gebhart/patrepeval huggingface dataset:
Site-directed mutagenesis in Arabidopsis thaliana using dividing tissue-targeted RGEN of the CRISPR/Cas system to generate heritable null alleles (2014)

Dividing tissue-targeted site-directed mutagenesis using RGEN of CRISPR/Cas system produces heritable mutations in Arabidopsis thaliana. Site-directed genome engineering in higher plants has great potential for basic research and molecular breeding. Here, we describe a method for site-directed mutagenesis of the Arabidopsis nuclear genome that efficiently generates heritable mutations using the RNA-guided endonuclease (RGEN) derived from bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 (CRISPR associated) protein system. To induce mutagenesis in proliferating tissues during embryogenesis and throughout the plant life cycle, the single guide RNA (sgRNA) and Cas9 DNA endonuclease were expressed from the U6 snRNA and INCURVATA2 promoters, respectively. After Agrobacterium-mediated introduction of T-DNAs encoding RGENs that targets FLOWERING LOCUS T (FT) and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 4 genes, somatic mutagenesis at the targeted loci was observed in T1 transformants. In the results of FT-RGEN, T1 plants often showed late flowering indicative of the presence of large somatic sectors in which the FT gene is mutated on both chromosomes. DNA sequencing analysis estimated that about 90 % of independent chromosomal DNA fragments carried mutations in the analyzed tissue of a T1 plant showing late flowering. The most frequently detected somatic polymorphism showed a high rate of inheritance in T2 plants, and inheritance of less frequent polymorphisms was also observed. As a result, late-flowering plants homozygous for novel, heritable null alleles of FT including a 1 bp insertion or short deletions were recovered in the following T2 and T3 generations. Our results demonstrate that dividing tissue-targeted mutagenesis using RGEN provides an efficient heritable genome engineering method in A. thaliana.
Pathogenesis, diagnosis and treatment of systemic amyloidosis (2001)

Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble fibrils that disrupt tissue structure and cause disease. Although about 20 different unrelated proteins can form amyloid fibrils in vivo, all such fibrils share a common cross-beta core structure. Some natural wild-type proteins are inherently amyloidogenic, form fibrils and cause amyloidosis in old age or if present for long periods at abnormally high concentration. Other amyloidogenic proteins are acquired or inherited variants, containing amino-acid substitutions that render them unstable so that they populate partly unfolded states under physiological conditions, and these intermediates then aggregate in the stable amyloid fold. In addition to the fibrils, amyloid deposits always contain the non-fibrillar pentraxin plasma protein, serum amyloid P component (SAP), because it undergoes specific calcium-dependent binding to amyloid fibrils. SAP contributes to amyloidogenesis, probably by stabilizing amyloid fibrils and retarding their clearance. Radiolabelled SAP is an extremely useful, safe, specific, non-invasive, quantitative tracer for scintigraphic imaging of systemic amyloid deposits. Its use has demonstrated that elimination of the supply of amyloid fibril precursor proteins leads to regression of amyloid deposits with clinical benefit. Current treatment of amyloidosis comprises careful maintenance of impaired organ function, replacement of end-stage organ failure by dialysis or transplantation, and vigorous efforts to control underlying conditions responsible for production of fibril precursors. New approaches under development include drugs for stabilization of the native fold of precursor proteins, inhibition of fibrillogenesis, reversion of the amyloid to the native fold, and dissociation of SAP to accelerate amyloid fibril clearance in vivo.
Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis (2006)

