gebhart/patrepeval huggingface dataset:
Neuronal survival using a resorbable synthetic conduit as an alternative to primary nerve repair (1999)

Clinically optimal situations for primary nerve repair are rarely observed. Crushed nerve ends result in either suboptimal repair or a need for nerve grafting. Functional results after nerve surgery are relatively poor, including major sensory deficits, which may be due to the death of primary sensory neurons that follows the nerve injury. The aim of this study was to determine if using polyhydroxybutyrate (PHB), a resorbable nerve conduit, could be an alternative to primary nerve repair in reducing loss of neurons. The superficial radial nerves in 20 cats were sectioned bilaterally and primarily repaired microsurgically by the use of two different strategies; either wrapping the nerve ends in sheets of PHB or epineurally suturing of the nerve. After 6 or 12 months, the surviving neurons within the dorsal root ganglia [C5-T1] were counted. No statistically significant differences were found between the two methods. This may imply a future possibility of using PHB as a synthetic nerve graft in situations where suboptimal primary repair or nerve grafts are the alternatives.
Improvement of the primary metabolism of cell cultures by introducing a new cytoplasmic pyruvate carboxylase reaction (1999)

Continuous mammalian cell lines are important hosts for the production of biological pharmaceuticals. However, these cell lines show some severe disorders in primary metabolism, which they have in common with many cancer cells. This leads to a high throughput of substrates giving a low energy yield and ample toxic side products such as lactate and ammonia. Because the enzymatic connection between glycolysis and the tricarboxylic acid cycle (TCA) is very poor, glucose is mainly degraded via oxidative glycolysis. It will be shown that introducing a pyruvate carboxylase gene expressed in the cytoplasma into a continuous BHK-21 cell line, and thus reconstituting the missing link between glycolysis and TCA, can reduce this problem. Thus, glucose consumption could be reduced by a factor of four and glutamine utilization up to a factor of two, compared with control. Moreover, a 1.4-fold-higher adenosine triphosphate (ATP) content was achieved. The flux of labeled [(14)C]-glucose into the TCA is shown to be enhanced, indicating a higher rate of oxidative glucose degradation. Host cell lines with an improved energy metabolism will therefore result in better exploitation of substrates, an increasing yield by the more efficient use of carbon source, and higher product integrity combined with lower production costs.
316. Evaluating AAV Hybrid Variants for Improved Tropism after Intravitreal Gene Delivery to the Retina (2015)

AAV-mediated gene therapy has shown promise for some ocular diseases when injected sub-retinally. Intravitreal AAV administration, while less invasive, is far less efficient due to the inner limiting membrane (ILM), which is a particularly profound barrier in the primate retina. Recently AAV2.7m8, which has a 10 amino acid (aa) peptide insertion in the surface exposed loop region of AAV2, was identified using in vivo directed evolution (Dalkara et al., 2013). This variant has been shown to effectively transduce outer retinal cells resulting in extensive gene expression in the non-human primate retina following intravitreal injection. The purpose of our study was to identify AAV variants that could not only penetrate the outer retina from the vitreous, but also have a favorable neutralizing antibody (nAb) titer to allow beneficial AAV-mediated gene expression. We tested whether the 10-aa peptide loop from AAV2.7m8 could be inserted into other capsid backbones, and investigated the tropism and nAb profile of these hybrid capsids. The 10-aa loop was inserted at seven different positions in the receptor binding region of loop IV of capsid 2.5T, which is a chimeric variant of the VP1 region of AAV2 and VP2 and VP3 regions of AAV5 containing a single A581T point mutation (Excoffon et al., 2009). A majority of the 2.5T/7m8 hybrid capsids were successfully packaged and resulted in varying levels of GFP transgene expression following transduction in vitro. Additionally, in vitro transduction was blocked to a lesser extent by nAbs (IVIg) when compared to AAV2, which indicates that the 2.5T/7m8 hybrids may not be impeded by preexisting immunity in human patients. Finally, significantly higher GFP expression was observed with one of the 2.5T/7m8 hybrid variants as compared to the parental 2.5T capsid, following intravitreal administration in rodents.
Localization of sulfated glycoprotein‐2/clusterin mRNA in the rat brain by in situ hybridization (1993)

