gebhart/patrepeval huggingface dataset:
One-shot design elevates functional expression levels of a voltage-gated potassium channel (2022)

Abstract Membrane proteins play critical physiological roles as receptors, channels, pumps, and transporters. Despite their importance, however, low expression levels often hamper the experimental characterization of membrane proteins. We present an automated and web-accessible design algorithm called mPROSS ( https://mPROSS.weizmann.ac.il ), which uses phylogenetic analysis and an atomistic potential, including an empirical lipophilicity scale, to improve native-state energy. As a stringent test, we apply mPROSS to the Kv1.2-Kv2.1 paddle chimera voltage-gated potassium channel. Four designs, encoding 9-26 mutations relative to the parental channel, were functional and maintained potassium-selective permeation and voltage dependence in Xenopus oocytes with up to 14-fold increase in whole-cell current densities. Additionally, single-channel recordings reveal no significant change in the channel-opening probability nor in unitary conductance, indicating that functional expression levels increase without impacting the activity profile of individual channels. Our results suggest that the expression levels of other dynamical channels and receptors may be enhanced through one-shot design calculations. Significance statement Heterologous expression levels of membrane proteins are often low, limiting research and applications. We combine homologous-sequence analysis with Rosetta atomistic calculations to enable one-shot design of dozens of mutations that improve native-state energy. Applied to a voltage-gated potassium channel, designs exhibited up to 14-fold improved functional expression levels in oocytes with almost no change in the single-channel activity profile. This design approach may accelerate research of many challenging membrane proteins, including receptors, channels, and transporters.
Role of PTP-1B in aortic smooth muscle cell motility and tyrosine phosphorylation of focal adhesion proteins (1999)

Recent studies have focused attention on the role of protein tyrosine kinases in vascular smooth muscle cell biology, but similar information regarding protein tyrosine phosphatases (PTP) is sparse. PTP-1B is a ubiquitous nonreceptor phosphatase with uncertain function and substrates that are mostly unidentified. We used antisense oligodeoxynucleotides (ODN) against PTP-1B to investigate the role of endogenous PTP-1B in motility of primary cultures of rat aortic smooth muscle cells (RASMC). Antisense ODN decreased PTP-1B protein levels and activity in a concentration-dependent fashion, whereas sense, scrambled, or three-base mismatch antisense ODN had little or no effect. Treatment of cells with antisense ODN, but not sense, scrambled, or three-base mismatch antisense ODN, enhanced cell motility and increased tyrosine phosphorylation levels of focal adhesion proteins paxillin, p130(cas), and focal adhesion kinase. Our findings indicate that PTP-1B is a negative regulator of RASMC motility via modulation of phosphotyrosine levels in several focal adhesion proteins and suggest the involvement of PTP-1B in events such as atherosclerosis and restenosis, which are associated with increased vascular smooth muscle cell motility.
Heavy Metal Mobility in Biosolids‐Amended Glaciated Soils (2001)

The mobility of heavy metals from one-time application of biosolids (i.e., compost, pellet, and cement kiln dust stabilized biosolids) onto glaciated soils (Paxton soil) was studied because previous work on metal leachate characteristics from different biosolids is limited for glaciated soils. Two types of batch tests were performed: first, a pH-edge adsorption study to evaluate the effect of pH on heavy metal adsorption to Paxton soil and, second, a pH-edge leaching study to evaluate the effect of pH on the leaching potential of heavy metals from biosolids-amended Paxton soil. Finally, a semicontinuous soil column study was performed to assess the mobility of heavy metals from biosolids-amended Paxton soil. The pH-edge leaching results showed that the leaching potential of heavy metals was lower with the compost product. Desorption concentrations for arsenic, chromium, and lead were found to be greatest in the cement kiln dust stabilized product whereas cadmium, copper, and nickel were present at the greatest concentrations in the pellets. The total organic carbon results measured during the pH-edge leaching study indicated that there is a minimum leachable concentration in the pH range of 4 to 5 for all three biosolids. Overall, the column studies indicated that heavy metals were not readily leached from the three biosolids-amended Paxton soils. The results from this study suggest that a one-time land application of these biosolids will not adversely affect groundwater quality.
Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive (2022)