Ventricular myocyte hypertrophy is an important compensatory growth response to pressure overload. However, pathophysiological cardiac hypertrophy is accompanied by reactive fibrosis and remodeling. The Rho kinase family, consisting of ROCK1 and ROCK2, has been implicated in cardiac hypertrophy and ventricular remodeling. However, these previous studies relied heavily on pharmacological inhibitors,and not on gene deletion. Here we used ROCK1knockout (ROCK1-/-) mice to investigate role of ROCK1 in the development of ventricular remodeling induced by transverse aortic banding. We observed that ROCK1 deletion did not impair compensatory hypertrophic response induced by pressure overload. However, ROCK1-/- mice exhibited reduced perivascular and interstitial fibrosis, which was observed at 3 wk but not at 1 wk after the banding. The reduced fibrosis in the myocardium of ROCK1-/- mice was closely associated with reduced expression of a variety of extracellular matrix (ECM) proteins and fibrogenic cytokines such as TGFbeta2 and connective tissue growth factor. This inhibitory effect of ROCK1 deletion on pathophysiological induction of fibrogenic cytokines was further confirmed in the myocardium of transgenic mice with cardiomyocyte-specific overexpression of Gq. Thus, these results indicate that ROCK1 contributes to the development of cardiac fibrosis and induction of fibrogenic cytokines in cardiomyocytes in response to pathological stimuli.
cDNA Cloning of a Novel Membrane Glycoprotein That Is Expressed Specifically in Glial Cells in the Mouse Brain (1996)

A cDNA encoding a protein designated as LIG-1 has been cloned and characterized. A fragment of this cDNA was found previously in a screen for genes up-regulated during neural differentiation in mouse P19 embryonal carcinoma cells. Comparative sequence analysis revealed LIG-1 to be a novel integral membrane glycoprotein (1091 amino acids) containing an extracellular region (794 amino acids) with a potential signal peptide, 15 leucine-rich repeats, 3 immnunoglobulin-like domains, and 7 potential N-glycosylation sites, a transmembrane region of 23 amino acids, and a cytoplasmic region of 274 amino acids. This protein, therefore, is a new member of both the leucine-rich repeat and the immunoglobulin superfamilies. Furthermore, Northern blot and in situ hybridization analyses showed LIG-1 gene expression to be predominantly in the brain, restricted to a small subset of glial cells such as Bergmann glial cells of the cerebellum and glial cells in the nerve fiber layer of the olfactory bulb. On the basis of its structural features and expression pattern, we propose that LIG-1 functions as a cell type-specific adhesion molecule or receptor at the glial cell surface, and plays a role in the nervous system in for example neuroglial differentiation, development, and/or maintenance of neural functions where it is expressed.
Chemical synthesis of a gene for human epidermal growth factor urogastrone and its expression in yeast. (1983)

We have chemically synthesized and expressed in yeast a gene coding for human epidermal growth factor (urogastrone), a 53-amino-acid polypeptide that has been shown to promote epithelial cell proliferation and to inhibit gastric acid secretion. The synthetic gene, consisting of 170 base pairs, was designed with yeast-preferred codons and assembled by enzymatic ligation of synthetic fragments produced by phosphoramidite chemistry. The DNA synthesis protocol used allows for facile synthesis of oligonucleotides larger than 50 bases. Yeast cells were transformed with plasmids containing the synthetic gene under control of a yeast glyceraldehyde-3-phosphate dehydrogenase gene promoter and were shown to synthesize a biologically active human epidermal growth factor.
Note on the use of the Wigner distribution for time-frequency signal analysis (1988)

It is shown that a correct use of the Wigner distribution (WD) for time-frequency signal analysis requires use of the analytic signal. This version, often referred to as the Wigner-Ville distribution (WVD), is straightforward to compute, does not exhibit any aliasing problem, and introduces no frequency artifacts. The problems introduced by the use of the Wigner distribution with a real signal are clarified.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Entropy-constrained trellis-coded quantization (1992)

Trellis-coded quantization is generalized to allow noiseless coding of the trellis branch reproduction symbols. An entropy-constrained trellis-coded quantization (ECTCQ) design algorithm is presented, based on the generalized Lloyd algorithm for trellis code design and the entropy-constrained vector quantization design algorithm. ECTCQ systems are designed for memoryless Gaussian and Laplacian sources, and for first- and second-order Gauss-Markov sources. With an 8-state trellis, the mean-squared error ECTCQ encoding performance for memoryless sources with smooth densities is within about 0.5 dB of the rate-distortion function. Small additional improvements are achieved with larger trellises. Similar, though not quite as good, performance is achieved for the Gauss-Markov sources by using the ECTCQ in a predictive coding structure.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
[Effects of calculi structure on the results of ESWL lithotripsy]. (2002)

