gebhart/patrepeval huggingface dataset:
Conformational flexibility of the catalytic Asp dyad in HIV-1 protease: An ab initio study on the free enzyme (2000)

The enzyme protease from the human immunodeficiency virus type 1 (HIV-1 PR) is one of the main targets for therapeutic intervention in AIDS. Computer modeling is useful for probing the binding of novel ligands, yet empirical force field-based methods have encountered problems in adequately describing interactions of the catalytic aspartyl pair. In this work we use ab initio dynamic methods to study the molecular interactions and the conformational flexibility of the Asp dyad in the free enzyme. Calculations are performed on model complexes that include, besides the Asp dyad, the conserved Thr26 and Gly27 residues and water molecules present in the active site channel. Our calculations provide proton location and binding mode of the active-site water molecule, which turn out to be different from those of the eukariotic isoenzyme. Furthermore, the calculations reproduce well the structural features of the aspartyl dyad in the protein. Finally, they allow the identification of both dipole/charge interactions and a low-barrier hydrogen bond as important stabilizing factors for the peculiar conformation of the active site. These findings are consistent with site-directed mutagenesis experiments on the 27, 27; positions (Bagossi et al., Protein Eng 1996;9:997-1003). The electric field of the protein frame (included in some of the calculations) does not affect significantly the chemical bonding at the cleavage site. Proteins 2000;39:26-36.
Role of antizyme in degradation of ornithine decarboxylase in HTC cells (1985)

A good correlation was observed between the reciprocal of the half-life of ornithine decarboxylase (ODC) activity in the presence of cycloheximide and the relative amount of ODC-antizyme complex to total ODC (free ODC plus complexed ODC) activity in HTC cells examined at various times after cell dilution or change of medium. Pretreatment of cells with putrescine increased the relative amount of ODC-antizyme complex and decreased the half-life of ODC decay. These results suggested that antizyme plays a key role in ODC degradation.
The BOADICEA model of genetic susceptibility to breast and ovarian cancer (2004)

Several genes conferring susceptibility to breast and ovarian cancer, notably BRCA1 and BRCA2, have been identified. The majority of the familial aggregation of breast cancer is, however, not explained by these genes. We have previously derived, using segregation analysis, a susceptibility model (BOADICEA, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) in which susceptibility to these genes is explained by mutations in BRCA1 and BRCA2 together with a polygenic component reflecting the joint multiplicative effect of multiple genes of small effect on breast cancer risk. Here, we consider the predictions made by this model. The overall familial risks of breast cancer predicted by this model are close to those observed in epidemiological studies. The predicted prevalences of BRCA1 and BRCA2 mutations among unselected cases of breast and ovarian cancer are also consistent with observations from population-based studies. These predictions are closer to the observed values than those obtained using the Claus model and BRCAPRO. The predicted mutation probabilities and cancer risks in individuals with a family history (FH) can differ markedly from those predicted by other models. We conclude that this model provides a rational basis for risk assessment in individuals with a FH of breast or ovarian cancer.
Recommendations for optimization of fortified and blended food aid products from the United States (2010)

Fortified blended foods (FBFs) were introduced into the Food for Peace program (also known as US Public Law 480) in the 1960s. Minimal changes have since been made to their formulations. A Food Aid Quality Enhancement Project to assess the nutritional adequacy of FBFs for vulnerable populations was conducted, and the findings indicate that FBFs do not meet the nutritional needs of infants and young children between the ages of 6 and 24 months. Improvements are also needed for FBFs intended for school-aged children and adults. Two separate products would better meet the varying nutritional needs of diverse groups of beneficiaries. Proposed here is a two-step strategy for better addressing the needs of today's food aid beneficiaries: 1) improving FBFs for general distribution to households, schools, and emergency settings, with potential efficiencies gained in manufacturing and formulation to reduce costs; 2) developing new products for infants and young children, which would deliver the nutrient density required for growth and development.
Determination of total and leachable arsenic and selenium in soils by continuous hydride generation inductively coupled plasma mass spectrometry (1994)

