gebhart/patrepeval huggingface dataset:
The Hermansky-Pudlak Syndrome 1 (HPS1) and HPS4 Proteins Are Components of Two Complexes, BLOC-3 and BLOC-4, Involved in the Biogenesis of Lysosome-related Organelles (2003)

Hermansky-Pudlak syndrome (HPS) is a genetic disease of lysosome, melanosome, and granule biogenesis. Mutations of six different loci have been associated with HPS in humans, the most frequent of which are mutations of the HPS1 and HPS4 genes. Here, we show that the HPS1 and HPS4 proteins are components of two novel protein complexes involved in biogenesis of melanosome and lysosome-related organelles: biogenesis of lysosome-related organelles complex-(BLOC) 3 and BLOC-4. The phenotypes of Hps1-mutant (pale-ear; ep) and Hps4-mutant (light-ear; le) mice and humans are very similar, and cells from ep and le mice exhibit similar abnormalities of melanosome morphology. HPS1 protein is absent from ep-mutant cells, and HPS4 from le-mutant cells, but le-mutant cells also lack HPS1 protein. HPS4 protein seems to be necessary for stabilization of HPS1, and the HPS1 and HPS4 proteins co-immunoprecipitate, indicating that they are in a complex. HPS1 and HPS4 do not interact directly in a yeast two-hybrid system, although HPS4 interacts with itself. In a partially purified vesicular/organellar fraction, HPS1 and HPS4 are both components of a complex with a molecular mass of approximately 500 kDa, termed BLOC-3. Within BLOC-3, HPS1 and HPS4 are components of a discrete approximately 200-kDa module termed BLOC-4. In the cytosol, HPS1 (but not HPS4) is part of yet another complex, termed BLOC-5. We propose that the BLOC-3 and BLOC-4 HPS1.HPS4 complexes play a central role in trafficking cargo proteins to newly formed cytoplasmic organelles.
Good and Bad Amyloid Antibodies (2003)

Antibodies that recognize an oligomeric state common to different amyloidogenic proteins described by R. Kayed et al. (“Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis,” Reports, 18 Apr., p. [486][1]) advance our understanding of Alzheimer's disease (AD)
Molecular characterization of NAD:arginine ADP-ribosyltransferase from rabbit skeletal muscle. (1992)

Mono-ADP-ribosylation is a reversible modification of proteins, with NAD:arginine ADP-ribosyltransferases (EC 2.4.2.31) and ADP-ribosylarginine hydrolases (EC 3.2.2.19) catalyzing the opposing reactions in an ADP-ribosylation cycle. A membrane-associated arginine-specific (mono)-ADP-ribosyltransferase was purified 215,000-fold from rabbit skeletal muscle. On the basis of the amino acid sequences of HPLC-purified tryptic peptides, degenerate oligonucleotide primers were synthesized and used in a polymerase chain reaction (PCR)-based procedure to generate cDNA. A specific probe, based on PCR-generated sequence, was used to screen a rabbit skeletal muscle cDNA library. A composite cDNA sequence, obtained from library screening and rapid amplification of the 5' end of the cDNA, contained a 981-base-pair open reading frame, encoding a 36,134-Da protein. The deduced amino acid sequence contained the sequences of the tryptic peptides, hydrophobic amino and carboxyl termini, and two potential sites for N-linked glycosylation. Escherichia coli cells transformed with an expression vector containing transferase-specific sequence expressed ADP-ribosyltransferase activity. A transferase-specific oligonucleotide probe recognized a 4-kilobase mRNA expressed primarily in rabbit skeletal and cardiac muscle. There was no extended similarity in deduced amino acid sequences of the muscle transferase and several bacterial ADP-ribosylating toxins. The hydrophobic amino and carboxyl termini may represent a signal peptide and a site for a glycosyl-phosphatidylinositol anchor, respectively.
Inhibition of Plasma Kallikrein by a Highly Specific Active Site Blocking Antibody (2014)

