gebhart/patrepeval huggingface dataset:
Impairment of elastin resynthesis in the lungs of hamsters with experimental emphysema induced by sequential administration of elastase and trypsin. (1985)

The nonelastolytic proteases trypsin and chymotrypsin were administered to hamsters 24 hours after intratracheal injection of elastase. Severity of the disease, extent of degradation and resynthesis, new cross-link formation, and the levels of the enzyme lysyl oxidase, which mediates the cross-link formation, were compared with the same parameters measured in hamsters with experimental emphysema induced by elastase alone. Increases in mean linear intercept indicated that a more severe form of the disease was produced. Although elastin degradation after 1 week was similar in both groups, resynthesis of the elastin destroyed by the elastolytic insult was significantly impaired in the animals injected sequentially with elastase and trypsin or chymotrypsin. Formation of new elastin as monitored by 14C-lysine incorporation into the elastin specific cross-links desmosine and isodesmosine was reduced approximately 40%, although there was no significant difference in the levels of lysyl oxidase activity. It is suggested that the most likely mechanism compatible with the recorded observations involves destruction of the microfibrillar component of the elastic fiber by trypsin or chymotrypsin, resulting in the absence of the requisite template for resynthesis of the pulmonary elastin.
Immunotoxin construction with a ribosome-inactivating protein from barley (1990)

The aim of this study was to determine the suitability of a ribosome-inactivating protein (RIP) from barley endosperm for use as an immunotoxin. This barley RIP is identical with the 30-kDa protein first reported by Coleman and Roberts [(1982) Biochim. Biophys. Acta 696, 239] and sequenced by Asano and co-workers [(1986) Carlsberg Res. Commun. 51, 75]. Use of the terms barley toxin I, II, and III is proposed to describe the three isoforms resolved by cation-exchange chromatography. An improved procedure for isolating the protein involving the steps of aqueous extraction, ammonium sulfate precipitation, and cation-exchange HPLC is described. Barley toxin II retained activity after exposure to ca. 40% acetonitrile and 0.1% trifluoroacetic acid or lyophilization. In a comparative study using the rabbit reticulocyte lysate assay, the protein was about 68% and 30% as potent as gelonin and ricin A-chain (RTA), respectively. Introduction of SH groups with 2-iminothiolane resulted in a substantial loss of activity as the number of thiol groups approached four. Therefore, it was necessary to limit thiolation to an average of one to two SH groups per toxin molecule. Anti-transferrin receptor-based immunotoxins constructed with RTA, gelonin, and barley toxin II exhibited comparable cytotoxicity against a human colon tumor cell line. We conclude that the availability of raw material, ease of purification, and stability of barley toxin II to lyophilization and denaturing conditions render it a suitable protein for the construction of immunotoxins.
Fluorescent labelling of cRNA for microarray applications (2003)

Microarrays of oligonucleotide expression libraries can be hybridised with either cDNA, generated from mRNA during reverse transcription, or cRNA, generated in an Eberwine mRNA amplification procedure. While methods for fluorescent labelling of cDNA have been thoroughly investigated, methods for cRNA labelling have not. To this purpose, we developed an aminoallyl-UTP (aa-UTP) driven cRNA labelling protocol and compared it in expression profiling studies using spotted 7.5 K 65mer murine oligonucleotide arrays with labelling via direct incorporation of Cy-UTPs. The presence of dimethylsulfoxide during coupling of aa-modified cRNA with N-hydroxysuccinimide-modified, fluorescent Cy dyes greatly enhanced the labelling efficiency, as analysed by spectrophotometry and fluorescent hybridisation signals. Indirect labelling using aa-UTP resulted in 2- to 3-fold higher degrees of labelling and fluorescent signals than labelling by direct incorporation of Cy-UTP. By variation of the aa-UTP:UTP ratio, a clear optimal degree of labelling was found (1 dye per 20-25 nt). Incorporation of more label increased Cy3 signal but lowered Cy5 fluorescence. This effect is probably due to quenching, which is more prominent for Cy5 than for Cy3. In conclusion, the currently developed method is an efficient, robust and inexpensive technique for fluorescent labelling of cRNA and allows sensitive detection of gene expression profiles on oligonucleotide microarrays.
Regional cerebral glucose utilization is modulated by the dosage of apolipoprotein E type 4 allele and α1-antichymotrypsin type A allele in Alzheimerʼs disease (1997)