A novel gas–liquid separator has been designed for continuous hydride generation inductively coupled plasma mass spectrometry, incorporating a water trap to remove solution droplets from the gas stream. The system has been applied to the determination of total and leachable arsenic and selenium in soils of the Western Cape region of South Africa. Samples were prepared by alkaline fusion for the determination of total concentrations, and leaching with 1 mol l–1 ammonium nitrate was used to determine the leachable content. Use of the hydride generation system confers a 40-fold increase in sensitivity over conventional nebulization, and eliminates argon chloride interferences. Detection limits were in the range 0.2–1.0 µg l–1. Certified reference materials were analysed, and good agreement was obtained.
The Release of Residual Monomeric Methyl Methacrylate from Acrylic Appliances in the Human Mouth: An Assay for Monomer in Saliva (1988)

A gas-liquid chromatography assay has been developed for the estimation of methyl methacrylate monomer (MMA) in whole saliva, with a lower limit of detection in the order of 1 microgram/mL. Healthy human dentate subjects wore recently made autopolymerized or heat-polymerized polymethyl methacrylate (PMMA) palatal appliances. MMA released into saliva was detected for up to one week after insertion of autopolymerized appliances, with a maximum concentration of 45 micrograms/mL in whole saliva or 180 micrograms/mL in the salivary film on the fitting surface. The MMA was not detected in blood or urine. MMA was also present in the saliva of volunteers wearing appliances which had been heat-polymerized at 70 degrees C for one hr but not cured at 70 degrees C for three hr. The maximum amount of monomer released by an autopolymerized base plate was 29.5 micrograms in the first hour, which, while not a toxic or primary irritant dose, could possibly sensitize patients or elicit an allergic reaction. For minimization of monomer release, autopolymerized appliances should be immersed for 24 hr in water before being worn.
Esophageal Adenocarcinoma Incidence: Are We Reaching the Peak? (2010)

Although definitive conclusions will require additional years of data, the plateau in early stage disease might portend stabilization in the overall incidence of esophageal adenocarcinoma.
Automated sample preparation using membrane microtiter extraction for bioanalytical mass spectrometry (1997)

The development and application of membrane solid phase extraction (SPE) in 96-well microtiter plate format is described for the automated analysis of drugs in biological fluids. The small bed volume of the membrane allows elution of the analyte in a very small solvent volume, permitting direct HPLC injection and negating the need for the time consuming solvent evaporation step. A programmable liquid handling station (Quadra 96) was modified to automate all SPE steps. To avoid drying of the SPE bed and to enhance the analytical precision a novel protocol for performing the condition, load and wash steps in rapid succession was utilized. A block of 96 samples can now be extracted in 10 min., about 30 times faster than manual solvent extraction or single cartridge SPE methods. This processing speed complements the high-throughput speed of contemporary high performance liquid chromatography mass spectrometry (HPLC/MS) analysis. The quantitative analysis of a test analyte (Ziprasidone) in plasma demonstrates the utility and throughput of membrane SPE in combination with HPLC/MS. The results obtained with the current automated procedure compare favorably with those obtained using solvent and traditional solid phase extraction methods. The method has been used for the analysis of numerous drug prototypes in biological fluids to support drug discovery efforts.
Anticancer activity of metal nanoparticles and their peptide conjugates against human colon adenorectal carcinoma cells (2017)

In the present study, nanoparticles of gold, iron oxide and zinc oxide (ZnO) were studied for cytotoxicity in the colorectal cancer cell HT 29. The metallic nanoparticles in the range of <50 and <100 nm were screened for anticancer activity by MTT assay. The nanoparticles were tested at concentrations ranging from 0.5 to 50 µg/ml. Zinc oxide exhibited significant anti-cancer activity in comparison to other nanoparticles. It had an IC50 value of 17.12 µg/ml. The mechanism of action was studied by fluorescence microscopy with acridine orange, propidium iodide and DAPI staining techniques. The ROS production of ZnO nanoparticles was determined by DCFH-DA. The ZnO nanoparticles were conjugated with novel hydrophobic peptides and evaluated for anticancer activity. It was observed that the nanoparticles peptide complex showed better cytotoxicity than either peptide or nanoparticle alone. Thus, the ZnO nanoparticles tested in our study has anticancer activity against colon cancer cells. It can also be conjugated with peptides and used for targeting cancer cells with higher efficacy.
Enhanced circuit switched data for real time services over GSM (1999)

