gebhart/patrepeval huggingface dataset:
Transport of Human Immunodeficiency Virus Type 1 Pseudoviruses across the Blood-Brain Barrier: Role of Envelope Proteins and Adsorptive Endocytosis (2001)

Blood-borne human immunodeficiency virus type 1 (HIV-1) crosses the blood-brain barrier (BBB) to induce brain dysfunction. How HIV-1 crosses the BBB is unclear. Most work has focused on the ability of infected immune cells to cross the BBB, with less attention devoted to the study of free virus. Since the HIV-1 coat glycoprotein gp120 can cross the BBB, we postulated that gp120 might be key in determining whether free virus can cross the BBB. We used radioactive virions which do (Env+) or do not (Env-) bear the envelope proteins to characterize the ability of HIV-1 to be taken up by the murine BBB. In vivo and in vitro studies showed that the envelope proteins are key to the uptake of free virus and that uptake was enhanced by wheat germ agglutinin, strongly suggesting that the envelope proteins induce viral adsorptive endocytosis and transcytosis in brain endothelia. Capillary depletion showed that Env+ virus completely crossed the vascular BBB to enter the parenchyma of the brain. Virus also entered the cerebrospinal fluid, suggesting passage across the choroid plexus as well. About 0.22% of the intravenously injected dose was taken up per g of brain. In vitro studies showed that postinternalization membrane cohesion (membrane binding not reversed with acid wash or cell lysis) was a regulated event. Intact virus was recovered from the brain endothelial cytosol and was effluxed from the endothelial cells. These results show that free HIV-1 can cross the BBB by an event related to adsorptive endocytosis and mediated by the envelope proteins.
Comparison of Six Methods of Extracting <i>Mycobacterium tuberculosis</i> DNA from Processed Sputum for Testing by Quantitative Real-Time PCR (2005)

Six methods of extracting Mycobacterium tuberculosis DNA from sputum for testing by quantitative PCR were compared: Tris-EDTA (TE) buffer, PrepMan Ultra, 2% sodium dodecyl sulfate (SDS)-10% Triton X with and without sonication, Infectio Diagnostics, Inc. (IDI) lysing tubes, and QIAGEN QIAamp DNA mini kit; all included a 15-min boiling step. Pooled digested and decontaminated sputum was spiked with M. tuberculosis ATCC 27294. Each extraction method was repeated eight times. Quantitative PCR was performed on the Smart Cycler and Rotor-Gene 3000 using primers targeting an 83-bp fragment of IS6110. An minor grove binding Eclipse probe with a fluorescent label was used for detection. An internal control was included to detect amplification inhibition. The limit of detection of M. tuberculosis DNA was 0.5 fg with both instruments. Calculated DNA concentrations (picograms) extracted using IDI, PrepMan, QIAGEN, and TE were 42.8, 30.4, 28.2, and 7.4, respectively, when run on the Smart Cycler, and 51.7, 20.1, 14.9, and 8.6, respectively, when run on Rotor-Gene. All extractions using SDS/Triton X with or without sonication were inhibited. Of the extraction methods evaluated, IDI lysis tubes provided the greatest yield of mycobacterial DNA, and the procedure can be completed in less than 1 h versus 2.5-3 h for the QIAGEN extraction.
Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by the iminosugar UV-4 (2016)

The antiviral activity of UV-4 was previously demonstrated against dengue virus serotype 2 (DENV2) in multiple mouse models. Herein, step-wise minimal effective dose and therapeutic window of efficacy studies of UV-4B (UV-4 hydrochloride salt) were conducted in an antibody-dependent enhancement (ADE) mouse model of severe DENV2 infection in AG129 mice lacking types I and II interferon receptors. Significant survival benefit was demonstrated with 10-20 mg/kg of UV-4B administered thrice daily (TID) for seven days with initiation of treatment up to 48 h after infection. UV-4B also reduced infectious virus production in in vitro antiviral activity assays against all four DENV serotypes, including clinical isolates. A set of purified enzyme, in vitro, and in vivo studies demonstrated that inhibition of endoplasmic reticulum (ER) α-glucosidases and not the glycosphingolipid pathway appears to be responsible for the antiviral activity of UV-4B against DENV. Along with a comprehensive safety package, these and previously published data provided support for an Investigational New Drug (IND) filing and Phases 1 and 2 clinical trials for UV-4B with an indication of acute dengue disease.
Cryptographic Key Generation based on Contextual Information: A Review (2016)

