gebhart/patrepeval huggingface dataset:
Sequence coding for the alphavirus nonstructural proteins is interrupted by an opal termination codon. (1983)

We have obtained the nucleotide sequence of the genomic RNAs of two alphaviruses, Sindbis virus and Middelburg virus, over an extensive region encoding the nonstructural (replicase) proteins. In both viruses in an equivalent position an opal (UGA) termination codon punctuates a long otherwise open reading frame. The nonstructural proteins are translated as polyprotein precursors that are processed by posttranslational cleavage into four polypeptide chains; the sequence data presented here indicate that the COOH-terminal polypeptide, ns72, may be produced by read-through of this opal codon. The high degree of amino acid homology between the ns72 polypeptides of the two viruses, in contrast to the lack of conserved sequence upstream from the read-through site, suggests that ns72 plays an important role in viral replication, possibly modulating the action of other replicase components.
Fungal Biofilms, Drug Resistance, and Recurrent Infection (2014)

A biofilm is a surface-associated microbial community. Diverse fungi are capable of biofilm growth. The significance of this growth form for infection biology is that biofilm formation on implanted devices is a major cause of recurrent infection. Biofilms also have limited drug susceptibility, making device-associated infection extremely difficult to treat. Biofilm-like growth can occur during many kinds of infection, even when an implanted device is not present. Here we summarize the current understanding of fungal biofilm formation, its genetic control, and the basis for biofilm drug resistance.
Alzheimer's disease (1983)

Local rates of cortical glucose metabolism were estimated by positron emission tomography in 13 right-handed patients with Alzheimer's disease. Individuals with disproportionate failure of language function had markedly diminished metabolism in the left frontal, temporal, and parietal regions. Patients with predominant visuo-constructive dysfunction evidenced a hypometabolic focus in the right parietal cortex. Patients with memory failure as the most apparent feature had no significant metabolic asymmetry in cortical regions. In all subjects, verbal competency generally correlated with metabolic activity in the left frontal and temporal areas, while visuo-constructive test performance was linked to glucose utilization in the right parietal lobe.
Copper(II) bis(thiosemicarbazone) complexes as potential tracers for evaluation of cerebral and myocardial blood flow with PET. (1988)

Wider application of positron emission tomography would be facilitated by the availability of positron-emitting radiopharmaceuticals labeled with nuclides, like 62Cu, that are available from parent/daughter generator systems. Using a longer-lived copper isotope (67Cu) we have examined three derivatives of copper(II) pyruvaldehyde bis(thiosemicarbazone) as potential tracers for evaluation of cerebral and myocardial blood flow: Cu(PTS), Cu(PTSM), and Cu(PTSM2) (where PTS = pyruvaldehyde bis(thiosemicarbazone), PTSM = pyruvaldehyde bis(N4-methylthiosemicarbazone), and PTSM2 = pyruvaldehyde bis(N4-dimethylthiosemicarbazone). All three lipophilic radiocopper complexes were obtained in high yield via a procedure that could be adapted to a "kit" formulation. In animal model systems Cu(PTSM) and Cu(PTSM2) show excellent uptake in the brain and heart following i.v. injection. These tracers differ in that Cu(PTSM) exhibits microsphere-like retention in the brain and heart, whereas Cu(PTSM2) substantially clears from these organs. The relative cerebral pharmacokinetics of [67Cu]Cu(PTSM) and [67Cu]Cu(PTSM2) are consistent with their known reactivity towards intracellular sulfhydryl groups.
Targeted cleavage of polynucleotides by complementary oligonucleotides covalently linked to iron-porphyrins (1986)

Oligothymidylates covalently linked to iron-porphyrins were synthesized to target the nuclease activity of Fe-porphyrin to complementary polynucleotides. In the presence of oxygen and a reducing agent, oligo(dT)7 bearing the reactive group attached to the 3'-phosphate was shown to be active in the cleavage of poly(dA) and poly(rA) but not poly(dT). When poly(dA) was used as a matrix, the reaction yield was higher at low temperature where the complexes are stable; upon increasing temperature, the reaction yield decreased in agreement with the dissociation of the oligonucleotide-polynucleotide complex as measured by absorption spectroscopy. Thus, oligonucleotides covalently linked to iron-porphyrin derivatives can be used to cleave selectively the target sequence of the oligonucleotide.
Coloring of a Landscape by Fuzzy Logic (1993)

