gebhart/patrepeval huggingface dataset:
The N-terminal Domain of Rat Liver Carnitine Palmitoyltransferase 1 Contains an Internal Mitochondrial Import Signal and Residues Essential for Folding of Its C-terminal Catalytic Domain (2001)

We have previously shown that the first 147 N-terminal residues of the rat liver carnitine palmitoyltransferase 1 (CPT1), encompassing its two transmembrane (TM) segments, specify both mitochondrial targeting and anchorage at the outer mitochondrial membrane (OMM). In the present study, we have identified the precise import sequence in this polytopic OMM protein. In vitro import studies with fusion and deletion CPT1 proteins demonstrated that none of its TM segments behave as a signal anchor sequence. Analysis of the regions flanking the TM segments revealed that residues 123-147, located immediately downstream of TM2, function as a noncleavable, matrix-targeting signal. They specify mitochondrial targeting, whereas the hydrophobic TM segment(s) acts as a stop-transfer sequence that stops and anchors the translocating CPT1 into the OMM. Heterologous expression in Saccharomyces cerevisiae of several deleted CPT1 proteins not only confirms the validity of the "stop-transfer" import model but also indicates that residues 1-82 of CPT1 contain a putative microsomal targeting signal whose cellular significance awaits further investigation. Finally, we identified a highly folded core within the C-terminal domain of CPT1 that is hidden in the entire protein by its cytosolic N-terminal residues. Functional analysis of the deleted CPT1 proteins indicates that this folded C-terminal core, which may belong to the catalytic domain of CPT1, requires TM2 for its correct folding achievement and is in close proximity to residues 1-47.
Vault Nanoparticles Containing an Adenovirus-Derived Membrane Lytic Protein Facilitate Toxin and Gene Transfer (2009)

Nonviral methods of gene delivery possess several advantages over that of viral-based vectors, including having increased safety. However, the ability to achieve effective transport of therapeutic molecules across host cell membranes via nonviral methods remains a significant goal. Cell-derived nanoparticles known as vaults have been proposed as novel candidate transfer vehicles for various foreign molecules. Recombinant vault particles enter cells via macropinocytosis or phagocytosis but lack demonstrable membrane penetrating activity. To explore the feasibility of improving vault penetration into target cells, we incorporated the membrane lytic domain of adenovirus protein VI (pVI) into the interior of recombinant vault particles via fusion to the vault poly(ADP-ribose) polymerase (VPARP) interaction domain. The membrane lytic activity of the pVI domain was retained upon incorporation into vault particles. Moreover, internalization of vault-pVI complexes into murine macrophages promoted co-delivery of a soluble ribotoxin or a cDNA plasmid encoding GFP. These findings indicate that vault particles can be modified to enhance cell transfer of selected biomolecules.
Ventilation control for airborne transmission of human exhaled bio-aerosols in buildings (2018)

The emergence of respiratory diseases, i.e., severe acute respiratory syndrome (SARS) epidemic in 2003, H1N1 influenza epidemic in 2011 and Middle East respiratory syndrome (MERS) outbreak, reiterated the significance of ventilation in buildings. The role of ventilation in removing exhaled airborne bio-aerosols and preventing cross infections has been multidisciplinary extensively studied after the SARS outbreak in 2003. The characteristics of droplet-borne, short-range airborne and long-range airborne transmission of infectious diseases were identified. Increasing ventilation rate can effectively reduce the risk of long-range airborne transmission, while it may be of little useful in preventing the droplet-borne transmission. To maintain the airflow direction from clean cubicles to dirty cubicles is an effective way to prevent the cross infection between cubicles, which is widely used in hospital isolation rooms. Field measurements showed that wrong air flow direction was due to poor construction quality or maintenance. The impacts of different airflow patterns on removing large droplets and fine droplet nuclei were discussed. Some new concepts in general ventilation systems and local personalized equipment were also introduced. This review updates current knowledge of the airborne transmission of pathogens and the improvement of ventilation efficiency concerning the infection prevention.
Discovery of Soybean Aphid Biotypes (2008)

