gebhart/patrepeval huggingface dataset:
Cellular Models of Aggregation-dependent Template-directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer Disease (2015)

Alzheimer disease (AD) is a degenerative tauopathy characterized by aggregation of Tau protein through the repeat domain to form intraneuronal paired helical filaments (PHFs). We report two cell models in which we control the inherent toxicity of the core Tau fragment. These models demonstrate the properties of prion-like recruitment of full-length Tau into an aggregation pathway in which template-directed, endogenous truncation propagates aggregation through the core Tau binding domain. We use these in combination with dissolution of native PHFs to quantify the activity of Tau aggregation inhibitors (TAIs). We report the synthesis of novel stable crystalline leucomethylthioninium salts (LMTX®), which overcome the pharmacokinetic limitations of methylthioninium chloride. LMTX®, as either a dihydromesylate or a dihydrobromide salt, retains TAI activity in vitro and disrupts PHFs isolated from AD brain tissues at 0.16 μM. The Ki value for intracellular TAI activity, which we have been able to determine for the first time, is 0.12 μM. These values are close to the steady state trough brain concentration of methylthioninium ion (0.18 μM) that is required to arrest progression of AD on clinical and imaging end points and the minimum brain concentration (0.13 μM) required to reverse behavioral deficits and pathology in Tau transgenic mice.
Precision Slotted-Line Impedance Measurements Using Computer Simulation for Data Correction (1970)

A precision slotted-line measurement system is described that provides rapid impedance measurements over a wide dynamic range for both active and passive devices. Phase accuracy of 0.1° at 7.0 GHz and magnitude accuracy of 0.5 percent are obtainable for high VSWR measurements. Phase-locked sources used for both the slotted-line drive and the receiver local oscillator provide greater than 70 dB of dynamic range for an incident power level of -50 dBm at the unknown. A micrometer positioner for the slotted-line probe provides an order of magnitude improvement in probe-position accuracy over that obtainable using the conventional slotted-line scale and micrometer. A computer program simulates the slotted line and its associated connector by several sections of lossy transmission line together with appropriate discontinuity capacitance and contact loss. This form of model has the advantage that frequency dependence is implicitly included. Impedance measurement is simple and rapid. The only data required are the frequency, the position of an unknown null, either the width of the minimum or the VSWR, and the desired reference plane extension. The corrected data may be plotted directly on a Smith chart. Printout is in a convenient format for data evaluation.
Pseudotyping of murine leukemia virus with the envelope glycoproteins of HIV generates a retroviral vector with specificity of infection for CD4-expressing cells (1997)

CD4-expressing T cells in lymphoid organs are infected by the primary strains of HIV and represent one of the main sources of virus replication. Gene therapy strategies are being developed that allow the transfer of exogenous genes into CD4(+) T lymphocytes whose expression might prevent viral infection or replication. Insights into the mechanisms that govern virus entry into the target cells can be exploited for this purpose. Major determinants of the tropism of infection are the CD4 molecules on the surface of the target cells and the viral envelope glycoproteins at the viral surface. The best characterized and most widely used gene transfer vectors are derived from Moloney murine leukemia virus (MuLV). To generate MuLV-based retroviral gene transfer vector particles with specificity of infection for CD4-expressing cells, we attempted to produce viral pseudotypes, consisting of MuLV capsid particles and the surface (SU) and transmembrane (TM) envelope glycoproteins gp120-SU and gp41-TM of HIV type 1 (HIV-1). Full-length HIV-1 envelope glycoproteins were expressed in the MuLV env-negative packaging cell line TELCeB6. Formation of infectious pseudotype particles was not observed. However, using a truncated variant of the transmembrane protein, lacking sequences of the carboxyl-terminal cytoplasmic domain, pseudotyped retroviruses were generated. Removal of the carboxyl-terminal domain of the transmembrane envelope protein of HIV-1 was therefore absolutely required for the generation of the viral pseudotypes. The virus was shown to infect CD4-expressing cell lines, and infection was prevented by antisera specific for gp120-SU. This retroviral vector should prove useful for the study of HIV infection events mediated by HIV-1 envelope glycoproteins, and for the targeting of CD4(+) cells during gene therapy of AIDS.
Uncertainty Management for Diagnostics and Prognostics of Batteries using Bayesian Techniques (2008)