Plasma kallikrein (pKal) proteolytically cleaves high molecular weight kininogen to generate the potent vasodilator and the pro-inflammatory peptide, bradykinin. pKal activity is tightly regulated in healthy individuals by the serpin C1-inhibitor, but individuals with hereditary angioedema (HAE) are deficient in C1-inhibitor and consequently exhibit excessive bradykinin generation that in turn causes debilitating and potentially fatal swelling attacks. To develop a potential therapeutic agent for HAE and other pKal-mediated disorders, we used phage display to discover a fully human IgG1 monoclonal antibody (DX-2930) against pKal. In vitro experiments demonstrated that DX-2930 potently inhibits active pKal (Ki = 0.120 ± 0.005 nM) but does not target either the zymogen (prekallikrein) or any other serine protease tested. These findings are supported by a 2.1-Å resolution crystal structure of pKal complexed to a DX-2930 Fab construct, which establishes that the pKal active site is fully occluded by the antibody. DX-2930 injected subcutaneously into cynomolgus monkeys exhibited a long half-life (t½ ∼ 12.5 days) and blocked high molecular weight kininogen proteolysis in activated plasma in a dose- and time-dependent manner. Furthermore, subcutaneous DX-2930 reduced carrageenan-induced paw edema in rats. A potent and long acting inhibitor of pKal activity could be an effective treatment option for pKal-mediated diseases, such as HAE.
Nearest-Neighbour Systems and the Auto-Logistic Model for Binary Data (1972)

Summary Bartlett (1966) and Whittle (1963), respectively, have proposed alternative, non-equivalent definitions of nearest-neighbour systems. The former, conditional probability definition, whilst the more intuitively attractive, presents several basic problems, not least in the identification of available models. In this paper, conditional probability nearest-neighbour systems for interacting random variables on a two-dimensional rectangular lattice are examined. It is shown that, in the case of 0, 1 variables and a homogeneous system, the only possibility is a logistic-type model but in which the explanatory variables at a point are the surrounding array variables themselves. A spatial–temporal approach leading to the same model is also suggested. The final section deals with linear nearest-neighbour systems, especially for continuous variables. The results of the paper may easily be extended to three or more dimensions.
Opposite Effects of PSD-95 and MPP3 PDZ Proteins on Serotonin 5-Hydroxytryptamine2CReceptor Desensitization and Membrane Stability (2006)

PSD-95/Disc large/Zonula occludens 1 (PDZ) domain-containing proteins (PDZ proteins) play an important role in the targeting and the trafficking of transmembrane proteins. Our previous studies identified a set of PDZ proteins that interact with the C terminus of the serotonin 5-hydroxytryptamine (5-HT)(2C) receptor. Here, we show that the prototypic scaffolding protein postsynaptic density-95 (PSD-95) and another membrane-associated guanylate kinase, MAGUK p55 subfamily member 3 (MPP3), oppositely regulate desensitization of the receptor response in both heterologous cells and mice cortical neurons in primary culture. PSD-95 increased desensitization of the 5-HT(2C) receptor-mediated Ca(2+) response, whereas MPP3 prevented desensitization of the Ca(2+) response. The effects of the PDZ proteins on the desensitization of the Ca(2+) response were correlated with a differential regulation of cell surface expression of the receptor. Additional experiments were performed to assess how PDZ proteins globally modulate desensitization of the 5-HT(2C) receptor response in neurons, by using a peptidyl mimetic of the 5-HT(2C) receptor C terminus fused to the human immunodeficiency virus type-1 Tat protein transduction domain, which disrupts interaction between the 5-HT(2C) receptor and PDZ proteins. Transduction of this peptide inhibitor into cultured cortical neurons increased the desensitization of the 5-HT(2C) receptor-mediated Ca(2+) response. This indicates that, overall, interaction of 5-HT(2C) receptors with PDZ proteins inhibits receptor desensitization in cortical neurons.
Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer's disease (2006)

Berberine might be beneficial to AD by intragastric administration though it might exaggerate the inflammation reaction.
Microstrip phased array antennas (1973)