The deployment of the HSCSD (high speed circuit switched data) is starting in GSM networks. This brings multislot capability to GSM and significantly enhances the available data rates together with the introduction of the 14.4 kbps per time slot data rate. The next step in the evolution of the real-time GSM services is the enhanced circuit switched data (ECSD) which is being developed in ETSI as GSM Phase 2+ work item (EDGE Phase I) parallel to enhanced general packet radio service (EGPRS). The ECSD radio interface deploys 8-PSK modulation in addition to GMSK and thus enables higher data throughput per time slot. The ECSD type radio interface can also be seen as a candidate in the development of real-time services for the evolving mobile networks. This paper focuses on the ECSD concept and presents its essential features as they are defined at the moment, before finalisation of the standard.
Overexpression of IL-8 in the cornea induces ulcer formation in the SCID mouse (2006)

Our results indicate that IL-8 overexpression in corneal tissue causes ulcer formation in the cornea through chemoattraction of neutrophils, suggesting the aetiological role of IL-8 in some types of corneal ulcers.
Entertainment feature of a game using skin conductance response (2004)

There are many computer games in the world, but generally game players challenge either the computer, or real players in the case of many person games. In view of the strong connectivity advocated between communication and entertainment in the field of entertainment computing, the use of biological signals for computer games is of interest. Here, a novel type of game using biological signals was developed as an entertainment device. The change in skin conductance caused by sweating was measured as a signal reflecting the player's agitation during the game. This type of game incorporates various characteristics relating to communication. First, players of the game challenge themselves because they are able to view their detected biological signals. In this situation, a kind of self-reference system is constructed. Second, the environments in which the game is played changed how the game was enjoyed. Third, the game system reveals differences of context between player and observer. From these characteristics, it is considered that the use of biological signals is attractive for entertainment computing.
High-precision mapping of protein–protein interfaces: an integrated genetic strategy combining en masse mutagenesis and DNA-level parallel analysis on a yeast two-hybrid platform (2007)

Understanding networks of protein-protein interactions constitutes an essential component on a path towards comprehensive description of cell function. Whereas efficient techniques are readily available for the initial identification of interacting protein partners, practical strategies are lacking for the subsequent high-resolution mapping of regions involved in protein-protein interfaces. We present here a genetic strategy to accurately map interacting protein regions at amino acid precision. The system is based on parallel construction, sampling and analysis of a comprehensive insertion mutant library. The methodology integrates Mu in vitro transposition-based random pentapeptide mutagenesis of proteins, yeast two-hybrid screening and high-resolution genetic footprinting. The strategy is general and applicable to any interacting protein pair. We demonstrate the feasibility of the methodology by mapping the region in human JFC1 that interacts with Rab8A, and we show that the association is mediated by the Slp homology domain 1.
The 8p11 Myeloproliferative Syndrome: A Distinct Clinical Entity Caused by Constitutive Activation of <i>FGFR1</i> (2002)

Several recurrent translocations that involve chromosome band 8p11 have been described in myeloid malignancies. These translocations target two distinct genes: (1) FGFR1, a receptor tyrosine kinase for fibroblast growth factors, and (2) MOZ, a putative histone acetyltransferase whose precise function remains to be defined. Disruption of FGFR1 is associated with a disease entity known as the 8p11 myeloproliferative syndrome (EMS)/stem cell leukemia-lymphoma syndrome, a chronic myeloproliferative disorder that frequently presents with eosinophilia and associated T-cell lymphoblastic lymphoma. The disease is aggressive and rapidly transforms to acute leukaemia, usually of myeloid phenotype. Currently, only allogeneic stem cell transplantation appears to be effective in eradicating or suppressing the malignant clone. To date, four gene fusions associated with distinct translocations have been described in EMS: the t(8;13)(p11;q12), t(8;9)(p11;q33), t(6;8)(q27;p11) and t(8;22)(p11q22) fuse ZNF198, CEP110, FOP and BCR, respectively, to FGFR1. The resulting fusion proteins have constitutive tyrosine kinase activity and activate multiple signal transduction pathways. These pathways and the fusion proteins are attractive targets for targeted signal transduction therapy.
RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. (1998)