Uncertainty management has always been the key hurdle faced by diagnostics and prognostics algorithms. A Bayesian treatment of this problem provides an elegant and theoretically sound approach to the modern Condition-Based Maintenance (CBM)/Prognostic Health Management (PHM) paradigm. The application of the Bayesian techniques to regression and classification in the form of Relevance Vector Machine (RVM), and to state estimation as in Particle Filters (PF), provides a powerful tool to integrate the diagnosis and prognosis of battery health. The RVM, which is a Bayesian treatment of the Support Vector Machine (SVM), is used for model identification, while the PF framework uses the learnt model, statistical estimates of noise and anticipated operational conditions to provide estimates of remaining useful life (RUL) in the form of a probability density function (PDF). This type of prognostics generates a significant value addition to the management of any operation involving electrical systems.
Receptor binding specificity of recent human H3N2 influenza viruses (2007)

Agglutination of chicken red cells does not correlate with altered binding to any oligosaccharide on the Glycan Array, and may result from increased avidity due to density of hemagglutinin and not increased affinity. Absence of alpha2-6 sialic acid does not protect a cell from influenza infection and the presence of high levels of alpha2-6-sialic acids on a cell surface does not guarantee productive replication of a virus with alpha2-6 receptor specificity.
Evaluation of carbon flux and substrate selection through alternate pathways involving the citric acid cycle of the heart by 13C NMR spectroscopy. (1988)

A previous 13C NMR technique (Malloy, C. R., Sherry, A.D., and Jeffrey, F.M.H. (1987) FEBS Lett. 212, 58-62) for measuring the relative flux of molecules through the oxidative versus anaplerotic pathways involving the citric acid cycle of the rat heart has been extended to include a complete analysis of the entire glutamate 13C spectrum. Although still simple in practice, this more sophisticated model allows an evaluation of 13C fractional enrichment of molecules entering both the oxidative and anaplerotic pathways under steady-state conditions. The method was used to analyze 13C NMR spectra of intact hearts or their acid extracts during utilization of 13C-enriched pyruvate, propionate, acetate, or various combinations thereof. [2-13C]Pyruvate was used to prove that steady-state flux of pyruvate through pyruvate carboxylase is significant during co-perfusion of pyruvate and acetate, and we demonstrate for the first time that a nine-line 13C multiplet may be detected in an intact, beating heart. Acetate or pyruvate alone provided about 86% of the acetyl-CoA; in combination, about 65% of the acetyl-CoA was derived from acetate, about 30% was derived from pyruvate, and the remainder from endogenous sources. Propionate reduced the contribution of exogenous acetate to acetyl-CoA to 77% and also reduced the oxidation of endogenous substrates. Equations are presented which allow this same analysis on multiply labeled substrates, making this technique extremely powerful for the evaluation of substrate selection and relative metabolic flux through anaplerotic and oxidative pathways in the intact heart.
Improved Outcome With Dose-Dense Chemotherapy (2004)

TO THE EDITOR: Citron et al [1] have tested the hypothesis that outcome is improved with increased dose density of chemotherapy. Although it is not stated, it is likely that the dose-dense arms received considerably more granulocyte colony-stimulating factor (G-CSF) than the conventionally scheduled arms. An assumption is that G-CSF had no effect other than increasing neutrophil count and activity against infection. However, G-CSF has been found to stimulate other potentially antitumor immune functions, including chemotaxis [2], adhesion [3], pre–B cells [4], and T helper cell type 2–inducing dendritic cells [5]. G-CSF can also have an anti-inflammatory effect [6]. Inflammation is thought to play an important role in cancer, and an antiinflammatory approach to cancer treatment has been proposed [7]. Is the improved outcome due to increased dose density of chemotherapy, to increased G-CSF use, or both? To answer that question, an appropriate trial would be “dose-dense” adjuvant chemotherapy (with scheduled G-CSF) versus “standard” adjuvant chemotherapy (with scheduled G-CSF in the same dose) versus “standard” adjuvant chemotherapy (with G-CSF as clinically indicated).
Organum vasculosum laminae terminalis contributes to increased sympathetic nerve activity induced by central hyperosmolality (2007)

