Miracle-dz/UniFAR-FTUs huggingface dataset:
Potentiating role of Gas6 and Tyro3, Axl and Mer (TAM) receptors in human and murine platelet activation and thrombus stabilization

Summary. Background: Interaction of murine Gas6 with the platelet Gas6 receptors Tyro3, Axl and Mer (TAM) plays an important role in arterial thrombus formation. However, a role for Gas6 in human platelet activation has been questioned. Objective: To determine the role of Gas6 in human and murine platelet activation and thrombus formation. Methods and Results: Gas6 levels appeared to be 20‐fold higher in human plasma than in platelets, suggesting a predominant role of plasma‐derived Gas6. Human Gas6 synergizes with ADP–P2Y12 by enhancing and prolonging the phosphorylation of Akt. Removal of Gas6 from plasma impaired ADP‐induced platelet aggregation. Under flow conditions, absence of human Gas6 provoked gradual platelet disaggregation and integrin αIIbβ3 inactivation. Recombinant human Gas6 reversed the effects of Gas6 removal. In mouse blood, deficiency in Gas6 or in one of the TAM receptors led to reduced thrombus formation and increased disaggregation, which was completely antagonized by external ADP. In contrast, collagen‐induced platelet responses were unchanged by the absence of Gas6 in both human and mouse systems. Conclusions: The ADP–P2Y12 and Gas6–TAM activation pathways synergize to achieve persistent αIIbβ3 activation and platelet aggregation. We postulate a model of thrombus stabilization in which plasma Gas6, by signaling via the TAM receptors, extends and enhances the platelet‐stabilizing effect of autocrine ADP, particularly when secretion becomes limited.
A new approach to the decomposition of incompletely specified multi-output functions based on graph coloring and local transformations and its application to FPGA mapping

An approach to the decomposition of incompletely specified Boolean functions is introduced, and its application to lookup-table-based field programmable gate array (FPGA) mapping is described. Three methods are developed: fast graph coloring to perform a quasi-optimum 'don't care' assignment; variable partitioning to quickly find the 'best' partitions; and local transformation to transform a nondecomposable function into several decomposable ones. The methods perform global optimization of the input function. A short description of a FPGA mapping program (TRADE) and an evaluation of its results are provided. <<ETX>>
Sparse non-negative matrix language modeling for geo-annotated query session data

The paper investigates the impact on query language modeling when using skip-grams within query as well as across queries in a given search session, in conjunction with the geo-annotation available for the query stream data. As modeling tool we use the recently proposed sparse non-negative matrix estimation technique, since it offers the same expressive power as the well-established maximum entropy approach in combining arbitrary context features. Experiments on the google.com query stream show that using session-level and geo-location context we can expect reductions in perplexity of 34% relative over the Kneser-Ney N-gram baseline; when evaluating on the '"local" subset of the query stream, the relative reduction in PPL is 51% - more than a bit. Both sources of context information (geo-location, and previous queries in session) are about equally valuable in building a language model for the query stream.
Device Simulation for Evaluating Effects of Inplane Biaxial Mechanical Stress on n-Type Silicon Semiconductor Devices

This paper presents a practical method of drift-diffusion device simulation for evaluating the effects of mechanical stress on n-type silicon semiconductor devices. The device simulation incorporates an electron mobility model for considering the effects of stress. In this paper, we focus on stress effects that are induced by applying inplane biaxial stress to the devices. Therefore, two physical phenomena that are attributed to mechanical stress are modeled in the electron mobility model, i.e., the changes in relative population and the momentum relaxation time (intervalley scattering) of electrons in conduction-band valleys. Stress-induced variations of direct-current characteristics on n-type metal-oxide-semiconductor (MOS) field-effect transistors are evaluated using a device simulation including the proposed electron mobility model. Then, the electron mobility model and the simulation method are verified by comparing with experimental results. It is demonstrated that experimental results can be reasonably estimated using this device simulation method. From discussions regarding the electron mobility model, it is suggested that the comprehensive stress sensitivity of MOS devices is larger than that of lightly doped silicon.
Identification of Gene Networks Associated with Acute Myeloid Leukemia by Comparative Molecular Methylation and Expression Profiling

