gebhart/patrepeval huggingface dataset:
Proteolytic fragmentation and peptide mapping of human carboxyamidomethylated tracheobronchial mucin (1989)

Human tracheobronchial mucin was isolated from lung mucosal gel by chromatography on Sepharose 4B in the presence of dissociating and reducing agents, and its thiol residues were carboxyamidomethylated with iodo[1(-14)C]acetamide. The 14C-carboxyamido-methylated mucin was purified by chromatography on Sepharose 2B. No low molecular weight components were detected by molecular sieve chromatography or polyacrylamide gel electrophoresis in the presence of dissociating and reducing agents or by analytical density centrifugation in CsCl/guanidinium chloride. After digestion of the purified 14C-mucin with trypsin-L-1-tosylamido-2-phenylethyl chloromethyl ketone, three fractions (TR-1, TR-2, and TR-3) were observed by chromatography on Sepharose 4B. TR-1, a 260-kDa mucin glycopeptide fragment, contained all of the neutral hexose and blood group activity and 20% of the radioactivity in the undigested mucin. TR-1 was refractory to a second incubation with trypsin but could be digested by papain or Pronase to a smaller mucin glycopeptide fraction, as judged by the slight decrease in apparent molecular weight on Sepharose CL-4B. These mucin glycopeptides contained approximately 50% of the radioactivity in the TR-1 fraction, indicating that the glycosylated domains of carboxyamidomethylated tracheobronchial mucin contained thiol residues. The remainder of the radioactivity from papain or Pronase digests of TR-1 eluted, like the TR-3 fractions, in the salt fraction on Sepharose CL-4B. Peptide mapping of the nonglycosylated TR-3 fraction by TLC and high voltage electrophoresis yielded six principal and several less intensely stained ninhydrin reactive components, with the radiolabel concentrated in one of the latter peptides. Peptide purification of the TR-3 fraction by high pressure liquid chromatography on a C18 reverse phase column demonstrated the presence of four major peptides, with TR-3A being the dominant component. The TR-3D peptide contained S-carboxy-aminomethylcysteine and had 69% sequence similarity to the sgs-7 salivary glue protein of Drosophila.
Nanotechnology for targeted cancer therapy (2007)

Cancer nanotechnology is currently under intense development for applications in cancer imaging, molecular diagnosis and targeted therapy. The basic rationale is that nanometer-sized particles, such as biodegradable micelles, semiconductor quantum dots and iron oxide nanocrystals, have functional or structural properties that are not available from either molecular or macroscopic agents. When linked with biotargeting ligands, such as monoclonal antibodies, peptides or small molecules, these nanoparticles are used to target malignant tumors with high affinity and specificity. In the 'mesoscopic' size range of 5-100 nm in diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic or magnetic) and therapeutic (e.g., anticancer) agents. Recent advances have led to multifunctional nanoparticle probes for molecular and cellular imaging, nanoparticle drugs for targeted therapy, and integrated nanodevices for early cancer detection and screening. These developments have opened exciting opportunities for personalized oncology in which cancer detection, diagnosis and therapy are tailored to each individual's molecular profile, and also for predictive oncology, in which genetic/molecular information is used to predict tumor development, progression and clinical outcome.
Fast and Robust Training of Recurrent Neural Networks for Offline Handwriting Recognition (2014)

In this paper we demonstrate a modified topology for long short-term memory recurrent neural networks that controls the shape of the squashing functions in gating units. We further propose an efficient training framework based on a mini-batch training on sequence level combined with a sequence chunking approach. The framework is evaluated on publicly available data sets containing English and French handwriting by utilizing a GPU based implementation. Speedups of more than 3x are achieved in training recurrent neural network models which outperform state of the art recognition results.
Safety Data of Injectable Nonanimal Stabilized Hyaluronic Acid Gel for Soft Tissue Augmentation (2002)

