gebhart/patrepeval huggingface dataset:
[1] Why purify enzymes? (1990)

This chapter explains how an enzyme catalyzes the conversion of one substance to another, and then enzyme purified away from the other enzymes and substances that make up a crude cell extract. It describes the classical approach to enzymology. This approach tracks the molecular basis of cellular function—alcoholic fermentation in yeast, glycolysis in muscle, luminescence in a fly, or the replication of DNA—by first observing the phenomenon in a cell-free system. The responsible enzyme is then isolated by fractionation of the cell extract and is purified to homogeneity. The structure and the regulatory and catalytic functions of the enzyme are then studied. The reverse approach is the neoclassical approach, which first obtains a structure and then looks for its function. The protein is preferably small and stable and is amplified by cloning or is commercially available.
Neurological Deficit and Extent of Neuronal Necrosis Attributable to Middle Cerebral Artery Occlusion in Rats (1995)

The histological effects of an intracranial arterial occlusion in the adult rat can be predicted on day 1 by the neurological score described in this report. Significant improvement can be obtained in these animals by reestablishing arterial flow 60 minutes or sooner after the ictus. The pattern of cortical pannecrosis observed after permanent occlusion (> or = 72 hours) was transformed into incomplete ischemic injury in most instances of transient occlusion.
A Versatile and Efficient Synthesis of Substituted 1H-Indazoles (1999)

A facile synthesis of substituted 1H-indazole 4 from aryl mesylate 3 is described. The reaction, which proceeds through the intermediate hydrazone, was general with regard to the substituents on the arene and was applicable to several hydrazines. It was also discovered that with p-methoxyphenylhydrazine, the indazole formation was more rapid than the competitive Fischer indole synthesis.
Transparent phase shifting mask (2002)

A transparent phase shifting mask has been demonstrated to improve the resolution of the conventional i-line stepper and to facilitate the fabrication of various deep submicron patterns for VLSI. This mask, having a single patterned layer of phase shifter, can be easily fabricated, and it is easy to inspect and repair compared to the conventional phase shifting mask with double patterned layers for the Cr layer and the phase shifter layer. The transparent phase shifting mask is promising for fabricating sub-half-micron patterns for 64 M DRAMs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Second Transmembrane Domain of the Human Type 1 Angiotensin II Receptor Participates in the Formation of the Ligand Binding Pocket and Undergoes Integral Pivoting Movement during the Process of Receptor Activation (2009)

The octapeptide hormone angiotensin II (AngII) exerts a wide variety of cardiovascular effects through the activation of the angiotensin II type-1 (AT(1)) receptor, which belongs to the G protein-coupled receptor superfamily. Like other G protein-coupled receptors, the AT(1) receptor possesses seven transmembrane domains that provide structural support for the formation of the ligand-binding pocket. In order to identify those residues in the second transmembrane domain (TMD2) that contribute to the formation of the binding pocket of the AT(1) receptor, we used the substituted cysteine accessibility method. All of the residues within the Leu-70 to Trp-94 region were mutated one at a time to a cysteine, and, after expression in COS-7 cells, the mutant receptors were treated with the sulfhydryl-specific alkylating agent methanethiosulfonate-ethylammonium (MTSEA). MTSEA reacts selectively with water-accessible, free sulfhydryl groups of endogenous or introduced point mutation cysteines. If a cysteine is found in the binding pocket, the covalent modification will affect the binding kinetics of the ligand. MTSEA substantially decreased the binding affinity of D74C-AT(1), L81C-AT(1), A85C-AT(1), T88C-AT(1), and A89C-AT(1) mutant receptors, which suggests that these residues orient themselves within the water-accessible binding pocket of the AT(1) receptor. Interestingly, this pattern of acquired MTSEA sensitivity was altered for TMD2 reporter cysteines engineered in a constitutively active N111G-AT(1) receptor background. Indeed, mutant D74C-N111G-AT(1) became insensitive to MTSEA, whereas mutant L81C-N111G-AT(1) lost some sensitivity and mutant V86C-N111G-AT(1) became sensitive to MTSEA. Our results suggest that constitutive activation of the AT(1) receptor causes TMD2 to pivot, bringing the top of TMD2 closer to the binding pocket and pushing the bottom of TMD2 away from the binding pocket.
Glutamic Acid 207 in Rodent T-cell RT6 Antigens Is Essential for Arginine-specific ADP-ribosylation (1996)