Around 80% of acute myeloid leukemia (AML) patients achieve a complete remission, however many will relapse and ultimately die of their disease. The association between karyotype and prognosis has been studied extensively and identified patient cohorts as having favourable [e.g. t(8; 21), inv (16)/t(16; 16), t(15; 17)], intermediate [e.g. cytogenetically normal (NK-AML)] or adverse risk [e.g. complex karyotypes]. Previous studies have shown that gene expression profiling signatures can classify the sub-types of AML, although few reports have shown a similar feature by using methylation markers. The global methylation patterns in 19 diagnostic AML samples were investigated using the Methylated CpG Island Amplification Microarray (MCAM) method and CpG island microarrays containing 12,000 CpG sites. The first analysis, comparing favourable and intermediate cytogenetic risk groups, revealed significantly differentially methylated CpG sites (594 CpG islands) between the two subgroups. Mutations in the NPM1 gene occur at a high frequency (40%) within the NK-AML subgroup and are associated with a more favourable prognosis in these patients. A second analysis comparing the NPM1 mutant and wild-type research study subjects again identified distinct methylation profiles between these two subgroups. Network and pathway analysis revealed possible molecular mechanisms associated with the different risk and/or mutation sub-groups. This may result in a better classification of the risk groups, improved monitoring targets, or the identification of novel molecular therapies.
Prognostic Significance of Activated AKT Expression in Soft-Tissue Sarcoma

Purpose: AKT is a serine/threonine kinase which is important in tumorigenesis. Several molecules involved in AKT pathway are dysregulated in various kinds of human cancers. Patients and Methods: Ninety-three patients (53 males and 40 females), ages ranging from 19 to 77 years (median, 57 years), with localized soft-tissue sarcomas arising in the trunk and extremities, were analyzed. Immunoperoxidase procedure (avidin-biotin complex method) was done on paraffin-embedded sections with anti–phosphorylated AKT (Thr308), anti–phosphorylated p44/42 extracellular signal–regulated kinase 1 and 2 (ERK1/2) (Thr202/Tyr204), anti–phosphorylated forkhead in rhabdomyosarcoma (FKHR) (Ser256), and anti-Ki 67 antibodies. Expression levels of phosphorylated AKT (p-AKT), phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated FKHR (p-FKHR) were categorized as either weaker (level 1) or equal to or stronger (level 2) compared with those in the endothelial cells of the same specimens. Percentage of cells showing intranuclear staining with Ki-67 was shown as the Ki-67 labeling index (LI). Cases were divided into two groups: level 1, Ki-67 LI < 20%; level 2, Ki-67 LI ≥ 20%. Results: Twenty-six (28.0%), 6 (6.5%), and 46 (44.1%) of the tumors showed level 2 expression for p-AKT, p-ERK1/2, and Ki-67 LI, respectively. Tumors with level 2 p-AKT expression showed a higher ratio of level 2 p-FKHR expression (P < 0.01). Multivariate analysis revealed p-AKT expression and Ki-67 LI to be independent prognosticators for overall survival, and p-AKT expression for disease-free survival. Conclusion: p-AKT expression level is a significant prognosticator in soft-tissue sarcoma.
Reconstruction of ancestral haplotypes in a 12-generation schizophrenia pedigree

