gebhart/patrepeval huggingface dataset:
Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor. (1995)

The insulin gene is one of the best paradigms of tissue-specific gene expression. It is developmentally regulated and is expressed exclusively in the pancreatic beta-cell. This restricted expression is directed by a tissue-specific enhancer, within the promoter, which contains an E-box sequence. The insulin E-box binds an islet-specific protein complex, termed 3a1. E-boxes bind proteins belonging to the basic helix-loop-helix (bHLH) family of transcription factors. The bHLH proteins function as potent transcriptional activators of tissue-specific genes by forming heterodimers between ubiquitous and cell-restricted family members. In addition, the cell-restricted bHLH members play an important role in specifying cell fate. To isolate the tissue-specific bHLH factor controlling insulin gene expression and study its role in islet cell differentiation, a modified yeast two-hybrid system was utilized to clone a novel bHLH factor, BETA2 (beta-cell E-box trans-activator 2), from a hamster insulin tumor (HIT) cell cDNA library. Northern analysis demonstrates that high-level expression of the BETA2 gene is restricted to pancreatic alpha- and beta-cell lines. As expected of tissue-specific bHLH members, BETA2 binds to the insulin E-box sequence with high affinity as a heterodimer with the ubiquitous bHLH factor E47. More importantly, antibody supershift experiments clearly show that BETA2 is a component of the native insulin E-box-binding complex. Transient transfection assays demonstrate that the BETA2/E47 heterodimer synergistically interacts with a neighboring beta-cell-specific complex to activate an insulin enhancer. In contrast, other bHLH factors such as MyoD and E47, which can bind to the insulin E-box with high affinity, fail to do so. Thus, a unique, cooperative interaction is the basis by which the insulin E-box enhancer discriminates between various bHLH factors to achieve tissue-specific activation of the insulin gene.
Identification of diverse nerve growth factor-regulated genes by serial analysis of gene expression (SAGE) profiling (2000)

Neurotrophic factors such as nerve growth factor (NGF) promote a wide variety of responses in neurons, including differentiation, survival, plasticity, and repair. Such actions often require changes in gene expression. To identify the regulated genes and thereby to more fully understand the NGF mechanism, we carried out serial analysis of gene expression (SAGE) profiling of transcripts derived from rat PC12 cells before and after NGF-promoted neuronal differentiation. Multiple criteria supported the reliability of the profile. Approximately 157,000 SAGE tags were analyzed, representing at least 21,000 unique transcripts. Of these, nearly 800 were regulated by 6-fold or more in response to NGF. Approximately 150 of the regulated transcripts have been matched to named genes, the majority of which were not previously known to be NGF-responsive. Functional categorization of the regulated genes provides insight into the complex, integrated mechanism by which NGF promotes its multiple actions. It is anticipated that as genomic sequence information accrues the data derived here will continue to provide information about neurotrophic factor mechanisms.
Efficacy and safety of piperacillin/tazobactam in skin and soft tissue infections. (1994)

Piperacillin/tazobactam has excellent in vitro activity against the most pathogens involved in skin infections. Two large multicentre studies recently evaluated the efficacy and safety of piperacillin/tazobactam in the treatment of skin and soft tissue infections in patients in hospital. The efficacy and safety of piperacillin/tazobactam (4 g/500 mg every 8 hours) have been assessed in an open study in Europe. Among 120 evaluable patients, 93% were clinically cured or improved. Only six patients were withdrawn from the study because of side effects. In another trial, piperacillin/tazobactam were compared with ticarcillin/clavulanate in a double-blinded prospective study in the United States. Of evaluable patients, 67 received piperacillin/tazobactam (3 g/375 mg every 6 hours) and 44 received ticarcillin/clavulanate (3 g/100 mg every 6 hours). At assessment, 76% of patients given piperacillin/tazobactam and 77% of patients given ticarcillin/clavulanate had responded favourably. The lower success rate in this trial may be attributed to more stringent inclusion criteria that resulted in the incorporation of a higher proportion of patients with more severe conditions including diabetic/ischaemic foot infections. The incidence of adverse reactions was similar in both groups. Piperacillin/tazobactam seems to be both effective and safe in the treatment of skin and soft tissue infections in patients confined to hospital.
Techniques for In Situ Corrosion Studies of 316L Stainless Steel in Sulfuric Acid Solutions (2012)

