gebhart/patrepeval huggingface dataset:
Making tissue-type plasminogen activator more fibrin specific (1993)

The fibrin specificity of tissue-type plasminogen activator can be increased by mutagenesis within at least four sites in the protease domain. These sites include residue I276, the new N-terminus formed by conversion to a two-chain structure, residues on either side of the active site cleft, KHRR 296-299 or DDD 364-366, a charged surface involved in fibrin interactions, which includes residues H432, R434, D460, R462 and a loop structure, PQANL 466-470, near the fibrin-binding patch. Variants with mutations at any of these sites have low fibrinogen-stimulated activity, whereas fibrin-stimulated activity is at least normal. Kinetic analysis reveals that mutations at these positions reduce the kcat in the presence of fibrinogen, but leave the molecules with normal kinetic constants in the presence of fibrin. A significant exception is found at positions 296-299, where the presence of fibrin manifests significant increases in both kcat and Km. Combinations of mutations at these sites appear to be additive with respect to fibrin specificity.
Binding of Perfluorooctanoic Acid to Rat and Human Plasma Proteins (2003)

Perfluorooctanoic acid (PFOA) is a commercially important organic fluorochemical and is considered to have a long half-life in human blood. In this paper, PFOA binding to rat and human plasma proteins was investigated. On the basis of results from size-exclusion chromatography and ligand blotting, most PFOA was in protein-bound form in male and female rat plasma, and the primary PFOA binding protein in plasma was serum albumin. PFOA binding to rat serum albumin (RSA) in the gas phase was observed by electrospray ionization MS. (19)F NMR experiments revealed that binding to RSA caused peak broadening and chemical shift changes of PFOA resonances, and on the basis of this observation, the dissociation constant was determined to be approximately 0.3 mM. The dissociation constants for PFOA binding to RSA and human serum albumin (HSA) and the numbers of PFOA binding sites on RSA and HSA were also determined by a separation method using microdesalting columns. No significant difference was found between PFOA binding to RSA and PFOA binding to HSA. The dissociation constants for binding of PFOA to RSA or HSA and the numbers of PFOA binding sites were in the range of 0.3-0.4 mM and 6-9, respectively. On the basis of these binding parameters and the estimated plasma concentration of serum albumin, greater than 90% of PFOA would be bound to serum albumin in both rat and human blood.
Laminin Receptors: From PC12 Cells to PNS (1990)

The spatial and functional organization of individual cells into tissues is an event at the heart of metazoan development. This organization attains extraordinary complexity in the nervous system where inputs and outputs are matched at the level of single neurons. For example, in the visual system of frogs the axons of retinal ganglion cells form an array of synaptic connections in the tectum that reflects, with elegant precision, the positions of their somata in the retina. This topographic projection of the retina onto the tectum led Sperry (1963) to propose the now-famous chemoaffinity hypothesis.
Technological Application of Maltodextrins According to the Degree of Polymerization (2015)

Maltodextrin (MX) is an ingredient in high demand in the food industry, mainly for its useful physical properties which depend on the dextrose equivalent (DE). The DE has however been shown to be an inaccurate parameter for predicting the performance of the MXs in technological applications, hence commercial MXs were characterized by mass spectrometry (MS) to determine their molecular weight distribution (MWD) and degree of polymerization (DP). Samples were subjected to different water activities (aw). Water adsorption was similar at low aw, but radically increased with the DP at higher aw. The decomposition temperature (Td) showed some variations attributed to the thermal hydrolysis induced by the large amount of adsorbed water and the supplied heat. The glass transition temperature (Tg) linearly decreased with both, aw and DP. The microstructural analysis by X-ray diffraction showed that MXs did not crystallize with the adsorption of water, preserving their amorphous structure. The optical micrographs showed radical changes in the overall appearance of the MXs, indicating a transition from a glassy to a rubbery state. Based on these characterizations, different technological applications for the MXs were suggested.
Complement regulatory activity of normal human intraocular fluid is mediated by MCP, DAF, and CD59. (2000)

Our results demonstrate that normal human intraocular fluid (aqueous humor and vitreous) contains complement inhibitory factors. Furthermore, the high-molecular-weight factors appear to be the soluble forms of MCP, DAF, and CD59.
Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats (2004)

