gebhart/patrepeval huggingface dataset:
Characterization of strand displacement synthesis catalyzed by bacteriophage T7 DNA polymerase. (1983)

The DNA polymerase induced after infection of Escherichia coli by bacteriophage T7 can exist in two forms. One distinguishing property of Form I, the elimination of nicks in double-stranded DNA templates, strongly suggests that this form of the polymerase catalyzes limited DNA synthesis at nicks, resulting in displacement of the downstream strand. In this paper, we document this reaction by a detailed characterization of the DNA product. DNA synthesis on circular, duplex DNA templates containing a single site-specific nick results in circular molecules bearing duplex branches. Analysis of newly synthesized DNA excised from the product shows that the majority of the branches are less than 500 base pairs in length and that they arise from a limited number of sites. The branches have fully base-paired termini but are attached by two noncomplementary DNA strands that have a combined length of less than 30 nucleotides. The product molecules are topologically constrained as a result of the duplex branch. DNA sequence analysis has provided an unequivocal structure of one such product molecule. We conclude that strand displacement synthesis catalyzed by Form I of T7 DNA polymerase is terminated by a template-switching reaction. We propose two distinct models for template-switching that we call primer relocation and rotational strand exchange. Strand displacement synthesis catalyzed by Form I of T7 DNA polymerase effectively converts T7 DNA circles that are held together by hydrogen bonds in their 160-nucleotide-long terminal redundancy to T7-length linear molecules. We suggest that strand displacement synthesis catalyzed by T7 DNA polymerase is essential in vivo to the processing of a T7 DNA concatemer to mature T7 genomes.
Inhibition of Gene Expression inEscherichia coliby Antisense Phosphorodiamidate Morpholino Oligomers (2003)

Antisense phosphorodiamidate morpholino oligomers (PMOs) were tested for the ability to inhibit gene expression in Escherichia coli. PMOs targeted to either a myc-luciferase reporter gene product or 16S rRNA did not inhibit luciferase expression or growth. However, in a strain with defective lipopolysaccharide (lpxA mutant), which has a leaky outer membrane, PMOs targeted to the myc-luciferase or acyl carrier protein (acpP) mRNA significantly inhibited their targets in a dose-dependent response. A significant improvement was made by covalently joining the peptide (KFF)(3)KC to the end of PMOs. In strains with an intact outer membrane, (KFF)(3)KC-myc PMO inhibited luciferase expression by 63%. A second (KFF)(3)KC-PMO conjugate targeted to lacI mRNA induced beta-galactosidase in a dose-dependent response. The end of the PMO to which (KFF)(3)KC is attached affected the efficiency of target inhibition but in various ways depending on the PMO. Another peptide-lacI PMO conjugate was synthesized with the cationic peptide CRRRQRRKKR and was found not to induce beta-galactosidase. We conclude that the outer membrane of E. coli inhibits entry of PMOs and that (KFF)(3)KC-PMO conjugates are transported across both membranes and specifically inhibit expression of their genetic targets.
Asymmetric Triaryldiamines as Thermally Stable Hole Transporting Layers for Organic Light-Emitting Devices (1998)

The synthesis of a series of asymmetric triaryldiamines has provided a number of materials with a wide range of thermal, electrochemical, and spectroscopic properties. The asymmetric materials described herein have two different diarylamine groups bound to a 1,4-phenylene or 4,4‘-biphenylene core, i.e., Ar1Ar2N−C6H4−NAr1‘Ar3 or Ar1Ar2N-biphenyl-NAr1‘Ar3, respectively. The diarylamines studied include diphenylamine, phenyl-m-tolylamine, naphthylphenylamine, iminostilbene, iminodibenzyl, and carbazole. These materials were prepared by copper- and palladium-catalyzed coupling of aryl halides and diarylamines. The asymmetry inherent in these compounds prevents these low molecular mass compounds from crystallizing, thus yielding higher thermal stability over that of the symmetric derivatives. In all cases, the asymmetric diamines form stable glasses, with glass transition temperatures up to 125 °C. HOMO levels for these materials, estimated by cyclic voltammetry, show a broad range of values, with oxidation potentials both lower and higher than those of common hole transport materials used in organic light emitting devices.
Serology for SARS-CoV-2: Apprehensions, opportunities, and the path forward (2020)

