gebhart/patrepeval huggingface dataset:
Expression and hypoxia-responsiveness of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 in mammary gland malignant cell lines. (2005)

Recently, we have shown that PFKFB4 gene which encodes the testis isoenzyme of PFKFB is also expressed in the prostate and hepatoma cancer cell lines. Here we have studied expression and hypoxic regulation of the testis isoenzyme of PFKFB4 in several malignant cell lines from a female organ--the mammary gland. Our studies clearly demonstrated that PFKFB4 mRNA is also expressed in mammary gland malignant cells (MCF-7 and T47D cell lines) in normoxic conditions and that hypoxia strongly induces it expression. To better understand the mechanism of hypoxic regulation of PFKFB4 gene expression, we used dimethyloxalylglycine, a specific inhibitor of HIF-1alpha hydroxylase enzymes, which strongly increases HIF-1alpha levels and mimics the effect of hypoxia. It was observed that PFKFB4 expression in the MCF7 and T47D cell lines was highly responsive to dimethyloxalylglycine, suggesting that the hypoxia responsiveness of PFKFB4 gene in these cell lines is regulated by HIF-1 proteins. Moreover, desferrioxamine and cobalt chloride, which mimic the effect of hypoxia by chelating or substituting for iron, had a similar stimulatory effect on the expression of PFKFB mRNA. In other mammary gland malignant cell lines (BT549, MDA-MB-468, and SKBR-3) hypoxia and hypoxia mimics also induced PFKFB4 mRNA, but to variable degrees. The hypoxic induction of PFKFB4 mRNA was equivalent to the expression of PFKFB3, Glut1, and VEGF, which are known HIF-1-dependent genes. Hypoxia and dimethyloxalylglycine increased the PFKFB4 protein levels in all cell lines studied except MDA-MB-468. Through site-specific mutagenesis in the 5'-flanking region of PFKFB4 gene the hypoxia response could be limited. Thus, this study provides evidence that PFKFB4 gene is also expressed in mammary gland cancer cells and strongly responds to hypoxia via an HIF-1alpha dependent mechanism. Moreover, the PFKFB4 and PFKFB3 gene expression in mammary gland cancer cells has also a significant role in the Warburg effect which is found in all malignant cells.
Optic Nerve Damage in Mice with a Targeted Type I Collagen Mutation (2004)

Transgenic Col1a1(r/r) mice develop sustained elevation of IOP and progressive optic nerve axon loss. This suggests that these mice may be useful as a mouse model of primary open angle glaucoma as well as for assessing the relationship between collagen type I metabolism and optic nerve axon loss.
Evidence of an Unusually Long Operator for the Fur Repressor in the Aerobactin Promoter of Escherichia coli (2000)

Production of the siderophore aerobactin in Escherichia coli is transcriptionally metalloregulated through the iron-dependent binding of the Fur (ferric uptake regulator) to a large region (>100 base pairs) within the cognate promoter in the pColV-K30 plasmid. We show in this article that such an unusually long operator results from the specific addition of degenerate repeats 5'-NAT(A/T)AT-3' and not from a fortuitous occupation of the DNA adjacent to the primary binding sites by an excess of the repressor. Furthermore, the protection pattern revealed by DNase I and hydroxyl radical footprinting reflected a side-by-side oligomerization of the protein along an extended DNA stretch. This type of DNA-protein interactions is more like those observed in some eukaryotic factors and nucleoid-associated proteins than typical of specific prokaryotic regulators.
Disruption of receptor-G protein coupling in yeast promotes the function of an SST2-dependent adaptation pathway. (1993)

