gebhart/patrepeval huggingface dataset:
Purification and in vitro activities of rabbit platelet microbicidal proteins (1997)

Recent in vitro studies have demonstrated that rabbit platelets release a small, cationic antimicrobial protein in response to thrombin stimulation under physiological conditions (M. R. Yeaman, S. M. Puentes, D. C. Norman, and A. S. Bayer, Infect. Immun. 60:1202-1209, 1992). This observation prompted our present investigation, focused on determining the array of antimicrobial proteins contained within rabbit platelets and their in vitro activity against common bloodstream pathogens. A group of small (6.0- to 9.0-kDa), cationic proteins with in vitro antimicrobial activity was purified from whole and thrombin-stimulated rabbit platelets by gel filtration and reversed-phase high-performance liquid chromatography. Purified proteins in micromolar concentrations (10 to 40 microg/ml) exerted in vitro microbiostatic and/or microbicidal activities against Staphylococcus aureus, Escherichia coli, and Candida albicans in a dose-dependent manner. The antimicrobial activities of proteins purified from rabbit platelet acid extracts were generally inversely related to pH, with maximal activity observed at pH 5.5. In contrast, the predominant protein isolated from thrombin-stimulated rabbit platelets, though biochemically and microbiologically similar to proteins extracted by acid, exhibited antimicrobial activities which were modestly enhanced at pH 7.2 compared with pH 5.5. Amino acid compositional analyses in combination with molecular mass determinations suggest that the majority of these proteins are distinct molecules not derived from a single common precursor. Collectively, these data indicate that rabbit platelets contain proteins which exert potent in vitro antimicrobial activity against bacterial and fungal pathogens which commonly invade the bloodstream. Moreover, several of these proteins were released from platelets stimulated with thrombin under physiological conditions and exerted potent antimicrobial activities in physiological pH ranges. These observations support the hypothesis that platelets serve an important role in host defense against infection, via localized release of antimicrobial proteins in response to stimuli associated with tissue injury or microbial colonization.
Bubble size and velocity measurement in gas—liquid systems: Application of fiber optic technique to pilot plant scale (1995)

Abstract A new fiber optic probe was developed for the detection and measurement of bubble sizes and velocities in a gas‐liquid column. The probe is made of a single 1 mm plastic fiber with a sharp wedge tip. The calibration was carried out on a laboratory scale unit using a cine‐photographic technique to verify the measurements. Bubble velocities were calculated using two identical parallel fibers and the cross‐correlation technique. With the velocities and the passage time determined, it was then possible to determine the bubble diameter. Bubble diameters were within 10% of the measurements obtained with the cine‐photographic technique. After calibration, measurements were carried out on a pilot scale unit.
Preclinical studies of BMS-582664, an alanine prodrug of BMS-540215, a potent, dual inhibitor of VEGFR-2 and FGFR-1 kinases (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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The growth, survival and dissemination of tumors is critically dependent on angiogenesis, the process of neovascularization which exploits the host’s preexisting vascular system. Initiation of angiogenesis in the cancer disease state is generally mediated by secretion from the tumor of a variety of growth factors including, among others, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The effects of these growth factors are mediated through their cognate receptors, VEGFR and FGFR, respectively. Inhibition of VEGFR-2 signaling, in particular, has been demonstrated to inhibit angiogenesis and subsequently tumor growth. As a result, we have targeted VEGFR-2 for inhibition by small molecule inhibitors. In the described studies, we characterize BMS-540215 and its orally active ester prodrug, BMS-582664, which is now in Phase 1 clinical trials. BMS-540215 demonstrates potent and selective inhibition of VEGFR-2 and FGFR-1. It also exhibits good selectivity for these two enzymes versus a panel of twenty receptor and non-receptor kinases as well as non-kinase targets. It selectively inhibits the proliferation of human umbilical vein endothelial cells when stimulated with VEGF or bFGF but not EGF (epidermal growth factor). As expected, and consistent with the targeted cell population and distribution of VEGFR-2, BMS-540215 does not inhibit the growth of the tumor cell lines, L2987 and H3396 in vitro when tested up to 10 uM but is active, along with BMS-582664, against these same tumor lines when grown in vivo . Both BMS-540215 and BMS-582664 demonstrate broad spectrum in vivo antitumor activity over multiple dose levels as well as being effective at inducing stasis in large tumors. BMS-582664 can also be safely dosed in combination with other targeted and cytotoxic drugs including Paclitaxel, resulting in enhanced antitumor activity as observed by a long period of tumor growth inhibition. Doses required for achieving complete tumor stasis do not produce overt toxicity as defined by weight loss, mortality or unkempt appearance and behavior. BMS-582664, which is completely hydrolyzed to BMS-540215 in vivo , has pharmacokinetic properties suitable for once a day or twice daily oral dosing. Finally, doses required for preclinical activity showed a good correlation with those which resulted in blood flow changes to the tumor as measured by DCE-MRI.
Plasma Cells and IL-4 in Chronic Bronchitis and Chronic Obstructive Pulmonary Disease (2007)

