gebhart/patrepeval huggingface dataset:
Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. (1984)

Bacteriophage P1 encodes a site-specific recombination system that consists of a site (loxP) at which recombination occurs and a gene, cre, whose protein product is essential for recombination. The loxP-Cre recombination event can be studied in greater detail by the use of an in vitro system that efficiently carries out recombination between two loxP sites. This paper presents a purification and characterization of the Cre protein (Mr = 35,000), which is the only protein required for the in vitro reaction. No high energy cofactors are needed. The purified Cre protein binds to loxP-containing DNA and makes complexes that are resistant to heparin. Cre efficiently converts 70% of the DNA substrate to products and appears to act stoichiometrically. The action of Cre on a loxP2 supercoiled substrate containing two directly repeated loxP sites results in product molecules that are topologically unlinked. Several models to account for the ability of Cre to produce free supercoiled products are discussed.
In Vitro and In Situ Expression of IL-23 by Keratinocytes in Healthy Skin and Psoriasis Lesions: Enhanced Expression in Psoriatic Skin (2006)

Keratinocytes contribute to cutaneous immune responses through the expression of cytokines. We investigated whether human keratinocytes can express IL-23, a newly defined IFN-gamma-inducing cytokine composed of a unique p19 subunit and a p40 subunit shared with IL-12. Cultured keratinocytes from normal and lesional psoriatic skin were found to express constitutively mRNA for both subunits of IL-23. Low but significant levels of the heterodimeric IL-23 protein could be detected in cell lysates and supernatants from stimulated keratinocytes by immunoblotting and ELISA. Functional analysis showed that these low levels of keratinocyte-derived IL-23 were sufficient to enhance the IFN-gamma production by memory T cells. Immunostaining of skin sections confirmed expression of both subunits of IL-23 by keratinocytes in situ and also revealed expression of this cytokine in the dermal compartment. IL-23 expression was significantly higher in psoriatic lesional skin, compared with normal and psoriatic nonlesional skin. The immunostained preparations of cultured cells and IL-23 levels in culture supernatants did not show any difference between normal and psoriatic keratinocytes indicating no intrinsic aberration of IL-23 expression in keratinocytes from psoriatic skin. Double staining of cytospin preparations demonstrated that IL-23 p19 is also expressed by epidermal Langerhans cells, dermal dendritic cells, and macrophages. Psoriasis is a chronic inflammatory skin disease mediated by IFN-gamma-expressing type 1 memory T cells. As IL-23 is important to activate memory T cells to produce IFN-gamma, its augmented expression of IL-23 by keratinocytes and cutaneous APC may contribute to the perpetuation of the inflammation process in this disease.
Wet-chemical approach for the cell-adhesive modification of polytetrafluoroethylene (2011)

Polytetrafluoroethylene (PTFE), a frequently utilized polymer for the fabrication of synthetic vascular grafts, was surface-modified by means of a wet-chemical process. The inherently non-cell-adhesive polymer does not support cellular attachment, a prerequisite for the endothelialization of luminal surface grafts in small diameter applications. To impart the material with cell-adhesive properties a treatment with sodium-naphthalene provided a basis for the subsequent immobilization of the adhesion promoting RGD-peptide using a hydroxy- and amine-reactive crosslinker. Successful conjugation was shown with cell culture experiments which demonstrated excellent endothelial cell growth on the modified surfaces.
The Tricarboxylic Acid Cycle in Cyanobacteria (2011)

It is generally accepted that cyanobacteria have an incomplete tricarboxylic acid (TCA) cycle because they lack 2-oxoglutarate dehydrogenase and thus cannot convert 2-oxoglutarate to succinyl-coenzyme A (CoA). Genes encoding a novel 2-oxoglutarate decarboxylase and succinic semialdehyde dehydrogenase were identified in the cyanobacterium Synechococcus sp. PCC 7002. Together, these two enzymes convert 2-oxoglutarate to succinate and thus functionally replace 2-oxoglutarate dehydrogenase and succinyl-CoA synthetase. These genes are present in all cyanobacterial genomes except those of Prochlorococcus and marine Synechococcus species. Closely related genes occur in the genomes of some methanogens and other anaerobic bacteria, which are also thought to have incomplete TCA cycles.
Targeting CAL as a Negative Regulator of ΔF508-CFTR Cell-Surface Expression (2006)

