Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I clinical trial of an allosteric AKT inhibitor, MK-2206, using a once weekly (QW) dose regimen in patients with advanced solid tumors.

3037^ Background: AKT is a key regulator of cellular proliferation, apoptosis and growth. A range of cancers have genetic aberrations that involve the PI3K/AKT pathway, leading to abnormal AKT hyperactivation and tumor progression. MK-2206 is a novel potent investigational AKT inhibitor, which was initially administered orally in a QOD schedule, where the maximum tolerated dose (MTD) was established at 60mg, based on safety and biomarker studies (Yap et al, ASCO 2010). In view of a long half-life (t1/2) (60-80h), a QW schedule was subsequently pursued to explore the potential of less frequent dosing to circumvent feedback activation of alternative signaling pathways in response to sustained and uninterrupted AKT inhibition. METHODS Eligible patients with advanced solid tumors were recruited in a phase I, multi-center, dose escalation study. Patients had regular safety assessments and blood sampling for pharmacokinetic (PK) studies. Pharmacodynamic (PD) and/or predictive biomarker analyses were undertaken on paired tumor samples (mandatory biopsies at MTD), platelet-rich plasma, hair follicles and circulating nucleic acids in plasma. RESULTS 30 patients (17 M; median age 60 yr; ECOG PS 0/1: 11/19) received MK-2206 at 90, 135, 200, 250 and 300 mg QW. Grade 3 rash was the dose limiting toxicity (DLT) at 300mg (n=3) and 250mg (n=2). Expansion of the 200mg QW resulted in grade 3 rash DLT in 4 of 15 patients. An intermediate dose of 150mg QW is being investigated. Common reversible MK-2206-related toxicities included rash (32.3%), fatigue (9.7%) and nausea, vomiting, diarrhea, pruritus, stomatitis, dry skin and dysguesia, each occurring at 6.5%. No MK-2206-related grade 5 toxicities were observed. PK analysis showed a median Tmax of 6 hr and a mean apparent terminal t1/2 of 78.6 hr. PD analysis of platelet-rich plasma at 200mg QW (n=9) showed suppression of pAKT up to 96 hours post-dose (p<0.001). Biomarker analyses of tumor samples are ongoing. CONCLUSIONS MK-2206 has shown an acceptable toxicology profile, significant and sustained AKT blockade and a PK-PD profile allowing for QW dosing.
Assessing different features for pose refinement

Describes results of using different features for the pose refinement of 3D objects i.e. find the best transformation between a 3D model and a 2D view of the object. This is a six degrees of freedom problem which is seen as essential to solve for 3D object recognition. Previous research has investigated various matching measure for pose refinement using edge points from the model and all edge pixels in the image, in the presence of noise and other objects. This paper extends the work to consider other features such as vertices and lines giving results to show the usefulness of each feature.
Wave propagation and scattering in random media

A volume in the IEEE/OUP Series on Electromagnetic Wave Theory Donald G. Dudley, Series Editor This IEEE Classic Reissue presents a unified introduction to the fundamental theories and applications of wave propagation and scattering in random media. Now for the first time, the two volumes of Wave Propagation and Scattering in Random Media previously published by Academic Press in 1978 are combined into one comprehensive volume. This book presents a clear picture of how waves interact with the atmosphere, terrain, ocean, turbulence, aerosols, rain, snow, biological tissues, composite material, and other media. The theories presented will enable you to solve a variety of problems relating to clutter, interference, imaging, object detection, and communication theory for various media. This book is expressly designed for engineers and scientists who have an interest in optical, microwave, or acoustic wave propagation and scattering. Topics covered include:
A scalable gaussian process analysis algorithm for biomass monitoring