High velocity aircraft, missiles, and rockets require conformai, thin antennas. Ideally, an antenna "paper thin" would best suit the aerodynamic and mechanical engineer. This antenna would neither, disturb the aerodynamic flow, nor would it protrude inwardly to disrupt the mechanical structure.
Permeability Estimation From Fracture Calibration Treatments (1993)

Abstract For data from fracture calibration treatments a methodology is introduced for the determination of the reservoir permeability as an addition to the usual variables of leakoff coefficient and closure pressure. The technique derives from the solution of the diffusivity equation for a well with an infinite-conductivity vertical fracture (as a multi-rate injection) with a superimposed varying filtercake skin effect. The transient reservoir response, which is found to be the essential feature, is then decoupled and used to determine the reservoir permeability.
On the Stability of a Partitioning Algorithm for Tridiagonal Systems (1998)

Componentwise error analysis for a parallel partitioning algorithm for tridiagonal systems is presented. Bounds on the equivalent perturbations are obtained, depending on three constants. Then bounds on the forward error are presented as well, depending on two types of condition numbers. Estimates on the first constant come directly from the roundoff error analysis of the tridiagonal Gaussian elimination [N. Higham, SIAM J. Matrix Anal. Appl., 11 (1990), pp. 521--530]. In the present paper, the second and third constants are bounded for some special classes of matrices, i.e., diagonally dominant (row or column), symmetric positive definite, M-matrices, and totally nonnegative. One of the features of the analysis is that the exact forward and backward errors are bounded, not just their first order approximations, with respect to the machine precision. In all the bounds, the linear terms are given separately to show that the terms of higher order are small enough.
NON-INVASIVE MONITORING OF REFLEXIVE SWALLOWING (1997)

Two standard techniques are used for the clinical examination of abnormal swallowing: Videofluoroscopy which depends on irradiation, and Cervical Auscultation, which makes use of a stethoscope. Both of these techniques have important disadvantages. The first does not lend itself to routine use and the second provides no reliable quantitative information. The aim of this work was to investigate the utility of some of the methods used in Speech and Hearing Sciences. These methods do not use radiation and have the potential to give more accurate timing information than can be derived from auditory/acoustic monitoring. Pilot data were obtained from the simultaneous use of four sensors: an ear-plug microphone of the type used successfully for the detection of otoacoustic emissions; a standard miniature electret microphone ordinarily used for speech recording; a miniature accelerometer of the type sometimes used for monitoring nasality; and a standard electrolaryngograph. Swallow measurements were made with twenty normal adult subjects. The most effective single signal was that provided by the use of standard electrolaryngograph
So What is the Reservoir Permeability? (2000)

Abstract In many reservoirs, permeability values are often available from one or as many as four sources. These permeability sources include core analysis, nuclear magnetic resonance log (NMR), wireline formation tester, and well testing (DST). However, permeability values from these sources often differ significantly. In many cases, this creates confusion as to which value of permeability should be used to best represent reservoir performance and well productivity. In this paper, permeability values, evaluation methods, scales and applicability of all measurements are discussed and verified with field data. Factors influencing each measurement technique are also discussed. Available permeability data from the various sources in a deep water Gulf of Mexico sandstone reservoir are considered to demonstrate how they may be used to build a model of well/reservoir performance. An accurate knowledge of permeability is critical to forecasting rates. Production facilities may be over- or under-designed if rates are inaccurately predicted, excessive capital expenditure for an over-designed facility or the inability to deliver at high rates for an under-designed facility can cost an operator and its partners dearly.
TUCAN, an Antiapoptotic Caspase-associated Recruitment Domain Family Protein Overexpressed in Cancer (2001)

