gebhart/patrepeval huggingface dataset:
SIRT3, a Mitochondrial Sirtuin Deacetylase, Regulates Mitochondrial Function and Thermogenesis in Brown Adipocytes (2005)

SIRT3 is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene, which mediates the effect of caloric restriction on life span extension in yeast and Caenorhabditis elegans. Because adipose tissue is essential in energy homeostasis and also plays a role in life span determination, we decided to investigate the function of sirtuin members in fat. We report here that murine SIRT3 is expressed in brown adipose tissue and is localized on the mitochondria inner membrane. Caloric restriction activates SIRT3 expression in both white and brown adipose. Additionally, cold exposure up-regulates SIRT3 expression in brown fat, whereas elevated climate temperature reduces the expression. Enforced expression of SIRT3 in the HIB1B brown adipocytes enhances the expression of the uncoupling protein PGC-1alpha, UCP1, and a series of mitochondria-related genes. Both ADP-ribosyltransferase and deacetylase activities of SIRT3 are required for this action. Furthermore, the SIRT3 deacetylase mutant exhibits a dominant negative effect by inhibiting UCP1 expression. This inhibitive effect can be abolished by the coexpression of PGC-1alpha, indicating a major role of PGC-1alpha in the SIRT3 action. In addition, SIRT3 stimulates CREB phosphorylation, which reportedly activates PGC-1alpha promoter directly. Functionally, sustained expression of SIRT3 decreases membrane potential and reactive oxygen species production while increasing cellular respiration. Finally, SIRT3, along with genes related to mitochondrial function, is down-regulated in the brown adipose tissue of several genetically obese mice. In summary, our results demonstrate that SIRT3 activates mitochondria functions and plays an important role in adaptive thermogenesis in brown adipose.
DO RECENT FINDINGS IN PLANT MITOCHONDRIAL MOLECULAR AND POPULATION GENETICS HAVE IMPLICATIONS FOR THE STUDY OF GYNODIOECY AND CYTONUCLEAR CONFLICT? (2008)

The coexistence of females and hermaphrodites in plant populations, or gynodioecy, is a puzzle recognized by Darwin. Correns identified cytoplasmic inheritance of one component of sex expression, now known as cytoplasmic male sterility (CMS). Lewis established cytonuclear inheritance of gynodioecy as an example of genetic conflict. Although biologists have since developed an understanding of the mechanisms allowing the joint maintenance of CMS and nuclear male fertility restorer genes, puzzles remain concerning the inheritance of sex expression and mechanisms governing the origination of CMS. Much of the theory of gynodioecy rests on the assumption of maternal inheritance of the mitochondrial genome. Here we review recent studies of the genetics of plant mitochondria, and their implications for the evolution and transmission of CMS. New studies of intragenomic recombination provide a plausible origin for the chimeric ORFs that characterize CMS. Moreover, evidence suggests that nonmaternal inheritance of mitochondria may be more common than once believed. These findings may have consequences for the maintenance of cytonuclear polymorphism, mitochondrial recombination, generation of gynomonoecious phenotypes, and interpretation of experimental crosses. Finally we point out that CMS can alter the nature of the cytonuclear conflict that may have originally selected for uniparental inheritance.
Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study (2008)

NCT00548834.
Low doses of cannabinoids enhance the antinociceptive effects of intracisternally administered mGluRs groups II and III agonists in formalin-induced TMJ nociception in rats (2008)