Structure of stones influences effects and sequelae of extracorporeal shock-wave lithotripsy (ESWL). Clinical sequelae of ESWL in oxalate stones are the worst because of the fragments size and physical qualities of these stones. Oxalates are firm and sharp. Such qualities may cause injury and swelling of the ureter when the fragments pass it. A JJ stent and catheter are proposed to prevent complications of oxalate stone ESWL in the stones size more than 1.5 cm.
High IL-6 and Low IL-10 in the Central Nervous System Are Associated with Protracted Relapsing EAE in DA Rats (1997)

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for multiple sclerosis (MS). The mechanisms behind differences in clinical course of EAE in different rat strains have not been defined. We induced acute EAE in Lewis rats and protracted relapsing EAE (PR-EAE) in DA rats and examined mRNA expression of IL-1β, IL-6, IL-10, IL-12, and TNF-β in brain tissue sections, cerebrospinal fluid (CSF) cells, and lymph node cells. IL-1β, IL-12 and TNF-β mRNA expression in brain tissue sections appeared early and peaked at the height of clinical signs in both acute and PR-EAE, consistent with a disease-promoting role for these cytokines. High levels of IL-6 mRNA-expressing cells were present in CNS and lymph node cells in PR-EAE, while almost absent in acute EAE. In contrast, IL-10 was very low in PR-EAE but strongly expressed in acute EAE, in particular during clinical recovery. Regulatory changes of IL-6 and IL-10 both systemically and within the CNS, but with temporal differences between compartments, seem pivotal for development of PR-EAE in DA rats. These findings could have relevance for pathogenesis and treatment of MS.
Mechanical properties of carbon nanotubes: theoretical predictions and experimental measurements (2003)

Mechanical properties of carbon nanotubes are discussed based on recent advances in both modeling and experiment.
Activation of Peroxisome Proliferator-activated Receptor γ Suppresses Nuclear Factor κB-mediated Apoptosis Induced by Helicobacter pylori in Gastric Epithelial Cells (2001)

Helicobacter pylori colonization leads to epithelial cell hyperproliferation within inflamed mucosa, but levels of apoptosis vary, suggesting that imbalances between rates of cell production and loss may contribute to differences in gastric cancer risk among infected populations. Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates inflammatory and growth responses of intestinal epithelial cells. We determined whether activation of PPARgamma modified H. pylori-induced apoptosis in gastric epithelial cells. PPARgamma was expressed and functionally active in gastric epithelial cell lines sensitive to H. pylori-induced apoptosis. PPARgamma ligands 15d-PGJ(2) and BRL-49653 significantly attenuated H. pylomicronri-induced apoptosis, effects that could be reversed by co-treatment with a specific PPARgamma antagonist. Cyclopentanone prostaglandins that do not bind and activate PPARgamma had no effects on H. pylori-induced apoptosis. The ability of H. pylori to activate nuclear factor (NF)-kappaB and increase levels of the NF-kappaB target IL-8 was blocked by co-treatment with PPARgamma agonists, and direct inhibition of NF-kappaB also abolished H. pylori-stimulated apoptosis. These results suggest that activation of the PPARgamma pathway attenuates the ability of H. pylori to induce NF-kappaB-mediated apoptosis in gastric epithelial cells. Because PPARgamma regulates a multitude of host responses, activation of this receptor may contribute to varying levels of cellular turnover as well as the diverse pathologic outcomes associated with chronic H. pylori colonization.
The Lam/Mpi Checkpoint/Restart Framework: System-Initiated Checkpointing (2005)

