gebhart/patrepeval huggingface dataset:
Transdermal and Transmucosal Powdered Drug Delivery (1999)

High-velocity powder injection is a promising new drug-delivery technique that provides needle- and pain-free delivery of traditional drugs, drugs from biotechnology such as proteins, peptides, and oligonucleotides as well as traditional and genetic vaccines. The energy of a transient helium gas jet accelerates fine drug particles of 20 microns-100 microns diameter to high velocities and delivers them into skin or mucosal sites. This review describes the configuration and operating principles of devices that accelerate the particles, the required properties of the particles, the characteristics of the target tissues, and features of the developmental test methods. Preclinical and clinical results that best characterize the technology and introduce its potential as a drug-delivery platform are presented.
Multiple components are required for sequence recognition of the AP1 site in the gibbon ape leukemia virus enhancer. (1989)

At least two subunits contributed to the formation in vitro of a specific complex binding to the AP1 consensus sequence (TGAGTCA) in the gibbon ape leukemia virus (GALV) enhancer in MLA144 cells. This complex can be dissociated on a monomeric GALV oligonucleotide affinity column. One protein, termed the core protein, was retained on the oligonucleotide affinity column. The second protein flowed through the oligonucleotide affinity column and, when alone, did not bind to DNA; however, when present with the core protein, it bound strongly and very specifically to the GALV sequence. MLA144 cells contained only trace amounts of c-fos and c-jun by immunoblot analysis, suggesting that the proteins specifically binding to the GALV AP1 site were distinct from c-fos and c-jun. In addition to the major complex that recognized the GALV element, MLA144 cells contained a minor complex that is chromatographically different from and antigenically related to c-fos. The factor in the flowthrough complemented a human T-cell nuclear extract (Jurkat cell line), which, when alone, had no assayable complex that specifically bound to the GALV enhancer; this complementation gave rise to a specific complex similar to that seen in MLA144 cells. Together, these results suggest that the GALV enhancer can interact with multicomponent protein complexes in a cell-line-specific manner.
Fiber‐knob modifications enhance adenoviral tropism and gene transfer in malignant glioma (2007)

These results indicate that modifications of adenoviral tropism can enhance gene transfer in tumors that are poorly susceptible to adenoviral vectors and warrant further development of Ad5-pk7 for glioma gene therapy.
A Versatile Assay for High-Throughput Gene Expression Profiling on Universal Array Matrices (2004)

We report a flexible, sensitive, and quantitative gene-expression profiling system for assaying more than 400 genes, with three probes per gene, for 96 samples in parallel. The cDNA-mediated annealing, selection, extension and ligation (DASL) assay targets specific transcripts, using oligonucleotides containing unique address sequences that can hybridize to universal arrays. Cell-specific gene expression profiles were obtained using this assay for hormone-treated cell lines and laser-capture microdissected cancer tissues. Gene expression profiles derived from this assay were consistent with those determined by qRT-PCR. The DASL assay has been automated for use with a bead-based 96-array matrix system. The combined high-throughput assay and readout system is accurate and efficient, and can cost-effectively profile the expression of hundreds of genes in thousands of samples.
Coupling efficiencies of amino acids in the solid phase synthesis of peptides. (1992)

The "classical" Merrifield method was used to synthesize over 500 peptides using Boc-benzyl strategy. The peptides were prepared either manually or on a Beckman 990B synthesizer or an Applied Biosystems 430A synthesizer. Each coupling of Boc amino acid to the growing peptide on the resin was monitored with the ninhydrin reaction. Couplings were considered "incomplete" if there was 99% or less coupling and "high incomplete" if there was 98% or less coupling. The efficiency of coupling was evaluated in regard to the specific amino acids involved in the coupling reaction and to the length of the peptide at the time of the coupling. The most difficult carboxyl-reacting amino acids were histidine, threonine, arginine, valine, isoleucine and glutamine; the most difficult amine reacting residues were glutamine, leucine, alanine, arginine and isoleucine. The number of "incomplete" and "high incomplete" couplings and the total number of monitored couplings of each of the 20 carboxyl-reacting amino acids when reacting with each of the 20 amine-reacting residues were tabulated. Coupling efficiencies decreased with the length of the peptide. The conclusion of this study is that, with the chemistries and methods used in this group of peptides, no amino acid coupling can be predicted to be complete with a single coupling reaction. The study points to the need for on-line determination of coupling efficiency during the synthesis in which a recoupling step is initiated when the first coupling is incomplete.
Synaptic Noise and Physiological Coupling Generate High-Frequency Oscillations in a Hippocampal Computational Model (2009)

