gebhart/patrepeval huggingface dataset:
Early Postnatal Cardiac Changes and Premature Death in Transgenic Mice Overexpressing a Mutant Form of Serum Response Factor (2001)

Serum response factor (SRF) is a key regulator of a number of extracellular signal-regulated genes important for cell growth and differentiation. A form of the SRF gene with a double mutation (dmSRF) was generated. This mutation reduced the binding activity of SRF protein to the serum response element and reduced the capability of SRF to activate the atrial natriuretic factor promoter that contains the serum response element. Cardiac-specific overexpression of dmSRF attenuated the total SRF binding activity and resulted in remarkable morphologic changes in the heart of the transgenic mice. These mice had dilated atrial and ventricular chambers, and their ventricular wall thicknesses were only 1/2 to 1/3 the thickness of that of nontransgenic mice. Also these mice had smaller cardiac myocytes and had less myofibrils in their myocytes relative to nontransgenic mice. Altered gene expression and slight interstitial fibrosis were observed in the myocardium of the transgenic mice. All the transgenic mice died within the first 12 days after birth, because of the early onset of severe, dilated cardiomyopathy. These results indicate that dmSRF overexpression in the heart apparently alters cardiac gene expression and blocks normal postnatal cardiac growth and development.
Osteoinduction by biomaterials—Physicochemical and structural influences (2006)

Osteoinduction by biomaterials has been shown to be a real phenomenon by many investigators in the last decade. The exact mechanism of this phenomenon is, however, still largely unknown. This in vivo study in goats was performed to get insight into processes governing the phenomenon of osteoinduction by biomaterials and had four main goals: (i) to further investigate the influence of physicochemical properties and structure on biomaterial osteoinductive potential, (ii) to investigate the influence of implant size on the amount of induced bone, (iii) to investigate implantation site dependence, and (iv) to investigate changes occurring on the surface of the material after implantation. Intramuscular implantations of four different biphasic calcium phosphate ceramics, consisting of hydroxyapatite and beta-tricalcium phosphate and a carbonated apatite ceramic, indicated that, for a maximal osteoinductive potential, there is an optimal specific surface area for each material type. It was further shown that a decrease of the implant size with a half significantly decreased the relative amount of induced bone. In addition, subcutaneous implantation did not give rise to ectopic bone formation in any of the animals, while bone was induced in most animals intramuscularly. Analysis of the surfaces of the materials after subcutaneous implantation inside diffusion chambers indicated that the increased specific surface area leads to more surface reactivity, which is hypothesized to be essential for osteoinductivity by biomaterials.
Mid-Infrared Fiber-Coupled Photoacoustic Sensor for Biomedical Applications (2013)

Biomedical devices employed in therapy, diagnostics and for self-monitoring often require a high degree of flexibility and compactness. Many near infrared (NIR) optical fiber-coupled systems meet these requirements and are employed on a daily basis. However, mid-infrared (MIR) fibers-based systems have not yet found their way to routine application in medicine. In this work we present the implementation of the first MIR fiber-coupled photoacoustic sensor for the investigation of condensed samples in the MIR fingerprint region. The light of an external-cavity quantum-cascade laser (1010-1095 cm(-1)) is delivered by a silver halide fiber, which is attached to the PA cell. The PA chamber is conically shaped to perfectly match the beam escaping the fiber and to minimize the cell volume. This results in a compact and handy sensor for investigations of biological samples and the monitoring of constituents both in vitro and in vivo. The performance of the fiber-coupled PA sensor is demonstrated by sensing glucose in aqueous solutions. These measurements yield a detection limit of 57 mg/dL (SNR = 1). Furthermore, the fiber-coupled sensor has been applied to record human skin spectra at different body sites to illustrate its flexibility.
CASENet: Deep Category-Aware Semantic Edge Detection (2017)

Boundary and edge cues are highly beneficial in improving a wide variety of vision tasks such as semantic segmentation, object recognition, stereo, and object proposal generation. Recently, the problem of edge detection has been revisited and significant progress has been made with deep learning. While classical edge detection is a challenging binary problem in itself, the category-aware semantic edge detection by nature is an even more challenging multi-label problem. We model the problem such that each edge pixel can be associated with more than one class as they appear in contours or junctions belonging to two or more semantic classes. To this end, we propose a novel end-to-end deep semantic edge learning architecture based on ResNet and a new skip-layer architecture where category-wise edge activations at the top convolution layer share and are fused with the same set of bottom layer features. We then propose a multi-label loss function to supervise the fused activations. We show that our proposed architecture benefits this problem with better performance, and we outperform the current state-of-the-art semantic edge detection methods by a large margin on standard data sets such as SBD and Cityscapes.
Total synthesis of isopavine and intermediates for the preparation of substituted amitriptyline analogs: facile routes to substituted dibenzocyclooctatrienes and dibenzocycloheptatrienes (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of isopavine and intermediates for the preparation of substituted amitriptyline analogs: facile routes to substituted dibenzocyclooctatrienes and dibenzocycloheptatrienesMichael E. Jung and Steven J. MillerCite this: J. Am. Chem. Soc. 1981, 103, 8, 1984–1992Publication Date (Print):April 1, 1981Publication History Published online1 May 2002Published inissue 1 April 1981https://pubs.acs.org/doi/10.1021/ja00398a019https://doi.org/10.1021/ja00398a019research-articleACS PublicationsRequest reuse permissionsArticle Views1279Altmetric-Citations32LEARN 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
Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation (2011)

