gebhart/patrepeval huggingface dataset:
Structure‐activity relationship and metabolic stability studies of backbone cyclization and N‐methylation of melanocortin peptides (2008)

Backbone cyclization (BC) and N-methylation have been shown to enhance the activity and/or selectivity of biologically active peptides and improve metabolic stability and intestinal permeability. In this study, we describe the synthesis, structure-activity relationship (SAR) and intestinal metabolic stability of a backbone cyclic peptide library, BL3020, based on the linear alpha-Melanocyte stimulating hormone analog Phe-D-Phe-Arg-Trp-Gly. The drug lead, BL3020-1, selected from the BL3020 library (compound 1) has been shown to inhibit weight gain in mice following oral administration. Another member of the BL3020 library, BL3020-17, showed improved biological activity towards the mMC4R, in comparison to BL3020-1, although neither were selective for MC4R or MC5R. N-methylation, which restrains conformational freedom while increasing metabolic stability beyond that which is imparted by BC, was used to find analogs with increased selectivity. N-methylated backbone cyclic libraries were synthesized based on the BL3020 library. SAR studies showed that all the N-methylated backbone cyclic peptides demonstrated reduced biological activity and selectivity for all the analyzed receptors. N-methylation of active backbone cyclic peptides destabilized the active conformation or stabilized an inactive conformation, rendering the peptides biologically inactive. N-methylation of backbone cyclic peptides maintained stability to degradation by intestinal enzymes.
QUANTITATIVE RATING OF DEPRESSIVE STATES (1975)

A step-by-step analysis of Beck's and Hamilton's rating scales showed that both scales failed to differentiate adequately between moderate and severe depression measured by a global clinical assessment. Each item of the scales was tested for calibration, ascending monotonicity, and dispersion parallel to the clinical assessment. Twelve items of Beck's scale and six items of Hamilton's scale were found valid with respect to these criteria. Those items should be taken into account in future research for baseline ratings and for change ratings of depressive states quantitatively.
Litholytische Lösungen: Toxikologische Untersuchungen (1988)

Um Harnkonkremente aufzulösen, können abhängig von der Steinart verschiedene chemische Substanzen vor allem zur Veränderung des Harn-pH und/oder zur direkten Beeinflussung des Steingefüges eingesetzt werden. Bisher klinisch angewandte Lösungen wie Renacidin, N-Acetylcystein oder Natriumbikarbonat sind bei sorgfältiger Handhabung toxikologisch unbedenklich; über mögliche Urothelschäden nach Irrigation des Harntraktes mit EDTA (Ethylendiamintetraessigsäure) sind die Ansichten geteilt (1, 3, 4). Da EDTA-haltige Spüllösungen nach eigenen Untersuchungen (2) effektiv Struvit lysieren und auch zur Chemolyse von Apatit- und Kalziumoxalatanteilen geeignet sind, wurden verschiedene experimentell hoch wirksame Spülsubstanzen sowie EDTA-haltige Spüllösungen im Vergleich zu klinisch gebräuchlichen Substanzen bezüglich ihrer Wirkung auf Bakterien- und Zellkulturen sowie das Urothel von Schweineharnleitern untersucht.
Le Kojiki (chronique des choses anciennes). Introduction, traduction intégrale et notes par Masumi et Maryse Shibata. pp. 268, tableau dépliant hors-texte. Paris, Éditions G-P. Maisonneuve et Larose, 1969. 30 F. (1971)

Le Kojiki (chronique des choses anciennes). Introduction, traduction intégrale et notes par Masumi et Maryse Shibata. pp. 268, tableau dépliant hors-texte. Paris, Éditions G-P. Maisonneuve et Larose, 1969. 30 F. - Volume 103 Issue 1
View & share (2009)