Sulfated glycoprotein-2 (SGP-2) gene expression seems to be constitutively expressed in a variety of tissues and organs, although levels of expression vary widely from one tissue to the other. SGP-2, also known as clusterin, has been reported to be expressed in the central nervous system (CNS). Some possible roles for brain SGP-2 have been postulated. In order to provide a substrate for a better understanding of the functions of this glycoprotein in the CNS, we investigated the detailed anatomical and cellular distribution of SGP-2 mRNA in the adult rat brain as well as the variation in its cellular expression after excitotoxin lesion. Transcripts for SGP-2 were found to be distributed throughout the rat CNS, although regional differences in their prevalence were readily observed. The ependymal lining of the ventricles showed the highest level of expression followed by various gray matter areas, some of which contained very intensively labeled cells. These cells were mostly found among several hypothalamic and brainstem nuclei, the habenular complex, as well as in the ventral horn of the spinal cord, which displayed striking hybridization signals over motoneurons. Occasional cells expressing high levels of SGP-2 transcripts were found in fiber tracts. Highly SGP-2 mRNA-positive resting glial cells were mainly located near the glial limitans and blood vessels. Two areas of relatively low constitutive SGP-2 mRNA expression are shown to produce strong hybridization signals 10 days after the local administration of the excitotoxin kainic acid. This overexpression of SGP-2 transcripts appears to involve GFAP-positive cells. Taken together, these results indicate that in the intact adult rat CNS, various cell populations, including neurons, constitutively express SGP-2 transcripts, whereas in the injured brain, reactive astrocytes become the major producers.
Enhanced wound‐healing quality with bone marrow mesenchymal stem cells autografting after skin injury (2006)

Adult stem cells exist in various tissues and organs and have the potential to differentiate into different cell lineages, including bone, cartilage, fat, tendon, muscle, and epithelial cells of the gastrointestinal tract. Here, we report that the in vitro expanded and purified bone marrow mesenchymal stem cells (MSCs) might take on phenotypes with characteristics of vascular endothelial cells (7% on day 3 and 15% on day 1) or epidermal cells (3% on day 3 and 13% on day 1) after being cultured under different lineage-specific culture conditions. Also, in vivo grafting experiments showed that 5-bromodeoxyuridine-labeled MSCs could convert into the phenotypes of vascular endothelial cells (3.43, 3.46, and 2.94% on days 7, 14, and 28, respectively) in granulation tissues, sebaceous duct cells, and epidermal cells (0-1.49%) in regenerated skin, implying that these grafted MSCs might have transdifferentiated into the above three cell types. Animal autografting experiments with MSCs further confirmed that indices pertaining to wound healing quality, such as the speed of reepithelialization, the number of epidermal ridges and thickness of the regenerated epidermis, the morphology and the number and arrangement of microvasculature, fibroblasts and collagen, were much enhanced. Our results indicate that locally delivered bone marrow MSCs can enhance wound healing quality, and may generate de novo intact skin, resulting in perfect skin regeneration after full-thickness injury.
Protein Kinase Cζ Is a Negative Regulator of Protein Kinase B Activity (1999)

Protein kinase B (PKB), also known as Akt or RAC-PK, is a serine/threonine kinase that can be activated by growth factors via phosphatidylinositol 3-kinase. In this article we show that PKCzeta but not PKCalpha and PKCdelta can co-immunoprecipitate PKB from CHO cell lysates. Association of PKB with PKCzeta was also found in COS-1 cells transiently expressing PKB and PKCzeta, and moreover we found that this association is mediated by the AH domain of PKB. Stimulation of COS-1 cells with platelet-derived growth factor (PDGF) resulted in a decrease in the PKB-PKCzeta interaction. The use of kinase-inactive mutants of both kinases revealed that dissociation of the complex depends upon PKB activity. Analysis of the activities of the interacting kinases showed that PDGF-induced activation of PKCzeta was not affected by co-expression of PKB. However, both PDGF- and p110-CAAX-induced activation of PKB were significantly abolished in cells co-expressing PKCzeta. In contrast, co-expression of a kinase-dead PKCzeta mutant showed an increased induction of PKB activity upon PDGF treatment. Downstream signaling of PKB, such as the inhibition of glycogen synthase kinase-3, was also reduced by co-expression of PKCzeta. A clear inhibitory effect of PKCzeta was found on the constitutively active double PKB mutant (T308D/S473D). In summary, our results demonstrate that PKB interacts with PKCzeta in vivo and that PKCzeta acts as a negative regulator of PKB.
Expression of Insulin-like Growth Factor Binding Proteins in Bronchoalveolar Lavage Fluid of Patients with Pulmonary Sarcoidosis (1998)

