gebhart/patrepeval huggingface dataset:
A signal peptide with a proline next to the cleavage site inhibits leader peptidase when present in a sec‐independent protein (1992)

Proline residues are rarely found in the three most C-terminal positions of bacterial signal peptides, and have never been found in position +1 immediately following the cleavage site. It was recently shown that a Pro+1 mutation in the E. coli maltose binding protein precursor not only prevents cleavage of the signal peptide but also inhibits the leader peptidase enzyme, resulting in cessation of cell growth (Barkocy-Gallagher, G.A. and Bassford, P.J. (1992) J. Biol. Chem. (in press)). Since maltose binding protein is dependent on the sec machinery for translocation across the inner membrane, it was not clear if this 'Pro+1' effect was restricted to sec-dependent proteins, or whether it applies also to proteins that do not require the sec functions for translocation. We now present data suggesting that the striking phenotypic effects of Pro+1 mutations can be elicited also by sec-independent proteins.
Measurement of von Willebrand factor as the marker of endothelial dysfunction in vascular diseases. (2004)

By measuring von Willebrand factor activity, a considerable, significant difference could be found between healthy people and chronic and acute vascular patients. The routine measurement of von Willebrand factor activity in vascular patients as an index of endothelial dysfunction may have clinical importance, because detection of this marker can be a noninvasive way of assisting diagnosis and indicating disease progression.
On building an accurate stereo matching system on graphics hardware (2011)

This paper presents a GPU-based stereo matching system with good performance in both accuracy and speed. The matching cost volume is initialized with an AD-Census measure, aggregated in dynamic cross-based regions, and updated in a scanline optimization framework to produce the disparity results. Various errors in the disparity results are effectively handled in a multi-step refinement process. Each stage of the system is designed with parallelism considerations such that the computations can be accelerated with CUDA implementations. Experimental results demonstrate the accuracy and the efficiency of the system: currently it is the top performer in the Middlebury benchmark, and the results are achieved on GPU within 0.1 seconds. We also provide extra examples on stereo video sequences and discuss the limitations of the system.
High-coercivity magnetic hard disks using glass substrates (1990)

A new structure for sputtered thin-film high-density longitudinal magnetic recording media using glass substrates has been proposed. The coercivity of Co alloy films is increased considerably by depositing a thin Ti layer between the Cr underlayer and the glass substrates. X-ray diffraction analysis indicates a change in the preferred orientation of the Cr layer. Transmission electron microscopy reveals that there is a significant change in the microstructure of the columnar Cr layer when Ti coating is used. It is proposed that the Ti film prevents oxygen from the glass substrates from reacting with the Cr and Co alloy magnetic layers.
Assessment of combined radioimmunotherapy and chemotherapy for treatment of medullary thyroid cancer. (1999)

We have shown previously significant antitumor effects using 90Y-MN-14 anti-CEA monoclonal antibody (MAb) for radioimmunotherapy (RAIT) of human medullary thyroid cancer (MTC) xenografts using the TT cell line. The purpose of this investigation was to determine the effect of combining chemotherapy and RAIT with 90Y-MN-14 in MTC. In particular, the toxicity and efficacy of various dose schedules of RAIT and doxorubicin were examined and compared with that at the maximum tolerated dose (MTD) of each single modality treatment. The MTD of RAIT of 105 microCi of 90Y-MN-14 was given alone and combined with 100 and 75% of the MTD of doxorubicin (60 mg/m2); and the MTD of doxorubicin was given alone and combined with 100 and 75% of the MTD of RAIT. In addition, 75% of each agent was also administered in combination. The MTD of RAIT was also evaluated in combination with 58 and 78% of the MTD of Taxol. Whereas 90Y-MN-14 (105 microCi) led to significant antitumor effects (P < 0.0001), doxorubicin at 60 mg/m2 or Taxol at 225 mg/m2 yielded only a slight tumor growth delay. The combinations of 100% of the MTD of RAIT and 75% of the MTD of doxorubicin and 100% of the MTD of doxorubicin and 75% of the MTD of RAIT were equitoxic to the MTD of RAIT alone and appear to result in improved efficacy compared with either RAIT or doxorubicin alone. For the 100% RAIT and 75% doxorubicin combination, the therapeutic efficacy was similar when doxorubicin was administered on the same day or 1 day after RAIT, but the treatment was less effective when doxorubicin was administered 2 days after RAIT (P < 0.03). Prolonged retardation of tumor progression was also observed in animals treated with the MTD of RAIT combined with 175 mg/m2 of Taxol, without increases in toxicity above that observed with RAIT alone. In conclusion, the combination of RAIT and chemotherapy appears to augment the antitumor effects of either treatment alone without a significant increase in toxicity. In addition, the timing of drug administration relative to RAIT in the combined therapy appears to be important.
Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation (2010)

