gebhart/patrepeval huggingface dataset:
Restructurable VLSI Program (1980)

Abstract : The objective of the Restructurable Very Large Scale Integration (RVLSI) Program is to develop and demonstrate techniques which will make possible integration of large systems as single-package modules. We are developing techniques for restructuring large-area IC chips after fabrication in order to provide access for testing, perform defect avoidance and customization, and reconfigure a system while it is being used. The DARPA-sponsored program is focused on development or architectural concepts for data- and signal-processing systems for RVLSI implementation, development of design aids for unique RVLSI design problems, and development of test techniques suitable for RVLSI applications. An overview of the goals and proposed techniques is given in Sec. II. In Sec. III the functional requirements on programmable connections or links are presented and three types of links are described and compared. In the near term the emphasis will be on laser programmed links and links made from standard logic circuitry; a longer-term goal is development of an electrically programmable nonvolatile link. In Sec. IV we describe a hardware description language designed for efficient description of hierarchical and iterative structures of digital circuits. Since each RVLSI chip may have a different wiring configuration, complete automation of the signal routing process is essential. Solutions for this problem are presented in Sec. IV. Results of an investigation of mapping a regular locally connected array of processing elements onto a physical array with defective elements are presented in Sec. V. An integrator for a spread-spectrum packet radio receiver has been chosen for a first implementation.
Cloning, sequencing and expression of cDNA for chick liver haem oxygenase. Comparison of avian and mammalian cDNAs and deduced proteins (1991)

A cDNA from a chick liver library that encodes for haem oxygenase has been cloned and sequenced. Positive clones were identified with monospecific antibodies to the purified enzyme from chick liver and a cDNA of rat haem oxygenase-1. The length of the cDNA is 1258 bases. An open reading frame of 888 bases was identified by comparison of nucleotide and amino acid sequences with those previously identified for haem oxygenase of mammalian or avian origin. The protein corresponding to this fragment of DNA is composed of 296 amino acid residues and has a molecular mass of 33,509 Da, which is similar to that previously estimated for haem oxygenase purified from chick liver. Unequivocal identification of this clone as that complementary to haem oxygenase was provided by (a) comparison of amino acid compositions and partial sequences with those previously established for the purified enzyme, (b) comparison with nucleotide and amino acid sequences for haem oxygenase from rat and human sources and (c) expression in Escherichia coli with production of high levels of mRNA, protein and haem oxygenase activity after exposure of the transfected bacteria to isopropyl beta-D-thiogalactopyranoside (IPTG). Overall, the similarity of chick haem oxygenase to rat and human haem oxygenase (nucleotides 66% and amino acids 62%) is moderately high. The region between proline-129 and alanine-157 is identical in all three enzymes, including histidine-135, which is proposed to play a key role in binding the substrate haem at the active centre of the enzyme. Northern blots also show that treatment of chicks with CdCl2, a potent inducer of haem oxygenase, results in increases in 1.65-1.70 kb mRNA, which hybridizes selectively to the full-length cDNA or to a synthetic 24-base oligonucleotide with sequence identical to that of a portion of the haem oxygenase cDNA. These results suggest that Cd-dependent induction of haem oxygenase is due to increased transcription of the gene or stabilization of its message.
Metal–Organic Frameworks with Precisely Designed Interior for Carbon Dioxide Capture in the Presence of Water (2014)

The selective capture of carbon dioxide in the presence of water is an outstanding challenge. Here, we show that the interior of IRMOF-74-III can be covalently functionalized with primary amine (IRMOF-74-III-CH2NH2) and used for the selective capture of CO2 in 65% relative humidity. This study encompasses the synthesis, structural characterization, gas adsorption, and CO2 capture properties of variously functionalized IRMOF-74-III compounds (IRMOF-74-III-CH3, -NH2, -CH2NHBoc, -CH2NMeBoc, -CH2NH2, and -CH2NHMe). Cross-polarization magic angle spinning (13)C NMR spectra showed that CO2 binds chemically to IRMOF-74-III-CH2NH2 and -CH2NHMe to make carbamic species. Carbon dioxide isotherms and breakthrough experiments show that IRMOF-74-III-CH2NH2 is especially efficient at taking up CO2 (3.2 mmol of CO2 per gram at 800 Torr) and, more significantly, removing CO2 from wet nitrogen gas streams with breakthrough time of 610 ± 10 s g(-1) and full preservation of the IRMOF structure.
Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma (2016)

