gebhart/patrepeval huggingface dataset:
Effects of Zinc on Particulate Methane Monooxygenase Activity and Structure (2014)

Particulate methane monooxygenase (pMMO) is a membrane-bound metalloenzyme that oxidizes methane to methanol in methanotrophic bacteria. Zinc is a known inhibitor of pMMO, but the details of zinc binding and the mechanism of inhibition are not understood. Metal binding and activity assays on membrane-bound pMMO from Methylococcus capsulatus (Bath) reveal that zinc inhibits pMMO at two sites that are distinct from the copper active site. The 2.6 Å resolution crystal structure of Methylocystis species strain Rockwell pMMO reveals two previously undetected bound lipids, and metal soaking experiments identify likely locations for the two zinc inhibition sites. The first is the crystallographic zinc site in the pmoC subunit, and zinc binding here leads to the ordering of 10 previously unobserved residues. A second zinc site is present on the cytoplasmic side of the pmoC subunit. Parallels between these results and zinc inhibition studies of several respiratory complexes suggest that zinc might inhibit proton transfer in pMMO.
Macromol. Biosci. 6/2008 (2008)

Cover: The cover shows the bioconjugation and characterization of aqueous suspendible polymer nanostructures prepared by simple microtome processing of electrospun nylon 6 nanofibers. Mechanically shortened, aqueous dispersed electrospun polymer nanofibers have potential application as enzyme scaffolds in chemiluminescent‐based assay systems. Further details can be found in the article by S. S. Mark, * S. I. Stolper, C. Baratti, J. Y. Park, M. A. Taku, J. J. Santiago‐Avilés, and L. J. Kricka on page 484.
Recombinant Human Butyrylcholinesterase As a New-Age Bioscavenger Drug: Development of the Expression System (2013)

Butyrylcholinesterase (BChE) is a serine hydrolase (EC 3.1.1.8) which can be found in most animal tissues. This enzyme has a broad spectrum of efficacy against organophosphorus compounds, which makes it a prime candidate for the role of stoichiometric bioscavenger. Development of a new-age DNA-encoded bioscavenger is a vival task. Several transgenic expression systems of human BChE were developed over the past 20 years; however, none of them has been shown to make economic sense or has been approved for administration to humans. In this study, a CHO-based expression system was redesigned, resulting in a significant increase in the production level of functional recombinant human butyrylcholinesterase as compared to the hitherto existing systems. The recombinant enzyme was characterized with Elman and ELISA methods.
Pharmacodynamics of Levofloxacin (1998)

Levofloxacin generated clinical and microbiological response rates of 95% and 96%, respectively. These response rates included fluoroquinolone "problem pathogens," such as Streptococcus pneumoniae and Staphylococcus aureus. Exposure to levofloxacin was significantly associated with successful clinical and microbiological outcomes. The principles used in these analyses can be applied to other classes of drugs to develop similar relationships between exposure and outcome. This pharmacokinetic modeling could be used to determine optimal treatment dose in clinical trials in a shorter time frame with fewer patients. This modeling also should be evaluated for its potential to improve outcomes (maximizing therapeutic response, preventing emergence of resistance, and minimizing adverse events) of patients treated with this drug.
Direct evidence that PKCα positively regulates wound re‐epithelialization: correlation with changes in desmosomal adhesiveness (2012)

