Miracle-dz/UniFAR-FTUs huggingface dataset:
Nasopharyngeal carcinoma: Significance of changes in epstein‐barr virus‐related antibody patterns following therapy

Sera were collected at intervals of 3 to 8 months over a 4‐ to 5‐year period from more than 103 patients with nasopharyngeal carcinomas (NPC) and examined for their spectra and titers of antibodies to Epstein‐Barr virus (EBV)‐related antigens. They were titrated for IgG, IgA and IgM antibodies to EB viral capsid antigen (VCA), for IgG and IgA antibodies to the D (diffuse) and R (restricted) components of the EBV‐determined early antigen (EA) complex, and for antibodies to the EBV‐associated nuclear antigen (EBNA). In the as yet untreated patients the incidences and titers of most of the antibodies increased with the stage of the disease; i.e., essentially with the total tumor burden. Such increases were observed in individual patients whose disease ultimately progressed to death, at times well in advance of the recognition of relapses or metastases. Increases were not noted or were only minor and delayed in some fatal cases if the tumor extended to the cranial cavity in the absence of significant involvement of cervical lymph nodes. In contrast, patients who responded well to therapy and remained clinically free of disease during the 4‐ or 5‐year observation period after, at most, early minor relapses, showed gradual, steady declines in the titers of all antibodies except anti‐EBNA. Thus, VCA‐specific IgA and D‐specific IgA and IgG became undetectable in time in many of the patients. In several long‐term survivors the declines were arrested at given levels or a reversal to increasing titers was noted which was followed in time by detection of a recurrent tumor or metastases in some cases, but not in others who remain under close observation. It would appear that serologic monitoring of NPC patients may warn of recurrent tumor activity well before it becomes clinically evident.
NeSC: Self-virtualizing nested storage controller

The emergence of high-speed, multi GB/s storage devices has shifted the performance bottleneck of storage virtualization to the software layers of the hypervisor. The hypervisor overheads can be avoided by allowing the virtual machine (VM) to directly access the storage device (a method known as direct device assignment), but this method voids all protection guarantees provided by filesystem permissions, since the device has no notion of client isolation. Recently, following the introduction of 10Gbs and higher networking interfaces, the PCIe specification was extended to include the SR-IOV specification for self-virtualizing devices, which allows a single physical device to present multiple virtual interfaces on the PCIe interconnect. Using SR-IOV, a hypervisor can directly assign a virtual PCIe device interface to each of its VMs. However, as networking interfaces simply multiplex packets sent from/to different clients, the specification does not dictate the semantics of a virtual storage device and how to maintain data isolation in a self-virtualizing device. In this paper we present the self-virtualizing, nested storage controller (NeSC) architecture, which includes a filesystem-agnostic protection mechanism that enables the physical device to export files as virtual PCIe storage devices. The protection mechanism maps file offsets to physical blocks and thereby offloads the hypervisor's storage layer functionality to hardware. Using NeSC, a hypervisor can securely expose its files as virtual PCIe devices and directly assign them to VMs. We have prototyped a 1GB/s NeSC controller using a Virtex-7 FPGA development board connected to the PCIe interconnect. Our evaluation of NeSC on a real system shows that NeSC virtual devices enable VMs to access their data with near-native performance (in terms of both throughput and latency).
Tracking Through Jamming Using Negative Information

Advances in characterizing the angle measurement covariance for phased array monopulse radar systems that use adaptive beamforming to null out a jammer source allow for the use of improved sensor models in tracking algorithms. Using a detection probability likelihood function consisting of a Gaussian sum that incorporates negative contact measurement information, four tracking systems are compared when used to track a maneuvering target passing into and through standoff jammer interference. Each tracker differs in how closely it replicates sensor performance in terms of accuracy of measurement covariance and the use of negative information. Only the tracker that uses both the negative contact information and corrected angle measurement covariance is able to consistently reacquire the target when it exits the jammer interference
Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia: A Systematic Review of Longitudinal 1H-MRS Studies

Schizophrenia is associated with brain glutamate dysfunction, but it is currently unclear whether antipsychotic administration can reduce the extent of glutamatergic abnormality. We conducted a systematic review of proton magnetic resonance spectroscopy (1H-MRS) studies examining the effects of antipsychotic treatment on brain glutamate levels in schizophrenia. The Medline database was searched to identify relevant articles published until December 2016. Inclusion required that studies examined longitudinal changes in brain glutamate metabolites in patients with schizophrenia before and after initiation of first antipsychotic treatment or a switch in antipsychotic treatment. The searches identified eight eligible articles, with baseline and follow-up measures in a total of 168 patients. The majority of articles reported a numerical reduction in brain glutamate metabolites with antipsychotic treatment, and the estimated overall mean reduction of 6.5% in Glx (the combined signal from glutamate and glutamine) across brain regions. Significant reductions in glutamate metabolites in at least one brain region were reported in four of the eight studies, and none of the studies reported a significant glutamatergic increase after antipsychotic administration. Relationships between the degree of change in glutamate and the degree of improvement in symptoms have been inconsistent but may provide limited evidence that antipsychotic response may be associated with lower glutamate levels before treatment and a greater extent of glutamatergic reduction during treatment. Further longitudinal, prospective studies of glutamate and antipsychotic response are required to confirm these findings.
UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy

Background Mutations in a novel gene, UBIAD1, were recently found to cause the autosomal dominant eye disease Schnyder corneal dystrophy (SCD). SCD is characterized by an abnormal deposition of cholesterol and phospholipids in the cornea resulting in progressive corneal opacification and visual loss. We characterized lesions in the UBIAD1 gene in new SCD families and examined protein homology, localization, and structure. Methodology/Principal Findings We characterized five novel mutations in the UBIAD1 gene in ten SCD families, including a first SCD family of Native American ethnicity. Examination of protein homology revealed that SCD altered amino acids which were highly conserved across species. Cell lines were established from patients including keratocytes obtained after corneal transplant surgery and lymphoblastoid cell lines from Epstein-Barr virus immortalized peripheral blood mononuclear cells. These were used to determine the subcellular localization of mutant and wild type protein, and to examine cholesterol metabolite ratios. Immunohistochemistry using antibodies specific for UBIAD1 protein in keratocytes revealed that both wild type and N102S protein were localized sub-cellularly to mitochondria. Analysis of cholesterol metabolites in patient cell line extracts showed no significant alteration in the presence of mutant protein indicating a potentially novel function of the UBIAD1 protein in cholesterol biochemistry. Molecular modeling was used to develop a model of human UBIAD1 protein in a membrane and revealed potentially critical roles for amino acids mutated in SCD. Potential primary and secondary substrate binding sites were identified and docking simulations indicated likely substrates including prenyl and phenolic molecules. Conclusions/Significance Accumulating evidence from the SCD familial mutation spectrum, protein homology across species, and molecular modeling suggest that protein function is likely down-regulated by SCD mutations. Mitochondrial UBIAD1 protein appears to have a highly conserved function that, at least in humans, is involved in cholesterol metabolism in a novel manner.
Exertional Heat Stroke: New Concepts Regarding Cause and Care

Abstract When athletes, warfighters, and laborers perform intense exercise in the heat, the risk of exertional heat stroke (EHS) is ever present. The recent data regarding the fatalities due to EHS within the confines of organized American sport are not promising: during the past 35 years, the highest number of deaths in a 5-year period occurred from 2005 to 2009. This reminds us that, regardless of the advancements of knowledge in the area of EHS prevention, recognition, and treatment, knowledge has not been translated into practice. This article addresses important issues related to EHS cause and care. We focus on the predisposing factors, errors in care, physiology of cold water immersion, and return-to-play or duty considerations.
Regioselective Hydroxylation of Omeprazole Enantiomers by Bacterial CYP102A1 Mutants

A large set of Bacillus megaterium CYP102A1 mutants are known to metabolize various drugs to form human metabolites. Omeprazole (OMP), a proton pump inhibitor, has been widely used as an acid inhibitory agent for the treatment of gastric acid hypersecretion disorders. It is primarily metabolized by human CYP2C19 and CYP3A4 to 5′-OH OMP and a sulfone product, respectively. It was recently reported that several CYP102A1 mutants can oxidize racemic and S-OMP to 5′-OH OMP and that these mutants can further oxidize 5′-OH racemic OMP to 5′-COOH OMP. Here, we report that the S- and R-enantiomers of OMP are hydroxylated by 26 mutants of CYP102A1 to produce 1 major metabolite (5′-OH OMP) regardless of the chirality of the parent substrates. Although the binding of R-OMP to the CYP102A1 active site caused a more apparent change of heme environment compared with binding of S-OMP, there was no correlation between the spectral change upon substrate binding and catalytic activity of either enantiomer. The 5′-OH OMP produced from racemic, S-, and R-OMP could be obtained with a high conversion rate and high selectivity when the triple R47L/F87V/L188Q mutant was used. These results suggest that bacterial CYP102A1 mutants can be used to produce the human metabolite 5′-OH OMP from both the S- and R-enantiomers of OMP.
A Spatial Analysis of Crime for the City of Omaha