Chronic arthritis induces hypermetabolism and cachexia. Ghrelin is a gastrointestinal hormone that has been proposed as a treatment to prevent cachexia. The aim of this work was to examine the effect of administration of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) to arthritic rats. Male Wistar rats were injected with Freund's adjuvant, and 15 days later arthritic and control rats were daily injected with GHRP-2 (100 microg/kg) or with saline for 8 days. Arthritis induced an increase in serum ghrelin (P < 0.01) and a decrease in serum concentrations of leptin (P < 0.01), whereas GHRP-2 administration increased serum concentrations of leptin. GHRP-2 increased food intake in control rats but not in arthritic rats. However, in arthritic rats GHRP-2 administration ameliorated the external symptoms of arthritis, as it decreased the arthritis score (10.4 +/- 0.8 vs. 13.42 +/- 0.47, P < 0.01) and the paw volume. In addition, circulating IL-6 and nitrites/nitrates were increased by arthritis, and GHRP-2 treatment decreased the serum IL-6 levels (P < 0.01). To elucidate whether GHRP-2 is able to modulate IL-6 release directly on immune cells, peritoneal macrophage cultures were incubated with GHRP-2 or ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor. Both GHRP-2 (10(-7) M) and ghrelin (10(-7) M) prevented endotoxin-induced IL-6 and decreased nitrite/nitrate release from peritoneal macrophages in vitro. These data suggest that GHRP-2 administration has an anti-inflammatory effect in arthritic rats that seems to be mediated by ghrelin receptors directly on immune cells.
Nuclear assembly shaped by microtubule dynamics (2014)

Maintenance of nuclear architecture is crucial for gene regulation, cell proliferation and tissue development. However, during every open mitosis and meiosis, chromosomes are exposed to cytoskeletal forces until they are fully reassembled into mature nuclei. Here we discuss our recent study of nuclear assembly in Xenopus egg extracts, where we showed that the DNA binding protein Developmental pluripotency associated 2 (Dppa2) directly inhibits microtubule polymerization during nuclear formation, and that this is essential for normal nuclear shape and replication. We explore mechanisms by which microtubule dynamics could regulate nuclear formation and morphology, and discuss the importance of both spatial and temporal regulation of microtubules in this process. Moreover, expression of Dppa2 is limited to the early embryo and pluripotent tissues, and we highlight the specific demands of mitosis in these often rapidly dividing cells, in which telophase nuclear assembly must be expedited and may facilitate developmental changes in nuclear architecture.
Improving video-on-demand server efficiency through stream tapping (2002)

Efficiency is essential for video-on-demand (VOD) to be successful. Conventional VOD servers are inefficient, they dedicate a disk stream for each client, quickly using up all available streams. However, several systems have been proposed that allow clients to share streams. We present a new system called stream tapping that allows a client to greedily "tap" data from any stream on the VOD server containing video data the client can use. This is accomplished through the use of a small buffer on the client set-top box and requires less than 20% of the disk bandwidth used by conventional systems for popular videos. We present a description and analysis of the stream tapping system as well as comparisons between it and other efficiency-improving systems.
68Ga-Labeled 2-{3-[5-(7-{1-benzyloxycarbonyl-5-[2-(4,7,10-tris-carboxymethyl-1,4,7,10-tetraazacyclododec-1-l)acetylamino]pentylcarbamoyl}-heptanoylamino)-1-carboxypentyl]ureido}pentanedioic acid (2010)

The prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein that is present primarily in the prostate and is overexpressed during all stages of the androgen-insensitive or the metastatic cancer of this organ (1). In addition, PSMA is expressed at lower levels (compared to the prostate) in the neovasculature of some solid tumors (for details, see Elsasser-Beile et al. (1)). Because of its high expression during the development and progression of a malignancy, PSMA is considered to be a good target for the imaging and treatment of prostate cancer (2). Several investigators have reported the use of radio-halogenated (e.g., 18F, 125I, etc.) and 99mTc-labeled small molecule inhibitors for the imaging of PSMA (3). Among these radionuclides, 18F is the most frequently used to label diverse positron emission tomography (PET) agents for diagnostic imaging because its addition to a molecule (usually by the replacement of a hydrogen atom) does not alter its chemical properties; however, due to its short half-life (~110 min), an on-site cyclotron is needed to produce this radio-halogen (4). Recently 68Ga (half-life, ~68 min) has been suggested to be a suitable alternative to the use of 18F for the production of PET imaging probes because 68Ga is easy to produce with a 68Ge/68Ga generator system that does not have to be on-site. However, it is necessary to mention that currently no 68Ge/68Ga generator system has been approved by the United States Food and Drug Administration (Eckelman: personal communication). In addition, 68Ga has been successfully used by some investigators to study cancer and tumor biology (4, 5). On the basis of these observations, and as an extension of their earlier work (for references, see Banerjee et al. (3)), Banerjee et al. developed two 68Ga-labeled, urea-based inhibitors of PSMA ([68Ga]-labeled 2-{3-[5-(7-{1-benzyloxycarbonyl-5-[2-(4,7,10-tris-carboxymethyl-1,4,7,10-tetraazacyclododec-1-l)acetylamino]pentylcarbamoyl}-heptanoylamino)-1-carboxypentyl]ureido}pentanedioic acid ([68Ga]3) and [68Ga]-labeled 2-[3-(1-carboxy-5-{7-[5-carboxy-5-(3-phenyl-2-{3-phenyl-2-[2-(4,7,10-tris-carboxymethyl-1,4,7,10-tetraazacyclododec-1-l)acetylamino]propionylamino}propionylamino)pentylcarbamoyl]heptanoylamino}pentyl)ureido]pentanedioic acid ([68Ga]6)) and evaluated them for biodistribution and the imaging of PSMA-expressing tumors in nude mice (3). This chapter details the results obtained with [68Ga]3. Results obtained with [68Ga]6 are presented in a separate chapter of MICAD ( www.micad.nih.gov ) (6).
Bone Marrow Cells Differentiate in Cardiac Cell Lineages After Infarction Independently of Cell Fusion (2004)

Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to differentiate into myocytes and coronary vessels. The claim has also been made that BMCs acquire a cell phenotype different from the blood lineages only by fusing with resident cells. Technical problems exist in the induction of myocardial infarction and the successful injection of BMCs in the mouse heart. Similarly, the accurate analysis of the cell populations implicated in the regeneration of the dead tissue is complex and these factors together may account for the negative findings. In this study, we have implemented a simple protocol that can easily be reproduced and have reevaluated whether injection of BMCs restores the infarcted myocardium in mice and whether cell fusion is involved in tissue reconstitution. For this purpose, c-kit-positive BMCs were obtained from male transgenic mice expressing enhanced green fluorescence protein (EGFP). EGFP and the Y-chromosome were used as markers of the progeny of the transplanted cells in the recipient heart. By this approach, we have demonstrated that BMCs, when properly administrated in the infarcted heart, efficiently differentiate into myocytes and coronary vessels with no detectable differentiation into hemopoietic lineages. However, BMCs have no apparent paracrine effect on the growth behavior of the surviving myocardium. Within the infarct, in 10 days, nearly 4.5 million biochemically and morphologically differentiated myocytes together with coronary arterioles and capillary structures were generated independently of cell fusion. In conclusion, BMCs adopt the cardiac cell lineages and have an important therapeutic impact on ischemic heart failure.
Antistaphylococcal Activity of WCK 771, a Tricyclic Fluoroquinolone, in Animal Infection Models (2004)