画像処理の研究は非常に多いが, その大部分はパターン認識, 輪郭線検出, ノイズ除去, 二次元画像の三次元化など記号的な処理にとどまっており, 画像の持つ情報内容に立ち入った研究は少ない.マルチメディアの問題など考えると, 今後は画像情報の意味論的な処理が重要になると思われる.人間と画像のコミュニケーションのうち, 画像から人間へのインパクトは心理学などで多少研究されているが, 人間が心中に抱くイメージを画像に伝えて表現する研究はほとんど行われていない.本論文はその第一歩として無着色の風景画に人間の季節イメージに合った着色を施すことを試みた.イメージは抽象的なものなのでそのままではコマンドにならない.また, 色というものは物理量であるとともに心理的な量でもあるので数式的扱いは困難である.そこで, まず, 四季の色彩イメージを言語で表現することを試み, つぎにそれをRGBに変換するルールを作ってCRT上で実現させた.これらのルールに現れる変数はいずれも感覚的・定性的なものなので、ファジィ集合で表すことによって微妙な着色が可能になった.さらに, 基本着色ルールに加えて, 季節や時刻が標準状態から外れた場合の調整ルールを作成し, ファジィ推論によって季節の中間や夕暮れ時のイメージを実現させた.これらルールによって数種類の風景画を着色してみたが, いずれの場合もほぼイメージに合った彩色をさせることができた.
Superconducting digital electronics (2001)

Superconducting devices have intrinsically superior characteristics to those of semiconductor devices. Presently, we can fabricate more than twenty thousand junctions on one chip using niobium technology. We have demonstrated the operation of a network system with a superconducting interconnection chip using voltage-state logic. Single flux quantum devices are promising for future superconducting applications because the clock frequency of SFQ logic is higher than that of voltage-state. We have proposed a high-end switch based on hybrid architecture using optical devices, semiconductors and SFQ devices. To demonstrate the high-speed operation of SFQ circuits, we developed an arbiter circuit that uses SFQ components and the arbiter circuit operates at 60 GHz. We also have developed a high Tc superconducting (HTS) SFQ sampler system for observing ultra-fast signal waveforms. In addition, we will discuss the prospects of future superconducting devices based on the fabrication technologies we developed.
Steady-state kinetic mechanism of ras farnesyl:protein transferase (1992)

The steady-state kinetic mechanism of bovine brain farnesyl:protein transferase (FPTase) has been determined using a series of initial velocity studies, including both dead-end substrate and product inhibitor experiments. Reciprocal plots of the initial velocity data intersected on the 1/[s] axis, indicating that a ternary complex forms (sequential mechanism) and suggesting that the binding of one substrate does not affect the binding of the other. The order of substrate addition was probed by determining the patterns of dead-end substrate and product inhibition. Two nonhydrolyzable analogues of farnesyl diphosphate, (alpha-hydroxyfarnesyl)phosphonic acid (1) and [[(farnesylmethyl)hydroxyphosphinyl]methyl]phosphonic acid (2), were both shown to be competitive inhibitors of farnesyl diphosphate and noncompetitive inhibitors of Ras-CVLS. Four nonsubstrate tetrapeptides, CV[D-L]S, CVLS-NH2, N-acetyl-L-penicillamine-VIM, and CIFM, were all shown to be noncompetitive inhibitors of farnesyl diphosphate and competitive inhibitors of Ras-CVLS. These data are consistent with random order of substrate addition. Product inhibition patterns corroborated the results found with the dead-end substrate inhibitors. We conclude that bovine brain FPTase proceeds through a random order sequential mechanism. Determination of steady-state parameters for several physiological Ras-CaaX variants showed that amino acid changes affected the values of KM, but not those of kcat, suggesting that the catalytic efficiencies (kcat/KM) of Ras-CaaX substrates depend largely upon their relative binding affinity for FPTase.
MHCPred: a server for quantitative prediction of peptide-MHC binding (2003)

Accurate T-cell epitope prediction is a principal objective of computational vaccinology. As a service to the immunology and vaccinology communities at large, we have implemented, as a server on the World Wide Web, a partial least squares-based multivariate statistical approach to the quantitative prediction of peptide binding to major histocom- patibility complexes (MHC), the key checkpoint on the antigen presentation pathway within adaptive cellular immunity. MHCPred implements robust statistical models for both Class I alleles (HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3301, HLA-A*6801, HLA-A*6802 and HLA-B*3501) and Class II alleles (HLA-DRB*0401, HLA-DRB*0401 and HLA-DRB*0701). MHCPred is available from the URL: http://www.jenner.ac.uk/MHCPred.
Cloning, expression and characterization of a novel four EF‐hand Ca2+‐binding protein from olive pollen with allergenic activity (2000)

