Miracle-dz/UniFAR-FTUs huggingface dataset:
The GTP binding proteins Gem and Rad are negative regulators of the Rho–Rho kinase pathway

The cytoskeletal changes that alter cellular morphogenesis and motility depend upon a complex interplay among molecules that regulate actin, myosin, and other cytoskeletal components. The Rho family of GTP binding proteins are important upstream mediators of cytoskeletal organization. Gem and Rad are members of another family of small GTP binding proteins (the Rad, Gem, and Kir family) for which biochemical functions have been mostly unknown. Here we show that Gem and Rad interface with the Rho pathway through association with the Rho effectors, Rho kinase (ROK) α and β. Gem binds ROKβ independently of RhoA in the ROKβ coiled-coil region adjacent to the Rho binding domain. Expression of Gem inhibited ROKβ-mediated phosphorylation of myosin light chain and myosin phosphatase, but not LIM kinase, suggesting that Gem acts by modifying the substrate specificity of ROKβ. Gem or Rad expression led to cell flattening and neurite extension in N1E-115 neuroblastoma cells. In interference assays, Gem opposed ROKβ- and Rad opposed ROKα-mediated cell rounding and neurite retraction. Gem did not oppose cell rounding initiated by ROKβ containing a deletion of the Gem binding region, demonstrating that Gem binding to ROKβ is required for the effects observed. In epithelial or fibroblastic cells, Gem or Rad expression resulted in stress fiber and focal adhesion disassembly. In addition, Gem reverted the anchorage-independent growth and invasiveness of Dbl-transformed fibroblasts. These results identify physiological roles for Gem and Rad in cytoskeletal regulation mediated by ROK.
Elevated Bone Turnover Markers after Risk-Reducing Salpingo-Oophorectomy in Women at Increased Risk for Breast and Ovarian Cancer

Background Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers. Premenopausal RRSO is hypothesized to increase fracture risk more than natural menopause. Elevated bone turnover markers (BTMs) might predict fracture risk. We investigated BTM levels after RRSO and aimed to identify clinical characteristics associated with elevated BTMs. Methods Osteocalcin (OC), procollagen type I N-terminal peptide (PINP) and serum C-telopeptide of type I collagen (sCTx) were measured in 210 women ≥ 2 years after RRSO before age 53. BTM Z-scores were calculated using an existing reference cohort of age-matched women. Clinical characteristics were assessed by questionnaire. Results BTMs after RRSO were higher than age-matched reference values: median Z-scores OC 0.11, p = 0.003; PINP 0.84, p < 0.001; sCTx 0.53, p < 0.001 (compared to Z = 0). After excluding women with recent fractures or BTM interfering medication, Z-scores increased to 0.34, 1.14 and 0.88, respectively. Z-scores for OC and PINP were inversely correlated to age at RRSO. No correlation was found with fracture incidence or history of breast cancer. Conclusions Five years after RRSO, BTMs were higher than age-matched reference values. Since elevated BTMs might predict higher fracture risk, prospective studies are required to evaluate the clinical implications of this finding.
Time-Coherent Expansion of MEG/EEG Cortical Sources

In this study we estimated the spatial extent of cortical areas of time-coherent activity using the inverse problem in magneto/electroencephalography (MEEG). The model discussed here uses classical regularization tools in order to force the inverse solution to be piecewise coherent. First, the cortex was seeded by focal dipolar sources. Then, a time-coherent expansion (TCE) onto the cortical surface was performed in order to obtain surface source models composed of patches with uniform current density. Patches represent extended cortical regions with one single time course per active area. Results obtained from synthetic data show that using the TCE method is relevant even with a low signal-to-noise ratio, although the final estimation is often slightly biased. We applied the TCE method to evoked magnetic fields obtained after electrical stimulation of fingers in order to estimate the somatotopic cortical maps of the primary somatosensory cortex.
Effect of Seminal Fluids in Mating Between M and S Forms of Anopheles gambiae

