gebhart/patrepeval huggingface dataset:
The new clinical trials on pharmacological treatment in pulmonary arterial hypertension (2002)

Past medical therapy for pulmonary arterial hypertension included the use of calcium-channel antagonists in acute vasoreactive subjects and oral anticoagulants and continuous intravenous administration of epoprostenol in the more severe cases. Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues treprostinil, beraprost and iloprost, and the endothelin receptor antagonist bosentan have been tested in clinical trials in >1,100 patients. Except for terbogrel, all compounds improved the mean exercise capacity by different degrees, as assessed by the 6-min walk test. In the evaluation of the clinical relevance of exercise capacity improvements, additional elements need to be considered, such as baseline functional class and concomitant favourable effects on combined clinical events (including hospitalisations, mortality and rescue therapies), quality of life and haemodynamics. No trials have shown effects on mortality, as the study protocols were not designed for assessing this end-point. Each new compound presents side-effects that are unpredictable in the individual patient and require appropriate attention upon treatment initiation and maintenance. These new therapeutic options will be available in the near future and will allow tailoring of the most appropriate treatment to the single patient, according to an individualised benefit-to-risk ratio.
Structure−Activity Relationships of the Melanocortin Tetrapeptide Ac-His-DPhe-Arg-Trp-NH<sub>2</sub> at the Mouse Melanocortin Receptors. 1. Modifications at the His Position (2002)

The melanocortin pathway is an important participant in obesity and energy homeostasis. The centrally located melanocortin-3 and melanocortin-4 receptors (MC3R, MC4R) are involved in the metabolic and food intake aspects of energy homeostasis and are stimulated by melanocortin agonists such as alpha-melanocyte stimulation hormone (alpha-MSH). The melanocortin agonists contain the putative message sequence "His-Phe-Arg-Trp", and it has been well documented that inversion of chirality of the Phe to DPhe results in a dramatic increase in melanocortin receptor potency. Herein, we report a tetrapeptide library based on the template Ac-His-DPhe-Arg-Trp-NH(2), consisting of 17 members that have been modified at the His(6) position (alpha-MSH numbering) and pharmacologically characterized for agonist activity at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R. These studies provide further experimental evidence that the His(6) position can determine MC4R versus MC3R agonist selectivity and that chemically nonreactive side chains may be substituted for the imidazole ring (generally needs to be side chain protected in synthetic schemes) in the design of MC4R-selective, small-molecule, non-peptide agonists. Specifically, the tetrapeptide containing the amino-2-naphthylcarboxylic acid (Anc) amino acid at the His position resulted in a potent agonist at the mMC4R (EC(50) = 21 nM), was a weak mMC3R micromolar antagonist (pA(2) = 5.6, K(i) = 2.5 microM), and possessed >4700-fold agonist selectivity for the MC4R versus the MC3R. Substitution of the His(6) amino acid in the tetrapeptide template by the Phe, Anc, 3-(2-thienyl)alanine (2Thi), and 3-(4-pyridinyl)alanine (4-Pal) resulted in equipotency or only up to a 7-fold decrease in potency, compared to the His(6)-containing tetrapeptide at the mMC4R, demonstrating that these amino acid side chains may be substituted for the imidazole in the design of MC4R-selective non-peptide molecules.
Capillary zone electrophoresis of albumin-depleted human serum using a linear polyacrylamide-coated capillary: Separation of serum α-and β-globulins into individual components (2000)

The separation of human serum globulins into individual components was investigated by capillary zone electrophoresis (CZE) using a linear polyacrylamide-coated capillary at pH 7.4. Prior to CZE analysis of globulin components present in serum, it was found that it was necessary to remove albumin. Preparation of albumin-depleted human serum with a HiTrap Blue column allowed the detection of alpha- and beta-globulin components as a series of peaks. Almost all the peaks, both narrow and broad, observed in CZE analysis could be assigned to six globulin components (alpha1-acid-glycoprotein, alpha1 -antitrypsin, haptoglobin, alpha2-macroglobulin, Gc-globulin, and transferrin) by using the technique of antibody-based indirect detection. The CZE results, obtained from serum preparations from three healthy adults and six patients, showed that the CZE system might be capable of detecting qualitative differences among individuals with regard to individual globulin components.
Acylation of 2′,3′,5′-tri-O-acetylguanosine (1977)

