gebhart/patrepeval huggingface dataset:
Very fast prediction and rationalization of pKa values for protein–ligand complexes (2008)

The PROPKA method for the prediction of the pK(a) values of ionizable residues in proteins is extended to include the effect of non-proteinaceous ligands on protein pK(a) values as well as predict the change in pK(a) values of ionizable groups on the ligand itself. This new version of PROPKA (PROPKA 2.0) is, as much as possible, developed by adapting the empirical rules underlying PROPKA 1.0 to ligand functional groups. Thus, the speed of PROPKA is retained, so that the pK(a) values of all ionizable groups are computed in a matter of seconds for most proteins. This adaptation is validated by comparing PROPKA 2.0 predictions to experimental data for 26 protein-ligand complexes including trypsin, thrombin, three pepsins, HIV-1 protease, chymotrypsin, xylanase, hydroxynitrile lyase, and dihydrofolate reductase. For trypsin and thrombin, large protonation state changes (|n| > 0.5) have been observed experimentally for 4 out of 14 ligand complexes. PROPKA 2.0 and Klebe's PEOE approach (Czodrowski P et al. J Mol Biol 2007;367:1347-1356) both identify three of the four large protonation state changes. The protonation state changes due to plasmepsin II, cathepsin D and endothiapepsin binding to pepstatin are predicted to within 0.4 proton units at pH 6.5 and 7.0, respectively. The PROPKA 2.0 results indicate that structural changes due to ligand binding contribute significantly to the proton uptake/release, as do residues far away from the binding site, primarily due to the change in the local environment of a particular residue and hence the change in the local hydrogen bonding network. Overall the results suggest that PROPKA 2.0 provides a good description of the protein-ligand interactions that have an important effect on the pK(a) values of titratable groups, thereby permitting fast and accurate determination of the protonation states of key residues and ligand functional groups within the binding or active site of a protein.
Transcriptional Control of T Lymphocyte Differentiation (2001)

Initiation of gene transcription by transcription factors (TFs) is an important regulatory step in many developmental processes. The differentiation of T cell progenitors in the thymus is tightly controlled by signaling molecules, ultimately activating nuclear TFs that regulate the expression of T lineage-specific genes. During the last 2 years, significant progress has been made in our understanding of the signaling routes and TFs operating during the earliest stages of thymic differentiation at the CD4(-)CD8(-) double negative stage. Here we will review the TF families that play an important role in differentiation of thymocytes, particularly focusing on recent new information with respect to the Tcf, bHLH, GATA, and CBF/HES TF families.
Aluminium‐organische Synthese im Bereich olefinischer Kohlenwasserstoffe (1952)

Abstract Der Verlauf einer neuartigen Additionsreaktion von α‐Olefinen an LiAIH 4 bzw. AlH 3 konnte aufgeklärt werden. Über die Additionsprodukte ist jetzt auch die CC‐—Bindung in bestimmten Olefinen mit LiAlH 4 bzw. AlH 3 reduzierbar. Auch Aluminiumtrialkyle vermögen sich an Äthylen oder α‐Olefine zu addieren. Bei Temperaturen von etwa 200°C verändern Aluminiumtrialkyle Äthylen und andere Olefine rein katalytisch unter Bildung höherer Olefine durch Polymerisation. Dieses Verfahren wurde bereits halbtechnisch erprobt. Die neuen Ergebnisse eröffnen der präparativen organischen Chemie und ihrer Technik neue Möglichkeiten.
Detection of urinary tract infections by rapid methods (1988)

A review of rapid urine screens for detection of bacteriuria and pyuria demonstrates a number of available alternatives to the culture method. Selection of one or more of these systems for routine use is dependent upon the laboratory and the patient population being tested. The laboratory approach to the diagnosis of urinary tract infection should consider the clinical diagnosis of the patient whenever possible. Keeping in mind that quantitative urine cultures alone cannot be used to detect infection in some patient populations unless lower colony counts are considered, a rapid screen may be a more practical approach. It has become accepted that 10(5) CFU/ml can no longer be used as the standard for all patient groups, that pyuria often is important in making the diagnosis of a urinary tract infection, and that most of the rapid screens are more sensitive than the culture method at 10(5) CFU/ml. Presently, no one approach can be recommended for all laboratories and all patient groups. However, each diagnostic laboratory should select one approach which is best for its situation. It is not practical, efficient, or cost effective to define a protocol for each possible clinical condition; however, all should be considered when developing a protocol. This protocol should be compatible with the patient population and communicated to the physicians. Use of a rapid screen should be beneficial to the patient, the physician, and the laboratory.
Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers (2011)