Serological testing for SARS-CoV-2 has enormous potential to contribute to COVID-19 pandemic response efforts. However, the required performance characteristics of antibody tests will critically depend on the use case (individual-level vs. population-level).
An improved synthesis of isopentenyl pyrophosphate (1967)

1. Isopentenol was converted into isopentenyl phosphate with phosphoryl chloride in ether containing pyridine. 2. The isopentenyl phosphate reacted in 2-methylpropan-2-ol-water with morpholine and dicyclohexylcarbodi-imide to give isopentenyl phosphoromorpholidate. 3. The isopentenyl phosphoromorpholidate, with inorganic phosphate in pyridine containing tributylamine, gave isopentenyl pyrophosphate. The yield of pyrophosphate from monophosphate was 80-85% and the yield of pyrophosphate from isopentenol 40-60%. [1-(14)C]-Isopentenyl pyrophosphate was prepared by this method. 4. The yield of isopentenyl pyrophosphate from isopentenyl phosphate was substantially improved, in comparison with the yields obtained by published methods via the phosphoramidate, by the use of the phosphoromorpholidate.
Role of TNF–TNF Receptor 2 Signal in Regulatory T Cells and Its Therapeutic Implications (2018)

Tumor necrosis factor α (TNFα) is a pleiotropic cytokine which signals through TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Emerging evidence has demonstrated that TNFR1 is ubiquitously expressed on almost all cells, while TNFR2 exhibits a limited expression, predominantly on regulatory T cells (Tregs). In addition, the signaling pathway by sTNF <i>via</i> TNFR1 mainly triggers pro-inflammatory pathways, and mTNF binding to TNFR2 usually initiates immune modulation and tissue regeneration. TNFα plays a critical role in upregulation or downregulation of Treg activity. Deficiency in TNFR2 signaling is significant in various autoimmune diseases. An ideal therapeutic strategy for autoimmune diseases would be to selectively block the sTNF/TNFR1 signal through the administration of sTNF inhibitors, or using TNFR1 antagonists while keeping the TNFR2 signaling pathway intact. Another promising strategy would be to rely on TNFR2 agonists which could drive the expansion of Tregs and promote tissue regeneration. Design of these therapeutic strategies targeting the TNFR1 or TNFR2 signaling pathways holds promise for the treatment of diverse inflammatory and degenerative diseases.
A prospective study analyzing the application of radiofrequency energy and high-voltage, ultrashort pulse duration electrical fields on the quantitative reduction of adipose tissue (2016)

Noninvasive fat reduction is claimed by many device manufacturers, but proof of efficacy has been difficult to establish. This prospective study was designed to measure the reduction of fat thickness and actual volume reduction in 20 female patients treated with an external radiofrequency (RF) device. This device combines RF heat, suction coupled vacuum, and oscillating electrical pulses that induce adipocyte death over time. Patients underwent pre- and post-treatment and intercurrent measurements of weight, body mass index, ultrasonic transcutaneous fat thickness, and 2D and 3D Vectra photography with independent calculation of circumferential and volumetric change. Mean transcutaneous ultrasound thickness at reproducible points was 2.78 cm; at 1-month post-treatment, the mean fat thickness was 1.71 cm. At 3-month post-treatment, the mean fat thickness reduction was 39.6%. Vectra circumference measurements were taken at 10-mm intervals, with postural and breathing cycle control. Independent analysis of serial measurements from + 60 to - 70 mm showed mean abdominal circumference measurement of 2.3 cm. Mean abdominal volume loss was 202.4 and 428.5 cc at 1- and 3-month post-treatment, respectively. Scanning electron microscopy confirmed that permanent cell destruction was caused by irreversible electroporation. Pyroptosis appears to be the mechanism of action.
THE MOLECULES OF MECHANOSENSATION (1997)