P. K. Bridson, W. T. Markiewicz and C. B. Reese, J. Chem. Soc., Chem. Commun., 1977, 791 DOI: 10.1039/C39770000791
ARMA-like and ML-like copy/DF approaches for signal-specific emitter location (1990)

A general approach for performing signal-specific high-resolution DF of cochannel emitter waveforms is reported. This approach, referred to here as the copy/DF approach, uses the signal copy vectors provided by a blind or nonblind signal extraction algorithm to construct a spatial spectrum for each signal captured by an antenna array, where each spectrum has a global maximum in the direction of the signal captured by that copy vector. The approach can be used with any signal extraction algorithm, and is particularly effective in environments containing strong cochannel interference. Two classes of techniques are presented: ARMA-like techniques, which form spatial spectra with zeroes in the directions of the received interferers and poles in the directions of the copied signals; and ML-like techniques, which approximate the nonblind maximum-likelihood estimate of the direction-of-arrival of the copied emitter waveforms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Thermodynamic analysis of ion effects on the binding and conformational equilibria of proteins and nucleic acids: the roles of ion association or release, screening, and ion effects on water activity (1978)

The purpose of this review is to examine the various effects of low- molecular-weight electrolytes on the associations and interactions of proteins and nucleic acids. Our primary interest is in general electrostatic effects, rather than chemical effects (specific interactions) of particular ions (e.g. transition metals, protons). We consider those interactions in which a variation in salt concentration has a significant effect on the macromolecular equilibrium, and analyse the effects of salt in these situations in terms of (i) direct participation of ions in the biopolymer reaction, (ii) Debye—Hückel screening by salt ions of the charge interactions on the biopolymers, and (iii) the reduction in water activity brought about at high salt concentrations.
Structural Motifs in RNA (1999)

An RNA motif is a discrete sequence or combination of base juxtapositions found in naturally occurring RNAs in unexpectedly high abundance. Because all the motifs examined so far have three-dimensional structures independent of the context in which they are embedded, they are important components of the "kit" of structural elements from which RNAs are constructed. This review discusses the structures of the motifs that have been identified so far and speculates on the importance of their role in determining RNA conformation and their evolutionary origin.
Synthetic bone substitutes (2000)

Bone transplantation via autograft or allograft is an essential component of surgical management for a variety of skeletal defects. The nondegradable poly(methylmethacrylate) finds use as a bone graft alternative in certain limited clinical situations. There is an array of degradable, synthetic alternatives to these existing choices on the clinical use horizon. These alternatives include a variety of polymeric and ceramic composite materials that can provide immediate structural stability to the reconstructed region. In addition, these materials can deliver cells and growth factors to direct the bone regeneration process. This review discusses recent work in this rapidly evolving field of bone tissue engineering.
Heterozygous Mutation in the Cholesterol Side Chain Cleavage Enzyme (P450scc) Gene in a Patient with 46,XY Sex Reversal and Adrenal Insufficiency (2001)

Cytochrome P450scc, the mitochondrial cholesterol side chain cleavage enzyme, is the only enzyme that catalyzes the conversion of cholesterol to pregnenolone and, thus, is required for the biosynthesis of all steroid hormones. Congenital lipoid adrenal hyperplasia is a severe disorder of steroidogenesis in which cholesterol accumulates within steroidogenic cells and the synthesis of all adrenal and gonadal steroids is impaired, hormonally suggesting a disorder in P450scc. However, congenital lipoid adrenal hyperplasia is caused by mutations in the steroidogenic acute regulatory protein StAR; it has been thought that P450scc mutations are incompatible with human term gestation, because P450scc is needed for placental biosynthesis of progesterone, which is required to maintain pregnancy. In studying patients with congenital lipoid adrenal hyperplasia, we identified an individual with normal StAR and SF-1 genes and a heterozygous mutation in P450scc. The mutation was found in multiple cell types, but neither parent carried the mutation, suggesting it arose de novo during meiosis, before fertilization. The patient was atypical for congenital lipoid adrenal hyperplasia, having survived for 4 yr without hormonal replacement before experiencing life-threatening adrenal insufficiency. The P450scc mutation, an in-frame insertion of Gly and Asp between Asp271 and Val272, was inserted into a catalytically active fusion protein of the P450scc system (H2N-P450scc-Adrenodoxin Reductase-Adrenodoxin-COOH), completely inactivating enzymatic activity. Cotransfection of wild-type and mutant vectors showed that the mutation did not exert a dominant negative effect. Because P450scc is normally a slow and inefficient enzyme, we propose that P450scc haploinsufficiency results in subnormal responses to ACTH, so that recurrent ACTH stimulation leads to a slow accumulation of adrenal cholesterol, eventually causing cellular damage. Thus, although homozygous absence of P450scc should be incompatible with term gestation, haploinsufficiency of P450scc causes a late-onset form of congenital lipoid adrenal hyperplasia that can be explained by the same two-hit model that has been validated for congenital lipoid adrenal hyperplasia caused by StAR deficiency.
Stroke prevention. An opportunity for efficient utilization of health care resources during the coming decade. (1994)

