gebhart/patrepeval huggingface dataset:
Binding of the General Anesthetics Propofol and Halothane to Human Serum Albumin (2000)

Human serum albumin (HSA) is one of the most abundant proteins in the circulatory system and plays a key role in the transport of fatty acids, metabolites, and drugs. For many drugs, binding to serum albumin is a critical determinant of their distribution and pharmacokinetics; however, there have as yet been no high resolution crystal structures published of drug-albumin complexes. Here we describe high resolution crystal structures of HSA with two of the most widely used general anesthetics, propofol and halothane. In addition, we describe a crystal structure of HSA complexed with both halothane and the fatty acid, myristate. We show that the intravenous anesthetic propofol binds at two discrete sites on HSA in preformed pockets that have been shown to accommodate fatty acids. Similarly we show that the inhalational agent halothane binds (at concentrations in the pharmacologically relevant range) at three sites that are also fatty acid binding loci. At much higher halothane concentrations, we have identified additional sites that are occupied. All of the higher affinity anesthetic binding sites are amphiphilic in nature, with both polar and apolar parts, and anesthetic binding causes only minor changes in local structure.
NKT cell-dependent leukemia eradication following stem cell mobilization with potent G-CSF analogs (2005)

NKT cells have pivotal roles in immune regulation and tumor immunosurveillance. We report that the G-CSF and FMS-like tyrosine kinase 3 ligand (Flt-3L) chimeric cytokine, progenipoietin-1, markedly expands the splenic and hepatic NKT cell population and enhances functional responses to alpha-galactosylceramide. In a murine model of allogeneic stem cell transplantation, donor NKT cells promoted host DC activation and enhanced perforin-restricted CD8+ T cell cytotoxicity against host-type antigens. Following leukemic challenge, donor treatment with progenipoietin-1 significantly improved overall survival when compared with G-CSF or control, attributable to reduced graft-versus-host disease mortality and paradoxical augmentation of graft-versus-leukemia (GVL) effects. Enhanced cellular cytotoxicity was dependent on donor NKT cells, and leukemia clearance was profoundly impaired in recipients of NKT cell-deficient grafts. Enhanced cytotoxicity and GVL effects were not associated with Flt-3L signaling or effects on DCs but were reproduced by prolonged G-CSF receptor engagement with pegylated G-CSF. Thus, modified G-CSF signaling during stem cell mobilization augments NKT cell-dependent CD8+ cytotoxicity, effectively separating graft-versus-host disease and GVL and greatly expanding the potential applicability of allogeneic stem cell transplantation for the therapy of malignant disease.
The involvement of coenzyme A esters in the dehydration of (R)‐phenyllactate to (E)‐cinnamate by Clostridium sporogenes (2000)

Phenyllactate dehydratase from Clostridium sporogenes grown anaerobically on L-phenylalanine catalyses the reversible syn-dehydration of (R)-phenyllactate to (E)-cinnamate. Purification yielded a heterotrimeric enzyme complex (130 +/- 15 kDa) composed of FldA (46 kDa), FldB (43 kDa) and FldC (40 kDa). By re-chromatography on Q-Sepharose, the major part of FldA could be separated and identified as oxygen insensitive cinnamoyl-CoA:phenyllactate CoA-transferase, whereas the transferase depleted trimeric complex retained oxygen sensitive phenyllactate dehydratase activity and contained about one [4Fe-4S] cluster. The dehydratase activity required 10 microM FAD, 0.4 mM ATP, 2.5 mM MgCl2, 0.1 mM NADH, 5 microM cinnamoyl-CoA and small amounts of cell-free extract (10 microg protein per mL) similar to that known for 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. The N-terminus of the homogenous FldA (39 amino acids) is homologous to that of CaiB (39% sequence identity) involved in carnitine metabolism in Escherichia coli. Both enzymes are members of an emerging group of CoA-transferases which exhibit high substrate specificity but apparently do not form enzyme CoA-ester intermediates. It is concluded that dehydration of (R)-phenyllactate to (E)-cinnamate proceeds in two steps, a CoA-transfer from cinnamoyl-CoA to phenyllactate, catalysed by FldA, followed by the dehydration of phenyllactyl-CoA, catalysed by FldB and FldC, whereby the noncovalently bound prosthetic group cinnamoyl-CoA is regenerated. This demonstrates the necessity of a 2-hydroxyacyl-CoA intermediate in the dehydration of 2-hydroxyacids. The transient CoA-ester formation during the dehydration of phenyllactate resembles that during citrate cleavage catalysed by bacterial citrate lyase, which contain a derivative of acetyl-CoA covalently bound to an acyl-carrier-protein (ACP).
Cell‐specific mechanisms and systemic signalling as emerging themes in light acclimation of C3 plants (2009)

