Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme.

PURPOSE This open-label, prospective, multicenter single-arm phase II study combined bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) for the treatment of newly diagnosed glioblastoma (GBM). The objectives were to determine the efficacy of this treatment combination and the associated toxicity. PATIENTS AND METHODS Seventy patients with newly diagnosed GBM were enrolled between August 2006 and November 2008. Patients received standard RT starting within 3 to 6 weeks after surgery with concurrent administration of daily TMZ and biweekly BV. After completion of RT, patients resumed TMZ for 5 days every 4 weeks and continued biweekly BV. MGMT promoter methylation was assessed on patient tumor tissue. A University of California, Los Angeles/Kaiser Permanente Los Angeles (KPLA) control cohort of newly diagnosed patients treated with first-line RT and TMZ who had mostly received BV at recurrence was derived for comparison. RESULTS The overall survival (OS) and progression-free survival (PFS) were 19.6 and 13.6 months, respectively, compared to 21.1 and 7.6 months in the University of California, Los Angeles/KPLA control cohort, and 14.6 and 6.9 months in the European Organisation for Research and Treatment of Cancer-National Cancer Institute of Canada cohort. Correlation of MGMT promoter methylation and improved OS and PFS was retained in the study group. Comparative subset analysis showed that poor prognosis patients (recursive partitioning analysis class V/VI) may derive an early benefit from the use of first-line BV. Toxicity attributable to RT/TMZ was similar, and additional toxicities were consistent with those reported in other BV trials. CONCLUSION Patients treated with BV and TMZ during and after RT showed improved PFS without improved OS compared to the University of California, Los Angeles/KPLA control group. Additional studies are warranted to determine if BV administered first-line improves survival compared to BV at recurrence.
Formulation and Delivery Mode Affect Disposition and Activity of Tyrphostin-Loaded Nanoparticles in the Rat Carotid Model

Poor drug residence in the arterial wall hinders clinical implementation of local drug delivery strategies for the treatment of restenosis. A rat carotid model of vascular injury and intraluminal delivery of tyrphostin-containing polylactic acid (PLA) nanoparticles (NPs) were used to determine the relationship between residence properties and biological activity of different formulations and administration modes. The effects of delivery modes (denudation and delivery time) and formulation variables (adsorbed vs encapsulated drug, and NP size) on arterial drug/NP retention were examined. Antirestenotic effects of large (160 nm) and small (90 nm) tyrphostin-containing NPs, surface-absorbed tyrphostin, and systemic treatment were compared. Fluorescent NPs were used to study the spatial distribution of the carrier in the arterial wall. The decrease in arterial tyrphostin level over time fitted a biexponential model. Delivery time and pressure, endothelium integrity, particle size, and drug-polymer association affected local pharmacokinetics and the antirestenotic results after 14 days. The PLA-based tyrphostin NP formulation ensured a prolonged drug residence at the angioplasty site after single intraluminal application. Several readily adjustable formulation and procedural factors considerably modified arterial ingress of the drug-loaded NPs and governed their subsequent redistribution, tissue binding, elimination, and ensuing antirestenotic effect.
An Investigation on the Variation of Software Development Productivity

The productivity of software development is one of the major concerns for project managers. Given the increasing complexity of the software being developed and the concomitant rise in the typical project size, the productivity has not consistently improved. By analyzing the latest release of ISBSG data repository with 4106 projects ever developed, we report on the factors found to significantly influence productivity, and present an original model for the estimation of productivity during project design. We further illustrate that software development productivity has experienced irregular variations between the years 1995 and 2005. Considering the factors significant to productivity, we found its variations are primarily caused by the variations of average team size for the development and the unbalanced use of the less productive development language 3GL. Keywords—Development Platform, Function Point, Language, Productivity, Software Engineering, Team Size.
Double cancer of gall bladder and bile duct not associated with anomalous junction of the pancreaticobiliary duct system.