In the yeast Saccharomyces cerevisiae, a G protein-linked signal transduction pathway mediates response to the oligopeptide mating pheromones a-factor and alpha-factor. Because cellular responses, including G1 arrest, occur transiently, cells can adapt or desensitize and resume growth. To address whether the balance between response and adaptation is influenced by the efficiency of receptor-G protein interaction, we introduced random point mutations in sequences that encode the third cytoplasmic loop of the alpha-factor receptor (STE2 gene product). Three mutations were identified that confer alpha-factor-resistant phenotypes, yet preserve normal cell-surface expression, ligand-binding affinity, and endocytosis of the receptor. However, these mutations confer partial signaling defects, as determined by cell cycle arrest and transcriptional induction assays, as well as in vitro assays of receptor-G protein interaction. Physiological tests suggested that receptors bearing third loop substitutions promote recovery from pheromone-induced growth arrest. Genetic evidence indicated that the third loop and the C-terminal domain of the receptor control independent recovery or adaptation processes. In contrast, receptor third loop substitutions caused rapid adaptation only if cells express a functional SST2 gene. Thus, disruption of pheromone receptor-G protein interaction concomitantly blunts signaling and specifically promotes the function of an SST2-dependent adaptation pathway. Possible functions for the Sst2 protein are discussed.
Single-graph multiple flows (2014)

We present the single-graph multiple-flows (SGMF) architecture that combines coarse-grain reconfigurable computing with dynamic dataflow to deliver massive thread-level parallelism. The CUDA-compatible SGMF architecture is positioned as an energy efficient design alternative for GPGPUs. The architecture maps a compute kernel, represented as a dataflow graph, onto a coarse-grain reconfigurable fabric composed of a grid of interconnected functional units. Each unit dynamically schedules instances of the same static instruction originating from different CUDA threads. The dynamically scheduled functional units enable streaming the data of multiple threads (or graph flows, in SGMF parlance) through the grid. The combination of statically mapped instructions and direct communication between functional units obviate the need for a full instruction pipeline and a centralized register file, whose energy overheads burden GPGPU We show that the SGMF architecture delivers performance comparable to that of contemporary GPGPUs while consuming 57% less energy on average.
Vitiligo: A review of the published work (2011)

Vitiligo is a common depigmenting skin disorder, characterized by acquired, idiopathic, progressive, circumscribed hypomelanosis of the skin and hair, with total absence of melanocytes microscopically. It occurs worldwide, with an incidence rate of between 0.1% and 2%. Vitiligo is an important skin disease having a major impact on the quality of life of the patient suffering from it. The causes of this condition are uncertain but seem to be dependent on the interaction of genetic, immunological and neurological factors. Vitiligo coexists with other autoimmune disorders, Sutton or halo nevus, and malignant melanoma. The substantial disfigurement associated with vitiligo can cause serious emotional stress for the patient, which necessitates treatment. Because its pathogenesis is still not understood, there is a plethora of different treatments. Among them, topical steroids and narrowband ultraviolet B monotherapy were the most common as current treatments for localized and generalized vitiligo, respectively. Cosmetic improvement can be achieved by camouflage products and self-tanning dyes. The course of vitiligo is unpredictable, but often progressive. Spontaneous repigmentation may occur in a few people (10–20%), mainly in children, but this tends to be only partial and on sun-exposed areas. In this article, we review vitiligo as a whole, including epidemiology, pathogenesis and etiology, histopathology, clinical manifestations, classification, clinical variants, diagnosis and differential diagnoses, specific investigation, treatment, prognosis, psychosocial view and its association with other disorders.
Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions (1990)

An amino acid sequence encodes a message that determines the shape and function of a protein. This message is highly degenerate in that many different sequences can code for proteins with essentially the same structure and activity. Comparison of different sequences with similar messages can reveal key features of the code and improve understanding of how a protein folds and how it performs its function.
Current practices for postoperative pain management in Europe and the potential role of the fentanyl HCl iontophoretic transdermal system (2006)