Chloroplasts perform essential signalling functions in light acclimation and various stress responses in plants. Research on chloroplast signalling has provided fundamental information concerning the diversity of cellular responses to changing environmental conditions. Evidence has also accumulated indicating that different cell types possess specialized roles in regulation of leaf development and stress acclimation when challenged by environmental cues. Leaf veins are flanked by a layer of elongated chloroplast-containing bundle sheath cells, which due to their central position hold the potential to control the flux of information inside the leaves. Indeed, a specific role for bundle sheath cells in plant acclimation to various light regimes is currently emerging. Moreover, perception of light stress initiates systemic signals that spread through the vasculature to confer stress resistance in non-exposed parts of the plant. Such long-distance signalling functions are related to unique characteristics of reactive oxygen species and their detoxification in bundle sheath cells. Novel techniques for analysis of distinct tissue types, together with Arabidopsis thaliana mutants with vasculature-specific phenotypes, have proven instrumental in dissection of structural hierarchy among regulatory processes in leaves. This review emphasizes the current knowledge concerning the role of vascular bundle sheath cells in light-dependent acclimation processes of C3 plants.
Neutralizing human monoclonal antibodies binding multiple serotypes of botulinum neurotoxin (2010)

Botulism, a disease of humans characterized by prolonged paralysis, is caused by botulinum neurotoxins (BoNTs), the most poisonous substances known. There are seven serotypes of BoNT (A-G) which differ from each other by 34-64% at the amino acid level. Each serotype is uniquely recognized by polyclonal antibodies, which originally were used to classify serotypes. To determine if there existed monoclonal antibodies (mAbs) capable of binding two or more serotypes, we evaluated the ability of 35 yeast-displayed single-chain variable fragment antibodies generated from vaccinated humans or mice for their ability to bind multiple BoNT serotypes. Two such clonally related human mAbs (1B18 and 4E17) were identified that bound BoNT serotype A (BoNT/A) and B or BoNT/A, B, E and F, respectively, with high affinity. Using molecular evolution techniques, it proved possible to both increase affinity and maintain cross-serotype reactivity for the 4E17 mAb. Both 1B18 and 4E17 bound to a relatively conserved epitope at the tip of the BoNT translocation domain. Immunoglobulin G constructed from affinity matured variants of 1B18 and 4E17 were evaluated for their ability to neutralize BoNT/B and E, respectively, in vivo. Both antibodies potently neutralized BoNT in vivo demonstrating that this epitope is functionally important in the intoxication pathway. Such cross-serotype binding and neutralizing mAbs should simplify the development of antibody-based BoNT diagnostics and therapeutics.
Perspectives for Improved and More Accurate Classification of Thyroid Epithelial Tumors (2008)

It is very likely that molecular definitions of thyroid tumors mentioned in the current World Health Organization classification will be further developed, leading to future progress in defining thyroid tumor types by an integrated histologic and molecular approach. These integrated classifications need to be evaluated for their specific impact on thyroid tumor diagnosis and prognosis.
High rates of thioredoxin secretion correlate with growth arrest in hepatoma cells. (1995)

