gebhart/patrepeval huggingface dataset:
Functional Characterization of Mitochondrial Carnitine Palmitoyltransferases I and II Expressed in the Yeast Pichia pastoris, (1997)

The rate-limiting step in beta oxidation is the conversion of long-chain acyl-CoA to acylcarnitine, a reaction catalyzed by the outer mitochondrial membrane enzyme carnitine palmitoyltransferase I (CPTI) and inhibited by malonyl-CoA. The acylcarnitine is then translocated across the inner mitochondrial membrane by the carnitine/acylcarnitine translocase and converted back to acyl-CoA by CPTII. Although CPTII has been examined in detail, studies on CPTI have been hampered by an inability to purify CPTI in an active form from CPTII. In particular, it has not been conclusively demonstrated that CPTI is even catalytically active, or whether sensitivity of CPTI to malonyl-CoA is an intrinsic property of the enzyme or is contained in a separate regulatory subunit that interacts with CPTI. To address these questions, the genes for CPTI and CPTII were separately expressed in Pichia pastoris, a yeast with no endogenous CPT activity. High levels of CPT activity were present in purified mitochondrial preparations from both CPTI- and CPTII-expressing strains. Furthermore, CPTI activity was highly sensitive to inhibition by malonyl-CoA while CPTII was not. Thus, CPT catalytic activity and malonyl-CoA sensitivity are contained within a single CPTI polypeptide in mammalian mitochondrial membranes. We describe the kinetic characteristics for the yeast-expressed CPTs, the first such report for a CPTI enzyme in the absence of CPTII. Yeast-expressed CPTI is inactivated by detergent solubilization. However, removal of the detergent in the presence of phospholipids resulted in the recovery of malonyl-CoA-sensitive CPTI activity, suggesting that CPTI requires a membranous environment. CPTI is thus reversibly inactivated by detergents.
Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma (2006)

Rhinovirus, C pneumoniae, and B pertussis are found in the sputum or pharyngeal swab specimens of asthmatic subjects without concurrent symptoms of infection or asthma exacerbation, as well as in some healthy controls. Positivity is associated with lower lung function and more frequent asthma symptoms.
High aspect ratio quarter-micron electroless copper integrated technology (1997)

Copper metallization is under intensive investigation for Ultra-Large-Scale-Integration (ULSI) applications and the electroless technology has been demonstrated as a promising technology for sub-0.25 μm features on large silicon wafers. In this work we demonstrate the integration of several electroless deposition recipes of different thin-film materials for the processing of high aspect ratio via contacts and trenches. The integrated process includes the deposition of both copper and barrier-material by electroless deposition from an aqueous solution due to an electrochemical oxidation-reduction reaction that takes place on the liquid-solid interface. The reaction starts on a seed layer and continues on the deposited layer as a self catalytic process. The deposition is very conformal due to the fact that the reaction is surface reaction limited. The ions diffusivity in the solution is high enough so there is a large enough supply of complexed ions inside the trench until its opening becomes very small. A simplified model is derived that shows that the conformality is improved as the ions concentration increased and the deposition rate is reduced. In this work we present also the material properties of the electroless barrier, the integration concepts, and experimental results of the fully integrated structure. Also presented is the integrated barrier/Cu/barrier process where the copper is positively patterned, planarized by a chemical mechanical process, and capped by a top barrier that is deposited by a self aligned process.
A Semisynthesis Platform for Investigating Structure−Function Relationships in the N-Terminal Domain of the Anthrax Lethal Factor (2010)