Pulmonary sarcoidosis involves development of parenchymal granulomata that usually resolve spontaneously; however, it remains unclear what pathogenic mechanisms are responsible for the progression to local or diffuse fibrosis with irreversible lung remodeling that occurs in 20% of patients. Alveolar macrophages have a pivotal role in sarcoidosis, releasing mediators including insulin-like growth factor (IGF)-1, a potent profibrogenic molecule. IGF-1 bioavailability in the lung is dependent on at least six high-affinity IGF-binding proteins (IGFBP), which mainly inhibit IGF-1 action. We have investigated their presence in patients with established stage III sarcoidosis to determine whether IGF-1 and IGFBP contribute to the fibrogenic process in these patients and as such contribute to the (clinical) progression of the disease. The fibroblast mitogenic potential of bronchoalveolar lavage fluid (BALF) was more than 3-fold higher (P < 0.005) in sarcoid patients. Sarcoid BALF-induced activity could be inhibited (P < 0.0005) by neutralizing antibodies to IGF-1. We established the IGFBP profile of BALF with Western ligand analysis and quantified expression of IGFBP-3 by immunoblotting. IGFBP-2 and IGFBP-4 predominate in normal and sarcoid BALF, but IGFBP-3 occurs only as a modified, smaller, 29-kD form, expression of which was raised (P < 0.003) in sarcoid patients. Gene expression of IGF-1 and IGFBP-3 was demonstrated by reverse transcription-polymerase chain reaction in BAL cells. Thus, local production of pro-fibrogenic IGF-1 may be subject to substantial post-translational regulation by associated IGFBP and IGFBP proteases that may contribute to enhanced fibrogenesis in sarcoidosis patients with evidence of progression or (development) of fibrosis.
High-resolution quantization theory and the vector quantizer advantage (1989)

The authors consider how much performance advantage a fixed-dimensional vector quantizer can gain over a scalar quantizer. They collect several results from high-resolution or asymptotic (in rate) quantization theory and use them to identify source and system characteristics that contribute to the vector quantizer advantage. One well-known advantage is due to improvement in the space-filling properties of polytopes as the dimension increases. Others depend on the source's memory and marginal density shape. The advantages are used to gain insight into product, transform, lattice, predictive, pyramid, and universal quantizers. Although numerical prediction consistently overestimated gains in low rate (1 bit/sample) experiments, the theoretical insights may be useful even at these rates.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Journal of Bioengineering and Technology Applied to Health: A New Journal of Health Institute of Technology - ITS/SENAI CIMATEC (2019)

ITS/SENAI CIMATEC created The Journal of Bioengineering and Technology Applied to Health (JBTH) in order to develop an instrument for innovative researchers and scientists to explore the advanced and latest research developments in the field of Biomedical Engineering and related disciplines that are applied to the development of new tools for diagnostics and treatment in the area of health.
Performance analysis of microelectrofluidic systems using hierarchical modeling and simulation (2001)

With the development of increasingly complex microelectrofluidic devices and systems, system-level performance analysis is becoming an important aspect of design. System-level performance analysis is challenging because coupled-energy dynamics link system-level performance with component-level operation, thus necessitating a hierarchical approach to modeling and simulation. This paper presents a hierarchical modeling and simulation method for microelectrofluidic systems, in particular, and composite microsystems, in general. High-level stochastic queueing modeling is combined with low-level nodal modeling to support simulation accuracy with low simulation times. Results are reported for a microchemical handling system. System-level performance analysis is carried out and applied to architectural design optimization.
Screening for antimitotic compounds using the cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34cdc2/cyclin Bcdc13 protein kinase. (1992)

A universal intracellular factor, the "M phase-promoting factor" (MPF), triggers the G2/M transition of the cell cycle in all organisms. In late G2, it is present as an inactive complex of tyrosine-phosphorylated p34cdc2 and unphosphorylated cyclin Bcdc13. In M phase, its activation as an active MPF displaying histone H1 kinase activity originates from the specific tyrosine dephosphorylation of the p34cdc2 subunit by the tyrosine phosphatase p80cdc25. We describe here a colorimetric assay of recombinant human cdc25A tyrosine phosphatase used as a cell cycle-specific target to screen for antimitotic compounds. The glutathione-S-transferase/cdc25A tyrosine phosphatase fusion protein is produced in large amounts of Escherichia coli and easily purified by affinity chromatography on glutathione-agarose. Optimal purification, storage and assay conditions (concentrations of enzyme, p-nitrophenylphosphate and dithiothreitol; duration of assay) have been determined. Using this system we tested 15 compounds currently used in cancer treatment; none of them displayed any inhibitory activity. However, the assay detected the inhibitory activity of vanadate, a reported tyrosine phosphatase inhibitor. The simplicity, speed and possible extensive automation of this assay using an essential cell cycle-regulating component provide a highly specific mechanism-based screen for antimitotic drugs discovery.
Bone Lengthening of the Human Mandible by Gradual Distraction (1991)

