gebhart/patrepeval huggingface dataset:
Genome walking in eukaryotes (2011)

Genome walking is a molecular procedure for the direct identification of nucleotide sequences from purified genomes. The only requirement is the availability of a known nucleotide sequence from which to start. Several genome walking methods have been developed in the last 20 years, with continuous improvements added to the first basic strategies, including the recent coupling with next generation sequencing technologies. This review focuses on the use of genome walking strategies in several aspects of the study of eukaryotic genomes. In a first part, the analysis of the numerous strategies available is reported. The technical aspects involved in genome walking are particularly intriguing, also because they represent the synthesis of the talent, the fantasy and the intelligence of several scientists. Applications in which genome walking can be employed are systematically examined in the second part of the review, showing the large potentiality of this technique, including not only the simple identification of nucleotide sequences but also the analysis of large collections of mutants obtained from the insertion of DNA of viral origin, transposons and transfer DNA (T-DNA) constructs. The enormous amount of data obtained indicates that genome walking, with its large range of applicability, multiplicity of strategies and recent developments, will continue to have much to offer for the rapid identification of unknown sequences in several fields of genomic research.
Eosinophilic airway inflammation in COPD (2006)

Chronic obstructive pulmonary disease is a common condition and a major cause of mortality. COPD is characterized by irreversible airflow obstruction. The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation. The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages. Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD. This airway eosinophilia is increased in exacerbations. Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD. Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation. In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions. Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation.
N-acetylcysteine increases the biosynthesis of recombinant EPO in apoptotic Chinese hamster ovary cells (1999)

Sodium butyrate (NaBu) is known to enhance the rate of biosynthesis of recombinant proteins in Chinese hamster ovary cells (CHO). Here we demonstrate that supplementation with NaBu during rapid growth brings about abrupt death of the cells. The death of the cells is due to apoptosis, as assessed by intranucleosomal DNA fragmentation. The promotion of apoptotic death of the cells could be partially blocked by treatment with the well-known antioxidant, N-acetylcysteine (NAC). Strikingly, the NAC treatment enhanced the production of recombinant EPO two-fold compared with that of the culture without NAC supplementation. These results showed that NaBu treatment supplemented with NAC not only inhibits apoptosis, but also exerts a synergistic effect on the biosynthesis of recombinant EPO.
Vaccination strategies for the treatment and prevention of cervical cancer (2004)

While successful prophylactic HPV vaccines have entered large clinical trials, therapeutic HPV vaccines, in spite of T cell induction, lack clinical responses due to the problem of tumor immune evasion. Adjuvants for systemic and local immune modulation will be mandatory for effective therapy.
Fecal Flora Reconstitution for Recurrent Clostridium difficile Infection: Results and Methodology (2010)

Fecal Flora Reconstitution is an effective, viable, and simple method of treatment for the difficult to treat patients with RCDI who fail standard therapy.
A Highly Diastereomerically Enriched Benzyllithium Compound: The Molecular Structure and the Stereochemical Course of Its Transformations (2002)

The solid state structure of the lithiated [(benzylsilyl)methyl]amine Me2Si{[R]-[CHLiPh]}(CH2SMP) [(R,S)-2] {SMP = 1-[(S)-2-(methoxymethyl)pyrrolidinyl]} and the absolute configuration at the metalated carbon center of this alkyllithium compound, which is highly diastereomerically enriched in solution, were determined by single-crystal X-ray diffraction methods. The stereochemical course of an integral sequence of transformations, starting from unmetalated [(benzylsilyl)methyl]amine 1, was experimentally clarified. For the selective reaction of [(R,S)-2] with MeI, inversion of the configuration at the metalated carbon center was found.
Molecular Design and Ordering Effects in π-Functional Materials for Transistor and Solar Cell Applications (2011)

Organic electronics are broadly anticipated to impact the development of flexible thin-film device technologies. Among these, solution-processable π-conjugated polymers and small molecules are proving particularly promising in field-effect transistors and bulk heterojunction solar cells. This Perspective analyzes some of the most exciting strategies recently suggested in the design and structural organization of π-functional materials for transistor and solar cell applications. Emphasis is placed on the interplay between molecular structure, self-assembling properties, nanoscale and mesoscale ordering, and device efficiency parameters. A critical look at the various approaches used to optimize both materials and device performance is provided to assist in the identification of new directions and further advances.
RGD-Based Strategies To Target Alpha(v) Beta(3) Integrin in Cancer Therapy and Diagnosis (2012)