WCK 771, the arginine salt of S-(-)-nadifloxacin, was evaluated in animal models of staphylococcal infection and in vitro. For 302 methicillin-susceptible strains the MIC at which 50% of isolates are inhibited (MIC50) and the MIC90 of WCK 771 were 0.03 and 0.03 microg/ml, respectively, and for 198 methicillin-resistant strains the MIC50 and the MIC90 were 0.5 and 1.0 microg/ml, respectively. All methicillin-susceptible staphylococci were quinolone susceptible, and almost all methicillin-resistant staphylococci were quinolone resistant. WCK 771 was more potent than moxifloxacin, trovafloxacin, levofloxacin, and ciprofloxacin and had potency comparable to that of clinafloxacin. Only WCK 771 and clinafloxacin demonstrated strong potencies against vancomycin-intermediate Staphylococcus aureus strains (MICs = 1 microg/ml). WCK 771 is not a substrate of the NorA pump, as evident from the lack of an effect of reserpine on the MICs and similar protective doses against infections caused by efflux-positive and -negative staphylococci. WCK 771 was effective by both the oral and the subcutaneous routes in mice infected intraperitoneally with quinolone-susceptible methicillin-susceptible S. aureus (MSSA) strains. For infections caused by quinolone-resistant methicillin-resistant S. aureus (MRSA) strains, the activity of WCK 771 administered subcutaneously was superior to those of trovafloxacin and sparfloxacin, with a 50% effective dose range of 27.8 to 46.8 mg/kg of body weight. The activity of WCK 771 was superior to those of moxifloxacin, vancomycin, and linezolid in a mouse cellulitis model of infection caused by one MSSA and two MRSA strains, with effective doses of 2.5 and 5 mg/kg for the MSSA strain and 10-fold higher effective doses for MRSA strains. WCK 771, like vancomycin and linezolid, eradicated MRSA from mouse liver, spleen, kidney, and lung when it was administered subcutaneously at a dose of 50 mg/kg for four doses. These studies have demonstrated the effectiveness of WCK 771, administered orally and parenterally, for the treatment of diverse staphylococcal infections in mice, including those caused by quinolone-resistant strains.
Role of cyclic AMP response element binding protein in human leukemias (2005)

Acute myeloid leukemia (AML) in adults has a 20% 5-year disease-free survival despite treatment with aggressive cytotoxic chemotherapy. Previous work from our laboratory demonstrated that the majority of patients with acute lymphoid and myeloid leukemia overexpress CREB in the bone marrow. CREB overexpression is associated with poor initial outcome of clinical disease in AML patients. CREB is a transcription factor that functions in glucose homeostasis, growth-factor-dependent cell survival, and memory. Signaling by hematopoietic growth factors, such as GM-CSF, results in activation of CREB and up-regulation of CREB target genes. To study its role in hematopoiesis, we overexpressed CREB in leukemia cell lines and in mice. CREB overexpression resulted in increased survival and proliferation of myeloid cells and blast-transformation of bone marrow progenitor cells from transgenic mice expressing CREB in the myeloid lineage. CREB transgenic mice also develop myeloproliferative disease after 1 year. Thus, CREB acts as a protooncogene to regulate hematopoiesis and contributes to the leukemia phenotype. Our results suggest that CREB-dependent pathways may serve as targets for directed therapies in leukemia in the future.
Cyclosporine and tacrolimus (FK506): A comparison of efficacy and safety profiles (1999)

Multicenter clinical trials conducted in the United States and Europe to compare the efficacy and safety of cyclosporine with tacrolimus (FK506) have demonstrated comparable long-term patient survival and graft survival in liver and renal transplant recipients. Importantly, treatment with tacrolimus was associated with reductions in the incidence and severity of acute rejection episodes. However, tacrolimus-based therapy was also associated with increased toxicities in comparison to conventional cyclosporine-based therapy. It is becoming increasingly accepted that earlier trials may have employed high or supratherapeutic doses of tacrolimus and may have been unbalanced with respect to study design. In addition, these pivotal comparative trials were performed with the original formulation of cyclosporine, and not the cyclosporine microemulsion preparation. This critical review of the literature focuses on the United States and European tacrolimus multicenter clinical trials and examines the efficacy and safety of the two primary immunosuppressants, cyclosporine and tacrolimus, obtained in these and other studies. The preliminary findings of ongoing studies comparing the efficacy and safety of the improved formulation, cyclosporine microemulsion, with tacrolimus are also discussed. The overall efficacy of the two agents appears to be similar. The safety profile shows differing toxicities of the two medications. The availability of these two immunosuppressants allows the clinician improved options when choosing an immunosuppressive regimen in solid organ transplantation.
Development of an Integrated Polymer Microfluidic Stack (2006)