Cenerimod, a sphingosine-1-phosphate 1 receptor modulator, is in development for the treatment of systemic lupus erythematosus, a disease mainly affecting women of childbearing potential. The effect of cenerimod on the pharmacokinetics (PK) of a combined oral contraceptive (COC, 100 µg levonorgestrel and 20 µg ethinylestradiol (EE)) was investigated. A randomized, double-blind, parallel-group study was performed in 24 healthy male and female subjects. A single oral dose of COC was administered alone and after 35 days of once daily (o.d.) administration of cenerimod 0.5 (n = 10) or 4 (n = 14) mg. Exposure to EE alone or in combination with cenerimod was comparable as reflected by the geometric mean ratios and the respective 90% confidence intervals, while a slight increase in exposure (approximately 10-25%) to levonorgestrel was observed at clinically relevant concentrations of cenerimod. Overall, COC alone or in combination with cenerimod was safe and well tolerated. Two subjects reported one adverse event each (one headache after COC alone, and gastroenteritis in combination with cenerimod 4 mg). In conclusion, cenerimod does not affect the PK of levonorgestrel or EE to a clinically relevant extent. Therefore, COC can be selected as method of contraception during and after cenerimod therapy without the risk of interaction.
Development of Functional Requirements for Ex Vivo Pathology Applications of In Vivo Microscopy Systems: A Proposal From the In Vivo Microscopy Committee of the College of American Pathologists (2019)

Consensus was achieved on FRs that would accommodate the selected EVM applications. Publication and dissemination of those FRs will provide guidance to engineers, researchers, and vendors on how to optimally adapt IVM technologies for EVM for widespread adoption by pathologists.
Chirurgische und pathologische Qualitätssicherung beim Rektumkarzinom - eine besondere Herausforderung mit Einfluss auf die Therapie? (2006)

Der Chirurg wird in der Therapie des Rektumkarzinoms als ein entscheidender Prognosefaktor angesehen. Seine Verantwortlichkeit für einen langfristigen Therapieerfolg liegt nicht nur in der Gewährleistung einer komplikationsarmen Operation (geringe Morbidität und Letalität), sondern auch im Erlernen moderner Resektionstechniken (z. B. der totalen mesorektalen Exzision, TME), im Erwerb profunder onkologischer Kenntnisse und in seiner Fähigkeit aktiv an interdisziplinären, multimodalen Konzepten (prä- und postoperative Radiochemotherapie) zur Behandlung lokal fortgeschrittener Rektumkarzinome (UICC-II/III-Stadien) teil zu haben. Gegenwärtig besitzt der histologisch überprüfte tumorfreie Resektionsrand, die R0-Klassifikation, den größten Einfluss auf das Überleben von Rektumkarzinom-Patienten. Insbesondere durch eine sorgfältige Untersuchung der zirkumferentiellen Resektionsränder am tumortragenden TME-Resektat kann der Pathologen jene Patienten identifizieren, die im weiteren postoperativen Verlauf ein hohes Risiko für ein Lokalrezidiv haben. Dabei führt ein zirkumferentieller Resektionsrand von < 1-2 mm (formal eine R0-Resektion) zu einer erhöhten Rate an Karzinomrezidiven. Zudem ist die Prognose der Rektumkarzinom-Patienten signifikant verschlechtert, sofern eine lymphatische Metastasierung vorliegt. Folglich ist eine umfassende histologische Untersuchung von Lymphknoten im TME-Rektum-Resektat unumgänglich. Verschiedene Untersuchungen haben gezeigt, dass je mehr Lymphknoten im Präparat analysiert werden, desto präziser das histopathologische Staging erfolgen kann. Es ist z. B. bekannt, dass die Prognose bei pN0-klassifizierten Patienten, bei denen der Pathologe weniger als 12 bis 14 Lymphknoten im Rektumresektat untersucht, deutlich schlechter ist im Vergleich zu Patienten mit > 18 untersuchten Lymphknoten. Dabei hängt die Anzahl der für das histopathologische Staging auswertbaren Lymphknoten sowohl von dem Training und der Präzision des chirurgischen Eingriffes als auch der Akribie der histopathologischen Aufarbeitung ab. Vor dem Hintergrund, dass das arterielle und venöse rektale Netzwerk innerhalb der mesorektalen Hüllfaszien verläuft und die Lymphbahnen parallel zu den Blutgefäßen verlaufen, liegt es nahe, dass eine lymphogene Tumorzell-Aussaat in die mesorektale Faszie ein frühzeitiges Lokalrezidiv nach TME-Resektion bedingen kann. Somit ist eine umfassende Aufarbeitung des Mesorektumresektates mitsamt der dort lokalisierten Lymphknoten unerlässlich. Zusammenfassend ist die Qualität des chirurgischen Vorgehens als auch der histopathologischen Aufarbeitung Grundlage für die weitere Therapieentscheidung und ausschlaggebend für die Prognose des Patienten.
Patient-specific ROM and load-based Target Zone for Total Hip Arthroplasty and its Application in a retrospective Analysis (2019)