The soybean aphid [ Aphis glycines Matsumura (Hemiptera: Aphididae)] is an invasive insect pest of soybean [ Glycine max (L.) Merr.] that was first reported in North America in 2000. There are currently no reports of soybean aphid biotype diversity and this information is needed before aphid resistance genes are deployed. The objective of this research was to test for aphid biotype variation. The response of two A. glycines isolates, one collected in Ohio and the other in Illinois, were compared by infesting eight soybean genotypes in nonchoice tests. The same genotypes also were tested with the Ohio isolate using a choice test. In the nonchoice test, there was a significant ( P &lt; 0.0001) effect of aphid isolate, genotype, and a significant aphid isolate by soybean genotype interaction for the number of aphids per plant 10 and 15 d after infestation. The responses of the eight genotypes to the Ohio isolate in the choice test were similar to their responses in nonchoice tests. PI 200538 and PI 567597C were resistant to both the Ohio and Illinois isolates and will be useful sources of resistance to both isolates. These tests confirm that there are at least two distinct biotypes of A. glycines in North America.
Alteration of the Amount of the Chloroplast Phosphate Translocator in Transgenic Tobacco Affects the Distribution of Assimilate between Starch and Sugar (1994)

Tobacco plants (Nicotiana tabacum L.) transformed with sense and antisense constructs of a cDNA encoding the tobacco phosphate-triose phosphate-3-phosphoglycerate translocator (phosphate translocator) were shown to contain altered amounts of phosphate translocator mRNA and protein. Phosphate translocator activity in intact chloroplasts isolated from transformed plants showed a 15-fold variation, from 20% of the wild-type activity in antisense transformants to 300% of the wild-type activity in sense transformants. However, the maximal rates of photosynthesis and the rates of photosynthetic carbon assimilation in ambient CO2 showed no consistent differences between transformants. Starch content was decreased by 20% and total soluble sugars were increased by 20% in leaves of antisense transformants compared to sense transformants. The 40% decrease in the ratio of starch to total soluble sugars in antisense transformants relative to sense transformants indicates that distribution of assimilate between starch and sugar had been altered. However, the amount of sucrose in the leaves was unchanged. The changes in total soluble sugars were accounted for completely by changes in glucose and fructose, suggesting the existence of a homeostatic mechanism for maintaining sucrose concentrations in the leaves at the expense of glucose and fructose.
SELF-SPLICING OF GROUP I INTRONS (1990)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Regulation of transcription by cyclic AMP-dependent protein kinase. (1989)

cAMP-dependent protein kinase (PKA; ATP: protein phosphotransferase; EC 2.7.1.37) appears to be the major mediator of cAMP responses in mammalian cells. We have investigated the role of PKA subunits in the regulation of specific genes in response to cAMP by cotransfection of wild-type or mutant subunits of PKA together with cAMP-inducible reporter genes. Overexpression of catalytic subunit induced expression from three cAMP-regulated promoters (alpha-subunit, c-fos, E1A) in the absence of elevated levels of cAMP but did not affect expression from two unregulated promoters (Rous sarcoma virus, simian virus 40). Cotransfection of a regulatory subunit gene containing mutations in both cAMP binding sites strongly repressed both basal and induced expression from the cAMP-responsive alpha-subunit promoter without affecting expression from the Rous sarcoma virus promoter. These experiments indicate that cAMP induces gene expression through phosphorylation by the catalytic subunit and that the ambient degree of phosphorylation dictates the level of basal as well as induced expression of the cAMP-regulated alpha-subunit gene.
Chemical Mechanical Polishing of Exfoliated III-V Layers (2008)

The chemical mechanical polishing of III-V materials including GaAs, InP, InAs, and GaSb is investigated with sodium hypochlorite and citric acid solutions. It is found that the surfaces can be polished to below 0.5 nm RMS surface roughness without the induction of crystalline damage using similar abrasive-free polishing solutions for all the materials with controlled polishing rates of 10 nm / min which is important for touch polishing of exfoliated III-V layers. The optimal composition of the slurry is adjusted for the particular material. A balance between reduced sub-surface mechanical damage and smooth surface morphology is obtained by adjusting the amount of citric acid. However, the damage-free planarization in these cases may be aided by an oxide formation as predicted by Pourbaix diagrams. Additionally, triple axis x-ray diffraction is found to be an extremely sensitive, non-destructive method for evaluating damage induced by the CMP process.
Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates? (2016)

Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted.
Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity (2011)