Viewing and sharing media on mobile devices are popular scenarios, however, the limited screen size results in multiple users having to gather around a single display leading to an undesirable viewing experience. Similarly, sharing a single image with a single person is cumbersome and requires several steps to complete. This demonstration paper presents an approach in which a mobile phone is coupled with a personal projector to overcome the output limitations of mobile phones. The large mobile projected display allows several users to simultaneously view media. We also present a group based sharing approach allowing users to intuitively and easily share media between mobile devices. We reverse the typical role of sharing and introduce a technique whereby the receiver of the media is responsible for performing the sharing interaction. This allows sharing with a single member or multiple members of the group. Sharing with every member of the group is also easily possible.
Osmotic blood-brain barrier opening to IgM monoclonal antibody in the rat (1986)

Pharmacokinetic parameters of iodinated monoclonal antibody (MAb) delivery to normal rat brain were examined. The mean cerebrovascular permeability-surface area (PA; permeability X capillary surface area) to immunoglobulin M (IgM) MAb (mol wt 1,000,000) 10 min after infusion was 0.40 X 10(-6) S-1. When osmotic blood-brain barrier (BBB) disruption is utilized, the PA increased to 8.36 X 10(-6) S-1. Neither intravenous nor intracarotid MAb administration significantly affected delivery to brain. However, osmotic BBB opening significantly (P less than 0.0005) increased MAb uptake independent of the route of administration. After BBB opening and intracarotid MAb the maximum concentration in brain at 1 h was 0.72% per gram of the total administered dose. For 6 h postdisruption, ipsilateral brain levels were 25- to 100-fold greater than in the contralateral hemisphere or nonbarrier-disrupted controls. MAb concentration in brain slightly decreased over 72 h (P less than 0.05). Antibody recovered from disrupted brain retained 90% of its immunological reactivity for at least 24 h. MAb delivery to ipsilateral brain after BBB disruption was linear over a dose of 0.5-5.0 micrograms IgM, whereas the percentage of the total administered dose remained unchanged. After osmotic treatment, barrier opening was maximal to MAb delivery for 1 min with delivery declining rapidly thereafter. The type of anesthesia used and the administration of a thyroid-blocking agent were found to affect brain MAb levels after BBB disruption.
Diagnostic tests in endocrinology and diabetes (1994)

Radioimmunoassay and immunoradiometric assay, R. Edwards and L. Rees investigation of hypothalamo-pituitary disorders, P.M. Bouloux thyroid disorders, J.H. Lazarus, et al Cushing's syndrome - diagnosis and differential diagnosis, P.J. trainer and L.H. Rees hypothalamic pituitary ovarian axis, D.M. White and S. Franks disorders of sexual differentiation, M.O. Savage and J.W. Honour diagnostic tests in calcium disorders, D.C. Anderson and P.C. Richardson diagnosis of multiple endocrine neoplasia syndromes, R.V. Thakker endocrine hypertension, P.L. Padfield and C.R.W. Edwards diagnostic tests in diabetes mellitus and hypoglycaemia, S.A. Amiel and E.A.M. Gale dyslipidaemias and their investigation, I. Jialal growth disorders, A.M. Cotterill and M.O. Savage investigation of testicular disorders, E. Ur and P.M. Bouloux the diagnosis of adrenal failure, P.J. Trainer and L.H. Rees disorders of the sympatho-adrenomedullary system, P.M. Bouloux imaging of the pituitary and other parasellar lesions, D.P.E. Kingsley investigation of hyponatraemia, P.M. Bouloux.
Inhibition of Adrenal Steroidogenesis by the Anesthetic Etomidate (1984)

The use of the intravenous anesthetic etomidate for prolonged sedation has been associated with low levels of plasma cortisol and increased mortality. We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway. One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued. Four surgical patients receiving etomidate during their operations were all found to have adrenal suppression four hours after the operation; mean (±S.D.) increases in cortisol and aldosterone after ACTH stimulation were only 1.8±0.5 μg per deciliter and 0.5±1.1 ng per deciliter, respectively. In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450–dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11β-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway. Physicians should be aware that etomidate Inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etomidate is used. (N Engl J Med 1984; 310:1415–21.)
Enantioselective Aldol Reaction of Trimethoxysilyl Enol Ethers with Aldehydes Catalyzed by p-Tol-BINAP · AgF Complex (2001)