An in situ optical microscopy and simultaneous electrochemical analysis method is presented for studying 316L stainless steel in sulfuric acid based solutions. The electrochemical methods involved potentiostatic and potentiodynamic analysis of 316L stainless steel surface in aerated and deaerated 1M-3.39M H2SO4 while varying Ni+ and Cl-. This technique is reviewed along with several other in situ surface analytical probes and patents such as scanning tunneling microscopy (STM), scanning electrochemical microscopy (SECM) and variations on SECM (near fieldalternating current) and the results are discussed in conjunction with various theories and applications. The results when compared to SECM data indicate that the SECM resolution, control and performance are improved. The results also illustrate the wide variety of corrosion behaviors possible for 316L stainless steel under potentiostatic and potentiodynamic test conditions. Analysis of these samples provides both a detailed visual account of the corrosion process in addition to standard electrochemical analysis regarding pitting potentials, corrosion potential and corrosion rate. Polarization data and analysis regarding the corrosion patterns observed is presented including in situ images of etching, surface layer changes and pitting. Images and analysis of chromium carbide and sulfide inclusion behaviors in sulfuric acid were performed showing the tendency of inclusions to dissolve and act as nucleation sites for pits. Keywords: Aerated, dearated, etching, grain boundaries, inclusions, in situ, optical, pitting, potentiostatic, potentiodynamic, polarization, SEM-EDS, 316L, 1M-3.39M H2SO4
Use of Molecular Recognition To Drive Chemical Evolution. 1. Controlling the Composition of an Equilibrating Mixture of Simple Arginine Receptors (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTUse of Molecular Recognition To Drive Chemical Evolution. 1. Controlling the Composition of an Equilibrating Mixture of Simple Arginine ReceptorsAlexey V. Eliseev and Marina I. NelenView Author Information Department of Medicinal Chemistry, School of Pharmacy State University of New York at Buffalo Buffalo, New York 14260 Cite this: J. Am. Chem. Soc. 1997, 119, 5, 1147–1148Publication Date (Web):February 5, 1997Publication History Received5 June 1996Revised13 December 1996Published online5 February 1997Published inissue 1 February 1997https://pubs.acs.org/doi/10.1021/ja961893rhttps://doi.org/10.1021/ja961893rrapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views584Altmetric-Citations95LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Genetics,Irradiation,Mixtures,Molecular structure,Receptors Get e-Alerts
Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. (1987)

A cell line established from a patient with acute lymphoblastic leukemia was found to express IL-2 binding sites with a novel, intermediate affinity compared with the characteristic high-affinity IL-2-receptors and low-affinity IL-2 binding sites described previously. Clones were isolated from this cell line that displayed solely this new IL-2-binding protein, and were found to be unreactive with anti-Tac, the mAb that competes with IL-2 for binding. Moreover, these same cloned cells did not express mRNA detectable by hybridization with radiolabeled cDNA encoding the Tac protein. In contrast, the original cell line and similar clones expressed low levels of Tac mRNA and cell surface Tac antigen, both of which could be augmented by exposure to medium conditioned by adult T leukemia cell lines. Particularly noteworthy, induction of Tac antigen expression was paralleled by an increase in the number of high-affinity IL-2-R detectable. Since the expression of the Tac antigen protein by itself makes only for low-affinity IL-2 binding, these data prompted a reevaluation of the structural composition of high-affinity IL-2-R. Analysis of the IL-2-binding proteins expressed by leukemic cell lines lacking high-affinity receptors revealed only a single protein, larger than the Tac antigen protein (Mr = 75,000 vs. 55,000). In contrast, clones induced to express high-affinity receptors had clearly both of these IL-2-binding proteins. Moreover, when IL-2 binding to normal T cells was performed under conditions that favored the proportion of high-affinity receptors occupied, two distinct proteins identical to those already identified on the leukemic cells could be crosslinked covalently to radiolabeled IL-2. The interpretations derived from these varied, assembled data, point to two IL-2-binding proteins, both of which are required for high-affinity IL-2 binding.
Functional amelioration of murine galactosialidosis by genetically modified bone marrow hematopoietic progenitor cells (2002)