According to the reported worldwide adverse events data, hypersensitivity to nonanimal hyaluronic acid gel is the major adverse event and is most likely secondary to impurities of bacterial fermentation. According to data from 2000, the incidence of hypersensitivity appears to be declining after the introduction of a more purified hyaluronic acid raw material.
Biological Significance of Prolactin in Gynecologic Cancers (2009)

There is increasing evidence that prolactin (PRL), a hormone/cytokine, plays a role in breast, prostate, and colorectal cancers via local production or accumulation. Elevated levels of serum PRL in ovarian and endometrial cancers have been reported, indicating a potential role for PRL in endometrial and ovarian carcinogenesis. In this study, we show that serum PRL levels are significantly elevated in women with a strong family history of ovarian cancer. We show dramatically increased expression of PRL receptor in ovarian and endometrial tumors as well as in endometrial hyperplasia, signifying the importance of PRL signaling in malignant and premalignant conditions. PRL mRNA was expressed in ovarian and endometrial tumors, indicating the presence of an autocrine loop. PRL potently induced proliferation in several ovarian and endometrial cancer cell lines. Binding of PRL to its receptor was followed by rapid phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, mitogen-activated protein kinase/ERK kinase 1, signal transducer and activator of transcription 3, CREB, ATF-2, and p53 and activation of 37 transcription factors in ovarian and endometrial carcinoma cells. PRL also activated Ras oncogene in these cells. When human immortalized normal ovarian epithelial cells were chronically exposed to PRL, a malignant transformation occurred manifested by the acquired ability of transformed cells to form clones, grow in soft agar, and form tumors in severe combined immunodeficient-beige mice. Transformation efficiency was diminished by a Ras inhibitor, providing proof that PRL-induced transformation uses the Ras pathway. In summary, we present findings that indicate an important role for PRL in ovarian and endometrial tumorigenesis. PRL may represent a risk factor for ovarian and endometrial cancers.
Binding of Neu Differentiation Factor with the Extracellular Domain of Her2 and Her3 (1995)

The interaction of neu differentiation factor (NDF) with the extracellular domains of Her2 (sHer2) and Her3 (sHer3) have been studied using native gels, light scattering, and sedimentation equilibrium. The full-length NDF beta 2 was shown to bind sHer3 with a dissociation constant of 26 +/- 9 nM, while it showed a 1000-fold weaker binding to sHer2. Taken together, these results demonstrate that NDF is a high affinity ligand for Her3, but not for Her2. No increase in affinity of the NDF beta 2 for sHer3 was observed upon addition of sHer2 to the NDF beta 2-sHer3 mixture. Binding of NDF beta 2 to sHer3 did not induce receptor dimerization or oligomerization, the stoichiometry being one sHer3 per one NDF molecule. This finding suggests that transmembrane and/or intracellular domains of receptor family members or perhaps additional unidentified components may be involved in NDF induced dimerization and autophosphorylation, or alternatively, that dimerization is not the mechanism for Her3 autophosphorylation and signal transduction.
World Bank policy research bulletin 2(5) (1991)

International trade and the environment. New research. Books. Journal. Discussion, technical, and related papers. Policy research working paper. Calendar.
Tuning the Pentium Pro microarchitecture (1996)

Designing a wholly new microprocessor is difficult and expensive. To justify this effort, a major new microarchitecture must improve performance one and a half or two times over the previous-generation microarchitecture, when evaluated on equivalent process technology. In addition, semiconductor process technology continues to evolve while the processor design is in progress. The previous-generation microarchitecture increases in clock speed and performance due to compactions and conversion to newer technology. A new microarchitecture must "intercept" the process technology to achieve a compounding of process and microarchitectural speedups. This paper looks at a large microprocessor development project which reveals some of the reasoning (for goals, changes, trade-offs, and performance simulation) that lay behind its final form.
Trypsin-pancreatic trypsin inhibitor association. Dynamics of the interaction and role of disulfide bridges (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTrypsin-pancreatic trypsin inhibitor association. Dynamics of the interaction and role of disulfide bridgesJean Pierre Vincent and Michel LazdunskiCite this: Biochemistry 1972, 11, 16, 2967–2977Publication Date (Print):August 1, 1972Publication History Published online1 May 2002Published inissue 1 August 1972https://pubs.acs.org/doi/10.1021/bi00766a007https://doi.org/10.1021/bi00766a007research-articleACS PublicationsRequest reuse permissionsArticle Views532Altmetric-Citations194LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
HMG1-related DNA-binding protein isolated with V-(D)-J recombination signal probes. (1991)