The prevention of stroke can be accomplished by the high-risk or mass approach or a combination of these approaches. The high-risk approach prevents strokes but is also expensive. The mass approach may be more cost-effective, which could lead to substantial savings, but this needs to be investigated.
Absorption of amino penicillins from everted rat intestine. (1977)

1. Using an in vitro everted gut sac method based on that of Wilson & Wiseman (1954), a number of amino penicillins were tested in order to identify the involvement of any specialized transport mechanisms in their absorption across rat intestine. 2. Only one of the amino penicillins, cyclacillin (1-amino-cyclohexyl penicillin) was shown to be actively transported. The other penicillins appeared to diffuse passively across the intestine. 3. Cyclacillin was found to concentrate against a gradient at 37 degrees C but not at 19 degrees C. 4. Transport of cyclacillin across the mucosal membrane was saturated at mucosal concentrations greater than 1000 microgram/ml. 5. The rate of the forward flux of cyclacillin was many times that of its back flux. 6. No relationship between the active transport of cyclacillin and that of amino acids could be demonstrated.
Photon-Gated Electron Transfer in Two-Component Self-Assembled Monolayers (1999)

The preparation and characterization of a photoactive, two-component self-assembled monolayer (SAM) consisting of 99:1 cis-p-(C6H5)NN(C6H4)O(CH2)11SH) (1) and trans-p,p-Fc(C6H4)NN(C6H4)(CH2)4SH (Fc = C5H4FeC5H5; 2) are reported. With this SAM, electron transfer between solution ferrocyanide and the Au substrate is forced to occur through mediating ferrocenyl sites in the film, resulting in a diode-like response. However, by photochemically converting large “footprint” cis-1 to the smaller footprint trans-1, the free volume within the film is increased, thereby allowing for direct electron transfer between the solution ferrocyanide and the electrode surface and a normal electrochemical response (i.e., ipa = ipc). All states of the film have been characterized by cyclic voltammetry, FTIR spectroscopy, and differential capacitance measurements. All data from these techniques are consistent with the conclusion that cis−trans azobenzene isomerization within the monolayer results in increased film porosity, which reduces the film's ability to block the access of solution redox-active species to the underlying Au electrode surface. This novel two-component structure establishes the concept for a new type of molecule-based electronic device, a “photoswitchable diode” that is capable of amplifying the signal associated with a photodriven event via an electrochemical response. With such a system, a small number of photons can release a relatively large number of electrons from the solution electron reservoir. Significantly, this system shows how one can regulate electron-transfer events involving SAMs through photochemical control over film structure and free volume.
On the use of approximate adders in carry-save multiplier-accumulators (2017)

Approximate computing improves digital circuit performance by relaxing the requirement of performing exact calculations. In this paper, we investigate the use of approximate adders in the final stage of a carry save multiplier-accumulator (MAC), designed for image filtering application. We propose a design flow based on synthesis tools, starting from HDL description. After a first step in which an exact carry-propagate adder is used, the synthesized netlist is simulated to extract the statistics of the terms summed in the carry-propagate adder. We then design the approximate adder, to meet the required error characteristics given the inputs statistics. The netlist is finally modified by substituting the exact adder with the approximate one, and a final synthesis and optimization is performed. The presented design example in 28nm CMOS shows that a 14% power gain can be obtained, with a limited image quality degradation.
Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the pleckstrin homology domain of phospholipase C δ1 (2002)