PDZ domains are ubiquitous peptide-binding modules that mediate protein-protein interactions in a wide variety of intracellular trafficking and localization processes. These include the pathways that regulate the membrane trafficking and endocytic recycling of the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel mutated in patients with cystic fibrosis. Correspondingly, a number of PDZ proteins have now been identified that directly or indirectly interact with the C terminus of CFTR. One of these is CAL, whose overexpression in heterologous cells directs the lysosomal degradation of WT-CFTR in a dose-dependent fashion and reduces the amount of CFTR found at the cell surface. Here, we show that RNA interference targeting endogenous CAL specifically increases cell-surface expression of the disease-associated DeltaF508-CFTR mutant and thus enhances transepithelial chloride currents in a polarized human patient bronchial epithelial cell line. We have reconstituted the CAL-CFTR interaction in vitro from purified components, demonstrating for the first time that the binding is direct and allowing us to characterize its components biochemically and biophysically. To test the hypothesis that inhibition of the binding site could also reverse CAL-mediated suppression of CFTR, a three-dimensional homology model of the CAL.CFTR complex was constructed and used to generate a CAL mutant whose binding pocket is correctly folded but has lost its ability to bind CFTR. Although produced at the same levels as wild-type protein, the mutant does not affect CFTR expression levels. Taken together, our data establish CAL as a candidate therapeutic target for correction of post-maturational trafficking defects in cystic fibrosis.
Design of Orally Active Iron Chelators (1996)

Three parameters which are critical for the development of non-toxic orally active iron chelators are identified: bioavailability, selectivity for iron (III) and distribution and toxicity. Each is discussed in detail. Arguments are presented for the use of bi- and tridentate ligands as opposed to hexadentate ligands. The discussion leads to the identification of 3-hydroxpyridin-4-ones as compounds with a unique potential for iron chelation under clinical conditions. The prodrug concept utilising efficient liver first-pass kinetics is introduced.
Cross Domain Automatic Transcription on the TC-STAR EPPS Corpus (2006)

This paper describes the ongoing development of the British English European Parliament Plenary Session corpus. This corpus will be part of the speech-to-speech translation evaluation infrastructure of the European TC-STAR project. Furthermore, we present first recognition results on the English speech recordings. The transcription system has been derived from an older speech recognition system built for the North-American broadcast news task. We report on the measures taken for rapid cross-domain porting and present encouraging results.
A discharge scoring system for patients with total hip replacement (1997)

Total hip replacement is a common and expensive procedure. Any attempt to shorten the length of hospital stay safely is desirable. Proposes a scoring system specifically designed for this patient population, to determine the optimal timing of safe discharge and postacute care placement. Discusses its implications for the quality of patient care.
L and E Selectins in Acute Myeloid Leukemia: Expression, Clinical Relevance and Relation to Patient Outcome (2002)

(1) AML blast cell express and release sL selectins but not sE selectin, (2) sE and sL selectins and cellular L selectin may be useful prognostic markers in evaluating AML patients at diagnosis.
Research and developments of software-defined radio technologies in Japan (2001)

Software-defined radio technologies are attractive for future mobile communication systems because of reconfigurable and multimode operation capabilities. The reconfigurable feature is useful for enhancing functions of equipment without replacing hardware. Multimode operation is essential for future wireless terminals because a number of wireless communication standards will still coexist. Research efforts on SDR have become very active in Japan, and various kinds of SDR prototypes have been developed. This article introduces the trends of Japanese wireless communication systems and the role of SDR technologies for the future wireless systems. R&D activities for the SDR in the field of academia and industry are also presented including examples of SDR prototypes.
Induction of differentiation of human promyelocytic leukemia cells (HL60) by metabolites of hexamethylene bisacetamide. (1988)

We studied the ability of five metabolites of hexamethylene bisacetamide (HMBA), which we had previously identified in patient urine, to induce differentiation or to influence differentiation induced by HMBA of a human promyelocytic cell line. Differentiation of HL60 cells was quantified by morphological changes and by the ability to reduce nitroblue tetrazolium. N-Acetyl-1,6-diaminohexane (NADAH), the deacetylated, first metabolite of HMBA, was a more potent inducer of HL60 differentiation than was HMBA. NADAH produced 20-30% differentiation at 0.25 mM and 30-40% differentiation at 0.5 mM. NADAH (1 mM) induced 2-3-fold more differentiation than did 1 mM HMBA. HL60 differentiation, induced by various combinations of HMBA and NADAH, reflected a combined effect of the two compounds. In contrast, 1,6-diaminohexane, at 0.5-5 mM, failed to induce HL60 differentiation. Similarly, 0.5-5 mM 6-acetamidohexanoic acid, the major metabolite of HMBA, and 6-aminohexanoic acid failed to induce differentiation of HL60 cells. However, 6-acetamidohexanoic acid, when combined with HMBA or NADAH at various concentrations and ratios, enhanced the differentiation of HL60 cells induced by these two compounds. This enhancement was most apparent with addition of 0.50-3.0 mM 6-acetamidohexanoic acid to HL60 cells incubated with 1.0-3.0 mM HMBA or 0.25-1.0 mM NADAH. 6-Aminohexanoic acid similarly enhanced HMBA-induced differentiation of HL60 cells. These in vitro results have implications in terms of the clinical application of HMBA and interpretation of the results of clinical trials performed to date and may provide some insight into the mechanism of HMBA-induced cellular differentiation.
Peptidic phosphonylating agents as irreversible inhibitors of serine proteases and models of the tetrahedral intermediates (1991)