Mechanosensation, the transduction of mechanical forces into a cellular electrochemical signal, enables living organisms to detect touch; vibrations, such as sound; accelerations, including gravity; body movements; and changes in cellular volume and shape. Ion channels directly activated by mechanical tension are thought to mediate mechanosensation in many systems. Only one channel has been cloned that is unequivocably mechanically gated: the MscL channel in bacteria. Genetic screens for touch-insensitive nematodes or flies promise to identify the proteins that constitute a mechanosensory apparatus in eukaryotes. In Caenorhabditis elegans, the mec genes thus identified encode molecules for a candidate structure, which includes a "degenerin" channel tethered to specialized extracellular and intracellular structural proteins. In hair cells of the inner ear, evidence suggests that an extracellular tip link pulls on a channel, which attached intracellularly to actin via a tension-regulating myosin 1beta. The channel and the tip link have not been cloned. Because degenerins and MscL homologs have not been found outside of nematodes and prokaryotes, respectively, and because intracellular and extracellular accessory structures apparently differ among organs and species, it may be that mechanosensory channel complexes evolved multiple times.
The database Wiki project (2011)

Databases and wikis have complementary strengths and weaknesses for use in collaborative data management and data curation. Relational databases, for example, offer advantages such as scalability, query optimization and concurrency control, but are not easy to use and lack other features needed for collaboration. Wikis have proved enormously successful as a means to collaborate because they are easy to use, encourage sharing, and provide built-in support for archiving, history-tracking and annotation. However, wikis lack support for structured data, efficiently querying data at scale, and localized provenance and annotation. To achieve the best of both worlds, we are developing a general-purpose platform for collaborative data management, called DBWIKI. Our system not only facilitates the collaborative creation of structured data; it also provides features not usually provided by database technology such as annotation, citability, versioning, and provenance tracking. This paper describes the technical details behind DBWIKI that make it easy to create, correct, discuss, and query structured data, placing more power in the hands of users while managing tedious details of data curation automatically.
PXA1, a possible Saccharomyces cerevisiae ortholog of the human adrenoleukodystrophy gene. (1995)

The adrenoleukodystrophy protein (ALDp) is an ATP-binding cassette (ABC) transporter in the human peroxisome membrane. It is defective in X chromosome-linked adrenoleukodystrophy (ALD), a neurodegenerative disorder with impaired peroxisomal oxidation of very long chain fatty acids. We report cloning and characterization of PXA1, a yeast gene encoding a protein (Pxa1p) exhibiting high similarity to ALDp. Disruption of PXA1 results in impaired growth on oleic acid and reduced ability to oxidize oleate. Pxa1p is peroxisome associated; however, in the PXA1 mutant yeast, as in ALD cells, peroxisomes are morphologically intact. Disruption of a second yeast gene, YKL741, which encodes a more distantly related ALDp homolog (Yk174p), in either wild-type or PXA1 mutant yeast, results in a growth phenotype identical to that of the PXA1 mutant. This result suggests that Yk1741p and Pxa1p may be subunits of the same transporter. Sequence analysis of Pxa1p, ALDp, and related ABC transporters reveals a possible fatty acid binding domain and a 14-amino acid EAA-like motif, previously described only in prokaryotes. Because of the similarities in sequence and function, we propose that Pxa1p is the Saccharomyces cerevisiae ortholog of ALDp.
Detection of hepatitis B virus DNA in serum by polymerase chain reaction amplification and microtiter sandwich hybridization (1990)

We have developed a microtiter sandwich hybridization assay for the detection of polymerase chain reaction (PCR)-amplified hepatitis B virus (HBV) sequences. This assay utilizes an enzyme-linked immunosorbent assay-like format in which cloned DNA containing a sequence complementary to half of one PCR product strand is immobilized in microtiter wells. A biotin-labeled DNA sequence complementary to the other portion of the same PCR product strand is used as the probe. The DNAs from 69 hepatitis B surface antigen-positive serum samples and 16 antigen-negative control samples were amplified by the PCR procedure, and the product was detected by Southern and sandwich hybridization. Both detection procedures were capable of detecting as few as five copies of HBV DNA. Compared with Southern hybridization, the sandwich hybridization assay exhibited a sensitivity of 100% and a specificity of 95% for the detection of amplified HBV sequences. Unlike Southern hybridization, however, the sandwich hybridization assay employs a nonradioactive probe and allows easy handling of large numbers of samples. DNA was detected in 74% of the antigen-positive samples. All of the antigen-negative samples (healthy blood donors) were negative for HBV DNA by both procedures.
Effect of Dietary Grape Pomace on Lipid Metabolism and Hepatic Morphology in Rats Fed a High Fat Diet (2010)

