gebhart/patrepeval huggingface dataset:
Protein Phosphatase 2A, a Negative Regulator of the ERK Signaling Pathway, Is Activated by Tyrosine Phosphorylation of Putative HLA Class II-associated Protein I (PHAPI)/pp32 in Response to the Antiproliferative Lectin, Jacalin (2004)

Protein phosphatase 2A (PP2A) is a family of mammalian serine/threonine phosphatases that is involved in the control of many cellular functions including those mediated by extracellular signal-regulated kinase (ERK) signaling. While investigating the reversible antiproliferative effect of the dietary lectin, jacalin, which binds the Thomsen-Friedenreich antigen (galactose beta1-3 N-acetylgalactosamine alpha-), we have found that this lectin (30 microg/ml) induces rapid, transient, tyrosine phosphorylation of putative human HLA-DR-associated protein I (PHAPI, also known as the tumor suppressor pp32) in HT29 human colon cancer cells. This is accompanied by the release of PP2A from association with PHAPI, allowing increased phosphatase activity of PP2A (by 42 +/- 10% at 10 min) and consequent complete dephosphorylation of the ERK kinase, MEK1/2, by 10 min and of ERK1/2 by 60 min. PHAPI knockdown by RNA interference abolished the effects of jacalin on PP2A activation and MEK inhibition. Thus phosphorylation of PHAPI/pp32 is a critical regulatory step in PP2A activation and ERK signaling.
Subclinical hyperthyroidism: controversies in management. (2002)

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. The thyroid-stimulating hormone value is typically measured in a third-generation assay capable of detecting approximately 0.01 microU per mL (0.01 mU per L). Subclinical hyperthyroidism may be a distinct clinical entity, related only in part to Graves' disease or multinodular goiter. Persons with subclinical hyperthyroidism usually do not present with the specific signs or symptoms associated with overt hyperthyroidism. A detailed clinical history should be obtained, a physical examination performed and thyroid function tests conducted as part of an assessment of patients for subclinical hyperthyroidism and to evaluate the possible deleterious effects of excess thyroid hormone on end organs (e.g., heart, bone). A reasonable treatment option for many patients is a therapeutic trial of low-dose antithyroid agents for approximately six to 12 months in an effort to induce a remission. Further research regarding the etiology, natural history, pathophysiology, and treatment of subclinical hyperthyroidism is warranted.
Novel approach toward a binder-free and current collector-free anode configuration: highly flexible nanoporous carbon nanotube electrodes with strong mechanical strength harvesting improved lithium storage (2012)

In this work, we developed a novel flexible nanoporous carbon nanotube film to use as a binder-free and current collector-free anode electrode for lithium ion batteries, providing a new approach to flexible energy devices. The proposed novel anode configuration shows better cycling performance and rate capability than the conventional electrode architecture. Moreover, this unique configuration exhibits good flexibility and robust mechanical strength, which has the potential to be applied to flexible lithium ion batteries. Our findings may provide a new anode configuration for lithium ion batteries with improved cycling stability and rate capability.
Promoters and serotypes: targeting of adeno‐associated virus vectors for gene transfer in the rat central nervous system in vitro and in vivo (2004)

The brain parenchyma consists of several different cell types, such as neurones, astrocytes, microglia, oligodendroglia and epithelial cells, which are morphologically and functionally intermingled in highly complex three-dimensional structures. These different cell types are also present in cultures of brain cells prepared to serve as model systems of CNS physiology. Gene transfer, either in a therapeutic attempt or in basic research, is a fascinating and promising tool to manipulate both the complex physiology of the brain and that of isolated neuronal cells. Viral vectors based on the parvovirus, adeno-associated virus (AAV), have emerged as powerful transgene delivery vehicles. Here we describe highly efficient targeting of AAV vectors to either neurones or astrocytes in cultured primary brain cell cultures. We also show that transcriptional targeting can be achieved by the use of small promoters, significantly boosting the transgene capacity of the recombinant viral genome. However, we also demonstrate that successful targeting of a vector in vitro does not necessarily imply that the same targeting works in the adult brain. Cross-packaging the AAV-2 genome in capsids of other serotypes adds additional benefits to this vector system. In the brain, the serotype-5 capsid allows for drastically increased spread of the recombinant vector as compared to the serotype-2 capsid. Finally, we emphasize the optimal targeting approach, in which the natural tropism of a vector for a specific cell type is employed. Taken together, these data demonstrate the flexibility which AAV-based vector systems offer in physiological research.
The Musculoskeletal Manifestations of Progeria: A Literature Review (1988)

Although a superficial similarity exists between the musculoskeletal disorders associated with natural aging and those of progeria, an in-depth analysis reveals profound differences in the pathophysiology between the two processes. The protean manifestations of progeria can best be explained on the basis of the vascular changes found at autopsy. A disorder of the vascular endothelium may predispose progeric vessels to atherosclerotic changes. The unique musculoskeletal manifestations of progeria arise from the effects of premature atherosclerosis on the vascularized connective tissues.
Imaging neuromuscular junctions by confocal fluorescence microscopy: individual endplates seen in whole muscles with vital intracellular staining of the nerve terminals (1998)

The mammalian neuromuscular junction has been extensively studied by different methods to understand better the biological aspects of its normal development, ageing and pathological conditions, such as disorders of neuromuscular transmission. In the present report, a new technique is described that combines confocal microscopy with the use of a vital nerve terminal dye (4-Di-2-ASP) and rhodamine-alpha-bungarotoxin to stain postsynaptic acetylcholine receptors in the same endplate. Nerve terminals in the sternomastoid muscles of living adult mice were stained with 4-Di-2-ASP, which labels intracellular compartments of the nerve terminal containing mitochondria. Slides of these muscles were viewed by confocal microscopy and images were stored on magnetic optical discs. This procedure was compatible with subsequent acetylcholine receptor staining with rhodamine-alpha-bungarotoxin and observation under the confocal microscope. Classical features of the adult neuromuscular junction were displayed, such as the branched-pattern distribution of the nerve terminals and receptors and their complete colocalisation. In addition, nerve fibres from intramuscular nerve branches with their neighbouring cells, nuclei and muscle fibre striations could also be visualised. We conclude that the present technique can complement existing methods of investigation of nerve terminal anatomy and pathology, particularly where preservation of 3-dimensional relationships is required and intracellular disturbances involving mitochondrial organisation, such as ageing or other degenerative disorders, may be present.
Prophylaxis versus Episodic Treatment to Prevent Joint Disease in Boys with Severe Hemophilia (2007)

Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).
Class D-E resonant DC/DC converter (1993)

A resonant DC/DC converter is introduced, along with its analysis and experimental results. It consists of a Class D resonant inverter and a Class E rectifier. The Class D inverter ensures a low peak voltage across the transistors and the Class E rectifier offers low switching losses and noise. An analysis leading to design equations is carried out. Experimental results are given for a 50-W converter. The converter can operate for load resistances ranging from full load to infinity. The DC output voltage is regulated against load and line variations by varying the switching frequency. The relative frequency range was about 70% as the load resistance was varied from a full load of 50 Omega to infinity. The measured parameters agreed well with theoretical predictions. The converter can be used in off-line power supplies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Immunocytochemical detection of 1,25-dihydroxyvitamin D3 receptor in breast cancer. (1987)

We have developed an immunocytochemical technique to visualize the receptor for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in cryostat sections of human breast tumors and normal human breast tissue utilizing a monoclonal antibody (9A7 gamma) to chick intestinal receptor which recognizes mammalian 1,25(OH)2D3 receptor. Specific staining was observed in the nuclei of tumor cells. Previous studies by our group have shown that a high proportion of breast tumors bind radiolabeled 1,25(OH)2D3 and we have confirmed this, demonstrating immunocytochemical 1,25(OH)2D3 receptor in 43 of 55 (78%) of breast carcinomas. No correlation with the presence of immunostainable estrogen receptor was found in these breast cancer specimens. Sections of normal breast showed immunoreactivity in the nuclei of epithelial cells of the lobules and ducts. Our results demonstrate that the receptor for 1,25(OH)2D3 resides predominantly in the nucleus of breast carcinoma cells. The reason for its prominent expression in breast cancers is not yet known but may be related to growth regulation.
Photochemical Inactivation of Deoxyribonucleic and Ribonucleic Acid Viruses by Chlorpromazine (1979)

Chlorpromazine, a widely used tranquilizing drug of the phenothiazine group, was found to be a very potent photochemical inactivator of both deoxyribonucleic acid and ribonucleic acid viruses in the presence of long-wave ultraviolet light (320 to 380 nm). Neither the light alone nor chlorpromazine alone caused any appreciable inactivation. The known chlorpromazine photoreactions with nucleic acids are somewhat similar to those of psoralen (furocoumarin) derivatives. As in the case of the psoralens, chlorpromazine is capable of photoinactivating viruses totally within a few minutes under near-physiological or other gentle conditions. The antiviral effects of the chlorpromazine photoreaction could make it valuable for the development of inactivated viral vaccines as well as for use in the photochemotherapy of viral dermatoses.
Effect of a Carbon Support Containing Large Mesopores on the Performance of a Pt−Ru−Ni/C Catalyst for Direct Methanol Fuel Cells (2009)

Direct methanol fuel cell (DMFC) catalysts, Pt−Ru−Ni, supported on carbon-containing large mesopores (LMC) or XC-72 carbon black were prepared by a chemical reduction method. The homemade carbon supports were characterized by X-ray diffraction (XRD), BET surface area, and scanning and transmission electron microscopy (TEM). Catalyst performance was tested through polarization and power density curves. Electrochemical impedance spectra of fuel cells were plotted at different cell voltages. The particle size, composition, and micromorphology of Pt−Ru−Ni nanoparticles were determined by XRD, energy dispersive analysis of X-ray (EDAX), and TEM, respectively. The results of physical characterization show that both supports have the same amorphous structure, and the only difference is the BET surface area and pore structure, which play an important role in improving catalyst performance. XRD analysis shows that both catalysts exhibit face-centered cubic structures and have smaller lattice parameters than Pt alone. Their sizes are relatively small, about 4.0 nm, and their size distributions are very homogeneous. The compositions of catalysts on the two different supports are almost the same. A remarkable enhancement in catalytic activity is observed when the Pt−Ru−Ni catalyst was supported on LMC. The main reasons for the significant improved performance of the DMFC are improved diffusion in the catalyst layer and increased utilization of the catalyst.
Decoding of stochastically assembled nanoarrays (2004)

A key challenge that face nanotechnologies is controlling the uncertainty introduced by stochastic self-assembly. In this paper we explore architectural and manufacturing strategies to cope with this uncertainty when assembling nanoarrays, crossbars composed of two orthogonal sets of coded parallel nanowires. Because the encodings of nanowires that are assembled into a nanoarray cannot be predicted in advance, a discovery process is needed and specialized decoding circuitry must be employed. We have developed a probabilistic method of analysis so that various design strategies can be evaluated.
STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade (2015)