The outcome of total hip arthroplasty (THA) depends on multiple alignment and design parameters. Unsuitable parameter settings could lead to impingement, dislocation, increased wear, and loosening. This work introduces a method for calculating a patient-specific target zone based on range of motion (ROM) related and load related criteria. Possible bone or prosthesis impingement are analyzed. The resulting hip force is calculated and compared to the pre-operative situation. The edge loading risk is analyzed. Pelvic tilt is considered for the calculation of the ROM and the load. THA parameters fulfilling all criteria are included in the target zone. The above described method has been applied to 30 cases retrospectively. All cases had been planned and navigated on the basis of CT data. From each patient, pre- and post-operative CT and EOS data and Harris Scores were acquired. The pre-operative data served as the input data for the target zone calculator. We hypothesized that cases with post-operative THA parameters inside the target zones have higher scores than other cases. The patients whose implants are within the target zones had higher scores than the remaining patients. Especially patients inside both target zones (combined target zone) had higher scores. The results also show that for 19 out of 30 patients, conventional CT-based planning and navigation does not provide optimal placement regarding the combined target zone. A further validation of the method with a larger sample size is part of our ongoing work.
Therapeutic concentrations of raloxifene augment nitric oxide‐dependent coronary artery dilatation in vitro (2007)

Raloxifene in therapeutically relevant concentrations augmented endothelial function in porcine coronary arteries in vitro through ICI 182,780-sensitive mechanisms that were associated with increased phosphorylation of eNOS but independent of changes in endothelial cell [Ca(2+)](i).
Comparative Evaluation of Three64Cu-LabeledE. coliHeat-Stable Enterotoxin Analogues for PET Imaging of Colorectal Cancer (2010)

Analogues of the E. coli heat-stable enterotoxin (STh) are currently under study as both imaging and therapeutic agents for colorectal cancer. Studies have shown that the guanylate cyclase C (GC-C) receptor is commonly expressed in colorectal cancers. It has also been shown that STh peptides inhibit the growth of tumor cells expressing GC-C. The ability to determine GC-C status of tumor tissue using in vivo molecular imaging techniques would provide a useful tool for the optimization of GC-C-targeted therapeutics. In this work, we have compared receptor binding affinities, internalization/efflux rates, and in vivo biodistribution patterns of an STh analogue linked to N-terminal DOTA, TETA, and NOTA chelating moieties and radiolabeled with Cu-64. The peptide F(19)-STh(2-19) was N-terminally labeled with three different chelating groups via NHS ester activation and characterized by RP-HPLC, ESI-MS, and GC-C receptor binding assays. The purified conjugates were radiolabeled with Cu-64 and used for in vitro internalization/efflux, in vivo biodistribution, and in vivo PET imaging studies. In vivo experiments were carried out using SCID mice bearing T84 human colorectal cancer tumor xenografts. Incorporation of DOTA-, TETA-, and NOTA-chelators at the N-terminus of the peptide F(19)-STh(2-19) resulted in IC(50)s between 1.2 and 3.2 nM. In vivo, tumor localization was similar for all three compounds, with 1.2-1.3%ID/g at 1 h pi and 0.58-0.83%ID/g at 4 h pi. The principal difference between the three compounds related to uptake in nontarget tissues, principally kidney and liver. At 1 h pi, (64)Cu-NOTA-F(19)-STh(2-19) demonstrated significantly (p < 0.05) lower uptake in liver than (64)Cu-DOTA-F(19)-STh(2-19) (0.36 +/- 0.13 vs 1.21 +/- 0.65%ID/g) and significantly (p < 0.05) lower uptake in kidney than (64)Cu-TETA-F(19)-STh(2-19) (3.67 +/- 1.60 vs 11.36 +/- 2.85%ID/g). Use of the NOTA chelator for coordination of Cu-64 in the context of E. coli heat-stable enterotoxin analogues results in higher tumor/nontarget tissue ratios at 1 h pi than either DOTA or TETA macrocycles. Heat-stable enterotoxin-based radiopharmaceuticals such as these provide a means of noninvasively determining GC-C receptor status in colorectal cancers by PET.
Improved efficacy of ramucirumab plus docetaxel after nivolumab failure in previously treated non‐small cell lung cancer patients (2019)