Twenty Alzheimer's disease (AD) patients with defined apolipoprotein E (APOE), alpha1-antichymotrypsin (ACT) and presenilin-1 (PS-1) intronic genotypes were examined to quantify the regional cerebral metabolic rate of glucose (rCMRglc) using positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG). The frontal rCMRglc was significantly increased in patients with the APOE epsilon4 allele in a dose-dependent fashion. In contrast, the temporo-parietal rCMRglc was significantly reduced in ACT type A allele (ACT*A) carriers compared with those in non-ACT*A carriers. The PS-1 type 1 intronic allele had no significant effects on rCMRglc in any cerebral region. These results suggest that both the APOE and ACT genes may play a distinct role in the progression of AD as monitored by imaging studies of cerebral glucose utilization.
Incremental Logic Synthesis through Gate Logic Structure Identification (1986)

This paper describes incremental logic synthesis for supporting function logic changes in the physical design stage of digital systems. The incremental logic synthesis is distinguished from logic synthesis in the respect that it updates only gate logic components, which must be changed due to the function logic changes, in the physically optimized gate logic structure. For making the incremental logic synthesis feasible, a gate logic structure identification and editing system has been developed with a corresponding gate matrix method as its core. This system has greatly contributed to the increase in design efficiency of the very large computer series M68XH.
Variance‐based color image quantization for frame buffer display (1990)

Abstract Color image quantization is a process of representing an image with a small number of well selected colors. In this article an algorithm for multidimensional data clustering (termed the variance‐based algorithm), based on the criterion of minimization of the sum‐of‐squared error, is applied to the problem of reducing the number of colors used to represent a given color image. The suitability of the sum‐of‐squared error criterion for measuring the similarity between the original and quantized images is examined using a digitized image and a computer‐generated image. The experimental results indicate that this error measure is basically consistent with the perceived quality of the quantized image. The performance of the variance‐based algorithm is compared with that of other algorithms for color image quantization in terms of quantization images generated using the colors selected by the variance‐based and the mediancut algorithms are also presented.
Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes (2002)

Initial combination treatment with glyburide/metformin tablets produces greater improvements in glycaemic control than either glyburide or metformin monotherapy. The superiority of initial therapy with glyburide/metformin tablets may arise from simultaneous treatment of both pathophysiological defects of type 2 diabetes.
A Parallel Stochastic Number Generator With Bit Permutation Networks (2017)

Stochastic computing (SC) is a promising paradigm to realize low-complexity digital circuits that are tolerant to soft errors. Stochastic circuits include a stochastic number generator (SNG) to generate a stochastic number that corresponds to a given binary number. Conventional SNGs, which employ linear feedback shift registers (LFSRs) to generate stochastic numbers in a serial manner would cost significantly in time. In this brief, a parallel SNG has been proposed, which can generate stochastic numbers in parallel by transforming the input binary number to a modified unary number and permuting it using a bit permutation network. Further, a method to share a single LFSR among multiple SNGs has been presented. Experimental results show that the proposed SNG can achieve improvement in SC correlation and energy-delay-product by 28.57% and 4.32×, respectively, when compared to the existing shared LFSR-based SNG. For applications, such as edge detector, multiplier, and complex multiplication, the proposed SNG has achieved reduction in execution time and area-delay-product by up to 1000× and 9×, respectively, as compared to others.
Therapeutic efficacy of a novel membrane-targeted complement regulator in antigen-induced arthritis in the rat (2000)

These results show that IA complement inhibition represents an effective therapeutic strategy in experimental arthritis, by demonstrating that the exogenous delivery of a membrane-targeting complement regulator can result in prolonged synovial cell surface binding and significant clinical benefit in vivo. Complement inhibitory strategies of this type should be considered as novel therapies in human inflammatory arthritis.
Properties and reaction mechanism of the bioluminescence system of the deep-sea shrimp Oplophorus gracilorostris (1978)