Haifeng Zhang, M,A. University of Nebraska, 2002 Advisor: Dr. Michael P. Peterson The spatial patterns of four types of crimes (assault, robbery, auto-theft, and burglary) and their relationships with the selected socio-economic characteristics for the City of Omaha, Nebraska, were examined in this research. The crime data were based on the 2000 police reported crime and the socio-economic data were extracted from the 1997 American Community Survey and land use data from the 2000 Omaha parcel file. The location quotients of crimes (LQCs) were used to measure the relative specialization and structure of crimes for each census tract, and as the dependent variables for the statistical analysis. GIS techniques such as geocoding, spatial aggregation, and spatial analysis were used for crime mapping and crime analysis. Factor analysis and multiple regression models were employed to reveal the crime-causation relationships. Major findings of this research include: (1) LQCs highlight the specialization of crime and can be effectively used for GIS-based visualization and statistical analysis of crime; (2) the North Omaha and the downtown areas (high-crime districts) have relatively higher occurrences of violent crime and diversified structure of crimes while west Omaha (low crime districts) has a relatively specialized crime structure that is dominated by property crimes; (3) a modest proportion of the variance of crimes can be significantly explained by the statistical models.
The effects of auditory-visual vowel identification training on speech recognition under difficult listening conditions.

PURPOSE The effective use of visual cues to speech provides benefit for adults with normal hearing in noisy environments and for adults with hearing loss in everyday communication. The purpose of this study was to examine the effects of a computer-based, auditory-visual vowel identification training program on sentence recognition under difficult listening conditions. METHOD Normal-hearing adults were trained and tested under auditory-visual conditions, in noise designed to simulate the effects of a hearing loss. After initial tests of vowel, word, and sentence recognition, 1 group of participants received training on identification of 10 American English vowels in CVC context. Another group of participants received no training. All participants were then retested on vowel, word, and sentence recognition. RESULTS Improvements were seen for trained compared with untrained participants, in auditory-visual speech recognition under difficult listening conditions, for vowels in monosyllables and key words in sentences. CONCLUSIONS Results from this study suggest benefit may be gained from this computer-based, auditory-visual vowel identification training method.
Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.
A New Framework for Credit Card Transactions Involving Mutual Authentication between Cardholder and Merchant

Electronic Commerce (e-Commerce) and ease in the onsite transactions have led to the exponential growth in the acceptance of credit cards among consumers of all the sections. But despite their remarkable advantages, consumers are still reluctant in their use, especially for online transactions and reason being the increasing credit card fraud rate. A number of security models have been proposed and deployed for secure online transactions but the sharing of sensitive credit card data over the Internet has made online transactions vulnerable to threats. In this paper, we discuss and analyze the current developments in online authentication procedures including biometrics, one-time-password systems and use of mobile device and Public Switched Telephone Network for cardholder authentication. Then we propose a complete new framework for both onsite and online (Internet shopping) credit card transactions. This framework is more secure, robust, enhances user privacy and does not involve the deployment of special hardware systems at the customer's site.
Comparison of Peripheral and Portal (Via the Umbilical Vein) Routes of Insulin Infusion in IDDM Patients

Twelve subjects with insulin-dependent diabetes mellitus were treated using continuous subcutaneous insulin infusion (CSII) and intraportal insulin infusion (IPII) via the umbilical vein for 4 mo. Glucose control improved in both CSII and IPII groups, but a decrease in glucose and HbA1c was more rapid and more significant in the IPII group than in CSII, even though insulin requirement was lower during IPII than CSII (40 ± 2 vs. 50 ± 2 U/day, P < 0.05). The insulin plasma fasting levels were different (88 ± 10.7 in the IPII group vs. 263 ± 23 pM in CSII, P < 0.001). High plasma levels of lactate, pyruvate, alanine, cortisol, and growth hormone were decreased in both groups, with their full normalization only in the IPII group. Glucagon concentrations were low in both groups at the beginning of the study (30.0 ± 4.1 in the CSII group and 32.3 ± 1.8 ng/L in IPII); they were equalized to control values in the IPII group and were low in the CSII group at the study's end (46.0 ± 3.7 in IPII vs. 31.7 ± 3.1 ng/L in CSII, P < 0.05. We conclude that intraportal administration of insulin via the umbilical vein at rates of 0.01–0.05 U · kg−1 hr−1 reduces plasma levels of glucose, three carbon precursors, cortisol, and growth hormone by a direct action on the liver, and the hepatic action of peripherally administered insulin is manifested only when the infusion rate is increased to 0.1–0.3 U · kg−1 · hr−1. Thus the intraportal route via the umbilical vein may offer improved physiological insulin delivery over the subcutaneous route.
A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma

ONC201 is an oral, small molecule selective antagonist of the G protein-coupled receptor DRD2 that causes p53-independent apoptosis in tumor cells via integrated stress response activation and Akt/ERK inactivation. We performed a Phase II study that enrolled 17 patients with recurrent, bevacizumab-naïve, IDH1/2 WT glioblastoma who received 625mg ONC201 every three weeks. Median OS was 41.6 weeks with OS6 of 71% and OS9 of 53%. Seven of 17 patients are alive. PFS6 was 11.8% with two patients remaining on study who continue to receive ONC201 for >12 months. One of these patients had a durable objective response with a secondary glioblastoma possessing a H3.3 K27M mutation, exhibiting regression by 85% in one lesion and 76% in the second lesion. The second patient who continues to receive ONC201 for >12 months remains disease-free after enrolling on this trial following a re-resection. No drug-related SAEs or treatment discontinuation due to toxicity occurred. Plasma PK at 2 hours post-dose was 2.6 ug/mL, serum prolactin induction was observed as a surrogate marker of target engagement, and DRD2 was expressed in all evaluated archival tumor specimens. In summary, ONC201 is well tolerated and may have single agent activity in recurrent glioblastoma patients.
A Cost-Minimization Analysis of Tissue-Engineered Constructs for Corneal Endothelial Transplantation

Corneal endothelial transplantation or endothelial keratoplasty has become the preferred choice of transplantation for patients with corneal blindness due to endothelial dysfunction. Currently, there is a worldwide shortage of transplantable tissue, and demand is expected to increase further with aging populations. Tissue-engineered alternatives are being developed, and are likely to be available soon. However, the cost of these constructs may impair their widespread use. A cost-minimization analysis comparing tissue-engineered constructs to donor tissue procured from eye banks for endothelial keratoplasty was performed. Both initial investment costs and recurring costs were considered in the analysis to arrive at a final tissue cost per transplant. The clinical outcomes of endothelial keratoplasty with tissue-engineered constructs and with donor tissue procured from eye banks were assumed to be equivalent. One-way and probabilistic sensitivity analyses were performed to simulate various possible scenarios, and to determine the robustness of the results. A tissue engineering strategy was cheaper in both investment cost and recurring cost. Tissue-engineered constructs for endothelial keratoplasty could be produced at a cost of US$880 per transplant. In contrast, utilizing donor tissue procured from eye banks for endothelial keratoplasty required US$3,710 per transplant. Sensitivity analyses performed further support the results of this cost-minimization analysis across a wide range of possible scenarios. The use of tissue-engineered constructs for endothelial keratoplasty could potentially increase the supply of transplantable tissue and bring the costs of corneal endothelial transplantation down, making this intervention accessible to a larger group of patients. Tissue-engineering strategies for corneal epithelial constructs or other tissue types, such as pancreatic islet cells, should also be subject to similar pharmacoeconomic analyses.
Specification of the NF-κB transcriptional response by p65 phosphorylation and TNF-induced nuclear translocation of IKKε

Here we investigated the regulation of NF-κB activity by post-translational modifications upon reconstitution of NF-κB p65-deficient cells with the wild-type protein or phosphorylation-defect mutants. Analysis of NF-κB target gene expression showed that p65 phosphorylations alone or in combination function to direct transcription in a highly target gene-specific fashion, a finding discussed here as the NF-κB barcode hypothesis. High-resolution microscopy and surface rendering revealed serine 536 phosphorylated p65 predominantly in the cytosol, while serine 468 phosphorylated p65 mainly localized in nuclear speckles. TNF stimulation resulted in the translocation of the cytosolic p65 kinase IKKε to the nucleus and also to promyelocytic leukemia (PML) nuclear bodies. This inducible IKKε translocation was dependent on p65 phosphorylation and was prevented by the oncogenic PML-RARα fusion protein. Chromatin immunoprecipitation experiments revealed the inducible association of IKKε to the control regions of several NF-κB target genes. In the nucleus, the kinase contributes to the expression of a subset of NF-κB-regulated genes, thus revealing a novel role of IKKε for the control of nuclear NF-κB activity.
Peopled online virtual worlds: a new home for cooperating communities, a new frontier for interaction design (panel)

Multi-user virtual worlds are proliferating on the Internet. These are two and three dimensional graphical environments inhabited by users represented as digital actors called “avatars”. Through this new medium for cooperating communities, a wide variety of Internet users are participating in a large scale social experiment and collaborating on a variety of projects. The inhabited virtual world is an exciting new medium for HCI professionals including interaction and graphic designers, and educators and researchers focused on distance learning and teleworking. It also appeals to children and ordinary users of the Internet as a vast new digital playground and a venue for personal expression. This panel will present a brief overview the inhabited virtual world medium and then discuss its merits and limitations as a medium for cooperating communities and interaction design.