In order to isolate cDNA clones for DNA-binding components of the V-(D)-J recombinase, phage libraries from a pre-B-cell line were screened with a radiolabeled probe containing recombination signal sequences (RSS). Among prospective clones, cDNA T160 was analyzed further. It produced a protein of 80.6 kDa which bound to DNA containing RSS but not to DNA in which the RSS had been mutated. A search of a data base revealed that the T160 protein has significant sequence homology (56%) to the nonhistone chromosomal protein HMG1 within the C-terminal region of 80 amino acids. DNA-binding analysis with truncated proteins showed that the HMG homology region is responsible for DNA binding. Using restriction fragment length polymorphisms, the T160 gene was mapped at the proximal end of mouse chromosome 2. Evidence was obtained for genetic linkage between the T160 gene and the recombination activator genes RAG-1 and RAG-2.
Structure of an Enteric Pathogen, Bovine Parvovirus (2014)

Bovine parvovirus (BPV), identified in the 1960s in diarrheic calves, is the type member of the Bocaparvovirus genus of the nonenveloped, single-stranded DNA (ssDNA) Parvoviridae family. The recent isolation of human bocaparvoviruses from children with severe respiratory and gastrointestinal infections has generated interest in understanding the life cycle and pathogenesis of these emerging viruses. We have determined the high-resolution structure of the BPV capsid assembled from its predominant capsid protein VP2, known to be involved in a myriad of functions during host cell entry, pathogenesis, and antigenicity for other members of the Parvovirinae. Our results show the conservation of the core secondary structural elements and the location of the N-terminal residues for the known bocaparvovirus capsid structures. However, surface loops with high variability in sequence and conformation give BPV a unique capsid surface topology. Similar analogous regions in other Parvovirinae type members are important as determinants of receptor recognition, tissue and host tropism, pathogenicity, and antigenicity.
The Regulatory T Cell Family: Distinct Subsets and their Interrelations (2003)

The immune system, a highly effective and dynamic cellular network, protects a host from pathogens. Therefore, the immune system must distinguish self from nonself structures, but also between harmful and innocuous foreign Ags to prevent nonessential and self-destructive immune responses. The
Fast quench reactor method (2023)

A fast quench reaction includes a reactor chamber having a high temperature heating means such as a plasma torch at its inlet and a means of rapidly expanding a reactant stream, such as a restrictive convergent-divergent nozzle at its outlet end. Metal halide reactants are injected into the reactor chamber. Reducing gas is added at different stages in the process to form a desired end product and prevent back reactions. The resulting heated gaseous stream is then rapidly cooled by expansion of the gaseous stream.
Quantifying architectural debts (2015)

In our prior research, we found that problematic architectural connections can propagate errors. We also found that among multiple files, the architectural connections that violate common design principles strongly correlate with the error-proneness of files. The flawed architectural connections, if not fixed properly and timely, can become debts that accumulate high interest in terms of maintenance costs over time. In this paper, we define architectural debts as clusters of files with problematic architectural connections among them, and their connections incur high maintenance costs over time. Our goal is to 1) precisely identify which and how many files are involved in architectural debts; 2) quantify the penalties of architectural debts in terms of maintenance costs; and 3) model the growth trend of penalties---maintenance costs---that accumulate due to architectural debts. We plan to provide a quantitative model for project managers and stakeholders as a reference in making decisions of whether, when and where to invest in refactoring.
Purified Allogeneic Hematopoietic Stem Cell Transplantation Blocks Diabetes Pathogenesis in NOD Mice (2003)