A novel allergenic member of the family of Ca(2+)-binding proteins has been cloned from olive tree pollen. The isolated DNA codes for a protein of 171 amino acid residues, which displays four EF-hand sequence motifs. The encoded protein was overproduced in Escherichia coli and purified. The protein (18¿ omitted¿795 Da), which binds Ca(2+) and IgE antibodies from patients allergic to olive pollen, undergoes Ca(2+)-dependent conformational changes. It is retained on a phenyl-Sepharose column, which indicates the existence of regulatory EF-hand domains. This fact suggests its involvement in Ca(2+)-dependent signal transduction events of the pollen grain. This allergen could be considered as a member of a new subfamily of EF-hand Ca(2+)-binding proteins since it displays a low amino acid sequence similarity with the so far known proteins.
Duodenal levodopa infusion for advanced Parkinson's disease: 12‐month treatment outcome (2007)

We assessed prospectively clinical and quality of life changes in 9 patients with Parkinson's disease (PD; H&Y > or = 3) with severe motor fluctuations and dyskinesia who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy. Seven patients completed the follow-up period. Duration of "off" periods and time with disabling dyskinesia shortened significantly in all patients (P < 0.01). Total daily dose of levodopa infused did not differ from baseline equivalents. There were significant improvements in UPDRS-II (activities of daily living) and -IV (motor complications) in the "on" condition (P < 0.02), and in four PDQ-39 domains (mobility, activities of daily living, stigma, bodily discomfort; P < 0.05). Two patients withdrew for adverse events. Our results demonstrate that a satisfactory therapeutic window can be achieved and maintained for several months in advanced PD patients.
Hemopoietic Growth Factors: A Review (1992)

The hemopoietic growth factors are peptide hormones that are known to be responsible for the in vitro and in vivo proliferation of bone marrow progenitor cells into mature differentiated cells. These cytokines have had a major impact on the management of patients with cytopenias and have been extensively used as an adjunct to the management of patients with hematologic malignancies, with or without prior intensive chemotherapy. Other potential uses, being rigorously studied, include the potential mobilization of stem cells as well as recruitment phase-specific cells into the cell cycle, thus providing a more sensitive environment for targeting specific chemotherapeutic agents.
Heterocycles. Part V. Reaction of α,β‐unsaturated carbonyl compounds with arylacetamides. A synthesis of 2‐pyridone derivatives (1984)

Abstract The reaction of 1,3‐diaryl‐2‐propene‐1‐ones I with arylacetamides II, in the presence of sodium ethoxide under reflux, for two hours, gave the corresponding 3,4,6‐triaryl‐3,4‐dihydro‐2(1 H )‐pyridones IV. However, when the reaction of these ketones was carried out in the presence of sodium hydride, they gave the corresponding 3,4,6‐triaryl‐2(1 H )‐pyridones VI or a mixture of IV and VI. When 1,3‐diaryl‐2‐propyne‐1‐ones V were reacted with arylacetamides, in the presence of sodium hydride, they yielded the corresponding 2‐pyridones VI. Treatment of compounds IV with selenium produced the corresponding 2‐pyridones VI. Acetylation of the latter compounds gave the corresponding 2‐acetyl derivatives VIII. The structure of all products was confirmed by chemical and spectroscopic evidence, and the mechanism of the reactions was discussed.
Serotherapy of acute lymphoblastic leukemia with monoclonal antibody (1981)

We tested the efficacy of passive serotherapy in the treatment of acute lymphoblastic leukemia in four patients who had relapsed while receiving standard chemotherapeutic agents. Each patient received multiple intravenous infusions of J-5 monoclonal antibody specific for common acute lymphoblastic leukemia antigen (CALLA). In the three patients with circulating leukemic cells, there was a rapid decrease in circulating blasts that began immediately after antibody infusion, but not all leukemic cells were cleared, and remaining cells appeared to be resistant to further serotherapy. Although J-5 antibody was also demonstrable on bone marrow lymphoblasts immediately after antibody infusion in one patient, there was no change in bone marrow cellularity or differential during serotherapy. Analysis of the cell surface phenotype of leukemic cells during serotherapy and in vitro studies with patient cells suggests that resistance to serotherapy was mediated in part by antigenic modulation of CALLA in response to J-5 antibody.
Vascular Disrupting Agents (VDA) in Oncology: Advancing Towards New Therapeutic Paradigms in the Clinic (2011)