The contribution of the organum vasculosum laminae terminalis (OVLT) in mediating central hyperosmolality-induced increases of sympathetic nerve activity (SNA) and arterial blood pressure (ABP) was assessed in anesthetized rats. Solutions of graded NaCl concentration (150, 375, and 750 mM) were injected (150 mul) into the forebrain vascular supply via an internal carotid artery (ICA). Time-control experiments (n = 6) established that ICA NaCl injections produced short-latency, transient increases of renal SNA (RSNA) and mean ABP (MAP) (P < 0.05-0.001). Responses were graded, highly reproducible, and unaltered by systemic blockade of vasopressin V1 receptors (n = 4). In subsequent studies, stimulus-triggered averaging of RSNA was used to accurately locate the OVLT. Involvement of OVLT in responses to ICA NaCl was assessed by recording RSNA and MAP responses before and 15 min after electrolytic lesion of the OVLT (n = 6). Before lesion, NaCl injections increased RSNA and MAP (P < 0.05-0.001), similar to time control experiments. After lesion, RSNA responses were significantly reduced (P < 0.05-0.001), but MAP responses were unaltered. To exclude a role for fibers of passage, the inhibitory GABA-A receptor agonist muscimol was microinjected into the OVLT (50 pmol in 50 nl) (n = 6). Before muscimol, hypertonic NaCl increased RSNA, lumbar SNA (LSNA), and MAP (P < 0.05-0.001). After muscimol, both RSNA and LSNA were significantly reduced in response to 375 and 750 mM NaCl (P < 0.05). MAP responses were again unaffected. Injections of vehicle (saline) into OVLT (n = 6) and muscimol lateral to OVLT (n = 5) each failed to alter responses to ICA NaCl. We conclude that OVLT neurons contribute to sympathoexcitation by central hyperosmolality.
Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. (2003)

Perifosine is a novel p.o. bioavailable alkylphospholipid. Perifosine has displayed significant antiproliferative activity in vitro and in vivo in several human tumor model systems and has recently entered phase I clinical trials. Recent studies have identified that perifosine could cause cell cycle arrest with induction of p21(WAF1/CIP1) in a p53-independent fashion; however, the basis for that effect is not known. Structurally, perifosine resembles naturally occurring phospholipids. Therefore, we hypothesized that perifosine might perturb pathways related to phospholipids modulated by growth factor action. We demonstrate here that perifosine causes dose-dependent inhibition of protein kinase B/Akt phosphorylation and thus activation at concentrations causing growth inhibition of PC-3 prostate carcinoma cells. Only the myristoylated form of Akt (MYR-Akt), which bypasses the requirement for pleckstrin homology (PH) domain-mediated membrane recruitment, abrogated perifosine-mediated decrease of Akt phosphorylation and cell growth inhibition by perifosine. We demonstrate further that perifosine decreases the plasma membrane localization of Akt, and this is substantially relieved by MYR-Akt along with relief of downstream drug effect on induction of p21(WAF1/CIP1). Perifosine does not directly affect phosphoinositide 3-kinase (PI3K), phosphoinositide-dependent kinase 1, or Akt activity at concentrations inhibiting Akt phosphorylation and membrane localization. Our results demonstrate that Akt is an important cellular target of perifosine action. In addition, these studies show that the membrane translocation of certain PH domain-containing molecules can be greatly perturbed by the alkylphospholipid class of drugs and imply further that the PI3K/Akt pathway contributes to regulation of p21(WAF1/CIP1) expression.
Secret sharing scheme realizing general access structure (1989)

Abstract As a method of sharing a secret, e.g., a secret key, Shamir's (k, n) threshold method is well known. However, Shamir's method has a problem in that general access structures cannot be realized. This paper shows that by providing the trustees with several information data concerning the distributed information of the (k, n) threshold method, any access structure can be realized. the update with the change of the secret trustees and the relation to the threshold graph are also discussed.
Alternative Forms of Max as Enhancers or Suppressors of Myc-Ras Cotransformation (1992)