This study provides the first demonstration that central cannabinoids modulate the antinociceptive actions of metabotropic glutamate receptors (mGluRs) on formalin-induced temporomandibular joint (TMJ) nociception. Noxious scratching behavior induced by formalin injection in the TMJ was used as a model of pain. Intracisternal injection of 30mug of WIN 55,212-2, a non-subtype selective cannabinoid receptor agonist, attenuated the number of scratches by 75% as compared with the vehicle-treated group, whereas vehicle alone or 3 or 10 microg of WIN 55,212-2 had no effect. To explore the postulated interaction between central cannabinoid receptors and mGluRs, effects of combined administration of sub-analgesic doses of WIN 55,212-2 and group II or III mGluR agonists were tested. Group II or III mGluRs agonists were administered intracisternally 10 min after intracisternal administration of WIN 55,212-2. Neither 100 nmol APDC, a group II mGluRs agonist, nor L-AP4, a group III mGluR agonist, altered nociceptive behavior when given alone but significantly inhibited the formalin-induced nociceptive behavior in the presence of a sub-threshold dose ( 3microg) of WIN 55,212-2. The ED50 value of APDC or L-AP4 was significantly reduced upon co-treatment with WIN 55,212-2 than in the vehicle-treated group, highlighting the important therapeutic potential of the combined administration of group II or III mGluR agonists with cannabinoids to effectively treat inflammatory pain associated with the TMJ. Potentiating effects of group II or III mGluRs agonists will likely permit the administration of cannabinoids at doses that do not achieve significant accumulation to produce undesirable motor dysfunction.
Familial and sporadic Alzheimer's disease (1996)

Whether all etiologic forms of Alzheimer's disease (AD) share a final common pathway is a major issue. We determined the severity and regional distribution of neuronal loss, amyloid plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs), and calculated the ratio of neuronal loss to NPs and NFTs in brains of 19 familial AD (FAD) patients with linkage to chromosome 14, six AD patients with mutations of chromosome 21 (codon 717 of the beta-amyloid percursor protein gene), and 11 sporadic AD (SAD) patients. There was no difference in the pattern of distribution of the various pathologic features or in the ratio of neuronal loss to NPs or NFTs in any AD group. However, FAD groups could be distinguished from SAD by the greater severity and the lack of influence of apolipoprotein E genotype on pathology. These differences may reflect differences in age at onset rather than different etiopathologic mechanisms. The similarity of pathologic findings in the different AD groups provides evidence for a final common pathophysiologic pathway in AD.
Noscapine inhibits human prostate cancer progression and metastasis in a mouse model. (2009)

Oral administration of noscapine limited tumour growth and lymphatic metastasis of PC3 human prostate cancer in this mouse model, supporting its therapeutic potential as a nontoxic and easily administered treatment for metastatic cancer.
Change in state of phosphorylation of acetylcholine receptor during maturation of the electromotor synapse in Torpedo marmorata electric organ. (1981)

Two populations of membrane fragments, both rich in acetylcholine receptor (AcChoR), appeared during subcellular fractionation by ultracentrifugation of neonatal Torpedo marmorata electric organs. One of these equilibrated at 38.5% (wt/wt) sucrose, as did AcChoR-rich membranes from adult fish; the other equilibrated at 36.8% sucrose. AcChoR purified from these light membrane fractions gave the same subunit profile as adult AcChoR (after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate) but was more susceptible to heat inactivation and focused at an isoelectric point more alkaline by 0.1 pH unit. Treatment of adult AcChoR with Escherichia coli alkaline phosphatase decreased its thermal stability and shifted its isoelectric point towards alkaline pH. However, identical treatment did not affect AcChoR purified from neonatal light membrane fractions. The gamma and delta chains of AcChoR can be phosphorylated in vitro by endogenous protein kinases, which copurify with AcChoR-rich membranes. Treatment of AcChoR from neonatal light membranes by E. coli alkaline phosphatase enhanced the phosphorylation of the gamma and delta chains but did so to a smaller extent than in the case of adult AcChoR. In conclusion, adult AcChoR appears to be more phosphorylated than AcChoR from neonatal light membranes, indicating that its state of phosphorylation changes during development.
A User’s Guide for Phase Separation Assays with Purified Proteins (2018)