The efficacy and favorable safety profile of daratumumab monotherapy in multiple myeloma (MM) was previously reported. Here, we present an updated pooled analysis of 148 patients treated with daratumumab 16 mg/kg. Data were combined from part 2 of a first-in-human phase 1/2 study of patients who relapsed after or were refractory to ≥2 prior therapies and a phase 2 study of patients previously treated with ≥3 prior lines of therapy (including a proteasome inhibitor [PI] and an immunomodulatory drug [IMiD]) or were double refractory. Among the pooled population, patients received a median of 5 prior lines of therapy (range, 2 to 14 prior lines of therapy), and 86.5% were double refractory to a PI and an IMiD. Overall response rate was 31.1%, including 13 very good partial responses, 4 complete responses, and 3 stringent complete responses. The median duration of response was 7.6 months (95% confidence interval [CI], 5.6 to not evaluable [NE]). The median progression-free survival (PFS) and overall survival (OS) were 4.0 months (95% CI, 2.8-5.6 months) and 20.1 months (95% CI, 16.6 months to NE), respectively. When stratified by responders vs stable disease/minimal response vs progressive disease/NE, median PFS was 15.0 months (95% CI, 7.4 months to NE) vs 3.0 months (95% CI, 2.8-3.7 months) vs 0.9 months (95% CI, 0.9-1.0 months), respectively, and median OS was NE (95% CI, NE to NE) vs 18.5 months (95% CI, 15.1-22.4 months) vs 3.7 months (95% CI, 1.7-7.6 months), respectively. No new safety signals were identified. In this pooled data set, daratumumab 16 mg/kg monotherapy demonstrated rapid, deep, and durable responses, with a clinical benefit that extended to patients with stable disease or better.
Conformational mapping of the N‐terminal peptide of HIV‐1 gp41 in lipid detergent and aqueous environments using 13C‐enhanced Fourier transform infrared spectroscopy (2004)

The N-terminal domain of HIV-1 glycoprotein 41,000 (gp41) participates in viral fusion processes. Here, we use physical and computational methodologies to examine the secondary structure of a peptide based on the N terminus (FP; residues 1-23) in aqueous and detergent environments. (12)C-Fourier transform infrared (FTIR) spectroscopy indicated greater alpha-helix for FP in lipid-detergent sodium dodecyl sulfate (SDS) and aqueous phosphate-buffered saline (PBS) than in only PBS. (12)C-FTIR spectra also showed disordered FP conformations in these two environments, along with substantial beta-structure for FP alone in PBS. In experiments that map conformations to specific residues, isotope-enhanced FTIR spectroscopy was performed using FP peptides labeled with (13)C-carbonyl. (13)C-FTIR results on FP in SDS at low peptide loading indicated alpha-helix (residues 5 to 16) and disordered conformations (residues 1-4). Because earlier (13)C-FTIR analysis of FP in lipid bilayers demonstrated alpha-helix for residues 1-16 at low peptide loading, the FP structure in SDS micelles only approximates that found for FP with membranes. Molecular dynamics simulations of FP in an explicit SDS micelle indicate that the fraying of the first three to four residues may be due to the FP helix moving to one end of the micelle. In PBS alone, however, electron microscopy of FP showed large fibrils, while (13)C-FTIR spectra demonstrated antiparallel beta-sheet for FP (residues 1-12), analogous to that reported for amyloid peptides. Because FP and amyloid peptides each exhibit plaque formation, alpha-helix to beta-sheet interconversion, and membrane fusion activity, amyloid and N-terminal gp41 peptides may belong to the same superfamily of proteins.
Effect of guanidine hydrochloride on the hydrodynamic and thermodynamic properties of human apolipoprotein A-I in solution. (1980)