A rat T-cell antigen RT6.1 catalyzes NAD glycohydrolysis but not ADP-ribose transfer, even though the antigen has significant amino acid identity with eucaryotic arginine-specific ADP-ribosyltransferases. Since a highly conserved Glu in the catalytic region of these transferases is substituted with Gln at position 207 in RT6.1, we replaced the Gln with Glu, Asp, or Ala, by site-directed mutagenesis. The Glu-207 mutant produced ADP-ribosylarginine during incubation with NAD and L-arginine. The Asp-207 mutant but not the Ala-207 mutant produced ADP-ribosylarginine, but at a lower rate. In contrast, these mutations affected NAD glycohydrolase activity of RT6.1 to a much lesser extent. Kinetic studies of transferase reaction revealed that kcat of the Glu-207 mutant increased compared to findings with the Asp-207 mutant. Moreover, the mouse homologue of rat RT6 lost arginine-specific ADP-ribosyltransferase activity when Glu-207 was replaced with Gln. Thus, Glu-207 in rodent T-cell RT6 antigens is essential for transfer reaction of ADP-ribose to arginine.
Selective enzyme purification by affinity chromatography. (1968)

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.
Cystathionine Protects against Endoplasmic Reticulum Stress-induced Lipid Accumulation, Tissue Injury, and Apoptotic Cell Death (2012)

Cystathionine (R-S-(2-amino-2-carboxyethyl)-l-homocysteine) is a non-proteinogenic thioether containing amino acid. In mammals, cystathionine is formed as an intermediate of the transsulfuration pathway by the condensation of serine and homocysteine (Hcy) in a reaction catalyzed by cystathionine β-synthase (CBS). Cystathionine is subsequently converted to cysteine plus ammonia and α-ketobutyrate by the action of cystathionine γ-lyase (CGL). Pathogenic mutations in CBS result in CBS-deficient homocystinuria (HCU) which, if untreated, results in mental retardation, thromboembolic complications and connective tissue disorders. Currently there is no known function for cystathionine other than serving as an intermediate in transsulfuration and to date, the possible contribution of the abolition of cystathionine synthesis to pathogenesis in HCU has not been investigated. Using both mouse and cell-culture models, we have found that cystathionine is capable of blocking the induction of hepatic steatosis and kidney injury, acute tubular necrosis, and apoptotic cell death by the endoplasmic reticulum stress inducing agent tunicamycin. Northern and Western blotting analysis indicate that the protective effects of cystathionine occur without any obvious alteration of the induction of the unfolded protein response. Our data constitute the first experimental evidence that the abolition of cystathionine synthesis may contribute to the pathology of HCU and that this compound has therapeutic potential for disease states where ER stress is implicated as a primary initiating pathogenic factor.
High mobility bottom gate InGaZnO thin film transistors with SiOx etch stopper (2007)

The authors report on the fabrication of thin film transistors (TFTs), which use an amorphous indium gallium zinc oxide (a-IGZO) channel, by rf sputtering at room temperature and for which the channel length and width are patterned by photolithography and dry etching. To prevent plasma damage to the active channel, a 100-nm-thick SiOx layer deposited by plasma enhanced chemical vapor deposition was adopted as an etch stopper structure. The a-IGZO TFT (W∕L=10μm∕50μm) fabricated on glass exhibited a high field-effect mobility of 35.8cm2∕Vs, a subthreshold gate swing value of 0.59V∕decade, a thrseshold voltage of 5.9V, and an Ion∕off ratio of 4.9×106, which is acceptable for use as the switching transistor of an active-matrix TFT backplane.
Phase III Trial of Long-Term Adjuvant Androgen Deprivation After Neoadjuvant Hormonal Cytoreduction and Radiotherapy in Locally Advanced Carcinoma of the Prostate: The Radiation Therapy Oncology Group Protocol 92–02 (2003)