BACKGROUND Simultaneous double cancers of the biliary tract are rare. Most of them are thought to be associated with pancreaticobiliary maljunction (PBM); however, the characteristics of tumours without PBM are still unclear. METHODS Histology, immunoreactivity with carcinoembryonic antigen, carbohydrate antigen 19-9 and p53 and mutations in the K-ras gene were examined in tumours resected from cases of simultaneous double cancers of the biliary tract. RESULTS Four cases of simultaneous double cancers of the biliary tract were identified among 108 patients with biliary tract cancer (3.7%). None of the four cases associated with PBM, and the results of histological, immunohistochemical and genetic examinations differed between the bile duct and gall bladder cancers in each case. CONCLUSION Even when they do not associate with PBM, double cancers in the biliary tract are more likely to be the result of multicentric development.
Fatigue crack growth and crack closure in an AlMgSi alloy

This study reports an experimental investigation of fatigue crack propagation in AlMgSi1-T6 aluminium alloy using both constant and variable load amplitudes. Crack closure was monitored in all tests by the compliance technique using a pin microgauge. For the constant amplitude tests four different stress ratios were analysed. The crack closure parameter U was calculated and related with DK and the stress ratio, R. The threshold of the stress intensity factor range, DKth, was also obtained. Fatigue crack propagation tests with single tensile peak overloads have been performed at constant load amplitude conditions. The observed transient post overload behaviour is discussed in terms of the overload ratio, DK baseline level and R. The crack closure parameter U trends are compared with the crack growth transients. Experimental support is given for the hypothesis that crack closure is the main factor determining the transient crack growth behaviour following overloads on AlMgSi1-T6 alloy for plane stress conditions.
White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome

The dynamic susceptibility contrast magnetic resonance imaging perfusion technique was used to investigate possible hemodynamic changes in normal appearing white matter and deep gray matter (DGM) of 30 patients with clinically isolated syndrome (CIS) and 30 patients with relapsing–remitting multiple sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood volume, cerebral blood flow (CBF), and mean transit time values were estimated. Normalization was achieved for each subject with respect to average values of CBF and mean transit time of the hippocampi's dentate gyrus. Measurements concerned three regions of normal white matter of normal volunteers, normal appearing white matter of CIS and patients with relapsing–remitting multiple sclerosis, and DGM regions, bilaterally. All measured normal appearing white matter and DGM regions of the patients with CIS had significantly higher cerebral blood volume and mean transit time values, while averaged DGM regions had significantly lower CBF values, compared to those of normal volunteers (P < 0.001). Regarding patients with relapsing–remitting multiple sclerosis, all measured normal appearing white matter and DGM regions showed lower CBF values than those of normal volunteers and lower cerebral blood volume and CBF values compared to patients with CIS (P < 0.001). These data provide strong evidence that hemodynamic changes—affecting both white and DGM—may occur even at the earliest stage of multiple sclerosis, with CIS patients being significantly different than relapsing–remitting multiple sclerosis patients. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Chloroplast to chromoplast transition in tomato fruit: spectral confocal microscopy analyses of carotenoids and chlorophylls in isolated plastids and time-lapse recording on intact live tissue.

BACKGROUND AND AIMS There are several studies suggesting that tomato (Solanum lycopersicum) chromoplasts arise from chloroplasts, but there is still no report showing the fluorescence of both chlorophylls and carotenoids in an intermediate plastid, and no video showing this transition phase. METHODS Pigment fluorescence within individual plastids, isolated from tomato fruit using sucrose gradients, was observed at different ripening stages, and an in situ real-time recording of pigment fluorescence was performed on live tomato fruit slices. KEY RESULTS At the mature green and red stages, homogenous fractions of chloroplasts and chromoplasts were obtained, respectively. At the breaker stage, spectral confocal microscopy showed that intermediate plastids contained both chlorophylls and carotenoids. Furthermore, an in situ real-time recording (a) showed that the chloroplast to chromoplast transition was synchronous for all plastids of a single cell; and (b) confirmed that all chromoplasts derived from pre-existing chloroplasts. CONCLUSIONS These results give details of the early steps of tomato chromoplast biogenesis from chloroplasts, with the formation of intermediate plastids containing both carotenoids and chlorophylls. They provide information at the sub-cellular level on the synchronism of plastid transition and pigment changes.
SEARCH FOR RAYLEIGH SCATTERING IN THE ATMOSPHERE OF GJ1214b