Extracellular regulation of signaling by transforming growth factor (TGF)-β family members is emerging as a key aspect of organ formation and tissue remodeling. In this study, we demonstrate that fibrillin-1 and -2, the structural components of extracellular microfibrils, differentially regulate TGF-β and bone morphogenetic protein (BMP) bioavailability in bone. Fibrillin-2-null (Fbn2(-/-)) mice display a low bone mass phenotype that is associated with reduced bone formation in vivo and impaired osteoblast maturation in vitro. This Fbn2(-/-) phenotype is accounted for by improper activation of latent TGF-β that selectively blunts expression of osterix, the transcriptional regulator of osteoblast maturation, and collagen I, the structural template for bone mineralization. Cultured osteoblasts from Fbn1(-/-) mice exhibit improper latent TGF-β activation as well, but mature faster because of increased availability of otherwise matrix-bound BMPs. Additional in vitro evidence excludes a direct role of microfibrils in supporting mineral deposition. Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-β and BMP signaling.
Efficient mining of frequent subgraphs in the presence of isomorphism (2004)

Frequent subgraph mining is an active research topic in the data mining community. A graph is a general model to represent data and has been used in many domains like cheminformatics and bioinformatics. Mining patterns from graph databases is challenging since graph related operations, such as subgraph testing, generally have higher time complexity than the corresponding operations on itemsets, sequences, and trees, which have been studied extensively. We propose a novel frequent subgraph mining algorithm: FFSM, which employs a vertical search scheme within an algebraic graph framework we have developed to reduce the number of redundant candidates proposed. Our empirical study on synthetic and real datasets demonstrates that FFSM achieves a substantial performance gain over the current start-of-the-art subgraph mining algorithm gSpan.
Treatment of irritable bowel syndrome (2010)

This review is the first to compile the available evidence on the efficacy of the various pharmacological treatments for IBS on the basis of IBS subtype and specific symptoms. This evidence is limited and more well-designed studies are required to better inform therapeutic decision-making in the management of this difficult syndrome.
Nanoparticle-Delivered Chemotherapy: Old Drugs in New Packages. (2017)

Cytotoxic chemotherapies have a narrow therapeutic window, with high peaks and troughs of plasma concentration. Novel nanoparticle formulations of cytotoxic chemotherapy drugs can enhance pharmacokinetic characteristics and facilitate passive targeting of drugs to tumors via the enhanced permeability and retention effect, thus mitigating toxicity. Nanoparticle vehicles currently in clinical use or undergoing clinical investigation for anticancer therapies include liposomes, polymeric micelles, protein-drug nanoparticles, and dendrimers. Multiple nanoparticle formulations of existing cytotoxic chemotherapies are approved for use in several indications, with clinical data indeed showing optimization of pharmacokinetics and different toxicity profiles compared with their parent drugs. There are also many new nanoparticle drug formulations in development and undergoing early- and late-phase clinical trials, including several that utilize active targeting or triggered release based on environmental stimuli. Here, we review the rationale for nanoparticle formulations of existing or previously investigated cytotoxic drugs, describe currently approved nanoparticle formulations of drugs, and discuss some of the most promising clinical trials currently underway.
Phase-referenced interferometer with subwavelength and subhertz sensitivity applied to the study of cell membrane dynamics (2001)