As high performance clusters continue to grow in size and popularity, issues of fault tolerance and reliability are becoming limiting factors on application scalability. To address these issues, we present the design and implementation of a system for providing coordinated checkpointing and rollback recovery for MPI-based parallel applications. Our approach integrates the Berkeley Lab BLCR kernel-level process checkpoint system with the LAM implementation of MPI through a defined checkpoint/restart interface. Checkpointing is transparent to the application, allowing the system to be used for cluster maintenance and scheduling reasons as well as for fault tolerance. Experimental results show negligible communication performance impact due to the incorporation of the checkpoint support capabilities into LAM/MPI.
Understanding Magnesium Corrosion—A Framework for Improved Alloy Performance (2003)

Abstract The purpose of this paper is to provide a succinct but nevertheless complete mechanistic overview of the various types of magnesium corrosion. The understanding of the corrosion processes of magnesium alloys builds upon our understanding of the corrosion of pure magnesium. This provides an understanding of the types of corrosion exhibited by magnesium alloys, and also of the environmental factors of most importance. This deep understanding is required as a foundation if we are to produce magnesium alloys much more resistant to corrosion than the present alloys. Much has already been achieved, but there is vast scope for improvement. This present analysis can provide a foundation and a theoretical framework for further, much needed research. There is still vast scope both for better fundamental understanding of corrosion processes, engineering usage of magnesium, and also on the corrosion protection of magnesium alloys in service.
On the cause of disability glare and its dependence on glare angle, age and ocular pigmentation (2003)

Disability glare is due to intraocular scatter and obeys, in the one-degree to 30-degree angular domain, albeit with great individual spread, the Age-adjusted Stiles-Holladay equation: (L(veil) /E(glare))(Age-adjusted Stiles-Holladay) = 10 (1 + [Age/70](4)).1/theta(2). Quantitative examples are given of the manifestation of disability glare, particularly in traffic.
Peptidic modulators of protein‐protein interactions: Progress and challenges in computational design (2009)

With the decline in productivity of drug-development efforts, novel approaches to rational drug design are being introduced and developed. Naturally occurring and synthetic peptides are emerging as novel promising compounds that can specifically and efficiently modulate signaling pathways in vitro and in vivo. We describe sequence-based approaches that use peptides to mimic proteins in order to inhibit the interaction of the mimicked protein with its partners. We then discuss a structure-based approach, in which protein-peptide complex structures are used to rationally design and optimize peptidic inhibitors. We survey flexible peptide docking techniques and discuss current challenges and future directions in the rational design of peptidic inhibitors.
Short‐term Prognosis of Community‐Acquired Bacteremia in Patients with Liver Cirrhosis or Alcoholism: A Population‐Based Cohort Study (2006)

Liver cirrhosis and alcoholism were associated with a poor short-term prognosis for community-acquired bacteremia. Liver cirrhosis and alcoholism may have independent effects on the prognosis for patients with liver cirrhosis and bacteremia.
Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects (2002)

Cyclophosphamide is an alkylating agent used to treat malignancies and immune-mediated inflammatory non-malignant processes such as lupus nephritis and immune-mediated neuropathies. It has been studied as a treatment for multiple sclerosis (MS) for the past 30 years and is used by physicians in selected cases of progressive or worsening MS. Review of published reports suggests that it is efficacious in cases of worsening MS that have an inflammatory component as evidenced by relapses and/or gadolinium (Gd)-enhancing lesions on magnetic resonance imaging (MRI) or in patients in earlier stages of disease where inflammation predominates over degenerative processes in the central nervous system (CNS). There is no evidence of efficacy in primary progressive MS or later stages of secondary progressive MS. Although a general immunosuppressant that affects both T- and B-cell function, cyclophosphamide has selective immune effects in MS by suppressing IL-12 and Th1-type responses and enhancing Th2/Th3 responses (IL-4, IL-10, TGF-beta; eosinophils in peripheral blood). Side effects include nausea, alopecia, infertility, bladder toxicity and risk of malignancy. The most commonly used regimens involve every 4- to 8-week outpatient i.v. pulse therapy given with or without corticosteroids and are usually well-tolerated by patients. Cyclophosphamide is currently used in patients whose disease is not controlled by beta-interferon or glatiramer acetate and those with rapidly worsening MS.
A precision CMOS bandgap reference (1984)