본 연구에서는 포도박이 고지방식이를 섭취한 흰쥐의 지질대사에 미치는 영향을 조사함으로써 포도박의 생리활성과 자원화에 필요한 기초자료를 얻고자 하였다. Sprague-Dawley계 수컷 흰쥐 48마리를 정상식이 대조군(C), 정상식이에 포도박을 첨가한 군(CP), 고지방식이 대조군(HF), 고지방식이에 포도박을 첨가한 군(HFP)으로 나누어 4주간 실험식이를 급여한 후 간 기능 관련 효소, 혈청과 간조직 및 변 중의 지질 함량, 변으로 배설되는 중성 스테로이드와 담즙산 함량을 측정하였고 간조직의 형태학적 변화를 관찰하였다. 식이섭취량은 정상식이군(C, CP)에 비하여 고지방식이군(HF, HFP)이 유의적으로 적은 양을 섭취하였으며 식이 효율은 고지방식이군에서 증가하였다. 체중증가량은 실험군 간에 유의적인 차이는 없었다. 간 기능을 나타내는 GOT와 GPT 활성은 대조군과 포도박을 첨가한 군 간의 유의적인차이를 나타내지 않았다. 혈청 중의 총 콜레스테롤 함량은 고지방식이와 포도박 분말의 급여에 의한 상호작용을 나타내었으며, HDL-콜레스테롤 함량은 CP군이 C군보다 유의적으로 증가되었다. 중성지질과 LDL-콜레스테롤 함량은 정상식이군에서는 유의적인 차이가 없었지만 고지방식이군에서는 HF군에 비하여 HFP군이 유의적으로 감소하였다. 간조직 중의 총 지질 함량과 총 콜레스테롤 함량은 고지방식이와 포도박 분말의 급여에 따른 상호작용을 나타내었으며 중성지질 함량은 대조군에 비하여 포도박을 첨가한 군이 유의적으로 감소하였다. 인지질 함량은 고지방식이군에서는 유의적인 차이가 없었지만 정상식이 군에서는 C군에 비하여 CP군이 유의적으로 증가하였다. 변 중의 총 지질 함량은 C군에 비하여 CP군이 유의적으로 증가하였으며 총 콜레스테롤 함량은 HFP군이 HF군에 비하여 유의적으로 증가하였다. 변 중 중성지질 함량은 대조군에 비하여 포도박 첨가군에서 배설이 증가되었다. 변으로 배설되는 coprostanol 함량은 모든 실험군 간에 유의적인 차이를 나타내지 않았다. Cholesterol과 coprostanone 함량의 합은 정상식이군보다 고지방식이군이 유의적으로 증가하였고, 고지방식이군에서 HF군보다 HFP이 유의적으로 증가하였다. 담즙산의 함량은 HF군과 HFP군 간의 유의적인 차이가 없었지만 C군에 비하여 CP군이 유의적으로 증가하였다. 간조직의 형태학적 관찰 결과를 보면 HF군의 간조직 표면이 심한 지방 침착으로 윤기와 탄력성이 저하되었다. HFP군에서는 세포질 내의 지방방울의 크기와 숫자는 유사하였으나 HF군에 비하여 지방세포 비대, 괴사 및 염증현상이 거의 관찰되지 않았다. 이상의 결과는 식이섬유와 폴리페놀 성분을 다량 함유한 포도박 식이는 혈청과 간조직의 지질 축적을 감소시키고 변으로 배설되는 지질 함량을 증가시켜 줌으로써 지질대사 관련한 만성질환의 예방효과를 가져올 수 있는 것으로 기대되었다. 포도박의 이러한 생리활성에 대한 연구결과는 향후 포도 가공중에 얻어지는 포도박 폐기물을 자원화 할 수 있는 기초자료로써 이용될 수 있다고 사료된다.
Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter (2000)