Thioredoxin (TRX), a disulfide-reducing intracellular dithiol enzyme, is synthesized by both normal liver cells and the hepatocarcinoma cell line HepG2. Only the former, however, secrete abundant TRX extracellularly. When cultured in mild reducing conditions, HepG2 cells but not normal hepatocytes increase the rate of TRX secretion and undergo growth inhibition accompanied by morphological changes. Also, recombinant TRX inhibits proliferation of HepG2 cells. In contrast, exogenous thiols and TRX stimulate proliferation of a B-cell lymphoma line, indicating that different cell types respond differently to variations in the extracellular redox potential.
Embracing the complexity of genomic data for personalized medicine (2006)

Numerous recent studies have demonstrated the use of genomic data, particularly gene expression signatures, as clinical prognostic factors in cancer and other complex diseases. Such studies herald the future of genomic medicine and the opportunity for personalized prognosis in a variety of clinical contexts that utilizes genome-scale molecular information. The scale, complexity, and information content of high-throughput gene expression data, as one example of complex genomic information, is often under-appreciated as many analyses continue to focus on defining individual rather than multiplex biomarkers for patient stratification. Indeed, this complexity of genomic data is often--rather paradoxically--viewed as a barrier to its utility. To the contrary, the complexity and scale of global genomic data, as representing the many dimensions of biology, must be embraced for the development of more precise clinical prognostics. The need is for integrated analyses--approaches that embrace the complexity of genomic data, including multiple forms of genomic data, and aim to explore and understand multiple, interacting, and potentially conflicting predictors of risk, rather than continuing on the current and traditional path that oversimplifies and ignores the information content in the complexity. All forms of potentially relevant data should be examined, with particular emphasis on understanding the interactions, complementarities, and possible conflicts among gene expression, genetic, and clinical markers of risk.
TCSPC upgrade of a confocal FCS microscope (2005)

We extended the measurement capabilities of the Carl Zeiss ConfoCor 1 FCS microscope by (a) using pulsed picosecond diode lasers instead of a continuous wave (CW) laser excitation, (b) introducing a fast single photon avalanche diode detector, and (c) exploiting the capabilities of the PicoQuant TimeHarp 200 board. When the time-tagged time-resolved (TTTR) mode of the TimeHarp is utilized, the complete fluorescence dynamics are recorded. That is, the time-evolution of the fluctuations and the fluorescence decay kinetics are captured simultaneously. Recording individual photon events (without on-the-fly data reduction like in hardware correlators) preserves the full information content of the measurement for virtually unlimited data analysis tasks and provides a much more detailed view of processes happening in the detection volume. For example, autocorrelation functions of dyes in a mixture can be separated and/or their cross-correlation can be investigated. These virtual two-channel measurements are performed utilizing a single detection channel setup. The time-resolved FCS is a powerful tool in biological studies and is demonstrated here on unilamellar vesicles giving clear evidence for Bodipy dye exchange between them. The described upgrade scenario is applicable to other confocal microscopes as well. In principle, any FCS system so far utilizing conventional CW lasers can benefit from pulsed excitation and the original functionality of the setup is fully preserved.
Electrocatalysis under Conditions of High Mass Transport:  Investigation of Hydrogen Oxidation on Single Submicron Pt Particles Supported on Carbon (2004)