The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage.
Highly Enantioselective Conjugate Additions of Potassium Organotrifluoroborates to Enones by Use of Monodentate Phosphoramidite Ligands (2004)

The use of phosphoramidite ligands in the rhodium-catalyzed asymmetric conjugate addition of potassium organotrifluoroborates to various enones in the absence of water is described. A systematic search for effective catalysts has been performed by use of high-throughput screening methods. Initially, we have screened reaction conditions, catalyst precursors, and focused ligand libraries. In the next stage we have used the monodentate ligand combination approach, and finally we have made a library of 96 different phosphoramidites by parallel synthesis in the robot (instant ligand libraries) and have tested these in the vinylation of cyclohexenone (up to 88% enantiomeric excess, ee) and 4-phenyl-3-buten-2-one (up to 42% ee). Arylation of cyclohexenone by use of potassium phenyltrifluoroborate gave 3-phenylcyclohexanone with 99% ee.
Deletion and Duplication Variants around the Long Repeats of Herpes Simplex Virus Type 1 Strain 17 (1987)

Three variants of herpes simplex virus type 1 strain 17 were isolated. One variant had a deletion of 2.5 X 10(6) Mr in IRL/UL and 0.8 X 10(6) Mr in TRL such that sequences were deleted from both long repeats. The deletion in UL removed the 20K and 22K open reading frames. The second variant had a deletion of 3.5 X 10(6) Mr in IRL/UL which again removed the 20K and 22K open reading frames. The third variant had a similar deletion in UL, but in this case the deleted sequences were replaced by sequences from the left end of UL, such that the long repeat was extended by 3 X 10(6) Mr and the overall genome size by 2 X 10(6) Mr. All three variants grew almost normally in vitro. The analysis of 11 isolates with extensive variation in the long repeats outside the 'a' sequence is also reported.
Hydrophobic cell wall protein glycosylation by the pathogenic fungus Candida albicans (1994)

Cell surface hydrophobicity influences adhesion and virulence of the opportunistic fungal pathogen Candida albicans. Previous studies have shown that cell surface hydrophobicity is due to specific proteins that are exposed on hydrophobic cells but are masked by long fibrils on hydrophilic cells. This observation suggests that hydrophobic cell wall proteins may contain little or no mannosylation. In the present study, the glycosylation levels of three hydrophobic cell wall proteins (molecular mass range between 36 and 40 kDa) derived from yeast cells were examined. One hydrophilic protein (90 kDa) was also tested. Various endoglycosidases (endoglycosidase F-N-glycosidase F, O-glycosidase, beta-mannosidase, N-glycosidase F), an exoglycosidase (alpha-mannosidase), and trifluoromethane sulfonic acid were used to deglycosylate the proteins. All four proteins were reactive to the lectin concanavalin A, demonstrating that they were mannoproteins. However, gel electrophoresis of the control and treated proteins revealed that mannosyl groups of hydrophobic proteins were less than 2 kDa in size, while the mannosyl group of the hydrophilic protein had a molecular mass of approximately 20 kDa. These results suggest that unlike many hydrophilic proteins, hydrophobic proteins may have low levels of glycosylation. Changes in glycosylation may determine exposure of hydrophobic protein regions at the cell surface.
Translocation of Phospholipids Is Facilitated by a Subset of Membrane-spanning Proteins of the Bacterial Cytoplasmic Membrane (2003)

The mechanism by which phospholipids are transported across biogenic membranes, such as the bacterial cytoplasmic membrane, is unknown. We hypothesized that this process is mediated by the presence of the membrane-spanning segments of inner membrane proteins, rather than by dedicated flippases. In support of the hypothesis, it was demonstrated that transmembrane alpha-helical peptides, mimicking the membrane-spanning segments, mediate flop of 2-6-(7-nitro-2,1,3-benzoxadiazol-4-yl) aminocaproyl (C6-NBD)-phospholipids (Kol, M. A., de Kroon, A. I., Rijkers, D. T., Killian, J. A., and de Kruijff, B. (2001) Biochemistry 40, 10500-10506). Here the dithionite reduction assay was used to measure transbilayer equilibration of C6-NBD-phospholipids in proteoliposomes, composed of Escherichia coli phospholipids and a subset of bacterial membrane proteins. It is shown that two well characterized integral proteins of the bacterial cytoplasmic membrane, leader peptidase and the potassium channel KcsA, induce phospholipid translocation, most likely by their transmembrane domains. In contrast, the ATP-binding cassette transporter from the E. coli inner membrane MsbA, a putative lipid flippase, did not mediate phospholipid translocation, irrespective of the presence of ATP. OmpT, an outer membrane protein from E. coli, did not facilitate flop either, demonstrating specificity of protein-mediated phospholipid translocation. The results are discussed in the light of phospholipid transport across the E. coli inner membrane.
Spreadsheet-based interactive graphics: from prototype to tool (1990)