Purified hematopoietic stem cells (HSCs) were transplanted into NOD mice to test whether development of hyperglycemia could be prevented. Engraftment of major histocompatibility complex-mismatched HSCs was compared with bone marrow (BM) grafts. HSCs differed from BM because HSCs were more strongly resisted and HSC recipients retained significant levels of NOD T-cells, whereas BM recipients were full donor chimeras. Despite persistent NOD T-cells, all HSC chimeras were protected from hyperglycemia, and attenuation of islet lesions was observed. T-cell selection was altered in allogeneic HSC recipients as demonstrated by deletion of both donor and host superantigen-specific T-cells. Syngeneic and congenic hematopoietic cell transplants were also performed to differentiate the influence of the preparative regimen(s) versus the allografts. Unlike the allogeneic HSC transplantations, syngeneic or congenic grafts did not retard diabetes development. In a pilot study, overtly diabetic NOD mice were cured by co-transplantation of allogeneic HSCs and donor-matched islets. We conclude that allogeneic HSC transplants block allo- and autoimmunity, despite residual host T-cell presence. These data demonstrate for the first time that purified HSC grafts block development of autoimmune diabetes and illuminate how HSC grafts alter thymic and peripheral T-cell responses against auto- and alloantigens.
Tolerance Strategies Employing Antigen-Coupled Apoptotic Cells and Carboxylated PLG Nanoparticles for the Treatment of Type 1 Diabetes (2012)

The development of therapies that specifically target autoreactive immune cells for the prevention and treatment of type 1 diabetes (T1D) without inducing generalized immunosuppression that often compromises the host's ability to clear non-self antigen is highly desired. This review discusses the mechanisms and potential therapeutic applications of antigen-specific T cell tolerance techniques using syngeneic apoptotic cellular carriers and synthetic nanoparticles that are covalently cross-linked to diabetogenic peptides or proteins through ethylene carbodiimide (ECDI) to prevent and treat T1D. Experimental models have demonstrated that intravenous injection of autoantigen decorated splenocytes and biodegradable nanoparticles through ECDI fixation effectively induce and maintain antigen-specific T cell abortive activation and anergy by T cell intrinsic and extrinsic mechanisms. The putative mechanisms include, but are not limited to, the uptake and processing of antigen-coupled nanoparticles or apoptotic cellular carriers for tolerogenic presentation by host splenic antigen-presenting cells, the induction of regulatory T cells, and the secretion of immune-suppressive cytokines, such as IL-10 and TGF-β. The safety profile and efficacy of this approach in preclinical animal models of T1D, including non-obese diabetic (NOD), BDC2.5 transgenic, and humanized mice, have been extensively investigated, and will be the focus of this review. Translation of this approach to clinical trials of T1D and other T cell-mediated autoimmune diseases will also be reviewed in this chapter.
Combining Gold Nanoparticles with Real-Time Immuno-PCR for Analysis of HIV p24 Antigens (2007)

We have improved real-time immuno-PCR (IPCR) with nanoparticle based amplification. Gold magnetic particles were functionalized with antibodies against the HIV capsid protein p24 and gold nanoparticles were functionalized with both oligonucleotide barcodes and antibodies against a non- overlapping region of the cognate p24. In the presence of p24, the gold magnetic particles and the gold nanoparticles form sandwiched structures that are magnetically separated from mixture. After dehybridization of the barcode DNA on the gold nanoparticle, the released barcodes are quickly identified by realtime PCR. The limit of detection was 100 copies of p24 antigens. Results show that the real-time IPCR through nanoparticle based barcode amplification offers an disruptive approach to p24 detection and quantification, thus may potentially shorten the window of HIV-1 diagnosis, and might be valuable to monitor the response to anti-retroviral treatment when RNA copy number is very below.
Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle (2015)