In the normal mouse embryo, Bmp4 is expressed in mesenchymal cells surrounding the Wolffian duct (WD) and ureter stalk, whereas bone morphogenetic protein (BMP) type I receptor genes are transcribed either ubiquitously (Alk3) or exclusively in the WD and ureter epithelium (Alk6). Bmp4 heterozygous null mutant mice display, with high penetrance, abnormalities that mimic human congenital anomalies of the kidney and urinary tract (CAKUT), including hypo/dysplastic kidneys, hydroureter, ectopic ureterovesical (UV) junction, and double collecting system. Analysis of mutant embryos suggests that the kidney hypo/dysplasia results from reduced branching of the ureter, whereas the ectopic UV junction and double collecting system are due to ectopic ureteral budding from the WD and accessory budding from the main ureter, respectively. In the cultured metanephros deprived of sulfated glycosaminoglycans (S-GAGs), BMP4-loaded beads partially rescue growth and elongation of the ureter. By contrast, when S-GAGs synthesis is not inhibited, BMP4 beads inhibit ureter branching and expression of Wnt 11, a target of glial cell-derived neurotrophic factor signaling. Thus, Bmp4 has 2 functions in the early morphogenesis of the kidney and urinary tract. One is to inhibit ectopic budding from the WD or the ureter stalk by antagonizing inductive signals from the metanephric mesenchyme to the illegitimate sites on the WD. The other is to promote the elongation of the branching ureter within the metanephros, thereby promoting kidney morphogenesis.
Adp-Ribosylating Toxins and G Proteins: Insights into Signal Transduction (1990)

Bacterial ADP-ribosyltransferases: toxins and related proteins Guanine nucleotide-binding proteins coupled to signal transduction in animal cells ADP ribosylation in bacteria and animal cells
Laminin γ2 chain as a stromal cell marker of the human bone marrow microenvironment (2002)

Laminins are large heterotrimeric molecules consisting of alpha, beta and gamma chains. At present, five alpha chains, three beta chains and three gamma chains have been characterized. Laminin-5 (alpha3beta3gamma2) is the only isoform known to date which contains a gamma2 chain. In human bone marrow, non-haematopoietic stromal cells expressed the laminin gamma2 chain, whereas bone marrow mononuclear cells did not. Co-localization of the gamma2 chain was detected with the laminin alpha4 and alpha5 chains, and co-immunoprecipitation studies revealed a new isoform consisting of alpha5, beta2 and gamma2 chains. The laminin gamma2 chain was also co-localized with alpha-sm-actin in bone marrow, but it was not expressed in endothelial cells or megakaryocytes, indicating that the gamma2 chain is exclusively expressed in vivo in bone marrow stromal cells. The laminin gamma2 chain containing isoform LN-5 was shown to be an adhesive substrate for a small subpopulation of bone marrow mononuclear cells and also for peripheral blood platelets. Taken together, these results indicate that (I) laminin isoforms containing the gamma2 chain can act as adhesive substrates for human haematopoietic cells, and (II) the laminin gamma2 chain can be used as a specific marker molecule for human bone-marrow-derived stromal cells.
Fluorescence detection and diagnosis of non‐melanoma skin cancer at an early stage (2009)

Diagnostic skin fluorescence using liposomal encapsulated 5-ALA and a specialised computerised detection and visualisation system offers the possibility for detection of NMSC at an early, pre-clinical stage. The technique is well suited to examine large areas of skin. It also identifies areas of most interest for performing confirmatory skin biopsies, as well as pre-operative assessment of boundaries of skin malignancies, and finally, the technique is applicable in the control and follow-up of skin cancer treatment.
Hysteresis Loops of Mixtures of Ferromagnetic Micropowders (1955)