We investigate the atmosphere of GJ1214b, a transiting super-Earth planet with a low mean density, by measuring its transit depth as a function of wavelength in the blue optical portion of the spectrum. It is thought that this planet is either a mini-Neptune, consisting of a rocky core with a thick, hydrogen-rich atmosphere, or a planet with a composition dominated by water. Most observations favor a water-dominated atmosphere with a small scale-height, however, some observations indicate that GJ1214b could have an extended atmosphere with a cloud layer muting the molecular features. In an atmosphere with a large scale-height, Rayleigh scattering at blue wavelengths is likely to cause a measurable increase in the apparent size of the planet toward the blue. We observed the transit of GJ1214b in the B band with the FOcal Reducing Spectrograph at the Very Large Telescope and in the g band with both ACAM on the William Herschel Telescope (WHT) and the Wide Field Camera at the Isaac Newton Telescope (INT). We find a planet-to-star radius ratio in the B band of 0.1162 ± 0.0017, and in the g band 0.1180 ± 0.0009 and 0.1174 ± 0.0017 for the WHT and INT observations, respectively. These optical data do not show significant deviations from previous measurements at longer wavelengths. In fact, a flat transmission spectrum across all wavelengths best describes the combined observations. When atmospheric models are considered, a small scale-height water-dominated model fits the data best.
Comparative Risk of Impaired Glucose Metabolism Associated with Cyclosporine Versus Tacrolimus in the Late Posttransplant Period

New onset diabetes after transplantation (NODAT) and impaired fasting glucose (IFG) are common in kidney transplant recipients (KTRs). Calcinuerin inhibitor (CNI) therapy is a causal risk factor. NODAT is associated with increased mortality and diminished graft survival. We studied the incidence of NODAT and IFG in KTRs before and after a medically indicated switch of CNI therapy from cyclosporine (CsA) to tacrolimus (Tac). The study population consisted of 704 nondiabetic KTRs. Of them, 171 underwent conversion from CsA to Tac (group I) and 533 remained on the CsA since transplantation (Group II). Time‐dependent Cox regression and generalized estimating equations were used to account for sequential CNI exposure. NODAT and IFG occurred in 15.2% and 22.1% of group I subjects and 15.6% and 25.8% of group II subjects, respectively (p = 0.90 for NODAT and p = 0.38 for IFG). Accounting for equal follow‐up time since conversion from CsA to Tac, the adjusted 5‐year NODAT‐free survival was 87.4% and 91.4% in group I and group II, respectively (p = 0.90). In conclusion, conversion to Tac, compared to continuous exposure to CsA, carries quantitatively similar risk of impaired glucose metabolism in KTRs in the late posttransplant period.
Scrambling Eggs: Meiotic Drive and the Evolution of Female Recombination Rates

Theories to explain the prevalence of sex and recombination have long been a central theme of evolutionary biology. Yet despite decades of attention dedicated to the evolution of sex and recombination, the widespread pattern of sex differences in the recombination rate is not well understood and has received relatively little theoretical attention. Here, we argue that female meiotic drivers—alleles that increase in frequency by exploiting the asymmetric cell division of oogenesis—present a potent selective pressure favoring the modification of the female recombination rate. Because recombination plays a central role in shaping patterns of variation within and among dyads, modifiers of the female recombination rate can function as potent suppressors or enhancers of female meiotic drive. We show that when female recombination modifiers are unlinked to female drivers, recombination modifiers that suppress harmful female drive can spread. By contrast, a recombination modifier tightly linked to a driver can increase in frequency by enhancing female drive. Our results predict that rapidly evolving female recombination rates, particularly around centromeres, should be a common outcome of meiotic drive. We discuss how selection to modify the efficacy of meiotic drive may contribute to commonly observed patterns of sex differences in recombination.
Private and Continual Release of Statistics