Non-healing wounds cause considerable patient morbidity and represent a significant economic burden. Central to wound repair is re-epithelialization, a crucial process involving the modulation of cell adhesion to allow keratinocyte migration to cover the exposed underlying tissues. The cellular mechanisms regulating the earliest stages of re-epithelialization are unclear. We present the first direct evidence that protein kinase Cα (PKCα) plays an important role in regulating wound re-epithelialization. In PKCα(-/-) mice re-epithelialization is delayed, while in novel bitransgenic mice over-expressing constitutively active PKCα it is accelerated. These effects are not due to changes in keratinocyte proliferation, apoptosis or intrinsic cell motility. Instead, they correlate with changes in desmosomal adhesiveness, delay being preceded by retained desmosomal hyper-adhesiveness and acceleration with a rapid switch to desmosomal Ca(2+) -dependence. We demonstrate mechanistic conservation in acute human wounds where PKCα localizes to wound edge desmosomes, which become Ca(2+) -dependent. However, in chronic wounds PKCα remains cytoplasmic and desmosomes fail to switch from the hyper-adhesive state. These results throw new mechanistic light on the earliest stages of wound re-epithelialization and suggest activation of PKCα as a new therapeutic strategy for non-healing wounds.
Treatment of Bacterial Prostatitis (2010)

Prostatitis is characterized by voiding symptoms and genitourinary pain and is sometimes associated with sexual dysfunction. Up to 25% of men receive a diagnosis of prostatitis in their lifetime, but <10% have a proven bacterial infection. The causes and treatment of nonbacterial prostatitis are largely unknown, but bacterial prostatitis is caused by infection with uropathogens, especially gram-negative bacilli, although infection is sometimes due to gram-positive and atypical microorganisms. Acute bacterial prostatitis is easily diagnosed (by abrupt urogential and often systemic symptoms, along with bacteriuria) and treated (by systemic antibiotic therapy). Chronic bacterial prostatitis is characterized by prolonged or recurrent symptoms and relapsing bacteriuria; diagnosis traditionally requires comparing urinary specimens obtained before with specimens obtained after prostatic massage. Treating chronic bacterial prostatitis requires prolonged therapy with an antibiotic that penetrates the prostate (ie, one with high lipid solubility, a low degree of ionization, high dissociation constant, low protein binding, and small molecular size). We review recent pharmacological and clinical data on treating bacterial prostatitis.
Endothelial cells in physiology and in the pathophysiology of vascular disorders. (1998)

THE ENDOTHELIUM has long been viewed as an inert cellophane-like membrane that lines the circulatory system with its primary essential function being the maintenance of vessel wall permeability. Shortly after the first description of circulating blood by William Harvey in 1628, the existence of a
Transcriptional and replicational activation functions in the bovine papillomavirus type 1 E2 protein are encoded by different structural determinants (1996)

A set of E2 proteins with mutations in the amino-terminal transactivation domain was made by a scheme called clustered charged-to-alanine scan. These mutant E2 proteins were tested for expression, stability, and compartmentalization in cells and for sequence-specific DNA binding, as well as in functional assays for transcriptional and replicational activation. We identified four groups of mutants. First, mutants K111A, K112A, and E176A were unable to activate replication and transcription because of oligomerization-induced retention of oligomers in the cytoplasm. Second, although fractions of the mutant proteins E74A and D143A/ R172C existed in the oligomeric form, they were localized in the nucleus. Certain fractions of these proteins existed as a dimer able to form a specific complex and activate replication; however, these proteins were inactive in transcriptional activation. Third, mutants R37A and D122A were localized in the nucleus, existed in the dimeric form, supported replication efficiently, and were severely crippled in transcriptional activation. The fourth group of mutants did not differ considerably from the wild-type protein. The activation of transcription by the wild type as well as mutant E2 proteins was dependent on the concentration of input E2 expression vector DNA and had a bell-like shape. We suggest that the reduction of transcriptional activation at higher E2 concentrations, the self-squelching activity, is caused by oligomerization of the E2 transactivator and is one of the mechanisms for the regulation of E2 activity. Our results also show that transcriptional and replicational activation activities are encoded by different determinants in the E2 protein.
Energy harvesting active networked tags (EnHANTs) for ubiquitous object networking (2010)

