceptibility for RF negative and RF positive polyarthritis JIA subgroups (p correction resulted in loss of significance). In contrast two alleles HLA-DRB1*07 and HLA-DRB1*14 were found decreased frequencies only patients RF positive polyarthritis JIA subgroup compared to the controls (pc=NS). CONCLUSION The profile of HLA-DRB1 alleles associations in Mexican with JIA were somewhat distinct from association typically found in Caucasians.
Second-Order Sliding-Mode Controlled Synchronous Buck DC–DC Converter

In this paper, second-order sliding-mode (SOSM) control approach is applied to synchronous buck dc-dc converters. The proposed SOSM controller can stabilize synchronous buck dc-dc converters using a simple digital state-machine structure, without requiring current sensing or an integral term in the control loop. The SOSM controller results in fast step-load and start-up transient responses, and is robust against parameter uncertainties. Fast transients and current limitation during start up can be accomplished by adjusting one controller parameter. Furthermore, a hysteresis method is introduced to control the switching frequency. The proposed approach is verified by experimental results on a 1.25-V 10-A prototype.
The Long and the Short of It: Associations Between 5-HTT Genotypes and Coping With Stress

Objective: To examine whether the strategies people use to cope with stress were associated with differing serotonin transporter (5-HTT) genotypes. The short (s) variant of the 5-HTT promoter polymorphism has been associated with an increased likelihood of depression after significant life stress and greater emotional reactivity to fear-invoking stimuli. Methods: Coping strategies were assessed within a longitudinal study in 1993. Ten years later, genomic DNA was obtained for 127 participants and genotypes for the 5-HTT promoter polymorphism were determined. Coping strategies were grouped into coping scales and also using an exploratory factor analysis. Using ordinal regression, associations were then examined between the coping scales and the 5-HTT genotype and gender. Results: The short variant of the 5-HTT promoter polymorphism was associated with the use of fewer problem-solving strategies. This genotype effect differed significantly between the sexes and was greatest for males. Conclusions: Our results indicate that coping is influenced by 5-HTT genotype, gender, and their interaction. We raise the possibility that a gene-related disposition to greater emotional reactivity may preclude those with the short variant of the 5-HTT promoter polymorphism from drawing on problem-solving strategies to deal with stress. 5-HTT = serotonin transporter; SCL6A4 = serotonin transporter gene; MD = major depression; ABM = antidepressive behavior measure; CUS = coping under stress.
Relationship between segmental and whole-body phase angle in peritoneal dialysis patients

The relation between the right-side (RS) electrical impedance phase angle (PA) and segmental PA in five configurations at 50 kHz was analyzed in 23 peritoneal dialysis male patients before complete drainage of the abdominal cavity. The impedance vector (Z/H) components were standardized by the height H of the subjects (R/H and Xc/H). BIVA software was used to analyze the individual RS vector. The Pearson correlation was used to analyze the correlation between RS and segmental configurations. Student's t test and Hotelling's T2 test were used to analyze the separation of groups obtained by BIVA. The highest significant Pearson correlation was between RS and right leg total (RLEGT) in a longitudinal direction (r = 0.925, P < 0.001). We obtained a significant difference (P < 0.05) in R/H, Xc/H (for RS and RLEGT) using Hotelling's T2 test, and in PA using Student's t test. The transverse measurement in the leg (RTRLEG) showed the lowest correlation (r = 0.261). In conclusion, we can obtain similar information through the phase angle, whether RS is measured or if we measure on RLEGT. The phase angle of the transverse measurements provides different information from the phase angle of the longitudinal measurements.
Distributed Slot Scheduling Algorithm for Hybrid CSMA/TDMA MAC in Wireless Sensor Networks

Wireless Sensor Networks(WSNs) consist of many self organized sensor nodes to monitor various activities like temperature, pressure, health condition, intrusion detection, etc. These sensor nodes mostly sense the events happening around them, process the sensed data, and send it to the base station using multiple hops. The base station is connected to the outside world who wants to access these sensed and processed data. In WSN, one of the most important challenge is to handle the collision during data transmission by multiple sensor nodes at the same point of time. The collision during data transmission is handled by proper MAC protocol. The MAC protocols for WSN are broadly categorized into 3 types, i.e. schedule, random, and hybrid. Among these 3 types of MAC protocols, the hybrid MAC protocols try to combine the advantage of both schedule and random based MAC protocols. In this paper, we proposed a distributed slot scheduling algorithm for hybrid MAC algorithm. This algorithm mainly focuses on preparing a schedule which bridges the gap between a feasible and an optimal schedule to handle the collision during the data transmission. In our proposed approach, first we find out two-hop neighbors of each node, then a particular slot is allotted to each node in order to prepare a feasible schedule using the RD-TDMA algorithm. Finally, the feasible schedule is fine tuned in a novel way to improve the efficiency in handling the collision by reducing the number of allotted slots. The proposed algorithm out performs the existing RD-TDMA algorithm in terms of number of slots required to handle the collision. The performance of the proposed protocol is carried out using Castalia simulator.
Identification of a Gene Encoding Heat-Resistant Agglutinin in Escherichia coli as a Putative Virulence Factor in Urinary Tract Infection

