Miracle-dz/UniFAR-FTUs huggingface dataset:
Anticancer effects of kaempferol in A375 human malignant melanoma cells are mediated via induction of apoptosis, cell cycle arrest, inhibition of cell migration and downregulation of m-TOR/PI3K/AKT pathway.

PURPOSE Melanoma is an aggressive form of human cancer with limited treatment options currently available. The present study was aimed to evaluate the anticancer activity of kaempferol (KAM) against the human malignant melanoma A375 cell line along with evaluation of its effects on apoptosis, cell cycle, cell migration and m-TOR/PI3K/AKT pathway. METHODS Effects on cell viability were assessed by MTT assay while clonogenic assay measured the effects of KAM on colony formation. Annexin V assay evaluated the apoptotic effects of KAM in these cells using flow cytometry. Effects on cell cycle were determined by using flow cytometry with propidium iodide (PI) as probe. The effects of KAM on m-TOR/ PI3K/AKT signalling pathway were evaluated by western blot assay. RESULTS MTT assay indicated that KAM exhibits a significant anticancer activity against A375 cells with an IC50 of 20 μM. These antiproliferative effects of KAM were also supported by the colony formation assay wherein KAM reduced the colony formation in a dose-dependent manner. The anticancer effect of KAM was found to be due to the initiation of apoptosis in human malignant melanoma A375 cells. Additionally, KAM also exhibited the capacity to trigger G2/M cell cycle arrest and to inhibit the cell migratory potential of A375 cells. KAM caused significant downregulation of m-TOR, phosphorylated (p) m-TOR, PI3K, p-PI3K and Akt protein levels in A375 malignantmelanoma cells. CONCLUSIONS KAM exerts potent anticancer effects via induction of apoptosis, G2/M cell cycle arrest, cell migration inhibition and downregulation of m-TOR, pm-TOR, PI3K, p-PI3K and Akt protein levels.
Direct Growth of Bacteria in Headspace Vials Allows for Screening of Volatiles by Gas Chromatography Mass Spectrometry

Bacterially produced volatile organic compounds (VOCs) can modify growth patterns of eukaryotic hosts and competing/cohabiting microbes. These compounds have been implicated in skin disorders and attraction of biting pests. Current methods to detect and characterize VOCs from microbial cultures can be laborious and low-throughput, making it difficult to understand the behavior of microbial populations. In this work we present an efficient method employing gas chromatography/mass spectrometry with autosampling to characterize VOC profiles from solid-phase bacterial cultures. We compare this method to complementary plate-based assays and measure the effects of growth media and incubation temperature on the VOC profiles from a well-studied Pseudomonas aeruginosa PAO1 system. We observe that P. aeruginosa produces longer chain VOCs, such as 2-undecanone and 2-undecanol in higher amounts at 37°C than 30°C. We demonstrate the throughput of this method by studying VOC profiles from a representative collection of skin bacterial isolates under three parallel growth conditions. We observe differential production of various aldehydes and ketones depending on bacterial strain. This generalizable method will support screening of bacterial populations in a variety of research areas.
Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells

Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRS-containing exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-&agr; and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.
Associations between Acetaminophen Use during Pregnancy and ADHD Symptoms Measured at Ages 7 and 11 Years

Objective Our aim was to replicate and extend the recently found association between acetaminophen use during pregnancy and ADHD symptoms in school-age children. Methods Participants were members of the Auckland Birthweight Collaborative Study, a longitudinal study of 871 infants of European descent sampled disproportionately for small for gestational age. Drug use during pregnancy (acetaminophen, aspirin, antacids, and antibiotics) were analysed in relation to behavioural difficulties and ADHD symptoms measured by parent report at age 7 and both parent- and child-report at 11 years of age. The analyses included multiple covariates including birthweight, socioeconomic status and antenatal maternal perceived stress. Results Acetaminophen was used by 49.8% of the study mothers during pregnancy. We found significantly higher total difficulty scores (Strengths and Difficulty Questionnaire parent report at age 7 and child report at age 11) if acetaminophen was used during pregnancy, but there were no significant differences associated with any of the other drugs. Children of mothers who used acetaminophen during pregnancy were also at increased risk of ADHD at 7 and 11 years of age (Conners’ Parent Rating Scale-Revised). Conclusions These findings strengthen the contention that acetaminophen exposure in pregnancy increases the risk of ADHD-like behaviours. Our study also supports earlier claims that findings are specific to acetaminophen.
Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX‐type gene cluster