This article presents the design challenges posed by a new class of ultra-low-power devices referred to as Energy-Harvesting Active Networked Tags (EnHANTs). EnHANTs are small, flexible, and self-reliant (in terms of energy) devices that can be attached to objects that are traditionally not networked (e.g., books, furniture, walls, doors, toys, keys, produce, and clothing). EnHANTs will enable the Internet of Things by providing the infrastructure for various novel tracking applications. Examples of these applications include locating misplaced items, continuous monitoring of objects, and determining locations of disaster survivors. Recent advances in ultra-low-power circuit design, ultra-wideband (UWB) wireless communications, and organic energy harvesting techniques will enable the realization of EnHANTs in the near future. The harvesting components and the ultra-low-power physical layer have special characteristics whose implications on the higher layers have yet to be studied (e.g., when using UWB communications, the energy required to receive a bit is significantly higher than the energy required to transmit a bit). In this article, we describe paradigm shifts associated with technologies that enable EnHANTs and demonstrate their implications on higher-layer protocols. Moreover, we describe some of the components we have designed for EnHANTs. Finally, we briefly discuss our indoor light measurements and their implications on the design of higher-layer protocols.
A centennial review; the 1890 tetanus antitoxin paper of von Behring and Kitasato and the related developments. (1991)

The significance of the 1890 tetanus antitoxin paper by von Behring and Kitasato in the development of a new discipline, immunology, is reviewed. The possible reasons why Kitasato lost the first Nobel Prize for medicine to von Behring are presented. These are as follows: (1) The Nobel selection committee literally interpreted Alfred Nobel's will to award the prize to "the person who has made the most important discovery." (2) In the late 19th century, diphtheria was a serious contagious disease which claimed many thousands of lives in the Europe and America; and von Behring's solely authored paper on diphtheria antitoxin clinched the award for him. (3) The merit of tetanus antitoxin to humans, which was the focal point of the 1890 paper on tetanus antitoxin jointly authored by von Behring and Kitasato, was not recognized at the time of the award in 1901; it became apparent only during the First World War.
Performance increase and benefit compensation in supply chains by partial information sharing and billing based on identification of returnable transport items (2008)

The hypothesis of performance-increase and benefit compensation within supply chains by partial information sharing and billing based on radio frequency identification (RFID) is verified within this paper. The concept is evaluated in a pilot project within the beverage industry. In supply chains, partial information sharing can be achieved based on RFID tags. In the pilot study, the tags are used to identify returnable transport items (RTI), because identification at item level would be too costly. The proposed integration of a billing system shall enable a compensation of benefits throughout the supply chain. In a first step, the billing model of the RTI pool operator is based on the proposed infrastructure. This approach is generic enough, though, to be adapted to many other scenarios and industries. A detailed description of RTI is given within the first paragraph. In the second paragraph, the technical applicability of ultra-high frequency (UHF) within the beverage supply chain is evaluated, and the modelling of the beverage supply chain is described. After logistical evaluation in Section 3, the fourth section describes the integration of a billing model. The pilot project carried out by the Bremen Research Cluster for Dynamics in Logistics was started in April 2008 to validate the proposed model in a real scenario within the beverage industry.
Microdomain Morphology of Poly(urethane urea) Multiblock Copolymers (2001)

As part of our continuing study of the solid-state morphology of poly(urethane urea) segmented block copolymers, we focus in the current paper on the use of atomic force microscopy to visualize the structure of phase-separated microdomains. Free surface and bulk images were obtained from two series of PUU films, for copolymers varying in hard segment content from 14 to 47 wt %. Using a progression of AFM tapping forces, the morphology of the hard domains at the free surfaces was found to be in the form of randomly oriented cylinders with additional spherical domains, both having lateral dimensions on the order of 5−10 nm. At higher tapping forces, phase images of microtomed surfaces of relatively high hard segment content PUU copolymers appear to exhibit hard segment-rich domains at two size scales. However, images of surfaces of specimens freeze-fractured at liquid N2 temperatures (and acquired at relatively low tapping forces) reveal the larger structures to be aggregates of smaller hard microdomains.
Design and synthesis of RNA miniduplexes via a synthetic linker approach. 2. Generation of covalently closed, double-stranded cyclic HIV-1 TAR RNA analogs with high Tat-binding affinity (1993)