The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown. The full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains <20 clonally represented gene alterations/case, including predominantly nonsilent mutations, and fewer copy number aberrations. These analyses led to the discovery of several genes not previously known to be altered in CLL. Although most of these genes were affected at low frequency in an expanded CLL screening cohort, mutational activation of NOTCH1, observed in 8.3% of CLL at diagnosis, was detected at significantly higher frequency during disease progression toward Richter transformation (31.0%), as well as in chemorefractory CLL (20.8%). Consistent with the association of NOTCH1 mutations with clinically aggressive forms of the disease, NOTCH1 activation at CLL diagnosis emerged as an independent predictor of poor survival. These results provide initial data on the complexity of the CLL coding genome and identify a dysregulated pathway of diagnostic and therapeutic relevance.
Grape seed and skin extract mitigates garlic-induced oxidative stress in rat liver (2012)

Garlic is a commonly used spice in folk medicine that can exert adverse health effects when given at a high dose. Grape seed and skin extract (GSSE) exhibits a variety of beneficial effects even at a high dose. In the present study we evaluated the toxicity of high-dose garlic treatment on liver and the protective effect of GSSE. Rats were intraperitoneally administered either with garlic extract (5 g·(kg body weight)(-1)) or GSSE (500 mg·(kg body weight)(-1)) or a combination of garlic and GSSE at the same doses daily for 1 month. Plasma and hepatic levels of cholesterol, triacylglycerol, and transaminases and liver antioxidant status were evaluated. Data showed that a high garlic dose induced liver toxicity and a pro-oxidative status characterized by increased malondialdehyde and decreased antioxidant enzyme activities as catalase, peroxidase, and superoxide dismutase. Garlic increased intracellular H(2)O(2) but decreased free iron and Ca(2+). GSSE alone or in co-treatment with garlic had the reverse effect and counteracted almost all garlic-induced deleterious impacts to near control levels. In conclusion, a high garlic dose induced a pro-oxidative state characterized by the Fenton reaction between H(2)O(2) and free iron, inducing Ca(2+) depletion, while GSSE exerted antioxidant properties and Ca(2+) repletion.
Effects of Weight Loss in Massive Obesity on Insulin and C-Peptide Dynamics: Sequential Changes in Insulin Production, Clearance, and Sensitivity* (1987)

In massively obese patients hyperinsulinemia and insulin insensitivity usually improve with weight loss. To clarify the mechanism of these reversible abnormalities eight nondiabetic massively obese patients were studied before and at intervals (3 months and 1 yr) after weight loss following gastroplasty. Insulin dynamics were studied during the hyperglycemic clamp (change in glucose, 7 mmol L-1 for 2 h) by measuring the area under the insulin and C-peptide response curves, representing, respectively, systemic insulin response and insulin production. Compared to lean age-matched normal subjects the massively obese patients had the expected fasting hyperinsulinemia and an exaggerated insulin response (P less than 0.05). Within 3 months and after an approximately 20% weight loss, they had a marked reduction in the systemic insulin response but no change in the C-peptide response. Therefore, the reduction in insulin response was due to enhanced hepatic insulin clearance rather than reduced insulin production. Thus, the liver serves a gate-keeping role in regulating the systemic insulin response to a glucose challenge. With additional weight loss of 14% and then weight maintenance, insulin clearance was further increased, and a reduction in insulin production became evident, since the C-peptide response was reduced. Exogenous insulin clearance was measured using the euglycemic clamp technique before and after weight loss. Insulin clearance was initially lower in the massively obese patients compared to that in the normal subjects (P less than 0.05) and increased toward normal with weight loss (P less than 0.05). Similarly, insulin sensitivity, as measured by the ratio of glucose metabolised per U endogenous insulin, normalized with weight loss and weight maintenance. Thus, after significant weight loss followed by weight maintenance at a reduced, but not ideal, level, insulin clearance, production, and sensitivity all reverted to normal. These findings suggest that adipose mass per se may not be exclusively responsible for altered insulin and glucose dynamics in obesity and that additional factors associated with obesity, such as nutrient load, adipose distribution, fat cell size, or fatty acid flux, play a contributing role.
Recent Advances of Hemorrhage Management in Severe Trauma (2014)

