Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of the Repaglinide Concentration Increase Produced by Gemfibrozil and Itraconazole Based on the Inhibition of the Hepatic Uptake Transporter and Metabolic Enzymes

The plasma concentration of repaglinide is reported to increase greatly when given after repeated oral administration of itraconazole and gemfibrozil. The present study analyzed this interaction based on a physiologically based pharmacokinetic (PBPK) model incorporating inhibition of the hepatic uptake transporter and metabolic enzymes involved in repaglinide disposition. Firstly, the plasma concentration profiles of inhibitors (itraconazole, gemfibrozil, and gemfibrozil glucuronide) were reproduced by a PBPK model to obtain their pharmacokinetic parameters. The plasma concentration profiles of repaglinide were then analyzed by a PBPK model, together with those of the inhibitors, assuming a competitive inhibition of CYP3A4 by itraconazole, mechanism-based inhibition of CYP2C8 by gemfibrozil glucuronide, and inhibition of organic anion transporting polypeptide (OATP) 1B1 by gemfibrozil and its glucuronide. The plasma concentration profiles of repaglinide were well reproduced by the PBPK model based on the above assumptions, and the optimized values for the inhibition constants (0.0676 nM for itraconazole against CYP3A4; 14.2 μM for gemfibrozil against OATP1B1; and 5.48 μM for gemfibrozil glucuronide against OATP1B1) and the fraction of repaglinide metabolized by CYP2C8 (0.801) were consistent with the reported values. The validity of the obtained parameters was further confirmed by sensitivity analyses and by reproducing the repaglinide concentration increase produced by concomitant gemfibrozil administration at various timings/doses. The present findings suggested that the reported concentration increase of repaglinide, suggestive of synergistic effects of the coadministered inhibitors, can be quantitatively explained by the simultaneous inhibition of the multiple clearance pathways of repaglinide.
Morphometric analysis of the corpus callosum using MR: correlation of measurements with aging in healthy individuals.

PURPOSE To analyze changes of the human corpus callosum and MR midsagittal brain structures during normal aging. METHODS A morphometric evaluation strategy for quantification of these brain structures on MR scans was developed. This computerized measuring program did allow the acquisition of more than 100 one- and two-dimensional parameters. RESULTS During normal aging, the anterior parts of the corpus callosum (genu and anterior parts of the trunk) were significantly decreased, suggesting alterations of frontal and temporal interhemispheric fiber systems. Further changes were seen in callosal thickness and callosal width of the anterior parts of the corpus callosum. The profile area of the telencephalon was significantly reduced during normal aging. The size of the mesencephalon showed age-specific changes. CONCLUSIONS The proposed computer program proved to be a powerful and reliable tool to get objective and reproducible quantitative data of corpus callosum and midsagittal brain structures. Specific age changes were found in the corpus callosum, indicating alteration of the frontotemporal interhemispheric fiber systems.
Pose estimation of an uncooperative spacecraft from actual space imagery

This paper addresses the preliminary design of a spaceborne monocular vision-based navigation system for on-orbit-servicing and formation-flying applications. The aim is to estimate the pose of a passive space resident object using its known three-dimensional model and single low-resolution two-dimensional images collected on-board the active spacecraft. In contrast to previous work, no supportive means are available on the target satellite (e.g., light emitting diodes) and no a-priori knowledge of the relative position and attitude is available (i.e., lost-in-space scenario). Three fundamental mechanisms – perceptual organisation, true perspective projection, and random sample consensus – are exploited to overcome the limitations of monocular passive optical navigation in space. The preliminary design is conducted and validated making use of actual images collected in the frame of the PRISMA mission at about 700 km altitude and 10 m inter-spacecraft separation.
Brucella TIR Domain-containing Protein Mimics Properties of the Toll-like Receptor Adaptor Protein TIRAP*