The bioluminescent reaction of Oplophorus takes place when the oxidation of coelenterazine (the luciferin) with molecular oxygen is catalyzed by Oplophorus luciferase, resulting in light of maximum intensity at 462 nm and the products CO2 and coelenteramide. Oplophorus luciferase has now been obtained in a highly purified state. Optimum luminescence occurs at pH 9 in the presence of 0.05--0.1 M NaCl at 40 degrees C, and, due to the unusual resistance of this enzyme to heat, visible luminescence occurs at temperatures above 70 degrees C when partially purified enzyme is used. The specific activity of purest preparations is 1.75 X 10(15) photons s-1 mg-1 at 23 degrees C. At pH 8.7, native luciferase has a molecular weight of approximately 130 000, apparently comprising 4 monomers of 31 000; at lower pHs, the native luciferase tends to polymerize. The quantum yield of coelenterazine is 0.34 at 22 degrees C with this enzyme. After the luminescent reaction, the spent solution is nonfluorescent, and likewise solutions of luciferase alone. When the bioluminescent reaction was carried out in the presence of 18O2, the product CO2 contained more than 50% C18O16O, supporting the dioxetane mechanism, but without ruling out the linear peroxide mechanism.
NH2-terminal globular domain of human platelet glycoprotein Ib alpha has a methionine 145/threonine145 amino acid polymorphism, which is associated with the HPA-2 (Ko) alloantigens. (1992)

The glycoprotein (GP) Ib/IX complex, a prominent platelet GP complex, is the primary receptor for vWF. Previously, we have established that an antigenic polymorphism of platelets, the HPA-2 or Ko alloantigen system, is located on the 45-kD amino-terminal globular domain of GPIb alpha. With the polymerase chain reaction, we have amplified two segments of the GPIb alpha gene coding for the first 382 amino acids of two HPA-2a and two HPA-2b homozygous individuals. Nucleotide sequence analysis revealed as the only difference a C-T polymorphism at position 434 of the coding region for the mature protein. This base change results in a substitution of threonine (ACG) in HPA-2a (Kob) to methionine (ATG) in HPA-2b (Koa) at amino acid position 145. The C-T polymorphism is reflected in a difference in restriction enzyme recognition, resulting in an Aha 2-site in the HPA-2b allele and a SfaN1 site in the HPA-2a allele. Restriction fragment length polymorphism analysis of the amplified DNA of 3 HPA-2(a-,b+), 2 HPA-2(a+,b+), and 11 HPA-2(a+,b-) donors showed that these restriction sites were associated with the HPA-2 alleles. DNA-typing for the HPA-2 alloantigen system on genomic DNA obtained from a small number of cells may be applied for determining the genotype of a fetus from an immunized mother or of severely thrombocytopenic patients.
High Density NAND Phase Change Memory with Block-Erase Architecture to Compromise Write and Disturb Requirements (2012)

This paper gives a design guideline for the phase change memory (PCM) with NAND strings. The phase change memory with NAND interface is proposed. NAND interface realizes 7.7-times fast write-speed compared with the conventional RAM interface due to long SET-time. In addition, the write-capability and write-disturb problems are investigated with the measurements. ERASE operation for the presented device structure can be realized with the same current compared with SET operation of a single cell. For a pass-transistor, about 4-times large on-current compared with the minimum RESET current of a single cell is needed to complete RESET operation and to compensate the write-disturb problem.
Loop antenna measurements (1956)

Experimental measurements on three loop antenna configurations are presented. The technique for obtaining impedance and current distributions using a single-wire transmission line over an image plane is described with particular attention given to the difficulties encountered. The results are reproduced in graphical form, and for loops where theoretical results are available, curves comparing theory and experiment are presented.
Design and implementation of an enhanced personal video recorder for DTV (2001)