Page 12298, Fig. 1: There is a single nucleotide error in the sequence of the RICK cDNA. Correction of this error extends the N terminus of RICK by 10 amino acids and results in a protein of 540 amino acids. The revised sequence of RICK is shown inpanel A. In panel C, the alignment of RICK and RIP is incorrect. A correct alignment is shown below.
1,25-Dihydroxyvitamin D3 Induces Differentiation of a Retinoic Acid–Resistant Acute Promyelocytic Leukemia Cell Line (UF-1) Associated With Expression of p21WAF1/CIP1 and p27KIP1 (1999)

Retinoic acid (RA) resistance is a serious problem for patients with acute promyelocytic leukemia (APL) who are receiving all-trans RA. However, the mechanisms and strategies to overcome RA resistance by APL cells are still unclear. The biologic effects of RA are mediated by two distinct families of transcriptional factors: RA receptors (RARs) and retinoid X receptors (RXRs). RXRs heterodimerize with 1, 25-dihydroxyvitamin D3 [1,25(OH)2D3] receptor (VDR), enabling their efficient transcriptional activation. The cyclin-dependent kinase (cdk) inhibitor p21(WAF1/CIP1) has a vitamin D3-responsive element (VDRE) in its promoter, and 1,25(OH)2D3 enhances the expression of p21(WAF1/CIP1) and induces differentiation of selected myeloid leukemic cell lines. We have recently established a novel APL cell line (UF-1) with features of RA resistance. 1,25(OH)2D3 can induce growth inhibition and G1 arrest of UF-1 cells, resulting in differentiation of these cells toward granulocytes. This 1, 25(OH)2D3-induced G1 arrest is enhanced by all-trans RA. Also, 1, 25(OH)2D3 (10(-10) to 10(-7) mol/L) in combination with RA markedly inhibits cellular proliferation in a dose- and time-dependent manner. Associated with these findings, the levels of p21(WAF1/CIP1) and p27(KIP1) mRNA and protein increased in these cells. Northern blot analysis showed that p21(WAF1/CIP1) and p27(KIP1) mRNA and protein increased in these cells. Northern blot analysis showed that p21(WAF1/CIP1) and p27(KIP1) transcripts were induced after 6 hours' exposure to 1,25(OH)2D3 and then decreased to basal levels over 48 hours. Western blot experiments showed that p21(WAF1/CIP1) protein levels increased and became detectable after 12 hours of 1,25(OH)2D3 treatment and induction of p27(KIP1) protein was much more gradual and sustained in UF-1 cells. Interestingly, the combination of 1, 25(OH)2D3 and RA markedly enhanced the levels of p27(KIP1) transcript and protein as compared with levels induced by 1, 25(OH)2D3 alone. In addition, exogenous p27(KIP1) expression can enhance the level of CD11b antigen in myeloid leukemic cells. In contrast, RA alone can induce G1 arrest of UF-1 cells; however, it did not result in an increase of p21(WAF1/CIP1) and p27(KIP1) transcript and protein expression in RA-resistant cells. Taken together, we conclude that 1,25(OH)2D3 induces increased expression of cdk inhibitors, which mediates a G1 arrest, and this may be associated with differentiation of RA-resistant UF-1 cells toward mature granulocytes.
NAD/NADH Models with Axial/Central Chiralities:  Superiority of the Quinoline Ring System (2001)