We searched for candidate chromosomal regions inherited identical by descent in 19 patients suffering from schizophrenia or schizoaffective disorder that are related 12 generations back, to an ancestral couple born in the middle of the seventeenth century. To accomplish this goal, we constructed complete chromosomal haplotypes for each patient using genotype data from 450 markers. In total, 12 haplotype regions (with sizes ranging from 0.6 to 10.9 cM) constituted by three markers each were identical in three or more of the affected individuals. The largest genomic segment was located on 6q25, a region previously shown to be significantly more frequent in patients than controls, and proposed to contain a schizophrenia susceptibility locus. For the remaining 11 candidate haplotypes, we estimated haplotype frequencies from all the 43 affected members collected from the same family and 46 unrelated control individuals. This analysis indicated that at least four of the 11 candidate haplotypes are ancestral, since the frequencies were significantly higher in patients than in controls. Five additional haplotypes showed higher estimated frequencies in the patients but the differences were not significant. Interestingly, five of these 11 genomic regions are located in, or close to, candidate regions previously suggested to contain susceptibility genes for schizophrenia. The regions are 5q21-23, 8p21-22, 10p13-15, 13q12-13 and 22q12-13. Several of these haplotypes are probably ancestral linkage disequilibrium blocks inherited from the original couple. There exists, however, the possibility that one or more of these regions harbour schizophrenia susceptibility loci that may have epistatic interactions among them.
S-Adenosyl-Methionine and Betaine Improve Early Virological Response in Chronic Hepatitis C Patients with Previous Nonresponse

Background/Aims Treatment of chronic hepatitis C (CHC) with pegylated interferon α (pegIFNα) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFNα signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFNα signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFNα on HCV replicons. We have performed a clinical study with the aim to evaluate efficacy and safety of the addition of SAMe and betaine to treatment of CHC with pegIFNα/ribavirin. Methods In this open-label pilot study, 29 patients with CHC who failed previous therapy with (peg)IFNα/ribavirin were treated with SAMe, betaine, pegIFNα2b and ribavirin. Treatment duration was 6 or 12 months, depending on genotype, and the protocol comprised a stopping rule at week 12 if early virological response (EVR) was not achieved. Virological and biochemical response and safety were assessed throughout the treatment. Results 29 patients were enrolled and treated according to the study protocol. 79% of the patients were infected with genotype 1, 72% had advanced fibrosis, 76% had previously received pegIFNα/ribavirin, and only 14% achieved EVR to the previous treatment. When treated with the study medications, 17 patients (59%) showed an EVR, only 3 (10%) however achieved a sustained virological response (SVR). SAMe and betaine were found to be safe when used with pegIFNα/ribavirin. Conclusion The addition of SAMe and betaine to pegIFNα/ribavirin improves early virological response in CHC. Trial Registration ClinicalTrials.gov NCT00310336
Relative carcinogenic effectiveness of derivatives of nitrosodiethylamine in rats.

The carcinogenicity of five derivatives of nitrosodiethylamine was compared with that of the parent compound by p.o. administration to rats. All were less potent than was nitrosodiethylamine. When nitrosobis(2-methoxyethyl)amine and nitrosobis(2-ethoxyethyl)amine were administered at equimolar doses in drinking water, there was a high incidence of liver tumors, but the animals died later than they did after nitrosodiethylamine treatment, which also induced esophageal tumors. Nitrosoiminodipropionitrile and nitrosobis(2,2-diethoxyethyl)amine failed to induce tumors at the same dose level. Nitrosobis(2-chloroethyl)amine was administered in oil by gavage at a dose lower than that of nitrosodiethylamine and produced a much weaker tumor response; 5 of 15 treated rats had forestomach papillomas, and 1 had olfactory adenocarcinoma and no other induced tumors.
Growth Pattern Changes of Meningiomas: Long-term Analysis