Microfluidic is a field of considerable interest. While significant research has been carried out to develop microfluidic components, very little has been done to integrate the components into a complete working system. We present a flexible modular system platform that addresses the requirements of a complete microfluidic system. A microfluidic stack system is demonstrated with the layers of the stack being modular for specific functions. The stack and accompanying infrastructure provides an attractive platform for users to transition their design concepts into a working microfluidic system quickly with very little effort. The concept is demonstrated by using the system to carry out a chemilumiscence experiment. Details regarding the fabrication, assembly and experimental methods are presented.
MemSpy: analyzing memory system bottlenecks in programs (1992)

To cope with the increasing difference between processor and main memory speeds, modern computer systems use deep memory hierarchies. In the presence of such hierarchies, the performance attained by an application is largely determined by its memory reference behavior—if most references hit in the cache, the performance is significantly higher than if most references have to go to main memory. Frequently, it is possible for the programmer to restructure the data or code to achieve better memory reference behavior. Unfortunately, most existing performance debugging tools do not assist the programmer in this component of the overall performance tuning task.
Material transport regimes and mechanisms for growth of molecular organic thin films using low-pressure organic vapor phase deposition (2001)

We determine the physical mechanisms controlling the growth of amorphous organic thin films by the process of low-pressure organic vapor phase deposition (LP-OVPD). In LP-OVPD, multiple host and dopant molecular sources are introduced into a hot wall reactor via several injection barrels using an inert carrier gas, allowing for controlled film growth rates exceeding 10 Å/s. The temperature and carrier flow rate for each source can be independently regulated, allowing considerable control over dopant concentration, deposition rate, and thickness uniformity of the thin films. The rate of film deposition is limited either by the rate of condensation on the substrate or by the rate of supply from the source. The source-limited regime can be further classified into equilibrium or kinetically limited evaporation, coupled to convection- or diffusion-limited deposition. Models are developed to relate the rate of film growth to source and substrate temperature, and carrier gas flow rate. These models characterize and predict the performance of the LP-OVPD system used to grow high performance organic light emitting devices.
Functional analysis of the sialyltransferase complexes in Escherichia coli K1 and K92 (1992)

The polysialyltransferase (polyST) structural gene, neuS, for poly alpha 2,8sialic acid (PSA) capsule synthesis in Escherichia coli K1 was previously mapped near the kps region 1 and 2 junction (S. M. Steenbergen and E. R. Vimr, Mol. Microbiol. 4:603-611, 1990). Present Southern and colony blot hybridization results confirmed that neuS was a region 2 locus and indicated apparent homology with neuS from E. coli K92, bacteria that synthesize a sialyl alpha 2,8-2,9-linked polymer. A K1- mutant with an insertion mutation in neuS was complemented in trans by K92 neuS, providing direct evidence that neuS encoded the PSA polymerase. A 2.9-kb E. coli K1 kps subclone was sequenced to better characterize polyST. In addition to neuS, the results identified a new open reading frame, designated neuE, the linker sequence between regions 1 and 2, and the last gene of region 1, kpsS. The kpsS translational reading frame was confirmed by sequencing across the junction of a kpsS'-lacZ+ fusion. PolyST was identified by maxicell analysis of nested deletions and coupled in vitro transcription-translation assays. PolyST's derived primary structure predicted a 47,500-Da basic polypeptide without extensive similarity to other known proteins. PolyST activity was increased 31-fold and was membrane localized when neuS was cloned into an inducible expression vector, suggesting, together with the polyST primary structure, that polyST is a peripheral inner membrane glycosyltransferase. However, polyST could not initiate de novo PSA synthesis, indicating a functional requirement for other kps gene products. The existence of a sialyltransferase distinct from polyST was suggested by identification of a potential polyprenyl-binding motif in a C-terminal membrane-spanning domain of the predicted neuE gene product. Direct evidence for a quantitatively minor sialyltransferase activity, which could function to initiate PSA synthesis, was obtained by phenotypic analysis of mutants with multiple defects in sialic acid synthesis, degradation, and polymerization. The results provide an initial molecular description of K1 and K92 sialyltransferase complexes and suggest a possible common function for accessory kps gene products.