The NoPumpG prototype [7,8] suggested that the spreadsheet model of computation could simplify the creation of some types of interactive graphical application when compared with other approaches. We report here experience in developing an enhanced follow-on system, NoPumpII, and describe three applications developed using it. We conclude that (1) the potential advantages of the spreadsheet model are realized in this application experience, (2) revisions to the prototype design have permitted an increase in the complexity and scale of applications, and (3) there remain limitations in the current design which, if redressed, would further enlarge the scope of application. More generally we conclude that alternative computational models are an important area of exploration for HCI research.
Folate antagonists. 6. Synthesis and antimalarial effects of fused 2,4‐diaminothieno[2,3‐d]pyrimidines (1972)

Abstract 2,4‐Diamino‐5,7‐dihydro‐6 H ‐thiopyrano[4′,3′:4,5]thieno[2,3‐ d ]pyrirnidine, 2,4‐diamino‐9 H ‐mdeno[1′,2′:4,5]thieno[2,3‐ d ]pyrimidine, 2,4‐diamino‐5 H ‐indeno[2′,1′:4,5]thieno[2,3‐ d ]pyrimidine, 9,11‐diamino‐5,6‐dihydronaphtho[1′,2′:4,5]thieno[2,3‐ d ]pyrimidine, 7,9‐diamino‐5,6‐dihydronaphtho[2′,1′:4,5]thieno[2,3‐ d ]pyrimidine, 2,4‐diamino‐7‐benzy]‐5,6,7,8‐tetrahydropyrido[4′,3′:4,5]thieno[2,3‐ d ]pyrimidine, and various 2,4‐diamino‐5,6,7,8‐tetrahydro‐[1]benzothieno[2,3‐ d ]pyrimidines were synthesized by cyclization of the requisite fused 2‐aminothio‐phenene‐3‐carbonitriles utilizing chloroformamidine hydrochloride in diglyme. Several compounds exhibited strong inhibitory effects against Streptococcus faecalis (MGH‐2), Staphylococcus aureus (UC‐76), Streptococcus faecium (ATCC 8043), Lactobacillus casei (ATCC 7469), and Pediococcus cerevisiae (ATCC 8081) in vitro , and three compounds displayed antimalarial activity against Plasmodium berghei in mice and P. falciparum (Uganda I) in vitro .
Joint visual-text modeling for automatic retrieval of multimedia documents (2005)

In this paper we describe a novel approach for jointly modeling the text and the visual components of multimedia documents for the purpose of information retrieval(IR). We propose a novel framework where individual components are developed to model different relationships between documents and queries and then combined into a joint retrieval framework. In the state-of-the-art systems, a late combination between two independent systems, one analyzing just the text part of such documents, and the other analyzing the visual part without leveraging any knowledge acquired in the text processing, is the norm. Such systems rarely exceed the performance of any single modality (i.e. text or video) in information retrieval tasks. Our experiments indicate that allowing a rich interaction between the modalities results in significant improvement in performance over any single modality. We demonstrate these results using the TRECVID03 corpus, which comprises 120 hours of broadcast news videos. Our results demonstrate over 14 % improvement in IR performance over the best reported text-only baseline and ranks amongst the best results reported on this corpus.
Heme oxygenase 1 is required for mammalian iron reutilization (1997)

The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis. Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation. Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.
Comparison of a 17 b multiplier in Dual-rail domino and in Dual-rail D/sup 3/L (D/sup 4/L) logic styles (2003)