New catalytic asymmetric Mukaiyama-type aldol reaction using trimethoxysilyl enol ethers was achieved using p-Tol-BINAP · AgF complex as a catalyst. High syn- and enantioselectivities were obtained both from the E- and Z-silyl enol ethers.
Controlled Fabrication of Microparticles with Complex 3D Geometries by Tunable Interfacial Deformation of Confined Polymeric Fluids in 2D Micromolds (2015)

Polymeric microparticles with complex shapes have attracted substantial attention in many application areas because particle shape is a critical parameter to impart programmable functionalities. The formation of specific three-dimensional (3D) microstructures in a simple, scalable, and controllable manner is difficult. Here, we report the controlled fabrication of microparticles with complex 3D shapes based on the simple tuning of mold swelling and capillarity. Specifically, a photocurable solution loaded in micromolds is spatially deformed into complex shapes depending on the degree of molding swelling and capillarity, thereby producing polymeric microparticles with controlled 3D shapes upon photopolymerization. The results show that highly uniform microparticles with controlled two-dimensional (2D) and 3D shapes were fabricated from identical 2D micromolds via the simple tuning of the wetting fluids. This technique can be extended to produce highly complex microarchitectures with controlled 3D geometric domains via 2D mold designs. Finally, multicompartment microparticles with independently controlled 3D shapes for each compartment are produced by a simple combination of fabrication sequences. We envision that this strategy of producing 3D microarchitectures from easily designed simple micromolds could provide a path to new materials and new properties.
Development of soft and distributed tactile sensors and the application to a humanoid robot (2003)

This paper describes soft and distributed tactile sensors which give contact information to humanoid robots. In this paper, two types of tactile sensor element are proposed: one is a multi-valued touch sensor which has multi-level pressure thresholds. It is capable of covering wide areas of robot surfaces. The driving circuit is made as a module and scans the 128 switch elements which have two pressure thresholds in 1[ms]. The first pressure threshold is set to 25[gf/cm/sup 2/]. The other sensor is made of conductive gel which has remarkable softness. This conductive gel has the advantage of its softness compared with other sheet type tactile sensors. The impedance of the gel changes by approximately 20% from 0 to 400 [gf/cm/sup 2/]. The tactile sensor consists of 8/spl times/8 sensing points on the intersection of the electrodes, and the processing module scans all the points in 30[ms]. We apply them to a wheeled humanoid robot referred to as "H4". The detail of the sensor system on the robot and some experiments on the robot using tactile information are shown.
Study of protein-DNA interactions by surface plasmon resonance (real time kinetics) (1991)

Journal Article Study of protein-DNA interactions by surface plasmon resonance (real time kinetics) Get access Jean-Pierre Jost, Jean-Pierre Jost Search for other works by this author on: Oxford Academic PubMed Google Scholar Oliver Munch, Oliver Munch Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Andersson Thomas Andersson 1Pharmacia Biosensor ABRapsgatan 7, Hus F61, S-75182, Uppsala, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 10, 11 May 1991, Page 2788, https://doi.org/10.1093/nar/19.10.2788 Published: 25 May 1991 Article history Accepted: 27 March 1991 Published: 25 May 1991
A Dinuclear Palladium Catalyst for α-Hydroxylation of Carbonyls with O2 (2011)

A chemo- and regioselective α-hydroxylation reaction of carbonyl compounds with molecular oxygen as oxidant is reported. The hydroxylation reaction is catalyzed by a dinuclear Pd(II) complex, which functions as an oxygen transfer catalyst, reminiscent of an oxygenase. The development of this oxidation reaction was inspired by discovery and mechanism evaluation of previously unknown Pd(III)-Pd(III) complexes.
Tumor vessel-injuring ability improves antitumor effect of cytotoxic T lymphocytes in adoptive immunotherapy (2012)