Abstract Previous studies have shown that sympatric populations of M and S molecular forms of Anopheles gambiae sensu stricto exhibit strong assortative mating. In the few documented cases of cross-mating between M and S forms, females that mated with a male of the alternative form were often also mated with a male of their own form. A potential explanation for the association between cross-mating and double mating could be that male accessory gland or sperm proteins that are responsible for inducing refractoriness to further mating by females have diverged between the M and S forms. This mechanism of postmating reproductive isolation would have important implications for our understanding of the speciation processes in the An. gambiae complex. We tested for this mechanism, by comparing the likelihood of mating, feeding, and laying eggs, as well as the fertility of females presented with males of their own form or the alternate form in the laboratory. We also compared the likelihood of remating in cross-mated and assortatively-mated females, and we analyzed their progeny to unravel patterns of sperm precedence. We found that cross-mated females differed from assortatively-mated females only in terms of egg-hatching rate and larval survival but that these effects could be attributed to hybrid vigor rather than differential response to seminal products. Cross-mating between forms was not associated with remating behavior. These results indicate that the sex proteins responsible for inhibiting further insemination and triggering the gonotrophic cycle in females have not diverged between these M and S populations. We discuss alternative explanations for the patterns of cross-mating and multiple mating observed in the field.
Optimal Discrete Rate Adaptation for Distributed Real-Time Systems

Many distributed real-time systems face the challenge of dynamically maximizing system utility and meeting stringent resource constraints in response to fluctuations in system workload. Thus, online adaptation must be adopted in face of workload changes in such systems. We present the multiparametric rate adaptation (MPRA) algorithm for discrete rate adaptation in distributed real-time systems with end-to-end tasks. The key novelty and advantage of MPRA is that it can efficiently produce optimal solutions in response to workload variations such as dynamic task arrivals. Through offline preprocessing MPRA transforms an NP-hard utility optimization problem to the evaluation of a piecewise linear function of the CPU utilization. At run time MPRA produces optimal solutions by evaluating the function based on the CPU utilization. Analysis and simulation results show that MPRA maximizes system utility in the presence of varying workloads, while reducing the online computation complexity to polynomial time.
A prediction model for high-frequency financial time series

A wide number of sophisticated models have been proposed in the literature to solve prediction problems. However, a drawback arises in the particular case of financial prediction problems and called the random walk dilemma (RWD). In this context, the concept of time phase adjustment can be used to overcome the problem for daily-frequency financial time series. However, the fast evolution of trading platforms increased the frequency for performing operations in the stock market for fractions of seconds, which makes the analysis of high-frequency financial time series very important in this current scenario. In this way, this paper presents a model, called the increasing decreasing linear neuron (IDLN), to predict high-frequency financial time series from the Brazilian stock market. Besides, a descending gradient-based method with automatic time phase adjustment is presented for the design of the proposed model, and the obtained results overcame those obtained by established prediction models in the literature.
The Ethics of Social Research with Children: An Overview†

This paper attempts to provide an overview of ethical issues related to social research with children. It sets the discussion in the context of current debates about researching children in the UK, and explores the extent to which children should be regarded as similar to, or different from, adults in social research, focusing on how children are positioned as vulnerable, incompetent and relatively powerless in society in general, and how this conceptualisation of children needs to be taken into account in social research. The paper concludes with some practical and methodological suggestions.
A review of research on playgroups

This paper reviews research on playgroups in the United Kingdom. Subjects covered include the geographical distribution of playgroups; the backgrounds of families who use them; the concept and practice of parental involvement; the position of playgroup workers; and the experience of children in playgroups. The review finds that the majority of children attend playgroup at some stage, mostly for 2 or 3 half‐day sessions per week. Parental involvement is higher in playgroups than in other pre‐school services, although there is much variation. Attendance at preschool appears to have benefits to the child, although the evidence is not such as to show whether playgroups are better or worse than other forms of provision in this respect. The review concludes that more research needs to be carried out into the provision and effectiveness of services for under‐5s.
A disruption-tolerant architecture for secure and efficient disaster response communications