Ramucirumab plus docetaxel achieved a higher response rate when administered immediately after nivolumab failure compared to regimens without prior nivolumab administration.
Supplementary information from Thymidine Kinase 1 Loss Confers Trifluridine Resistance without Affecting 5-Fluorouracil Metabolism and Cytotoxicity (2023)

&lt;p&gt;Materials and methods for the supplementary figures.&lt;/p&gt;
Antiretroviral Therapy with a Twice-Daily Regimen Containing 400 Milligrams of Indinavir and 100 Milligrams of Ritonavir in Human Immunodeficiency Virus Type 1-Infected Women during Pregnancy (2008)

ABSTRACT We evaluated the safety and efficacy of a twice daily regimen containing 400 mg of indinavir and 100 mg of ritonavir in 32 human immunodeficiency virus (HIV)-infected women during pregnancy. The median indinavir trough concentration was 208 ng/ml during the third trimester. At delivery, 26 of 28 women on indinavir-ritonavir had HIV RNA levels of &lt;200 copies/ml. No infant was HIV infected. These data are encouraging for the use of this combination for prevention of mother-to-child transmission of HIV.
Per Anhalter durch die Politikwissenschaft: Urteile und Vorurteile (1994)

ZusammenfassungFür einen Wissenschaftler gibt es weltweit kein größeres Renommee, als den Nobelpreis zu erhalten (und einen prächtigen Batzen Geld dazu). Neben den besonders begehrten Preisen für Literatur und Frieden gibt es wissenschaftliche Nobelpreise für Medizin, Chemie, Physik, Biologie und seit einigen Jahren auch für Wirtschaftswissenschaften, aber keinen für Politikwissenschaft, Soziologie oder Psychologie. Warum? Sind dies keine anerkannten Wissenschaften? Dies ist die falsch gestellte Frage. Auch die Philosophen ehrt kein Nobelpreiskomitee. Dennoch zweifelt keiner an ihrer wissenschaftlichen Dignität. Die Frage ist falsch, aber typisch: Selbst Politologen benagt manchmal der Zweifel an ihrer eigenen Professionalität, außerdem schlägt ihnen Zweifel an ihrer Wissenschaft von außen entgegen. Trost bildet die Erkenntnis, daß Zweifel der Anfang aller Wissenschaft ist.
Revealing the influence of the solvent in combination with temperature, concentration and pH on the modification of TiO2 with 3PA (2016)

Functionalization of titanium dioxide with propylphosphonic acid (3PA). Solvent, temperature and amount 3PA together affects degree and type of functionalization. Ordered layers are formed already at low concentration of 3PA in toluene. Titanium propylphosphonates (TiPP) and surface grafting can both be formed in water. Formation of TiPP rises with temperature and concentration in water.
Studies dealing with the intramolecular ene reaction of cyclopropene derivatives (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies dealing with the intramolecular ene reaction of cyclopropene derivativesAlbert Padwa, William F. Rieker, and Robert J. RosenthalCite this: J. Am. Chem. Soc. 1985, 107, 6, 1710–1717Publication Date (Print):March 1, 1985Publication History Published online1 May 2002Published inissue 1 March 1985https://pubs.acs.org/doi/10.1021/ja00292a042https://doi.org/10.1021/ja00292a042research-articleACS PublicationsRequest reuse permissionsArticle Views429Altmetric-Citations13LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Modeling of Failure Prediction Bayesian Network with Divide‐and‐Conquer Principle (2014)