Toll-like receptors (TLRs) play essential roles in the activation of innate immune responses against microbial infections. TLRs and downstream adaptor molecules contain a conserved cytoplasmic TIR domain. TIRAP is a TIR domain-containing adaptor protein that recruits the signaling adaptor MyD88 to a subset of TLRs. Many pathogenic microorganisms subvert TLR signaling pathways to suppress host immune responses to benefit their survival and persistence. Brucella encodes a TIR domain-containing protein (TcpB) that inhibits TLR2- and TLR4-mediated NF-κB activation. Sequence analysis indicated a moderate level of similarity between TcpB and the TLR adaptor molecule TIRAP. We found that TcpB could efficiently block TIRAP-induced NF-κB activation. Subsequent studies revealed that by analogy to TIRAP, TcpB interacts with phosphoinositides through its N-terminal domain and colocalizes with the plasma membrane and components of the cytoskeleton. Our findings suggest that TcpB targets the TIRAP-mediated pathway to subvert TLR signaling. In vivo mouse studies indicated that TcpB-deficient Brucella is defective in systemic spread at the early stages of infection.
Midostaurin in Advanced Systemic Mastocytosis.

The use of midostaurin, a multikinase inhibitor, has been associated with a response in 60% of patients with systemic mastocytosis, including mast-cell leukemia; the median overall survival was 28 months. A second, smaller trial in France showed a 71% response rate.
Clinical outcome of 251 patients with extrahepatic metastasis at initial diagnosis of hepatocellular carcinoma: Does transarterial chemoembolization improve survival in these patients?

Background and Aims: The therapeutic efficacy of transarterial chemoembolization (TACE) has not been evaluated in hepatocellular carcinoma (HCC) patients with extrahepatic metastasis. We investigated the efficacy of TACE with/without systemic chemotherapy (s‐chemo) in these patients.
Analysis of Discrete-Time MIMO OFDM-Based Orthogonal Time Frequency Space Modulation

Orthogonal Time Frequency Space (OTFS) is a novel modulation scheme designed in the Doppler-delay domain to fully exploit time and frequency diversity of general time-varying channels. In this paper, we present a novel discrete-time analysis of OFDM-based OTFS transceiver with a concise and vectorized input-output relationship that clearly characterizes the contribution of each underlying signal processing block in such systems. When adopting cyclic prefix in the time domain, our analysis reveals that the proposed MIMO OTFS and OFDM systems have the same ergodic capacity despite the well-known fact that the former has great advantages in low-complexity receiver design for high Doppler channels. The proposed discrete-time vectorized formulation is applicable to general fast fading channels with arbitrary window functions. It also enables practical low-complexity receiver design for which such a concise formulation of the input-output relationship is of great benefits.
Developing a framework for risk-based surveillance of tuberculosis in cattle: a case study of its application in Scotland

SUMMARY Due to its substantially lower prevalence of bovine tuberculosis (bTB) relative to other areas of Great Britain, Scotland was designated as an officially (bovine) TB-free region in 2009. This paper investigates resultant possibilities for reducing surveillance by developing risk-based alternatives to current 4-year testing of eligible herds. A model of freedom of infection was used to develop strategies that specifically tested herds that are at risk of infection but would probably not be identified by slaughterhouse meat inspection. The performance of current testing is mimicked by testing all herds that slaughter fewer than 25% of their total stock per year and regularly import animals from high-incidence areas of England and Wales or from Ireland. This system offers a cost reduction by requiring 25% fewer herd and animal tests and 25% fewer false positives.
Unitary Precoders for ST-OFDM Systems Using Alamouti STBC

This paper studies unitary precoders for space-time coded orthogonal frequency division multiplexing (ST-OFDM) systems using Alamouti space-time block codes (STBC). We consider two channel models: (1) the LTI case where the channels are invariant for two consecutive OFDM blocks; (2) the time-varying case where the channels are invariant within one OFDM block but they vary slightly between two OFDM blocks. For the LTI case, we derive the optimal precoder for QPSK modulation. It is shown that the optimal precoder is channel independent and can greatly enhance the performance of the ST-OFDM system. For the time-varying case, the channel variation will cause inter-carrier interference (ICI) in the ST-OFDM system and can result in serious performance degradation. We will show that by properly designing the precoder, we can average the output error variance and hence greatly alleviate the ICI effect. As a result, the bit error rate (BER) performance can be significantly improved.
Management of cancer of the prostate.