With the capabilities of computing increasing by leaps and bounds, the need for trusted communication also rises. The present state of ensuring secure communication between devices largely relies on the use of cryptographic keys. The primitive and advanced key generation strategies involve the use of password only, biometric, quantum, PRNG technologies. Recently, the use of contextual information to generate highly secure keys has proven to be a realistic and unobstructed method in the field of cryptography. Contextual information like temperature, luminance and ambient audio may be used for this purpose. This paper presents a detailed survey on the cryptographic techniques for key generation based on contextual information. A brief comparison on the current techniques is also presented in this survey.
Phase 2 study of TAS-117, an allosteric akt inhibitor in advanced solid tumors harboring phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene mutations (2021)

TAS-117 is a potent and selective allosteric pan-v-akt murine thymoma viral oncogene homolog (Akt) inhibitor. We conducted a single-arm single-center phase 2 study of TAS-117 in heavily treated patients with tumors refractory to systemic chemotherapy and harboring phosphatidylinositol 3-kinase (PI3K)/Akt mutations. Patients with gastrointestinal (GI) cancers were orally administered 16 mg TAS-117 daily, and those with non-GI tumors were administered 24 mg on a 4 days on/3 days off schedule. The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, safety, and tolerability. Thirteen patients were enrolled: eight with non-GI (breast, ovarian, endometrial, and non-small cell lung) and five with GI (colon, rectal, gastric, and gallbladder) cancers. Ten patients were treated with TAS-117 after ≥ 4 lines of therapy. Twelve patients showed PIK3 catalytic subunit alpha (PIK3CA) mutations; one harbored an Akt1<sup>E17K</sup> mutation. The median treatment duration was 1.4 months; the median number of treatment cycles was 2. The ORR was 8 %, and DCR was 23 %. The median PFS and OS were 1.4 and 4.8 months, respectively. Grade 3-4 treatment-related adverse events were anorexia (grade 3, 8 %) and hyperglycemia (grade 3, 8 %; grade 4, 8 %).Grade 3-4 treatment-related adverse events occurred in 27 % of grade 3 anorexia (9 %) and hyperglycemia (grade 3, 8 %; grade 4, 9\%). TAS-117 showed limited antitumor activity and manageable toxicity. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations and in patients with breast cancer harboring PIK3CA H1047R and Akt1<sup>E17K</sup> mutations.Trial registration: This study was retrospectively registered with ClinicalTrial.gov (NCT03017521 on January 11, 2017).
Fall-Detection Algorithm Using 3-Axis Acceleration: Combination with Simple Threshold and Hidden Markov Model (2014)

Falls are a serious medical and social problem among the elderly. This has led to the development of automatic fall-detection systems. To detect falls, a fall-detection algorithm that combines a simple threshold method and hidden Markov model (HMM) using 3-axis acceleration is proposed. To apply the proposed fall-detection algorithm and detect falls, a wearable fall-detection device has been designed and produced. Several fall-feature parameters of 3-axis acceleration are introduced and applied to a simple threshold method. Possible falls are chosen through the simple threshold and are applied to two types of HMM to distinguish between a fall and an activity of daily living (ADL). The results using the simple threshold, HMM, and combination of the simple method and HMM were compared and analyzed. The combination of the simple threshold method and HMM reduced the complexity of the hardware and the proposed algorithm exhibited higher accuracy than that of the simple threshold method.
Evaluation of the human airway with multi-detector x-ray-computed tomography and optical imaging (2004)

Defining the healthy human airway is important in enhancing our understanding of pulmonary disease states such as inflammation and cancer. The structure of the human airway, both static and dynamic, can be assessed using multi-detector CT (MDCT) scanning. This modality also allows for the evaluation of structures outside of the airway. The airway wall can be directly visualized using CCD chip high-resolution color optical imaging through endoscopy allowing bronchial wall evaluation by traditional biopsy methods, as well as by newer optically based strategies. We suggest that these two imaging modalities, MDCT and optical imaging, provide complementary information about the normal airway, and the airway in various diseases. Methods for evaluating the human airway using MDCT images are presented facilitating automatic airway segmentation, branchpoint finding and airway dimension analysis. The airway wall color is objectively evaluated as an important surrogate for airway wall inflammation and cancer formation, and the integration of the color endoscopic information into the MDCT scan data set is currently ongoing. The amalgamation of these two digital imaging modalities appears increasingly useful for enabling biopsy techniques, and for relating structure and function of the airway. In addition, these developments may be progressively more useful in understanding the normal airway structure and function, for defining airway diseases patterns and for guiding biopsy and therapeutic procedures.
Antioxidant activity of phenolic and related compounds: a density functional theory study on the O–H bond dissociation enthalpy (2004)