Caspase-associated recruitment domains (CARDs) are protein interaction domains that participate in activation or suppression of CARD-carrying members of the caspase family of apoptosis-inducing proteases. A novel CARD-containing protein was identified that is overexpressed in some types of cancer and that binds and suppresses activation of procaspase-9, which we term TUCAN (tumor-up-regulated CARD-containing antagonist of caspase nine). The CARD domain of TUCAN selectively binds itself and procaspase-9. TUCAN interferes with binding of Apaf1 to procaspase-9 and suppresses caspase activation induced by the Apaf1 activator, cytochrome c. Overexpression of TUCAN in cells by stable or transient transfection inhibits apoptosis and caspase activation induced by Apaf1/caspase-9-dependent stimuli, including Bax, VP16, and staurosporine, but not by Apaf1/caspase-9-independent stimuli, Fas and granzyme B. High levels of endogenous TUCAN protein were detected in several tumor cell lines and in colon cancer specimens, correlating with shorter patient survival. Thus, TUCAN represents a new member of the CARD family that selectively suppresses apoptosis induced via the mitochondrial pathway for caspase activation.
The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis (2002)

Higher testosterone and lower LH, FSH and prolactin levels were good prognostic factors for patients with metastatic prostatic cancer under hormonal treatment, irrespective of tumour grading.
A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis (2006)

Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis. Adhesion-molecule inhibitors hold promise as an effective treatment for relapsing multiple sclerosis. (ClinicalTrials.gov number, NCT00027300.).
The NAC Transcription Factors NST1 and NST2 ofArabidopsisRegulate Secondary Wall Thickenings and Are Required for Anther Dehiscence (2005)

In plants, secondary wall thickenings play important roles in various biological processes, although the factors regulating these processes remain to be characterized. We show that expression of chimeric repressors derived from NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1) and NST2 in Arabidopsis thaliana resulted in an anther dehiscence defect due to loss of secondary wall thickening in anther endothecium. Plants with double, but not single, T-DNA-tagged lines for NST1 and NST2 had the same anther-indehiscent phenotype as transgenic plants that expressed the individual chimeric repressors, indicating that NST1 and NST2 are redundant in regulating secondary wall thickening in anther walls. The activity of the NST2 promoter was particularly strong in anther tissue, while that of the NST1 promoter was detected in various tissues in which lignified secondary walls develop. Ectopic expression of NST1 or NST2 induced ectopic thickening of secondary walls in various aboveground tissues. Epidermal cells with ectopic thickening of secondary walls had structural features similar to those of tracheary elements. However, among genes involved in the differentiation of tracheary elements, only those related to secondary wall synthesis were clearly upregulated. None of the genes involved in programmed cell death were similarly affected. Our results suggest NAC transcription factors as possible regulators of secondary wall thickening in various tissues.
Therapeutic synergism of tiazofurin and selected antitumor drugs against sensitive and resistant P388 leukemia in mice. (1986)

Tiazofurin is a synthetic "C" nucleoside analogue with a promising spectrum of experimental antitumor activity and a relatively novel mechanism of action. Previous work in our laboratories had revealed indications of collateral sensitivity and therapeutic synergism for selected murine tumor models treated with tiazofurin alone or in combination with an antimetabolite or an alkylating agent. Elucidation by others of biochemical indicators of tiazofurin activity provided the rationale for extending our studies to include the tiazofurin combinations reported here. Young, adult, female, BALB/c X DBA/2 F1 mice bearing body burdens of about 4 X 10(7) cells at the start of treatment were used. Cells were implanted either i.p. or s.c. Tiazofurin plus cisplatin or the 5'-palmitate of 1-beta-D-arabinofuranosylcytosine (ara-C) was evaluated against the parent P388/O leukemia line. Tiazofurin plus 6-thioguanine was evaluated against the ara-C-resistant P388. All drug treatments were i.p. injections given daily for 9 days. The experimental design permitted comparison of optimal nontoxic single-agent and two-drug combination regimens on the basis of the estimated log10 change in tumor cell burden at the end of treatment. Concurrent untreated control mice bearing tumor burdens ranging from approximately one to 10(7) cells permitted estimates of cells surviving treatment. Optimal treatment with each of these combinations afforded tumor burden reductions that were greater by 1 to 7 orders of magnitude than the effects of the respective single agents. Optimal single-agent and combination dosages (mg per kg per dose) were as follows: tiazofurin, 500; cisplatin, 2.0; the 5'-palmitate of ara-C, 25; 6-thioguanine, 0.8; tiazofurin, 330 plus cisplatin, 0.58; tiazofurin, 220 plus the 5'-palmitate of ara-C, 20; tiazofurin, 100 plus 6-thioguanine, 0.8. The observed therapeutic synergism of these drugs with tiazofurin in animal models suggests the possibility that treatment with tiazofurin combinations may yield clinical results superior to those obtained with the single agents alone. Therapeutic synergism can be most readily maximized when biochemical markers of drug action are available to provide appropriate clinical-laboratory correlations. Extension of these approaches to the use of tiazofurin, for which biochemical markers and experimental combination chemotherapy leads are now available, would support the rational clinical development of tiazofurin combinations.
Forced Degradation Studies to Identify Critical Process Parameters for the Purification of Infectious Measles Virus (2019)