There is great interest in the role of coherent oscillations in the brain. In some cases, high-frequency oscillations (HFOs) are integral to normal brain function, whereas at other times they are implicated as markers of epileptic tissue. Mechanisms underlying HFO generation, especially in abnormal tissue, are not well understood. Using a physiological computer model of hippocampus, we investigate random synaptic activity (noise) as a potential initiator of HFOs. We explore parameters necessary to produce these oscillations and quantify the response using the tools of stochastic resonance (SR) and coherence resonance (CR). As predicted by SR, when noise was added to the network the model was able to detect a subthreshold periodic signal. Addition of basket cell interneurons produced two novel SR effects: 1) improved signal detection at low noise levels and 2) formation of coherent oscillations at high noise that were entrained to harmonics of the signal frequency. The periodic signal was then removed to study oscillations generated only by noise. The combined effects of network coupling and synaptic noise produced coherent, periodic oscillations within the network, an example of CR. Our results show that, under normal coupling conditions, synaptic noise was able to produce gamma (30-100 Hz) frequency oscillations. Synaptic noise generated HFOs in the ripple range (100-200 Hz) when the network had parameters similar to pathological findings in epilepsy: increased gap junctions or recurrent synaptic connections, loss of inhibitory interneurons such as basket cells, and increased synaptic noise. The model parameters that generated these effects are comparable with published experimental data. We propose that increased synaptic noise and physiological coupling mechanisms are sufficient to generate gamma oscillations and that pathologic changes in noise and coupling similar to those in epilepsy can produce abnormal ripples.
Viterbi Decoder for High-Speed Ultra-Wideband Communication Systems (2006)

Ultra-wideband (UWB) communication systems have attracted both academic research and commercial interests due to their potential high throughput and precise ranging capability. Convolutional codes are widely used in different proposals for high-speed UWB communication systems. In this paper, a novel Viterbi decoder architecture is studied for the multiband orthogonal frequency division multiplexing (MB-OFDM) UWB system. In the Viterbi decoder, sliding block, 2-step lookahead and 2 parallel techniques are combined to achieve the highest desired data rate. For lower data rates, it is possible to disable some parts of the decoder for power saving by proper analysis of the effects of puncturing on word length and trace back length. At the same time, in the add-compare-select (ACS) unit, a pipelined most-significant bit (MSB) first ACS unit is also utilized to shorten the length of the critical path.
Limitation of glycolysis by hexokinase in rat brain synaptosomes during intense ion pumping (1996)

