gebhart/patrepeval huggingface dataset:
A New Concept for the Mechanism of Action of Chymotrypsin:  The Role of the Low-Barrier Hydrogen Bond (1997)

The basicities of the diad H57-D102 at N(epsilon)2 in the tetrahedral complexes of chymotrypsin with the peptidyl trifluoromethyl ketones (TFK) N-acetyl-L-Leu-DL-Phe-CF3 and N-acetyl-DL-Phe-CF3 have been studied by 1H-NMR. The protons bridging His 57 and Asp 102 in these complexes are engaged in low-barrier hydrogen bonds (LBHBs). In 1H-NMR spectra at pH 7.0, these protons appear at delta 18.9 and 18.6 ppm, and the pK(a)s of the diads are 12.0 +/- 0.2 and 10.8 +/- 0.1, respectively. The difference indicates that removal of leucine from the second aminoacyl site S2 of chymotrypsin weakens the LBHB and decreases the basicity of the H57-D102 diad relative to the case in which S2 is occupied by leucine. Consideration of the available structural data on chymotrypsin and other serine proteases, together with the high pK(a)s of the hemiketals formed with TFKs, suggests that LBHB formation in catalysis arises through a substrate-induced conformational transition leading to steric compression between His 57 and Asp 102. Because the N-O distance in the LBHB is shorter than the Van der Waals contact distance, the LBHB is proposed to stabilize the tetrahedral intermediate through relief of steric strain between these residues. In this mechanism, substrate-induced steric compression within the diad increases the basicity of N(epsilon)2 in His 57, making it a more effective base for abstracting a proton from Ser 195 in the formation of the tetrahedral intermediate. The values of pK(a) for N(epsilon)2 in TFK adducts lie between those of Ser 195 (pK(a) approximately 14) and the leaving group in tetrahedral adducts (pK(a) approximately 9), making N(epsilon)2 of the H57-D102 diad strong enough as a base to abstract the proton from Ser 195 in tetrahedral adduct formation but not so strong that its conjugate acid cannot protonate the leaving group. According to this theory, the "normal" pK(a) of His 57 in free chymotrypsin arises from the use of part of the stabilization energy provided by the LBHB to drive the conformational compression required for its formation. In catalysis, the energy for conformational compression is supplied by the binding of remote portions of the substrate, including the side chains of P1 and P2.
Sensitive titration microcalorimetric study of the binding of Salmonella O‐antigenic oligosaccharides by a monoclonal antibody (1991)

The binding of several oligosaccharide haptens by a monoclonal antibody, Se155-4, specific for Salmonella serogroup B O-antigen was studied by titration microcalorimetry. In the software developed by Wiseman et al. [Wiseman, T., Williston, S. & Brandts, J.F. (1989) Anal. Biochem. 17, 131-137] the number of binding sites/macromolecule is one of the optional regression parameters in the non-linear least-squares analysis of the calorimetric data. Instead, an approach was adopted in which the concentration of binding sites was treated as a regression parameter, obviating the requirement for precise values of antibody absorption coefficients and minimizing effects due to partially inactive antibody preparations. Furthermore, performing the least-squares analysis in two steps, first using a differential heat mode and then an integral heat mode, was shown to yield the most accurate results. The technique gave accurate results using not more than 1-2 mumol ligand and less than 7 mg antibody. Haptens 2-5 were oligomers of the O-antigenic repeating unit varying in chain length by 2-5 repeating units and a trisaccharide glycoside 1, which filled the binding site. The latter hapten exhibited a favourable entropy contribution to binding (delta Go = -31 kJ.mol-1; delta Ho = -21 kJ.mol-1 and -T delta So -10 kJ.mol-1), while all four oligomers 2-5 showed a constant binding energy delta Go = -33 kJ.mol-1, composed of increasingly stronger enthalpy forces compensated by an increasingly unfavourable entropy contribution. These observations are compared with results from enzyme immunoassays and a high-resolution crystal structure for the dodecasaccharide 3 bound to the Fab derived from Se155-4.
A Cloud Architecture Using Smart Nodes (2011)

