gebhart/patrepeval huggingface dataset:
Cyclin B1, unlike cyclin G1, increases significantly during colorectal carcinogenesis and during later metastasis to lymph nodes (2003)

In collaboration with p53, cyclins B1 and G1 regulate the G2/M transition, a key checkpoint in the active cell cycle, which can be monitored by Ki67. However, the cyclin B1 expression remains unclear during colorectal carcinogenesis and during later metastasis to lymph nodes, and cyclin G1 expression is not clear in colorectal tumors. To clarify the variations of the two cyclins in colorectal tumors, cyclin B1, cyclin G1, p53, and Ki67 were immunohistochemically stained in 22 normal mucosa, 62 adenomas, 17 carcinomas in adenomas, 194 primary carcinomas, and 21 lymph node metastases; and the two cyclins were examined by Western blot in other 10 pairs of normal mucosa and primary carcinomas. Located in cytoplasms, nuclei or both, cyclin B1 expression increased significantly from normal mucosa through adenomas to primary carcinomas, from adenomas with mild dysplasia through those with moderate to those with severe, from peripheral adenomas to their central carcinomas, and from primary to metastatic foci. These increased expressions were confirmed by Western blot. Cyclin B1 expression, however, declined significantly in primary carcinomas showing large size, mucinous type, deep invasion, or short postoperative-patient-survival time. High cyclin B1 was linked to high p53 in adenomas, and to high Ki67 in adenomas and primary carcinomas. In contrast, found limited to nuclei, cyclin G1 expression did not vary significantly from normal mucosa through to metastatic carcinomas, and was not associated with clinicopathological parameters, p53 or Ki67. The unchanged expressions were confirmed by Western blot. Thus, increased cyclin B1, but not cyclin G1, may promote colorectal carcinogenesis and later metastasis to lymph nodes.
Histidine-proline-rich glycoprotein has potent antiangiogenic activity mediated through the histidine-proline-rich domain. (2002)

Histidine-proline-rich glycoprotein (HPRG) is an abundant multidomain plasma protein evolutionarily related to high-molecular-weight kininogen. The cleaved form of high-molecular-weight kininogen has recently been demonstrated to exhibit antiangiogenic activities in vitro (J. C. Zhang et al., FASEB J., 14: 2589-2600, 2000), mediated primarily through domain 5. HPRG contains a histidine-proline-rich (H/P) domain with sequence and functional similarities to HKa-D5. We hypothesized that HPRG may also have antiangiogenic properties, localized within its H/P domain. The H/P domain is highly conserved among species, and because rabbit H/P domain is more resistant to internal proteolytic cleavage than the human domain, the rabbit HPRG (rbHPRG) was primarily used to assess the antiangiogenic activity of HPRG. Rabbit HPRG inhibited human umbilical vein endothelial cell (HUVEC) tube formation stimulated by fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor on a Matrigel surface as well as cell proliferation of FGF-2 stimulated HUVECs. The antiangiogenic activity of rbHPRG was localized to the H/P domain by use of proteolytic fragments of rbHPRG and was further confirmed and characterized in two in vivo models of angiogenesis: the chorioallantoic membrane of the chick assay and the mouse Matrigel plug assay. Caspase-3 activation was observed in HUVECs stimulated with FGF-2 in the presence of rbHPRG, suggesting that apoptosis of activated endothelial cells may be one of the mechanisms underlying its antiangiogenic activity. Finally, the H/P domain of rbHPRG reduced tumor cell number when tumor cells were co-inoculated in the Matrigel plug assay. In conclusion, the H/P domain within HPRG induces the apoptosis of activated endothelial cells leading to potent antiangiogenic effects.
Isolation and Characterisation of a Low Molecular Weight Inhibitor (of Chymotrypsin and Human Granulocytic Elastase and Cathepsin G) from Leeches (1977)