OBJECTIVE:Although tumors are generally expected to grow exponentially, it is not known whether meningiomas retain a constant growth rate or not because of the lack of long-term follow-up. We analyzed the long-term growth pattern of meningiomas. METHODS:Twenty patients with a total of 31 meningiomas were radiologically followed for 4.1 to 18.3 years (median, 10.1 yr). Seven patients (including two neurofibromatosis cases) had incidental tumors. Another 13 patients with symptomatic tumors were followed after surgery. Their volumes were measured, and their time-volume curves were plotted. RESULTS:The growth curves of four atypical meningiomas fitted better to an exponential curve (R > 0.95). Two calcified tumors did not grow. Although the other benign tumors grew exponentially or linearly, their tumor volume doubling times in the initial phase were shorter than those in the later phase in most cases. Meningiomas without calcification tended to grow exponentially, whereas those with calcification were likely to reveal a linear growth pattern (P = 0.002, &khgr;2 test). This was supported by the observation that in two patients, the tumor growth pattern changed from exponential to linear and from linear to no growth with progression of calcification. CONCLUSION:Three growth patterns of meningiomas were demonstrated. Atypical meningiomas grew exponentially. Conversely, benign meningiomas revealed exponential, linear, or no growth. The growth pattern of the latter may change with the appearance of calcification.
Experiments in Finding Chinese and Japanese Answer Documents at NTCIR-7

We describe evaluation experiments conducted by submitting retrieval runs for the natural language Simplified Chinese, Traditional Chinese and Japanese questions of the Information Retrieval for Question Answering (IR4QA) Task of the Advanced Crosslingual Information Access (ACLIA) Task Cluster of the 7th NII Test Collection for IR Systems Workshop (NTCIR-7). In a sampling experiment, we found that, on average per topic, the percentage of answer documents assessed was less than 65% for Simplified Chinese, 32% for Traditional Chinese and 41% for Japanese. However, our preferred measure for this task, Generalized Success@10, only considers the rank of the first answer document retrieved for each topic, as one good document answering the question is all that a user needs for this task. We experimented with different techniques (words vs. n-grams, removing question words and blind feedback) and found that the choice of technique can have a substantial impact on the rank of the first answer document for particular questions. Keywords: Simplified Chinese, Traditional Chinese, Japanese, evaluation, robust retrieval, extreme topics, sampling.
Characterization of Covert Channels in DNS

Malware families utilize different protocols to establish their covert communication networks. It is also the case that sometimes they utilize protocols which are least expected to be used for transferring data, e.g., Domain Name System (DNS). Even though the DNS protocol is designed to be a translation service between domain names and IP addresses, it leaves some open doors to establish covert channels in DNS, which is widely known as DNS tunneling. In this paper, we characterize the malicious payload distribution channels in DNS. Our proposed solution characterizes these channels based on the DNS query and response messages patterns. We performed an extensive analysis of malware datasets for one year. Our experiments indicate that our system can successfully determine different patterns of the DNS traffic of malware families.
A comparison between microperimetry and standard achromatic perimetry of the central visual field in eyes with glaucomatous paracentral visual-field defects

Background and aims: The aim was to correlate retinal sensitivity as determined by scanning laser ophthalmoscope microperimetry (SLO-MP) in glaucomatous eyes with paracentral visual field (VF) defects detected by standard automated perimetry (SAP). Methods: Twenty eyes with glaucomatous optic neuropathy and an SAP VF defect involving the central 16 test points (at least one point with p<1% in the 24–2 VF) were enrolled. Eyes with diseases other than glaucoma were excluded. All patients underwent SLO-MP and SAP of the central 10°. Results from each eye were divided into four quadrants for analysis. Normal and abnormal quadrants by SAP were compared with the corresponding normal and abnormal quadrants by SLO-MP. Regression analysis was used to correlate the mean threshold values (dB) of SLO-MP and SAP in each quadrant. Macular optical coherence tomography (OCT) was performed when there was a disagreement between functional tests. Results: The mean age and VF mean deviation were 60.8 (13.4) years and −7.3 (6.1) dB, respectively. There was a significant correlation between SLO-MP and SAP results in all quadrants (r2⩾0.68, p<0.001). All abnormal SAP quadrants had a corresponding abnormal SLO-MP quadrant. However, 21% of the normal SAP quadrants had an abnormal corresponding microperimetry result; a corresponding significant reduction in total macular thickness measured by OCT was present in 75% of these quadrants. Conclusions: Macular sensitivity evaluated by SLO-MP correlates significantly with SAP paracentral VF defects. SLO-MP detected retinal sensitivity reduction in areas of OCT structural damage with normal SAP and suggests that subtle paracentral functional deficits may be present in many more eyes with established glaucoma than generally assumed.
An intelligent learning strategy for managing users' mobility in UMTS networks