Vascular Disrupting Agents (VDA) are a potential new class of oncology drugs that have garnered attention recently as a number of these agents have entered into Phase 2-3 studies. Currently available data suggest how the subsequent evolution of these agents into clinical practice may proceed, with new therapeutic paradigms based on similarities, differences and interactions with current standard of care agents. In particular, the broadly successful group of agents targeting angiogenesis through the Vascular Endothelial Growth Factor (VEGF) pathway, can be contrasted to the VDAs that principally disrupt established tumor vasculature through a different set of molecular targets. Although the angiogenesis inhibitors may benchmark where other vascularly targeted agents such as VDAs may be successful, the differences in terms of efficacy and safety profiles lead to important differentiation in how VDAs are likely to be used. Although the majority of VDAs bind tubulin, significant differences also exist between VDAs and cytotoxic agents, including tubulin targeted agents such as taxanes and vinca alkyloids. Clinical trial data is now available for several VDAs allowing such assessment. Data of yet has been the strongest in NSCLC, with indications of how these drugs may be developed beneficially in subsets of patients such as those with squamous cell histology or at risk of bleeding events. Other indications being aggressively pursued include prostate carcinoma, ovarian carcinoma, sarcomas and astrocytomas. The field also continues to advance with investigation into how to optimally schedule administration of VDAs and what effects might be class effects and/or markers of efficacy.
Individual differences in the cardiovascular responses to tonic muscle pain: parallel increases or decreases in muscle sympathetic nerve activity, blood pressure and heart rate (2012)

We recently showed that acute muscle pain, induced by bolus intramuscular injection of hypertonic saline, causes a sustained increase in muscle sympathetic nerve activity (MSNA) and a modest increase in blood pressure and heart rate. However, it is not known whether long-lasting (tonic) pain, which more closely resembles chronic pain, causes a sustained increase in MSNA and blood pressure. We tested this hypothesis by recording MSNA in 12 healthy subjects. Tonic pain was induced for ~60 min by slow intramuscular infusion of hypertonic saline (7%) into the ipsilateral tibialis anterior muscle. Pain was sustained at a tolerable level (5/10 to 6/10 on a visual analog scale). Seven subjects showed progressive increases in mean MSNA amplitude during tonic pain, increasing to 154 ± 17% (SEM) at 45 min and remaining essentially constant for the duration of the infusion. In these subjects, blood pressure and heart rate also increased. Conversely, for the other five subjects MSNA showed a progressive decline, with a peak fall of 67 ± 11% at 40 min; blood pressure and heart rate also fell in these subjects. We conclude that tonic muscle pain has long-lasting effects on the sympathetic control of blood pressure, causing a sustained increase in some subjects yet a sustained decrease in others. This may have implications for individual differences in the cardiovascular consequences of chronic pain.
Gross and microscopic anatomy of the canine intrinsic cardiac nervous system (1994)

The canine intrinsic cardiac nervous system contains a variety of neurons interconnected via plexuses of nerves, the distribution of which is wider than previously assumed.
Computer Simulations of Electrokinetic Injection Techniques in Microfluidic Devices (2000)

Computer simulations are used to study electrokinetic injections on microfluidic devices (microchips). The gated and pinched injection techniques are considered. Each injection technique uses a unique sequence of steps with different electric field distributions and field magnitudes in the channels to effectuate a virtual valve. The goal of these computer simulations is to identify operating parameters providing optimal valve performance. In the pinched injection, the conditions of both loading and dispensing steps were analyzed to reach a compromise between the sample plug spatial extent and its concentration. For the gated injection, the condition of leakage free valve operation was found for the sample loading step. The simulation results for the gated valve are compared with experimental data.
Integration of self assembly for semiconductor microelectronics (2006)

Self assembling polymers can autonomously form regular patterns at sublithographic dimensions. Integration of these materials with semiconductor processing enables high-resolution patterning of microelectronic circuit elements and offers a nontraditional pathway for continued improvements in integrated circuit performance. We discuss our efforts in IBM to demonstrate key applications of self assembly for semiconductor device fabrication.
Strict peptide length is not required for the induction of cytotoxic T lymphocyte‐mediated antiviral protection by peptide vaccination (1993)