Oncolytic measles virus (MV) is a promising treatment for cancer but titers of up to 10<sup>11</sup> infectious particles per dose are needed for therapeutic efficacy, which requires an efficient, robust, and scalable production process. MV is highly sensitive to process conditions, and a substantial fraction of the virus is lost during current purification processes. We therefore conducted forced degradation studies under thermal, pH, chemical, and mechanical stress to determine critical process parameters. We found that MV remained stable following up to five freeze-thaw cycles, but was inactivated during short-term incubation (< 2 h) at temperatures exceeding 35 °C. The infectivity of MV declined at pH < 7, but was not influenced by different buffer systems or the ionic strength/osmolality, except high concentrations of CaCl<sub>2</sub> and MgSO<sub>4</sub>. We observed low shear sensitivity (dependent on the flow rate) caused by the use of a peristaltic pump. For tangential flow filtration, the highest recovery of MV was at a shear rate of ~5700 s<sup>-1</sup>. Our results confirm that the application of forced degradation studies is important to identify critical process parameters for MV purification. This will be helpful during the early stages of process development, ensuring the recovery of high titers of active MV particles after purification.
Transarterial aortic valve replacement with a self expanding stent in pigs (2004)

Percutaneous aortic valve replacement with a self expanding nitinol stent in the beating heart is possible. The device was safe under pharmacological stress test. After successful chronic animal experiments, this concept may become a feasible option for treating patients with relevant aortic valve disease but where open heart surgery would be risky.
Modeling and Experiments on a Legged Microrobot Locomoting in a Tubular, Compliant and Slippery Environment (2006)

This paper presents the concept and preliminary modeling of a legged microrobot locomoting in a tubular, compliant and slippery environment. The envisaged application field is related to capsular endoscopy, i.e., the development of a mobile swallowable capsule for navigation inside the gastrointestinal tract for diagnosis and therapy. After introducing and discussing the issue of autonomous locomotion of endoscopic devices, with reference to worldwide ongoing research in the field, the legged solution is proposed and peculiarities of this approach are described. The importance of simulation for developing a legged device is discussed and a locomotion model is presented. Experimental results are described for the definition of biomechanical parameters necessary in the model. Thanks to this work first simulations have been obtained, in which the microrobot’s body moves according to arbitrary gait patterns for the legs and to its interaction with tissue. The resulting tool will be used for the design synthesis, for defining the optimal number of legs and the best number of degrees of freedom for each leg. It will be also used for controlling the device, by identifying the gait pattern to be adopted in order to obtain different capsule movements.
Efficacy of Risperidone Augmentation to Antidepressants in the Management of Suicidality in Major Depressive Disorder (2008)

clinicaltrials.gov Identifier: NCT00167154.
Parasitics and design considerations on oxide-implant VCSELs (2001)

Vertical-cavity surface-emitting lasers (VCSELs) are the enabling technology for low-cost high bit rate communication systems. However, the device parasitics typically limit the high-speed performance. In this letter, the modulation responses of oxide-confined and oxide-implant VCSELs are compared. Both of the configurations were fabricated side by side on the same sample and were thoroughly examined. In oxide-implant VCSELs, the low frequency parasitic rolloff is removed by additional implantation. A VCSEL radiatively coupled model is shown to match the experimental data very well without any fitting parameters. This model can be used to design the device geometry and eliminate the parasitic limitation on high-speed performance.