To further define its properties in solution, the course of denaturation of apolipoprotein A-I (apo-A-I) was studied as a function of various concentrations of guanidine hydrochloride (GdmCl) using the techniques of circular dichroism, ultraviolet difference spectroscopy, analytical ultracentrifugation, viscometry, and densitometry. At low molarities of GdmCl (0 to 0.4 M), apoA-I exhibited anomalous ellipticity changes which were dependent upon apo-A-I concentration; from ultracentrifugal studies, these changes were interpreted as related to the dissociation of protein oligomers into a new equilibrium attended by a preferential interaction with GdmCl (0.07 g/g of apo-A-I and an increase in molar volume, 197 ml). On the other hand, the frictional (1.68) and axial (5.7) ratios were similar to those in the native state. At molarities of GdmCl between 0.4 M and 6 M, apo-A-I dissociated into monomers by a cooperative denaturation process which was independent of protein concentration: both dissociation and denaturation were thermodynamically reversible with an apparent free energy of stabilization, = 3.70 kcal/mol. Between 2 and 6 M GdmC1, changes in the conformation, intrinsic viscosity, and volume of apo-A-I were noted as assessed by spectroscopic, viscometric, and partial specific volume measurements. These changes appeared related to the number of moles of GdmCl bound to apo-A-I (at 2 M GdmC1, 63 mol; at 6 M, 181 mol).
Handmade Somatic Cell Cloning in Cattle: Analysis of Factors Contributing to High Efficiency In Vitro1 (2003)

Widespread application of somatic cell cloning has been hampered by biological and technical problems, which include complicated and time-consuming procedures requiring skilled labor. Recently, zona-free techniques have been published with limited or no requirement for micromanipulators. The purpose of the present work was to optimize certain steps of the micromanipulator-free (i.e., handmade) procedure, to analyze the morphology of the developing blastocysts, and to explain factors involved in the high efficiencies observed. Optimization of the procedure included selection of the appropriate medium for enucleation, orientation of pairs at fusion, timing of fusion, and culture conditions. As a result of these improved steps, in vitro efficiency as measured by blastocysts per reconstructed embryo and blastocysts per working hour was among the highest described so far. The cattle serum used in our experiments was superior to other protein sources for in vitro embryo development. One possible explanation of this effect is the considerable mitogenic activity of the cattle serum compared with that of commercially available fetal calf serum. Morphological analysis of blastocysts by inverted microscopy, inner cell mass-trophoblast differential staining, and transmission electron microscopy revealed high average quality. A high initial pregnancy rate was achieved after the transfer of single blastocysts derived by aggregation of two nuclear transfer embryos into recipients. The improved handmade somatic cell nuclear transfer method may become a useful technology as a simple, inexpensive, and efficient alternative to traditional somatic cell nuclear transfer.
Complexation of Two Proteic Insect Inhibitors to the Active Site of Chymotrypsin Suggests Decoupled Roles for Binding and Selectivity (2001)

The crystal structures of two homologous inhibitors (PMP-C and PMP-D2v) from the insect Locusta migratoria have been determined in complex with bovine alpha-chymotrypsin at 2.1- and 3.0-A resolution, respectively. PMP-C is a potent bovine alpha-chymotrypsin inhibitor whereas native PMP-D2 is a weak inhibitor of bovine trypsin. One unique mutation at the P1 position converts PMP-D2 into a potent bovine alpha-chymotrypsin inhibitor. The two peptides have a similar overall conformation, which consists of a triple-stranded antiparallel beta-sheet connected by three disulfide bridges, thus defining a novel family of serine protease inhibitors. They have in common the protease interaction site, which is composed of the classical protease binding loop (position P5 to P'4, corresponding to residues 26-34) and of an internal segment (residues 15-18), held together by two disulfide bridges. Structural divergences between the two inhibitors result in an additional interaction site between PMP-D2v (position P10 to P6, residues 21-25) and the residues 172-175 of alpha-chymotrypsin. This unusual interaction may be responsible for species selectivity. A careful comparison of data on bound and free inhibitors (from this study and previous NMR studies, respectively) suggests that complexation to the protease stabilizes the flexible binding loop (from P5 to P'4).
Sulfate-reducing pathway in Escherichia coli involving bound intermediates (1976)