Biomass monitoring is vital for studying the carbon cycle of earth's ecosystem and has several significant implications, especially in the context of understanding climate change and its impacts. Recently, several change detection methods have been proposed to identify land cover changes in temporal profiles (time series) of vegetation collected using remote sensing instruments, but do not satisfy one or both of the two requirements of the biomass monitoring problem, that is, operating in online mode and handling periodic time series. In this paper, we adapt Gaussian process (GP) regression to detect changes in such time series in an online fashion. While GP have been widely used as a kernel‐based learning method for regression and classification, their applicability to massive spatiotemporal data sets, such as remote sensing data, has been limited owing to the high computational costs involved. We focus on addressing the scalability issues associated with the proposed GP based change detection algorithm. This paper makes several significant contributions. First, we propose a GP based online time series change detection algorithm and demonstrate its effectiveness in detecting different types of changes in Normalized Difference Vegetation Index (NDVI) data obtained from a study area in IA, USA. Second, we propose an efficient Toeplitz matrix based solution which significantly improves the computational complexity and memory requirements of the proposed GP based method. Specifically, the proposed solution can analyze a time series of length t in O(t2) time while maintaining a O(t) memory footprint, compared to the O(t3) time and O(t2) memory requirement of standard matrix manipulation based methods. Third, we describe a parallel version of the proposed solution which can be used to simultaneously analyze a large number of time series. We study three different parallel implementations: using threads, Message Passing Interface (MPI), and a hybrid implementation using threads and MPI. Experimental results show that the hybrid implementation scales better than the multithreaded and MPI based implementations. The application of the proposed scalable algorithm is demonstrated in analyzing massive remote sensing observation data. The hybrid implementation, using 1536 computing cores, can analyze an NDVI data set for the Iowa study area in nearly 5 s, while a serial algorithm, using standard Cholesky decomposition based routines, takes several days to process the same data set. © 2011 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 4: 430–445, 2011
Using the polymerase chain reaction in detecting infectious agents.

REFERENCES Anders KH, Guerra WF, Tomiyasu U, et al: The neuropathology of AIDSUCLA experience and review. Am J Pathol 1986; 124:537-558 Koyanagi Y, Miles S, Mitsuyasu RT, et al: Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 1987; 236:819-822 Navia BA, Cho ES, Petito CK, et al: The AIDS dementia complex: II. Neuropathology. Ann Neurol 1986; 19:525-535 Navia BA, Jordan BD, Price RW: The AIDS dementia complex: I. Clinical features. Ann Neurol 1986; 19:517-524 Wiley CA, Schrier RD, Nelson JA, et al: Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 1986; 83:7089-7093
Evaluation of Iohexol Clearance to Estimate Glomerular Filtration Rate in Normal Horse Foals

In adult horses and foals, renal dysfunction can occur as a secondary complication to gastrointestinal disorders, dehydration, septicemia, endotoxemia and nephrotoxic drug administration. Measurement of renal function is an important feature not only in the diagnosis, but also in the prognosis and management of renal disease. Commonly used drugs such as phenylbutazone and gentamicin can be highly nephrotoxic under certain conditions. Of particular concern are those drugs, including the aminoglycoside antibiotics, that are eliminated almost exclusively by the kidney. Knowledge of a patients renal status prior to treatment would direct efforts at; 1) restoring kidney function prior to protracted therapy with potentially damaging drugs, 2) adjusting the dose of a life-saving drug based on the magnitude of dysfunction, or 3) selecting a drug that is not dependant on renal function for elimination. Estimation of the glomerular filtration rate (GFR), accepted as one of the earliest and most sensitive indicators of renal dysfunction, can be determined in horses using standard techniques
Extensive Host Sharing of Central European Tula Virus

ABSTRACT To examine the host association of Tula virus (TULV), a hantavirus present in large parts of Europe, we investigated a total of 791 rodents representing 469 Microtus arvalis and 322 Microtus agrestis animals from northeast, northwest, and southeast Germany, including geographical regions with sympatric occurrence of both vole species, for the presence of TULV infections. Based on serological investigation, reverse transcriptase PCR, and subsequent sequence analysis of partial small (S) and medium (M) segments, we herein show that TULV is carried not only by its commonly known host M. arvalis but also frequently by M. agrestis in different regions of Germany for a prolonged time period. At one trapping site, TULV was exclusively detected in M. agrestis, suggesting an isolated transmission cycle in this rodent reservoir separate from spillover infections of TULV-carrying M. arvalis. Phylogenetic analysis of the S and M segment sequences demonstrated geographical clustering of the TULV sequences irrespective of the host, M. arvalis or M. agrestis. The novel TULV lineages from northeast, northwest, and southeast Germany described here are clearly separated from each other and from other German, European, or Asian lineages, suggesting their stable geographical localization and fast sequence evolution. In conclusion, these results demonstrate that TULV represents a promiscuous hantavirus with a large panel of susceptible hosts. In addition, this may suggest an alternative evolution mode, other than a strict coevolution, for this virus in its Microtus hosts, which should be proven in further large-scale investigations on sympatric Microtus hosts.
Crossing the Boundary to East Asian: A Political Context Analysis of Female Labor Policy-Making in Taiwan