Botulinum neurotoxins are highly toxic substances and are all encoded together with one of two alternative gene clusters, the HA or the OrfX gene cluster. Very little is known about the function and structure of the proteins encoded in the OrfX gene cluster, which in addition to the toxin contains five proteins (OrfX1, OrfX2, OrfX3, P47, and NTNH). We here present the structures of OrfX2 and P47, solved to 2.1 and 1.8 Å, respectively. We show that they belong to the TULIP protein superfamily, which are often involved in lipid binding. OrfX1 and OrfX2 were both found to bind phosphatidylinositol lipids.
EMS Patients and Walk-In Patients Presenting With Severe Sepsis: Differences in Management and Outcome

Objectives Sepsis is a significant problem. The differences between patients with sepsis who walk into the emergency department (ED) and those who are transported via emergency medical services (EMS) have not been clarified. The aim of the study was to determine whether there was a difference in outcome between patients arriving by EMS and those presenting directly to the ED. Methods We prospectively collected and reviewed a cohort of all cases of severe sepsis and septic shock admitted to the medical intensive care unit from the ED from November 2009 to March 2012. Extracted data were basic demographic information (including mode of ED arrival), clinical data, and treatments. We calculated Systemic Inflammatory Response Syndrome criteria, Acute Physiology and Chronic Health Evaluation II scores, and Sequential Organ Failure Assessment (SOFA) scores. The primary outcome was mortality in severely ill patients with sepsis. Results A total of 378 subjects (78%) presented by EMS and 107 subjects were walk-in patients (22%). Patients transported via EMS were older (P < 0.01), had fewer lactates >4 (P < 0.02), a more altered mental status (P < 0.01), and higher respiratory rates (P < 0.05) than did walk-in patients. Patients transported by EMS had worse disease severity when measured by an Acute Physiology and Chronic Health Evaluation II score (P < 0.01) but not by SOFA score. EMS patients had a shorter time to receiving antibiotics (P = 0.02) and central line placement (P < 0.01) than did walk-in patients. In a logistic model, mortality was associated with increasing age (adjusted odds ratio 1.3; 95% confidence interval [CI] 1.2–1.4), higher first-measured ED lactates (1.2; 95% CI 1.1–1.2), and increased initial SOFA score (adjusted odds ratio 1.2; 95% CI 1.1–1.3) but not EMS arrival or prehospital fluids. Conclusions Neither arrival by EMS nor fluid administration by EMS is associated with decreased mortality in severe sepsis.
Predicting Students’ Decisions in a Training Simulation: A Novel Application of TrueSkill

Can TrueSkill predict student choices in graph-based training scenarios? We examine this question using data collected from students who engaged with a dozen branching scenarios using a browser-based training application. Students played through the graph-based scenarios to learn effective interaction skills in unfamiliar situations, during which their performance was measured against predefined learning objectives. Branching points in the scenario graph were annotated by experts as correct or incorrect with respect to one or more learning objectives. The application allowed students to re-run scenarios and presented tutoring information to guide learning. In this paper, we model student performance by giving each student multiple skill ratings, one for each learning objective. Unlike most applications of TrueSkill, students never play directly against each other; instead, each time the student makes a decision at a branch in the scenario graph, we treat this action as if the student played a game with the skill rating of the decision point. Using this model, we are able to predict student choices to a high degree of accuracy. Additionally, we show that training using the browser-based application results in a significant increase in average student skill rating for a subset of the learning objectives.
Effect of Groove Geometry on Rolling Contact Fatigue of PEEK Thrust Bearings in Water

Bearings have been used in various environments. Recently, small and light-weight bearings are developed in order to downsize mechanical components. Polymer bearings, such as PEEK (Poly-Ether-Ether-Ketone), PTFE (Poly-Tetra Fluoro-Ethylene) and PPS (Poly-Phenylene-Sulfide-Resin), are designed because of advantages of light weight, high corrosion resistance and self-lubricating. However, industrial design standards of these bearings have not been established yet, i.e., the relation between working conditions, shape, geometry, and lives of bearing components under RCF (Rolling Contact Fatigue) is not fully understood as well as crack propagation, wear and/or failure. In this study, we focused on the manufacture process of groove curvature decreasing contact stress, and observed cracks and flaking failures on groove surfaces and cross sections. Based on these observations, we investigated the relation between the groove geometry and lives of all-PEEK thrust bearings in water.
Development of a Fiber Location Search Based Image Analysis Method for Transverse Strain Distribution Measurement in CFRP Laminate