Prostate cancer is the second leading cause of death from cancer among men; 25 percent of men with prostate cancer die of the disease1. Moreover, many patients who do not die of prostate cancer require treatment to ameliorate symptoms such as pain, bleeding, and urinary obstruction. Thus, prostate cancer is also a major cause of suffering and of health care expenditures. The high rate of mortality from prostate cancer may be due to late detection. In recent studies, screening for prostate cancer has combined the measurement of serum prostate-specific antigen (PSA) -- the most accurate single test for the .
Generation of Bovine Respiratory Syncytial Virus (BRSV) from cDNA: BRSV NS2 Is Not Essential for Virus Replication in Tissue Culture, and the Human RSV Leader Region Acts as a Functional BRSV Genome Promoter

ABSTRACT In order to generate recombinant bovine respiratory syncytial virus (BRSV), the genome of BRSV strain A51908, variant ATue51908, was cloned as cDNA. We provide here the sequence of the BRSV genome ends and of the entire L gene. This completes the sequence of the BRSV genome, which comprises a total of 15,140 nucleotides. To establish a vaccinia virus-free recovery system, a BHK-derived cell line stably expressing T7 RNA polymerase was generated (BSR T7/5). Recombinant BRSV was reproducibly recovered from cDNA constructs after T7 RNA polymerase-driven expression of antigenome sense RNA and of BRSV N, P, M2, and L proteins from transfected plasmids. Chimeric viruses in which the BRSV leader region was replaced by the human respiratory syncytial virus (HRSV) leader region replicated in cell culture as efficiently as their nonchimeric counterparts, demonstrating that allcis-acting sequences of the HRSV promoter are faithfully recognized by the BRSV polymerase complex. In addition, we report the successful recovery of a BRSV mutant lacking the complete NS2 gene, which encodes a nonstructural protein of unknown function. The NS2-deficient BRSV replicated autonomously and could be passaged, demonstrating that NS2 is not essential for virus replication in cell culture. However, growth of the mutant was considerably slower than and final infectious titers were reduced by a factor of at least 10 compared to wild-type BRSV, indicating that NS2 provides a supporting factor required for full replication capacity.
7,8-dihydroxyflavone ameliorates scopolamine-induced Alzheimer-like pathologic dysfunction.

Scopolamine (Sco) can induce amyloid β (Aβ) deposition, oxidative stress, synaptic dysfunction, and learning/memory impairment as observed in Alzheimer's disease (AD), the most common form of dementia affecting more than 25 million elderly people worldwide. Herein we explored the protective effect of 7,8-dihydroxyflavone (7,8-DHF) on Sco-induced Aβ deposition, oxidative stress, synaptic dysfunction, and learning/memory defects. Rats were randomly divided into four groups (n=12 for each group). The control group received normal saline (NS); the Sco group received Sco (1 mg/kg per day) intraperitoneally (i.p.) for 2 weeks. Mice in the Sco+7,8-DHF group received 1 mg/kg per day 7,8-DHF i.p. for 2 weeks, followed by Sco (1 mg/kg per day)+1 mg/kg per day 7,8-DHF (i.p.) for another 2 weeks. The 7,8-DHF group received 1 mg/kg per day 7,8-DHF (i.p.) for 4 weeks. Results showed that the supplement of 7,8-DHF significantly reversed Aβ deposition, oxidative stress, synaptic dysfunction, and cognitive defects. Our data suggest that 7,8-DHF might serve as a promising therapeutic candidate for attenuating Sco-induced AD-like pathological dysfuntion.
Running title : AQ resistant malaria in Afghanistan

Amodiaquine resistance in Plasmodium falciparum malaria is associated with 1 the pfcrt 72-76 SVMNT allele in Afghanistan 2 3 Khalid Beshir, Colin J. Sutherland, Ioannis Merinopoulos, Naeem Durrani, 4 Toby Leslie, Mark Rowland, Rachel L. Hallett * 5 6 Department of Infectious and Tropical Diseases, London School of Hygiene & 7 Tropical Medicine, London, UK. 8 Merlin International, House 3, Street 55-A, F6/4 Islamabad, Pakistan. 9 10 11 Running title: AQ resistant malaria in Afghanistan 12 13 14 15 16 17 *Author for correspondence: 18 Dr Rachel L. Hallett, Department of Infectious and Tropical Diseases, London School 19 of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United 20 Kingdom. 21 Tel: +44 (0)20 7927 2338 22 Fax: +44 (0)20 7636 8739 23 Email: Rachel.Hallett@lshtm.ac. uk 24 25 Copyright © 2010, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved. Antimicrob. Agents Chemother. doi:10.1128/AAC.00358-10 AAC Accepts, published online ahead of print on 14 June 2010
Design of low-noise CMOS MEMS accelerometer with techniques for thermal stability and stable DC biasing