Stimulator of interferon genes (STING) is a cytosolic receptor that senses both exogenous and endogenous cytosolic cyclic dinucleotides (CDNs), activating TBK1/IRF3 (interferon regulatory factor 3), NF-κB (nuclear factor κB), and STAT6 (signal transducer and activator of transcription 6) signaling pathways to induce robust type I interferon and proinflammatory cytokine responses. CDN ligands were formulated with granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing cellular cancer vaccines--termed STINGVAX--that demonstrated potent in vivo antitumor efficacy in multiple therapeutic models of established cancer. We found that rationally designed synthetic CDN derivative molecules, including one with an Rp,Rp dithio diastereomer and noncanonical c[A(2',5')pA(3',5')p] phosphate bridge structure, enhanced antitumor efficacy of STINGVAX in multiple aggressive therapeutic models of established cancer in mice. Antitumor activity was STING-dependent and correlated with increased activation of dendritic cells and tumor antigen-specific CD8(+) T cells. Tumors from STINGVAX-treated mice demonstrated marked PD-L1 (programmed death ligand 1) up-regulation, which was associated with tumor-infiltrating CD8(+)IFNγ(+) T cells. When combined with PD-1 (programmed death 1) blockade, STINGVAX induced regression of palpable, poorly immunogenic tumors that did not respond to PD-1 blockade alone.
Neuroprotection for Ischaemic Stroke: Translation from the Bench to the Bedside (2012)

Neuroprotection seeks to restrict injury to the brain parenchyma following an ischaemic insult by preventing salvageable neurons from dying. The concept of neuroprotection has shown promise in experimental studies, but has failed to translate into clinical success. Many reasons exist for this including the heterogeneity of human stroke and the lack of methodological agreement between preclinical and clinical studies. Even with the proposed Stroke Therapy Academic Industry Roundtable criteria for preclinical development of neuroprotective agents for stroke, we have still seen limited success in the clinic, an example being NXY-059, which fulfilled nearly all the Stroke Therapy Academic Industry Roundtable criteria. There are currently a number of ongoing trials for neuroprotective strategies including hypothermia and albumin, but the outcome of these approaches remains to be seen. Combination therapies with thrombolysis also need to be fully investigated, as restoration of oxygen and glucose will always be the best therapy to protect against cell death from stroke. There are also a number of promising neuroprotectants in preclinical development including haematopoietic growth factors, and inhibitors of the nicotinamide adenine dinucleotide phosphate oxidases, a source of free radical production which is a key step in the pathophysiology of acute ischaemic stroke. For these neuroprotectants to succeed, essential quality standards need to be adhered to; however, these must remain realistic as the evidence that standardization of procedures improves translational success remains absent for stroke.
Acetaminophen and its toxicity (1983)

Acetaminophen (APAP) is considered one of the safest of all minor analgesics, but when taken in large doses (greater than 10 g) toxicity occurs. Severely poisoned patients experience hepatic and/or renal failure. The major metabolic pathway of APAP is formation of glucuronide and sulfate conjugates. A minor pathway is formation of a reactive metabolite that conjugates with glutathione (GSH). When GSH is depleted, the reactive metabolite causes necrosis of hepatic and other tissues. Treatment of APAP toxicity involves supplying alternate sulfhydryl donors or inhibiting oxidative formation of the reactive metabolite. Estimation of plasma APAP levels is necessary for effective treatment.
Neuron‐glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electonmicroscopic study in Macacus rhesus (1971)