We recently developed an approach which allows rapid generation of short, double-stranded oligonucleotides whereby one end of the duplex was joined and stabilized by a synthetic linker of specific design (miniduplexes)(6). Model miniduplexes based on the HIV-1 TAR RNA hairpin were shown to be thermodynamically stable and good substrates for binding by the HIV-1 Tat protein which normally bind to natural TAR (6). In this study, we have extended our studies to the design, synthesis and analysis of the binding properties of covalently closed, double-stranded, cyclic RNA miniduplexes. A strategy using automated chemical synthesis and T4 RNA ligase-catalyzed cyclization was employed to generate cyclic oligoribonucleotides. When both ends of a shortened, wild-type TAR RNA stem (9 bp) were covalently linked through either nucleotidic loops (4-6 nt) or synthetic linkers (derivatized from hexaethylene glycol), the resulting cyclic TAR RNA analogs were good substrates for binding by both Tat-derived peptide or full-length Tat protein. Interestingly, the cyclic TAR analogs failed to show any binding if the synthetic linker was reduced in length (e.g. derivatized from triethylene glycol), although such linkers are acceptable in the hairpin-shaped miniduplexes series (6). This implies that RNA conformational changes are required for Tat binding and that these changes are restricted in certain cyclic variants. Our findings suggest that covalently-closed nucleic acid miniduplexes may be useful both to study nucleic acid-protein interactions as well as to provide a basis for therapeutic intervention as transcription decoys.
In vivo OCT imaging of hard and soft tissue of the oral cavity (1998)

We use optical coherence tomography (OCT) to perform a comprehensive program of in vivo and in vitro structural imaging of hard and soft tissues within the oral cavity. We have imaged the different types of healthy oral mucosa as well as normal and abnormal tooth structure. OCT is able to differentiate between the various types of keratinized and non-keratinized mucosa with high resolution. OCT is also able to provide detailed structural information on clinical abnormalities (caries and non-caries lesions) in teeth and provide guidance in dental restorative procedures. Our investigations demonstrate the utility of OCT as a diagnostic imaging modality in clinical and research dentistry.
Searching the web: The public and their queries (2001)

In studying actual Web searching by the public at large, we analyzed over one million Web queries by users of the Excite search engine. We found that most people use few search terms, few modified queries, view few Web pages, and rarely use advanced search features. A small number of search terms are used with high frequency, and a great many terms are unique; the language of Web queries is distinctive. Queries about recreation and entertainment rank highest. Findings are compared to data from two other large studies of Web queries. This study provides an insight into the public practices and choices in Web searching.
Recommendations for Use of Free Light Chain Assay in Monoclonal Gammopathies (2009)

Recommendations for Use of Free Light Chain Assay in Monoclonal Gammopathies The serum immunoglobulin free light chain assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the free light chain assay in the evaluation and management of multiple myeloma and related plasma cell disorders. In the context of screening, the serum free light chain assay in combination with serum protein electrophoresis and immunofixation yields high sensitivity, and negates the need for 24-hour urine studies for diagnoses other than light chain amyloidosis. Second, the baseline free light chains measurement is of major prognostic value in virtually every plasma cell disorder. Third, the free light chain assay allows for quantitative monitoring of patients with oligosecretory plasma cell disorders, including AL, oligosecretory myeloma, and nearly twothirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial free light chains measurements outperform protein electrophoresis and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial free light chains measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using free light chain assay in place of 24-hour urine electrophoresis for monitoring or for serial measurements in plasma cell disorders with measurable disease by serum or urine electrophoresis.
Epitopes on CA 125 fron cervical mucus and ascites fluid and characterization of six new antibodies - Third report from the ISOM TD-1 workshop (2002)