Many bacterial toxins act by covalently altering molecular targets within the cytosol of mammalian cells and therefore must transport their catalytic moieties across a membrane. The Protective-Antigen (PA) moiety of anthrax toxin forms multimeric pores that transport the two enzymatic moieties, the Lethal Factor (LF) and the Edema Factor, across the endosomal membrane to the cytosol. The homologous PA-binding domains of these enzymes contain N-terminal segments of highly charged amino acids that are believed to enter the pore and initiate N- to C-terminal translocation. Here we describe a semisynthesis platform that allows chemical control of this segment in LF(N), the PA-binding domain of LF. Semisynthetic LF(N) was prepared in milligram quantities by native chemical ligation of synthetic LF(N)(14-28)alphathioester with recombinant N29C-LF(N)(29-263) and compared with two variants containing alterations in residues 14-28 of the N-terminal region. The properties of the variants in blocking ion conductance through the PA pore and translocating across planar phospholipid bilayers in response to a pH gradient were consistent with current concepts of the mechanism of polypeptide translocation through the pore. The semisynthesis platform thus makes new analytical approaches available to investigate the interaction of the pore with its substrates.
New “multicolor” polypeptide diamagnetic chemical exchange saturation transfer (DIACEST) contrast agents for MRI (2008)

An array of 33 prototype polypeptides was examined as putative contrast agents that can be distinguished from each other based on the chemical exchange saturation transfer (CEST) mechanism. These peptides were chosen based on predictions of the chemical exchange rates of exchangeable amide, amine, and hydroxyl protons that produce this contrast, and tested at 11.7T for their CEST suitability. Artificial colors were assigned to particular amino acid units (lysine, arginine, threonine, and serine) based on the separate resonance frequencies of these exchangeable protons. The magnitude of the CEST effect could be fine-tuned by altering the amino acid sequence, and these three exchangeable groups could be distinguished in an MR phantom based on their different chemical shifts ("colors"). These new diamagnetic CEST (DIACEST) agents possess a wide range of electrostatic charges, compositions, and protein stabilities in vivo, making them potentially suitable for a variety of biological applications such as designing MR reporter genes for imaging cells and distinguishing multiple targets within the same MR image.
Computer Architectures for Pictorial Information Systems (1981)

In the international search for the optimal image processing computer architecture, image parallelism is the key to cost effectiveness.
The Role of Intracellularly Released Formaldehyde and Butyric Acid in the Anticancer Activity of Acyloxyalkyl Esters (2005)

Previous studies described a family of anticancer histone deacetylase inhibitor prodrugs of formula Me(CH(2))(2)COOCH(R)OR(1), which upon intracellular hydrolysis release acids and aldehydes. This study examines the mechanisms by which the prodrugs affect tumor cells and the contribution of the released aldehyde (formaldehyde or acetaldehyde) and acids to their anticancer activity. Type I prodrugs release 2 equiv of a carboxylic acid and 1 equiv of an aldehyde, and of Type II release 2 equiv of acids and 2 equiv of an aldehyde. SAR studied inhibition of proliferation, induction of differentiation and apoptosis, histone acetylation, and gene expression. Formaldehyde, measured intracellularly, was the dominant factor affecting proliferation and cell death. Among the released acids, butyric acid elicited the greatest antiproliferative activity, but the nature of the acid had minor impact on proliferation. In HL-60 cells, formaldehyde-releasing prodrugs significantly increased apoptosis. The prodrugs affected to a similar extent the wild-type HL-60 and MES-SA cell lines and their multidrug-resistant HL-60/MX2 and MES-Dx5 subclones. In a cell-free histone deacetylase (HDAC) inhibition-assay only butyric acid inhibited HDAC activity. The butyric acid and formaldehyde induced cell differentiation and increased p53 and p21 levels, suggesting that both affect cancer cells, the acid by inhibiting HDAC and the aldehyde by an as yet unknown mechanism.
Regeneration of Meniscal Cartilage with Use of a Collagen Scaffold. Analysis of Preliminary Data* (1997)