We ask the question: how can Web sites and data aggregators continually release updated statistics, and meanwhile preserve each individual user’s privacy? Suppose we are given a stream of 0’s and 1’s. We propose a differentially private continual counter that outputs at every time step the approximate number of 1’s seen thus far. Our counter construction has error that is only poly-log in the number of time steps. We can extend the basic counter construction to allow Web sites to continually give top-k and hot items suggestions while preserving users’ privacy.
Visualization of Synaptic Inhibition with an Optogenetic Sensor Developed by Cell-Free Protein Engineering Automation

We describe an engineered fluorescent optogenetic sensor, SuperClomeleon, that robustly detects inhibitory synaptic activity in single, cultured mouse neurons by reporting intracellular chloride changes produced by exogenous GABA or inhibitory synaptic activity. Using a cell-free protein engineering automation methodology that bypasses gene cloning, we iteratively constructed, produced, and assayed hundreds of mutations in binding-site residues to identify improvements in Clomeleon, a first-generation, suboptimal sensor. Structural analysis revealed that these improvements involve halide contacts and distant side chain rearrangements. The development of optogenetic sensors that respond to neural activity enables cellular tracking of neural activity using optical, rather than electrophysiological, signals. Construction of such sensors using in vitro protein engineering establishes a powerful approach for developing new probes for brain imaging.
Value of the Glasgow coma scale, age, and arterial blood pressure score for predicting the mortality of major trauma patients presenting to the emergency department.

BACKGROUND The purpose of this study is to detect the mortality predictive power of new Glasgow coma scale, age, and arterial pressure (GAP) scoring system in major trauma patients admitted to the emergency department (ED). METHODS A total of 100 major trauma patients admitted to Uludağ University Faculty of Medicine ED who were 18 years of age or more were included in the study. In this prospective study, revised trauma score (RTS), injury severity score (ISS), trauma-related ISS (TRISS), Mechanism, GAP (MGAP) and GAP scores of the patients were calculated. RESULTS A significant positive correlation was established between ISS, TRISS, MGAP, and GAP in predicting in-hospital mortality (p<0.0001). Short-term (24 hours) and long-term (4-week) mortality prediction rates and area under the curve in receiver operating characteristics analysis were 0.727-0.680 for RTS, 0.863-0.816 for ISS, 0.945-0,911 for TRISS, 0.970-0.938 for MGAP, and 0.910-0.904 for GAP. All calculated trauma scoring systems revealed a significant mortality prediction power (p<0.001). GAP score was found statistically and significantly selective and sensitive in predicting both in-ED and in-hospital mortality (p=0.0001). CONCLUSION In major trauma patients, GAP score is an easily calculable system both in the field and at the time of admission in the EDs by providing emergency physicians with future decision-making schemes by means of mortality prediction of the patients.
Three-phase high frequency transformer isolated AC to DC converter for EV battery quick charging

This paper proposed a three phase AC to DC converter, which is isolated by high frequency transformer, for EV battery quick charging. EV battery chargers normally need a transformer to isolate the power grid from battery system for safety. Different types of chargers exist. Some types that are isolated by commercial frequency transformer are of large volume and weight. By increasing frequency, the volume and weight of transformer can be greatly reduced. But the material that is proper for very high frequency can hardly be used for large power applications, by the reason of manufacturing and cost. The principle and design of this converter was studied. The fundamental operations were confirmed by 37 kW experimental results. Weight of transformer is reduced to about 1/7 and total efficiency is higher than 90%. 2-ARM-PWM method is studied for the purpose of loss reduction.
A new model system identifies epidermal growth factor receptor–human epidermal growth factor receptor 2 (HER2) and HER2–human epidermal growth factor receptor 3 heterodimers as potent inducers of oesophageal epithelial cell invasion