We report a highly sensitive means of measuring cellular dynamics with a novel interferometer that can measure motional phase changes. The system is based on a modified Michelson interferometer with a composite laser beam of 1550-nm low-coherence light and 775-nm CW light. The sample is prepared on a coverslip that is highly reflective at 775 nm. By referencing the heterodyne phase of the 1550-nm light reflected from the sample to that of the 775-nm light reflected from the coverslip, small motions in the sample are detected, and motional artifacts from vibrations in the interferometer are completely eliminated. We demonstrate that the system is sensitive to motions as small as 3.6 nm and velocities as small as 1 nm/s. Using the instrument, we study transient volume changes of a few (approximately three) cells in a monolayer immersed in weakly hypotonic and hypertonic solutions.
Engineering of Glycerol-stimulated Insulin Secretion in Islet Beta Cells (1997)

Insulin secretion from beta cells in the islets of Langerhans can be stimulated by a number of metabolic fuels, including glucose and glyceraldehyde, and is thought to be mediated by metabolism of the secretagogues and an attendant increase in the ATP:ADP ratio. Curiously, glycerol fails to stimulate insulin secretion, even though it has been reported that islets contain abundant glycerol kinase activity and oxidize glycerol efficiently. We have reinvestigated this point and find that rat islets and the well differentiated insulinoma cell line INS-1 contain negligible glycerol kinase activity. A recombinant adenovirus containing the bacterial glycerol kinase gene (AdCMV-GlpK) was constructed and used to express the enzyme in islets and INS-1 cells, resulting in insulin secretion in response to glycerol. In AdCMV-GlpK-treated INS-1 cells a greater proportion of glycerol is converted to lactate and a lesser proportion is oxidized compared with glucose. The two fuels are equally potent as insulin secretagogues, despite the fact that oxidation of glycerol at its maximally effective dose (2-5 mM) occurs at a rate that is similar to the rate of glucose oxidation at its basal, nonstimulatory concentration (3 mM). We also investigated the possibility that glycerol may signal via expansion of the glycerol phosphate pool to allow enhanced fatty acid esterification and formation of complex lipids. Addition of Triacsin-C, an inhibitor of long-chain acyl-CoA synthetase, to AdCMV-GlpK-treated INS-1 cells did not inhibit glycerol-stimulated insulin secretion despite the fact that it blocked glycerol incorporation into cellular lipids. We conclude from these studies that glycerol kinase expression is sufficient to activate glycerol signaling in beta cells, showing that the failure of normal islets to respond to this substrate is due to a lack of this enzyme activity. Further, our studies show that glycerol signaling is not linked to esterification or oxidation of the substrate, but is likely mediated by its metabolism in the glycerol phosphate shuttle and/or the distal portion of the glycolytic pathway, either of which can lead to production of ATP and an increased ATP:ADP ratio.
Activation of complement system by porins extracted from Salmonella typhimurium (1984)

The effect of porins purified from Salmonella typhimurium on the complement system was investigated both in vitro and in vivo. Incubation of porins with either human or guinea pig serum resulted in the consumption of the total complement activity when an amount of porins ranging from 8 to 10 micrograms per 100 microliters of serum was used. The activation of the complement system was temperature dependent, suggesting an active process rather than passive adsorption of the complement components by porins. In addition, the activation had a fast kinetic and proceeded mainly through the classical pathway. This conclusion is supported by the consumption of C1s and C4 in normal human serum treated with porins and also by the depletion of C3 activity in the C1s-deficient serum which was marked only when purified C1s was added to the serum before incubation with porins. Injection of 100 micrograms of porins into guinea pigs induced profound complement consumption at 6 h postinjection that persisted up to 12 h. We conclude from this study that porins can effectively contribute to complement activation and to subsequent biological events induced by gram-negative bacteria.
Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses (2010)