ABSTRACT Escherichia coli causes the vast majority of urinary tract infections (UTI) in both ambulatory and hospital patients. Several uropathogenic virulence factors have been identified, but half of all E. coli isolates that cause UTI have none or only one of the known virulence factors. Thus, it is reasonable to presume that other bacterial factors may be important in UTI pathogenesis. In order to find additional uropathogenic E. coli genes, we used genomic subtraction to identify DNA regions present in a uropathogenic strain of E. coli (1128-11). Genomic subtraction yielded 40 tester-specific fragments, including a novel heat-resistant agglutinin (hra) gene fragment. hra occurred in 55% of 486 UTI strains compared to 28% of 165 rectal strains (P = 0.001). The hra gene in 1128-11 was cloned, sequenced, and found to have 91% homology to the hra gene from E. coli meningitis strain RS218. The genetic organization of genes flanking hra in 1128-11 is distinct from the hra found in E. coli strains J96 and RS218. In our UTI and rectal specimen collections, hra was positively associated with a number of known virulence genes, including pathogenicity island genes hly and cnf, which are absent in 1128-11. The presence of hra in 1128-11 independent of hly/cnf suggests multiple mechanisms by which hra can be acquired by pathogenic E. coli strains. The flanking genes suggest that in 1128-11, hra may be part of a novel variant of a pathogenicity island V.
The effect of measurement unreliability on sleep and respiratory variables.

INTRODUCTION Unreliability associated with scoring sleep variables is a potentially problematic issue in clinical and research studies. When scoring unreliability is unrecognized, it can contribute to the following: increase variability in the measures of interest, decrease a study's ability to detect important relationships, attenuate correlation coefficients, and increase clinical trial costs. METHODS This paper first models the relationship between scoring variability and reliability in commonly studied sleep variables. The paper then models the relationship between unreliability and sample size requirements and statistical power. Standard methods are used to model reliability using the intraclass correlation coefficient. RESULTS The analysis shows that when scoring unreliability is minimized (i.e., scoring reliability is maximized), correlation coefficients are more robust, sample size requirements are reduced, statistical power is increased, and clinical trial costs are reduced. DISCUSSION When scoring unreliability is recognized, research studies can compensate by increasing the number of research subjects studied; however, it is at the cost of increasing the costs of research and exposing greater numbers of subjects to possible study risks. An effective solution is to implement rigorous initial and ongoing training efforts to maintain high inter-rater and intra-rater reliability coefficients.
Effects of strength training on the incidence and progression of knee osteoarthritis.

OBJECTIVE Quadriceps weakness is a risk factor for incident knee osteoarthritis (OA). We describe a randomized controlled trial of effects of lower-extremity strength training on incidence and progression of knee OA. METHODS A total of 221 older adults (mean age 69 years) were stratified by sex, presence of radiographic knee OA, and severity of knee pain, and were randomized to strength training (ST) or range-of-motion (ROM) exercises. Subjects exercised 3 times per week (twice at a fitness facility, once at home) for 12 weeks, followed by transition to home-based exercise after 12 months. Assessments of isokinetic lower-extremity strength and highly standardized knee radiographs were obtained at baseline and 30 months. RESULTS Subjects in both groups lost lower-extremity strength over 30 months; however, the rate of loss was slower with ST than with ROM. Compared with ROM, ST decreased the mean rate of joint space narrowing (JSN) in osteoarthritic knees by 26% (P = not significant). However, the difference between ST and ROM groups with respect to frequency of knee OA progression in JSN consensus ratings was marginally significant (18% versus 28%; P = 0.094). In knees that were radiographically normal at baseline, JSN >0.50 mm was more common in ST than in ROM (34% versus 19%; P = 0.038). Incident JSN was unrelated to exercise adherence or changes in quadriceps strength or knee pain. CONCLUSION The ST group retained more strength and exhibited less frequent progressive JSN over 30 months than the ROM group. The increase in incident JSN >0.50 mm in ST is unexplained and requires confirmation.