This study examines the political context in female labor poli cy domain of Taiwan. What state and pressure groups are deployed and negotiated to achieve their collective interests in the diverse levels of institutional in vestigations. The discussion combines the institutional system of structure and agency in a systematic discussion of the policymaking. At the national level, it is importan t to note that the relationship between dependency and distribution of resources may be structuralized; however, they are not permanently fixed in the policy events , which have to be understood in dynamic terms. Policy outcome is determined by the dynamic interaction between institutional structures and the behavior of policy actors. The resources of organizational actors and their reciprocal relation ships would be changed across the events in the diverse policy stages. Different forms of organizational interactions among the female organizational actors will mutuall y influence their choices, which affect the outcomes of labor events policy decision -making. Basing on the Gender Equality in Employment Act case study indicates the organizational involvements and
Mucosal Immunization of Rhesus Monkeys against Respiratory Syncytial Virus Subgroups A and B and Human Parainfluenza Virus Type 3 by Using a Live cDNA-Derived Vaccine Based on a Host Range-Attenuated Bovine Parainfluenza Virus Type 3 Vector Backbone

ABSTRACT Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide.
464XLAT: Combination of Stateful and Stateless Translation

This document describes an architecture (464XLAT) for providing limited IPv4 connectivity across an IPv6-only network by combining existing and well-known stateful protocol translation (as described in RFC 6146) in the core and stateless protocol translation (as described in RFC 6145) at the edge. 464XLAT is a simple and scalable technique to quickly deploy limited IPv4 access service to IPv6-only edge networks without encapsulation.
Psychologic stress, immunity, and cancer.

by Takayama et al. were initiated today. In light of the apparent lack of human relevance of the rodent data on saccharin carcinogenicity and the impracticality of longterm, large-scale studies involving nonhuman primates, in what direction should we be moving to revise our current methods for risk assessment? Two-year carcinogenicity bioassays in rodents may be relevant as long as positive findings do not result in knee-jerk extrapolations to humans before evidence is available that similar mechanisms are likely to be operative at human exposure levels. Bioassays in presumably more relevant species, i.e., nonhuman primates, are more expensive and impractical because, once again, one cannot use large enough numbers and because of public sensitivity to the use of animals, particularly primates. Neither of these choices is ideal; yet the need to adequately test for safety and efficacy remains compelling. More effort must be devoted to developing better methods of risk assessment, in essence a new paradigm possibly relying on extrapolation from mechanistic data from in vitro studies on human tissues as well as from tiered, mechanistic strategies in animals. Noninvasivein vivohuman studies, e.g., those designed to look at biomarkers, can also shed light on exposure and mechanisms of toxicity in humans. Better mechanistically based in vitro tests using cells and tissues from animals must also be designed and conducted side by side with in vitro tests on human tissues to ascertain interspecies variabilities early, before longterm expensive bioassays are conducted. The U.S. Food and Drug Administration has been very forward in its thinking and has established a Subcommittee on Toxicology as part of its Science Board to make recommendations on revising current animal testing strategies that address some of these concepts. Similarly, the National Institute of Environmental Health Sciences has taken the lead in the establishment of the Interagency Coordinating Committee on the Validation of Alternative Methods. One would hope that the time has come to identify our basic science needs and to apply these data to risk assessment.
Two distinct factors interact with the promoter regions of several liver‐specific genes.

A segment of the human alpha 1‐antitrypsin (alpha 1AT) 5′‐flanking region comprising nucleotides −137 to −37 from the start of transcription is sufficient to drive liver‐specific transcription from the homologous alpha 1AT promoter and from the heterologous SV40 promoter. In this paper we characterize two proteins, LF‐A1 and LF‐B1, whose ability to bind wild‐type and mutant alpha 1AT promoter segments correlates with the ability of these segments to activate transcription in vivo. DNase I protection and methylation interference analysis reveals that LF‐A1 recognizes sequences present in the regulatory region of the human alpha 1‐antitrypsin, apolipoprotein A1 and haptoglobin‐related genes. These sequences share a common 5′ TGG/A A/C CC 3′ motif. LF‐B1 binds to the palindrome 5′ TGGTTAAT/ATTCACCA 3′ which is present in the human alpha 1‐antitrypsin gene between positions −78 and −62 from the start of transcription. LF‐B1 also recognizes a related sequence present in the human albumin gene between −66 and −50. These results suggest that LF‐A1 and LF‐B1 are common positive trans‐acting factors which are required for the expression of several genes in the hepatocyte.
Genetic Markers of a Munc 13 Protein Family Member , BAIAP 3 , Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans

Anxiety disorders have high lifetime prevalence rates (1) and exhibit a remarkable comorbidity with substance use disorders (2–4). This association worsens treatment outcomes for both conditions (5) and represents a significant burden on individuals and society. Both anxiety disorders and substance use disorders are complex disorders that arise from a combination of genetic influence and environmental factors. To improve upon established treatment options, which include pharmacological as well as cognitive-behavioral therapies (6,7), a more detailed picture of the etiology of these disorders is instrumental. Estimates of heritability from twin and family studies are in the range of 20–40% across the different anxiety disorders (8,9) and in the range of 40–70% for the major substance use disorders (10). Recent studies point to the involvement of a large number of genes with relatively small effect sizes for both anxiety disorder (11,12) and substance use disorder (13–15). Although the interaction between anxiety disorders and substance use disorders is likely bidirec-
Modelling consequence relationships between two action, state or process Vietnamese sentences for improving the quality of new meaning-summarizing sentence

Purpose – The purpose of this paper is to enhance the quality of new reducing sentence in sentence-generation-based summarizing method by establishing consequence relationship between two action, state or process Vietnamese sentences. Design/methodology/approach – First, types of pairs of Vietnamese sentences based on presupposition about the consequence relationship is classified: the verb indicating action or state at the first sentence is considered as the consequence of the verb indicating action, state or process at the second sentence. Then main predicates in Discourse Representation Structure – a logical form which represents the semantic of a given pair of sentences – is analyzed and inner- and inter-sentential relationships are determined. The next step is to generate the syntactic structure of the new reducing sentence. Finally, a combination with the built set of lexicons is done to complete the new meaning-summarizing Vietnamese sentence. Findings – This method makes the new meaning-summarizin.
Optimal Feature Selection Technique for Mel Frequency Cepstral Coefficient Feature Extraction in Classifying Infant Cry with Asphyxia

Mel Frequency Cepstral Coefficient is an efficient feature representation method for extracting human-audible audio signals. However, its representation of features is large and redundant. Therefore, feature selection is required to select the optimal subset of Mel Frequency Cepstral Coefficient features. The performance of two types of feature selection techniques; Orthogonal Least Squares and F-ratio for selecting Mel Frequency Cepstral Coefficient features of infant cry with asphyxia was examined. OLS selects the feature subset based on their contribution to the reduction of error, while F-Ratio selects them according to their discriminative abilities. The feature selection techniques were combined with Multilayer Perceptron to distinguish between asphyxiated infant cry and normal cry signals. The performance of the feature selection methods was examined by analysing the Multilayer Perceptron classification accuracy resulted from the combination of the feature selection techniques and Multilayer Perceptron. The results indicate that Orthogonal Least Squares is the most suitable feature selection method in classifying infant cry with asphyxia since it produces the highest classification accuracy.
Phase diagram of URu 2 – x Fe x Si 2 in high magnetic fields

aDepartment of Physics, University of California, San Diego, La Jolla, CA 92093; bCenter for Advanced Nanoscience, University of California, San Diego, La Jolla, CA 92093; cMaterials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093; dNational High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32313; eNational High Magnetic Field Laboratory, Los Alamos National Laboratory, Los Alamos, NM 87545; and fDepartment of Physics, The Clarendon Laboratory, University of Oxford, Oxford OX1 2JD, United Kingdom
New constraints on dust grain size and distribution in CQ Tau

Grain growth in circumstellar disks is expected to be the first step towards the formation of planetary systems. There is now evidence for grain growth in several disks around young stars. Radially resolved images of grain growth in circumstellar disks are believed to be a powerful tool to constrain the dust evolution models and the initial stage for the formation of planets. In this paper we attempt to provide these constraints for the disk surrounding the young star CQ Tau. This system was already suggested from previous studies to host a population of grains grown to large sizes. We present new high angular resolution (0.3-0.9 arcsec) observations at wavelengths from 850um to 3.6cm obtained at the SMA, IRAM-PdBI and NRAO-VLA interferometers. We perform a combined analysis of the spectral energy distribution and of the high-resolution images at different wavelengths using a model to describe the dust thermal emission from the circumstellar disk. We include a prescription for the gas emission from the inner regions of the system. We detect the presence of evolved dust by constraining the disk averaged dust opacity coefficient beta (computed between 1.3 and 7mm) to be 0.6+/-0.1. This confirms the earlier suggestions that the disk contains dust grains grown to significant sizes and puts this on firmer grounds by tightly constraining the gas contamination to the observed fluxes at mm-cm wavelengths. We report some evidence of radial variations in dust properties, but current resolution and sensitivity are still too low for definitive results.