Trauma is one of the most common causes of mortality worldwide with a substantial percentage of deaths resulting secondary to haemorrhages, which are preventable and treatable when adequately managed. This paper offers a review of the current literature on how to successfully resuscitate patients with major haemorrhage.
Controlled release of dopamine from a polymeric brain implant: In vivo characterization (1989)

Intracerebral microdialysis was used to evaluate the long-term in vivo release of dopamine from ethylene-vinyl acetate (EVAc)-dopamine copolymer matrix discs for up to 65 days following striatal implantation. Dopamine release occurred through a single cavity present on one side of the disc, which was otherwise fully coated with an additional, impermeable layer of EVAc. At 20 days following implantation of the device, extracellular concentrations of dopamine within the striatum reached micromolar levels, over 200-fold greater than control values. Release of dopamine was shown to be stable and maintained for the 2-month duration of the experiment. Histological examination confirmed the biocompatible nature of the implant. There are potential applications of this technology to the treatment of Parkinson's disease and other neurological and psychiatric disorders.
Cytokine therapeutics: lessons from interferonalpha. (1994)

Cytokines are soluble proteins that allow for communication between cells and the external environment. Interferon (IFN) alpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of growth and differentiation, affecting cellular communication and signal transduction pathways as well as immunological control. This review focuses on the biological and clinical activities of the cytokine. Originally discovered as an antiviral substance, the efficacy of IFN-alpha in malignant, viral, immunological, angiogenic, inflammatory, and fibrotic diseases suggests a spectrum of interrelated pathophysiologies. The principles learned from in vivo studies will be discussed, particularly hairy cell leukemia, chronic myelogenous leukemia, certain angiogenic diseases, and hepatitis. After the surprising discovery of activity in a rare B-cell neoplasm, IFN-alpha emerged as a prototypic tumor suppressor protein that represses the clinical tumorigenic phenotype in some malignancies capable of differentiation. Regulatory agencies throughout the world have approved IFN-alpha for treatment of 13 malignant and viral disorders. The principles established with this cytokine serve as a paradigm for future development of natural proteins for human disease.
Bioinformatics Analysis for Circulating Cell-Free DNA in Cancer (2019)

Molecular analysis of cell-free DNA (cfDNA) that circulates in plasma and other body fluids represents a "liquid biopsy" approach for non-invasive cancer screening or monitoring. The rapid development of sequencing technologies has made cfDNA a promising source to study cancer development and progression. Specific genetic and epigenetic alterations have been found in plasma, serum, and urine cfDNA and could potentially be used as diagnostic or prognostic biomarkers in various cancer types. In this review, we will discuss the molecular characteristics of cancer cfDNA and major bioinformatics approaches involved in the analysis of cfDNA sequencing data for detecting genetic mutation, copy number alteration, methylation change, and nucleosome positioning variation. We highlight specific challenges in sensitivity to detect genetic aberrations and robustness of statistical analysis. Finally, we provide perspectives regarding the standard and continuing development of bioinformatics analysis to move this promising screening tool into clinical practice.
Growth and form of gold nanorods prepared by seed-mediated, surfactant-directed synthesis (2002)

Gold nanorods were prepared via a seed-mediated sequential growth process involving the use of citrate-stabilised seed crystals and their subsequent growth in a series of reaction solutions containing [AuCl4]−, ascorbic acid and the cationic surfactant cetyltrimethylammonuim bromide (CTAB). Electron diffraction analysis and HRTEM images of mature nanorods showed superpositions of two specific pairs of crystallographic zones, either <112> and <100> or <110> and <111>, which were consistent with a cyclic penta-twinned crystal with five {111} twin boundaries arranged radially to the [110] direction of elongation. The nanorods have an idealised 3-D prismatic morphology with ten {111} end faces and five {100} or {110} side faces, or both. TEM studies of crystals at various stages of growth indicated that the seed crystals are initially transformed by growth and aggregation into decahedral penta-twinned crystals, 4% of which become elongated when a fresh reaction solution is added, whilst the remaining twins grow isometrically. Reiteration of this procedure increases the length of the existing nanorods, induces further transformation of isometric particles to produce a second (and third) population of shorter, wider nanorods, and increases the size of the isometric crystals. The data indicate that symmetry breaking in fcc metallic structures to produce anisotropic nanoparticles is based on an intrinsic structural mechanism (twinning) that is subsequently modulated extrinsically during growth in solution by specific adsorption of AuI–surfactant complexes on the side faces/edges of the isometric penta-twinned crystals and which is responsible for the preferential growth along the common [110] axis. We propose that the coupling of multiple twinning and habit modification is a general mechanism that applies to other experimental procedures (electrochemical, inverse micellar media) currently used to prepare metallic nanoparticles with a high aspect ratio.
A primate T-lymphotropic virus, PTLV-L, different from human T-lymphotropic viruses types I and II, in a wild-caught baboon (Papio hamadryas). (1994)