Abstract The cytology of the postmitotic migratory granule cell and its relationship to Bergmann glial processes was examined with Golgi staining and electron microscopy in the three cardinal planes in the developing cerebellar cortex of Macacus rhesus at various late fetal and early postnatal ages. After final mitosis the granule cell body transforms from a nearly round shape in the superficial zone of the external granular layer to a horizontal bipolar form with elongated processes oriented longitudinally to the folium, at the outer border of the molecular layer. Another descending process develops, and the cell soma becomes a pyramid flattened in the plane longitudinal to the folium. The nucleus moves into the descending process and the cell soma assumes a vertically oriented spindle shape while migrating among previously formed parallel fibers deeper in the molecular layer, and finally attains a round shape again when it lies deep to the Purkinje cell layer. During these transformations, the cell cytoplasm becomes more voluminous and contains a prominent Golgi apparatus, numerous free ribosomes, mitochondria, multivesicular and dense bodies, and fascicles of microtubules Longitudinally oriented microtubules concentrated in the vertical leading process disappear by the time the cell soma enters the granular layer. The slender trailing process loss most of its cytoplasmic organelles, acquires microtubules and together with the horizontal processes forms the characteristic T‐shaped axon. The axon forms synapses with Purkinje and stellate cell dendrites at a time when other granule cells are still migrating among them. During the entire course of their migration across the molecular layer, granule cells are directly apposed to vertically oriented Bergmann fibers belonging to the Golgi epithelial cells. The sequence of developmental stages indicates that Golgi epithelial cells are a type of protoplasmic astrocyte. The Bergmann fibers were present at all stages examined, and their constant apposition to granule cells suggests a role in the lartter's migration. Numerous electronluscent beady enlargements are seen along the fiber except at sites were the surface is in contact with migrating cells; probably these enlargements change position as the granule cells pass along the Bergmann fiber. Lamellate expansions also project from the main shaft of the glial fiber and envelop the synaptic sites on spines of Purkinje cell dendrites. These expansions seem more durable, and the young neuron appears to avoid collision with them by sprialling around the glial shaft during its descent to the granular layer. The neuron‐glia relationship apparently provides the necessary conditions for the migration of the young granule cell. Especially at late developmental stages when the molecular layer is more than 250 μ wide and is densely packed with highly oriented cell processes that have already established synaptic connections.
A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors (2007)

Although most pituitary tumors are benign, some are invasive or aggressive. In the absence of specific markers of malignancy, only tumors with metastases are considered malignant. To identify markers of invasion and aggressiveness, we focused on prolactin (PRL) tumors in the human and rat. Using radiology and histological methods, we classified 25 human PRL tumors into three groups (non-invasive, invasive, and aggressive-invasive) and compared them with a model of transplantable rat PRL tumors with benign and malignant lineages. Combining histological(mitoses and labeling for Ki-67, P53, pituitary transforming tumor gene (PTTG), and polysialic acid neural cell adhesion molecule) and transcriptomic (microarrays and q-RTPCR) methods with clinical data (post-surgical outcome with case-control statistical analysis), we found nine genes implicated in invasion (ADAMTS6, CRMP1, and DCAMKL3) proliferation (PTTG, ASK, CCNB1, AURKB, and CENPE), or pituitary differentiation (PITX1) showing differential expression in the three groups of tumors (P = 0.015 to 0.0001). A case-control analysis, comparing patients in remission (9 controls) and patients with persistent or recurrent tumors (14 cases) revealed that eight out of the nine genes were differentially up- or downregulated (P = 0.05 to 0.002), with only PTTG showing no correlation with clinical course (P = 0.258). These combined histological and transcriptomic analyses improve the pathological diagnosis of PRL tumors, indicating a reliable procedure for predicting tumor aggressiveness and recurrence potential. The similar gene profiles found between non-invasive human and benign rat tumors, as well as between aggressive-invasive human and malignant rat tumors provide new insights into malignancy in human pituitary tumors.
Product differentiation in a mixed duopoly (2005)

This paper analyzes a mixed duopoly with horizontal product differentiation using the unconstrained Hotelling model with quadratic transport costs. Firms play a noncooperative two-stage game on locations (first stage) and prices (second stage), and we consider that the firms move simultaneously or sequentially in both stages. We examine how the presence of a public firm affects both locations (the nature and degree of differentiation) and prices at equilibrium, and we compare these with the results of the private duopoly, in order to determine the effects of privatization. We find that, save in cases where the private firm is leader on prices where there are multiple equilibria, in the remainder of the cases there are two symmetrical equilibria (depending on whether one firm is located to the left or right of the other); the degree of differentiation of the product and the prices are lower; and the social welfare is higher than in the private duopoly. Privatization of the public firm is therefore not socially desirable