The formation of membrane-less organelles and compartments by protein phase separation is an important way in which cells organize their cytoplasm and nucleoplasm. In vitro phase separation assays with purified proteins have become the standard way to investigate proteins that form membrane-less compartments. By now, various proteins have been purified and tested for their ability to phase separate and form liquid condensates in vitro. However, phase-separating proteins are often aggregation-prone and difficult to purify and handle. As a consequence, the results from phase separation assays often differ between labs and are not easily reproduced. Thus, there is an urgent need for high-quality proteins, standardized procedures, and generally agreed-upon practices for protein purification and conducting phase separation assays. This paper provides protocols for protein purification and guides the user through the practicalities of in vitro protein phase separation assays, including best-practice approaches and pitfalls to avoid. We believe that this compendium of protocols and practices will provide a useful resource for scientists studying the phase behavior of proteins.
A neural controller for collision-free movement of general robot manipulators (1988)

An approach is presented for the collision-free control of general robot manipulators moving among a changing set of obstacles. The controller, based on a layered, neural network architecture, adapts to the specific eye/hand and arm/body kinematics of any arbitrarily shaped robot during an initial, unsupervised training phase. After training, the robot selects a target point by 'glancing' at it and the controller moves the end-effector into position. This approach, which combines neural and systolic computing principles, has several advantages over traditional algorithmic solutions and extends previous work on neural manipulator control. Results of a simulation are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
SpotFi (2015)

This paper presents the design and implementation of SpotFi, an accurate indoor localization system that can be deployed on commodity WiFi infrastructure. SpotFi only uses information that is already exposed by WiFi chips and does not require any hardware or firmware changes, yet achieves the same accuracy as state-of-the-art localization systems. SpotFi makes two key technical contributions. First, SpotFi incorporates super-resolution algorithms that can accurately compute the angle of arrival (AoA) of multipath components even when the access point (AP) has only three antennas. Second, it incorporates novel filtering and estimation techniques to identify AoA of direct path between the localization target and AP by assigning values for each path depending on how likely the particular path is the direct path. Our experiments in a multipath rich indoor environment show that SpotFi achieves a median accuracy of 40 cm and is robust to indoor hindrances such as obstacles and multipath.
Primary Induction of Human CD8+Cytotoxic T Lymphocytes and Interferon‐γ–Producing T Cells after Smallpox Vaccination (2002)

This study measured the ability of a standard smallpox vaccine, given by scarification (by bifurcated needle), to induce primary human vaccinia virus-specific cytotoxic and interferon (IFN)-gamma-producing T lymphocyte responses. Because protection against smallpox may be mediated in part by T cell memory responses induced by vaccination, an analysis of the induction of primary human cytotoxic T lymphocytes (CTL) and IFN-gamma-producing T cell responses was performed. Although smallpox is no longer an epidemic threat under natural conditions, vaccination is still recommended for persons working with vaccinia viruses in the laboratory and for those who may be at risk from the potential use of smallpox virus as a bioterrorism agent. The results demonstrate that smallpox vaccine given by bifurcated needle induces strong vaccinia virus-specific CD8(+) CTL and IFN-gamma-producing T cell responses and provide baseline information useful for planning the immunologic assessment of future smallpox vaccines.
Review Article—Dielectrophoresis: Status of the theory, technology, and applications (2010)