Protective protein/cathepsin A (PPCA), a lysosomal carboxypeptidase, is deficient in the neurodegenerative lysosomal disorder galactosialidosis (GS). PPCA(-/-) mice display a disease course similar to that of severe human GS, resulting in nephropathy, ataxia, and premature death. Bone marrow transplantation (BMT) in mutant animals using transgenic BM overexpressing the corrective enzyme in either erythroid cells or monocytes/macrophages has proven effective for the improvement of the phenotype, and encouraged the use of genetically modified BM cells for ex vivo gene therapy of GS. Here, we established stable donor hematopoiesis in PPCA(-/-) mice that received hematopoietic progenitors transduced with a murine stem cell virus (MSCV)-based, bicistronic retroviral vector overexpressing PPCA and the green fluorescent protein (GFP) marker. We observed complete correction of the disease phenotype in the systemic organs up to 10 months after transplantation. PPCA(+) BM-derived cells were detected in all tissues, with the highest expression in liver, spleen, BM, thymus, and lung. In addition, a lysosomal immunostaining was seen in nonhematopoietic cells, indicating efficient uptake of the corrective protein by these cells and cross-correction. Expression in the brain occurred throughout the parenchyma but was mainly localized on perivascular areas. However, PPCA expression in the central nervous system was apparently sufficient to delay the onset of Purkinje cell degeneration and to correct the ataxia. The long-term expression and internalization of the PPCA by cells of systemic organs and the clear improvement of the neurologic phenotype support the use of this approach for the treatment of GS in humans. (Blood. 2002;99:3169-3178)
Sparse Signal Recovery from Quadratic Measurements via Convex Programming (2013)

In this paper we consider a system of quadratic equations $|\langle \bm{z_j}, \bm{x}\rangle|^2=b_j, j=1,\ldots,m$, where $\bm{x} \in \mathbb{R}^n$ is unknown while normal random vectors $\bm{z_j} \in \mathbb{R}^n$ and quadratic measurements $b_j \in \mathbb{R}$ are known. The system is assumed to be underdetermined, i.e., $m<n$. We prove that if there exists a sparse solution $\bm{x}$, i.e., at most $k$ components of $\bm{x}$ are nonzero, then by solving a convex optimization program, we can solve for $\bm{x}$ up to a multiplicative constant with high probability, provided that $k\leq O(\sqrt{m\over{\log n}})$. On the other hand, we prove that $k \leq O(\log n\sqrt{m})$ is necessary for a class of natural convex relaxations to be exact.
Enhancing Skills of Paraeducators: A Training Program Available to Utah School Districts (1996)

Ocular demodicosis is a risk factor for pterygium recurrence, especially for conjunctival recurrence, presumably by perpetuating chronic inflammation mediated by T-helper (Th)17 lymphocytes.
From oligonucleotide shapes to genomic SELEX: Novel biological regulatory loops (1997)

The SELEX method and oligonucleotide combinatorial chemistry discovery process yields high-affinity/high-specificity ligands for virtually any molecular target. Typically, the enormous starting libraries used in the SELEX process contain 10(14)-10(15) sequences. We now ask if the smaller sequences, complexity of extant organisms, and evolutionary history provide useful interactions between oligonucleotides and at least some unexpected targets. That is, do organisms contain a robust "linkage map" between their oligonucleotides and proteins and/or small molecules that enriches life?
Iron-Regulated Biofilm Formation inStaphylococcus aureusNewman Requiresicaand the Secreted Protein Emp (2008)