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). Posttransplant immunosuppressive drugs incompletely control GVHD and increase susceptibility to opportunistic infections. In this study, we used flagellin, a TLR5 agonist protein (∼50 kDa) extracted from bacterial flagella, as a novel experimental treatment strategy to reduce both acute and chronic GVHD in allogeneic HSCT recipients. On the basis of the radioprotective effects of flagellin, we hypothesized that flagellin could ameliorate GVHD in lethally irradiated murine models of allogeneic HSCT. Two doses of highly purified flagellin (administered 3 h before irradiation and 24 h after HSCT) reduced GVHD and led to better survival in both H-2(b) → CB6F1 and H-2(K) → B6 allogeneic HSCT models while preserving >99% donor T cell chimerism. Flagellin treatment preserved long-term posttransplant immune reconstitution characterized by more donor thymic-derived CD4(+)CD25(+)Foxp3(+) regulatory T cells and significantly enhanced antiviral immunity after murine CMV infection. The proliferation index and activation status of donor spleen-derived T cells and serum concentration of proinflammatory cytokines in flagellin-treated recipients were reduced significantly within 4 d posttransplant compared with those of the PBS-treated control recipients. Allogeneic transplantation of radiation chimeras previously engrafted with TLR5 knockout hematopoietic cells showed that interactions between flagellin and TLR5 expressed on both donor hematopoietic and host nonhematopoietic cells were required to reduce GVHD. Thus, the peritransplant administration of flagellin is a novel therapeutic approach to control GVHD while preserving posttransplant donor immunity.
124I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of 131I-L19-SIP radioimmunotherapy (2009)

(124)I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with (124)I-L19-SIP appeared qualified for sensitive imaging of tumour neovasculature and for predicting (131)I-L19-SIP biodistribution.
KLP38B: A Mitotic Kinesin-related Protein That Binds PP1 (1997)

We have identified a new member of the kinesin superfamily in Drosophila, KLP38B (kinesin-like protein at 38B). KLP38B was isolated through its two-hybrid interaction with the catalytic subunit of type 1 serine/threonine phosphoprotein phosphatase (PP1). We demonstrate that recombinant KLP38B and PP1 associate in vitro. This is the first demonstration of direct binding of a kinesin-related protein to a regulatory enzyme. Though most closely related to the Unc-104 subfamily of kinesin-related proteins, KLP38B is expressed only in proliferating cells. KLP38B mutants show cell proliferation defects in many tissues. KLP38B is required for normal chromatin condensation as embryos from KLP38B mutant mothers have undercondensed chromatin at metaphase and anaphase. This is the first time that a kinesin-related protein has been shown to have such a role. Incomplete lethality of a strong KLP38B allele suggests partial redundancy with one or more additional kinesin-related proteins.
Development of the First Optical Videodisc (1982)

The idea of recording television signals on a disc apparently originated with James Logie Baird in the early 1930's. He made several records using audio record cutting techniques. In 1961, 3M realized that the surface of a phonograph record was smooth enough and the replicated detail had enough resolution to carry full-bandwidth television signals. The company then contracted with SRI International to determine the feasibility of making television discs. After considering alternatives, SRI decided to concentrate on optical recording on high-resolution photographic plates using light from a high-pressure mercury arc. By June 1963, a number of videodiscs containing motion picture programs had been made. Working independently, 3M developed electron beam recording equipment that permitted real-time recording with improved resolution, as well as techniques for replicating videodiscs using cast plastic coatings.
Fabrication of fully embedded board-level optical interconnects and optoelectronic printed circuit boards (2009)

The manufacturing processes of an optoelectronic printed circuit board (OEPCB) with an embedded board-level polymeric waveguide and vertical-optical channel interconnection are presented in this paper. The optoelectronic packages contain one vertical cavity surface emitting laser (VCSEL), one photo detector (PD), surface mount technology (SMT) components and one fully embedded board-level optical interconnects. The first step is to fabricate a polymeric waveguide structure with two 45-degree mirrors, and then embedded the waveguide in the center with two prepreg to form a horizontal optical channel inside a printing circuit board by a two-step laminating process. The vertical-optical channel is made by a three-step process, conformal mask forming, laser ablating and copper etching. This vertical channel is connected to the mirror of the horizontal waveguide. A wide, collimated optical beam couples a package board across a narrow, long air gap and provides a large tolerance to misalignment during the SMT process. Key process steps will be discussed and X-ray images will be presented in this paper. Also, characterization measurements of the important electrical and optical parameters are discussed in this paper.
Dexterous manipulation of microparticles using Bessel-function acoustic pressure fields (2013)