The propensity of helminths, such as schistosomes, to immunomodulate the host's immune system is an essential aspect of their survival. Previous research has demonstrated how soluble schistosomal egg antigens (SEA) dampen TLR-signaling during innate immune responses. We show here that the suppressive effect by SEA on TLR signaling is simultaneously coupled to the activation of the Nlrp3 (NLR family, pyrin domain containing 3) inflammasome and thus IL-1β production. Therefore, the responsible protein component of SEA contains the second signal that is required to trigger proteolytic pro-IL-1β processing. Moreover, the SEA component binds to the Dectin-2/FcRγ (Fc receptor γ chain) complex and activates the Syk kinase signaling pathway to induce reactive oxygen species and potassium efflux. As IL-1β has been shown to be an essential orchestrator against several pathogens we studied the in vivo consequences of Schistosoma mansoni infection in mice deficient in the central inflammasome adapter ASC and Nlrp3 molecule. These mice failed to induce local IL-1β levels in the liver and showed decreased immunopathology. Interestingly, antigen-specific Th1, Th2, and Th17 responses were down-regulated. Overall, these data imply that component(s) within SEA induce IL-1β production and unravel a crucial role of Nlrp3 during S. mansoni infection.
Transforming growth factor-β enhances fracture healing in rabbit tibiae (1993)

The ability of exogenous Transforming Growth Factor-beta (TGF-beta) to stimulate bone formation in fracture healing was investigated. TGF-beta was continuously applied in doses of 1 and 10 micrograms/day for 6 weeks to 2 groups of adult rabbits with unilateral plated mid-tibial osteotomies. A group receiving solvent without TGF-beta served as control. Fracture healing was evaluated by mechanical tests, bone morphometry and bone densitometry. Increased maximal bending strength and callus formation were demonstrated in the groups receiving TGF-beta. TGF-beta had no effect on bending-stiffness, bone mineral content, cortical thickness or haversian canal diameter. We conclude that local application of exogenous TGF-beta may enhance fracture healing in rabbits.
Induction of Long-Term Memory CD8+T Cells for Recall of Viral Clearing Responses against Influenza Virus (2002)

Induction of cytotoxic T-cell-mediated virus-clearing responses by influenza virus T cell determinant-containing peptide immunogens was examined. The most potent synthetic immunogens for eliciting pulmonary viral-clearing responses contained peptides representing determinants for CD4 and CD8 T cells (TH and CTL peptides, respectively) together with two or four palmitic acid (Pal) groups. Inoculated in adjuvant, these Pal2- or Pal4-CTL-TH lipopeptides and the nonlipidated CTL peptide induced equivalent levels of cytolytic activity in the primary effector phase of the response. The ability to recall lytic responses, however, diminished much more rapidly in CTL peptide-primed than in lipopeptide-primed mice. By 15 months postpriming, the recalled lytic activity in lipopeptide-inoculated mice remained potent, but the response induced by the CTL peptide was weak. Enumeration of specific gamma interferon-secreting CD8 T cells revealed that a greater number of these T cells had entered or remained in the memory pool in lipopeptide-primed mice, arguing for a quantitative rather than qualitative enhancement of the response on recall. Addition of either the lipid or the TH peptide to the CTL peptide was not sufficient to provide these long-lived antiviral responses, but inclusion of both components augmented the response. CD4 T cells elicited by the lipopeptides did not influence the rate of viral clearance upon challenge and most likely had a role in induction or maintenance of the memory response. It therefore appears that the lipopeptide immunogens, although not significantly superior at inducing primary effector CD8 T cells, elicit a much more effective memory population, the recall of which may account for their superiority in inducing pulmonary protection after viral challenge.
Physics of polypeptide multilayer films (2006)

Polypeptide multilayer films are promising for the development of coatings for implant devices, biosensors, and artificial cells. This paper discusses aspects of the physics of these films. Three sub-topics in the physics of peptide adsorption in multilayer film assembly covered here are peptide structure at the film/solid support interface, adsorbed layer thickness, and dynamics of peptide adsorption. A synopsis of work in these areas is preceded by an introduction to the subject and a review of some aspects of polymer theory.
Simultaneous Measurement of Soil Penetration Resistance and Water Content with a Combined Penetrometer–TDR Moisture Probe (2001)