Recruitment of endogenous progenitors is critical during tissue repair. The inner ear utricle requires mechanosensory hair cells (HCs) to detect linear acceleration. After damage, non-mammalian utricles regenerate HCs via both proliferation and direct transdifferentiation. In adult mammals, limited transdifferentiation from unidentified progenitors occurs to regenerate extrastriolar Type II HCs. Here we show that HC damage in neonatal mouse utricle activates the Wnt target gene Lgr5 in striolar supporting cells. Lineage tracing and time-lapse microscopy reveal that Lgr5+ cells transdifferentiate into HC-like cells in vitro. In contrast to adults, HC ablation in neonatal utricles in vivo recruits Lgr5+ cells to regenerate striolar HCs through mitotic and transdifferentiation pathways. Both Type I and II HCs are regenerated, and regenerated HCs display stereocilia and synapses. Lastly, stabilized ß-catenin in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt-regulated, damage-activated HC progenitors and may help uncover factors driving mammalian HC regeneration.
An ultrastructural study of lipoprotein accumulation in cardiac valves of the rabbit. (1994)

Heart valves are composed chiefly of extracellular matrix surrounded by an endothelial cell monolayer and as a result are an excellent model of the intima. Heart valves from rabbits fed a high-cholesterol diet accumulate lipids within the matrix and over time develop fatty streaks similar to those seen in the aorta. In this study we demonstrate that the heart valves (atrioventricular and aortic) can be isolated and used as an in vitro preparation to control and follow low-density lipoprotein (LDL) uptake and deposition. Using thin-section and freeze-etch microscopy we found that LDL rapidly associates with collagen within the extracellular matrix. As it accumulates along the collagen fibers the LDL appears to undergo structural changes in size and surface topography. This association of LDL with collagen may be a key step in lipid aggregation in the intima.
Direct Detection of HIV-1 RNA from AIDS and ARC Patient Samples (1988)

Human immunodeficiency virus (HIV), formerly termed human T-lymphotropic virus (HTLVIII/LAV), is the etiological agent of acquired immune deficiency syndrome (AIDS). Direct detection of HIV-1 nucleic acid sequences in patient tissue or blood samples is possible in only a minor fraction of cases due to the low percentage of infected cells (Shaw et al., 1984). We report a modification of the polymerase chain reaction method (PCR) (Saiki et al., 1985), in which we amplify sequences from HIV-1 RNA templates, for the identification of HIV-1 in peripheral blood and tissue samples obtained from AIDS and AIDS-related complex (ARC) patients. This method of HIV-1 detection is at least six orders of magnitude more sensitive than standard nucleic acid detection methods and has direct clinical applications. In vitro tissue culturing of the virus is not required for HIV-1 detection. Using this technique, the sequence in the orfB region of HIV-1 has been amplified and detected from less than 1 microgram of total RNA prepared from a few milliliters of peripheral blood samples. This technique enables the rapid and unambiguous clinical detection of potential HIV-infected individuals and can be used to assay the efficacy of anti-HIV-1 drugs. To enhance the efficiency of this technique, we have appended the prokaryotic T7 RNA polymerase promoter sequence to one of the priming oligonucleotides. After several cycles of PCR with the promoter-containing oligo, a small aliquot of the reaction can be utilized to direct specific and efficient T7 RNA polymerase-mediated transcription of the amplified sequences, thus enhancing the sensitivity and simplifying the labor of the experiment.
Nucleic acid approaches for detection and identification of biological warfare and infectious disease agents (2003)

Biological warfare agents are the most problematic of the weapons of mass destruction and terror. Both civilian and military sources predict that over the next decade the threat from proliferation of these agents will increase significantly. In this review we summarize the state of the art in detection and identification of biological threat agents based on PCR technology with emphasis on the new technology of microarrays. The advantages and limitations of real-time PCR technology and a review of the literature as it applies to pathogen and virus detection are presented. The paper covers a number of issues related to the challenges facing biological threat agent detection technologies and identifies critical components that must be overcome for the emergence of reliable PCR-based DNA technologies as bioterrorism countermeasures and for environmental applications. The review evaluates various system components developed for an integrated DNA microchip and the potential applications of the next generation of fully automated DNA analyzers with integrated sample preparation and biosensing elements. The article also reviews promising devices and technologies that are near to being, or have been, commercialized.