Incubation of rat brain synaptosomes under conditions of either increased energy utilization (addition of Na+ channel opener, veratridine, or ionophores, monensin and nigericin) or inhibition of oxidative phosphorylation (addition of rotenone), or a combination thereof, decreased [ATP], increased [ADP] and stimulated glycolysis. The rates of lactate generation were linear over a 15-min interval in the presence of rotenone alone but decreased in the other two conditions. During the first 5 min, the amount of lactate formed with veratridine, monensin or nigericin was as high or higher than with rotenone, but it was lower in the last 10 min. With a combination of one of the stimulators of ion movements and rotenone the rate of glycolysis was always markedly lower than with each compound added singly. The stimulated rates of lactate formation correlated positively with the synaptosomal content of [ATP]. After 15 min, [ATP] was 0.9-1.0 nmol/mg with rotenone, 0.5-0.9 nmol/mg with veratridine (or ionophores), and <0.3 nmol/mg with a combination of the two. Under the conditions used, calcium did not affect glycolytic activity directly. The Lineweaver-Burk plot of the rate of lactate formation against [ATP] yielded a straight line with a Km for ATP of about 0.1 mM, which is very similar to the Km for this nucleotide of brain hexokinase bound to mitochondria. In C6 cells glycolytic rate measured with a combination of an ionophore and rotenone was higher than with each of these compounds added singly while [ATP] never declined below about 9 nmol/mg prot. It is concluded that in synaptosomes, the high rate of energy utilization required for intense ion movement decreases [ATP] to a level that limits hexokinase activity kinetically. This may contribute to a reduction in the rate of glycolysis and hence energy production in brain hypoxia and ischemia.
The Bone Regenerative Effect of Growth Hormone on Consolidation in Mandibular Distraction Osteogenesis of a Dog Model (2003)

The purpose of this project was to study the effect of growth hormone on early bony consolidation in distraction osteogenesis of a dog model. Sixteen dogs were used for this study. The vertical osteotomy on the mandibular body was extended downward. An external distraction device was applied to the mandibular body and the mandibular distraction was started 5 days after the operation at a rate of 1 mm/d up to a 10-mm distraction. The experimental group was divided into a control group and growth hormone group. Dogs in the growth hormone group received a daily subcutaneous injection of 100 microg (1 IU) of recombinant human growth hormone per kilogram of body weight. The daily administration of growth hormone was performed from the day of the osteotomy through the whole distraction period to the sacrifice. Normal saline was injected in the control group. Eight dogs were allocated to each group. Two dogs in each group, a total of four dogs, were killed at 2 weeks after completion of distraction, four dogs were killed at 4 weeks, and the other eight dogs were killed at 6 weeks. The level of serum IGF-I in the growth hormone group was elevated and peaked between 8 days and 12 days after systemic administration of growth hormone. Bone mineral density was higher in the growth hormone group and lower in the control group for the whole period. Bone mechanical strength was 300% higher in the growth hormone group than in the control group. However, results were more suggestive than conclusive. On histological examination, the formation of a substantial amount of active woven bone was observed throughout the distracted zone at six weeks in the growth hormone group. In the control group, new bone was generated from the edge to the center of the distracted zone. In addition, most of the central area of the distracted zone was filled with fibrous tissue at six weeks. In conclusion, these findings suggest that growth hormone appears to be effective in early bony consolidation in distraction osteogenesis.
Study on the clinical efficacy of specific phosphodiesterase inhibitor in patients with pulmonary hypertension due to left heart disease (2018)

Pulmonary hypertension due to left heart disease (PH-LHD) is caused by left ventricular (LV) systolic and/or diastolic dysfunction and left heart valve disease. LV diseases lead to left ventricular filling pressure increases, pulmonary venous obstruction and pulmonary venous pressure increases, and thus to secondary PH. Exercise tolerance is lower and fatality rates are higher in patients with PH-LHD than those in subjects with normal pulmonary arterial pressure. In spite of the progress in the study of the mechanisms of PH-LHD in recent years, no specific treatment is currently available. The efficacy and safety of targeted therapies for pulmonary arterial hypertension remain to be fully established. In the present study, PH-LHD patients were treated with milrinone injection. It was concluded that milrinone significantly reduces pulmonary artery systolic pressure (PASP) in patients with PH-LHD, and significantly improves the cardiac structure, cardiac function and biochemical indexes. PASP was significantly correlated with the left atrial diameter, LV end diastolic diameter, LV ejection fraction, tricuspid annular plane systolic excursion, right ventricular fractional area change, N-terminal pro-B-type natriuretic peptide and hypersensitive C-reactive protein.
Cardiac Stem Cells in the Failing Human Heart (2005)