Inflammatory cells are increased in bronchial submucosal glands and mucosa of large airways in smokers with CB. Gland-associated plasma cells express IL-4, and these likely promote mucus hypersecretion.
The Structure of Apolipoprotein A-I in High Density Lipoproteins (2007)

Not long ago, high density lipoproteins (HDL) 2 were second class citizens with regard to therapeutic strategies for lowering the risk of atherosclerosis and coronary artery disease (CAD). To date, most successful approaches have focused on the better understood pathways of cholesterol synthesis and low density lipoprotein (LDL) production, the "forward" cholesterol transport pathway. For example, the statin class of cholesterol synthesis inhibitors significantly reduces LDL levels resulting in a less atherogenic plasma lipoprotein profile. However, the relatively modest improvements in mortality conferred by these drugs suggest that other factors also play significant roles in defining CAD risk. The recent discoveries of HDL-interacting cell surface proteins such as scavenger receptor BI (SR-BI) and ATP-binding cassette transporters A1 (ABCA1) and G1 (for recent reviews see Refs. 1 and 2) have helped define the steps of reverse cholesterol transport (RCT), i.e. the movement of cholesterol from the periphery to the liver for catabolism (3, 4). Additionally, there is growing evidence that HDL anti-inflammatory properties may contribute significant protective effects (5), apparently via specific cell signaling pathways (6). These discoveries have fueled a new interest in HDL as a target for CAD treatment (7). Unfortunately, a complete understanding of HDL function has been hampered by a lack of information on its structure and the molecular basis of its interactions with other proteins. This review summarizes the latest efforts in understanding the structure of the defining protein component of HDL, apoA-I, in the various stages of the RCT pathway.
Riser Lift Pump for Deep Water Drilling (1998)

Abstract A new riser system consisting of a lift pump located a distance down in a conventional marine drilling riser with a separate mud return line from the lift pump and up is used to reduce the hydrostatic head of the drilling fluid in the bore hole. The upper section of the riser above the pump outlet is vented to the atmosphere. A lower mud level allows a higher mud weight to be used. However, determined by the position of the fluid level it will result in a lower pressure at the casing shoe. The hydrostatic head of the drilling fluid and the seawater will be sufficient to control the bottom hole pressure after an emergency disconnection of the marine-drilling riser at the seabed. The riser joint which houses the pump can be located anywhere in the riser section depending on water depth, formation pore pressure etc., typically 200 - 300 m below the sea level. The system also allows the bottom hole pressure to be quickly adjusted by simply adjusting the air/mud level above the pump outlet in the marine-drilling riser. P. 299
Self-formation of highly aligned metallic, semiconducting and single chiral single-walled carbon nanotubes assemblies via a crystal template method (2014)

The fabrication of an aligned array of single-walled carbon nanotubes (SWCNTs) with a single chiral state has been a significant challenge for SWCNT applications as well as for basic science research. Here, we developed a simple, unique technique to produce assemblies in which metallic, semiconducting, and single chiral state SWCNTs were densely and highly aligned. We utilized a crystal of surfactant as a template on which mono-dispersed SWCNTs in solution self-assembled. Micro-Raman measurements and scanning electron microscopy measurements clearly showed that the SWCNTs were highly and densely aligned parallel to the crystal axis, indicating that approximately 70% of the SWCNTs were within 7° of being parallel. Moreover, the assemblies exhibited good field effect transistor characteristics with an on/off ratio of 1.3 × 105.
Homology between DNA polymerases of poxviruses, herpesviruses, and adenoviruses: nucleotide sequence of the vaccinia virus DNA polymerase gene. (1986)