Two protein proteinase inhibitors were isolated and purified from the leech Hirudo medicinalis by means of gel filtration and ion-exchange chromatography. They inhibit chymotrypsin, subtilisin and the granulocytic neutral proteases elastase and cathepsin G. They proved to be homogeneous in polyacrylamide and dodecylsulfate gel electrophoresis and by end group analysis; only threonine was found as N-terminal amino acid residue using the dansylation technique. These inhibitors, which we call eglins, are stable in neutral and weakly acid (pH 3) solutions and resist non-specific proteolysis. From the amino acid compositions, a molecular weight of 6 600 - 6 800 is calculated for both inhibitory proteins, which is in good agreement with a value of about 6000 estimated by dodecylsulfate electrophoresis. The eglins contain an unusually large amount of hydrophobic amino acid residues but no methionine, isoleucine or--a rarity--cysteine residues or disulfide bridges. To our knowledge, the eglins are the first examples of proteinase inhibitors of the protein type which are not stabilized by disulfide bridges.
Determination of the Catalytic Activities of mTOR and Other Members of the Phosphoinositide-3-Kinase-Related Kinase Family (2004)

Members of the phosphoinositide-3-kinase-related kinase (PIKK) family, which includes mTOR, ATM, ATR, and hSMG-1, play important roles in regulating the cellular response to environmental stimuli. Despite the similarity of their catalytic domain to that of phosphoinositide-3-kinase, these extremely large (>250 kDa) polypeptides function as serine/threonine protein kinases. The catalytic activities of these PIKK family members can now be measured in immune-complex kinase assays. This assay involves isolation of the kinase by immunoprecipitation and the in vitro phosphorylation of a specific substrate in the presence of radio-labeled ATP. Here we describe, in detail, the determination of PIKK catalytic activity with a standardized immune-complex kinase assay protocol.
Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices (2012)

Diagnostic tools for biomolecular detection need to fulfill specific requirements in terms of sensitivity, selectivity and high-throughput in order to widen their applicability and to minimize the cost of the assay. The nucleic acid amplification is a key step in DNA detection assays. It contributes to improving the assay sensitivity by enabling the detection of a limited number of target molecules. The use of microfluidic devices to miniaturize amplification protocols reduces the required sample volume and the analysis times and offers new possibilities for the process automation and integration in one single device. The vast majority of miniaturized systems for nucleic acid analysis exploit the polymerase chain reaction (PCR) amplification method, which requires repeated cycles of three or two temperature-dependent steps during the amplification of the nucleic acid target sequence. In contrast, low temperature isothermal amplification methods have no need for thermal cycling thus requiring simplified microfluidic device features. Here, the use of miniaturized analysis systems using isothermal amplification reactions for the nucleic acid amplification will be discussed.
Observation in Laparoscopic Surgery: Overview of Impeding Effects and Supporting Aids (2000)

Within a Dutch research program on minimally invasive surgery, a large literature survey has been carried out. This article describes the state of the art in research on observation in laparoscopy. It gives an overview of factors impeding the surgeon and technical developments designed to overcome these problems. A large number of journals, proceedings, patents, and books starting from the year 1991 have been consulted. The survey was completed with a thorough MEDLINE search. The survey showed that many authors have an incomplete background in the fundamentals of visual perception. This leads to a lack of understanding and to the design of supporting aids that often are not very useful. The new aspect of this study is that it gives a complete and structured overview of laparoscopic observation problems and current solutions. The observation problems are structured according to visual perception theory. The solutions are critically considered, and their benefits and drawbacks are identified. The study shows that the benefits of stereo-endoscopes and motorized endoscope positioners are questionable. The addition of shadows and movement parallax is still a very important research topic.
Discrete-Time Signal Processing (1989)

For senior/graduate-level courses in Discrete-Time Signal Processing. THE definitive, authoritative text on DSP -- ideal for those with an introductory-level knowledge of signals and systems. Written by prominent, DSP pioneers, it provides thorough treatment of the fundamental theorems and properties of discrete-time linear systems, filtering, sampling, and discrete-time Fourier Analysis. By focusing on the general and universal concepts in discrete-time signal processing, it remains vital and relevant to the new challenges arising in the field --without limiting itself to specific technologies with relatively short life spans.
Synthesis, Crystal Structure, Structure−Activity Relationships, and Antiviral Activity of a Potent SARS Coronavirus 3CL Protease Inhibitor (2006)