DNA methylation at the 5-position of cytosines (5 mC) represents an important epigenetic modification involved in tissue differentiation and is frequently altered in cancer. Recent evidence suggests that 5 mC can be converted to 5-hydroxymethylcytosine (5 hmC) in an enzymatic process involving members of the TET protein family. Such 5 hmC modifications are known to be prevalent in DNA of embryonic stem cells and in the brain, but the distribution of 5 hmC in the majority of embryonic and adult tissues has not been rigorously explored. Here, we describe an immunohistochemical detection method for 5 hmC and the application of this technique to study the distribution of 5 hmC in a large set of mouse and human tissues. We found that 5 hmC was abundant in the majority of embryonic and adult tissues. Additionally, the level of 5 hmC closely tracked with the differentiation state of cells in hierarchically organized tissues. The highest 5 hmC levels were observed in terminally differentiated cells, while less differentiated tissue stem/progenitor cell compartments had very low 5 hmC levels. Furthermore, 5 hmC levels were profoundly reduced in carcinoma of the prostate, breast and colon compared to normal tissues. Our findings suggest a distinct role for 5 hmC in tissue differentiation, and provide evidence for its large-scale loss in cancers.
Heterogeneous enzyme immunoassay of alpha-fetoprotein in maternal serum by flow-injection amperometric detection of 4-aminophenol (1990)

A sandwich-type heterogeneous enzyme immunoassay with flow-injection analysis for alpha-fetoprotein (AFP) in human serum has been developed. 4-Aminophenol, the product of enzymatic reaction, is detected amperometrically. The interassay CV for this electrochemical enzyme immunoassay was less than 8.2%, with a minimum detection limit for AFP of 0.163 micrograms/L. The calibration curve had a linear range of 0.316-100 micrograms/L. Studies with 48 human maternal serum samples, comparing results by this method with those by a commercial kit, showed a good correlation (r = 0.961). This procedure provides an alternative method for determining low concentrations of AFP in human maternal serum.
Glycoproteins: Isolation from Cell Membranes with Lithium Diiodosalicylate (1971)

A glycoprotein has been extracted in water-soluble form from human red cell membranes with lithium diiodosalicylate. After extraction of the membranes and phosphocellulose chromatography a homogeneous preparation is obtained which was 60 percent carbohydrate and 40 percent protein (by weight). The preparation contains AB and MN blood group antigens, receptors for influenza virus, and various phytohemagglutinins.
Diagnosis and management of dilated cardiomyopathy (2000)

Dilated cardiomyopathy is a heart muscle disorder defined by the presence of a dilated and poorly functioning left ventricle in the absence of abnormal loading conditions (hypertension, valve disease) or ischaemic heart disease sufficient to cause global systolic impairment. A large number of cardiac and systemic diseases can cause systolic impairment and left ventricular dilatation, but in the majority of patients no identifiable cause is found—hence the term “idiopathic” dilated cardiomyopathy (IDC). There are experimental and clinical data in animals and humans suggesting that genetic, viral, and immune factors contribute to the pathophysiology of IDC.#### Causes of dilated cardiomyopathy

Young

Adolescent/adults

### Clinical presentation

The first presentation of IDC may be with systemic embolism or sudden death, but patients more typically present with signs and symptoms of pulmonary congestion and/or low cardiac output, often on a background of exertional symptoms and fatigue for many months or years before their diagnosis. Intercurrent illness or the development of arrhythmia, in particular atrial fibrillation, may precipitate acute decompensation in such individuals. Increasingly, IDC is diagnosed incidentally in asymptomatic individuals during routine medical screening or family evaluation of patients with established diagnosis.

A careful family history facilitates diagnosis of inherited causes of IDC by characterising the family phenotype, and also defines the scope of family screening.1 At least 25% of patients have evidence for familial disease with predominantly autosomal dominant inheritance. Clinically, familial disease is defined by the presence of two or more affected individuals in a single family and should also be suspected in all patients with …
Compact Oxford dictionary and thesaurus (2009)

The Compact Oxford Dictionary & Thesaurus is the ultimate one-stop reference, containing both a dictionary and a thesaurus in one handy reference volume. The dictionary and thesaurus texts have an integrated design which has been tried and tested with users to speed up browsing and look-up. The dictionary has excellent coverage of everyday English, containing over 90,000 words, phrases and definitions and incorporating the newest words and phrases from Oxford's language research programmes. The thesaurus provides over 100,000 synonyms and antonyms. This dictionary and thesaurus is ideal for anyone who needs an all-in-one reference work. Explore our language resources on oxforddictionaries.com, Oxford's home for dictionaries and language reference. Updated regularly with the latest changes to words and meanings, the site provides hundreds of thousands of definitions, synonyms, and pronunciations in a range of languages. Access the highest quality language content, built from our extensive research, for free on your desktop or device.
Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer (2004)