Peptide analogues incorporating an electrophilic phosphorus moiety (2-6) have been synthesized and studied as inhibitors of a variety of serine proteases. Inhibition is irreversible and, for alpha-lytic protease (ALP), shown to result from covalent binding to the active site serine hydroxyl [Bone, R., Sampson, N. S., Bartlett, P.A., & Agard, D. A. (1991) Biochemistry (following paper in this issue)]. For reaction of human leukocyte elastase (HLE) with the thiophenyl esters 6s-V (Boc-AAPV psi [P = O(SPh)O]AA-OMe), 4s-V (BocAAPV psi [P = O(SPh)O]-Me), and 3s-V (Boc-V psi [P = O(SPh)O]AA-OMe), evidence is presented to suggest that the S4-S1 subsites, but not the S1' and S2' positions, are occupied by the inhibitors during the inactivation process. The selectivity that is observed between the proteases and the hexapeptide phosphonates 6o-V (Boc-AAPV psi [P = O(OPh)O]AA-OMe) and 6o-F (Boc-AAPF psi [P = O(OPh)O]AA-OMe) parallels that between these enzymes and their substrates: ALP and HLE are selectively inactivated by the ValP-containing analogue 6o-V, while subtilisin (SUB) shows a preference for the PheP derivative 6o-F. A detailed kinetic analysis of the enzyme-inhibitor interactions was complicated by the susceptibility of the inhibitors to enzymatic degradation. The configuration at phosphorus was found not to have a significant influence on the rate at which the inhibitors react with the peptidases. Moreover, in the case of inactivation of ALP by the hexapeptide 6o-V, the same covalent adduct is formed from both stereoisomers (Bone et al., 1991), indicating that one of these diastereomers undergoes substitution with retention of configuration.
Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 (2020)

Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV-host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the "<i>Complementary Exposure</i>" pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.
Physiopathology and Regulation of Factor XIII (2001)

Factor XIII is a plasma transglutaminase. Transglutaminases are at least 8 enzymes which cross-link a number of proteins. This type of reaction not only enhances the original functions of substrate proteins, but also adds new functions to them. Factor XIII in plasma is a tetramer (A2B2), and the A subunit contains the active site. Although transglutaminases are homologous, the nucleotide sequences in their 5'-flanking region differ significantly. Accordingly, transcription factors play a major role in the cell type-specific expression of each transglutaminase. A variety of missense and nonsense mutations, and deletions/insertions with or without out-of-frame shift/premature termination and splicing abnormalities have been identified in the genes for A and B subunits in factor XIII deficiency. In some cases, the mRNA level of the A or B subunit was severely reduced. Molecular and cellular bases have also been explored by expression experiments and by molecular modeling. In most cases, impaired folding and/or conformational change of the mutant A or B subunit leads to both intra- and extra-cellular instability, which is responsible for factor XIII deficiency.
Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update (2017)

Although survival of multiple myeloma patients has at least doubled during recent years, most patients eventually relapse, and treatment at this stage may be particularly complex. At the time of relapse, the use of alternative drugs to those given upfront is current practice. However, many new options are currently available for the treatment of relapsed multiple myeloma, including recently approved drugs, such as the second- and third-generation proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal antibodies daratumumab and elotuzumab and the histone deacetylase inhibitor panobinostat, but also new targeted agents are under active investigation (e.g. signal transduction modulators, kinesin spindle protein inhibitors, and inhibitors of NF-kB, MAPK, AKT). We here describe a new paradigm for the treatment of relapsed multiple myeloma. The final goal should be finding a balance among efficacy, toxicity, and cost and, at the end of the road, achieving long-lasting control of the disease and eventually even cure in a subset of patients.
Polymers as Surface-Based Tethers with Photolytic Triggers Enabling Laser-Induced Release/Desorption of Covalently Bound Molecules (1996)