Survey results continue to reveal that postoperative pain is insufficiently managed throughout Europe and the rest of the world. However, the efficient use of existing resources, as well as the introduction of novel technologies, may aid in its improvement. Use of an acute pain service has the potential to improve pain management through specialized patient care and utilization of effective analgesic techniques. Multimodal analgesic techniques, which include adjuvant non-opioids and/or regional analgesic techniques, can provide effective analgesia and reduce the amount of systemic opioids (or obviate the need) for postoperative pain management. Patient-controlled analgesia modalities may also offer improvements to pain management, as in practice they provide pain relief superior to the intermittent administration of bolus doses of opioids. A novel patient-controlled analgesia modality that has been approved by the European Medicines Evaluation Agency (EMEA) for the treatment of acute, moderate-to-severe pain is the needle-free, pre-programmed fentanyl HCl iontophoretic transdermal system. This system was shown in a recent US clinical trial to be comparable in efficacy to a standard regimen of morphine intravenous patient-controlled analgesia. Adverse events associated with the use of the fentanyl iontophoretic transdermal system are generally similar to those experienced by patients using intravenous morphine patient-controlled analgesia. Considerations regarding the selection of patients for treatment with the fentanyl iontophoretic transdermal system are similar to those with other patient-controlled analgesia modalities; sufficient upper limb mobility and alertness are required to operate the system. Utilization of the fentanyl iontophoretic transdermal system, together with the guidance of an effective acute pain service, may lead to improvements in postoperative pain management.
Differential desensitization and phosphorylation of three cloned and transfected alpha 2-adrenergic receptor subtypes (1994)

Genes encoding 3 distinct subtypes of human alpha 2-adrenergic receptor are known and are found, respectively, on chromosome 10, 4, and 2 (alpha 2-C10, alpha 2-C4, and alpha 2-C2 adrenergic receptors). All 3 receptors inhibit adenylyl cyclase via Gi proteins. To study and compare their regulatory properties we assessed the ability of each to undergo agonist-promoted desensitization and phosphorylation. When Chinese hamster ovary cells stably expressing each of the three receptor genes were incubated with epinephrine for 20 min, a marked decrease in sensitivity to subsequent agonist-mediated inhibition of adenylyl cyclase was observed for the alpha 2-C10 and alpha 2-C2 receptors but not for the alpha 2-C4 receptors. When similar incubations were performed with 32Pi-labeled cells and the receptors were immunoprecipitated with specific antibodies, alpha 2-C10 and alpha 2-C2 receptors were found to undergo an approximately 3-fold increase in receptor phosphorylation after epinephrine exposure. When transfected into COS cells epinephrine also stimulated phosphorylation of alpha 2-C10 and alpha 2-C2 receptors while having only a slight effect on alpha 2-C4 receptors. Cotransfection of the cells with the cDNA encoding the beta-adrenergic receptor kinase further increased receptor phosphorylation for alpha 2-C10 and alpha 2-C2 receptors while having little or no effect on alpha 2-C4 receptors. Moreover purified and reconstituted recombinant alpha 2-C10 receptors could be phosphorylated in an agonist-dependent fashion whereas alpha 2-C4 receptors could not. These observations suggest receptor subtype-specific differences in susceptibility to regulatory phosphorylation and desensitization.
Peptide agonists of the thrombopoietin receptor (1998)

We have screened a variety of L-amino acid peptide libraries against the extracellular domain of the human thrombopoietin (HuTPO) receptor, c-Mpl. A large number of peptide ligands were recovered and categorized into two families. Peptides from each family compete with the binding of HuTPO and with the binding of peptides from the other familiy. Representative peptides were synthesized and found to activate the full-length HuTPO receptor expressed in Ba/F3 cells to promote proliferation. These peptide families show no apparent homology to the primary sequence of TPO. We have focused our optimization efforts on one of the peptides, a linear 14-mer (IEGPTLRQWLAARA) with an IC50 of 2 nM in a competition binding assay and an EC50 of 400 nM in the proliferation assay. In order to enhance the potency of the compound, we constructed dimeric peptides by linking the carboxy-termini of the 14-mers to a lysine branch. These molecules exhibited slightly higher affinity (0.5 nM) and greatly increased potency (0.1 nM). The EC50 of the dimeric peptide was equivalent to that of the 332 aa form of baculovirus-expressed recombinant HuTPO. As previously shown for the erythropoietin-mimetic peptides, the TPO-mimetic peptides probably activate the TPO receptor by binding and inducing receptor dimerization. This supposition is supported by the observation that covalent dimerization of the peptide enhances its potency by 4,000-fold over that of the monomer. The peptide dimer is also active in stimulating in vitro proliferation of progenitors and maturation of megakaryocytes from human bone marrow, and in promoting an increase in platelet count when administered to normal mice.
Dynamic holograms for wavelength division multiplexing. (1997)

Available from British Library Document Supply Centre-DSC:D214949 / BLDSC - British Library Document Supply Centre
Paroxysmal extreme pain disorder (previously familial rectal pain syndrome) (2007)

Paroxysmal extreme pain disorder is a highly distinctive sodium channelopathy with incompletely carbamazepine-sensitive bouts of pain and sympathetic nervous system dysfunction. It is most likely to be misdiagnosed as epilepsy and, particularly in infancy, as hyperekplexia and reflex anoxic seizures.
An outline of the hundred-year history of PDT. (2004)

Photosensitizing drugs have been known and applied in medicine for several thousand years. However, the scientific basis for such use was vague or non-existent before about 1900. Photodynamic therapy, PDT, has now become an established treatment modality for several medical indications. Notably, in the cases of skin actinic keratosis, several forms of cancer and blindness due to age-related macular degeneration, PDT has been successful. PDT is the combined application of a lesion-localizing photosensitizer and light. PDT with porphyrin derivatives as photosensitizing drugs was developed from about 1960. The basic, underlying mechanisms for tumour localization of photosensitizers and processes explaining the effect of PDT on tumours were elucidated from about that time. It has become clear that PDT is efficient only in the presence of oxygen, and that the oxygen dependency of PDT is similar to that of X-rays. Singlet oxygen, 1O2, a short-lived product of the reaction between an excited sensitizer molecule and oxygen, plays a key role. In contrast to radiation therapy and chemotherapy, PDT has a low mutagenic potential and, except for skin phototoxicity, few adverse effects. Approvals for clinical use of PDT now exist in many countries. The annual number of scientific articles on PDT, clinical as well as basic, steadily increases and new aspects and applications of it continue to be discovered. Many of the new investigators are obviously not aware of the early work in the field and repeat many of the experiments that had been reported before the Internet and modern data bases were established. Therefore, in the present historical review, the early work is weighted more heavily than recent work that is more easily accessible to the readers.
Interleukin‐3 and Interleukin‐3 Receptors in the Braina (1998)

We have previously demonstrated that interleukin 3 (IL-3) has a neurotrophic effect on central cholinergic neurons and have demonstrated the presence of IL-3 receptor (IL-3R)beta subunits in septal cholinergic neurons by reverse-transcribed polymerase chain reaction (RT-PCR) and immunohistochemistry. In order to confirm that the expressed IL-3R is functional, we conducted experiments to show an alpha subunit of IL-3R. The alpha subunit was clearly demonstrated by RT-PCR in the central cholinergic neuronal hybrid cell line SN6, but not in its mother cell line N18TG2, and the expression was slightly upregulated after IL-3 treatment. Choline acetyltransferase and vesicular acetylcholine transporter mRNAs were significantly increased in SN6 after treatment with IL-3. Immunohistochemically, IL-3R alpha-positive cells were mainly present in the medial septal and basal forebrain region, and the stained cells were similar to choline acetyltransferase-positive cells in shape and distribution. The IL-3R alpha-positive cells slightly increased two days after fimbria-fornix transection and decreased seven days after. These findings suggest that functional IL-3 receptors are expressed in the central cholinergic neurons and contribute to some physiological roles such as the differentiation and maintenance of these neurons.
Backpropagation based on the logarithmic error function and elimination of local minima (1991)

It is has previously been pointed out that, in backpropagation learning of neural networks, using a logarithmic error function instead of the familiar quadratic error function yields remarkable reductions in learning times. In the present work, it is shown theoretically and experimentally that learning based on the logarithmic error function has the effect of reducing the density of local minima. It is proved mathematically that, in a particular sense, the logarithmic error function provides a lower (at most equal) density of local minima in any network. the logarithmic error function also alleviates the problem of getting stuck in local minima.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Design and Theoretical Evaluation of Micro-Surgical Manipulators for Orbital Manipulation and Intraocular Dexterity (2007)

This paper addresses the design considerations and dexterity evaluation of a novel hybrid two-armed micro-surgical slave robot equipped with intraocular dexterity devices. A unified framework for the kinematic modeling of this robot is presented while using the kinematic constraints stemming from the constrained motion of the eye. An augmented Jacobian describing the kinematics of the eye and the relative motion of each one of the two intraocular dexterity robots (IODR) is presented. Using this framework, the capabilities of this two-armed robot in performing dexterous intraocular operations are evaluated and compared to a similar robot without intraocular dexterity. The kinematic conditioning index (KCI) for the proposed robot is shown to be significant. The results presented show an increase of approximately 33% and 47% in translational and rotational KCI respectively
A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis. (1990)

Paired helical filaments (PHFs) are prominent components of Alzheimer disease (AD) neurofibrillary tangles (NFTs). Rather than isolating NFTs, we selected for PHF populations that can be extracted from AD brain homogenates. About 50% of PHF immunoreactivity can be obtained in 27,200 x g supernatants following homogenization in buffers containing 0.8 M NaCl. We further enriched for PHFs by taking advantage of their insolubility in the presence of zwitterionic detergents and 2-mercaptoethanol, removal of aggregates by filtration through 0.45-microns filters, and sucrose density centrifugation. PHF-enriched fractions contained two to five proteins of 57-68 kDa that displayed the same antigenic properties as PHFs. Since the 57- to 68-kDa PHF proteins are antigenically related to tau proteins, they are similar to the tau proteins previously observed in NFTs. However, further analysis revealed that PHF-associated tau can be distinguished from normal, soluble tau by PHF antibodies that do not recognize human adult tau and by one- and two-dimensional PAGE.
Biochemical Characterization of Patients With In-Frame or Out-of-FrameDMDDeletions Pertinent to Exon 44 or 45 Skipping (2013)

Exon 44 or 45 skipping will likely yield lower levels of dystrophin than exon 51 skipping, although the resulting protein is functional enough to often maintain a mild BMD phenotype. Dystrophin transcript stability is an important indicator of dystrophin expression, and transcript instability in DMD compared with BMD should be explored as a potential biomarker of response to AOs. This study is beneficial for the planning, execution, and analysis of clinical trials for exon 44 and 45 skipping.
Selamectin versus ivermectin for cheyletiellosis in pet rabbits (2016)

BestBETs for Vets are generated by the Centre for Evidence-based Veterinary Medicine at the University of Nottingham to help answer specific questions and assist in clinical decision making. Although evidence is often limited, they aim to find, present and draw conclusions from the best available evidence, using a standardised framework. A more detailed description of how BestBETs for Vets are produced was published last year (VR, April 4, 2015, pp 354-356).
Human Tissue Kallikreins: Physiologic Roles and Applications in Cancer (2004)

Abstract Tissue kallikreins are members of the S1 family (clan SA) of trypsin-like serine proteases and are present in at least six mammalian orders. In humans, tissue kallikreins (hK) are encoded by 15 structurally similar, steroid hormone–regulated genes (KLK) that colocalize to chromosome 19q13.4, representing the largest cluster of contiguous protease genes in the entire genome. hKs are widely expressed in diverse tissues and implicated in a range of normal physiologic functions from the regulation of blood pressure and electrolyte balance to tissue remodeling, prohormone processing, neural plasticity, and skin desquamation. Several lines of evidence suggest that hKs may be involved in cascade reactions and that cross-talk may exist with proteases of other catalytic classes. The proteolytic activity of hKs is regulated in several ways including zymogen activation, endogenous inhibitors, such as serpins, and via internal (auto)cleavage leading to inactivation. Dysregulated hK expression is associated with multiple diseases, primarily cancer. As a consequence, many kallikreins, in addition to hK3/PSA, have been identified as promising diagnostic and/or prognostic biomarkers for several cancer types, including ovarian, breast, and prostate. Recent data also suggest that hKs may be causally involved in carcinogenesis, particularly in tumor metastasis and invasion, and, thus, may represent attractive drug targets to consider for therapeutic intervention.