We show that Bessel-function acoustic pressure fields can be used to trap and controllably position microparticles. A circular, 16-element ultrasound array generates and manipulates an acoustic field within a chamber, trapping microparticles and agglomerates. Changes in the phase of the sinusoidal signals applied to the array elements result in the movement of the Bessel-function pressure field and hence the microparticles. This demonstrates ultrasonic manipulation analogous to holographic optical tweezers. The manipulation limits of the device are explained by the existence of unwanted resonances within the manipulation chamber.
[Enhancement of reversing drug resistance of K562/A02 cells to adriamycin by ultrasound-induced cavitation]. (2008)

This study was aimed to investigate the effects of low frequency and power ultrasound combined with adriamycin on apoptosis of drug-resistant leukemia cell line K562/A02 in vitro, to find out the parameters of optimal exposure, and to explore the possible mechanism reversing drug-resistance of K562/A02 cells. The K562/A02 cells in logarithmic growth phase were used in experiments. The experiments were divided into 4 groups: group control, group adriamycin (A02) alone, group ultrasound (US) alone and group A02+US. The trypan blue dye exclusion test and MTT assay were used to determine the cell viability; Wright's staining was used to detect the apoptosis; the flow cytometry was used to analyze the drug concentration, and the scanning electron microscopy was used to observe the changes of cell surface. The results showed that the significant differences in cell viability, intracellular adriamycin concentration and changes of cell membrane were found between ultrasound-treated and untreated cells in the presence of various concentration of adriamycin. The exposure to ultrasound at 20 kHZ, 0.25 W/cm2 for 60 seconds could obviously decrease LC50 of adriamycin to K562/A02 cells, while the exposure to ultrasound at 20 kHZ, 0.05 W/cm2 for 60 seconds could kill K562/A02 cells at once. After being treated by low frequency ultrasound, the small holes with diameter about 1-2 microm in the cell surface appeared. The ultrasound increased the adriamycin concentration in the cells, accelerated the formation of apoptotic bodies, and promoted apoptosis of adriamycin-resistant cells. It is concluded that the ultrasound at optimal parameters enhances inhibitory effect of adriamycin on drug-resistant cell line, thereby reverses drug-resistance of drug-resistant cell line through sound-hole effect in tumor cells resulting from ultrasound induced cavitation.
Dyspnea scales as a measure of health-related quality of life in patients with idiopathic pulmonary fibrosis. (2002)

Dyspnea ratings correlate with HRQL measurements in IPF patients. Dyspnea scales can be used as a measure of HRQL in special circumstances.
Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model (2014)

We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (i.v.) bolus injection had no effect. The aim of the present study was to characterize whether continuous i.v. infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of i.v. S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered i.v. over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by i.v. lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by i.v. S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by i.v. S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of i.v. S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport.
Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control? (2008)

Type 2 diabetes mellitus is associated with progressive decreases in pancreatic beta-cell function. Most patients thus require increasingly intensive treatment, including oral combination therapies followed by insulin. Fear of hypoglycemia is a potential barrier to treatment adherence and glycemic control, while weight gain can exacerbate hyperglycemia or insulin resistance. Administration of insulin can roughly mimic physiologic insulin secretion but does not address underlying pathophysiology. Glucagon-like peptide 1 (GLP-1) is an incretin hormone released by the gut in response to meal intake that helps to maintain glucose homeostasis through coordinated effects on islet alpha- and beta-cells, inhibiting glucagon output, and stimulating insulin secretion in a glucose-dependent manner. Biological effects of GLP-1 include slowing gastric emptying and decreasing appetite. Incretin mimetics (GLP-1 receptor agonists with more suitable pharmacokinetic properties versus GLP-1) significantly lower hemoglobin A1c, body weight, and postprandial glucose excursions in humans and significantly improve beta-cell function in vivo (animal data). These novel incretin-based therapies offer the potential to reduce body weight or prevent weight gain, although the durability of these effects and their potential long-term benefits need to be studied further. This article reviews recent clinical trials comparing therapy with the incretin mimetic exenatide to insulin in patients with oral treatment failure, identifies factors consistent with the use of each treatment, and delineates areas for future research.