An integrated high-sensitivity CMOS MEMS capacitive accelerometer with thermal stability has been designed and demonstrated in this work. Issue of obtaining stable DC bias at input terminals is particularly addressed. Sensitivity of 595 mV/g is achieved in the accelerometer and the overall noise floor is 50 µg/√Hz, which corresponds to an effective capacitance noise floor of 0.024 aF/√Hz. The zero-g thermal variation is as low as 1.68 mg/°C.
In Vivo MR Imaging of Intraarterially Delivered Magnetically Labeled Mesenchymal Stem Cells in a Canine Stroke Model

Background This study aimed to evaluate the feasibility of intraarterial (IA) delivery and in vivo MR imaging of superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in a canine stroke model. Methodology MSCs harvested from beagles’ bone marrow were labeled with home-synthesized SPIO. Adult beagle dogs (n = 12) were subjected to left proximal middle cerebral artery (MCA) occlusion by autologous thrombus, followed by two-hour left internal carotid artery (ICA) occlusion with 5 French vertebral catheter. One week later, dogs were classified as three groups before transplantation: group A: complete MCA recanalization, group B: incomplete MCA recanalization, group C: no MCA recanalization. 3×106 labeled-MSCs were delivered through left ICA. Series in vivo MRI images were obtained before cell grafting, one and 24 hours after transplantation and weekly thereafter until four weeks. MRI findings were compared with histological studies at the time point of 24 hours and four weeks. Principal Findings Home-synthesized SPIO was useful to label MSCs without cell viability compromise. MSCs scattered widely in the left cerebral hemisphere in group A, while fewer grafted cells were observed in group B and no cell was detected in group C at one hour after transplantation. A larger infarction on the day of cell transplantation was associated with more grafted cells in the brain. Grafted MSCs could be tracked effectively by MRI within four weeks and were found in peri-infarction area by Prussian blue staining. Conclusion It is feasible of IA MSCs transplantation in a canine stroke model. Both the ipsilateral MCA condition and infarction volume before transplantation may affect the amount of grafted cells in target brain. In vivo MR imaging is useful for tracking IA delivered MSCs after SPIO labeling.
Crying Wolf: An Empirical Study of SSL Warning Effectiveness

Web users are shown an invalid certificate warning when their browser cannot validate the identity of the websites they are visiting. While these warnings often appear in benign situations, they can also signal a man-in-the-middle attack. We conducted a survey of over 400 Internet users to examine their reactions to and understanding of current SSL warnings. We then designed two new warnings using warnings science principles and lessons learned from the survey. We evaluated warnings used in three popular web browsers and our two warnings in a 100- participant, between-subjects laboratory study. Our warnings performed significantly better than existing warnings, but far too many participants exhibited dangerous behavior in all warning conditions. Our results suggest that, while warnings can be improved, a better approach may be to minimize the use of SSL warnings altogether by blocking users from making unsafe connections and eliminating warnings in benign situations.
mTOR: a link from the extracellular milieu to transcriptional regulation of oligodendrocyte development

Oligodendrocyte development is controlled by numerous extracellular signals that regulate a series of transcription factors that promote the differentiation of oligodendrocyte progenitor cells to myelinating cells in the central nervous system. A major element of this regulatory system that has only recently been studied is the intracellular signalling from surface receptors to transcription factors to down-regulate inhibitors and up-regulate inducers of oligodendrocyte differentiation and myelination. The current review focuses on one such pathway: the mTOR (mammalian target of rapamycin) pathway, which integrates signals in many cell systems and induces cell responses including cell proliferation and cell differentiation. This review describes the known functions of mTOR as they relate to oligodendrocyte development, and its recently discovered impact on oligodendrocyte differentiation and myelination. A potential model for its role in oligodendrocyte development is proposed.
Ethnic and sex differences in suicide rates relative to major depression in the United States.