Angiogenesis is required for normal physiologic processes, but it is also involved in tumor growth, progression and metastasis. Here, we report the development of an immune-based antiangiogenic strategy based on the generation of T lymphocytes that possess killing specificity for cells expressing vascular endothelial growth factor receptor 2 (VEGFR2). To target VEGFR2-expressing cells, we engineered cytotoxic T lymphocyte (CTL) expressing chimeric T-cell receptors (cTCR-CTL) comprised of a single-chain variable fragment (scFv) against VEGFR2 linked to an intracellular signaling sequence derived from the CD3ζ chain of the TCR and CD28 by retroviral gene transduction methods. The cTCR-CTL exhibited efficient killing specificity against VEGFR2 and a tumor-targeting function in vitro and in vivo. Reflecting such abilities, we confirmed that the cTCR-CTL strongly inhibited the growth of a variety of syngeneic tumors after adoptive transfer into tumor-bearing mice without consequent damage to normal tissue. In addition, CTL expressing both cTCR and tumor-specific TCR induced complete tumor regression due to enhanced tumor infiltration by the CTL and long-term antigen-specific function. These findings provide evidence that the tumor vessel-injuring ability improved the antitumor effect of CTLs in adoptive immunotherapy for a broad range of cancers by inducing immune-mediated destruction of the tumor neovasculature.
P1‐112: Effects of 12 months of treatment with the PPARγ agonist rosiglitazone on brain glucose metabolism in Alzheimer's Disease: A 18F‐FDG PET study (2009)

Alzheimer's Disease (AD) leads to a progressive reduction of brain metabolism, which correlates with disease severity and is detectable with 18F-FDG PET, Rosiglitazone was demonstrated to have a favorable effect on cognitive function in AD 1., 2.. We assessed the effects of rosiglitazone on brain metabolism over a 12-month period in a pilot double-blind, placebo controlled, randomized parallel group study. Eighty patients with mild-to-moderate AD (MMSE 16-23) were randomized in a 1:1 ratio to receive a daily dose of either rosiglitazone (8 mg extended release), or placebo, and underwent four 18F-FDG PET scans (baseline, 1, 6 and 12 months) and three T1 weighted structural MRI (baseline, 6 and 12 months). Commonly used clinical inventories (ADAS-Cog, CIBIC+), specific cognitive domain tests, APOϵ4 genotype and a variety of plasma biomarkers were also collected. Dynamic PET emission data, and discrete venous blood 18F-FDG samples were used to calculate a cerebral metabolic rate for glucose index (CMRgluI) - a parameter directly proportional to brain glucose metabolism - in brain regions known to be involved in early stages of AD (Posterior Cingulate, Posterior Temporal, Parietal, Frontal, Medial Temporal), and the cerebellum. A GlobalGrey region comprising the whole brain grey matter was also assessed. Individual patient CMRgluI were analyzed using separate mixed-effects models for repeated measures, primary inference being changes at 12 months. Data from 78 patients were used in the analysis of the PET study. GMRgluI change was similar in all brain regions examined, hence the figures below refer to the GlobalGrey. The decline in CMRgluI in the rosiglitazone group was lower than in the placebo group at all points (6.3% vs 13.1%, 2. 6% vs. 7.1% and -1.5% vs 4.7% at 12, 6 and 1 months, respectively). However, group differences did not reach statistical significance (p=0.17, 0.25 and 0.23 at 12, 6 and 1 months, respectively). No statistically significant differences were seen in the clinical assessments conducted. Subjects treated with Avandia XR showed a trend towards a lower rate of decline in CMRgluI compared to patients treated with placebo, but statistical significance was not reached.
Identification of a Mutation in Porcine Ryanodine Receptor Associated with Malignant Hyperthermia (1991)

Malignant hyperthermia (MH) causes neurological, liver, and kidney damage and death in humans and major economic losses in the swine industry. A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (ryr1) was found to be correlated with MH in five major breeds of lean, heavily muscled swine. Haplotyping suggests that the mutation in all five breeds has a common origin. Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs.
Bandgap narrowing in moderately to heavily doped silicon (1979)