A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, Ki = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 microM) for SARS CoV and 5.2 log (at 1.25 microM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 A) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.
Molecular Genetic Studies in Atrial Fibrillation (2003)

Atrial fibrillation is a complex disease. Its etiologies are diverse and genetic factors may also contribute to this disease. With the advent of modern molecular biology technology, it is now possible to explore the genetic components in the pathogenesis of atrial fibrillation. Past molecular genetic studies on atrial fibrillation in the literature can be divided into linkage analysis studies and association studies. The subjects for linkage analysis studies are pedigrees of probands with Mendelian hereditary atrial fibrillation. The first locus identified for autosomal dominant atrial fibrillation locates at 10q22-q24. However, the exact gene is still unknown. Another linkage analysis study in Chinese revealed that LQT1 gene (I(Ks) alpha-subunit) was the responsible gene. A missense mutation in the I(Ks) alpha-subunit results in a gain of function, which is important in causing atrial fibrillation. The third known locus for familial atrial fibrillation locates at 6q14-16. The responsible gene remains still unknown. The other type of studies takes the case-control design (association studies) and the subjects have multigenic atrial fibrillation. In a study in a Japanese population, it was reported that the angiotensin-converting enzyme insertion/deletion polymorphism was not associated with atrial fibrillation. On the other hand, researchers in Taiwan reported that a nonsynonymous single nucleotide polymorphism of the LQT5 gene (I(Ks) beta-subunit) is associated with atrial fibrillation. In summary, there is growing evidence showing that genetic factors are important in the pathogenesis of atrial fibrillation. We expect that more genes responsible for or contributing to atrial fibrillation will be identified in the future and these will elucidate the molecular mechanisms of atrial fibrillation.
Optimizing the production of suspension cells using the G-Rex “M” series (2014)

Broader implementation of cell-based therapies has been hindered by the logistics associated with the expansion of clinically relevant cell numbers ex vivo. To overcome this limitation, Wilson Wolf Manufacturing developed the G-Rex, a cell culture flask with a gas-permeable membrane at the base that supports large media volumes without compromising gas exchange. Although this culture platform has recently gained traction with the scientific community due to its superior performance when compared with traditional culture systems, the limits of this technology have yet to be explored. In this study, we investigated multiple variables including optimal seeding density and media volume, as well as maximum cell output per unit of surface area. Additionally, we have identified a novel means of estimating culture growth kinetics. All of these parameters were subsequently integrated into a novel G-Rex "M" series, which can accommodate these optimal conditions. A multicenter study confirmed that this fully optimized cell culture system can reliably produce a 100-fold cell expansion in only 10 days using 1L of medium. The G-Rex M series is linearly scalable and adaptable as a closed system, allowing an easy translation of preclinical protocols into the good manufacturing practice.
Collagen-stimulated Activation of Syk but Not c-Src Is Severely Compromised in Human Platelets Lacking Membrane Glycoprotein VI (1997)

Activation of circulating platelets by subendothelial collagen is an essential event in vascular hemostasis. In human platelets, two membrane glycoprotein (GP) abnormalities, integrin alpha2 beta1 deficiency and GPVI deficiency, have been reported to result in severe hyporesponsiveness to fibrillar collagen. Although it has been well established that integrin alpha2 beta1, also known as the GPIa-IIa complex, functions as a primary platelet adhesion receptor for collagen, the mechanism by which GPVI contributes to collagen-platelet interaction has been ill defined to date. However, our recent observation that GPVI cross-linking couples to cyclic AMP-insensitive activation of c-Src and Syk tyrosine kinases suggested a potential role for GPVI in regulating protein-tyrosine phosphorylation by collagen (Ichinohe, T., Takayama, H., Ezumi, Y., Yanagi, S., Yamamura, H., and Okuma, M. (1995) J. Biol. Chem. 270, 28029-28036). To further investigate this hypothesis, here we examined the collagen-induced protein-tyrosine phosphorylation in GPVI-deficient platelets expressing normal amounts of alpha2 beta1. In response to collagen, these platelets exhibited alpha2 beta1-dependent c-Src activation accompanied by tyrosine phosphorylation of several substrates including cortactin. In contrast, severe defects were observed in collagen-stimulated Syk activation and tyrosine phosphorylation of phospholipase C-gamma2, Vav, and focal adhesion kinase, implicating a specific requirement of GPVI for recruiting these molecules to signaling cascades evoked by collagen-platelet interaction.
Screen Coverage: A Pen-Interaction Problem for PDA's and Touch Screen Computers (2007)