Myocardial regeneration occurs in humans following ischemic injury The recent identification of cardiac stem cells (CSCs) in the mammalian heart CSCs are distributed throughout the heart raising the possibility that those located within the infarct or in its proximity could divide and differentiate reconstituting dead myocardium. If this were the case, strategies may be developed to enhance myocyte and vascular growth promoting partial restoration of the infarct. This response would increase the number of myocytes and vessels, reduce infarct size, improve function and decrease mortality.
Interactions of Benzodiazepine Derivatives with Annexins (1998)

Human annexins III and V, members of the annexin family of calcium- and membrane-binding proteins, were complexed within the crystals with BDA452, a new 1,4-benzodiazepine derivative by soaking and co-crystallization methods. The crystal structures of the complexes were analyzed by x-ray crystallography and refined to 2.3- and 3.0-A resolution. BDA452 binds to a cleft which is located close to the N-terminus opposite to the membrane binding side of the proteins. Biophysical studies of the interactions of various benzodiazepine derivatives with annexins were performed to analyze the binding of benzodiazepines to annexins and their effects on the annexin-induced calcium influx into phosphatidylserine/phosphatidylethanolamine liposomes. Different effects were observed with a variety of benzodiazepines and different annexins depending on both the ligand and the protein. Almost opposite effects on annexin function are elicited by BDA250 and diazepam, its 7-chloro-derivative. We conclude that benzodiazepines modulate the calcium influx activity of annexins allosterically by stabilizing or destabilizing the conducting state of peripherally bound annexins in agreement with suggestions by Kaneko (Kaneko, N., Ago, H., Matsuda, R., Inagaki, E., and Miyano, M. (1997) J. Mol. Biol., in press).
Lysophosphatidic acid: a novel growth and survival factor for renal proximal tubular cells (1997)

Lysophosphatidic acid (LPA) is the smallest and structurally simplest of all glycerophospholipids. LPA is a normal constituent of serum and binds with high affinity to albumin while retaining its biological activity. The effects of LPA are pleiotropic and range from mitogenesis to stress fiber formation. In this report, we demonstrate two novel functions for LPA. LPA acts as a survival factor to inhibit apoptosis of primary cultures of mouse renal proximal tubular (MPT) cells. LPA also acts as a potent mitogen for MPT cells. The ability of LPA to act as both a survival factor and a mitogen is mediated by the lipid kinase phosphatidylinositol 3-kinase (PI3K), since these activities were completely blocked by wortmannin or LY-294002, two structurally dissimilar inhibitors of PI3K. The identification of LPA as a proliferative and anti-apoptotic factor suggests a potential role for this lipid mediator during the injury and/or recovery phases following tubular damage.
An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults (2011)

Adults with attention-deficit/hyperactivity disorder (ADHD) are more frequently presenting for diagnosis and treatment. Medication is considered to be appropriate among available treatments for ADHD; however, the evidence supporting the use of pharmacotherapeutics for adults with ADHD remains less established. In this article, the effectiveness and dosing parameters of the various agents investigated for adult ADHD are reviewed. In adults with ADHD, short-term improvements in symptomatology have been documented through the use of stimulants and antidepressants. Studies suggest that methylphenidate and amphetamine maintained an immediate onset of action, whereas the ADHD response to the nonstimulants appeared to be delayed. At a group level, there appears to be some, albeit not entirely consistent, dose-dependent responses to amphetamine and methylphenidate. Generally speaking, variability in diagnostic criteria, dosing parameters and response rates between the various studies was considerable, and most studies were of a relatively short duration. The aggregate literature shows that the stimulants and catecholaminergic nonstimulants investigated had a clinically significant beneficial effect on treating ADHD in adults.
Experience of pain after subcutaneous administration of different preparations of recombinant human erythropoietin: a randomized, double-blind crossover study. (1991)