Soil mechanical impedance affects root growth and water flow, and controls nutrient and contaminant transport below the rooting zone. Among the soil parameters affecting soil strength, soil water content and bulk density are the most significant. However, field water content changes both spatially and temporally, limiting the application of cone penetrometers as an indicator of soil strength. Considering the presence of large water content variations within a soil profile and across a field and the large influence of water content on soil strength, there is need for a combined penetrometer–moisture probe to provide simultaneous field water content and soil resistance measurements. Such a probe was developed, which uses the time domain reflectometry (TDR) technique to determine water content and its influence on soil penetration resistance. The coiled TDR moisture probe consists of two parallel copper wires, each 0.8 mm in diameter and 30 cm long, coiled around a 5‐cm‐long polyvinyl chloride (PVC) core with a 3‐mm separation between wires. Calibration curves relating the soil bulk dielectric constant measured by the coiled probe to water content were obtained in the laboratory for a Columbia fine sand loam (coarse‐loamy, mixed, superactive, nonacid, thermic Oxyaquic Xerofluvent), a Yolo silt clay loam (fine‐silty, mixed, nonacid, thermic Typic Xerorthent), and washed sand, and data were analyzed based on a mixing model approach. Subsequently, field experiments were conducted to measure simultaneously the penetration resistance (PR) and water content along a soil profile. Results showed a detailed water content profile with excellent correlation with the gravimetric method, whereas the depth distribution of PR was similar to that of dry bulk density as determined from soil cores.
Effects of traps on charge storage characteristics in metal-oxide-semiconductor memory structures based on silicon nanocrystals (1998)

Charge storage characteristics have been investigated in metal-oxide-semiconductor memory structures based on silicon nanocrystals, where various interface traps and defects were introduced by thermal annealing treatment. The observations demonstrate that traps have strong influence on the charge storage behavior, in which the traps and defects at the internal/surface of silicon nanocrystals and the interface states at the SiO2/Si substrate play different roles, respectively. It is suggested that the injected charges are mainly stored at the deep traps of nanocrystals instead of the conduction band in long-term retention mode. The long-term charge-loss process is dominantly determined by the direct tunneling of the trapped charges to the interface states in the present experiment. An optimum way to improve the retention time would be to introduce a certain number of deep trapping centers in nanocrystals and to decrease the interface states at SiO2/Si substrate.
.mu.-Conotoxin GIIIA, a peptide ligand for muscle sodium channels: chemical synthesis, radiolabeling and receptor characterization (1989)

The peptide conotoxin GIIIA from Conus geographus L. venom, which specifically blocks sodium channels in muscle, has been synthesized by a solid-phase method. The three disulfide bridges were formed by air oxidation. After HPLC purification, the synthetic product was shown to be identical with the native conotoxin GIIIA from Conus geographus. A high specific activity, 125I derivative of mu-conotoxin was prepared and used for binding assays to the Na channel from Electrophorus electric organ. Specific binding could be abolished by competition with tetrodotoxin. The radiolabeled toxin was specifically cross-linked to the Na channel. These studies demonstrate that mu-conotoxin GIIIA can be used to define the guanidinium toxin binding site and will be a useful ligand for understanding functionally important differences between Na channel subtypes.
Using particles to sample and control implicit surfaces (2005)

We present a new particle-based approach to sampling and controlling implicit surfaces. A simple constraint locks a set of particles onto a surface while the particles and the surface move. We use the constraint to make surfaces follow particles, and to make particles follow surfaces. We implement control points for direct manipulation by specifying particle motions, then solving for surface motion that maintains the constraint. For sampling and rendering, we run the constraint in the other direction, creating floater particles that roam freely over the surface. Local repulsion is used to make floaters spread evenly across the surface. By varying the radius of repulsion adaptively, and fissioning or killing particles based on the local density, we can achieve good sampling distributions very rapidly, and maintain them even in the face of rapid and extreme deformations and changes in surface topology.