The integrin α(v)β(3) plays an important role in angiogenesis. It is expressed on tumoral endothelial cells as well as on some tumor cells. RGD peptides are well-known to bind preferentially to the α(v)β(3) integrin. In this context, targeting tumor cells or tumor vasculature by RGD-based strategies is a promising approach for delivering anticancer drugs or contrast agents for cancer therapy and diagnosis. RGD-based strategies include antagonist drugs (peptidic or peptidomimetic) of the RGD sequence, RGD-conjugates, and the grafting of the RGD peptide or peptidomimetic, as targeting ligand, at the surface of nanocarriers. Although all strategies are overviewed, this review aims to particularly highlight the position of RGD-based nanoparticles in cancer therapy and imaging. This review is divided into three parts: the first one describes the context of angiogenesis, the role of the integrin α(v)β(3), and the binding of the RGD peptide to this integrin; the second one focuses on RGD-based strategies in cancer therapy; while the third one focuses on RGD-based strategies in cancer diagnosis.
Biotechnology and the improvement of forage legumes (1997)

Introduction to problems in the production of forage legumes breeding methods for forage legumes tannins and forage quality temperature and drought stress salinity and aluminium stress resistance to insect pests resistance to fungal pathogens engineering for resistance to virus diseases applying plant-microbe signalling concepts to alfalfa - roles of secondary metabolites competition among rhizobia for nodulation of legumes nitrogen fixing capacity RAPD and RFLP mapping synthetic seeds germplasm conservation production of industrial enzymes in transgenic alfalfa somatic hybridization and embryo rescue for the introduction of wild germplasm.
Oligonucleotide Analogs Containing Dephospho- Internucleoside Linkages (2003)

Nonionic oligonucleotide analogs have attracted much interest in recent years as potential candidates for oligonucleotide-based therapeutics. Compared to their natural parent molecules, they are expected to have the advantage of:
Interaction with constraints in 3D modeling (1991)

The purpose of our research is to simplify and improve the effectiveness of the interactive definition of geometric objects in computer aided geometric modeling. To achieve this goal, two ways of defining geometric objects are combined and interfaced 1) the definition of objects by graphical interaction and 2) the specification of objects by geometric constraints. To demonstrate the practicability of the proposed approach, a geometric modeling system was implemented. In this system, interactive modeling operations automatically generate constraints to maintain the properties intended by their invocatio~and constraints, in turn, determine the degrees of freedom for further int eractive mouse-controlled modeling operations. A symbolic geometric constraint solver is employed for solvings ystems of constraints. Group hierarchies are utilized for representing dependencies and for locfllzing systems of constraints. 1
CD47 Regulates Bone Mass and Tumor Metastasis to Bone (2009)

CD47, also called integrin-associated protein, plays a critical role in the innate immune response and is an atypical member of the immunoglobulin superfamily that interacts with and activates beta3 integrins. beta3 integrin(-/-) mice have defective platelet and osteoclast function and are protected from bone metastasis. The role of CD47 in skeletal homeostasis and bone metastasis has not been described. CD47(-/-) mice had increased bone mass and defective osteoclast function in vivo. Although the number of functional osteoclasts formed by differentiating CD47(-/-) bone marrow macrophages was decreased, high doses of RANKL rescued differentiation and function of CD47(-/-) osteoclasts ex vivo and rescued the osteoclast defect in CD47(-/-) mice. Inhibition of nitric oxide (NO) synthase, which is expressed at higher levels in CD47(-/-) osteoclasts, also rescued the osteoclast defect in CD47(-/-) cells. We then examined the consequences of this osteoclast defect in bone metastasis. In a model of tumor metastasis to bone, bone tumor burden was decreased in the CD47(-/-) mice compared with wild-type (WT) controls, with no decrease in s.c. tumor growth in CD47(-/-) mice. There was decreased tumor-associated bone destruction in the CD47(-/-) mice compared with WT controls, consistent with a defect in osteoclast function that was not rescued by the presence of tumor. Our data show that CD47 regulates osteoclastogenesis, in part, via regulation of NO production, and its disruption leads to a decrease in tumor bone metastasis. CD47 is a novel therapeutic target to strengthen bone mass and diminish metastatic tumor growth in bone.
Role of renal sympathetic nerves in mediating hypoperfusion of renal cortical microcirculation in experimental congestive heart failure and acute extracellular fluid volume depletion. (1985)