The mechanism and kinetics of the hydrogen oxidation reaction (hor) has been investigated using carbon-supported single particles of Pt electrocatalyst with radii as small as 40 nm. The high mass transport rates on such small particles enable us to investigate the rapid kinetics of the hor in the absence of diffusion limitations. Surface kinetic controlled polarization curves during the electrochemical oxidation of hydrogen molecules in acid solution have been obtained in the entire H UPD region, showing features obviously different from those obtained on normal micrometer electrodes or in RDE experiments. For instance, two current plateaus rather than one are seen during the steady-state polarization of the hor on electrodes made of small particles. Upon decreasing the size of the Pt particles, the two current plateaus show greater separation and become better defined. A theoretical model for the steady-state polarization of the hor has been developed in which UPD H atoms of various states are considered as the reactive intermediates and the Frumkin adsorption mode is assumed for the atomic H on Pt electrodes. It is shown that the first current plateau represents the limiting reaction rate under adsorption or combined adsorption−diffusion control while the second plateau current corresponds to the limiting diffusion-controlled reaction rate. It is pointed out that Tafel plots that have been frequently used for kinetics analysis in the hor are meaningless, especially in the potential region below 0.05V vs RHE. The polarization curves are fitted with a general polarization equation derived according to our model. The fitting shows that the hor on Pt proceeds most likely via the Tafel−Volmer reaction mechanism rather than the Heyrovsky−Volmer mechanism. These results have significant implications on the understanding and modeling of the reactions in solid polymer electrolyte fuel cells.
On Abstract Task Models and Conversation Policies (2001)

It is possible to define conversation policies, such as communication or dialogue protocols, that are based strictly on what messages and, respectively, what performatives may follow each other. While such an approach has many practical applications, such protocols support only in a conversation. In a mixed-initiative dialogue between two agents cooperating on some joint task, there must be a in both the conversation and in the task they are trying to accomplish. Recognition of agent intentions about the joint task is essential for this global coherence, but there are further mechanisms needed to ensure that both local and global coherence are jointly maintained. This paper presents a general yet practical approach to designing, managing, and engineering agents that can engage in mixed-initiative dialogues. In this approach, we promote developing abstract task models and designing conversation policies in terms of such models.
Regional Variations of Credits Obtained by LEED 2009 Certified Green Buildings—A Country Level Analysis (2017)

Leadership in Energy and Environmental Design (LEED) is one of the most widely recognized green building rating systems. With more than 20% of the projects certified in non-United States (US) countries, LEED’s global impact has been increasing and it is critically important for developers and regulatory authorities to understand LEED’s performance at the country level to facilitate global implementation. This study therefore aims to investigate the credit achievement pattern of LEED 2009, which is one of the well-developed versions of LEED, by using 4021 certified projects in the US, China, Turkey, and Brazil. The results show that significant differences can be identified on most rating categories, including sustainable sites, water efficiency, energy and atmosphere, indoor environmental quality, and innovation in design. Using a post hoc analysis, country-specific credit allocation patterns are also identified to help developers to understand existing country-specific green building practices. In addition, it is also found that there is unbalanced achievement of regional priority credits. The study offers a useful reference and benchmark for international developers and contractors to understand the regional variations of LEED 2009 and for regulatory authorities, such as the U.S. Green Building Council, to improve the rating system, especially on designing regional priority credits.
Structural alterations of the nucleolus in mutants of Saccharomyces cerevisiae defective in RNA polymerase I. (1993)

We have previously constructed mutants of Saccharomyces cerevisiae in which the gene for the second-largest subunit of RNA polymerase I (Pol I) is deleted. In these mutants, rRNA is synthesized by RNA polymerase II from a hybrid gene consisting of the 35S rRNA coding region fused to the GAL7 promoter on a plasmid. These strains thus grow in galactose but not glucose media. By immunofluorescence microscopy using antibodies against the known nucleolar proteins SSB1 and fibrillarin, we found that the intact crescent-shaped nucleolar structure is absent in these mutants; instead, several granules (called mininucleolar bodies [MNBs]) that stained with these antibodies were seen in the nucleus. Conversion of the intact nucleolar structure to MNBs was also observed in Pol I temperature-sensitive mutants at nonpermissive temperatures. These MNBs may structurally resemble prenucleolar bodies observed in higher eukaryotic cells and may represent a constituent of the normal nucleolus. Furthermore, cells under certain conditions that inhibit rRNA synthesis did not cause conversion of the nucleolus to MNBs. Thus, the role of Pol I in the maintenance of the intact nucleolar structure might include a role as a structural element in addition to (or instead of) a functional role to produce rRNA transcripts. Our study also shows that the intact nucleolar structure is not absolutely required for rRNA processing, ribosome assembly, or cell growth and that MNBs are possibly functional in rRNA processing in the Pol I deletion mutants.
Modification of transmembrane and GPI-anchored proteins on living cells by efficient protein trans-splicing using the Npu DnaE intein (2011)