This paper describes a new method for measuring microscopic strain distribution in carbonfiberreinforcedplastics(CFRP). Thismethodaimstoevaluatetheeffectofheterogeneity, e.g.voids caused bydifferent pressureconditions in curing process,on transversecrack initiation. LocalAreaGrayLevelThresholding (LAGT)methodisanewfeature-basedmatchingmethodthat uses gray level difference between fibers and matrix in scanning electron microscope (SEM) pictures.ThispaperalsoproposesimprovedLAGT methodadjusting graylevelin localevaluating area. LAGT method and improved LAGT method were compared to existing methods, such as Phase-Only Correlation (POC)and Zero-mean Normalized Cross Correlation (ZNCC). Among these 4 methods, improved LAGT is less influenced by the noise from optical system and its measurementaccuracyisbettereven ifgraylevelgradientchangeslocallyinevaluating area.The microscopicstraindistribution in 90°layersundertransversetensileloading wereobtainedbyfiber location search based on image analysis using the improved LAGT method, and the measured strainscorrespondedwellwiththestrainscalculatedbybeamtheoryandlaminatetheory.Applying theabove-mentioned method to the laminates including voids, it becamepossible to evaluate the effect ofvoid onmicroscopicstrain distribution experimentally.
Semantic Slicing of Software Version Histories

Software developers often need to transfer functionality, e.g., a set of commits implementing a new feature or a bug fix, from one branch of a configuration management system to another. That can be a challenging task as the existing configuration management tools lack support for matching high-level, semantic functionality with low-level version histories. The developer thus has to either manually identify the exact set of semantically-related commits implementing the functionality of interest or sequentially port a segment of the change history, “inheriting” additional, unwanted functionality. In this paper, we tackle this problem by providing automated support for identifying the set of semantically-related commits implementing a particular functionality, which is defined by a set of tests. We formally define the semantic slicing problem, provide an algorithm for identifying a set of commits that constitute a slice, and propose techniques to minimize the produced slice. We then instantiate the overall approach, CSlicer, in a specific implementation for Java projects managed in Git and evaluate its correctness and effectiveness on a set of open-source software repositories. We show that it allows to identify subsets of change histories that maintain the functionality of interest but are substantially smaller than the original ones.
Design Implementation With Noninteger Multiple-Height Cells for Improved Design Quality in Advanced Nodes

Standard-cell libraries can be developed with different cell heights (e.g., in FinFET technology, corresponding to different numbers of fins). Larger cell heights provide higher drive strengths, but at the cost of larger area and power consumption as well as pin capacitance. Cells with smaller heights are relatively smaller in area, but have weaker drive strengths and are more likely to suffer from routing congestion and pin accessibility issues. Existing design methodologies and tool flows are able to mix cells with different heights at the block level (i.e., each block contains cells with heights being integer multiples of a particular “single row” cell height). To our knowledge, no design methodology in the literature or in production mixes cells with different, noninteger multiple heights in a fine-grained manner. In this paper, we propose a novel physical design optimization flow to implement design blocks with mixed cell heights in a fine-grained manner. Our optimization resolves the “chicken-and-egg” loop between floorplan site definition and the optimized choices of cell heights after placement with full comprehension of the constraints and costs of mixing cells of different heights (e.g., the “breaker cell” area overheads of row alignment between sub-blocks of 8 T and 12 T cell rows), our optimization achieves up to over 30% area and power reductions versus 12 T-only implementation while maintaining the same performance, and up to over 10% performance improvement along with power and area reductions versus 8 T-only implementation.
New Tagging Paradigms for Content Recommendation in Web 2.0 Portals

With this paper we tie in with what we presented during last year's workshop (5) where we illustrated how to analyze users' tag- ging and rating behavior to construct user- and context models that can be used to perform adaptations and to issue recommendations in order to create more user-tailored Web Portals. This time we want to present more sophisticated tagging paradigms and their inuence on users col- laboration behavior and the construction of user- and context-models. The concepts presented are currently been prototypically implemented within IBM's WebSphere Portal and can be presented in a live demo at the workshop.
Engineered ligand‐based VEGFR antagonists with increased receptor binding affinity more effectively inhibit angiogenesis

Abstract Pathologic angiogenesis is mediated by the coordinated action of the vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling axis, along with crosstalk contributed by other receptors, notably αvβ3 integrin. We build on earlier work demonstrating that point mutations can be introduced into the homodimeric VEGF ligand to convert it into an antagonist through disruption of binding to one copy of VEGFR2. This inhibitor has limited potency, however, due to loss of avidity effects from bivalent VEGFR2 binding. Here, we used yeast surface display to engineer a variant with VEGFR2 binding affinity approximately 40‐fold higher than the parental antagonist, and 14‐fold higher than the natural bivalent VEGF ligand. Increased VEGFR2 binding affinity correlated with the ability to more effectively inhibit VEGF‐mediated signaling, both in vitro and in vivo, as measured using VEGFR2 phosphorylation and Matrigel implantation assays. High affinity mutations found in this variant were then incorporated into a dual‐specific antagonist that we previously designed to simultaneously bind to and inhibit VEGFR2 and αvβ3 integrin. The resulting dual‐specific protein bound to human and murine endothelial cells with relative affinities of 120 ± 10 pM and 360 ± 50 pM, respectively, which is at least 30‐fold tighter than wild‐type VEGF (3.8 ± 0.5 nM). Finally, we demonstrated that this engineered high‐affinity dual‐specific protein could inhibit angiogenesis in a murine corneal neovascularization model. Taken together, these data indicate that protein engineering strategies can be combined to generate unique antiangiogenic candidates for further clinical development.
SWAY - Designing for Balance and Posture Awareness