A collagen scaffold was designed for use as a template for the regeneration of meniscal cartilage and was tested in ten patients in an initial, Food and Drug Administration-approved, clinical feasibility trial. The goal of the study was to evaluate the implantability and safety of the scaffold as well as its ability to support tissue ingrowth. The study was based on the findings of in vitro and in vivo investigations in dogs that had demonstrated cellular ingrowth and tissue regeneration through the scaffold. Nine patients remained in the study for at least thirty-six months, and one patient voluntarily withdrew after three months for personal reasons. The collagen scaffold was found to be implantable and to be safe over the three-year period. Histologically, it supported regeneration of tissue in meniscal defects of various sizes. No adverse immunological reactions were noted on sequential serological testing. On second-look arthroscopy, performed either three or six months after implantation, gross and histological evaluation revealed newly formed tissue replacing the implant as it was resorbed. At thirty-six months, the nine patients reported a decrease in the symptoms. According to a scale that assigned 1 point for strenuous activity and 5 points for an inability to perform sports activity, the average score was 1.5 points before the injury, 3.0 points after the injury and before the operation, and 2.4 points at six months postoperatively, 2.2 points at twelve months, 2.0 points at twenty-four months, and 1.9 points at thirty-six months. According to a scale that assigned 0 points for no pain and 3 points for severe pain, the average pain score was 2.2 points preoperatively and 0.6 point thirty-six months postoperatively. One patient, who had had a repair of a bucket-handle tear of the medial meniscus and augmentation with the collagen scaffold, had retearing of the cartilage nineteen months after implantation. Another patient had debridement because of an irregular area of regeneration at the scaffold-meniscus interface twenty-one months after implantation. Magnetic resonance imaging scans demonstrated progressive maturation of the signal within the regenerated meniscus at three, six, twelve, and thirty-six months. These findings suggest that regeneration of meniscal cartilage through a collagen scaffold is possible. Additional studies are needed to determine long-term efficacy.
Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. (1994)

Heme oxygenase-1 is an important enzyme that degrades heme, a pro-oxidant, leading to the formation of antioxidant molecules. In this study we demonstrate by immunocytochemistry close association of heme oxygenase-1 with Alzheimer neurofibrillary pathology and with the neurofibrillary tangles found in progressive supranuclear palsy and subacute sclerosing panencephalitis. In Alzheimer's disease, using two different rabbit antisera against heme oxygenase-1 protein, we localized, using immunocytochemical methods, heme oxygenase-1 to neurofibrillary tangles, senile plaque neurites, granulovacuolar degeneration, and neuropil threads. Only light background staining was seen in young controls and sporadic lesion-related immunoreactivity in age-matched controls. The increase in heme oxygenase-1 protein in association with the neurofibrillary pathology of Alzheimer's disease and other diseases characterized by neurofibrillary tangles supports the notion that the generation of free radicals and oxidative stress plays a role in the pathogenesis of neurofibrillary pathology.
Nanospray mass spectrometry in protein and peptide chemistry (2000)

The introduction of electrospray in the mid-1980s revolutionised biological mass spectrometry, in particular in the field of protein and peptide sequence analysis. Electrospray is a concentration-dependent, rather than a mass-dependent process, and maximum sensitivity is achieved at low flow rates with high-concentration, low-volume samples. This has lead to the development of nanoelectrospray, microelectrospray and related low flow-rate forms of electrospray which offer high sensitivity with low sample consumption. In this chapter the physical chemistry of low flow-rate electrospray is discussed, and a brief review of the types of low flow-rate electrospray interfaces is made. An indication of the performance obtainable on various instruments is given, along with some comments from the author's own experience of these techniques.
Mesothelin Overexpression Promotes Mesothelioma Cell Invasion and MMP-9 Secretion in an Orthotopic Mouse Model and in Epithelioid Pleural Mesothelioma Patients (2012)

Our data provide evidence elucidating a biologic role for MSLN as a factor promoting tumor invasion and MMP-9 expression in MSLN expressing MPM. As regional invasion is the characteristic feature in MSLN expressing solid cancers (MPM, pancreas, and ovarian), our observations add rationale to studies investigating MSLN as a therapeutic target.
Recombinant Protein Synthesis in Chinese Hamster Ovary Cells Using a Vaccinia Virus/Bacteriophage T7 Hybrid Expression System (1996)

The vaccinia virus/bacteriophage T7 expression system was adapted to Chinese hamster ovary (CHO) cells. Vaccinia virus undergoes abortive infection in CHO cells, which is characterized by a sharp reduction in protein synthesis at the stage of viral intermediate gene expression. We determined that expression of a T7 promoter-regulated chloramphenicol acetyltransferase gene was at least 20 times more efficient in permissive BS-C-1 than in CHO cells. The encephalomyocarditis virus 5'-untranslated region, which confers cap-independent translatability to mRNA, stimulated recombinant protein synthesis by 10-fold in both cell lines, maintaining the advantage of the BS-C-1 cells over CHO cells. Since the cowpox virus hr gene overcomes vaccinia virus host range restriction in CHO cells, we constructed a recombinant virus that carries an intact hr gene in addition to the T7 RNA polymerase gene. With this virus, synthesis of T7 RNA polymerase was enhanced and production of a recombinant protein occurred in CHO cells at the level observed in permissive cell lines. Extension of the vaccinia virus/bacteriophage T7 expression system to CHO cells should be of wide interest, as these cells have advantages for preparation of recombinant proteins in research and biotechnology.
Tissue microarrays for comparing molecular features with proliferation activity in breast cancer (2005)

Tissue microarrays (TMAs) are potentially suited to find associations between molecular features and clinical outcome. Enhanced cell proliferation, as measured by Ki67 immunohistochemistry, is related to poor patient prognosis in many different tumor types. Ki67 expression shows considerable intratumoral heterogeneity. It is unclear if the TMA format is suitable for the analysis of potentially heterogeneous markers because of the small size of TMA spots. We have analyzed a breast cancer TMA containing 2,517 breast tissues, including 2,222 neoplastic and 295 normal or premalignant samples, for Ki67 labeling index (Ki67 LI) and additional markers with a known relationship to Ki67 LI by immunohistochemistry (ER, PR, Bcl-2, Egfr, p16, p53) and Fluorescence in situ hybridization (HER2, MDM2, CCND1, MYC). A high Ki67 LI was linked to tumor phenotype including grade (p < 0.0001), stage (p < 0.0001), nodal stage (p = 0.0018), and patient prognosis (p < 0.0001), elevated protein levels of p53, p16 and Egfr, reduced levels of Bcl2, ER, and PR (p < 0.0001 each), as well as amplifications of HER2, MYC, CCND1 and MDM2 (p < 0.0001 each). In summary, all expected associations between Ki67 and the analyzed molecular markers could be reproduced with high statistical significance using a TMA containing only one tissue sample per tumor, measuring 0.6 mm in diameter. We conclude that associations with cell proliferation can be reliably analyzed in a TMA format.
Modeling a Vuggy Carbonate Reservoir, McElroy Field, West Texas (1999)

The McElroy field produces approximately 17,000 BOPD (barrels of oil per day) under a mature waterflood from the Permian Grayburg Formation. The main pay zone in the reservoir is primarily peloidal dolograinstones/packstones with interparticle/intercrystalline porosities. The central portion of the field is more heterogeneous because of thin high-porosity and high-permeability vuggy zones. The occurrence of these zones is confirmed by core description and measurements, porosity logs, tracer studies, and injectivity measurements. These thin high-porosity and high-permeability vuggy zones diminish waterflood effectiveness and leave millions of barrels of bypassed oil in the lower permeability matrix. A method was developed to identify the vuggy zones on logs, create geostatistical models of porosity and permeability incorporating the vuggy zones, and characterize them in simulation models. The methodology involved the following: (1) developing a log trace to identify zones of high secondary porosity, mainly vuggy porosity, in the area of the field that was modeled, (2) creating a detailed geostatistical model (1 million cells) of total porosity using well-log data, (3) creating a geostatistical permeability model based on total porosity, (4) creating a separate detailed geostatistical model of secondary porosity, and (5) superimposing exceptionally high permeability in areas of the permeability model defined by high secondary porosities. The detailed permeability models were scaled-up to 12,000-cell models for simulation studies. The models incorporating vuggy permeability distributions showed a far superior history match of primary and waterflood processes than did models that did not incorporate vuggy permeability; these models also showed good-quality history matches for individual wells. Successful history matching of the simulation models validates our method and indicates that core data underestimate the permeability of vuggy zones due to sampling and measurement issues.
LASER THERAPY: SCIENTIFIC BASIS AND CLINICAL ROLE (1993)