Although a sulfate-reducing pathway in Escherichia coli involving free sulfite and sulfide has been suggested, it is shown that, as in Chlorella, a pathway involving bound intermediates is also present. E. coli extracts contained a sulfotransferase that transferred the sulfonyl group from a nucleosidephosphosulfate to an acceptor to form an organic thiosulfate. This enzyme was specific for adenosine 3'-phosphate 5'-phosphosulfate, did not utilize adenine 5'-phosphosulfate, and transferred to a carrier molecule that was identical with thioredoxin in molecular weight and amino acid composition. In the absence of thioredoxin, only very low levels of the transfer of the sulfo group to thiols was observed. As in Chlorella, thiosulfonate reductase activity that reduced glutathione-S-SO3- to bound sulfide could be detected. In E. coli, this enzyme used reduced nicotinamide adenine dinucleotide phosphate and Mg2+, but did not require the addition of ferredoxin or ferredoxin nicotinamide adenine dinucleotide phosphate reductase. Although in Chlorella the thiosulfonate reductase appears to be a different enzyme from the sulfite reductase, the E. coli thiosulfonate reductase and sulfite reductase may be activities of the same enzyme.
Influence of marinen-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis (2012)

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (ARA) is the precursor of inflammatory eicosanoids which are involved in RA. Some therapies used in RA target ARA metabolism. Marine n-3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) found in oily fish and fish oils decrease the ARA content of cells involved in immune responses and decrease the production of inflammatory eicosanoids from ARA. EPA gives rise to eicosanoid mediators that are less inflammatory than those produced from ARA and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving, although little is known about these latter mediators in RA. Marine n-3 PUFAs can affect other aspects of immunity and inflammation relevant to RA, including dendritic cell and T cell function and production of inflammatory cytokines and reactive oxygen species, although findings for these outcomes are not consistent. Fish oil has been shown to slow the development of arthritis in animal models and to reduce disease severity. A number of randomised controlled trials of marine n-3 PUFAs have been performed in patients with RA. A systematic review included 23 studies. Evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs.
Tribological Effects on DNA Translocation in a Nanochannel Coated with a Self-Assembled Monolayer (2010)

A biomimetic nanochannel coated with a self-assembled monolayer (SAM) can be used for sensing and analyzing biomolecules. The interaction between a transported biomolecule and a SAM governs the mechanically or electrically driven motion of the molecule. To investigate the translocation dynamics of a biomolecule, we performed all-atom molecular dynamics simulations on a single-stranded DNA in a solid-state nanochannel coated with a SAM that consists of octane or octanol polymers. Simulation results demonstrate that the interaction between DNA and a hydrophobic or a hydrophilic SAM is effectively repulsive or adhesive, respectively, resulting in different translocation dynamics of DNA. Therefore, with proper designs of SAMs coated on a channel surface, it is possible to control the translocation dynamics of a biomolecule. This work also demonstrates that traditional tribology methods can be deployed to study a biological or biomimetic transport process.
Lentivector Immunization Stimulates Potent CD8 T Cell Responses against Melanoma Self-Antigen Tyrosinase-Related Protein 1 and Generates Antitumor Immunity in Mice (2009)