Max is a basic-helix-loop-helix-leucine zipper protein capable of forming sequence-specific DNA binding complexes with Myc proteins. An alternatively spliced messenger RNA has been identified that encodes a form of Max truncated at the COOH-terminus. This delta Max protein retained the ability to bind to the CACGTG motif in a complex with c-Myc but lacks the nuclear localization signal and the putative regulatory domain of Max. When tested in a myc-ras cotransformation assay in rat embryo fibroblasts, Max suppressed, whereas delta Max enhanced, transformation. Thus, the max gene may encode both a negative and a positive regulator of c-Myc function.
Effectiveness of Digital Medicines to Improve Clinical Outcomes in Patients with Uncontrolled Hypertension and Type 2 Diabetes: Prospective, Open-Label, Cluster-Randomized Pilot Clinical Trial (2017)

Clinicaltrials.gov NCT02827630; https://clinicaltrials.gov/show/NCT02827630 (Archived by WebCite at http://www.webcitation.org/6rL8dW2VF).
Prognostic accuracy of an artificial neural network in patients undergoing radical cystectomy for bladder cancer: a comparison with logistic regression analysis (2007)

The ANN accurately predicted the survival of patients undergoing radical cystectomy for bladder cancer and had a prognostic performance comparable with that of LR. As ANNs are based on easy-to-use software that can identify nonlinear interactions between variables, they might become the preferred tool for predicting outcome.
Using Fault Augmented Modelica Models for Diagnostics (2014)

We propose a model-based diagnosis framework in which Modelica models of faulted behavior are used in combination with a Bayesian approach. The fault augmented models are automatically generated through a process developed as part of our Fault Augmented Model Extension (FAME) work. Fault diagnosis using a Bayesian approach is based on computing a set of probability density functions, a process that is usually intractable for any reasonably complex system. We use Approximate Bayesian Computation (ABC) to bound the numerical and computational complexity. The basic idea is to use fault augmented Modelica models to create probability distributions of possible outcomes and then compare those distributions against actual observations to perform parameter estimation. The detection of faults is treated as a model selection problem and the inference of their severity levels is treated as parameter estimation. The diagnostic precision of this approach is evaluated on a Modelica vehicle drive line model.
Immune and histopathological responses in animals vaccinated with recombinant vaccinia viruses that express individual genes of human respiratory syncytial virus (1987)

Previous reports have established that vaccinia virus (VV) recombinants expressing G, F, or N protein of respiratory syncytial (RS) virus protect small animals against intranasal challenge with live RS virus. This work demonstrates that a variety of parameters affect the protection induced by recombinant viruses. The route of vaccination, the subtype of challenge virus, and the species used influenced the antibody titers and extent of protection. During these studies, observations were also made on the subclass of antibody generated, and pulmonary histopathological changes induced by challenge after vaccination were noted. The effect of route of inoculation on host response was examined by vaccinating mice intranasally, intraperitoneally, or by scarification with a recombinant VV expressing the RS virus G glycoprotein. Intranasal vaccination induced 25-fold-higher titers of antibody to RS virus in the lung than the intraperitoneal route did, but both routes resulted in complete suppression of virus replication after intranasal challenge 21 days after vaccination. Scarification was a less effective method of vaccination. The antibody induced by recombinant VV in mice was mostly immunoglobulin G2a (IgG2a) with some IgG2b. No antibody to RS virus was detected in the IgA, IgM, IgG1, or IgG3 subclass irrespective of the vaccination route. The G and F glycoproteins were shown to elicit similar subclasses of antibody. However, animals vaccinated with the G and F vectors differed strikingly in their response to challenge by heterologous virus. Mice or cotton rats vaccinated with recombinant VV carrying the G gene of RS virus were protected against challenge only with homologous subtype A virus. Vaccination with a recombinant VV expressing the F glycoprotein induced protection against both homologous and heterologous subtype B virus challenge. The protection induced in mice was greater than that detected in cotton rats, indicating that the host may also affect immunity. Finally, this report describes histological examination of mouse lungs after vaccination and challenge. Vaccinated mice that were subsequently challenged had significantly greater lung lesion scores than unvaccinated challenged mice. The lesions were primarily peribronchiolar and perivascular infiltrations of polymorphonuclear cells and lymphocytes. Further work will establish whether these pulmonary changes are a desirable immune response to virus invasion or a potential immunopathogenic hazard. The results have important implications for planning a strategy of vaccination against RS virus and emphasize potential dangers that may attend the use of recombinant VV as vaccines.
Synthesis and Characterization of Amorphous Hydrated FePO[sub 4] and Its Electrode Performance in Lithium Batteries (2002)