A treatment is given of the hysteresis loops of dilute mixtures of various sizes of ferromagnetic particles. Three ranges of particle size are considered: very small particles called ``super-paramagnetic'' which are single domain and equilibrate resulting from thermal vibrations, single domain particles which are large enough that they do not equilibrate, and particles large enough to contain many domains in equilibrium. The results are compared to experiment.
Glycoprotein Ibα inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques (2007)

Anti-platelet drugs are used to prevent intra-arterial thrombus formation after rupture of atherosclerotic plaques. Until now, the inhibitory effect of present and future anti-platelet drugs such as aspirin, ADP receptor P2Y(1)/P2Y(12) antagonists and glycoprotein (GP) Ibalpha inhibitors on the interaction of platelets with human plaques is not known. To study those effects we obtained human atherosclerotic plaques by surgical endarterectomy. Plaques induced maximal platelet aggregation in hirudinized platelet-rich plasma (PRP) and blood that was effectively inhibited by aspirin, the P2Y(1) antagonist MRS2179 and the P2Y(12) antagonist AR-C69931MX, but not by GPIbalpha blockade with the mAB 6B4. Inhibition of platelet aggregation by MRS2179 was 74 +/- 37% and 68 +/- 20%, by AR-C69931MX 94 +/- 7% and 80 +/- 6%, and by aspirin 88 +/- 19% and 64 +/- 28%, in PRP and blood, respectively (mean +/- SD; n = 6-12 with plaques from 6 patients). The combination of both ADP receptor antagonists completely inhibited plaque-induced platelet aggregation in hirudinized PRP and blood. Under arterial flow conditions (1,500s(-1)), blockade of platelet GPIbalpha resulted in a strong decrease of plaque-stimulated platelet adhesion/aggregate formation of 77 +/- 5% (mean +/- SD; n = 4). Furthermore, MRS2179, AR-C69931MX and their combination reduced plaque-dependent platelet aggregate formation by 35 +/- 14%, 32 +/- 13% and 58 +/- 12% (mean +/- SD; n = 5), respectively. Aspirin was without significant effect. In conclusion, a GPIbalpha-blocking antibody, as well as P2Y(1) and P2Y(12) receptor antagonists, alone or in combination, reduce in contrast to aspirin human plaque-induced platelet thrombus formation under arterial flow. Although these new anti-platelet agents inhibit platelet thrombus formation after plaque rupture, more efficient platelet blockers are required.
Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study (2013)

Budesonide MMX 9 mg was safe and more effective than placebo at inducing combined clinical and endoscopic remission in patients with active, mild-to-moderate UC.
NNAlign_MA; MHC Peptidome Deconvolution for Accurate MHC Binding Motif Characterization and Improved T-cell Epitope Predictions (2019)

The set of peptides presented on a cell's surface by MHC molecules is known as the immunopeptidome. Current mass spectrometry technologies allow for identification of large peptidomes, and studies have proven these data to be a rich source of information for learning the rules of MHC-mediated antigen presentation. Immunopeptidomes are usually poly-specific, containing multiple sequence motifs matching the MHC molecules expressed in the system under investigation. Motif deconvolution -the process of associating each ligand to its presenting MHC molecule(s)- is therefore a critical and challenging step in the analysis of MS-eluted MHC ligand data. Here, we describe NNAlign_MA, a computational method designed to address this challenge and fully benefit from large, poly-specific data sets of MS-eluted ligands. NNAlign_MA simultaneously performs the tasks of (1) clustering peptides into individual specificities; (2) automatic annotation of each cluster to an MHC molecule; and (3) training of a prediction model covering all MHCs present in the training set. NNAlign_MA was benchmarked on large and diverse data sets, covering class I and class II data. In all cases, the method was demonstrated to outperform state-of-the-art methods, effectively expanding the coverage of alleles for which accurate predictions can be made, resulting in improved identification of both eluted ligands and T-cell epitopes. Given its high flexibility and ease of use, we expect NNAlign_MA to serve as an effective tool to increase our understanding of the rules of MHC antigen presentation and guide the development of novel T-cell-based therapeutics.