Touch screens at electronic kiosk systems, pen based PDAs or smart phones, have become more popular over the recent years. The direct interaction on the display by fingers, hands or pens implies the problem of covering the screen. The coverage depends on the interface organization and the use of the interaction elements. This paper describes a basic approach of measuring the coverage of the interface, as well as determination and definitions of basic parameters concerning the ratio between visualization and interaction areas. The metric determination of the coverage leads to analytic testimonies and provides new predictions for resent and future usability tests.
Structural Characterization of HIV gp41 with the Membrane-proximal External Region (2010)

Human immunodeficiency virus, type 1 (HIV-1) envelope glycoprotein (gp120/gp41) plays a critical role in virus infection and pathogenesis. Three of the six monoclonal antibodies considered to have broadly neutralizing activities (2F5, 4E10, and Z13e1) bind to the membrane-proximal external region (MPER) of gp41. This makes the MPER a desirable template for developing immunogens that can elicit antibodies with properties similar to these monoclonal antibodies, with a long term goal of developing antigens that could serve as novel HIV vaccines. In order to provide a structural basis for rational antigen design, an MPER construct, HR1-54Q, was generated for x-ray crystallographic and x-ray footprinting studies to provide both high resolution atomic coordinates and verification of the solution state of the antigen, respectively. The crystal structure of HR1-54Q reveals a trimeric, coiled-coil six-helical bundle, which probably represents a postfusion form of gp41. The MPER portion extends from HR2 in continuation of a slightly bent long helix and is relatively flexible. The structures observed for the 2F5 and 4E10 epitopes agree well with existing structural data, and enzyme-linked immunosorbent assays indicate that the antigen binds well to antibodies that recognize the above epitopes. Hydroxyl radical-mediated protein footprinting of the antigen in solution reveals specifically protected and accessible regions consistent with the predictions based on the trimeric structure from the crystallographic data. Overall, the HR1-54Q antigen, as characterized by crystallography and footprinting, represents a postfusion, trimeric form of HIV gp41, and its structure provides a rational basis for gp41 antigen design suitable for HIV vaccine development.
Effects of Chronic Prazepam Administration on Drug Metabolism in Man and Rat (1972)

Chronic administration of prazepam produced opposite effects on drug metabolism in man and rat. After an oral dose of 10 mg t.i.d. for 7 days, prazepam prolonged antipyrine half-lives in all but 1 of 12 healthy Negro volunteers. In 5 of these subjects who also received a single dose of 14C-prazepam before and after the 7-day course of unlabelled prazepam, the plasma half-life of 14C-prazepam was
Genetic stability of protein expression systems in yeast. (1994)

For the expression of recombinant proteins in yeast, genetic stability is monitored using a combination of standard microbiology and nucleic acid testing procedures. Process consistency during the cell amplification and product expression phases of fermentation are also reliable indicators of stability. The potential for instability arising from point mutation, gene conversion or recombination has been shown to occur at a low frequency and does not generally affect protein product quality.
Effect ofBifidobacterium bifidumandLactobacillus acidophiluson gut mucosa and peripheral blood B lymphocytes (1992)

In 15 elderly individuals lyophilized Bifidobacterium bifidum (BB) and Lactobacillus acidophilus (LA) (Infloran) were administered in capsules (two capsules 4 times per day) for 28 days, while in 10 elderly controls placebo were given the same posology and for an equal period of time. The effects of this treatment on the immune system both at the periphery or the intestinal level were investigated. Results show that BB and LA significantly reduced the colonic inflammatory infiltration, without altering T, B and Leu7 + cell percentage. At the same time, a significant increase of B cell frequency in the peripheral blood was noted, in comparison to controls. The overall results suggest that the regular administration of BB and LA leads to a modulation of the immunological and inflammatory response in elderly subjects.
Health Libraries in El Salvador (2002)

ABSTRACT El Salvador is a paradox. A perfect tropical climate coupled with an amiable population makes it a veritable paradise. Approximately the size of Massachusetts, this Central American country is divided into 14 departments with a population of 6.2 million as of 1999. More than 47 percent exist below or at the poverty level and 42 percent live in rural areas. Libraries in El Salvador have never received high priority, so Salvadoran librarians face formidable challenges, but their commitment and dedication are strong. Like librarians everywhere, they find providing information fulfilling and rewarding.
Partial purification of thrombopoietin from the plasma of thrombocytopenic rabbits (1979)

Partially purified thrombopoiesis-stimulating activity was prepared from the plasma of thrombocytopenic rabbits using ammonium sulfate precipitation and DEAE cellulose, Sephadex, and carboxymethyl cellulose chromatography. The protein fraction precipitated by an ammonium sulfate saturation of 60%-80%, previously shown to contain thrombopoiesis-stimulating activity, was used as starting material. Column chromatography was carried out at room temperature at pH 5.6. Under these conditions, thrombopoiesis-stimulating activity (thrombopoietin) was retained by DEAE cellulose (0/03 M citrate- phosphate buffer) and carboxymethyl cellulose (0/003 M citrate- phosphate buffer), and eluted with 0.4 M NaCl. Thrombopoietin was retarded by Sephadex G-100; the ratio of the elution volume to the void volume was 1.32:1. Immunoelectrophoretic analysis of partially purified thrombopoietin indicated that following removal of most of the albumin by DEAE chromatography, only proteins with the mobilities of beta- globulins and albumin and traces of other anodally migrating proteins were detectable in the fractions that contained thrombopoiesis- stimulating activity. Thrombopoietin was not dialyzable and was stable from at least pH 5.6 to 7.5. It was approximately 1000-fold purified following sequential chromatography with DEAE and carboxymethyl cellulose. Although the three fractions described reproducibly stimulated thrombopoiesis, as measured by increased levels of selenomethionine-75Se (75SeM) in the circulating platelets, platelet counts did not increase.
Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. (1993)

Recently, a novel M(r) 100,000 prostate-specific membrane glycoprotein (PSM) has been detected by the prostate-specific monoclonal antibody 7E11-C5, raised against the human prostatic carcinoma cell line LNCaP. The PSM antigen is expressed exclusively by normal and neoplastic prostate cells and metastases. We now report the molecular cloning of a full-length 2.65-kilobase complementary DNA encoding the PSM antigen from a human LNCaP complementary DNA library by polymerase chain reaction using degenerate oligonucleotide primers. Analysis of the complementary DNA sequence has revealed that a portion of the coding region, from nucleotide 1250 to 1700, has 54% homology to the human transferrin receptor mRNA. The deduced polypeptide has a putative transmembrane domain enabling the delineation of intra- and extracellular portions of this antigen. In contrast to prostate-specific antigen and prostatic acid phosphatase which are secreted proteins, PSM as an integral membrane protein may prove to be effective as a target for imaging and cytotoxic targeting modalities.
Shock and Tissue Injury Induced by Recombinant Human Cachectin (1986)

Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. Recombinant human cachectin was infused into rats in an effort to determine whether cachectin, by itself, can elicit the derangements of host physiology caused by administration of endotoxin. When administered in quantities similar to those produced endogenously in response to endotoxin, cachectin causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes to hours, as a result of respiratory arrest. Hyperglycemia and hyperkalemia were also observed after infusion. At necropsy, diffuse pulmonary inflammation and hemorrhage were apparent on gross and histopathologic examination, along with ischemic and hemorrhagic lesions of the gastrointestinal tract, and acute renal tubular necrosis. Thus, it appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.