A novel design for surface-based macromolecular docking and release is presented together with a strategy to improve and extend biopolymer structure determination capabilities. Polymeric surfaces with arrays of tethers for covalent molecular attachment were designed with photolytic triggers to enable spatially defined, laser-induced uncoupling/desorption of the tethered molecules. Upon photolytic cleavage, a defined portion of the tether ("tail") remains attached to the biomolecule as a probe. Chemically defined memory, determined by the number of reporter tails, reflects the biomolecule interaction with tether-probe devices encountered (i.e., footprint) on the probe surface. To demonstrate function, a surface of poly(4-vinylpyridine) was extended through the pyridinium nitrogens with spacer arms (-N-ethylsuccinamyl-) producing photolytic pyridinium nitrogen bonds. The photolabile tether was terminated with leaving groups (N-hydroxysulfosuccinimide) for covalent attachment of biopolymers. An 18-residue peptide (N terminus of human beta-casein) was covalently docked to these tether-probes, irradiated with coherent UV light, and released with two reporter tails of a mass predicted by tether formation at the two primary amine groups and subsequent photolytic cleavage at the intended site. This is the first demonstration of polymeric surface structure enabling the covalent docking and laser-induced uncoupling/desorption of intact macromolecules through the use of photolytic tethers. Surface-based tether-probe devices, operated by coherent light, should advance our ability to explore covalent modifications in biopolymer structure and alterations in conformation, generated either in advance of tethering or through chemical/enzymatic manipulations performed directly in situ.
Vaccine T-cell epitope selection by a peptide competition assay. (1989)

The binding of several peptides derived from the Plasmodium falciparum circumsporozoite protein (CS protein) to the human major histocompatibility complex class II proteins HLA-DR5 and -DRw6 was examined in a competition assay. Fixed antigen-presenting cells (APCs) were incubated with various concentrations of each peptide and suboptimal concentrations of stimulator peptides. The binding of the CS peptides to DR5 or DRw6 proteins was then determined in a proliferation assay using two established DR5 or DRw6-restricted T-cell clones with specificity for the stimulator peptides as responder cells. One of five CS peptides, comprising together about 50% of the CS protein sequence, was found to compete with the binding of the stimulator peptides to DR5 and DRw6. The CS peptide CS-(378-398), binding to DR5 and DRw6, was then shown to be able to induce primary in vitro responses of T cells from donors with DR5 and DRw6 haplotypes. CS-(378-398)-induced T-cell clones responded not only to the homologous peptide but also to the native CS protein in the presence of appropriate APCs. The strategy we have applied is of considerable general interest for the engineering of vaccines against any pathogen, since it greatly facilitates the selection of appropriate T-cell epitopes to be incorporated in the vaccine.
White lighting for residential applications (2012)

The lighting industry relies on colour-rendering index (CRI) and correlated colour temperature (CCT) to communicate the colour properties of light sources. While advances have been made in recent years to develop new metrics for colour rendering, not much attention has been given to the validity or utility of CCT for communicating the appearance of illumination. Recently, it was shown that a wide range of chromaticities can appear ‘white’ or with minimal perceived ‘tint’. Importantly, these chromaticities do not follow the line of blackbody radiation, the reference for CCT. The present study builds on this previous research to determine whether ‘white’ illumination is preferred in simulated residential applications. Results presented here support the hypothesis that people prefer ‘white’ or minimally ‘tinted’ sources of illumination.
Loop thermosyphons for cooling of electronics (2003)

Recent innovations to loop thermosyphon (LTS) design are anticipated to have a significant impact on electronics thermal solutions. Future electronics systems including high-density desktop computers, multi-processor rack mounted servers, and telecommunications cabinets are reaching volumetric thermal densities beyond the limits of direct air-cooling. Therefore, alternative cooling solutions need to be developed, for example, using loop thermosyphons. This paper presents experimental data obtained on two innovative loop thermosyphons with capillary structures that are prime candidates for electronics cooling solutions to replace typical air-cooled systems, where commercially available heat pipes cannot be used due to the high power and transport length limitations. The performance characteristics of the two loop thermosyphons with capillary structures are discussed: (a) with a horizontal square U-tube evaporator and (b) with horizontal transport lines and a flat evaporator heated from both sides.
A screen for genes that suppress loss of contact inhibition: Identification of ING4 as a candidate tumor suppressor gene in human cancer (2004)

We have devised a screen for genes that suppress the loss of contact inhibition elicited by overexpression of the protooncogene MYCN. The initial application of this screen detected nine distinctive suppressors within a representative human cDNA library. One of these genes was ING4, a potential tumor suppressor gene that maps to human chromosome 12p13. Ectopic expression of ING4 suppressed the loss of contact inhibition elicited by either MYCN or MYC but had no direct effect on cellular proliferation. Pursuing the possibility that ING4 might be a tumor suppressor gene, we found inactivating mutations in ING4 transcripts from various human cancer cell lines. In addition, we used comparative genomic hybridization to detect deletion of the ING4 locus in 10-20% of human breast cancer cell lines and primary breast tumors. Ectopic expression of ING4 attenuated the growth of T47D human breast cancer cells in soft agar. We conclude that ING4 is a strong candidate as a tumor suppressor gene.
In Vitro Construction of Urinary Bladder Wall using Porcine Primary Cells Reseeded on Acellularized Bladder Matrix and Small Intestinal Submucosa (2003)

Our results document successful generation of tissue engineered urinary bladder wall, which can be used in further large animal transplantation experiments.