Staphylococcus aureus biofilm formation is induced in iron-restricted growth conditions in vitro. In this study, we showed that Emp and Eap play important roles in low-iron-induced biofilm formation of S. aureus Newman. Eap and Emp are secreted proteins which are non-covalently attached to the S. aureus cell surface and have previously been implicated in a number of aspects of S. aureus pathogenesis. We showed here that the transcription of these important virulence factors is induced by growth in low-iron medium, reflective of the in vivo environment. Our results show that iron regulation of Eap and Emp is Fur independent. However, Fur is required for full induction of eap and emp expression in low-iron conditions. In this study, we demonstrated that in addition to Fur, low-iron-induced biofilm formation requires Sae, Agr, and SarA. In iron-restricted growth conditions, Sae and Agr are essential for Emp and Eap expression and hence for biofilm formation, whereas SarA appears to have a less-significant role. We also showed that expression of the ica operon is required for biofilm formation in iron-restricted growth conditions. We demonstrated that in fact, ica is required for the expression of the important multifunctional virulence determinants eap and emp.
Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models (2010)

KRAS is one of the most frequently mutated human oncogenes. In some settings, oncogenic KRAS can trigger cellular senescence, whereas in others it produces hyperproliferation. Elucidating the mechanisms regulating these 2 drastically distinct outcomes would help identify novel therapeutic approaches in RAS-driven cancers. Using a combination of functional genomics and mouse genetics, we identified a role for the transcription factor Wilms tumor 1 (WT1) as a critical regulator of senescence and proliferation downstream of oncogenic KRAS signaling. Deletion or suppression of Wt1 led to senescence of mouse primary cells expressing physiological levels of oncogenic Kras but had no effect on wild-type cells, and Wt1 loss decreased tumor burden in a mouse model of Kras-driven lung cancer. In human lung cancer cell lines dependent on oncogenic KRAS, WT1 loss decreased proliferation and induced senescence. Furthermore, WT1 inactivation defined a gene expression signature that was prognostic of survival only in lung cancer patients exhibiting evidence of oncogenic KRAS activation. These findings reveal an unexpected role for WT1 as a key regulator of the genetic network of oncogenic KRAS and provide important insight into the mechanisms that regulate proliferation or senescence in response to oncogenic signals.
Interpretation of Animal Dose and Human Equivalent Dose for Drug Development (2010)

Objectives : To introduce to TKM scientific dose conversion methods of human to animal or animal to human for new drug investigations. Methods : We searched guidelines of the FDA and KFDA, and compared them with references for drug-dose conversion from various databases such as PubMed and Google. Then, we analyzed the potential issues and problems related to dose conversion in safety documentation of new herbal drugs based on our experiences during Investigational New Drug (IND) applications of TKM. Results : Dose conversion from human to animal or animal to human must be appropriately translated during new drug development. From time to time, investigators have some difficulty in determining the appropriate dose, because of misunderstandings of dose conversion, especially when they estimate starting dose in clinical or animal studies to investigate efficacy, toxicology and mechanisms. Therefore, education of appropriate dose calculation is crucial for investigators. The animal dose should not be extrapolated to humans by a simple conversion method based only on body weight, because many studies suggest the normalization method is based mainly on body surface area (BSA). In general, the body surface area seems to have good correlation among species with several parameters including oxygen utilization, caloric expenditure, basal metabolism, blood volume and circulating plasma protein. Likewise, a safety factor should be taken into consideration when deciding high dose in animal toxicology study. Conclusion : Herein, we explain the significance of dose conversion based on body surface area and starting dose estimation for clinical trials with safety factor.
Macrophages ingest and are activated by bacterial DNA (1996)

