gebhart/patrepeval huggingface dataset:
Pathophysiology of Peripheral Neuropathic Pain: Immune Cells and Molecules (2007)

Damage to the peripheral nervous system often leads to chronic neuropathic pain characterized by spontaneous pain and an exaggerated response to painful and/or innocuous stimuli. This pain condition is extremely debilitating and usually difficult to treat. Although inflammatory and neuropathic pain syndromes are often considered distinct entities, emerging evidence belies this strict dichotomy. Inflammation is a well-characterized phenomenon, which involves a cascade of different immune cell types, such as mast cells, neutrophils, macrophages, and T lymphocytes. In addition, these cells release numerous compounds that contribute to pain. Recent evidence suggests that immune cells play a role in neuropathic pain in the periphery. In this review we identify the different immune cell types that contribute to neuropathic pain in the periphery and release factors that are crucial in this particular condition.
HQK-1001 Has Additive HbF-Inducing Activity in Combination with Hydroxyurea and Decitabine. (2009)

Abstract Abstract 977 Several classes of HbF inducers, including chemotherapeutic agents, ESAs, and short chain fatty acids (SCFADs) have demonstrated efficacy in inducing HbF in beta hemoglobinopathy and thalassemia patients, but broad clinical application of agents except Hydroxyurea (HU) has been limited by requirements for parenteral administration, high doses and toxicity concerns for long-term use. Yet, combination therapy is likely necessary to achieve the high fetal globin expression levels necessary to ameliorate anemia in the severe beta thalassemias. HQK-1001 is an oral, non-mutagenic SCFAD, which induces fetal globin gene expression through displacement of a repressor complex from the gamma globin gene promoter, and has shown a favorable safety and PK profile with a T1/2 of 11 hours with once daily oral doses from 5-20 mg/kg in normal human volunteers. To investigate whether HQK-1001 has additive activity with other fetal globin inducing agents with different mechanisms of action, dose-escalation studies of HQK-1001 were performed in baboons, and PK profiles and fetal globin mRNA were compared to treatment with HU. Fetal globin mRNA increased with escalating doses of HQK-1001 from 50-150 mg/kg, reaching peak effects at an AUClast of 1267 h.micrograms/ml, comparable to a human equivalent dose of 20 mg/kg (AUClast = 1174-2205 h. microgram/ml), while a significantly higher AUClast (11,817 h.microgram/ml) was observed at a 200 mg/kg/dose and associated with gamma globin suppression. In baboons treated with sequentially administered Hydroxyurea (HU) (3 days/week), gamma globin mRNA increased by 80-120% above baseline, treatment with HQK-1001 increased γ globin mRNA by 290% above baseline, while the 2-agent combination increased γ globin mRNA by 360%. In Bfu-e cultures comparing HQK-1001 +/− decitabine, F-cells increased above baseline in cultures treated with HQK-1001 alone by 32-71%, with decitabine alone by 66-104%, and with the 2 agents together by 147% above F-cell levels in control cultures. In cultures containing SCF, Bfu-e numbers increased by 25% over controls with both agents added to a peak decitabine conc. of 0.1 microM; erythroid growth declined at higher concentrations of decitabine. These studies together demonstrate higher gamma globin gene induction with HQK-1001 in combination with HU and with decitabine, and with reduced cytotoxicity with added HQK-1001. Dose-escalating Phase 2 clinical trials of HQK-1001 have begun in patients with beta thalassemia. Disclosures: Perrine: HemaQuest Pharmaceuticals: Employment, Equity Ownership, Patents &amp; Royalties, Research Funding. Faller:HemaQuest Pharmaceuticals: Consultancy, Equity Ownership, Patents &amp; Royalties, Research Funding. Boosalis:HemaQuest Pharmaceuticals: Equity Ownership. Thomson:HemaQuest Pharmaceuticals: Employment, Equity Ownership. Berenson:hemaQuest Pharmaceuticals: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.
The critical band coder--Digital encoding of speech signals based on the perceptual requirements of the auditory system (2005)

The development of a digital encoding system designed to exploit the limited detection ability of the auditory system is described. By dynamically shaping the encoding error spectrum as a function of the input speech signal, the error is masked by the speech. Psychoacoustic experiments and results from the literature provide a basis for determining the system parameters that ensure that the error is inaudible. The encoder is a multi-channel system, each channel approximately of critical bandwidth. The input signal is filtered into 17 frequency channels via the quadrature mirror filter technique. Each channel is then coded using block-companding adaptive PCM. For 4.1 kHz bandwidth speech, the differential threshold of the encoding degradation occurs at a bit rate of 34.4 kbps. At 16 kbps, the encoder produces toll quality speech output.
The microarray data analysis process: From raw data to biological significance (2006)