We consider the problem of providing situational awareness when citizens in a disaster are willing to contribute their own devices, such as laptops and smart phones, to gather data (text, images, audio or video) and to help forward data gathered by others. A situational awareness service processes all received data and creates annotated maps to visualize a disaster site (e
Longer Telomeres Are Associated with Cancer Risk in MMR-Proficient Hereditary Non-Polyposis Colorectal Cancer

Aberrant telomere length measured in blood has been associated with increased risk of several cancer types. In the field of hereditary non-polyposis colorectal cancer (CRC), and more particularly in Lynch syndrome, caused by germline mutations in the mismatch repair (MMR) genes, we recently found that cancer-affected MMR gene mutation carriers had shorter telomeres and more pronounced shortening of telomere length with age than controls and unaffected MMR gene mutation carriers. Here we evaluate blood telomere length in MMR-proficient hereditary non-polyposis CRC, i.e. familial CRC type X (fCRC-X). A total of 57 cancer-affected and 57 cancer-free individuals from 34 Amsterdam-positive fCRC-X families were analyzed and compared to the data previously published on 144 cancer-affected and 100 cancer-free MMR gene mutation carriers, and 234 controls. Relative telomere length was measured using a monochrome multiplex quantitative PCR method, following strict measures to avoid sources of bias and adjusting by age. Despite the retrospective nature of our study, the results show that longer telomeres associate with cancer risk in fCRC-X, thus identifying different patterns of telomere length according to the status of the MMR system.
Defibrillation testing at the time of implantation of cardioverter defibrillator in the clinical practice: a nation-wide survey.

AIMS Despite an effective defibrillation testing (DT) is considered mandatory to be consistent with the rules of good clinical practice, some physicians are concerned about the risk of complications related to the induction test, and in real world clinical practice, several implant procedures are performed without any induction test. We conducted a systematic nation-wide retrospective survey in order to determine the DT rate and its complications. METHODS AND RESULTS An ad hoc questionnaire was sent to all 343 Italian implanting centres and the data from the 229 (67%) centres that answered were analysed. During the year 2005, a total of 7857 patients underwent a first implantation of cardioverter defibrillator (ICD), 38% of which with cardiac resynchronization therapy (CRT). Of these, 2356 (30%) were implanted without any induction test. In 35 (15%) centres, the induction test was performed in < 25% of the patients, whereas in 136 (59%) centres, it was performed in > 75% of the patients. At multivariable analysis, performed in a subset of 1206 patients from 107 centres, CRT device (OR = 1.82) and primary prevention (OR = 1.47) were independent predictors of the decision to not perform DT. However, altogether, the clinical variables accounted only for 35% of the total variance, whereas the remaining 65% was probably unrelated to clinical factors. There was a total of 22 (0.4%) life-threatening complications as a consequence of the induction test: 4 deaths (0.07%), 8 cardiopulmonary arrests requiring resuscitation manoeuvres (0.15%), 6 cardiogenic shocks (0.11%), 3 strokes (0.05%), and 1 pulmonary embolism (0.02%). CONCLUSION In real world practice, DT is not performed in a substantial number of patients, most of these in the absence of legitimate reasons. The clinical impact of DT vs. no DT remains unclear until the not negligible complication rate is compared against the long-term potential benefit.
Genetic Determinants of Osteoporosis: Common Bases to Cardiovascular Diseases?

Osteoporosis is the most common and serious age-related skeletal disorder, characterized by a low bone mass and bone microarchitectural deterioration, with a consequent increase in bone fragility and susceptibility to spontaneous fractures, and it represents a major worldwide health care problem with important implications for health care costs, morbidity and mortality. Today is well accepted that osteoporosis is a multifactorial disorder caused by the interaction between environment and genes that singularly exert modest effects on bone mass and other aspects of bone strength and fracture risk. The individuation of genetic factors responsible for osteoporosis predisposition and development is fundamental for the disease prevention and for the setting of novel therapies, before fracture occurrence. In the last decades the interest of the Scientific Community has been concentrated in the understanding the genetic bases of this disease but with controversial and/or inconclusive results. This review tries to summarize data on the most representative osteoporosis candidate genes. Moreover, since recently osteoporosis and cardiovascular diseases have shown to share common physiopathological mechanisms, this review also provides information on the current understanding of osteoporosis and cardiovascular diseases common genetic bases.
Toward a more informative psychological science of eyewitness evidence