We report here on calculations at the hybrid DFT/HF (B3-LYP/6-31G(d, p)) level of the O-H bond dissociation enthalpy (O-H BDE) of phenylpropenoic acids (caffeic, ferulic, p-coumaric and cinnamic) and phenolic acids and related compounds (gallic, methylgallate, vanillic and gentisic) in order to gain insight into the understanding of structure-antioxidant activity relationships. The results were correlated and discussed mainly on the basis of experimental data in a companion work (Galato D, Giacomelli C, Ckless K, Susin MF, Vale RMR, Spinelli A. Antioxidant capacity of phenolic and related compounds: correlation among electrochemical, visible spectroscopy methods and structure-antioxidant activity. Redox Report 2001; 6: 243-250). The O-H BDE values showed remarkable dependence on the hydroxyl position in the benzene ring and the existence of additional interaction due to hydrogen bonding. For parent molecules, the experimental antioxidant activity (AA) order was properly obeyed only when intramolecular hydrogen bonding was present in the radicalized structures of o-dihydroxyl moieties. In structurally related compounds, excellent correlation with experimental data was in general observed (0.64 < rho < 0.99). However, it is shown that excellent correlation can also be obtained for this series of compounds considering p-radicalized structures which were not stabilized by intramolecular hydrogen bonding, but this had no physical meaning. These findings suggested that the antioxidant activity evaluation of phenolic and related compounds must take into consideration the characteristics of each particular compound.
RC interconnect synthesis—a moment fitting approach (1994)

Presently, delays due to the physical interconnect between logic gates account for large portions of the overall path delays. For this reason, synthesis of the logic gate fanout structure is of paramount importance during performance optimization. This paper presents a methodology for on-chip RC interconnect synthesis. Moment sensitivities are used to vary the wire widths of the branches in an RC interconnect tree to achieve performance targets. In this paper, signal slopes and delays at critical fanout nodes are the targets, and the impact on total metal area is considered. An O(MN2) procedure for computing the exact moment sensitivities in an RC tree is described.
Ontology-based Text Document Clustering. (2002)

Text clustering typically involves clustering in a high dimensional space, which appears difficult with regard to virtually all practical settings. In addition, given a particular clustering result it is typically very hard to come up with a good explanation of why the text clusters have been constructed the way they are. In this paper, we propose a new approach for applying background knowledge during preprocessing in order to improve clustering results and allow for selection between results. We preprocess our input data applying an ontology-based heuristics for feature selection and feature aggregation. Thus, we construct a number of alternative text representations. Based on these representations, we compute multiple clustering results using KMeans. The results may be distinguished and explained by the corresponding selection of concepts in the ontology. Our results compare favourably with a sophisticated baseline preprocessing strategy.
Risk minimization by median-of-means tournaments (2019)

We consider the classical statistical learning/regression problem, when the value of a real random variable Y is to be predicted based on the observation of another random variable X . Given a class of functions \mathcal F and a sample of independent copies of (X,Y) , one needs to choose a function \widehat{f} from \mathcal F such that \widehat{f}(X) approximates Y as well as possible, in the mean-squared sense. We introduce a new procedure, the so-called median-of-means tournament, that achieves the optimal tradeoff between accuracy and confidence under minimal assumptions, and in particular outperforms classical methods based on empirical risk minimization.
Minoxidil specifically decreases the expression of lysine hydroxylase in cultured human skin fibroblasts (1992)

The levels of lysine hydroxylase protein and the levels of the mRNAs for lysine hydroxylase and the alpha- and beta-subunits of proline 4-hydroxylase were measured in cultured human skin fibroblasts treated with 1 mM-minoxidil. The data demonstrate that minoxidil decreases the amount of lysine hydroxylase protein, this being due to a decrease in the level of lysine hydroxylase mRNA. The effect of minoxidil appears to be highly specific, as no changes were observed in the amounts of mRNAs for the alpha- and beta-subunits of proline 4-hydroxylase.
The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders (2014)

Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.
Stability, cellular uptake, biotransformation, and efflux of tea polyphenol (-)-epigallocatechin-3-gallate in HT-29 human colon adenocarcinoma cells. (2002)