In this paper, a new family of dynamic logic gates called Dual-rail Data-Driven Dynamic Logic (D/sup 4/L) is introduced. In this logic family, the synchronization clock signal has been eliminated and correct precharge and evaluation sequencing is maintained by appropriate use of data instances. The methodology and characteristics of D/sup 4/L are demonstrated in the design of a CLA 32-b adder and a 17-b high-speed multiplier. Based on VHDL simulations, the D/sup 4/L implemented 32-b adder has 23% less switching-activity than a comparable domino adder and for D/sup 4/L multiplier switching-activity is 14.5% less than its domino rival. HSPICE simulation in a 0.6 /spl mu/m CMOS process shows that D/sup 4/L has a 17% power saving over domino in a 32-b CLA adder design and a 10% saving in a 17-b multiplier design while a D/sup 4/L adder has 8% less delay than a domino one.
A micromachined high throughput Coulter counter for bioparticle detection and counting (2007)

We describe a micromachined Coulter counter with multiple sensing microchannels for quantitative measurement of polymethacrylate particles and pollen. A unique design with sensing microelectrodes in the center of the microchannels is demonstrated. This design creates isolation resistances among channels, and thus circumvents the crosstalk caused by automatic electrical connection among microchannels. When implemented using microfluidic channels, this design is appropriate for the sensing of microscale particles in deionized water or in dilute electrolyte solution. Our design has multiple channels operating in parallel, but integrated with just one sample reservoir and one power source. The results with a four-channel device show that this device is capable of differentiating and counting micro polymethacrylate particles and Juniper pollen rapidly. Moreover, the device throughput is improved significantly in comparison to a single-channel device. The concept can be extended to a large number of sensing channels in a single chip for significant improvement in throughput.
Tyrosine phosphorylation is an obligatory event in IL-2 secretion. (1990)

Activation of T lymphocytes leads to the production of the T cell growth factor IL-2 that regulates T cell proliferation. This activation is associated with several potential intracellular signalling events including increased activity of phospholipase C (PLC) and resultant increases in production of inositol phosphates and diacylglycerols. In addition, phosphorylation of specific intracellular proteins on serine, threonine, and tyrosine residues increases. The role of each of these events in IL-2 production is unclear. Using Western blotting with antiphosphotyrosine antibodies, we demonstrate that activation of murine T cells with mitogenic lectins or anti-CD3 antibodies leads to a rapid increase in tyrosine phosphorylation of proteins of 120, 72, 62, 55, and 40 kDa. Similar patterns of antiphosphotyrosine antibodies reactivity were observed in splenocytes, a T cell hybridoma, and a T lymphoma. Tyrosine phosphorylation was detectable within minutes of addition of mitogenic lectins and persisted for at least 6 h. Pretreatment of the cells with pertussis toxin did not inhibit tyrosine phosphorylation indicating that a pertussis toxin-sensitive G protein is not involved in signal transduction. Neither increasing cytosolic-free calcium nor activating protein kinase C mimicked the effects of mitogenic lectins suggesting that tyrosine phosphorylation was not a consequence of activation of PLC. This was confirmed by demonstrating that mitogenic lectins induced similar patterns of tyrosine phosphorylation in cells in which activation of the TCR leads to increased PLC activity and in cells in which PLC is not stimulated. To test whether tyrosine phosphorylation is linked to IL-2 secretion, we determined the effect of three specific tyrosine kinase inhibitors (tyrphostins) on tyrosine phosphorylation, IL-2 secretion, and cellular proliferation. The concentration dependence of inhibition of tyrosine phosphorylation and IL-2 production were similar. However, higher concentrations of the tyrphostins were required to inhibit constitutive proliferation of the T cell line indicating that inhibition of IL-2 secretion was not secondary to nonspecific toxic effects of the tyrphostins. Addition of the tyrphostins after mitogenic lectin decreased the amount of tyrosine phosphorylation and IL-2 secretion in parallel. This indicates that both tyrosine kinases and phosphatases are activated and that continuous tyrosine phosphorylation is likely required for IL-2 secretion. Therefore, tyrosine phosphorylation appears to represent an obligatory event in the transmembrane signaling processes that lead to IL-2 secretion.