Most Infrastructure As A Service (IaaS) cloud platforms are implemented with a cluster of machines having multiple worker nodes and a single master node, which acts as the cloud front-end. In such an architecture the control regarding the Virtual Machine (VM) scheduling and policies compliance etc. lies largely with the front-end node of the cluster. Decision making in such IaaS cloud does not have any intelligent and real time participation from the worker nodes. This is undesirable for scenarios where the cloud is composed from nodes that are semi/fully autonomous and/or when their ownership is hierarchical in nature. It becomes even more significant issue in cases where the hyper visor is a Type-2 (i.e. hosted) kind. This is because a Type-2 hyper visor runs as a regular operating system (OS) process subjected to local OS policies regarding resource allocation and security etc. To address these issues, we propose here an architecture which makes use of real time system-state information from the cluster nodes and decentralizes the cluster node policy management etc., among other design decisions. We show that the scalability, security, availability and reliability of the IaaS cloud gets improved with our proposed architecture. We apply the proposed architecture to a real use case where it helps utilize the untapped computing capacity of large pool of powerful PCs without violating the unique Quality of Service (QoS) needs of their regular owners and users.
Production of Encephalitis Restricted to the Temporal Lobes by Experimental Reactivation of Herpes Simplex Virus (1986)

A model was developed in which reactivation of latent infections with herpes simplex virus type 1 was induced in trigeminal ganglia and central nervous system olfactory centers of rabbits by administration of cyclophosphamide and dexamethasone. Latent infections were reactivated at a significantly higher frequency in rabbits infected with a highly virulent strain of virus than in those infected with a strain of lower neurovirulence. Electroencephalographic abnormalities that were largely confined to the posterior lateral cerebral hemispheres and corresponding inflammatory lesions were seen in rabbits acutely infected with the highly virulent strain, whereas no brain electrical abnormalities and only mild inflammatory lesions were seen in rabbits acutely infected with the strain of low neurovirulence. Reactivation of the highly neurovirulent strain produced focal brain necrosis restricted to the temporal lobes, which was similar to the disease produced in humans and which correlated with progressive worsening of brain electrical abnormalities.
A new bandwidth efficient transmit antenna modulation diversity scheme for linear digital modulation (2002)

A system is proposed and analyzed, which uses several transmit antennas to achieve diversity in a flat fading mobile radio environment. The signals at different antennas carry the same digital information, but have different modulation parameters (modulation diversity). In contrast to other proposals, no bandwidth expansion is required. Modulation diversity for quadrature amplitude modulation (QAM) type modulation is achieved by using different partial response type base pulses. Simulation results confirm the expected gain.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analysis of the control of the anti-gal immune response in a non-human primate by galactose ??1-3 galactose trisaccharide-polyethylene glycol conjugate (2002)

These alpha-gal polyethylene glycol conjugates may have the potential to control the anti-gal antibody response in a pig to primate organ transplant setting and may be a useful therapeutic agent in prolonging graft survival.
Have inadequate delivery systems hampered the clinical success of inhaled disodium cromoglycate? Time for reconsideration (2010)

Pharmacological efficacy of DSCG has been demonstrated in animals and humans. If the drug is delivered to the site of inflammation in an effective dose, a reliable therapeutic effect can be expected. DSCG has extra properties and potential unspecific antiviral properties and may offer new therapeutic treatment aspects for asthma and viral-induced bronchiolitis in early childhood.
tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c (2000)