To evaluate the pathophysiologic importance of renal nerves in regulating the renal vasomotor tone, we measured several parameters of renal cortical microcirculation before and after acute renal denervation (DNx) in the following three groups of anesthetized Munich-Wistar rats: (group 1) congestive heart failure after surgically induced myocardial infarction (n = 10), (group 2) acute extracellular fluid volume depletion after deprivation of drinking water for 48 h (n = 8), and (group 3) sham or nontreated controls (n = 6). In the myocardial-infarcted rats, DNx led to a uniform increase in glomerular plasma flow rate of, on average, 36%. Single nephron glomerular filtration rate of myocardial-infarcted rats also increased despite a reduction in glomerular capillary hydraulic pressure. These changes were associated with a fall in arteriolar resistances, particularly in the efferent arteriole. The glomerular capillary ultrafiltration coefficient rose in all but one myocardial-infarcted animal. A similar hemodynamic pattern was seen after DNx in water-deprived animals. In every water-deprived animal, glomerular plasma flow rate and single nephron GFR increased on average by 28 and 14%, respectively. Again, afferent and efferent arteriolar resistances decreased significantly. Furthermore, the ultrafiltration coefficient increased uniformly and substantially with DNx. To ascertain the potential importance of the interaction between the renal nerves and angiotensin II in these circumstances, we compared the renal cortical hemodynamics in additional groups of water-deprived rats (group 4) after DNx (n = 15), (group 5) during inhibition of angiotensin II with saralasin (n = 15), and (group 6) during treatment with both saralasin and DNx (n = 15). No appreciable difference was detected between group 4 vs. 6. In contrast, substantial differences were noted between group 5 vs. 6: on average, the glomerular plasma flow rate was 26% higher and the afferent and efferent arteriolar resistances 25% and 27% lower, respectively, in group 6. These observations provide direct evidence to indicate pathophysiologic importance of renal nerves in the profound intrarenal circulatory adjustments in prerenal circulatory impairment. The vasoconstrictive effects of renal nerves appear to be mediated in part by their stimulatory influence on angiotensin II release and their direct constrictor actions on pre- and post-glomerular vessels as well.
Fluorophore Targeting to Cellular Proteins via Enzyme-Mediated Azide Ligation and Strain-Promoted Cycloaddition (2012)

Methods for targeting of small molecules to cellular proteins can allow imaging with fluorophores that are smaller, brighter, and more photostable than fluorescent proteins. Previously, we reported targeting of the blue fluorophore coumarin to cellular proteins fused to a 13-amino acid recognition sequence (LAP), catalyzed by a mutant of the Escherichia coli enzyme lipoic acid ligase (LplA). Here, we extend LplA-based labeling to green- and red-emitting fluorophores by employing a two-step targeting scheme. First, we found that the W37I mutant of LplA catalyzes site-specific ligation of 10-azidodecanoic acid to LAP in cells, in nearly quantitative yield after 30 min. Second, we evaluated a panel of five different cyclooctyne structures and found that fluorophore conjugates to aza-dibenzocyclooctyne (ADIBO) gave the highest and most specific derivatization of azide-conjugated LAP in cells. However, for targeting of hydrophobic fluorophores such as ATTO 647N, the hydrophobicity of ADIBO was detrimental, and superior targeting was achieved by conjugation to the less hydrophobic monofluorinated cyclooctyne (MOFO). Our optimized two-step enzymatic/chemical labeling scheme was used to tag and image a variety of LAP fusion proteins in multiple mammalian cell lines with diverse fluorophores including fluorescein, rhodamine, Alexa Fluor 568, ATTO 647N, and ATTO 655.
Characterization of anti-DNA B cells that escape negative selection (1999)

One of the challenges in the study of autoimmunity is to understand which autoreactive cells are subject to regulation and what mechanisms of regulation are operative.In mice transgenic for the R4A-+ 2b heavy chain of an anti-double stranded (ds) DNA antibody, the + 2b heavy chain can pair with the full spectrum of endogenous light chains to produce a multitude of antibodies, including anti-dsDNA antibodies of different affinities and fine specificities.We have previously demonstrated the existence of two populations of anti-DNA B cells in non-autoimmune hosts: a high-affinity population which is rendered anergic in vivo, and a second high-affinity population which is deleted.We have now identified a third population of dsDNA-binding B cells.These cells produce germ-line-encoded antibodies with an apparent affinity for dsDNA that is 1 to 4 logs lower than the apparent affinities of antibodies made by anergic or deleted B cells, and represent a non-tolerized population which escapes regulation.Based on its characterization, we can define a molecular threshold for tolerance induction, and can speculate on the fate of these B cells when they are recruited to an immune response and undergo somatic mutation to become high-affinity anti-DNA B cells.
The β actin promoter (1989)