Ptd(4,5)P2 is thought to promote and organize a wide range of cellular functions, including vesicular membrane traffic and cytoskeletal dynamics, by recruiting functional protein complexes to restricted locations in cellular membranes. However, little is known about the distribution of PtdIns(4,5)P2 in the cell at high resolution. We have used the pleckstrin homology (PH) domain of phospholipase δ1 (PLCδ1), narrowly specific for PtdIns(4,5)P2, to map the distribution of the lipid in astrocytoma and A431 cells. We applied the glutathione S-transferase-tagged PLCδ1 PH domain (PLCδ1PH—GST) in an on-section labelling approach which avoids transfection procedures. Here we demonstrate PtdIns(4,5)P2 labelling in the plasma membrane, and also in intracellular membranes, including Golgi (mainly stack), endosomes and endoplasmic reticulum, as well as in electron-dense structures within the nucleus. At the plasma membrane, labelling was more concentrated over lamellipodia, but not in caveolae, which contained less than 10% of the total cell-surface labelling. A dramatic decrease in signal over labelled compartments was observed on preincubation with the cognate headgroup [Ins(1,4,5)P3], and plasma-membrane labelling was substantially decreased after stimulation with thrombin-receptor-activating peptide (SFLLRN in the one-letter amino acid code), a treatment which markedly diminishes PtdIns(4,5)P2 levels. Thus we have developed a highly selective method for mapping the PtdIns(4,5)P2 distribution within cells at high resolution, and our data provide direct evidence for this lipid at key functional locations.
Final Results of a Safety and Efficacy Trial of Preoperative Sequential Chemoradiation Therapy for the Nonsurgical Treatment of Early Breast Cancer: Japan Clinical Oncology Group Study JCOG0306 (2013)

The pCR rate was not high enough, even though preoperative sequential chemoradiation therapy did not increase the risk of operative complications and could achieve a high rate of breast-conserving surgery.
THROMBUS FORMATION AND ARTIFICIAL SURFACES (1978)

Journal Article THROMBUS FORMATION AND ARTIFICIAL SURFACES Get access CHARLES D FORBES, MD FRCP, CHARLES D FORBES, MD FRCP University Department of Medicine Royal InfirmaryGlosgow Search for other works by this author on: Oxford Academic PubMed Google Scholar COLIN R M PRENTICE, MD FRCP COLIN R M PRENTICE, MD FRCP University Department of Medicine Royal InfirmaryGlosgow Search for other works by this author on: Oxford Academic PubMed Google Scholar British Medical Bulletin, Volume 34, Issue 2, May 1978, Pages 201–207, https://doi.org/10.1093/oxfordjournals.bmb.a071492 Published: 01 May 1978
Reproducible fabrication of AlGaAs/GaAs circular buried heterostructure (CBH) surface-emitting lasers with low thresholds (1988)

The fabrication process for circular buried-heterostructure surface-emitting lasers has been improved to increase the uniformity of the active region diameter. Circular mesas of 8 μm diameter can now be consistently prepared and lowthreshold surface-emitting lasers (30–60 mA at room temperature pulsed conditions) are obtained.
Lamoille Canyon nappe in the Ruby Mountains metamorphic core complex, Nevada (1987)

Abstarct The Ruby Mountains form a high and rugged range in northeastern Nevada. Lamoille Canyon in the Ruby Mountains is an easy half-hour drive by passenger car from the town of Elko (Fig. 1). From Elko, located on 1–80, take Nevada 227 southeast for 19 mi (30 km) to a sign marking a right turn onto the Lamoille Canyon road. This paved road leads south into the Ruby Mountains and ascends Lamoille Canyon for 10 mi (16 km) to an elevation of 8,730 ft (2,661 m). The site is best visited in summer, for the canyon is generally snowbound from November to May. The Lamoille Canyon road offers spectacular mountain scenery and a U.S. Forest Service campground. Geologic features are well exposed in roadside outcrops and in glaciated canyon walls 2,000 to 4,000 ft (600 to 1,200 m) high. To enhance your visit, bring a camera, a geologic road log (Snoke and Howard, 1984), a colored 1:125,000-scale geologic map (Howard and others, 1979), and the Lamoille, Nevada, 15-minute topographic quadrangle published by the U.S. Geological Survey.
Cellular immunity induced by the recombinant <i>Plasmodium falciparum</i> malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia (2004)