Recent evidence suggests that bacterial DNA activates immune responses. Here we showed that TNF-alpha mRNA was induced in bone marrow-derived macrophages and the macrophage cell line RAW 264 by plasmid DNA, but not by DNaseI-digested plasmid, plasmid methylated on CpG dinucleotides, or by vertebrate genomic DNA, which is naturally largely methylated on these sequences. Synthetic polynucleotides poly d(I-C) and poly I x poly C also induced TNF-alpha. IL-1 beta and plasminogen activator inhibitor-2 mRNAs were induced by plasmid DNA, and IFN-gamma-pretreated macrophages responded to DNA with induction of inducible nitric oxide synthase. The HIV-1 long terminal repeat was activated by exogenous DNA in a manner similar to TNF-alpha, and was also activated by a CpG-containing oligonucleotide. Transcription factor nuclear factor-kappa B (NF-kappa B) is involved in regulation of the HIV-1 long terminal repeat and many inflammatory response genes. NF-kappa B binding activity was increased by plasmid DNA. An important question is whether these effects involve DNA binding to a cell surface receptor that signals to the interior, or whether internalization is necessary. Here we found that plasmid was taken up by RAW 264 cells and remained sufficiently intact to code for luciferase protein. Results suggest that DNA is taken up by macrophages and characteristic bacterial DNA sequences, which include an unmethylated CpG sequence, activate a signaling cascade leading to activation of NF-kappa B and inflammatory gene induction. Relevance to DNA vaccination, gene therapy, antisense, and transfection studies is discussed.
A Mild Chemically Cleavable Linker System for Functional Proteomic Applications (2007)

An amicable split: Small-molecule probes can be applied for the enrichment of specific protein targets from a complex proteome. A cleavable linker system, which prevents the release of unwanted, nonspecifically bound proteins, can be used for a very mild and highly selective cleavage of probe-labeled proteins.
Toxicity of Bupivacaine Encapsulated into Liposomes and Injected Intravenously (1993)

The acute central nervous system and cardiac toxicities of 0.25% bupivacaine, without adrenalin, encapsulated in multilamellar liposomes were compared with 0.25% plain solutions with and without adrenalin after intravenous infusion at a rate of 0.15 mg.kg-1 x min-1 with an increase of 0.036 mg.kg-1 x min-1 every 10 min. Three groups of six anesthetized, unventilated rabbits were studied. The doses of bupivacaine (in mg.kg-1) which produced seizure, ventricular tachycardia, and asystole were determined. The doses of bupivacaine inducing seizure and ventricular tachycardia were significantly higher for liposomal bupivacaine than for the two plain solutions. A statistical comparison of the cumulative lethal doses of bupivacaine 0.25% with adrenalin and of liposomal bupivacaine led to a P = 0.06. Adrenalin did not modify the systemic toxicity of the local anesthetic. This study showed a reduction of nervous and cardiac toxicity of bupivacaine encapsulated in multilamellar liposomes when infused intravascularly.
Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease (2004)

24S-hydroxycholesterol is a side-chain oxidized oxysterol formed in the brain that is continuously crossing the blood-brain barrier to reach the circulation. There may be an opposite flux of 27-hydroxycholesterol, which is formed to a lower extent in the brain than in most other organs. Here we measured cholesterol, lathosterol, 24S- and 27-hydroxycholesterol, and plant sterols in four different brain areas of deceased Alzheimer's disease (AD) patients and controls. 24S-hydroxycholesterol was decreased and 27-hydroxycholesterol increased in all the brain samples from the AD patients. The difference was statistically significant in four of the eight comparisons. The ratio of 27-hydroxycholesterol to 24S-hydroxycholesterol was significantly increased in all brain areas of the AD patients and also in the brains of aged mice expressing the Swedish Alzheimer mutation APP751. Cholesterol 24S-hydroxylase and 27-hydroxylase protein was not significantly different between AD patients and controls. A high correlation was observed between the levels of 24S-hydroxycholesterol and lathosterol in the frontal cortex of the AD patients but not in the controls. Most probably the high levels of 27-hydroxycholesterol are due to increased influx of this steroid over the blood-brain barrier and the lower levels of 24S-hydroxycholesterol to decreased production. The high correlation between lathosterol and 24-hydroxycholesterol is consistent with a close coupling between synthesis and metabolism of cholesterol in the frontal cortex of the AD brain.