The naturally split Npu DnaE intein can be used for ligation of an exogenous polypeptide to membrane proteins on living cells. No reducing agents or other factors are required. The approach is rapid and virtually traceless, because the intein removes itself during the reaction.
Crystallization of Nucleic Acids and Proteins (1999)

Crystallography is the major method of determining structures of biological macromolecules yet crystallization techniques are still regarded as difficult to perform. This new edition of Crystallization of Nucleic Acids and Proteins: A Practical Approach continues in the vein of the first edition by providing a detailed and rational guide to producing crystals of proteins and nucleic acids of sufficient quantity and quality for diffraction studies. It has been thoroughly updated to include all the major new techniques such as the uses of molecular biology in structural biology (maximizing expression systems, sequence modifications to enable crystallization, and the introduction of anomalous scatterers); diagnostic analysis of prenucleation and nucleation by spectroscopic methods; and the two- dimensional electron crystallography of soluble proteins on planar lipid films. As well as an introduction to crystallogenesis, the other topics covered are: Handling macromolecular solutions, experimental design, seeding, proceeding from solutions to crystals Crystallization in gels Crystallization of nucleic acid complexes and membrane proteins Soaking techniques Preliminary characterization of crystals in order to tell whether they are suitable for diffraction studies. As with all Practical Approach books the protocols have been written by experienced researchers and are tried an tested methods. The underlying theory is brought together with the laboratory protocols to provide researchers with the conceptual and methodological tools necessary to exploit these powerful techniques. Crystallization of Nucleic Acids and Proteins: A Practical Approach 2e will be an invaluable manual of practical crystallization methods to researchers in molecular biology, crystallography, protein engineering, and biological chemistry.
Tight Junctions in Epithelial Cells of Human Fetal Hindgut, Normal Colon, and Colon Adenocarcinoma<xref ref-type="fn" rid="FN2">2</xref> (1980)

The structural patterns of tight junctions in normal human colon mucosa, colon adenocarcinomas, and fetal colon were studied and compared by the freeze-fracturing technique. The zonula occludens of the normal colon cells at the upper, more differentiated part of the crypts of Lieberkühn appeared as continuous belts made of about eight parallel strands. At the less differentiated bases of the crypts, the zonula occludens was less regular and contained fewer, mostly beaded strands. In the colons of 10-week fetuses, early stages of tight junction assembly were observed. At the same time, vesicles bearing remnants of tight junction elements were observed within the cytoplasm. This finding suggested that during the early development and organization of the fetal gut, mechanisms of assembly and disassembly of tight junctions are operating concomitantly. In well-differentiated adenocarcinomas, the cells in the luminal region retained their polarity and had seven or eight parallel junctional elements. In infiltrating cells, however, tight junctions appeared as fascia occludens and resembled the junctional organization of 10-week fetuses.
The First Clinical Application of a “Hands-On” Robotic Knee Surgery System (2001)

The performance of a novel “hands-on” robotic system for total knee replacement (TKR) surgery is evaluated. An integrated robotic system for accurately machining the bone surfaces in TKR surgery is described. Details of the system, comprising an “active constraint” robot, called Acrobot, a “gross positioning” robot, and patient clamps, are provided. The intraoperative protocol and the preoperative, CT-based, planning system are also described. A number of anatomical registration and cutting trials, using plastic bones, are described, followed by results from two preliminary clinical trials, which demonstrate the accuracy achieved in the anatomical registration. Finally, the first clinical trial is described, in which the results of the anatomical registration and bone cutting are seen to be of high quality. The Acrobot system has been successfully used to accurately register and cut the knee bones in TKR surgery. This demonstrates the great potential of a “hands-on” robot for improving accuracy and increasing safety in surgery.