Present generation mobile systems provide access to a wide range of services and enable mobile users to communicate regardless of their geographical location and their roaming characteristics. Due to the growing number of mobile users, global connectivity, and the small size of cells, one of the most critical issues regarding these networks is location management. In recent years, several strategies have been proposed to improve the performance of the location management procedure in UMTS networks. In this paper, we present a user pattern learning strategy (UPL) using scaled conjugate gradient (SCG) back propagation to reduce the location update signaling cost by increasing the intelligence of the location procedure in UMTS. This strategy associates to each user a list of cells where the user is likely to be with a given probability in each time interval. The implementation of this strategy has been subject to extensive tests. The results obtained confirm the efficiency of UPL in significantly reducing the costs of both location updates and call delivery procedures when compared to the UMTS standard and with other strategies well-known in the literature.
A Quest for a Framework to Improve Software Security : Vulnerability Black Markets Scenario

The discovery and management of software vulnerabilities after a product is released to the public is an important element of improving software quality and stability. The discovery of vulnerabilities enables exploitation and stimulates the development of patches or other protections, which in turn may or may not be deployed by product users. Various approaches have been developed to facilitate discovery and reduce vulnerabilities, including mechanisms for secret reporting, full-disclosure, responsible disclosure, and market-driven approaches. Our research focuses on the development of vulnerability black market which emerged as Internet-enabled communication among malicious hackers as a means to sell exploits and malware that take advantage of software flaws. The model in this paper draws on empirical observation on black markets and theories of market-based activity to generate a dynamic simulation model of vulnerability black market structure and behavior over time The model results suggest that efficient legal markets may attract malicious hackers to enter the legal markets and may reduce their likelihood to be involved in vulnerability black markets. We also find that adopting better patching management on the vendor side may mitigate the abuse of software vulnerabilities.
Effects of cluster galaxies on arc statistics

We present the results of a set of numerical simulations evaluating the effect of cluster galaxies on arc statistics. We perform a first set of gravitational lensing simulations using three independent projections for each of nine different galaxy clusters obtained from N-body simulations. The simulated clusters consist of dark matter only. We add a population of galaxies to each cluster, mimicking the observed luminosity function and the spatial galaxy distribution, and repeat the lensing simulations including the effects of cluster galaxies, which themselves act as individual lenses. Each galaxy is represented by a spherical Navarro, Frenk & White (1997) density profile. We consider the statistical distributions of the properties of the gravitational arcs produced by our clusters with and without galaxies. We find that the cluster galaxies do not introduce perturbations strong enough to significantly change the number of arcs and the distributions of lengths, widths, curvature radii and length-to-width ratios of long arcs. We find some changes to the distribution of short-arc properties in presence of cluster galaxies. The differences appear in the distribution of curvature radii for arc lengths smaller than 12 ′′ , while the distributions of lengths, widths and length-to-width ratios are significantly changed only for arcs shorter than 4 ′′ .
BlueSniff: Eve Meets Alice and Bluetooth

Much of Bluetooth's data remains confidential in practice due to the difficulty of eavesdropping it. We present mechanisms for doing so, therefore eliminating the data confidentiality properties of the protocol. As an additional security measure, devices often operate in "undiscoverable mode" in order to hide their identity and provide access control. We show how the full MAC address of such master devices can be obtained, therefore bypassing the access control of this feature. Our work results in the first open-source Bluetooth sniffer.
Safety assessment of immunomodulatory biologics: The promise and challenges of regulatory T-cell modulation

Regulatory T-cell (Treg) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with Treg modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from Treg modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting Treg and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with Treg modulation, but not all, suggesting a continued need to explore and validate predictive models.