For system failure prediction, automatically modeling from historical failure dataset is one of the challenges in practical engineering fields. In this paper, an effective algorithm is proposed to build the failure prediction Bayesian network (FPBN) model with data mining technology. First, the conception of FPBN is introduced to describe the state of components and system and the cause‐effect relationships among them. The types of network nodes, the directions of network edges, and the conditional probability distributions (CPDs) of nodes in FPBN are discussed in detail. According to the characteristics of nodes and edges in FPBN, a divide‐and‐conquer principle based algorithm (FPBN‐DC) is introduced to build the best FPBN network structures of different types of nodes separately. Then, the CPDs of nodes in FPBN are calculated by the maximum likelihood estimation method based on the built network. Finally, a simulation study of a helicopter convertor model is carried out to demonstrate the application of FPBN‐DC. According to the simulations results, the FPBN‐DC algorithm can get better fitness value with the lower number of iterations, which verified its effectiveness and efficiency compared with traditional algorithm.
ChemInform Abstract: QUINOLONE ANTIMICROBIAL AGENTS. 2. METHYLENEDIOXY POSITIONAL ISOMERS OF OXOLINIC ACID (1980)

Abstract Die Isomeren (VII) und (XII) von Oxolinsäure (XIII) werden ausgehend von 2,3‐Dihydroxybenzaldehyd über (III) bzw. (VIII) dargestellt.
Information gain from count corrections in SPECT image reconstruction and classification (1990)

The authors present a method for quantifying the impact of count correction side information on the capability of a SPECT (single-photon-emission computed tomography) projective tomography system to perform image (emitter) reconstruction and feature classification. The method involves computing the image or feature related information gain which results from the presence of count correction side information at the detector. For image reconstruction this information gain is computed using Shannon's mutual information, while for feature classification the cutoff rate of the SPECT information channel is used. For reconstruction the gain is proportional to the information divergence between the spatially dependent probability of deletion of a gamma -ray originating at a particular emitter location and the spatially independent average deletion probability. For classification the gain is proportional to the difference between the arithmetic mean and the geometric mean of the average number of gamma -ray deletions for each of the image classes. Results of analysis and numerical study are presented which indicate that the information gain associated with using count correction data is much more significant for reconstruction of the emitters than for classification of the emitter density when the total detected fluence is low.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Technology for High Density Optical Integration on Silicon (2006)

The main objective of the research towards high density optical integration is to realize ultra-dense optical planar integrated circuits that combine passive and active optical functionalities as well as electronics playing control and logic functions. The most desirable output would be to have available for a designer a set of monolithically integrated building blocks incorporating all the necessary optical and electronic functions upon a single silicon substrate. Here we will present some of the contributions made towards highly integrated photonic circuits by a collaborative groups of the Joint Research Center of Photonics of the Royal Institute of Technology and Zhejiang University: directional coupler wavelength selective filter based on dispersive ID Bragg reflection waveguide, vertically coupled photonic crystal filter], compact arrayed waveguide grating demultiplexer based on amorphous silicon nanowires and polarization beam splitter based on two-dimensional photonic crystal of pillar type.
ChemInform Abstract: METALLIC CONDUCTIVITY IN METAL TETRAAZA(14)ANNULENE IODIDES: THE CRYSTAL STRUCTURES OF DIHYDRODIBENZO(B,I)‐1,4,8,11‐TETRAAZACYCLOTETRADECINENICKEL AND ‐PALLADIUM IODIDES (1981)

Abstract Durch Co‐Sublimation oder Lösen der Makrocyclen und Zugabe von Iod im Überschuß werden Iod‐gedopte Produkte der Metalltetraazaannulene (I) erhalten.
The effect of soluble E-selectin on tumor progression and metastasis (2016)

Our data suggest that circulating sE-selectin stimulates a broad range of circulating cells via CD44 and mediates pleiotropic effects that promote migration and shear-resistant adhesion in an endothelial E-selectin independent fashion, in turn accelerating tissue infiltration of leukocytes and cancer cells.
Issues in the combination of visual and haptic interaction (2001)

This paper discusses possibilities and problems arising in the design of usable interactive systems when both visual and haptic interaction modes are available. Communicational and operational features of such a system are studied, and first set of problems that can arise for a typical end user are identified. Some experimental results are reported that give indications on how to face some of these problems integrating the two interaction modes.