Like Hugo Munsterberg, we believe that psychological science can inform the courts and police regarding eyewitness evidence. But 100 years into the enterprise, the body of knowledge acquired to date demands considerable circumspection, both in the claims expert psychological witnesses make in court and in the recommendations psychologists tender to investigating officers. There are a number of points regarding eyewitness evidence that psychologists can offer with considerable confidence, but many matters are as yet open to debate (and some issues are likely to remain unsettled for a long time). We encourage researchers, law enforcement and the legal community to (a) identify and prioritize the problems to be solved, (b) focus on a more integrative empirical approach, including more of the field experiments currently in use, as well as new descriptive research, especially on base rates and (c) use basic psychological theory and principles to consolidate the wide range of phenomena present in individual cases. Copyright © 2008 John Wiley & Sons, Ltd.
Balancing the Local and the Global in Infrastructural Information Systems

A considerable body of literature has demonstrated-- empirically as well as analytically--that information systems need to be situated to the local context of use. Yet for infrastructural information systems that span numerous contexts spread out globally, this is literally prohibitive. For these systems to work, it is necessary to strike a balance between sensitiveness to local contexts and a need to standardize across contexts. We analyze a key element in this, namely, spelling out the (largely invisible) "costs" that the different actors pay to achieve working solutions. Empirically, we draw from an ongoing case study. We analyze the attempts of a maritime classification company with 5500 employees located in 300 sites in 100 countries to develop an infrastructural information system to support the surveying of ships globally. We elaborate design implications and concepts relevant to developing information infrastructures that also apply to the context of developing countries.
Push-pull osmotic pump for zero order delivery of lithium carbonate: Development and in vitro characterization

Lithium carbonate, a drug with narrow therapeutic index, needs therapeutic drug monitoring and dose adjustment to maintain lithium level within the therapeutic window. Conventional formulations of lithium carbonate exhibit immediate drug release causing swing/fluctuations in the plasma concentration of lithium, consequently leading to unfavorable side-effects and make dose adjustment difficult. The push-pull osmotic pump has been developed for zero order delivery of lithium carbonate for a period of 24 h. The effect of various formulation variables on bilayer core tablet and its semi permeable coating along with orifice diameter have been investigated and optimized for desired drug release profile. Drug release was found to be inversely proportional to the membrane thickness but directly related to the amount of pore formers in the semipermeable membrane. Images from a scanning electron microscope confirmed the presence of pores in the semipermeable membrane which facilitated the required water penetration. No distortion or change in orifice shape was noticed prior to and after the dissolution study. Drug release from the developed formulation was found to be independent of pH, agitation intensity and agitation mode but depended on osmotic pressure of dissolution media.
Human face classification based on localized blur descriptors

In our proposed work localized patch based geometric blur point descriptors are accumulated to generate a global similarity matrix for every pair of focal and query image. A focal image is a randomly selected template image that represents each class and a query image symbolizes all other images that belong to the same class. The similarity matrix is dimensionally reduced using the proposed bidirectional 2-dimensional principal component analysis technique to generate distinctive feature sets. These feature sets are used for training and testing an extreme learning machine classifier. The proposed face recognition structure handles variations in head positions, lighting conditions, facial expressions and cluttered background by exclusively matching template and query images. Extensive experiments are performed using challenging face databases and significant improvements in recognition accuracy were achieved.
Concentration and composition of free amino acids and osmolalities of porcine oviductal and uterine fluid and their effects on development of porcine IVF embryos