Caveolin-1 and -2 (CAV1, CAV2) are closely linked genes localised to the fragile region of 7q31 (FRA7G), and loss of heterozygosity involving this region has been reported in breast cancer. Several studies have suggested that CAV1 is a negative regulator of HER2/neu signal transduction in vitro. However, the clinical significance of CAV1 in breast cancer has not yet been clarified. We examined quantitatively the mRNA levels of CAV1, CAV2 and HER2/neu in 162 cases of breast cancer using real-time PCR. Caveolin-1 and -2 protein expression was also examined by Western blotting and immunohistochemistry. We then evaluated for correlations between CAV1, CAV2 and HER2/neu gene expression and clinicopathologic factors in the 162 breast cancer cases. Results showed higher HER2/neu mRMA levels and lower CAV1 and CAV2 mRMA levels in breast cancer tissues than in corresponding normal tissues (P<0.001). Caveolin-1 and -2 protein expression levels were also suppressed in cancer tissues compared to normal tissues by Western blotting. Immunohistochemistry revealed that CAV1 and CAV2 proteins were abundantly expressed in mammary gland myoepithelial cells, but only weakly in ductalepithelial cells. Reduced CAV1 mRNA level was significantly associated with increasing tumour size (P=0.041), and negative oestrogen receptor status (P=0.021). There was also a significant association between low CAV2 mRNA level and negative progesterone receptor status (P=0.013), and between high HER2/neu mRNA level and negative hormonal receptor status (ER, P=0.029, PgR, P=0.019). While there was no relationship between HER2/neu and CAV1 mRNA levels, a significant association between CAV1 and CAV2 mRNA levels was observed (P<0.001). Our results indicated that CAV1 suppression correlated closely with that of CAV2 in breast cancer, that CAV1 level was inversely correlated with tumour size, and that CAV1 and CAV2 levels were correlated with hormonal receptor status. Therefore, CAV1 and CAV2 play an important role in tumour progression in breast cancer patients.
InterPro in 2011: new developments in the family and domain prediction database (2011)

InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.
Mean-field theory for scale-free random networks (1999)

Random networks with complex topology are common in Nature, describing systems as diverse as the world wide web or social and business networks. Recently, it has been demonstrated that most large networks for which topological information is available display scale-free features. Here we study the scaling properties of the recently introduced scale-free model, that can account for the observed power-law distribution of the connectivities. We develop a mean-field method to predict the growth dynamics of the individual vertices, and use this to calculate analytically the connectivity distribution and the scaling exponents. The mean-field method can be used to address the properties of two variants of the scale-free model, that do not display power-law scaling.
A Strategic Assessment of PLA Theatre Missile and ASAT Capabilities (2010)

China’s intermediate range ballistic and cruise missile forces have increased in capability over the past decade and are now starting to pose a considerable conventional strategic risk to nations within South East, South and West Asia as well as Russia. The DF-11 and DF-15 missiles no longer required opposite Taiwan could be deployed to threaten India and the countries bordering the South China Sea. The intended OTH-B radar network provides a tripwire early warning capability against aircraft and provides initial targeting of United States carrier battle groups, with potential capability against incoming ballistic and cruise missiles. The ongoing growth in targeting capabilities is of special concern to the United States, as is China’s continued development and deployment of new ballistic and cruise missile systems, as its regional neighbours embark upon an arms race, equipping their forces with both offensive and defensive systems to counter China’s growth in strategic weapons.
Design and Implementation of New, Silicon-Based, Cross-Coupling Reactions:  Importance of Silicon−Oxygen Bonds (2002)

This Account chronicles the conceptual development, proof of principle, exploration of scope, and mechanistic investigations of a newly developed class of palladium-catalyzed cross-coupling reactions of silicon derivatives. Under the influence of fluoride activation a myriad of oxygen-containing silicon moieties undergo mild and stereospecific cross-coupling. The diversity of methods for introduction of silicon groupings into organic molecules and the range of organic electrophiles that can be used are outlined.
Development of a knowledge-based electronic patient record. (1996)

To help clinicians care for patients with HIV infection, we developed an interactive knowledge-based electronic patient record that integrates rule-based decision support and full-text information retrieval with an online patient record. This highly interactive clinical workstation now allows the clinicians at a large primary care practice (30,000 ambulatory visits per year) to use online information resources and fully electronic patient records during all patient encounters. The resulting practice database is continually updated with outcome data on a cohort of 700 patients with HIV infection. As a byproduct of this integrated system, we have developed improved statistical methods to measure the effects of electronic alerts and reminders.
Membrane Damage Effect of Continuous Wave Ultrasound on K562 Human Leukemia Cells (2012)