We have developed a PVR (personal video recorder) that is capable of simultaneous playback and recording of HD quality MPEG-2 streams for digital TV. It provides viewers with some advanced features as well as pause, instant replay, skip forward and fast forward/rewind found in conventional PVRs for analog TV. This paper describes the enhanced and innovative features that are implemented on our PVR.
The efficient handling of guards in the design of RPython's tracing JIT (2012)

Tracing just-in-time (JIT) compilers record linear control flow paths, inserting operations called guards at points of possible divergence. These operations occur frequently in generated traces and therefore it is important to design and implement them carefully to find the right trade-off between deoptimization, memory overhead, and (partly) execution speed. In this paper, we perform an empirical analysis of runtime properties of guards. This is used to guide the design of guards in the RPython tracing JIT.
Pesticide metabolism in plants and microorganisms (2003)

Abstract Understanding pesticide metabolism in plants and microorganisms is necessary for pesticide development, for safe and efficient use, as well as for developing pesticide bioremediation strategies for contaminated soil and water. Pesticide biotransformation may occur via multistep processes known as metabolism or cometabolism. Cometabolism is the biotransformation of an organic compound that is not used as an energy source or as a constitutive element of the organism. Individual reactions of degradation–detoxification pathways include oxidation, reduction, hydrolysis, and conjugation. Metabolic pathway diversity depends on the chemical structure of the xenobiotic compound, the organism, environmental conditions, metabolic factors, and the regulating expression of these biochemical pathways. Knowledge of these enzymatic processes, especially concepts related to pesticide mechanism of action, resistance, selectivity, tolerance, and environmental fate, has advanced our understanding of pesticide science, and of plant and microbial biochemistry and physiology. There are some fundamental similarities and differences between plant and microbial pesticide metabolism. In this review, directed to researchers in weed science, we present concepts that were discussed at a symposium of the American Chemical Society (ACS) in 1999 and in the subsequent book Pesticide Biotransformation in Plants and Microorganism: Similarities and Divergences, edited by J. C. Hall, R. E. Hoagland, and R. M. Zablotowicz, and published by Oxford University Press, 2001. Nomenclature: American Chemical Society; fenchlorazole-ethyl; glutathione; glutathione-S-transferase; naphthalic anhydride; polyaromatic hydrocarbons; polychlorinated biphenyls; reductive dehalogenation; trichloroethylene.
Viral Activation of Heparanase Drives Pathogenesis of Herpes Simplex Virus-1 (2017)

Herpes simplex virus-1 (HSV-1) causes lifelong recurrent pathologies without a cure. How infection by HSV-1 triggers disease processes, especially in the immune-privileged avascular human cornea, remains a major unresolved puzzle. It has been speculated that a cornea-resident molecule must tip the balance in favor of pro-inflammatory and pro-angiogenic conditions observed with herpetic, as well as non-herpetic, ailments of the cornea. Here, we demonstrate that heparanase (HPSE), a host enzyme, is the molecular trigger for multiple pathologies associated with HSV-1 infection. In human corneal epithelial cells, HSV-1 infection upregulates HPSE in a manner dependent on HSV-1 infected cell protein 34.5. HPSE then relocates to the nucleus to regulate cytokine production, inhibits wound closure, enhances viral spread, and thus generates a toxic local environment. Overall, our findings implicate activated HPSE as a driver of viral pathogenesis and call for further attention to this host protein in infection and other inflammatory disorders.
Role of the constant uridine in binding of yeast tRNA<sup>Phe</sup>anticodon arm to 30S ribosomes (1982)

Twenty-two anticodon arm analogues were prepared by joining different tetra, penta, and hexaribonucleotides to a nine nucleotide fragment of yeast tRNAPhe with T4 RNA ligase. The oligomer with the same sequence as the anticodon arm of tRNAPhe bind poly U programmed 30S ribosomes with affinity similar to intact tRNAPhe. Analogues with an additional nucleotide in the loop bind ribosomes with a weaker affinity whereas analogues with one less nucleotide in the loop do not bind ribosomes at all. Reasonably tight binding of anticodon arms with different nucleotides on the 5' side of the anticodon suggest that positions 32 and 33 in the tRNAPhe sequence are not essential for ribosome binding. However, differences in the binding constants for anticodon arms containing modified uridine residues in the "constant uridine" position suggest that both of the internal "U turn" hydrogen bonds predicted by the X-ray crystal structure are necessary for maximal ribosome binding.
Computational Analysis of Behavior (2016)