The concentration of free amino acids and the osmolalities in porcine oviductal (OF) and uterine fluids (UFs) on day 3 (D3) and day 5 (D5) were measured by HPLC and Vapor Pressure Osmometer, respectively. Based on these measurements we designed new media based on PZM3 by modifying the amino acid composition and osmolality. The effectiveness of the modified PZM3 on the development of porcine IVF embryos was then investigated. A total of 24 free amino acids were measured, including 20 protein and 4 nonprotein amino acids (β‐alanine, taurine, ornithine, and citrulline). There was no significant difference in the total concentration of amino acids among D3OF (13.06 ± 3.63 mmol/L), D3UF (10.54 ± 5.16 mmol/L), or D5UF (10.23 ± 6.69 mmol/L). But the total concentration of amino acids in D5OF (5.89 ± 1.47 mmol/L) was significantly lower than the three fluids above. Some individual amino acids varied significantly depending on where they were collected and from which day. The blastocyst rates of porcine IVF embryos were not improved when embryos were cultured in PZM3 with amino acids at D3OF (PZM3‐D3OF, 20.3 ± 7.9%) or D5UF (PZM3‐D5UF, 14.3 ± 10.7%) concentrations or in PZM3‐D3OF for the first 48 (20.5 ± 15.1), 72 (25.6 ± 10.4), and 96 (18.7 ± 10.0) hr and then transferred into PZM3‐D5UF compared with PZM3 with Sigma amino acid solution (PZM3‐SAA) (30.8 ± 9.1%). However, when IVF embryos were cultured in PZM3‐D5UF, the average nuclear number per blastocyst (57.6 ± 8.3) was increased compared to PZM3‐SAA (40.5 ± 3.5). The osmolalities in D3OF, D3UF, D5OF, and D5UF were 318 ± 8, 320 ± 32, 321, and 293 ± 8 mOsM, respectively. When the IVF embryos were cultured in PZM3‐SAA and PZM3‐D3OF at a variety of osmolalities (150–360 mOsM), higher blastocyst rates were obtained at 270–300 mOsM in the PZM3‐SAA group (24.6–33.9%) and 270–290 mOsM in PZM3‐D3OF group (22.4–24.2%). The blastocyst rate gradually decreased when the osmolality was increased or decreased in both groups. When the embryos were cultured in PZM3‐SAA at 330 mOsM for the first 72 hr and then transferred to 250 mOsM (33.3 ± 3.4%), the blastocyst rate was higher than original PZM3 (21.2 ± 2.2%) (288 mOsM). Mol. Reprod. Dev. 74: 1228–1235, 2007. © 2007 Wiley‐Liss, Inc.
Evaluation of Left Atrial Appendage Functions According to Different Etiologies of Atrial Fibrillation with a Tissue Doppler Imaging Technique by Using Transesophageal Echocardiography

Background: Atrial fibrillation (AF) occurs due to various etiologies that carry different risks for thromboembolism. However, the effect of different etiologies on left atrial appendage (LAA) function has not been investigated. This study aimed to examine the LAA function in AF that occurred under various etiologies and to compare the findings with a novel tissue Doppler imaging (TDI) technique by using transesophageal echocardiography (TEE). Methods: LAA function was assessed in 84 patients with permanent AF according to various etiologies [mitral stenosis in 20 (24%), hypertension in 44 (52%), and hyperthyroidism in 20 (24%) patients] and in 23 controls with sinus rhythm. LAA area change, PW‐Doppler and tissue velocities of LAA were measured. The presence of SEC or thrombus and their relation to LAA function was evaluated. Results: LAA velocities were lowest in mitral stenosis and highest in hyperthyroidism. Moderate–severe LAA SEC was detected in 61 and thrombi in 23 patients. Factors associated with the severity of SEC were the percentage of the LAA area change, PW‐Doppler peak emptying velocity, and TDI septal wall downward velocity. The percent of the LAA area change and PW‐Doppler peak emptying velocity were the significantly related factors for the presence of thrombi (OR = 0.84, 95% CI = 0.74–0.95, P = 0.005 and OR = 0.85, 95% CI = 0.74–0.98, P = 0.02, respectively). Conclusion: LAA function deteriorated most severely in mitral stenosis and least in hyperthyroidism. The LAA area change and PW‐Doppler emptying velocity were important predictors for SEC or thrombi. Although TDI was not superior to classical methods, it provided complementary data to PW‐Doppler velocities for predicting SEC and thrombi.