Vaccination of malaria-naive humans with recombinant RTS,S/AS02, which includes the C-terminus of the circumsporozoite protein (CS), has been shown to induce strong T cell responses to both the whole protein antigen and to peptides from CS. Here we show that strong T cell responses were also observed in a semi-immune population in The Gambia, West Africa. In a Phase I study, 20 adult male volunteers, lifelong residents in a malaria-endemic region, were given three doses of RTS,S/AS02 at 0, 1 and 6 months. Responses to RTS,S, hepatitis B surface antigen and peptides from CS were tested using lymphocyte proliferation, interferon (IFN)-gamma production in microcultures, and IFN-gamma ex vivo and cultured ELISPOT, before and after vaccination. Cytotoxic responses were tested only after vaccination and none were detected. Before vaccination, the majority of the volunteers (15/20) had detectable responses in at least one of the tests. After vaccination, responses increased in all assays except cytotoxicity. The increase was most marked for proliferation; all donors responded to RTS,S after the third dose and all except one donor responded to at least one peptide after the second or third dose. There was a lack of close association of peptide responses detected by the different assays, although in microcultures IFN-gamma responses were found only when proliferative responses were high, and responses by cultured ELISPOT and proliferation were found together more frequently after vaccination. We have therefore identified several peptide-specific T cell responses induced by RTS,S/AS02 which provides a mechanism to investigate potentially protective immune responses in the field.
Characterization of Insulin-Like Growth Factor-Binding Protein-Related Proteins (IGFBP-rPs) 1, 2, and 3 in Human Prostate Epithelial Cells: Potential Roles for IGFBP-rP1 and 2 in Senescence of the Prostatic Epithelium (2000)

Insulin-like growth factor (IGF)-binding protein (IGFBP)-related proteins (IGFBP-rPs) are newly described cysteine-rich proteins that share significant aminoterminal structural similarity with the conventional IGFBPs and are involved in a diversity of biological functions, including growth regulation. IGFBP-rP1 (MAC25/Angiomodulin/prostacyclin-stimulating factor) is a potential tumor-suppressor gene that is differentially expressed in meningiomas, mammary and prostatic cancers, compared with their malignant counterparts. We have previously shown that IGFBP-rP1 is preferentially produced by primary cultures of human prostate epithelial cells (HPECs) and by poorly tumorigenic P69SV40T cells, compared with the cancerous prostatic LNCaP, DU145, PC-3, and M12 cells. We now show that IGFBP-rP1 increases during senescence of HPEC. IGFBP-rP2 (also known as connective tissue growth factor), a downstream effector of transforming growth factor (TGF)-β and modulator of growth for both fibroblasts and endothelial cells, was detected in most of the normal and malignant prostatic epithelial cells tested, with a marked up-regulation of IGFBP-rP2 during senescence of HPEC. Moreover, IGFBP-rP2 noticeably increased in response to TGF-β1 and all-trans retinoic acid (atRA) in HPEC and PC-3 cells, and it decreased in response to IGF-I in HPEC. IGFBP-rP3 [nephroblastoma overexpressed (NOV)], the protein product of the NOV protooncogene, was not detected in HPEC but was expressed in the tumorigenic DU145 and PC-3 cells. It was also synthesized by the SV40-T antigen-transformed P69 and malignant M12 cells, where it was down-regulated by atRA. These observations suggest biological roles of IGFBP-rPs in the human prostate. IGFBP-rP1 and IGFBP-rP2 are likely to negatively regulate growth, because they seem to increase during senescence of the prostate epithelium and in response to growth inhibitors (TGF-β1 and atRA). Although the data collected on IGFBP-rP3 in prostate are modest, its role as a growth stimulator and/or protooncogene is supported by its preferential expression in cancerous cells and its down-regulation by atRA.