The damaging effects of ultrasound on the cell membrane and cell viability were intensity dependent. The membrane potential changes may be due to acoustic cavitation accompanied by alterations in the balance of ions on opposite sides of the cellular membrane.
Acyl Carrier Protein (1969)

Abstract The fluxes of radioactive pantothenate between the cellular components 4'-phosphopantetheine, coenzyme A, and acyl carrier protein (ACP) and the medium have been measured in a pantothenate auxotroph of Escherichia coli. Radioactive fluxes generated with two alternate computer models for pantothenate metabolism were compared with the experimental data. One model was consistent with all the data with the same set of rate constants; the other model was not. The successful model has CoA as the immediate precursor of ACP and features rapid turnover of the 4'-phosphopantetheine prosthetic groups of ACP and of CoA in exponentially growing cells; such turnover was directly observable under certain conditions. The rate of ACP turnover was four times the rate of growth of the ACP pool.
Energetics and efficiency of photoinactivation of murine tumor cells containing hematoporphyrin. (1976)

Hematoporphryrin derivative at an intracellular concentration in TA-3 mouse mammary carcinoma cells of 0.6 or 0.9 mM required input of 3.0 X 3.6 X 10(9) quanta/cell of red light (620 nm) to achieve a 90% kill. At an intracellular concentration of 1.2 mM, this light requirement drops to 1.5 X 10(9)quanta/cell. The energy for this photodynamic process is about 100 times higher than that required for ionizing radiation to achieve the same level of kill for these cells. The quantum yield for singlet oxygen formation (the cytotoxic agent in most photodynamic processes) from hematoporphyrin derivative is 0.75 +/- 0.07 in ethanol but only 0.16 +/- 0.07 within TA-3 cells, indicating possible intracellular complexing and quenching.
AIP1: a new player in TNF signaling (2003)

Apoptosis signal–regulating kinase 1 (ASK1) is an upstream activator of JNK and p38 MAPK signaling cascades. Evidence now shows that the ASK1-interacting protein, AIP1, plays an important role in TNF-α–induced ASK1 activation by facilitating dissociation from its inhibitor.
Signaling Games and Stable Equilibria (1987)

Games in which one party conveys private information to a second through messages typically admit large numbers of sequential equilibria, as the second party may entertain a wealth of beliefs in response to out-of-equilibrium messages. By restricting those out-of-equilibrium beliefs, one can sometimes eliminate many unintuitive equilibria. We present a number of formal restrictions of this sort, investigate their behavior in specific examples, and relate these restrictions to Kohlberg and Mertens' notion of stability.
DVD Demystified (1998)

From the Publisher:
This brand new, comprehensive edition of the best-selling guide to DVD technology is a must-read for DVD hardware/software developers, A/V publishers, IT/MIS professionals, and video/audio professionals. Includes a new chapter on DVD production, and completely new DVD-ROM demo material. Covers the use of DVD with computers -- plus rewritable DVD, DVD audio, DIVX, and other new technologies.
Evaluation of Rapidly Disintegrating Tablets Prepared by a Direct Compression Method (1999)

To make rapidly disintegrating tablets with sufficient mechanical integrity as well as a pleasant taste, microcrystalline cellulose (MCC), Tablettose (TT), and crosslinked sodium carboxymethyl cellulose (Ac-di-sol) or erythritol (ET) were formulated. Tablets were made by a direct compression method (I). Tablet properties such as porosity, tensile strength, and disintegration time were determined. The tensile strength and disintegration time were selected as response variables, tablet porosity and parameters representing the characteristics of formulation were selected as controlling factors, and their relation was determined by the polynomial regression method. Response surface plots and contour plots of tablet tensile strength and disintegration time were also constructed. The optimum combination of tablet porosity and formulation was obtained by superimposing the contour diagrams of tablet tensile strength and disintegration time. Rapidly disintegrating tablets with durable structure and desirable taste could be prepared within the obtained optimum region.
Functional Immobilization of a Ligand-Activated G-Protein-Coupled Receptor (2002)

G-protein-coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters. They are the largest family of receptors in the human genome and constitute the largest class of targets for drug discovery. To facilitate studies of GPCR activation and interactions with other proteins, we developed a simple method to immobilize a functional, detergent-solubilized GPCR on gold and glass surfaces. The beta(2) adrenergic receptor (beta(2)AR), a prototypical GPCR, was purified and labeled with a reporter fluorophore at a conformationally sensitive site. The detergent-soluble fluorescent beta(2)AR was immobilized through its amino-terminal FLAG epitope on a surface layered with biotinylated bovine serum albumin, avidin, and biotinylated M1 antibody. Agonist activation of the beta(2)AR was monitored in real time by fluorescence microscopy. This approach will make it possible to study conformational dynamics of single immobilized receptors and to generate arrays of functional GPCRs for novel high-throughput screening strategies.