Despite advances in microarray technology that have led to increased reproducibility and substantial reductions in the cost of microarrays, the successful use of this technology is still elusive for many researchers, and microarray data analysis in particular presents a substantial bottleneck for many biomedical researchers. There are many reasons for this, including the expense of and a lack of adequate training in the use of analysis software. An additional reason is that microarray data analysis has largely been treated in the past as a set of separate steps, with the majority of emphasis being placed on statistical analysis and visualization of the data. For many biomedical researchers determining the biological significance of the data has been the greatest challenge and in the last several years more emphasis has been placed on this aspect of the analysis process. Despite this broadening of the scope of analysis there are still several aspects of the process that continue to be neglected, including additional related and interdependent aspects, such as experimental design, data accessibility, and platform selection. Though not traditionally thought of as integral to the data analysis process, these factors have profound effects on the analysis process. This article will discuss the importance of these additional aspects, as well as statistical analysis and determination of biological significance of microarray data. A summary of currently available software options will also be presented with a focus on the aspects discussed.
Revisiting the Valence and Conduction Band Size Dependence of PbS Quantum Dot Thin Films (2016)

We use a high signal-to-noise X-ray photoelectron spectrum of bulk PbS, GW calculations, and a model assuming parabolic bands to unravel the various X-ray and ultraviolet photoelectron spectral features of bulk PbS as well as determine how to best analyze the valence band region of PbS quantum dot (QD) films. X-ray and ultraviolet photoelectron spectroscopy (XPS and UPS) are commonly used to probe the difference between the Fermi level and valence band maximum (VBM) for crystalline and thin-film semiconductors. However, we find that when the standard XPS/UPS analysis is used for PbS, the results are often unrealistic due to the low density of states at the VBM. Instead, a parabolic band model is used to determine the VBM for the PbS QD films, which is based on the bulk PbS experimental spectrum and bulk GW calculations. Our analysis highlights the breakdown of the Brillioun zone representation of the band diagram for large band gap, highly quantum confined PbS QDs. We have also determined that in 1,2-ethanedithiol-treated PbS QD films the Fermi level position is dependent on the QD size; specifically, the smallest band gap QD films have the Fermi level near the conduction band minimum and the Fermi level moves away from the conduction band for larger band gap PbS QD films. This change in the Fermi level within the QD band gap could be due to changes in the Pb:S ratio. In addition, we use inverse photoelectron spectroscopy to measure the conduction band region, which has similar challenges in the analysis of PbS QD films due to a low density of states near the conduction band minimum.
Cannabinoid Type 2 Receptor as a Target for Chronic - Pain (2008)

Availability of selective pharmacological tools enabled a great advance of our knowledge of cannabinoid receptor 2 (CB2) role in pathophysiology. In particular CB2 emerged as an interesting target for chronic pain treatment as demonstrated by several studies on inflammatory and neuropathic preclinal pain models. The mechanisms at the basis of CB2-mediated analgesia are still controversial but data are pointing out in two main directions: an effect on inflammatory cells and/or an action on nociceptors and spinal cord relay centers. In this review will be described the second messenger pathways activated by CB2 agonists, the data underpinning the analgesic profile of CB2 selective agonists and the mechanisms invoked to explain their analgesic action. Finally the ongoing clinical trials and the potential issues for the development of a CB2 agonist drug will be examined.
Adrenergic Responses to Stress (2008)

Stress effects on adrenergic responses in rats were examined in adrenal medulla, the primary source of circulating epinephrine (Epi). Irrespective of duration, immobilization (IMMO) increased adrenal corticosterone to the same extent. In contrast, Epi changed little, suggesting that Epi synthesis replenishes adrenal pools and sustains circulating levels for the heightened alertness and physiological changes required of the "flight or fight" response. IMMO also induced the Epi-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT). The rise in its mRNA and protein was preceded by increases in Egr-1 and Sp1 mRNA, protein, and protein-DNA binding complex formation. With repeated and prolonged stress, PNMT protein did not reflect the magnitude of change in mRNA. The latter suggests that post-transcriptional, in addition to transcriptional mechanisms, regulate PNMT responses to stress. To further reveal molecular mechanisms underlying stress-induced changes in adrenergic function, the effects of hypoxia on PNMT promoter-driven gene expression are being examined in adrenal medulla-derived PC12 cells. Hypoxia activates the PNMT promoter to increase PNMT promoter-driven luciferase reporter gene expression and endogenous PNMT in PC12 cells. Induction of both appear mediated via activation of multiple signaling pathways and downstream activation of hypoxia inducible factor and PNMT transcriptional activators, Egr-1 and Sp1. Hypoxia generates both partially and fully processed forms of PNMT mRNA. The former reportedly is translated into a truncated, nonfunctional protein, and the latter into enzymatically active PNMT. Together, findings suggest that stress increases PNMT gene transcriptional activity but post-transcriptional regulatory mechanisms limit the biological end-point of functional PNMT enzyme and, thereby, Epi.
Body weight patterns from 20 to 49 years of age and subsequent risk for diabetes mellitus: the Johns Hopkins Precursors Study. (1999)