CA 125 is found in body fluids in a variety of molecular weight forms. The largest species are found in normal abdominal fluid and cervical mucus. The present study therefore incorporated CA 125 derived from these sources as well as ascites fluid to investigate if the source of CA 125 influenced epitope characterization. Ascites-derived CA 125 varied in size from about 190 to about 2,700 kD. Cervical mucus-derived CA 125 treated with ultrasound changed its apparent size from more than 20,000 to 700 kD. Epitope mapping of antibodies was not grossly influenced by the size or source of CA 125 used as target. However, low-molecular-weight CA 125, i.e. ascites fractions CA 17/E, CA 17/F and CA 10/7, did show differences in certain assay combinations and cross-inhibition patterns which probably can be explained by steric effects due to the smaller size compared with the most abundant forms of CA 125 present in serum and other body fluids. The specificity of six new monoclonal antibodies to CA 125 was tested by cross-inhibition and immunometric assay combinations and compared to reference antibodies. One antibody, X306, belonged to the OC125-like antibodies. Four antibodies, X52, X75, X325 and VK8, were M11-like. The sixth antibody, 7C12, reacted with an epitope which was difficult to define. This antibody was inhibited by M11-like antibodies and OV197. However, used as an inhibitor, 7C12 inhibited only itself. We grouped it as an OV197-like antibody, but clearly different from OV197. The topography of epitopes was studied by analyzing all antibody pairs in immunoradiometric assays. These results confirmed the grouping of antibodies described above and are in accordance with previous findings that the highest signal is obtained using an OC125-like antibody or OV197 on the solid phase and an M11-like antibody as tracer. The composition of the sample in terms of high- and low-molecular-weight species of CA 125 was measured, with different responses depending on the antibody pair used. This might be one reason for discrepancies between assay results for CA 125 using different assays. Copyright (C) 2002 S. Karger AG, Basel.
Frame synchronization of OFDM systems in frequency selective fading channels (2002)

This paper investigates the topic of frame synchronization for systems based on the OFDM principle. After introducing the system model we discuss the task of a frame-synchronization and analyze the effects of a frame offset. From this we derive an appropriate criterion to measure the performance of synchronization algorithms under multipath conditions. We examine two algorithms for frame synchronization: the first algorithm is based on an evaluation of periodic structures. Since it is completely independent of a frequency offset it may be applied for system acquisition and burst synchronization. If the requirements are very high as in terrestrial TV broadcasting a second algorithm is needed to attain sufficient accuracy. The algorithm presented for this purpose is based on the evaluation of the channel estimate, so no further training data is required.
Heptahelical and Other G-Protein-Coupled Receptors (GPCRs) Signaling (2005)

Heptahelical receptors are coupled to heterotrimeric GTP-binding proteins (G-proteins) which transduce most signals through their alpha and betagamma subunits to effectors, enzymes and ion channels. Of the 367 heptahelical receptors for endogenous ligands, about 330 are potential targets for drug discovery with agonist, antagonist or inverse agonist properties. The term G-protein-coupled receptors (GPCRs) is a broader functional definition rather than a structural one referring to heptahelical receptors specifically. Non-heptahelical putative GPCRs include some transmembrane receptors with tyrosine-kinase activity on their cytosolic endings (EGF, insulin and IGF-1 receptors), other transmembrane receptors (mannose-6-phosphate/IGF-2 receptor and integrin-associated protein IAP or CD47), and some receptors belonging to the class of glycosylphosphatidylinositol (GPI)-anchored proteins and located on the outer face of the plasma membrane. Also, activators of G-protein signaling (AGS) proteins that regulate vesicular trafficking activate heterotrimeric G-proteins in the Golgi independently of receptor activation. Main effectors activated through their direct interactions with alpha subunits or betagamma dimers of heterotrimeric G-proteins include adenylylcyclases, cGMP-phosphodiesterase, phospholipases Cbeta, phosphoinositide 3-kinase gamma, Ca(V2) calcium channels, GIRK/Kir3 potassium channels, and guanine nucleotide exchange factors RasGEF and RhoGEF leading to small G-proteins and MAP-kinases activation. Current signaling cascades leading to final cell responses are depicted.