Searching for clues to the evolution of the primate T-lymphotropic viruses (PTLVs), which include the human and the simian T-lymphotropic viruses (HTLV and STLV), we have identified another PTLV, which differs sufficiently from the known PTLV-I and PTLV-II types to be designated here PTLV-L. The virus was isolated from a wild-born baboon (Papio hamadryas) from Eritrea. In a cDNA library a 1802-bp-long fragment was identified that extends from the env region, including the complete transmembrane protein gene, to part of the tax/rex gene. Homologies at the nucleotide sequence level of PTLV-L, prototype simian T-lymphotropic virus-PH969, with HTLV-I and -II, respectively, were 62% and 64% overall, 65% and 70% in the env region, and 80% and 80% in the partial tax/rex sequence. In the 5' part of the pX region a significant homology was seen only with HTLV-II (52%). Phylogenetic analysis based on the gene encoding the transmembrane protein indicates that PTLV-L represents a PTLV type with a long independent evolution, longer than any strain within the PTLV-I or PTLV-II groups. The finding of another PTLV type in African baboons is further evidence of the wide variety of PTLV found on this continent. Whether PTLV-L resembles PTLV-I and PTLV-II in the extension of its host range to other primates, including humans, remains to be seen.
Alteration of chromosome numbers by generation of minichromosomes – Is there a lower limit of chromosome size for stable segregation? (2001)

Practical applications of minichromosomes, generated by de novo composition or by truncation of natural chromosomes, rely on stable transmission of these chromosomes. Functional centromeres, telomeres and replication origins are recognized as prerequisites for minichromosome stability. However, it is not yet clear whether, and if yes, to what degree the chromatin content has a qualitative or quantitative impact on stable chromosome transmission. A small translocation chromosome, which arose after X-irradiation of a reconstructed field bean karyotype, comprised approximately 5% of the haploid metaphase complement and was found to consist of three pieces of duplicated chromatin and a wild-type centromere. This chromosome was stably transmitted through all meristematic and pollen grain mitoses but was frequently lost during meiosis (66% loss in hemizygous and 33% in homozygous condition). This minichromosome was only a little smaller than stably segregating translocation chromosomes (comprising approximately 6% of the genome) of a euploid field bean karyotype. The duplications specific for this minichromosome did not influence meiotic segregation when associated with non-duplicated chromatin of other chromosomes. In comparison with minichromosomes of other species, the possibility of a lower size limit for a stable chromosome transmission must therefore be considered which might be based, for instance, on insufficient lateral support of centromeres or on insufficient bivalent stability due to the incapability of chiasma formation.
Bacteriophage Endolysins as a Novel Class of Antibacterial Agents (2006)

Endolysins are double-stranded DNA bacteriophage-encoded peptidoglycan hydrolases produced in phage-infected bacterial cells toward the end of the lytic cycle. They reach the peptidoglycan through membrane lesions formed by holins and cleave it, thus, inducing lysis of the bacterial cell and enabling progeny virions to be released. Endolysins are also capable of degrading peptidoglycan when applied externally (as purified recombinant proteins) to the bacterial cell wall, which also results in a rapid lysis of the bacterial cell. The unique ability of endolysins to rapidly cleave peptidoglycan in a generally species-specific manner renders them promising potential antibacterial agents. Originally developed with a view to killing bacteria colonizing mucous membranes (with the first report published in 2001), endolysins also hold promise for the treatment of systemic infections. As potential antibacterials, endolysins possess several important features, for instance, a novel mode of action, a narrow antibacterial spectrum, activity against bacteria regardless of their antibiotic sensitivity, and a low probability of developing resistance. However, there is only one report directly comparing the activity of an endolysin with that of an antibiotic, and no general conclusions can be drawn regarding whether lysins are more effective than traditional antibiotics. The results of the first preclinical studies indicate that the most apparent potential problems associated with endolysin therapy (e.g., their immunogenicity, the release of proinflammatory components during bacteriolysis, or the development of resistance), in fact, may not seriously hinder their use. However, all data regarding the safety and therapeutic effectiveness of endolysins obtained from preclinical studies must be ultimately verified by clinical trials. This review discusses the prophylactic and therapeutic applications of endolysins, especially with respect to their potential use in human medicine. Additionally, we outline current knowledge regarding the structure and natural function of the enzymes in phage biology, including the most recent findings.