In this review, we discuss the emerging field of computational behavioral analysis-the use of modern methods from computer science and engineering to quantitatively measure animal behavior. We discuss aspects of experiment design important to both obtaining biologically relevant behavioral data and enabling the use of machine vision and learning techniques for automation. These two goals are often in conflict. Restraining or restricting the environment of the animal can simplify automatic behavior quantification, but it can also degrade the quality or alter important aspects of behavior. To enable biologists to design experiments to obtain better behavioral measurements, and computer scientists to pinpoint fruitful directions for algorithm improvement, we review known effects of artificial manipulation of the animal on behavior. We also review machine vision and learning techniques for tracking, feature extraction, automated behavior classification, and automated behavior discovery, the assumptions they make, and the types of data they work best with.
Abstract 2399: LAG-3/PD-L1 mAb2 can overcome PD-L1-mediated compensatory upregulation of LAG-3 induced by single-agent checkpoint blockade (2019)

Abstract FS118, currently tested in Phase I clinical trial in patients with advanced malignancies (NCT03440437), is a first-in-class bispecific antagonistic antibody (known as mAb2) targeting LAG-3 (Lymphocyte-Activation Gene 3) and PD-L1 (Programmed Death-Ligand 1), two immune checkpoint molecules that promote tumour escape from immune surveillance. Resistance to anti-PD-1 treatment is associated with upregulation of other checkpoint inhibitor receptors such as LAG-3. Dual targeting in immune checkpoint blockade (ICB) using bispecific monoclonal antibodies could potentially overcome this resistance, further increase the clinical benefit of ICB therapy and prevent relapse or resistance after immunotherapy. In a syngeneic model we used a surrogate mAb2 of FS118 (blocking both mPD-L1 and mLAG-3 binding to their receptors) to determine the effect of dual checkpoint blockade on tumour growth and to elucidate the modulation of the underlying immune mechanisms following treatment with the mAb2. Dual blockade of LAG-3 and PD-L1 with the surrogate mAb2 in the MC38 tumour-bearing mice model resulted in an increased anti-tumour activity comparable to a combination of the single agents targeting LAG-3 and PD-L1. Moreover, the mAb2 and single agent combination resulted in distinct modulations of LAG-3 and PD-L1 cell surface expression within the spleen and tumour microenvironment (TME). While both the mAb2 and combination therapy significantly reduced the number of free PD-L1 binding sites on CD4+ and CD8+ T cells in spleen and TME, total LAG-3 cell surface expression increased following treatment with the combination, whereas it reduced with mAb2 treatment. In addition, analysis of serum samples collected at various timepoints confirmed evidence of drug target engagement with increasing levels of both soluble LAG-3 (sLAG-3) and soluble PD-L1 (sPD-L1) in the mAb2 treated animals. Modulation of sPD-L1 levels in the serum of treated animals was also observed in cynomolgus monkeys treated with FS118. These data provide a strong rationale for investigating both cell surface and soluble LAG-3 and PD-L1 levels as potential pharmacodynamic biomarkers in further clinical development. Citation Format: Mustapha Faroudi, Matthew Kraman, Natalie Fosh, Claire Reader, Daniel Gliddon, Claire Seal, Christa Lucas, Alexander Koers, Mateusz Wydro, Michelle Morrow, Neil Brewis. LAG-3/PD-L1 mAb2 can overcome PD-L1-mediated compensatory upregulation of LAG-3 induced by single-agent checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2399.
Small interfering RNA‐mediated down‐regulation of <i>SPAG9</i> inhibits cervical tumor growth (2009)

These results suggest that SPAG9 expression may play a pivotal role in tumor growth and could contribute to the early spread of cervical cancer. Small interfering RNA-mediated down-regulation of SPAG9 represents a promising therapeutic approach for the treatment of cervical cancer.