Oesophageal squamous cell carcinomas and oesophageal adenocarcinomas show distinct patterns of ErbB expression and dimers. The functional effects of specific ErbB homodimers or heterodimers on oesophageal (cancer) cell behaviour, particularly invasion during early carcinogenesis, remain unknown. Here, a new cellular model system for controlled activation of epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) and EGFR–HER2 or HER2–human epidermal growth factor receptor 3 (HER3) homodimers and heterodimers was studied in non‐neoplastic squamous oesophageal epithelial Het‐1A cells. EGFR, HER2 and HER3 intracellular domains (ICDs) were fused to dimerization domains (DmrA/DmrA and DmrC), and transduced into Het‐1A cells lacking ErbB expression. Dimerization of EGFR, HER2 or EGFR–HER2 and HER2–HER3 ICDs was induced by synthetic ligands (A/A or A/C dimerizers). This was accompanied by phosphorylation of the respective EGFR, HER2 and HER3 ICDs and activation of distinct downstream signalling pathways, such as phospholipase Cγ1, Akt, STAT and Src family kinases. Phenotypically, ErbB dimers caused cell rounding and non‐apoptotic blebbing, specifically in EGFR–HER2 and HER2–HER3 heterodimer cells. In a Transwell assay, cell migration velocity was elevated in HER2 dimer cells as compared with empty vector cells. In addition, HER2 dimer cells showed in increased cell invasion, reaching significance for induced HER2–HER3 heterodimers (P = 0.015). Importantly, in three‐dimensional organotypic cultures, empty vector cells grew as a superficial cell layer, resembling oesophageal squamous epithelium. In contrast, induced HER2 homodimer cells were highly invasive into the matrix and formed cell clusters. This was associated with partial loss of cytokeratin 7 (when HER2 homodimers were modelled) and p63 (when EGFR–HER2 heterodimers were modelled), which suggests a change or loss of squamous cell differentiation. Controlled activation of specific EGFR, HER2 and HER3 homodimers and heterodimers caused oesophageal squamous epithelial cell migration and/or invasion, especially in a three‐dimensional microenvironment, thereby functionally identifying ErbB homodimers and heterodimers as important drivers of oesophageal carcinogenesis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The contribution of emotional empathy to approachability judgments assigned to emotional faces is context specific

Previous research on approachability judgments has indicated that facial expressions modulate how these judgments are made, but the relationship between emotional empathy and context in this decision-making process has not yet been examined. This study examined the contribution of emotional empathy to approachability judgments assigned to emotional faces in different contexts. One-hundred and twenty female participants completed the questionnaire measure of emotional empathy. Participants provided approachability judgments to faces displaying angry, disgusted, fearful, happy, neutral, and sad expressions, in three different contexts—when evaluating whether they would approach another individual to: (1) receive help; (2) give help; or (3) when no contextual information was provided. In addition, participants were also required to provide ratings of perceived threat, emotional intensity and label facial expressions. Emotional empathy significantly predicted approachability ratings for specific emotions in each context, over and above the contribution of perceived threat and intensity, which were associated with emotional empathy. Higher emotional empathy predicted less willingness to approach people with angry and disgusted faces to receive help, and a greater willingness to approach people with happy faces to receive help. Higher emotional empathy also predicted a greater willingness to approach people with sad faces to offer help, and more willingness to approach people with happy faces when no contextual information was provided. These results highlight the important contribution of individual differences in emotional empathy in predicting how approachability judgments are assigned to facial expressions in context.