Sendai virus nuclear protein peptides of different lengths were titrated in peptide vaccination experiments. We observed that peptide length was not important in inducing cytotoxic T lymphocyte-mediated protective immunity in vivo against a challenge with a lethal dose of virus. These results suggest that long peptides are trimmed in vivo to peptides that fit into the groove of major histocompatibility complex class I molecules. In addition several adjuvants were screened for their effectiveness in peptide vaccination protocols. Incomplete Freund's adjuvant and Titermax turned out to be useful, whereas alum was much less effective.
Biochemical Analysis of the Biosynthetic Pathway of an Anticancer Tetracycline SF2575 (2009)

SF2575 1 is a tetracycline polyketide produced by Streptomyces sp. SF2575 and displays exceptionally potent anticancer activity toward a broad range of cancer cell lines. The structure of SF2575 is characterized by a highly substituted tetracycline aglycon. The modifications include methylation of the C-6 and C-12a hydroxyl groups, acylation of the 4-(S)-hydroxyl with salicylic acid, C-glycosylation of the C-9 of the D-ring with D-olivose and further acylation of the C4'-hydroxyl of D-olivose with the unusual angelic acid. Understanding the biosynthesis of SF2575 can therefore expand the repertoire of enzymes that can modify tetracyclines, and facilitate engineered biosynthesis of SF2575 analogues. In this study, we identified, sequenced, and functionally analyzed the ssf biosynthetic gene cluster which contains 40 putative open reading frames. Genes encoding enzymes that can assemble the tetracycline aglycon, as well as installing these unique structural features, are found in the gene cluster. Biosynthetic intermediates were isolated from the SF2575 culture extract to suggest the order of pendant-group addition is C-9 glycosylation, C-4 salicylation, and O-4' angelylcylation. Using in vitro assays, two enzymes that are responsible for C-4 acylation of salicylic acid were identified. These enzymes include an ATP-dependent salicylyl-CoA ligase SsfL1 and a putative GDSL family acyltransferase SsfX3, both of which were shown to have relaxed substrate specificity toward substituted benzoic acids. Since the salicylic acid moiety is critically important for the anticancer properties of SF2575, verification of the activities of SsfL1 and SsfX3 sets the stage for biosynthetic modification of the C-4 group toward structure-activity relationship studies of SF2575. Using heterologous biosynthesis in Streptomyces lividans, we also determined that biosynthesis of the SF2575 tetracycline aglycon 8 parallels that of oxytetracycline 4 and diverges after the assembly of 4-keto-anhydrotetracycline 51. The minimal ssf polyketide synthase together with the amidotransferase SsfD produced the amidated decaketide backbone that is required for the formation of 2-naphthacenecarboxamide skeleton. Additional enzymes, such as cyclases C-6 methyltransferase and C-4/C-12a dihydroxylase, were functionally reconstituted.
Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene. (1992)

The HER2 protooncogene encodes a 185-kD transmembrane phosphoglycoproteins, human epidermal growth factor receptor 2 (p185HER2), whose amplified expression on the cell surface can lead to malignant transformation. Overexpression of HER2/p185HER2 is strongly correlated with progression of human ovarian and breast carcinomas. Recent studies have shown that human T cells can be targeted with bispecific antibody to react against human tumor cells in vitro. We have developed a bispecific F(ab')2 antibody molecule consisting of a humanized arm with a specificity to p185HER2 linked to another arm derived from a murine anti-CD3 monoclonal antibody that we have cloned from UCHT1 hybridoma. The antigen-binding loops for the anti-CD3 were installed in the context of human variable region framework residues, thus forming a fully humanized BsF(ab')2 fragment. Additional variants were produced by replacement of amino acid residues located in light chain complementarity determining region 2 and heavy chain framework region 3 of the humanized anti-CD3 arm. Flow cytometry analysis showed that the bispecific F(ab')2 molecules can bind specifically to cells overexpressing p185HER2 and to normal human peripheral blood mononuclear cells bearing the CD3 surface marker. In additional experiments, the presence of bispecific F(ab')2 caused up to fourfold enhancement in the cytotoxic activities of human T cells against tumor cells overexpressing p185HER2 as determined by a 51Cr release assay. These bispecific molecules have a potential use as therapeutic agents for the treatment of cancer.
Biophysical and engineering aspects of cryosurgery (1981)

A review is presented. Investigations of the techniques and biological results of cryosurgery have considerably advanced the author's understanding of the freezing process in tissues and have enabled cryosurgery to become a powerful and respected tool in the service of medicine. However, if cryosurgery is to become a precise and controllable form of therapy, the design of cryoprobes and the freezing regimes used need to be directed towards providing the necessary thermal environment for maximum cell death, rather than simply providing a cold tip.