Although beta actin mRNA is down-regulated during myogenesis, the beta actin promoter confers constitutive expression when joined to heterologous genes transfected into a variety of different cell backgrounds, including differentiated muscle. Normal promoter activity is dependent upon the binding of a ubiquitous factor to the CCAAT-box element. Loss or reduction in factor binding correlates with a major reduction in promoter activity both in vivo and in vitro. The binding domain covers approximately 23 base pairs as determined by DNase footprinting. Methylation of A and G residues in and adjacent to the CCAAT box results in the loss of factor binding. Mutations across the binding domain indicate that the sequence GCCAATCAG within the domain is sufficient as a recognition sequence for factor binding. This binding is not competed by the alpha cardiac actin CCAAT sequence. Bandshift experiments demonstrate a predominant single band of similar mobility in nuclear extracts from various cells and tissues, with the exception of HeLa cells. The prevalence of the factor and its recognition sequence in a variety of promoters suggests that this factor has a common role in the transcriptional activation of several eukaryotic promoters.
Photoinduced Electron Transfer from a Conducting Polymer to Buckminsterfullerene (1992)

Evidence for photoinduced electron transfer from the excited state of a conducting polymer onto buckminsterfullerene, C(60), is reported. After photo-excitation of the conjugated polymer with light of energy greater than the pi-pi* gap, an electron transfer to the C(60) molecule is initiated. Photoinduced optical absorption studies demonstrate a different excitation spectrum for the composite as compared to the separate components, consistent with photo-excited charge transfer. A photoinduced electron spin resonance signal exhibits signatures of both the conducting polymer cation and the C(60) anion. Because the photoluminescence in the conducting polymer is quenched by interaction with C(60), the data imply that charge transfer from the excited state occurs on a picosecond time scale. The charge-separated state in composite films is metastable at low temperatures.
The max-min hill-climbing Bayesian network structure learning algorithm (2006)

We present a new algorithm for Bayesian network structure learning, called Max-Min Hill-Climbing (MMHC). The algorithm combines ideas from local learning, constraint-based, and search-and-score techniques in a principled and effective way. It first reconstructs the skeleton of a Bayesian network and then performs a Bayesian-scoring greedy hill-climbing search to orient the edges. In our extensive empirical evaluation MMHC outperforms on average and in terms of various metrics several prototypical and state-of-the-art algorithms, namely the PC, Sparse Candidate, Three Phase Dependency Analysis, Optimal Reinsertion, Greedy Equivalence Search, and Greedy Search. These are the first empirical results simultaneously comparing most of the major Bayesian network algorithms against each other. MMHC offers certain theoretical advantages, specifically over the Sparse Candidate algorithm, corroborated by our experiments. MMHC and detailed results of our study are publicly available at http://www.dsl-lab.org/supplements/mmhc_paper/mmhc_index.html.
[Recurrent supraventricular tachycardia. The efficacy of a radio frequency system inserted into the coronary sinus]. (1978)

The case is reported of a man of 66 with attacks of recurrent supraventricular tachycardia (SVT) which failed to respond to the standard medical treatment and which, because of their frequency, led to mental disturbances. The electrophysiological features of SVT are discussed, and the possibilities of recording potentials from the SA node. A definitive pacemaker was placed in the coronary sinus, and linked to a simple stimulator working at radio frequency (and activated by the patient himself); this led to an almost immediate reduction in the attacks of SVT.
GlycoMinestruct: a new bioinformatics tool for highly accurate mapping of the human N-linked and O-linked glycoproteomes by incorporating structural features (2016)

Glycosylation plays an important role in cell-cell adhesion, ligand-binding and subcellular recognition. Current approaches for predicting protein glycosylation are primarily based on sequence-derived features, while little work has been done to systematically assess the importance of structural features to glycosylation prediction. Here, we propose a novel bioinformatics method called GlycoMine<sup>struct</sup>(http://glycomine.erc.monash.edu/Lab/GlycoMine_Struct/) for improved prediction of human N- and O-linked glycosylation sites by combining sequence and structural features in an integrated computational framework with a two-step feature-selection strategy. Experiments indicated that GlycoMine<sup>struct</sup> outperformed NGlycPred, the only predictor that incorporated both sequence and structure features, achieving AUC values of 0.941 and 0.922 for N- and O-linked glycosylation, respectively, on an independent test dataset. We applied GlycoMine<sup>struct</sup> to screen the human structural proteome and obtained high-confidence predictions for N- and O-linked glycosylation sites. GlycoMine<sup>struct</sup> can be used as a powerful tool to expedite the discovery of glycosylation events and substrates to facilitate hypothesis-driven experimental studies.