TNFR1/Fas engagement results in the cleavage of cytosolic BID to truncated tBID, which translocates to mitochondria. Immunodepletion and gene disruption indicate BID is required for cytochrome c release. Surprisingly, the three-dimensional structure of this BH3 domain-only molecule revealed two hydrophobic alpha-helices suggesting tBID itself might be a pore-forming protein. Instead, we demonstrate that tBID functions as a membrane-targeted death ligand in which an intact BH3 domain is required for cytochrome c release, but not for targeting. Bak-deficient mitochondria and blocking antibodies reveal tBID binds to its mitochondrial partner BAK to release cytochrome c, a process independent of permeability transition. Activated tBID results in an allosteric activation of BAK, inducing its intramembranous oligomerization into a proposed pore for cytochrome c efflux, integrating the pathway from death receptors to cell demise.
Sequence-dependent oligonucleotide-target duplex stabilities: rules from empirical studies with a set of twenty-mers. (1990)

We were interested in developing a better method to predict the thermal stability of specific oligonucleotide-target duplexes. Recognizing that the base sequence can have important effects, we investigated the use of a simple parameter based on nearest-neighbor stacking interactions, the mean stacking temperature. We took values for doublet stabilities from the literature and used a computer program to calculate mean stacking temperatures for all oligonucleotides of specified length and G + C content in the M13 phage genome. As expected, the program predicted a fairly broad range of stabilities for different sequences of equal G + C content. We selected 20-mer sequences representing the highest and lowest mean stacking temperatures at 25%, 50% and 75% G + C and synthesized them for use as probes against M13 DNA immobilized on filters. By hybridizing and washing at different temperatures, we demonstrated that mean stacking temperatures correlate well with observed stabilities. Relative stabilities of the six oligos were predicted correctly in every case. We used conditions appropriate to oligonucleotide probing and polymerase chain reaction and we were able to derive simple linear equations relating the empirical data and mean stacking temperature for both. These observations should be useful in planning experiments with oligonucleotides.
Generation, Isolation, and Maintenance of Human Mast Cells and Mast Cell Lines Derived from Peripheral Blood or Cord Blood (2010)

Antigen-mediated mast cell activation is a pivotal step in the initiation of allergic disorders including anaphylaxis and atopy. To date, studies aimed at investigating the mechanisms regulating these responses, and studies designed to identify potential ways to prevent them, have primarily been conducted in rodent mast cells. However, to understand how these responses pertain to human disease, and to investigate and develop novel therapies for the treatment of human mast cell-driven disease, human mast cell models may have greater relevance. Recently, a number of systems have been developed to allow investigators to readily obtain sufficient quantities of human mast cells to conduct these studies. These mast cells release the appropriate suite of inflammatory mediators in response to known mast cell activators including antigen. These systems have also been employed to examine the signaling events regulating these responses. Proof of principle studies has also demonstrated utility of these systems for the identification of potential inhibitors of mast cell activation and growth. In this unit, techniques for the development and culture of human mast cells from their progenitors and the culture of human mast cell lines are described. The relative merits and drawbacks of each model are also described.
The effects of stem length and core placement on shRNA activity (2011)

We conclude that there is no fixed correlation between stem length and suppressive activity. Instead, core selection and placement likely have a greater influence on the effectiveness of shRNA-based silencing.
Stable Integration Vector for Nutrient Broth-Based Selection of AttenuatedListeria monocytogenesStrains with Recombinant Antigen Expression (2008)

Recombinant Listeria monocytogenes strains induce strong cellular immune responses and may prove useful for antigen delivery for the vaccination of humans. However, the genetic systems currently available for the stable expression of recombinant antigens by L. monocytogenes rely on the use of antibiotic resistance genes. We report on a derivative, pPL2dalGlnA, of the Listeria monocytogenes pPL2 integration vector that completely lacks drug resistance genes. The selectable markers in pPL2dalGlnA are glutamine synthetase (GlnA) and alanine racemase (Dal). This novel vector was stably maintained in auxotropic L. monocytogenes strains that normally require d-alanine. The pPL2dalGlnA vector also partially restored the ability of an L. monocytogenes Deltadal Deltadat strain to colonize the spleens and livers of infected mice. A novel, highly attenuated strain of L. monocytogenes with quadruple deletions was also engineered by deleting the L. monocytogenes actA and plcB virulence genes from a Deltadal Deltadat strain. Infection of mice with recombinants of this mutant strain that express the antigen from pPL2dalGlnA were shown to elicit CD8(+) T-cell responses to human immunodeficiency virus Tat. This vector system is thus useful for stable antigen expression and vaccination studies.
Individual medicine in inflammatory bowel disease: Monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies (2009)