Precursors of NAD model compounds 1c and 3a,b were successfully resolved into their atropisomers with respect to carbamoyl rotation. Atropisomers of quinoline derivatives are much more stable than pyridine derivatives as determined by cyclic voltammetry and X-ray crystallography. The 1,4-reduction of NAD model compound 4 was successfully achieved, affording novel NADH model compound 5. The rotational properties of the side chain of 5 were investigated by means of dynamic NMR. The rotational rate and syn/anti ratio, which indicate the orientation between carbonyl oxygen and hydrogen at the 4-position, are significantly affected by addition of magnesium ion. In the rotational transition state, the double-bond character of the C(carbonyl)-N(amide) bond is disrupted judging from the activation parameters. The oxidation of chiral 5 with p-benzoquinone in the presence of magnesium ion catalyst gave predominantly one enantiomer of 4. On the other hand, oxidation of 5 with p-chloranil (tetrachloro-p-benzoquinone) in the absence of magnesium ions affords the opposite enantiomer of 4 as the major product. The product enantiomer ratio is parallel to the syn/anti ratio in the starting material, indicating the importance of ground state conformation to stereochemistry of the reaction.
The packing density in proteins: standard radii and volumes 1 1Edited by J. M. Thornton (1999)

The sizes of atomic groups are a fundamental aspect of protein structure. They are usually expressed in terms of standard sets of radii for atomic groups and of volumes for both these groups and whole residues. Atomic groups, which subsume a heavy-atom and its covalently attached hydrogen atoms into one moiety, are used because the positions of hydrogen atoms in protein structures are generally not known. We have calculated new values for the radii of atomic groups and for the volumes of atomic groups. These values should prove useful in the analysis of protein packing, protein recognition and ligand design. Our radii for atomic groups were derived from intermolecular distance calculations on a large number (approximately 30,000) of crystal structures of small organic compounds that contain the same atomic groups to those found in proteins. Our radii show significant differences to previously reported values. We also use this new radii set to determine the packing efficiency in different regions of the protein interior. This analysis shows that, if the surface water molecules are included in the calculations, the overall packing efficiency throughout the protein interior is high and fairly uniform. However, if the water structure is removed, the packing efficiency in peripheral regions of the protein interior is underestimated, by approximately 3.5 %.
Die chirurgische Behandlung der Lungentuberkulose (1964)

Die chirurgische Behandlung der Lungentuberkulose, die durch die Einführung des künstlichen Pneumothorax durch Forlanini im Jahre 1892 ihren Anfang genommen und namentlich durch den Ausbau der Thorakoplastik durch Brauer und Friedrich und dann in allererster Linie durch Sauerbruch allgemeine Anerkennung gefunden hat, hat auch heute trotz der großen Fortschritte, die durch die neuzeitlichen Tuberculostatica erreicht worden sind, ihre Bedeutung nicht verloren.
Assessment of PCR of the D17S30 Locus for Forensic Identification (1994)

PCR analysis of the VNTR locus D17S30 was assessed for its potential use in forensic identification analysis. "Allelic drop-out," the inefficient amplification of some alleles, complicates the interpretation of DNA typing at this locus. PCR conditions were varied in an effort to improve amplification of the alleles at this locus. Such changes included the use of denaturants, formamide and DMSO, to overcome any incomplete denaturation of template strands due to GC content or allele size. Lowering the annealing temperature during the PCR cycle enhanced the amplification of a larger fragment, but this was not related to the D17S30 locus. It appears that the structure of the genome of some individuals rendered PCR amplification inefficient at this locus.
Pilot Reactions to Optical Defects Found in F-111 Bird Impact Resistant Windscreens. (1980)

A field study was conducted to assess the scope and severity of mission-related optical problems associated with the new F-111 Bird Impact Resistant Transparency (BIRT) windscreen. Data for this study was gathered from an 81-item questionnaire and used to scale the opinions of 33 USAFE pilots. Principal findings indicate that: (1) Distortion is perceived as the most disruptive optical factor followed in order by multiple images, haze and rainbowing. (2) The worst combination of optical defect and flight task is multiple images during night approach and landing. (3) The extent to which BIRT optical problems are perceived as impairing mission performance is sufficiently great to further justify research for improving windscreen optical quality. (4) Pilots with very limited amounts of BIRT flying time (20-80 hours) are less likely to perceive windscreen optical problems than a middle experience group (with 100 to 180 flying hours). This difference is attributed to a lack of exposure to the optical effects; and (5) Pilots with relatively extensive BIRT flying experience (over 200 hours) are also less prone to perceive windscreen problems than the middle experience group. This difference is attributed to the effect of a period of adjustment to the optical anomalies.