Recombinant lentivector immunization has been demonstrated to induce potent CD8 T cell responses in vivo. In this study, we investigated whether lentivector delivering a self/tumor Ag, tyrosinase related protein 1 (TRP1), could stimulate effective antitumor T cell responses. We found that immunization with lentivector expressing mutated TRP1 Ag elicited potent CD8 T cell responses against multiple TRP1 epitopes. Importantly, the activated CD8 T cells effectively recognize wild-type TRP1 epitopes. At peak times, as many as 10% of CD8 T cells were effector cells against TRP1 Ag. These cells killed wild-type TRP1 peptide-pulsed target cells in vivo and produced IFN-gamma after ex vivo stimulation. The CD8 T cell responses were long-lasting (3-4 wk). Immunized mice were protected from B16 tumor cell challenge. In a therapeutic setting, lentivector immunization induced potent CD8 T cell responses in tumor bearing mice. The number of infiltrating T cells and the ratio of CD8/CD4 were dramatically increased in the tumors of immunized mice. The tumor-infiltrating CD8 T cells were functional and produced IFN-gamma. The potent CD8 T cell responses stimulated by lentivector immunization eliminated small 3-day s.c. B16 tumors and strongly inhibited the growth of more established 5-day tumors. These studies demonstrate that genetic immunization with lentivector expressing mutated self/tumor Ag can generate potent CD8 T cell immune responses and antitumor immunity that prevent and inhibit B16 tumor growth, suggesting that lentivector immunization has the potential for tumor immunotherapy and immune prevention.
The measurement of thrombin in clotting blood by radioimmunoassay. (1976)

We have developed a radioimmunoassay for human thrombin using rabbit anti-human thrombin IgG. The assay can measure 2 ng thrombin/ml plasma, 500-fold more sensitive than clotting assays. Human prothrombin is less reactive in the assay than thrombin by at least four orders of magnitude, and there is no demonstrable cross-reactivity with human factor Xa, the clotting factor structurally most similar to thrombin. The assay does not detect thrombin bound to anthithrombin III. Using the assay, we have demonstrated that plasma from 20 normal subjects does not contain detectable thrombin. We measured thrombin generation in clotting blood in polypropylene tubes and observed that thrombin appears (approximately equal to 3 ng/ml) within 45 S-5 min after venipuncture. This material is thrombin, not intermediates of prothrombin activation, since it disappears after addition of heparin, which promotes thrombin antithrombin III complex formation. After a plateau of 2-10 min, there is further thrombin generation, which results in clotting after 15-27 min at a level of 40-50 ng thrombin/ml. The thrombin generated 9-25 min before clotting may activate factors V and VIII and stimulate platelet aggregation and release. In contrast, the cascade hypothesis assigns a role for thrombin only late in blood clotting. Radioimmunoassay of thrombin and other clotting factors will be useful for clinical and physiological studies of blood clotting especially since the assay seems specific for thrombin and is independent of other activities that affect bioassays.
The Alzheimer family of diseases: Many etiologies, one pathogenesis? (1997)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Chemoenzymatic synthesis and application of glycopolymers containing multivalent sialyloligosaccharides with a poly(L-glutamic acid) backbone for inhibition of infection by influenza viruses (2002)

Highly water-soluble glycopolymers with poly(alpha-L-glutamic acid) (PGA) backbones carrying multivalent sialyl oligosaccharides units were chemoenzymatically synthesized as polymeric inhibitors of infection by human influenza viruses. p-Aminophenyl disaccharide glycosides were coupled with gamma-carboxyl groups of PGA side chains and enzymatically converted to Neu5Acalpha2-3Galbeta1-4GlcNAcbeta-, Neu5Acalpha2-6Galbeta1-4GlcNAcbeta-, Neu5Acalpha2-3Galbeta1-3GalNAcalpha-, and Neu5Acalpha2-3Galbeta1-3GalNAcbeta- units, respectively, by alpha2,3- or alpha2,6-sialytransferases. The glycopolymers synthesized were used for neutralization of human influenza A and B virus infection as assessed by measurement of the degree of cytopathic inhibitory effect in virus-infected MDCK cells. Among the glycopolymers tested, alpha2,6-sialo-PGA with a high molecular weight (260 kDa) most significantly inhibited infection by an influenza A virus, strain A/Memphis/1/71 (H3N2), which predominantly binds to alpha2-6 Neu5Ac residue. The alpha2,6-sialo-PGA also inhibited infection by an influenza B virus, B/Lee/40. The binding preference of viruses to terminal sialic acids was affected by core determinants of the sugar chain, Galbeta1-4GlcNAcbeta- or Galbeta1-3GalNAcalpha/beta- units. Inhibition of infection by viruses was remarkably enhanced by increasing the molecular weight and sialic acid content of glycopolymers.