Antibody constructs targeting tumour necrosis factor-alpha (TNF) have become important in the management of several chronic immunoinflammatory diseases. Four recombinant anti-TNF drugs are currently approved for clinical use in patients with various chronic inflammatory diseases, three of which are effective in chronic inflammatory bowel disease. These proteins can dramatically lower disease activity and, in some patients, induce remission. Unfortunately, however, not all patients respond favourably to anti-TNF antibodies. For example, patients suffering from Crohn's disease do not benefit from etanercept, and some patients treated with the other anti-TNF constructs either do not respond at all (primary response failure), or they respond initially but have later relapses (secondary response failure) despite increased dosage and/or more frequent administration of the drugs. The reason(s) for these response failures are not clear but inter-individual and even intra-individual differences in bioavailability and pharmacokinetics may contribute. Furthermore, immunogenicity of the drugs, causing patients to develop anti-drug antibodies (ADAs), contributes to treatment failure. Monitoring patients for circulating levels of functional anti-TNF drugs and ADAs is therefore warranted so that treatment can be tailored to the individual patient (individual medicine or personal medicine) in order that effective and economical long-term therapy can be given with minimal risks to the patients.
A New Silicon-Containing Bis(cyanate) Ester Resin with Improved Thermal Oxidation and Moisture Resistance (2006)

A new cyanate ester monomer was prepared from bis(4-cyanatophenyl)dimethylsilane (SiMCy) and fully characterized by analytical and spectroscopic techniques. The monomer was found to have a melting point about 20 °C lower than that of the commercial bis(4-cyanatophenyl)dimethylmethane (BADCy) with similar melt viscosity, curing kinetics, and postcure glass transition temperature. Analysis of the single-crystal molecular structure by X-ray diffraction showed that intermolecular packing was dominated by weak hydrogen-bonding attractions between the aromatic rings and the −OCN nitrogen atoms. In contrast, the packing interactions found in BADCy are dominated by dipole−dipole interactions of the OCN groups. These differences may explain the 50% reduction in moisture uptake observed in SiMCy as compared to BADCy during exposure to boiling water. In addition, thermogravimetric analysis revealed that SiMCy exhibited a significantly higher char yield in air than BADCy, presumably due to the formation of silicates at high temperature. The combination of improved thermooxidative stability and reduced moisture absorption without significant loss in ease of processing or mechanical properties makes SiMCy an important potential "drop in" replacement for BADCy and demonstrates the power of the molecular level approach to designing new high-temperature polymer materials.
tRNA and amino acid recognition by class II aminoacyl-tRNA synthetases (1996)

Similarities and differences in the modes of recognition of tRNAs and amino acids by their cognate aminoacyl-tRNA synthetases will be discussed with reference to crystal structures of substrate complexes of three Thermus thermophilus class II synthetases: seryl-, lysyl-and histidyl-tRNA synthetases.
Nuclear localization of Semliki Forest virus-specific nonstructural protein nsP2 (1990)