The simple circuit uses naturally occurring vertical n-p-n bipolar transistors as reference diodes. Use is made of p-tub diffusions as temperature-dependent resistors to provide current bias, and an op-amp is used for voltage gain. Only two reference diodes, three p-tube resistors, and one op-amp are necessary to produce a reference with fixed voltage of -1.3 V. An additional op-amp with two p-tub resistors will adjust the output to any desired value. The criteria for temperature compensation are presented and it is shown that the properly compensated circuit can in principle produce thermal drift which is less than 10 p.p.m.//spl deg/C. Process sensitivity analysis shows that in practical applications it is possible to control the output to better than 2%, while keeping thermal drift below 40 p.p.m.//spl deg/C. Test circuits have been designed and fabricated. The output voltage produced was -1.3/spl plusmn/0.025 V with thermal drift less than 7 mV from 0/spl deg/C to 125/spl deg/C. Significant improvements in performance, at modest cost in circuit complexity, can be achieved if the op-amp offset contribution to the output voltage is reduced or eliminated.
Orientación para el mercado. Percepción de su presencia en los Institutos Politécnicos de Enseñanza Superior portugueses (2016)

Esta investigación busca conceptualizar y poner en práctica la orientación para el mercado en el contexto de la educación superior. Una revisión de la literatura se realizó para profundizar en el estudio de las investigaciones se presentan como concepto fundamental en la construcción y la discusión, lo que permite su funcionamiento para centrarse en los factores que influyen en el nivel de políticas para el mercado de la educación superior. Después de probar el modelo propuesto, se concluye que el modelo tiene la consistencia, a través de su unidimensionalidad. Incluso se concluye que hay un deconocimiento débil del problema como relevante para el desempeño de las instituciones de enseñanza superior. Cabe señalar que los diferentes autores que abordan el tema en la educación superior reconocen que, si bien existe la necesidad de una nueva dinámica agresiva en el sector, esta tiende a no ocurrir u ocurre lentamente.
Small-Animal PET of Tumors with <sup>64</sup>Cu-Labeled RGD-Bombesin Heterodimer (2009)

Compared with other tracers, (64)Cu-NOTA-RGD-bombesin showed favorable in vivo kinetics and enhanced tumor uptake, which warrants its further investigation for targeting tumors that express integrin or GRPR or that coexpress integrin and GRPR for imaging and therapeutic applications. The synergistic effect of RGD-bombesin heterodimers observed in this study also encourages further investigations of novel heterodimers recognizing other cell surface receptors for tumor targeting.
Collagen-Induced Arthritis as a Model of Rheumatoid Arthritis (1994)

Collagen-induced arthritis (CIA) is an animal model for the human autoimmune disease rheumatoid arthritis (RA). CIA can be induced in several species including primates by immunization with heterologous type-II collagen (CII). Polyclonal antibodies are formed upon immunization with CII that exhibit a broad range of epitope specificities (some that cross-react with hose CII); however, only antibodies directed against certain specific epitopes on CII are arthritogenic. Recently, the importance of cognate interactions between T-cells and B-cells to the induction of CIA was demonstrated by administration of monoclonal antibodies against a T-cell surface protein, gp39. Blocking the interaction of T-cell gp39, with its receptor/ligand on the surface of B-cells (CD40), completely blocked induction of CIA in mice. A concomitant reduction in the level of anti-CII IgG produced in anti-gp39-treated animals was observed, demonstrating the crucial importance of T-cell:B-cell interactions via gp39:CD-40 binding to the primary immune response to CII in vivo and therefore to the induction of CIA. Other features of CIA are important in elucidating the condition and this article will deal with some important issues.