Amorphous iron(III) phosphate was synthesized by spontaneous precipitation from equimolar aqueous solutions of Fe(NH4)(2)(SO4)(2).6H(2)O and NH4H2PO4, using hydrogen peroxide as the oxidizing agent. The material was characterized by chemical analysis, thermogravimetrical analysis, differential thermoanalysis, X-ray powder diffraction, and scanning electron microscopy. The material was tested as a cathode in nonaqueous lithium cells. Galvanostatic intermittent titration technique was used to follow the lithium intercalation process. The effect of firing on the specific capacity was also tested. The material fired at 400degreesC showed the best electrochemical performance, delivering about 0.108 Ah g(-1) when cycled at C/10 rate. The capacity fade upon cycling was found as low as 0.075% per cycle. (C) 2002 The Electrochemical Society.
Modified Excipients in Novel Drug Delivery: Need of the Day (2013)

Drug products not only contain “actives” that confer the intended therapeutic benefits such as pain relief or act on particular part of the body, but contain other materials that are also “functional” with respect to the drug product. These are known as excipients and specific functionality which they confer to a particular product is independent upon the process used to add the excipient to the formulation and its exact location within the final dosage form. Introduction of novel drug delivery systems and new drug moieties lead to the need for new excipients with varied characteristics. Development of new excipient entities and their evaluation is a costly procedure; modification of existing excipients is very easy, more economical and less time consuming. The development of excipients that are capable of fulfilling multifunctional roles such as enhancing drug bioavailability and drug stability as well as controlling the release of the drug according to the therapeutic needs is one of the most important prerequisites for further progress in the design of novel drug delivery systems. The main focus of this article is on synthetic novel excipients that perform multiple functions in pharmaceutical formulations.
Protein Sequences Encoded by the relA and the spoT Genes of Escherichia coli Are Interrelated (1989)

relA and spoT are designations for two unlinked Escherichia coli genes whose products function in the synthesis and degradation of guanosine 3',5'-bispyrophosphate during the stringent regulatory response to amino acid deprivation. The RelA protein catalyzes an ATP:GTP 3'-pyrophosphoryl group transfer reaction, and the SpoT protein has a guanosine 3',5'-bispyrophosphate 3'-pyrophosphohydrolyase activity. Both genes have been sequenced recently; the relA gene produces an 84-kDa protein, and the spoT gene is deduced to encode a 79-kDa protein. We report here that the protein sequences of the relA and spoT genes are extensively interrelated.
Highly luminescent palladium(ii) complexes with sub-millisecond blue to green phosphorescent excited states. Photocatalysis and highly efficient PSF-OLEDs (2016)

Pd(<sc>II</sc>) complexes with long-lived emissive excited states found applications in photo-catalysis and PSF-OLEDs.
Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer (2009)

Here, we determined the possible association of stromal caveolin-1 (Cav-1) levels with DCIS recurrence and/or progression to invasive breast cancer. An initial cohort of 78 DCIS patients with follow-up data was examined. As ER-positivity was associated with recurrence, we focused our analysis on this subset of 56 patients. In this group, we observed that DCIS progressed to invasive breast cancer in approximately 14% of the patient population (8/56), in accordance with an expected progression rate of 12-15%. Nearly ninety percent of DCIS patients (7/8) that underwent recurrence to invasive breast cancer had reduced or absent levels of stromal Cav-1. Remarkably, an absence of stromal Cav-1 (score = 0) was specifically associated with early disease progression to invasive breast cancer, with reduced time to recurrence and higher recurrence rate. All DCIS patients with an absence of stromal Cav-1 underwent some form of recurrence (5/5) and the majority (4/5) underwent progression to invasive breast cancer. This represents an overall cumulative incidence rate of 100% for recurrence and 80% for progression. An absence of stromal Cav-1 in DCIS lesions was also specifically associated with the presence of inflammatory cells. Conversely, ninety-seven percent of ER(+) DCIS patients (35/36) with high levels of stromal Cav-1 (score = 2) did not show any invasive recurrence over the duration of follow-up (4-208 mo), and 89% of such patients are estimated to remain free of invasive recurrence, even after 15 y. Thus, determination of stromal Cav-1 levels may be a useful new biomarker for guiding the treatment of ER(+) DCIS patients.