A review is presented of the present status of the theory, the developed technology and the current applications of dielectrophoresis (DEP). Over the past 10 years around 2000 publications have addressed these three aspects, and current trends suggest that the theory and technology have matured sufficiently for most effort to now be directed towards applying DEP to unmet needs in such areas as biosensors, cell therapeutics, drug discovery, medical diagnostics, microfluidics, nanoassembly, and particle filtration. The dipole approximation to describe the DEP force acting on a particle subjected to a nonuniform electric field has evolved to include multipole contributions, the perturbing effects arising from interactions with other cells and boundary surfaces, and the influence of electrical double-layer polarizations that must be considered for nanoparticles. Theoretical modelling of the electric field gradients generated by different electrode designs has also reached an advanced state. Advances in the technology include the development of sophisticated electrode designs, along with the introduction of new materials (e.g., silicone polymers, dry film resist) and methods for fabricating the electrodes and microfluidics of DEP devices (photo and electron beam lithography, laser ablation, thin film techniques, CMOS technology). Around three-quarters of the 300 or so scientific publications now being published each year on DEP are directed towards practical applications, and this is matched with an increasing number of patent applications. A summary of the US patents granted since January 2005 is given, along with an outline of the small number of perceived industrial applications (e.g., mineral separation, micropolishing, manipulation and dispensing of fluid droplets, manipulation and assembly of micro components). The technology has also advanced sufficiently for DEP to be used as a tool to manipulate nanoparticles (e.g., carbon nanotubes, nano wires, gold and metal oxide nanoparticles) for the fabrication of devices and sensors. Most efforts are now being directed towards biomedical applications, such as the spatial manipulation and selective separationenrichment of target cells or bacteria, high-throughput molecular screening, biosensors, immunoassays, and the artificial engineering of three-dimensional cell constructs. DEP is able to manipulate and sort cells without the need for biochemical labels or other bioengineered tags, and without contact to any surfaces. This opens up potentially important applications of DEP as a tool to address an unmet need in stem cell research and therapy.
Correlation between the tumoral expression of β3-integrin and outcome in cervical cancer patients who had undergone radiotherapy (2004)

Integrins are cell-surface receptors, which mediate cell-to-cell and cell-to-extracellular matrix adhesion. Besides playing an important role in tumour angiogenesis, beta3-integrin is also expressed in several types of epithelial cancer cells. It was the purpose of the present study to evaluate the prognostic value of beta3-integrin expression in patients with cervical cancer. Biopsies were taken from 82 patients with squamous cell or adenocarcinomas of the uterine cervix who had undergone external-beam radiotherapy with or without brachytherapy. These tissue samples were analysed immunohistochemically for the expression of beta3-integrin. The impact of immunoreactivity for beta3-integrin on survival end points was assessed by univariate and multivariate analyses, and its correlation with clinicopathological characteristics evaluated by crosstabulations. beta3-integrin was expressed in 61% (50 of 82) of the patients. Kaplan-Meier curves revealed local progression-free survival, distant metastasis-free survival and cause-specific survival to be significantly shorter (P-values according to the log-rank test: 0.002, 0.04 and 0.01, respectively) in patients with beta3-integrin expression. The prognostic impact of this parameter was even higher than for other well-known prognostic parameters and remained statistically significant in the multivariate analyses. beta3-integrin, which is expressed in the majority of patients with advanced cervical cancer, has a significant prognostic impact on outcome according to univariate and multivariate analyses.
The dynamics of methylammonium ions in hybrid organic–inorganic perovskite solar cells (2015)

Methylammonium lead iodide perovskite can make high-efficiency solar cells, which also show an unexplained photocurrent hysteresis dependent on the device-poling history. Here we report quasielastic neutron scattering measurements showing that dipolar CH3NH3(+) ions reorientate between the faces, corners or edges of the pseudo-cubic lattice cages in CH3NH3PbI3 crystals with a room temperature residence time of ∼14 ps. Free rotation, π-flips and ionic diffusion are ruled out within a 1-200-ps time window. Monte Carlo simulations of interacting CH3NH3(+) dipoles realigning within a 3D lattice suggest that the scattering measurements may be explained by the stabilization of CH3NH3(+) in either antiferroelectric or ferroelectric domains. Collective realignment of CH3NH3(+) to screen a device's built-in potential could reduce photovoltaic performance. However, we estimate the timescale for a domain wall to traverse a typical device to be ∼0.1-1 ms, faster than most observed hysteresis.
Development of protegrins for the treatment and prevention of oral mucositis: Structure-activity relationships of synthetic protegrin analogues (2000)