A 5400-base-pair segment of the vaccinia virus genome was sequenced and an open reading frame of 938 codons was found precisely where the DNA polymerase had been mapped by transfer of a phosphonoacetate-resistance marker. A single nucleotide substitution changing glycine at position 347 to aspartic acid accounts for the drug resistance of the mutant vaccinia virus. The 5' end of the DNA polymerase mRNA was located 80 base pairs before the methionine codon initiating the open reading frame. Correspondence between the predicted Mr 108,577 polypeptide and the 110,000 purified enzyme indicates that little or no proteolytic processing occurs. Extensive homology, extending over 435 amino acids, was found upon comparing the DNA polymerase of vaccinia virus and DNA polymerase of Epstein-Barr virus. A highly conserved sequence of 14 amino acids in the carboxyl-terminal regions of the above DNA polymerases is also present at a similar location in adenovirus DNA polymerase. This structure, which is predicted to form a turn flanked by beta-pleated sheets, may form part of an essential binding or catalytic site that accounts for its presence in DNA polymerases of poxviruses, herpesviruses, and adenoviruses.
Infection with Hepatitis A and TT Viruses and Socioeconomic Status in Rio de Janeiro, Brazil (2001)

The prevalence of antibodies directed against the enterically transmitted hepatitis A virus (HAV) was measured in 2 groups of people living in Rio de Janeiro, Brazil. Of 1,056 health care workers (HCWs), 778 (73.7%) were anti-HAV positive. A high prevalence of anti-HAV antibodies (85.7%) was also found among 274 voluntary blood donors (BDs). TT virus (TTV) is a DNA virus that has been found in the sera of patients with post-transfusion hepatitis of unknown etiology. Occurrence of virus shedding suggests that the fecal-oral route may be an important mode of TTV transmission, particularly in the developing world. The presence of TTV DNA was analyzed by PCR in the sera of 191 HCWs and 151 BDs. TTV was detected in 65.4% of HCWs and 79.5% of BDs. In both groups, a family income of < US$400 per month and a level of education of < 11 y of schooling were found to be risk factors for HAV infection. Furthermore, a low family income was associated with TTV viremia in the HCW group. However, the presence of TTV DNA was associated with neither low level of education nor anti-HAV positivity.
Static and dynamic transport in parity-sensitive systems (1995)

A microscopic theory has been constructed to investigate tunneling current and shot noise in a normal-superconductor-normal (NSN) single-electron transistor (SET). In contrast to the time-averaged current, the time-dependent current that determines the shot noise depends on where in the circuit it is measured. For an even-parity superconducting ground state the pair-tunneling in the dominating Andreev channel will be suppressed as one or both of two single-particle channels open up at increased bias voltages. With further increase of bias, Andreev tunneling between odd-parity charge states contributes significantly to the current. Threshold voltages for these tunneling processes vary with circuit parameters and can be identified with the normalized shot noise, which is more sensitive to both the switching of charge transport channels and the circuit parameters of the NSN SET than the time-averaged current. Our calculated results have been compared with recent experiments.
Oral and Pharyngeal Reflexes in the Mammalian Nervous System: Their Diverse Range in Complexity and the Pivotal Role of the Tongue (2002)

The oral cavity and pharynx are anatomically separate but functionally integrated regions of the head. The two regions are involved in complex motor responses that include feeding, chewing, swallowing, speech, and respiration. The multiple sensory receptors that innervate these two regions provide the first link in reflexes that control muscles of the entire head, upper gastrointestinal tract, and airway. Most of the reflexes affect the diversity of muscles that compose the tongue, which is vital to all stages of feeding and which continually affects the patency of the airway. Oral-pharyngeal reflexes are evident in the mammalian fetus and continually emerge as the animal or human matures. Some of the first reflexes in the oral region are geared toward nourishment. As the central nervous system matures and the oral and pharyngeal regions develop morphologically, new reflexes develop. Many of these reflexes are protective both of the tissue in the oral cavity, such as the tongue, and of the upper airway in preventing aspiration. While simple reflexes can be evoked in isolation, most reflexes combine with more complex oral and pharyngeal responses such as chewing and vocalization. Oral-pharyngeal reflexes demonstrate a range in complexity. Some sensory stimuli will evoke a series of responses, as is often evident in the infant, and other stimuli will evoke a complex multiple-level recruitment of muscles in a sequence, as in pharyngeal swallowing. Certain sensory inputs evoke an entire motor behavior pattern, such as taste avoidance or facial expression. The oral-pharyngeal reflexes are critical to maintaining life and ultimately serve functions that the oral and pharyngeal regions have in common, such as communication, feeding, and breathing.
Purification and properties of a 23 kDa Ca2+-binding protein from Drosophila melanogaster (1990)

Recent reports have shown that there exists in mammalian brain a number of heat-stable Ca2(+)-binding proteins that are distinct from calmodulin [McDonald & Walsh (1985) Biochem. J. 232, 559-567]. We have attempted to characterize equivalent Ca2(+)-binding proteins from Drosophila. Affigel-phenothiazine chromatography, which can be used to purify calmodulin and other Ca2(+)-binding proteins, allowed the identification of a possible heat-stable 23 kDa Ca2(+)-binding protein. A purification procedure for this protein has been devised. Purified 23 kDa protein shows characteristics typical of a Ca2(+)-binding protein; there is a mobility shift on SDS/polyacrylamide gels in the presence of EGTA, and Western blotting, followed by the use of the 45Ca2+ overlay technique, confirms that the 23 kDa protein does bind Ca2+. 45Ca2+ binding studies indicate that this protein binds 1 mol of Ca2+/mol of protein, with Kd 1.9 microM. A single band with pI 5.2 is obtained on isoelectric focusing. Analysis of Western blots of Drosophila tissues probed with antibodies to the Ca2(+)-binding protein indicates that it has a widespread distribution, but is absent from muscle tissue. The antibodies also cross-react with a protein of identical molecular mass in extracts of sheep brain. The possible similarity between this Drosophila Ca2(+)-binding protein and mammalian proteins is discussed, and comparison is made between this Drosophila protein and other Ca2(+)-binding proteins purified from vertebrates.
A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff (2012)

We describe a new computer program, SnpEff, for rapidly categorizing the effects of variants in genome sequences. Once a genome is sequenced, SnpEff annotates variants based on their genomic locations and predicts coding effects. Annotated genomic locations include intronic, untranslated region, upstream, downstream, splice site, or intergenic regions. Coding effects such as synonymous or non-synonymous amino acid replacement, start codon gains or losses, stop codon gains or losses, or frame shifts can be predicted. Here the use of SnpEff is illustrated by annotating ~356,660 candidate SNPs in ~117 Mb unique sequences, representing a substitution rate of ~1/305 nucleotides, between the Drosophila melanogaster w(1118); iso-2; iso-3 strain and the reference y(1); cn(1) bw(1) sp(1) strain. We show that ~15,842 SNPs are synonymous and ~4,467 SNPs are non-synonymous (N/S ~0.28). The remaining SNPs are in other categories, such as stop codon gains (38 SNPs), stop codon losses (8 SNPs), and start codon gains (297 SNPs) in the 5'UTR. We found, as expected, that the SNP frequency is proportional to the recombination frequency (i.e., highest in the middle of chromosome arms). We also found that start-gain or stop-lost SNPs in Drosophila melanogaster often result in additions of N-terminal or C-terminal amino acids that are conserved in other Drosophila species. It appears that the 5' and 3' UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus. As genome sequencing is becoming inexpensive and routine, SnpEff enables rapid analyses of whole-genome sequencing data to be performed by an individual laboratory.
Macrophages Sequentially Change Their Functional Phenotype in Response to Changes in Microenvironmental Influences (2005)

Recent studies have described the development of distinct functional subsets of macrophages in association with cancer, autoimmune disease, and chronic infections. Based on the ability of Th1 vs Th2 cytokines to promote opposing activities in macrophages, it has been proposed that macrophages develop into either type 1 inflammatory or type 2 anti-inflammatory subsets. As an alternative to the concept of subset development, we propose that macrophages, in response to changes in their tissue environment, can reversibly and progressively change the pattern of functions that they express. As demonstrated herein, macrophages can reversibly shift their functional phenotype through a multitude of patterns in response to changes in cytokine environment. Macrophages display distinct functional patterns after treatment with IFN-gamma, IL-12, IL-4, or IL-10 and additional functional patterns are displayed depending on whether the cytokine is present alone or with other cytokines and whether the cytokines are added before or concomitantly with the activating stimulus (LPS). Sequential treatment of macrophages with multiple cytokines results in a progression through multiple functional phenotypes. This ability to adapt to changing cytokine environments has significant in vivo relevance, as evidenced by the demonstration that macrophage functional phenotypes established in vivo in aged or tumor-bearing mice can be altered by changing their microenvironment. A concept of functional adaptivity is proposed that has important implications for therapeutic targeting of macrophages in chronic diseases that result in the dominance of particular functional phenotypes of macrophages that play a significant role in disease pathology.
Cyclosporin A-mediated inhibition of mitogen-induced gene transcription is specific for the mitogenic stimulus and cell type. (1989)

We have examined the effect of cyclosporin A (CSA) on the mitogen-induced expression of 11 genes previously cloned from mitogen-activated T lymphocytes. Levels of induced gene expression in the human T cell line Jurkat were determined by mRNA blotting and nuclear run-on assay, after stimulation with one or combinations of the mitogens PMA, PHA, and the ionophore A23187. In the presence of CSA, gene expression induced with PMA alone was not inhibited, whereas PHA-induced increases in gene expression were inhibited by CSA. For one group of genes, including IL-2 and two novel genes with sequences suggestive of lymphokines, A23187 plus PMA-induced gene expression was inhibited by CSA. In contrast, another group of induced genes was unaffected by CSA after A23187 and PMA induction. This finding implies that A23187 and PMA stimulate gene induction by more than one mechanism, and that not all activation signals mediated through calcium fluxes are sensitive to CSA. In addition, 8 of the 11 genes were expressed in the fibroblast cell line Mrc 5 after stimulation with PMA, A23187, or serum; CSA had no effect on genes induced with these agents in Mrc 5 cells in both mRNA blotting and run-on experiments, although 5 of these genes were markedly inhibited by CSA in Jurkat after PMA/PHA induction. These data indicate that separate pathways for induction of identical genes exist, and that the inciting stimulus and cell type are determining factors in the ability of CSA to inhibit gene expression.
Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells (2004)

Most small cell lung cancers (SCLC) coexpress the c-kit protein tyrosine receptor kinase and its ligand stem cell factor, resulting in an autocrine loop. As SCLC growth is also driven by insulin-like growth factor-1 receptor (IGF-1R) signalling, tyrphostins AG 1024 and 1296 (inhibitors of IGF-1R and c-kit activity, respectively) were used to co-target these receptors in H 209 SCLC cells. Combination treatment caused synergy in proliferation inhibition and in apoptosis induction, and also enhanced reduction in phosphorylation of Erk1/Erk2, suggesting that co-targeting IGF-1R and c-kit in SCLC may be more effective than single-agent therapies.
The secure distribution of digital contents (2002)

A report is given on the development of a system for the distribution of encrypted digital contents via freely accessible distribution media. To be able to use this information, the key needed for decryption has to be ordered from a key management system. The distribution of the keys required for decryption is restricted whereas the distribution of the encrypted contents is not. The key is sent to the customer only if sufficient payment has been authorised. The system described in this paper is designed (i) to be independent of the method used for distribution of the encrypted contents, (ii) to support many different payment systems, (iii) to support casual customers (nonregistered users), (iv) to avoid complicated software setup, contract conclusion and registration processes, and (v) to support re-selling of other manufacturer's contents in simple way without extra contracts. In addition, (vi) the system can be easily adapted to support workflow management in a business-to-business environment.