A model of bandgap reduction in silicon through the stored electrostatic energy of majority-minority carrier pairs is developed and compared with experimental results in the doping range from 3 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">17</sup> to 1.5 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">20</sup> /cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> at room temperature. An analytic expression for the bandgap reduction in nondegenerate material is obtained <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\delta\epsilon _{g} = 3q^{2}/(16\pi \epsilon) \cdot (q^{2}n/\epsilon</tex> kT) <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</sup> having a square-root dependence on the majority carrier concentration. At room temperature this becomes <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\delta\epsilon _{g} = 22.5 (n/10^{18})^{1/2}</tex> meV. In degenerate material, the bandgap reduction is independent of temperature, following the relationship <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\delta \epsilon _{g} = 162 (n/10^{20})^{1/6}</tex> meV. The experimental data at room temperature are in excellent agreement with this theory. Plots of bandgap narrowing as a function of doping level are presented for a number of temperatures.
INVERSE EXPRESSION OF NEUROTROPHINS AND NEUROTROPHIN RECEPTORS AT THE INVASION FRONT OF HUMAN-MELANOMA BRAIN METASTASES (1995)

Neurotrophins (NT), such as nerve growth factor (NGF), stimulate the growth and differentiation of several neuronal subpopulations in a distinct yet overlapping manner. Brain-metastatic human melanoma cells overexpress p75(NTR), the low-affinity neurotrophin receptor, and treatment of brain-metastatic cells with NGF stimulates extracellular matrix invasion and production of degradative enzymes in relation to the cellular expression of p75(NTR) Although human melanoma cells express high affinity neurotrophin receptors, such as TrkC (the putative receptor for NT-3), they do not express TrkA, the high-affinity NGF receptor. Using digoxigenin-labeled sense/antisense riboprobes against human p75(NTR) and NGF for in situ hybridization, we determined whether the expression of p75(NTR) and NGF mRNAs are related to brain metastasis of human melanoma. We detected p75(NTR) mRNA at the invasion front of human melanoma brain metastases, whereas p75(NTR) expression was not found in adjacent tissues. In contrast, human NGF mRNA levels were increased in tissues surrounding the melanoma lesions, supporting the notion that NGF and NT are important in determining melanoma brain-metastatic microenvironment. Using antibodies specific to p75(NTR), TrkC, NGF and related NT we found high but heterogeneous levels of p75(NTR) and TrkC expression in malignant melanomas metastatic to the brain. Lower levels of expression were found in primary melanomas or in metastatic melanomas to sites other than brain. Additionally, we found elevated levels of synthesis of NGF and NT-3 but not brain-derived neurotrophic factor (BDNF) or NT-4/5 in the brain tissues surrounding melanoma lesions. These studies support a role for NT and their receptors in the progression of melanomas to the brain-metastatic phenotype.
Basic cancer medicine (1997)

This resource provides an overview of the diagnosis and management of cancer. It covers basic topics of interest including the aetiology, biology, genetics, and epidemiology of cancer, symptom management of cancer patients, oncologic emergencies, the use of tumour markers, and the management of paraneoplastic syndromes. New approaches in cancer management and unproven methods of cancer treatment are also discussed.
Small Molecule and Novel Treatments for Chronic Hepatitis C Virus Infection (2007)

The development of molecular-based therapies for the treatment of chronic hepatitis C virus (HCV) infection is an area of intense clinical research, driven by the inability of the current standard of care, combination therapy with pegylated interferon alfa (PEG-IFNalpha) and ribavirin (RBV), to achieve a sustained virologic response (SVR) in a large proportion of patients and by the lack of approved alternative therapies for PEG-IFNalpha/RBV nonresponders and relapsers. Agents being developed against specific HCV viral proteins have recently been termed Specifically Targeted Antiviral Therapy for HCV (STAT-C). Preliminary data for several agents show they have high antiviral activity, especially when used in combination with PEG-IFNalpha, and are tolerable, but resistance mutations have been identified. Further study is needed to clarify the safety, tolerability, and efficacy of these compounds. Once established, the potential for shorter treatment strategies could then be evaluated. Other novel therapies in development that may improve both outcomes and tolerability include a prodrug of RBV and an albumin-modified IFNalpha. In conclusion, small molecule and novel therapies for HCV infection are showing promise in clinical trials, and research to develop new agents and optimize treatment regimens is ongoing.