Subcutaneous erythropoietin (SCEPO) is considered to be more effective than intravenously administered erythropoietin. Patient compliance with SC injections will be important in long-term therapy as there have been reports of pain associated with SCEPO. A double-blind randomized study was performed upon 18 ESRD hemodialysis patients receiving regular subcutaneous erythropoietin replacement therapy for treatment of their anemia. The study involved pain assessment by a visual analogue scale VAS and a verbal descriptive scale VDS following 2 subcutaneous injections of preparation A: rhEPO 2000 IU in 1 ml (Cilag), preparation B: rhEPO 2000 IU in 1 ml (Boehringer Mannheim) and 0.9% saline 1 ml (placebo) over a two-week period. The injections were all administered by the same person and replaced the normal EPO injections for the patient during the study period. Results by VAS and VDS based upon 107 responses showed that preparation A was significantly more painful than preparation B (p less than 0.001) or saline (p less than 0.01). An unexpected finding was that preparation B was less painful than the placebo for VAS (p less than 0.05). It seems unlikely that the erythropoietin itself was responsible for the difference. Further work will be necessary to determine the pain causing factor in preparation A, and the possible local anaesthetic factor in preparation B.
[Gastric cancer]. (2009)

The prognostic significance of histologic type is unclear in patients with gastric cancer. However, the regimen has been actually selected by histologic type from clinical reports and clinical experiences. The differentiated type is related to metastasis in the liver and the undifferentiated type to the peritoneum metastasis. The S-1+CDDP combined therapy that is standard treatment has no difference in antitumor effect by the histologic type factor. CPT-11 and CPT-11+ CDDP combined therapy, which is the second-line therapy, can be expected to be effective in a gastric cancer patient with target lesion like liver metastasis. With paclitaxel and docetaxel, the second-line therapy, the effect is expected in a gastric cancer patient without a target lesion like peritoneal metastasis.
Very Deep Convolutional Networks for Text Classification (2017)

The dominant approach for many NLP tasks are recurrent neural networks, in particular LSTMs, and convolutional neural networks. However, these architectures are rather shallow in comparison to the deep convolutional networks which have pushed the state-of-the-art in computer vision. We present a new architecture (VD-CNN) for text processing which operates directly at the character level and uses only small convolutions and pooling operations. We are able to show that the performance of this model increases with the depth: using up to 29 convolutional layers, we report improvements over the state-ofthe-art on several public text classification tasks. To the best of our knowledge, this is the first time that very deep convolutional nets have been applied to text processing.
Mitochondrial ATP-Dependent Potassium Channels (1998)

Our results demonstrate that diazoxide targets mitochondrial but not sarcolemmal KATP channels and imply that mitochondrial KATP channels may mediate the protection from KATP channel openers.
Did dinosaurs have megakaryocytes? New ideas about platelets and their progenitors (2005)

Biological evolution has struggled to produce mechanisms that can limit blood loss following injury. In humans and other mammals, control of blood loss (hemostasis) is achieved through a combination of plasma proteins, most of which are made in the liver, and platelets, anucleate blood cells that are produced in the bone marrow by megakaryocytes. Much has been learned about the underlying mechanisms, but much remains to be determined. The articles in this series review current ideas about the production of megakaryocytes from undifferentiated hematopoietic precursors, the steps by which megakaryocytes produce platelets, and the molecular mechanisms within platelets that make hemostasis possible. The underlying theme that connects the articles is the intense investigation of a complex system that keeps humans from bleeding to death, but at the same time exposes us to increased risk of thrombosis and vascular disease.
The American College of Radiology Mammography Accreditation Program. (1990)

Robert McLelland1 R. Edward Hendnck2 Mane D. Zinninger3 Pamela A. Wilcox3 This article discusses the background, goals, criteria, current results, impact, and future directions of the American College of Radiology’s (ACR’s) Mammography Accreditation Program. To date, approximately one half of the mammographic units in the United States have voluntarily applied for accreditation through the ACR program, with approximately one quarter of the units in the United States now accredited. Application rates have increased steadily since the start of the program in August 1987. The equipment performance criteria and professional criteria defined and employed in the ACR Mammography Accreditation Program have been adopted as standards for the performance of screening mammography by the ACR and have served as a basis for quality assurance standards in state and federal legislation on mammography.