OBJECTIVE Suicide rates differ between ethnic groups in the United States. Since suicide is commonly associated with a mood disorder, the authors compared suicide rates relative to depression rates in five ethnic groups in the United States. METHOD Rates of major depression were generated from the Epidemiologic Catchment Area study and the Hispanic Health and Nutrition Epidemiologic Survey. Sociodemographic effects were determined by examining depression rates for respondents who were separated or divorced, earning low incomes, or not working for pay. The survey data were analyzed with age and sex standardization to generate 1-year prevalence rates of major depression. The depression rates of the different ethnic groups were compared and were examined in relation to suicide rates. RESULTS The 1-year prevalence rates of major depression were 3.6% for whites, 3.5% for blacks, 2.8% for Mexican Americans, 2.5% for Cuban Americans, and 6.9% for Puerto Ricans. Compared to the rate for whites, the rate of depression was significantly higher in Puerto Ricans and significantly lower in Mexican Americans. Relative to the depression rates, the annual suicide rates were higher for males than for females. Mexican American and Puerto Rican males had lower relative suicide rates than white males. CONCLUSIONS Identifying reasons for differences in suicide rates relative to depression among ethnic groups and between males and females may suggest interventions to reduce suicide rates. Some possibilities are that depression differs in form or severity or that unidentified factors protect against suicide in different subgroups.
Abstracting abstract machines

the gOal Of program analysis is to statically predict runtime properties of programs without running them. The semantic approach to program analysis originates in Cousot's path-breaking work on abstract interpretation: start from a formal mathematical model of program execution—a semantics—and approximate it with Galois connections (or similar means) into a computable model based on lattices of runtime properties that accounts for all possible execution paths. Each program gives rise to a collection of equations that are then typically solved by fixed-point iteration. Semantics-based program analysis therefore requires one to (1) start from a " friendly " semantics; design a " congenial " lattice of runtime properties; (3) associate a " relevant " set of equations to a program; and (4) solve these equations efficiently. Each of these requirements is fraught with difficulties: 1. Among the varieties of formal semantics that exist (operational, deno-tational, axiomatic, among others) and their sub-varieties (for example, small step or big step), where is your friendly semantics? Ideally, it should lend itself to a good approximation into a computable model. 2. What is a congenial lattice of run-time properties? How wide should it be? How high? Ideally, it should lend itself to a good widening operator that accelerates the convergence of fixed-point iteration without compromising the precision of its result. 3. What is a relevant set of equa-tions? Ideally, each equation should mimic the friendly semantics as closely as possible. 4. What is the best representation of equations and the most efficient way to solve them? This is an algorithmics problem. Effective answers to each of these questions have been found before, but it is like each of them is a tour de force. In the following paper, David Van Horn and Matthew Might take a radical bet of simplicity and effectiveness: ˲ ˲ Since most semantic artifacts are inter-derivable, without loss of generality , they select abstract machines— deterministic state-transition systems with potentially infinite state spaces— as their friendly semantics. ˲ ˲ They then refactor each abstract machine into a non-deterministic state-transition system with a finite state space. Their methodology is concretely useful: it enables program-analysis designers to start from an existing abstract machine rather than from an ad hoc, tailored one, and then factor it uniformly into an abstraction-friendly semantic artifact. Their methodology is effective: it scales to a variety of computational situations involving realistic programming-language constructs, for example, exceptions. Their methodology is structural …
Posttraumatic growth in mothers after infant admission to neonatal intensive care unit

Hospitalization in neonatal intensive care units (NICUs) is stressful and traumatic for mothers (1), even in the absence of clinical or pathological concerns (2). Several studies involving mothers of infants hospitalized in NICU identifi ed diff erent sources of parental stress, defi ned as the physical and psychological aspects of a situation that impose demands on individuals (1, 3, 4). High stress is an important risk factor for poor parent-infant relationships during early childhood and has long-term negative outcomes (5). Research indicates that parents whose infants have been admitted to NICU experience emotional reactions such as guilt, depression, fear, anxiety, acute stress disorder, etc. (6-9).