This paper presents the SWAY prototype that encourages people to explore aspects around balance and posture in a playful way. The prototype senses small movements and shifts in posture using a Kinect sensor, and translates these movements to the tilting of a platform holding a set of marbles, and to haptic feedback in the form of vibrations. The prototype provides an interactive experience focusing on building body awareness with a particular focus on balance and posture. The design inquiry provided new insights with respect to reinforcement of bodily experiences and how different modalities affect the guiding of attention.
Defect Location and Sizing by Ultrasonic Phased Array on Aero Grade Material Aluminum He-15

This paper gives the orientation and inspection of aero grade material by using Ultrasonic Phased Array over conventional methods. The dimension of material sample HE15 is 150*120*10. Two defragmented aluminum alloys are joined by welding process known as Tungsten Inert Gas Welding. Inspection of material is carried out by various Non Destructive Testing methods namely ultrasonic method, radiography method, liquid penetrant and Phased array technique. Sensitivity of material is noticed by scanning of ultrasonic phased array and pulse echo technique method alternatively defects are detected by other NDT methods namely X-ray, Ultrasonic phased array technique and LPT. Few surface flaws are noticed at a depth of 2mm by LPT method. Porosity and inclusion defects are better traceout through phased array and X-ray radiography respectively. Ultrasonic Phased Array sectorial scan technique produces immediate images, allowing straight forward visualization of the internal structure and simplifying data interpretation of weld joint. The defect is identified and located by Ultrasonic Phased array Dynamic depth focusing Technique.
Outcomes of nondisplaced intracapsular femoral neck fractures with internal screw fixation in elderly patients: a systematic review

Introduction: Although the preferred treatment for displaced femoral neck fractures in the elderly is hip arthroplasty, the treatment for impacted or undisplaced femoral neck fractures (UFNF) is still a subject of controversy. Our purpose was to systematically review studies of elderly patients with UFNF treated with internal fixation using screws: (i) what is the reported mortality; (ii) what is the reoperation rate; (iii) what are the clinical and radiological outcomes; and (iv) what is the methodological quality of the included studies? Methods: This systematic review was performed through a search of PubMed and the Cochrane database using a structured search algorithm including studies enrolling patients older than 60 years old, with UFNF treated with internal fixation using screws. Our literature search returned 950 studies and 11 were selected for final abstraction. Results: 6 studies reported mortality rate. At 1-year follow-up mortality was reported by 3 studies: 18.8%; 22%, and 19%. At 5 years, 1 study reported mortality rate of 42%. Overall reoperation rate was reported by 9 studies and ranged from 8%-19%, while conversion to hip arthroplasty was performed in the range between 8% and 16% according to 6 studies. Conclusions: Internal fixation with cannulated screws for UFNF in the elderly is a valuable option, although it has substantial reoperation and mortality rates. Further prospective high-quality, randomised controlled trials are required to establish the optimal approach for the treatment of UFNF.
Securing Home IoT Environments with Attribute-Based Access Control

Rapid advances in ıotn~ have led to the proliferation of several end-user ıot devices. A modern day home ıot environment now resembles a complete network ecosystem with a variety of devices co-existing and operating concurrently. It is necessary that these devices do not disrupt the operations of other devices, either accidentally or maliciously. Accidental disruptions are usually due to misconfigured devices, which may, for instance, result in a device sending network broadcasts and flooding the network. Malicious disruptions may be caused by devices being compromised by attackers or due to devices purchased from untrusted manufacturers. An intentional disruption can include sending control information to other devices to manipulate their operations, and requesting for sensitive information such as surveillance videos or camera pictures. One way of preventing such disruptions is by enforcing access control on ıot devices. Attribute-Based Access Control is the most appropriate model because of its ability to enforce access control based on the attributes of the devices, users, and environment context. We consider the NIST Next Generation Access Control (NGAC) specification for our ABAC requirements because of several reasons, including its support for adaptive policies, efficiency, and ease of policy management.
Conservative therapeutic management of carpal tunnel syndrome

ABSTRACT Carpal tunnel syndrome is the most prevalent nerve compression and can be clinically or surgically treated. In most cases, the first therapeutic alternative is conservative treatment but there is still much controversy regarding the most effective modality of this treatment. In this study, we critically evaluated the options of conservative treatment for carpal tunnel syndrome, aiming to guide the reader through the conventional options used in this therapy.