McCarthy, J. G. MD; Schreiber, J. S. MD; Karp, N. MD; Thome, C. H. MD; Grayson, B. G. MD Author Information
Mass Spectrometry:  Recent Advances and Future Directions (1996)

The discipline of mass spectrometry is nearly a century old. Like any experimental scientific endeavor, the machines and the science get irretrievably mixed with the development of one stimulating the other in a symbiotic manner. In this paper the authors select a few of the important recent successes to highlight the incredible growth of mass spectrometry over the past several decades. The topic choices made are personal but hopefully serve as an indicator of the current excitement in this rapidly evolving field. Selections are made from nuclear physics, through the broad spectrum of the chemical sciences, to the borders of biology.
7-Azetidinylquinolones as antibacterial agents. Synthesis and structure-activity relationships (1993)

A series of novel antibacterial quinolones and naphthyridones has been prepared which contain 7-azetidinyl substituents in place of the usual piperazine or aminopyrrolidine groups. These azetidinyl derivatives were evaluated for in vitro activity by determining minimum inhibitory concentrations against a variety of bacteria. In vivo efficacy in the mouse infection model and blood levels in the mouse were determined for several compounds. The influence on the structure-activity relationships of varying substituents in the azetidine ring and at position 8 (CH, CF, CCl, N) and N-1 (ethyl, fluoroethyl, cyclopropyl, tert-butyl, 4-fluorophenyl, and 2,4-difluorophenyl) was also studied. Compounds with outstandingly broad-spectrum activity, particularly against Gram-positive organisms, improved in vivo efficacy, and high blood levels were identified in this work. 7-Azetidinyl-8-chloroquinolones were considered as warranting further development.
Model Misspecification in ABC: Consequences and Diagnostics (2017)

We analyze the behavior of approximate Bayesian computation (ABC) when the model generating the simulated data differs from the actual data generating process; i.e., when the data simulator in ABC is misspecified. We demonstrate both theoretically and in simple, but practically relevant, examples that when the model is misspecified different versions of ABC can yield substantially different results. Our theoretical results demonstrate that even though the model is misspecified, under regularity conditions, the accept/reject ABC approach concentrates posterior mass on an appropriately defined pseudo-true parameter value. However, under model misspecification the ABC posterior does not yield credible sets with valid frequentist coverage and has non-standard asymptotic behavior. In addition, we examine the theoretical behavior of the popular local regression adjustment to ABC under model misspecification and demonstrate that this approach concentrates posterior mass on a completely different pseudo-true value than accept/reject ABC. Using our theoretical results, we suggest two approaches to diagnose model misspecification in ABC. All theoretical results and diagnostics are illustrated in a simple running example.
RecombinantSaccharomyces cerevisiaeStrain Expressing a Model Cytochrome P450 in the Rat Digestive Environment: Viability and Bioconversion Activity (2007)

An innovative "biodrug" concept, based on the oral administration of living recombinant microorganisms, has recently emerged for the prevention or treatment of various diseases. An engineered Saccharomyces cerevisiae strain expressing plant P450 73A1 (cinnamate-4-hydroxylase [CA4H] activity) was used, and its survival and ability to convert trans-cinnamic acid (CIN) into p-coumaric acid (COU) were investigated in vivo. In rats, the recombinant yeast was resistant to gastric and small intestinal secretions but was more sensitive to the conditions found in the large intestine. After oral administration of yeast and CIN, the CA4H activity was shown in vivo, with COU being found throughout the rat's digestive tract and in its urine. The bioconversion reaction occurred very fast, with most of the COU being produced within the first 5 min. The gastrointestinal sac technique demonstrated that the recombinant yeast was able to convert CIN into COU (conversion rate ranging from 2 to 5%) in all the organs of the rat's digestive tract: stomach, duodenum, jejunum, ileum, cecum, and colon. These results promise new opportunities for the development of drug delivery systems based on engineered yeasts catalyzing a bioconversion reaction directly in the digestive tract.
UCSF Chimera—A visualization system for exploratory research and analysis (2004)

The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/.
Autoimmune Cytopenias In Common Variable Immunodeficiency (2012)

Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20-50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4-20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical "prima facie" that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID.