gebhart/patrepeval huggingface dataset:
Mechanism of regulation of Hsp70 chaperones by DnaJ cochaperones (1999)

Hsp70 chaperones assist a large variety of protein folding processes within the entire lifespan of proteins. Central to these activities is the regulation of Hsp70 by DnaJ cochaperones. DnaJ stimulates Hsp70 to hydrolyze ATP, a key step that closes its substrate-binding cavity and thus allows stable binding of substrate. We show that DnaJ stimulates ATP hydrolysis by Escherichia coli Hsp70, DnaK, very efficiently to >1000-fold, but only if present at high (micromolar) concentration. In contrast, the chaperone activity of DnaK in luciferase refolding was maximal at several hundredfold lower concentration of DnaJ. However, DnaJ was capable of maximally stimulating the DnaK ATPase even at this low concentration, provided that protein substrate was present, indicating synergistic action of DnaJ and substrate. Peptide substrates were poorly effective in this synergistic action. DnaJ action required binding of protein substrates to the central hydrophobic pocket of the substrate-binding cavity of DnaK, as evidenced by the reduced ability of DnaJ to stimulate ATP hydrolysis by a DnaK mutant with defects in substrate binding. At high concentrations, DnaJ itself served as substrate for DnaK in a process considered to be unphysiological. Mutant analysis furthermore revealed that DnaJ-mediated stimulation of ATP hydrolysis requires communication between the ATPase and substrate-binding domains of DnaK. This mechanism thus allows DnaJ to tightly couple ATP hydrolysis by DnaK with substrate binding and to avoid jamming of the DnaK chaperone with peptides. It probably is conserved among Hsp70 family members and is proposed to account for their functional diversity.
Antitumor Agents. 49. Tricin,Kaempferol-3-0-β-D-Glucopyranoside and (+)-Nortrachelogenin, Antileukemic Principles From Wikstroemia indica (1981)

Bioassay-directed isolation of the antitumor extract of Wikstroemia indica (Thymelaeaceae) has led to the characterization of tricin, kaempferol-3-O-beta-D-glucopyranoside, and (+)-nortrachelogenin as the major antileukemic constituents. In addition, daphnoretin was identified as the potent antitumor principle in vivo against the Ehrlich ascites carcinoma growth in mice.
Addition of Clonidine Enhances Postoperative Analgesia from Epidural Morphine (1990)

This study was undertaken to evaluate the analgesic effect of the combination of epidural morphine and clonidine versus epidural morphine alone in patients with postoperative pain. A randomized double-blind design was used, and 91 patients scheduled for post-operative pain relief by epidural morphine were studied. Patients received either a continuous epidural infusion of morphine and clonidine (group 1; n = 45) or morphine alone (group 2; n = 46) over the 72 h after major abdominal surgery. In the first 24 h, the dose of morphine was 6 mg per 24 h; during the second 24 h, it was decreased to 4 mg per 24 h; and in the final 24 h, it was decreased to 2 mg per 24 h in both groups. Group 1 patients received clonidine (450 micrograms) during each 24-h period. Additional epidural bolus injections of 2 mg morphine and intravenous meperidine were given on demand. The pain score, blood pressure, heart rate, respiratory rate, and relative forced vital capacity were measured at fixed times during the first 72 h after operation. Total consumption of analgesics and side effects were recorded. Although the total consumption of analgesics was significantly higher in group 2 (P less than 0.05), pain scores were lower in group 1 than group 2 during the entire observation period (P less than 0.05). Epidural clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. Due to the better pain relief in group 1, the forced vital capacity was increased (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The Phosphatidylinositol 3‐Kinase Inhibitors Wortmannin and LY294002 Inhibit Autophagy in Isolated Rat Hepatocytes (1997)

Recent studies indicate that phosphatidylinositol 3-kinase is essential in the regulation of many processes dependent on membrane flow. Autophagy is a complex pathway in which cell material, including proteins, can be degraded. Membrane flow plays a pivotal role in this process. To find out whether phosphatidylinositol 3-kinase is also required for autophagy, we tested the effects on autophagy of two structurally unrelated phosphatidylinositol 3-kinase inhibitors, wortmannin and 2-(4-morpholinyl)-8-phenylchromone (LY294002). The addition of low concentrations of each of these inhibitors to incubations of hepatocytes in the absence of amino acids resulted in a strong inhibition of proteolysis. The antiproteolytic effect of wortmannin (IC50 30 nM) and LY294002 (IC50 10 microM) was accompanied by inhibition of autophagic sequestration and not by an increase in lysosomal pH or a decrease in intracellular ATP. No further inhibition of proteolysis by the two compounds was observed when autophagy was already maximally inhibited by high concentrations of amino acids. 3-Methyladenine, which is commonly used as a specific inhibitor of autophagic sequestration, was an inhibitor of phosphatidylinositol 3-kinase, thus providing a target for its action. It is proposed that phosphatidylinositol 3-kinase activity is required for autophagy. 3-Methyladenine inhibits autophagy by inhibition of this enzyme.
Lack of protection following immunisation withH. pyloriouter membrane vesicles highlights antigenic differences betweenH. felisandH. pylori (1998)

Helicobacter pylori-induced inflammation is associated with the development of gastritis, peptic ulcer disease and gastric cancer in humans. Immunisation against this bacterium would ultimately have a major impact on H. pylori-related disease, notably global gastric cancer rates. To date, several potential H. pylori vaccine candidates have been identified. In this study, the Helicobacter felis/murine model was used to assess the immunogenicity of a previously undescribed H. pylori outer membrane vesicle fraction in immune protection.
Reliable management of voice in a distributed system (2021)

The ubiquitous personal computer has found its way into most office environments. As a result, widespread use of the Local Area Network (LAN) for the purposes of sharing distributed computing resources has become common. Another technology, the Private Automatic Branch Exchange (PABX), has benefited from large research and development by the telephone companies. As a consequence, it is cost effective and has widely infiltrated the office world. Its primary purpose is to switch digitised voice but, with the growing need for communication between computers it is also being adapted to switch data. However, PABXs are generally designed around a centralised switch in which bandwidth is permanently divided between its subscribers. Computing requirements need much larger bandwidths and the ability to connect to several services at once, thus making the conventional PABX unsuitable for this application. Some LAN technologies are suitable for switching voice and data. The additional requirement for voice is that point to point delay for network packets should have a low upper-bound. The 10 Mb/s Cambridge Ring is an example of this type of network, but is relatively low bandwidth gives it limited application in this area. Networks with larger bandwidths (up to 100 Mb/s) are now becoming available comercially and could support a realistic population of clients requiring voice and data communication. Transporting voice and data in the same network has two main advantages. Firstly, from a practical point of view, wiring is minimised. Secondly, applications which integrate both media are made possible, and hence digitised voice may be controlled by client programs in new and interesting ways. In addition to the new applications, the original telephony facilities must also be available. They should, at least by default, appear to work in an identical way to our tried and trusted impression of a telephone. However, the control and management of a network telephone is now in the domain of distributed computing. The voice connections between telephones are virtual circuits. Control and data information can be freely mixed with voice at a network interface. The new problems that result are the management issues related to the distributed control of real-time media. This thesis describes the issues as a distributed computing problem and proposes solutions, many of which have been demonstrated in a real implementation. Particular attention has been paid to the quality of service provided by the solutions. This amounts to the design of helpful operator interfaces, flexible schemes for the control of voice from personal workstations and, in particular, a high reliability factor for the backbone telephony service. This work demonstrates the advantages and the practicality of integrating voice and data services within the Local Area Network.
Design principles for tamper-resistant smartcard processors (1999)

We describe techniques for extracting protected software and data from smartcard processors. This includes manual microprobing, laser cutting, focused ion-beam manipulation, glitch attacks, and power analysis. Many of these methods have already been used to compromise widely-fielded conditional-access systems, and current smartcards offer little protection against them. We give examples of low-cost protection concepts that make such attacks considerably more difficult.
Logic Gates and Elementary Computing by Enzymes (2006)

Different selected enzymes, glucose oxidase (GOx), catalase (Cat), glucose dehydrogenase (GDH), horseradish peroxidase (HRP), and formaldehyde dehydrogenase (FDH), are used alone or coupled to construct eight different logic gates. The added substrates for the respective enzymes, glucose and H(2)O(2), act as the gate inputs, while the biocatalytically generated gluconic acid or NADH are the output signals that follow the operation of the gates. Different enzyme-based gates are XOR, INHIBIT A, INHIBIT B, AND, OR, NOR, Identity and Inverter gates. By combining the AND and XOR or the XOR and INHIBIT A gates, the half-adder and half-subtractor are constructed, respectively, opening the way to elementary computing by the use of enzymes.
The Involvement of Aromatic Amino Acids in Biological Activity of Bovine Fibrinogen as Assessed by Gamma-Irradiation (1976)

Purified bovine fibrinogen in aqueous solution (1 mg/ml) was subjected to gamma-irradiation (0-100 kR) in the presence and absence of free radical scavengers. The absorption and emission spectra along with the data on amino acid composition indicated loss of tryptophan and tyrosine residues in the protein concomitant with the dose of radiation exposure. This could be correlated with the decrease in clottability of fibrinogen and the increase in clotting time. Sodium nitrate, an electron scavenger, did not exert protective action, either on these amino acids or on the biological activity of the protein as the substrate of thrombin. On the other hand, potassium iodide, a scavenger of OH. radicals preserved both of these to the extent of 90-95 percent. The results suggest that aromatic residues have a role in the clotting function of bovine fibrinogen and that gamma-radiation could serve as a probe to ascertain their involvement in the biological integrity of nonenzyme proteins. (auth)
The development of competence in resting B cells. The induction of cyclic AMP and ornithine decarboxylase activity after direct contact between B and T helper cells (1991)

In the present communication, an experimental approach is utilized that facilitates the study of biochemical processes induced in B cells after their interaction with Th cells. In this approach, Th cell clones are stimulated for 18 h upon anti-CD3-coated plates, fixed with paraformaldehyde, and added at a 2 to 3:1 ratio to small, resting B cells (isolated from Percoll gradients). Th cells not stimulated on anti-CD3-coated plates, but fixed with paraformaldehyde, serve as controls for these experiments. The activated, fixed Th cells induce a transient, sixfold increase in B cell levels of cAMP, as well as an increase in B cell expression of ornithine decarboxylase (ODC) activity. This enzyme initiates the synthesis of polyamines and has been shown to be increased as cells enter the growth phase. In addition, previous studies have shown that the cellular levels of ODC activity are controlled by a multi-tiered regulatory cascade. To examine this aspect, polyclonally stimulated B cells were studied. Such cells demonstrated a gradual increase in ODC mRNA levels that peaked between 6 and 15 h and can be partially explained by a three- to fourfold increase in mRNA stability but not by changes in the enzyme affinity for substrate. The increase in ODC mRNA occurs in the absence of protein synthesis, suggesting that the ODC gene is a member of the immediate/early gene family. Finally, the early increase in ODC mRNA was enhanced in cells in which cAMP levels were artificially elevated, suggesting the possibility that the cAMP-dependent signaling pathway participates during the regulation of this gene expression. The significance of these experimental results concerning the process of B cell activation is discussed.
Physico‐chemical requirements for cellular uptake of pAntp peptide (2001)

The pAntp peptide, corresponding to the third helix of the Antennapedia homeodomain, is internalized by a receptor-independent process into eucaryotic cells. The precise mechanism of entry remains unclear but the interaction between the phospholipids of plasma membrane and pAntp is probably involved in the translocation process. In order to define the role of peptide-lipid interaction in this mechanism and the physico-chemical properties that are necessary for an efficient cellular uptake, we have carried out an Ala-Scan mapping. The peptides were labeled with a fluorescent group (7-nitrobenz-2-oxo-1,3-diazol-4-yl-; NBD) and their cell association was measured by flow cytometry. Furthermore, we determined the fraction of internalized peptide by using a dithionite treatment. Comparison between cell association and cell uptake suggests that the affinity of pAntp for the plasma membrane is required for the import process. To further investigate which are the physico-chemical requirements for phospholipid-binding of pAntp, we have determined the surface partition coefficient of peptides by titrating them with phospholipid vesicles having different compositions. In addition, we estimated by circular dichroism the conformation adopted by these peptides in a membrane-mimetic environment. We show that the phospholipid binding of pAntp depends on its helical amphipathicity, especially when the negative surface charge density of phospholipid vesicles is low. The cell uptake of pAntp, related to lipid-binding affinity, requires a minimal hydrophobicity and net charge. As pAntp does not seem to translocate through an artificial phospholipid bilayer, this might indicate that it could interact with other cell surface components or enters into cells by a nonelucidated biological mechanism.
Reduction of architecture vulnerability factor using Modified Razor flipflops (2007)

Research has shown that microprocessors and structures of the microprocessors are vulnerable to alpha Single Event Upsets that affect program correctness and reliability. In this thesis, we have explored the use of Modified Razor flip-flops in the microprocessor to increase the overall reliability of the microprocessor. We have adopted Architecturally Correct Execution (ACE) time based techniques to measure the Architecture Vulnerability Factor (AVF) of high performance microprocessors and their internal structures using the SPEC 2000 integer benchmarks. We have computed the reduction in AVF with the introduction of Modified Razor flip-flops for various combinations of bit-fields that have high vulnerability. However, introduction of Modified Razor flip-flops results in higher area requirement on the die and higher power consumption. We have identified the most cost-effective solution by identifying the fields of these microarchitectural structures - where Modified Razor flip-flops are introduced - that result in the highest percentage decrease in AVF per unit area-power product.
A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer (2018)

Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE.
Low-temperature specific heat and thermal conductivity of silica aerogels (1991)

Specific-heat and thermal-conductivity measurements were made on a series of base-catalyzed silica aerogels at temperatures between 0.05 and 20 K. Evidence for a crossover between regimes of characteristically different excitations was observed. The data analysis indicates a ``bump'' in the density of vibrational states g(\ensuremath{\omega}) at the crossover frequency from phonon to fracton behavior.
Doppler asymmetric spatial heterodyne spectroscopy (DASH): an innovative concept for measuring winds in planetary atmospheres (2006)

We introduce an innovative concept for inferring altitude profiles of horizontal wind in planetary atmospheres by measuring the Doppler shift of multiple emission lines versus altitude. Instruments using this approach will be especially well suited for interplanetary missions because they will be compact, rugged, and lightweight while minimizing power consumption and maximizing sensitivity, all without moving parts.
Antisense Bcl-2 oligodeoxynucleotides inhibit progression to androgen-independence after castration in the Shionogi tumor model. (1999)

Progression to androgen-independence remains the main obstacle to improving survival for patients with advanced prostate cancer. Although Bcl-2 expression in normal prostatic epithelial cells is low or absent, Bcl-2 is highly up-regulated in prostate cancer cells after androgen withdrawal and during progression to androgen-independence. Here, we test the efficacy of antisense Bcl-2 oligodeoxynucleotide (ODN) therapy administered adjuvantly after castration to delay time to androgen-independent recurrence in the androgen-dependent mouse Shionogi tumor model. Treatment of Shionogi tumor cells in vitro with antisense Bcl-2 ODN inhibited Bcl-2 expression in a dose-dependent and sequence-specific manner. Systemic administration of antisense Bcl-2 ODN in mice bearing Shionogi tumors beginning 1 day postcastration resulted in a more rapid regression of tumors and a significant delay of emergence of androgen-independent recurrent tumors. Furthermore, despite significant reduction of Bcl-2 expression in tumor tissues, antisense Bcl-2 ODN had no effect on Bcl-2 expression in normal mouse organs. These findings illustrate the potential utility of antisense Bcl-2 therapy for prostate cancer in an adjuvant setting with androgen ablation.
The Oxford desk dictionary and thesaurus (2002)

An all-in-one reference providing convenience, value, and the authority of Oxford dictionaries. The Oxford American Desk Dictionary & Thesaurus Third Edition is the ideal all-in-one reference, with a dictionary and a thesaurus combined in one handy, integrated volume. A word's meanings, synonyms, and antonyms are given in the same entry, allowing the user access to all this information at a glance. The text is fully updated with the latest lexical content, informed by Oxford's extensive language research program, including the Oxford English Corpus, a unique electronic database of more than two billion words that allows us to offer the fullest, most accurate picture of the English language today. Hundreds of new words cover computing, ecology, technology, and many other subjects. The Dictionary & Thesaurus includes helpful extra features such as a center Reference section, which includes thoroughly updated appendices. Within the text, usage tip boxes help users write more effective English. A completely redesigned interior lends an open, readable look that makes this reference accessible and easy to use.
The major dog allergens, Can f 1 and Can f 2, are salivary lipocalin proteins: cloning and immunological characterization of the recombinant forms (1997)

Canis familiaris allergen 1 (Can f 1) and Canis familiaris allergen 2 (Can f 2) are the two major allergens present in dog dander extracts. We now report the isolation of cDNAs encoding both proteins and present their nucleotide and deduced amino acid sequences. Can f 1, produced by tongue epithelial tissue, has homology with the von Ebner's gland (VEG) protein, a salivary protein not previously thought to have allergenic properties. Can f 2, produced by tongue and parotid gland, has homology with mouse urinary protein (MUP), a known allergen. Both VEG protein and MUP are members of the lipocalin family of small ligand-binding proteins. Recombinant forms of Can f 1 and Can f 2 were produced and tested for immunoglobulin E (IgE) reactivity. Among dog-allergic subjects, 45% had IgE directed exclusively to rCan f 1, and 25% had IgE to both rCan f 1 and rCan f 2. In addition, both recombinant proteins were able to cross-link IgE and elicit histamine release from peripheral blood leucocytes in vitro. These findings confirm that Can f 1 and Can f 2 are major and minor dog allergens, respectively, and demonstrate that recombinant forms of dog allergens retain at least some IgE-binding epitopes.