About 50% of Semliki Forest virus-specific nonstructural protein nsP2 is associated with the nuclear fraction in virus-infected BHK cells. Transport into the nucleus must be specific, since only trace amounts of nsP3 and nsP4 and about 13% of nsP1, all derived from the same polyprotein, were found in the nucleus. Subfractionation of [35S]methionine-labeled Semliki Forest virus-infected cells showed that 80 to 90% of the nuclear nsP2 was associated with the nuclear matrix. Indirect immunofluorescence, with anti-nsP2 antiserum, showed the most intensive staining of structures which by Nomarski optics appeared to be nucleoli. In the presence of 1 to 5 micrograms of dactinomycin per ml the nuclei were stained evenly and no nucleoli could be found. Transport of nsP2 into the nucleus occurred early in infection and was fairly rapid. A cDNA encoding the complete nsP2 was isolated by the polymerase chain reaction technique and ligated into a simian virus 40 expression vector derivative. When BHK cells were transfected with this pSV-NS2 vector by the lipofection procedure, nsP2 was expressed in about 1 to 5% of the cells, as shown by indirect immunofluorescence. In positively transfected cells the immunofluorescence stain was most intensive in the nucleoli. Thus, Semliki Forest virus-specific nsP2 must have information which directs it into the nuclear matrix and, more specifically, into the nucleoli.
Robot Modeling and Control (2006)

Preface. 1. Introduction. 2. Rigid Motions and Homogeneous Transformations. 3. Forward and Inverse Kinematics. 4. Velocity Kinematics-The Jacobian. 5. Path and Trajectory Planning. 6. Independent Joint Control. 7. Dynamics. 8. Multivariable Control. 9. Force Control. 10. Geometric Nonlinear Control. 11. Computer Vision. 12. Vision-Based Control. Appendix A: Trigonometry. Appendix B: Linear Algebra. Appendix C: Dynamical Systems. Appendix D: Lyapunov Stability. Index.
Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1α (2000)

The switch to an angiogenic phenotype is a fundamental determinant of neoplastic growth and tumor progression. We demonstrate that homozygous deletion of the p53 tumor suppressor gene via homologous recombination in a human cancer cell line promotes the neovascularization and growth of tumor xenografts in nude mice. We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1α subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. Loss of p53 in tumor cells enhances HIF-1α levels and augments HIF-1-dependent transcriptional activation of the vascular endothelial growth factor ( VEGF ) gene in response to hypoxia. Forced expression of HIF-1α in p53-expressing tumor cells increases hypoxia-induced VEGF expression and augments neovascularization and growth of tumor xenografts. These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis.
Piezoresistive pressure sensors based on system in packaging technology of MEMS (2010)

The die of piezoresistance based pressure sensor and its driving circuits has been integrated into one printed circuit board which is specially designed. Then the whole PCB is packaged into a metal shell by SIP technology and special packaging techniques to form a full pressure sensor. Tests have proved that this kind of pressure sensor has good performance. Compared with traditional pressure sensors, these sensors based on SIP have small volume, low cost, and could compatible with the strict standard of vehicle.
A Sentimental Education: Sentiment Analysis Using Subjectivity Summarization Based on Minimum Cuts (2004)

Sentiment analysis seeks to identify the viewpoint(s) underlying a text span; an example application is classifying a movie review as "thumbs up" or "thumbs down". To determine this sentiment polarity, we propose a novel machine-learning method that applies text-categorization techniques to just the subjective portions of the document. Extracting these portions can be implemented using efficient techniques for finding minimum cuts in graphs; this greatly facilitates incorporation of cross-sentence contextual constraints.
Circularization of oligonucleotides by disulfide bridge formation (1995)

An effective, convenient method for the circularization of oligonucleotides has been developed. This procedure involved preparation of an oligonucleotide with backbone-linked 5'- and 3'-terminal hexamethylenethiol groups, followed by oxidation of the thiol groups with air of oxygen to produce the corresponding circular sequence bridged via a bis(hexamethylene)-disulfide moiety. The method has been applied to the circularization of oligodeoxynucleotide sequences of varying lengths (5, 10, 15, 20, 30 and 40 bases), and the circularization process was highly efficient as shown by HPLC or gel electrophoresis of the crude reaction mixtures. Competing reactions such as dimerization were not significant except for the longer sequences (30 and 40 bases). The circularization of an eight base RNA sequence was also accomplished, as well as hexa-ethylene glycol bridged poly-T sequences capable of triplex formation.