Protegrin antimicrobial peptides possess activity against gram-positive and gram-negative bacteria and yeasts. An extensive structure-activity relationship (SAR) study was conducted on several hundred protegrin analogues to gain understanding of the relationship between the primary and secondary structure of the protegrins and their antimicrobial activities, and to identify a protegrin analogue for clinical development. Native sequence protegrins are cationic, amphiphilic peptides that are characterized by the presence of a beta-sheet structure that is maintained by two disulfide bridges. The presence of the beta-sheet is key to the stability of the protegrin structure; linearized analogues or analogues that have amino acid substitutions that eliminate hydrogen bonding across the beta-sheet have reduced activity, especially in the presence of physiological concentrations of NaCl. Also, maintaining amphiphilicity of the beta-sheet is key; analogues with substitutions of polar amino acids in the hydrophobic face have reduced activity. Analogues with reduced positive charge tend to be less active, an observation that is more marked for gram-negative than gram-positive bacteria, and may implicate binding to lipopolysaccharide as a key mechanistic step in the killing of gram-negative bacteria. A very large number of amino acid substitutions are tolerated by the protegrin structure, implying that overall structural features such as amphiphilicity, charge, and shape are more important to activity than the presence of specific amino acids. This lack of importance of specific stereochemistry is supported by the fact that completely D-amino acid substituted protegrins are fully potent. Based on the SAR studies, and on the microbiological data from an animal model, one protegrin analogue, IB-367, was selected for clinical development as a topical agent to prevent the oral mucositis associated with cancer therapy.
Apolipoprotein B mRNA Editing: A Key Controlling Element Targeting Fats to Proper Tissue (1993)

Apolipoprotein B (apo B) circulates in two distinct forms referred to as apo B100 and apo B48. Apo B48 is colinear with the amino-terminal half of apo B100 and arises as a result of a post-transcriptional modification, termed apo B mRNA editing. This process changes a single cytidine nucleotide in apo B100 mRNA thereby altering a CAA codon, encoding glutamine in apo B100, to a UAA codon, which specifies an in-frame stop codon in apo B48. The functional consequences of apo B mRNA editing include the divergent catabolism of plasma lipoproteins expressing either apo B100 or B48, and also the ability to generate the hybrid lipoprotein, Lp(a). These differences arise because the requisite regions of apo B for interaction either with the low-density lipoprotein receptor or with apolipoprotein (a) are contained within the carboxyl terminus of apo B100. Apo B mRNA editing is regulated by species, tissue and cell-specific factors, one of which has been recently cloned. The further characterization of apo B mRNA editing, the first example of a mammalian gene regulated by post-transcriptional nucleotide alteration, will be important for an understanding of lipoprotein assembly.
In vivostudy of novel nanofibrous intra-luminal guidance channels to promote nerve regeneration (2010)

A novel nanofibrous construct for promoting peripheral nerve repair was fabricated and tested in a rat sciatic nerve defect model. The conduit is made out of bilayered nanofibrous membranes with the nanofibers longitudinally aligned in the lumen and randomly oriented on the outer surface. The intra-luminal guidance channel is made out of aligned nanofibrous yarns. In addition, biomolecules such as laminin and nerve growth factor were incorporated in the nanofibrous nerve construct to determine their efficacy in in vivo nerve regeneration. Muscle reinnervation, withdrawal reflex latency, histological, axon density and electrophysiology tests were carried out to compare the efficacy of nanofibrous constructs with an autograft. Our study showed mixed results when comparing the artificial constructs with an autograft. In some cases, the nanofibrous conduit with aligned nanofibrous yarn as an intra-luminal guidance channel performs better than the autograft in muscle reinnervation and withdrawal reflex latency tests. However, the axon density count is highest in the autograft at mid-graft. Functional recovery was improved with the use of the nerve construct which suggested that this nerve implant has the potential for clinical usage in reconstructing peripheral nerve defects.