Miracle-dz/UniFAR-FTUs huggingface dataset:
Independent replication establishes the CD247 gene as a genetic systemic sclerosis susceptibility factor

The first large genome-wide association (GWA) study of systemic sclerosis (SSc) recently included 2296 SSc patients and 5014 healthy controls from four case–control series of Caucasian individuals and involved the analysis of about 280 000 single nucleotide polymorphisms (SNPs). 1 Outside the HLA region, SNPs mapping to the known TNPO3 - IRF5 and STAT4 regions showed the strongest association but three other loci reached genome-wide significance (namely CD247 locus in 1q22–23, CDH7 in 18q22 and EXOC2 - IRF4 near 6p25) although only one ( CD247 ) could be replicated in the second set of samples. Given the major challenge of separating the many false-positive associations from the few true-positive associations with disease in GWA studies, resulting in a stratification bias, a critical strategy is replication of results in independent samples.2 Therefore, we herein provide an attempt of …
Modelling the cardiovascular effects of ephedrine.

AIMS Recent reports have called into question the safety of ephedra supplements especially with regards to their cardiovascular effects. The purpose of this analysis was to characterize, via pharmacokinetic/pharmacodynamic modelling, the cardiovascular effects of ephedrine, the main active ingredient of ephedra, in apparently healthy, overweight volunteers. METHODS In a randomized, double-blind, crossover, placebo-controlled study, eight subjects received either placebo, 0.25, 0.5 or 1.0 mg kg(-1) ephedrine sulphate by mouth with a 7-day washout between treatments. Plasma ephedrine concentrations, heart rate and blood pressure were determined for 8 h postdose. RESULTS The pharmacokinetics of ephedrine were best described by a one-compartment model with first-order absorption and elimination. The percentage change in heart rate was described by a linear model with a resulting slope of 0.14%. l microg(-1) (CV = 59%). The percentage change in systolic blood pressure demonstrated clockwise hysteresis, and a sigmoidal tolerance model was used to describe the data. The mean maximum predicted effect (Emax) was 53.7% (CV = 41%) with an EC50 of 107 microg.l(-1) (CV = 65%) and an inhibitory maximum (Imax) of 39.8% (CV = 60%). Tolerance developed with a mean half-life of 15 min (range 6-140 min). CONCLUSIONS This is the first study to apply a comprehensive pharmacokinetic/pharmacodynamic model to the cardiovascular effects of orally administered ephedrine. Although systolic blood pressure increases quickly after administration, the increase is nearly abolished by compensatory mechanisms.
Bonding-friendly pcPDMS: Depositing Parylene C into PDMS matrix at an elevated temperature

This paper reported a simple and effective process of bonding-friendly Parylene C-caulked PDMS (pcPDMS) for low-permeability required microfluidics. Parylene C was deposited into PDMS matrix at an elevated temperature (higher than 135°C) to caulk the permeable sites. The so-prepared pcPDMS can be directly bonded with oxygen plasma treatment just as pristine PDMS. SEM EDAX and Laser scanning confocal microscopy (LSCM) were introduced to characterize the Parylene C caulked status in the PDMS matrix based on the specific Cl element component and the firstly-found temperature-sensitive autofluorescence of Parylene C. The preliminary results indicated that the present bonding-friendly pcPDMS can successfully suppress the diffusion of small molecules into the PDMS matrix.
Performance Evaluation of QoS Based Forwarding and Non Forwarding Energetic Node Selection Algorithm for Reducing the Flooding in Multihop Routing in Highly Dynamic MANET

The aim of this paper is to propose a novel technique to guarantee Quality of Service (QoS) in a highly dynamic environment. The MANET changes its topology dynamically as the nodes are moved frequently. This will cause link failure between mobile nodes. MANET cannot ensure reliability without delay. The relay node is selected based on achieving QoS in previous transmission. It considers one more factor Connection Existence Period (CEP) to ensure reliability. CEP is to find out the period during that connection exists between the nodes. The node with highest CEP becomes a next relay node. The relay node is selected dynamically to avoid frequent failure. The bandwidth of each link changed dynamically based on service rate and request rate. This paper proposes Active bandwidth setting up algorithm to guarantee the QoS. The series of results obtained by using the Network Simulator (NS-2) demonstrate the viability of our proposed techniques. Keywords—Bandwidth, Connection Existence Period (CEP), Mobile Adhoc Network (MANET), Quality of Service (QoS), Relay node.
Cycling activity of benign prostatic epithelial cells during long‐term androgen blockade: evidence for self‐renewal of luminal cells

Combined androgen blockade (CAB) therapy (LHRH agonist and flutamide) for 6 months leads to marked regressive changes of the prostate gland. This is associated with a reduction in the ratio of luminal to basal cells in the peripheral zone (PZ) in hyperplastic glands of the transitional zone (TZ). To examine the cycling activity of luminal and basal cells, double immunostaining was performed. For precise definition of basal cells, the basal cell‐specific antibody 34βE12 was used, while cycling cells were identified by the MIB‐1 antibody. In 6‐month‐treated specimens, the fraction of cycling luminal cells increased from 03 to 25 per cent in the PZ and from 02 to 39 per cent in the TZ. This was associated with an inversion of the ratio of MIB‐1‐labelled luminal to basal cells, with values of 57:1 (PZ) and 39:1 (TZ), compared with 1:4 (PZ) and 1:5 (TZ) in untreated specimens. The predominance continued for at least 11 years of CAB. The findings strongly suggest that luminal cells are capable of self‐renewal under conditions of low androgen levels. The substantial decrease of prostatic volume on long‐term CAB implies that cell loss outweighs cell proliferation. Copyright © 1998 John Wiley & Sons, Ltd.
Corticosteroid resistant interstitial pneumonitis in dermatomyositis/polymyositis: prediction and treatment with cyclosporine.

OBJECTIVE To determine the characteristics of corticosteroid resistant interstitial pneumonitis (IP) in dermatomyositis (DM) and polymyositis (PM), and to evaluate the effect of cyclosporine on corticosteroid resistant IP in DM/PM. METHODS We analyzed retrospectively the incidence, clinical features, and corticosteroid responses of IP in 111 patients with DM (56) or PM (55). All patients with DM/PM were treated with prednisolone, and corticosteroid resistant IP was defined as a progression of IP despite administration of 1 mg/kg/day prednisolone for more than 4 weeks. We also evaluated the effect of cyclosporine on corticosteroid resistant IP in patients with DM/PM. RESULTS IP occurred in 24 of 56 DM and 12 of 55 PM patients. We then classified IP in DM/PM according to serum CPK levels at the onset of IP; IP associated with high CPK levels (type I) (19) and IP associated with normal CPK levels (type II) (17). Only 2 of 19 (11%) type I IP were resistant to prednisolone therapy, while 14 of 17 (82%) type II IP were resistant to prednisolone therapy. Thus, patients with type II IP showed poorer prognosis than those with type I IP (one year survival rate: type I 89% vs type II 31%). Cyclosporine was effective in all 5 cases with corticosteroid resistant IP in DM/PM (one year survival rate 80%). CONCLUSION (1) Corticosteroid resistant IP develops mostly in patients with DM/PM without CPK elevation at the onset of IP (type II IP), and (2) cyclosporine is effective for the corticosteroid resistant IP in DM/PM and significantly prolongs survival of patients.
Is Cardiac Resynchronization Therapy for Right Ventricular Failure in Pulmonary Arterial Hypertension of Benefit?

Pulmonary arterial hypertension is a manifestation of a group of disorders leading to pulmonary vascular remodeling and increased pulmonary pressures. The right ventricular (RV) response to chronic pressure overload consists of myocardial remodeling, which is in many ways similar to that seen in left ventricular (LV) failure. Maladaptive myocardial remodeling often leads to intraventricular and interventricular dyssychrony, an observation that has led to cardiac resynchronization therapy (CRT) for LV failure. CRT has proven to be an effective treatment strategy in subsets of patients with LV failure resulting in improvement in LV function, heart failure symptoms, and survival. Current therapy for pulmonary arterial hypertension is based on decreasing pulmonary vascular resistance, and there is currently no effective therapy targeting the right ventricle or maladaptive ventricular remodeling in these patients. This review focuses on the RV response to chronic pressure overload, its effect on electromechanical coupling and synchrony, and how lessons learned from left ventricular cardiac resynchronization might be applied as therapy for RV dysfunction in the context of pulmonary arterial hypertension.
Neuro-cognitive performance of very preterm or very low birth weight adults at 26 years.

BACKGROUND Children born very preterm (VP <32 weeks gestation) and/or with very low birth weight (VBLW <1500 g; subsequently VP/VLBW) have been previously reported to have more cognitive impairment and specific executive functioning problems than term children; however, it remains unclear whether these problems persist into adulthood. This study aimed to examine general intelligence (IQ) and executive functioning (EF) of adults born VP/VLBW in comparison to term controls. Additionally, the effects of smallness for gestational age (SGA) and family socioeconomic status (SES) at birth were investigated. METHODS The Bavarian Longitudinal Study is a geographically defined prospective cohort study of neonatal at-risk children born in 1985/86 in Southern Germany. A total of 217 VP/VLBW and 197 controls completed the battery of IQ and EF tests at 26 years of age. RESULTS VP/VLBW adults scored significantly lower than controls in IQ and EF. There was a 1.16 standard deviation (SD) unit difference between the VP/VLBW and controls in Full-Scale IQ. VP/VLBW adults were found to have general and multiple cognitive problems rather than specific deficits in EF. SGA was not a significant predictor of cognitive impairment. Family SES had a significant impact on general intelligence in both VP/VLBW and term controls. The SES effects amounted to 1.13 SD units between individuals born into high versus low SES. CONCLUSIONS No narrowing of cognitive deficits between VP/VLBW and term control adults to previous childhood assessments at 6 years of age was found. VP/VLBW adults do not outgrow their cognitive problems despite many receiving special educational support in childhood. Low family SES at birth has similar additive adverse effects on cognitive performance in VP/VLBW and term offspring.
A 1.8 V LDO voltage regulator with foldback current limit and thermal protection

This paper introduces the design of a l.8 V low dropout voltage regulator (LDO) and a foldback current limit circuit which limits the output current to 3 mA when load over-current occurs. The LDO was implemented in a 0.18 μm CMOS technology. The measured result reveals that the LDO's power supply rejection (PSR) is about −58 dB and −54 dB at 20 Hz and 1 kHz respectively, the response time is 4 μs and the quiescent current is 20 μA. The designed LDO regulator can work with a supply voltage down to 2.0 V with a drop-out voltage of 200 mV at a maximum load current of 240 mA.
A review on the treatment of relapsed/metastatic head and neck cancer

The efficacy of traditional chemotherapy in inducing objective responses and prolonging survival in recurrent or metastatic head and neck cancer has been disappointing. More recent drugs have not proven superior to the classic regimen of cisplatin and 5-fluorouracil. Anti-EGFR monoclonal antibodies, either as single agents or associated to chemotherapy, have been shown to be active and little toxic. Among them, cetuximab has proven to be the most promising. Indeed the Extreme study, which compared the classic couple cisplatin (CDDP) + 5-fluorouracil with the same regimen plus cetuximab, has constituted a remarkable innovation. The results of that trial seem to indicate a third agent added to CDDP and 5-fluorouracil improved both progression-free survival and overall survival in the recurrent or metastatic setting. Unfortunately, the results obtained with the tyrosine kinase inhibitors are less impressive, and additional studies are needed to explore the potentiality of this class of drug. As far as antiangiogenetics are concerned, the research is insufficient for any conclusion to be drawn in terms of efficacy. It is hoped that, in the near future, the most active combination between biological agents and traditional chemotherapy will be found, so that the path successfully taken in other neoplastic diseases may be retraced.
Foraging behavior of three Tasmanian macropodid marsupials in response to present and historical predation threat

It is often essential to understand historical selection regimes to explain current traits. We studied antipredator behavior of three Tasmanian macropodid marsupials – Forester kangaroos Macropus giganteus, Bennett's wallabies M. rufogriseus, and Tasmanian pademelons Thylogale billardierii– to understand how antipredator behavior functions in a relatively intact predator community. We also compared behavior of the kangaroos and wallabies on a predator-free island where they were translocated from mainland Tasmania 30 yr ago. Both species allowed humans to get closer to them on the predator-free island; a finding consistent with a reduced risk of predation on the island. Neither kangaroos, nor wallabies, exhibited group size effects – they did not modify time allocated to foraging or antipredator vigilance as a function of group size at either site. Nor did overall time allocation vary in any consistent way. In contrast, mainland Australian sibling-species of Forester kangaroos and Bennett's wallabies have both been reported to have group size effects. It is possible either that the extinction of the thylacine Thylacinus cynocephalus in the last century has led to an evolutionary loss of group size effects and other antipredator behavior, or that thylacines were never that important a predator on Tasmanian subspecies. In contrast, Tasmanian pademelons studied on the Tasmanian mainland modified time allocation as a function of group size suggesting that they perceived safety in numbers. Pademelons, because of their body size, are relatively more vulnerable than larger-bodied macropodids to the rich community of marsupial carnivores in Tasmania, and used a mix of social and individual strategies to manage predation risk.
ON THE FINE STRUCTURE OF THE DISTRIBUTION OF MULTIPLE SCLEROSIS

It has been possible to evaluate statistically the distribution of multiple sclerosis (MS) from prevalence studies in Scandinavia and Switzerland on the basis of the frequency of the disease within the major administrative units of these lands, the counties ( K u r t z k e 1966a1). Highly significant variations were found, and the high frequency counties tended to be contiguous, appearing as clusters or foci of MS. With an evaluation of familial cases ( K u r t z k e 1965a) and of medical facilities ( K u r t z k e 1965b) in these lands, the conclusion was reached that these foci were an essential reflection of the disease, and that MS could therefore be considered as an acquired exogenous disease. Realizing however that the county is a rather large region, it seemed advisable to determine whether the foci so defined are still found when smaller administrative divisions of the country are used as the unit for evaluating the distribution of hlS within these nations. This is especially pertinent for the vast cxpanse of Sweden, and probably for the mountainous tcrrain of Switzerland. Use of the smallest units possible would also serve to provide a more accurate picture of the actual distribution of the disease than is feasible with the large and frequently irregular areas defined by the counties. The amount of accord or discrepancy between the small unit and county distributions would also determine the degrce with which association of environmental factors with MS could be relied upon, for those factors where only county distributions are available. In addition, for factors that cannot be easily quantitated, the use of the smallest units testable would be especially desirable. In reassessing these studies, we are limited to the prevalence works of Sullstrom (1942) for Sweden, Hyllested (1956) for Denmark, and
Effect of Reward on Employee Performance: A Case of Kenya Power and Lighting Company Ltd., Nakuru, Kenya

Today’s organizations are operating in a very dynamic and highly competitive environment. To remain relevant inthe market, they have to be able to respond quickly to ever changing customer demands. Reward management isone of the ways used by organizations for attracting and retaining suitable employees as well as facilitating themto improve their performance. KPLC is an organization that offers essential energy services that support othersectors of the economy. The management has established rewards in their organization in pursuit of increasingemployee performance so as to ensure prompt and quality service. However, the extent to which the rewardsadopted at KPLC have influenced employee performance is not established. This study therefore aimed atdetermining the effect of reward on employee performance at KPLC. Specifically the study sought to determinethe effect of cash bonus on employee performance. The research adopted correlation research design. 68management employees responded. Data was collected using questionnaires. Descriptive statistics (frequencytables, percentages) were used to present data. Inferential statistics (chi-square) was used to analyze therelationship between cash bonuses and employee performance. Data was analyzed with the help of the StatisticalPackage for Social Sciences (SPSS) computer programme. The findingsof the study showed that cash bonus haveno effect on employee performance (p=0.8). This is because those who received cash bonuses and those who didnot all agree that the cash bonus affects their performance the same. The organization should focus on changingthe intrinsic nature and content of jobs. This will increase employee motivation as employees will get moreautonomy more challenging job assignments and responsibilities. Further research can be done to find out impactof other rewards on performance e.g. owning equity. Research can also be done to identify other factors whichmay affect performance. Such findings can enhance management of performance.
A broadband low profile microstrip filter-antenna with an omni-directional pattern

A broadband low profile microstrip filter-antenna with an omni-directional pattern is presented. A coupled line is used to connect a microstrip antenna and the second resonator of a filter as admittance inverter. In the design, the antenna performs as a radiator; meanwhile it is also the last resonator of the bandpass filter. Therefore, the loss is reduced between the filter and the microstrip antenna. The proposed filter-antenna can provide 15% impedance bandwidth, a low profile of 3.8mm, an omni-directional pattern and high suppression in the stopband. The proposed antenna simulated results are presented.
Stochastic Petri Net Representation of Discrete Event Simulations

In the context of discrete event simulation, the marking of a stochastic Petri net (SPN) corresponds to the state of the underlying stochastic process of the simulation and the firing of a transition corresponds to the occurrence of an event. A study is made of the modeling power of SPNs with timed and immediate transitions, showing that such Petri nets provide a general framework for simulation. The principle result is that for any (finite or) countable state GSMP (generalized semi-Markov process) there exists an SPN having a marking process that mimics the GSMP in the sense that the two processes (and their underlying general state-space Markov chains) have the same finite dimensional distributions. >
Leptin levels at birth and infant growth: the EPOCH study.

OBJECTIVE To examine the association of cord blood leptin with body mass index (BMI) growth velocity from birth to 12 months of age among infants exposed and not exposed to over-nutrition in utero (defined as maternal overweight/obesity or presence of gestational diabetes). METHODS 185 infants enrolled in the Exploring Perinatal Outcomes among Children study (76 exposed and 109 not exposed) had leptin and insulin measured in cord blood. Longitudinal weight and length measures in the first 12 months of life (average 4 per participant) obtained from medical records were used to compute BMI growth rates. Mixed models were used to examine associations of cord blood leptin with growth. RESULTS Compared with unexposed infants, those exposed had significantly higher cord blood insulin (8.64 v. 6.97 uU/ml, P<0.01) and leptin levels (8.89 v. 5.92 ng/ml, P=0.05) as well as increased birth weights (3438.04 v. 3306.89 g, P=0.04). There was an inverse relationship between cord leptin levels and BMI growth from birth to 12 months of age (P=0.005); however, exposure to over-nutrition in utero did not significantly modify this association (P=0.59). CONCLUSION We provide support of a possible operational feedback mechanism by which lower cord blood leptin levels are associated with faster infant growth in the first year of life. Our data do not tend to support the hypothesis that this mechanism is altered in infants exposed to over-nutrition in utero; however our sample is too small to provide sufficient evidence. Larger epidemiological studies are needed to elucidate the mechanisms responsible for increased propensity for obesity in exposed offspring.
Interaction of caveolin‐1, nitric oxide, and nitric oxide synthases in hypoxic human SK‐N‐MC neuroblastoma cells

Neuroblastoma cells are capable of hypoxic adaptation, but the mechanisms involved are not fully understood. We hypothesized that caveolin‐1 (cav‐1), a plasma membrane signal molecule, might play a role in protecting neuroblastoma cells from oxidative injury by modulating nitric oxide (NO) production. We investigated the alterations of cav‐1, cav‐2, nitric oxide synthases (NOS), and NO levels in human SK‐N‐MC neuroblastoma cells exposed to hypoxia with 2% [O2]. The major discoveries include: (i) cav‐1 but not cav‐2 was up‐regulated in the cells exposed to 15 h of hypoxia; (ii) NO donor 1‐[N, N‐di‐(2‐aminoethyl) amino] diazen‐1‐ium‐1, 2‐diolate up‐regulated the expression of cav‐1, whereas the non‐selective NOS inhibitor NG‐nitro‐l‐arginine methyl ester and inducible NOS (iNOS) inhibitor 1400W each abolished the increase in cav‐1 expression in the hypoxic SK‐N‐MC cells. These results suggest that iNOS‐induced NO production contributes to the up‐regulation of cav‐1 in the hypoxic SK‐N‐MC cells. Furthermore, we studied the roles played by cav‐1 in regulating NO, NOS, and apoptotic cell death in the SK‐N‐MC cells subjected to 15 h of hypoxic treatment. Both cav‐1 transfection and cav‐1 scaffolding domain peptide abolished the induction of iNOS, reduced the production of NO, and reduced the rates of apoptotic cell death in the hypoxic SK‐N‐MC cells. These results suggest that increased expression of cav‐1 in response to hypoxic stimulation could prevent oxidative injury induced by reactive oxygen species. The interactions of cav‐1, NO, and NOS could be an important signal pathway in protecting the neuroblastoma cells from oxidative injury, contributing to the hypoxic tolerance of neuroblastoma cells.