The biological effects of (-)-epigallocatechin-3-gallate (EGCG) have been extensively investigated in cell lines, but its stability and interactions with cells under culture conditions are unclear. In the present study, the stability, uptake, biotransformation, and efflux of [(3)H]EGCG in HT-29 human colon adenocarcinoma cells were investigated. EGCG was unstable in McCoy's 5A culture media with a half-life of less than 30 min, and the half-life increased to 130 min in the presence of cells. The major oxidative products were theasinensin (M(r) 914) and another dimer with M(r) 884. Addition of EGCG (50 micro M) to cell culture media caused the production of H(2)O(2) (up to 25 micro M), and the amount was lower and gradually decreased in the presence of cells. The uptake of EGCG was concentration dependent and did not plateau, even at 640 micro M, suggesting a passive diffusion process. Approximately 75% of the [(3)H]EGCG was found in the cytoplasmic fraction when the cells were incubated with 0.5-20 micro M [(3)H]EGCG for 15 min. The membrane-associated radioactivity increased with time, apparently because of the binding of dimers to the membrane. The accumulation of [(3)H]EGCG in the cells was significantly higher at 4 degrees C than at 37 degrees C. Multidrug-resistant protein inhibitors, such as indomethacin and probenecid, effectively increased the accumulation of EGCG 4"-glucuronide and 4"-methyl EGCG in the cell. These results suggest that EGCG is metabolized in the cell and that the metabolites are pumped out by MRPs. The present study provides fundamental information on the stability, uptake, biotransformation, and efflux of EGCG under cell culture conditions and suggests the need for careful interpretation of related results on the biological activities of EGCG.
Intraportal islet transplantation: the impact of the liver microenvironment (2017)

The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver microenvironment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver microenvironment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood-mediated inflammatory reaction, the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets. It identifies the potential, or already applied, clinical interventions for improving intraportal islet survival, and pinpoints those promising areas still lacking preclinical research. Future interventions on clinical intraportal islet transplantation need to take into account the global context of the liver microenvironment, with multi-point interventions being most likely to improve early islet survival and engraftment.
Prevalence of Diabetes and Impaired Fasting Glucose in Adults in the U.S. Population (2006)

Although the prevalence of diagnosed diabetes has increased significantly over the last decade, the prevalences of undiagnosed diabetes and IFG have remained relatively stable. Minority groups remain disproportionately affected.
A framework for optimal battery management for wireless nodes (2003)

The focus of this paper is to extend the lifetime of a battery powered node in wireless context. The lifetime of a battery depends on both the manner of discharge and the transmission power requirements. We present a framework for computing the optimal discharge strategy which maximizes the lifetime of a node by exploiting the battery characteristics and adapting to the varying power requirements for wireless operations. The complexity of the optimal computation is linear in the number of system states. However, since the number of states can be large, the optimal strategy can only be computed offline and executed via a table-lookup. We also present a simple discharge strategy which can be executed online without any table lookup, and attains near maximum battery lifetime. Finally, we use state space reduction techniques to approximate the optimal computation in significantly lower complexity.
Isolation of brain .alpha.-actinin. Its characterization and a comparison of its properties with those of muscle .alpha.-actinins (1984)

A rapid purification procedure has been developed for the isolation of alpha-actinin from chicken brain. Brains were homogenized in cold water containing 0.5 mM phenylmethanesulfonyl fluoride (PMSF), the homogenate was centrifuged, and the alpha-actinin was extracted from the pelleted material in a low ionic strength buffer for 30 min at 22 degrees C. Purification of the protein to homogeneity on sodium dodecyl sulfate containing polyacrylamide gels required an ammonium sulfate precipitation step followed by chromatography on columns of DEAE-cellulose, hydroxylapatite, and Sepharose CL-6B. The alpha-actinins from chicken pectoral muscle (skeletal) and gizzard (smooth muscle) were purified in a similar fashion but without the DEAE-cellulose chromatography step. All three alpha-actinins have an identical Stokes radius of 7.1 nm determined by gel filtration chromatography. The individual proteins are homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis but do not comigrate; however, all three alpha-actinins have identical retardation coefficients, obtained from electrophoretic mobilities at different acrylamide concentrations, which indicates that they all have similar subunit molecular weights (about 105 000). All three proteins behave similarly on isoelectric focusing gels (pI of native proteins congruent to 4.7-4.9) and have similar UV and CD spectroscopic properties. Significant differences exist both in their amino acid composition and in their peptide maps, obtained from limited proteolysis, which indicates that the proteins are all unique gene products.(ABSTRACT TRUNCATED AT 250 WORDS)