The ability of laser irradiation to destroy tissue is well known. Less well known is the fact that the same radiation, at much lower intensities, can non-destructively alter cellular function. This latter phenomenon, which occurs in the absence of significant heating, is now a basis for the conservative treatment of a variety of musculoskeletal, neurological, and soft tissue conditions in many parts of the world. This review first examines the 25-year history and scientific basis of "laser therapy." Clinical applications are discussed and the reasons for its relative lack of acceptance in the US are examined. The article concludes with an overview of current research and the impact it will have on laser therapy's role in US clinical practice.
Issues in Funding the Activities of Small Firms through SBICs (1997)

Small business; Bank investments
Evaluation of a novel hybrid bioartificial liver based on a multi-layer flat-plate bioreactor (2012)

The HBAL showed great efﬁciency and safety in the treatment of acute liver failure.
Precise Epitope Mapping of Malaria Parasite Inhibitory Antibodies by TROSY NMR Cross-Saturation (2004)

We have applied NMR cross-saturation with TROSY detection to the problem of precisely mapping conformational epitopes on complete protein antigen molecules. We have investigated complexes of the Fab fragments of two antibodies that have parasite inhibitory activity, bound to the important malaria vaccine candidate antigen, Plasmodium falciparum MSP1(19). The results indicate remarkable overlap between these epitopes for inhibitory antibodies, and will provide a basis for theoretical modeling of the antibody-antigen interface.
Predicting Molecular Geometry (2001)

Chapter eight discusses a number of issues pertaining to molecular geometry. These issues include representation in program inputs, and choice of coordinate space for optimization calculations. The relative merits of various geometry optimization algorithms are discussed.
Functional Analysis of Glycosyltransferases Encoded by the Capsular Polysaccharide Biosynthesis Locus of Streptococcus pneumoniae Serotype 14 (1997)

Bacteria belonging to the species Streptococcus pneumoniae vary in their capsule. Presently, 90 capsular serotypes are known, all possessing their own specific polysaccharide structure. Little is known about the biosynthesis of these capsular polysaccharides. The cps locus of S. pneumoniae serotype 14 was cloned. So far, 7 open reading frames have been sequenced, cps14B to cps14H. The gene products are similar to proteins involved in bacterial polysaccharide biosynthesis, both of Gram-negative and -positive micro-organisms. Gene-specific mutants were created for cps14D to cps14H by insertional mutagenesis. All mutants no longer agglutinated with a monoclonal antibody against type 14 capsule polysaccharides. The biosynthetic function of cps14E and cps14G was determined by analysis of the intermediates in the synthesis of the oligosaccharide subunit, formed in membrane preparations of the wild-type and mutant strains and in membrane preparations of Escherichia coli expressing the pneumococcal glycosyltransferases. The enzyme encoded by cps14E is a glucosyl-1-phosphate transferase that links glucose to a lipid carrier, the first step in the biosynthesis of the type 14 repeating unit. The gene product of cps14G encodes a beta-1,4-galactosyltransferase, the enzyme responsible for the second step in the subunit synthesis, the transfer of galactose to lipid-linked glucose.
A mutant of the major apple allergen, Mal d 1, demonstrating hypo‐allergenicity in the target organ by double‐blind placebo‐controlled food challenge (2005)

A moderate decrease in IgE-binding potency translates into a potent inhibition of biological activity. This is the first study that confirms by DBPCFC that a mutated recombinant major food allergen is clinically hypo-allergenic. This paves the way towards safer immunotherapy for the treatment of food-allergic patients.
Multiplex Pyrosequencing (2002)

We describe here the development of a new and simple single-tube multiplex Pyrosequencing assay. Genomic DNA or cDNA was employed to PCR amplify region(s) using biotinylated and normal primer(s). Subsequent to capture of PCR products on streptavidin-coated beads, single-stranded DNA separation and hybridization of multiple sequencing primers, Pyrosequencing was performed. The obtained pyrogram resulted in a unique pattern in which the intensity of the signal determined the number of incorporated nucleotide(s). Here, we demonstrate the use of this multiplex Pyrosequencing for single nucleotide polymorphisms genotyping and microbial typing.