In men, overweight at 25 years of age strongly predicts diabetes risk in middle age, largely through its association with overweight at 45 years of age and high average BMI to 49 years of age.
Cloning of the Lipooligosaccharide α-2,3-Sialyltransferase from the Bacterial Pathogens Neisseria meningitidis and Neisseria gonorrhoeae (1996)

The genes encoding the alpha-2,3-sialyltransferases involved in lipooligosaccharide biosynthesis from Neisseria meningitidis and Neisseria gonorrhoeae have been cloned and expressed in Escherichia coli. A high sensitivity enzyme assay using a synthetic fluorescent glycosyltransferase acceptor and capillary electrophoresis was used to screen a genomic library of N. meningitidis MC58 L3 in a "divide and conquer" strategy. The gene, denoted lst, was found on a 2. 0-kilobase fragment of DNA, and its sequence was determined and then used to design probes to amplify and subsequently clone the corresponding lst genes from N. meningitidis 406Y L3, N. meningitidis M982B L7, and N. gonorrhoeae F62. Functional sialyltransferase was produced from the genes derived from both L3 N. meningitidis strains and the N. gonorrhoeae F62. However, the N. meningitidis M982B L7 gene contained a frameshift mutation that renders it inactive. The expression of the lst gene was easily detected using the enzyme assay, and the protein expression could be detected when an immunodetection tag was added to the COOH-terminal end of the protein. Using the synthetic acceptor N-acetyllactosamine-aminophenyl-(6-(5-(fluorescein-carboxamido)-hexan oic acid amide), the alpha-2,3 specificity of the enzyme was confirmed by NMR examination of the reaction product. The enzyme could also use synthetic acceptors with lactose or galactose as the saccharide portion. This study is the first example of the cloning, expression, and examination of alpha-2,3-sialyltransferase activity from a bacterial source.
Rapid blood clearance of immunoglobulin G2a and immunoglobulin G2b in nude mice. (1991)

An extremely rapid blood clearance rate of murine IgG2a antibodies was found in all strains tested of outbred Swiss nu/nu mice, including mice from the major commercial suppliers. The clearance half-life was less than 5 h, in comparison to a 4-5-day half-life in BALB/c mice. Therefore, most of the IgG2a antibody injected i.v. in such mice is cleared before it can reach interstitial fluid, which interferes with immunotherapy and immunodetection experiments. Individual nude mice varied greatly in their IgG2a clearance rates, which hampered investigation of the phenomena. In our experience, approximately three-fourths of nude mice had a rapid or intermediate clearance rate, whereas the remainder had an approximately normal clearance rate. The clearance rate in nude mice was age-dependent, at least in some instances, in that a rapid clearance rate was observed at 2 months of age, whereas the same mice retested at 4 months of age had a normal clearance rate. Rapid clearance could be inhibited by increasing the dose injected: 100 micrograms/mouse resulted in a normal clearance rate, whereas 30 micrograms/mouse was insufficient to inhibit rapid clearance. The clearance rate of IgG2b antibodies was affected similarly to that of IgG2a, whereas the clearance rate of IgG1 and IgG3 was not affected. The Fc region of IgG2a was required in order for rapid clearance to occur. Biodistribution experiments demonstrated that rapid blood clearance was due, at least partially, to binding to the liver and spleen. To determine the genetic basis for rapid IgG2a clearance, approximately 20 inbred and outbred mouse strains were tested. Unexpectedly, nu/+ as well as nu/nu outbred Swiss mice displayed rapid clearance, whereas control +/+ mice did not, so this phenotype appears to be a dominant effect of the nu mutation. BALB/c nu/nu and nu/+ mice did not display rapid clearance, which may be due to expression of the Igh-1a gene, which codes for the IgG2a present in BALB/c mice and in the monoclonal antibodies used in these studies. In conclusion, this clearance effect must be considered in experiments involving murine IgG2a or IgG2b antibodies in outbred Swiss nude mice, except those in which high antibody doses of greater than 0.1 mg/mouse are used. One method of circumventing this problem is to increase the antibody dose injected; a better but more long-range method is to develop strains of outbred nude mice that do have this characteristic.
Backpropagation Applied to Handwritten Zip Code Recognition (1989)

The ability of learning networks to generalize can be greatly enhanced by providing constraints from the task domain. This paper demonstrates how such constraints can be integrated into a backpropagation network through the architecture of the network. This approach has been successfully applied to the recognition of handwritten zip code digits provided by the U.S. Postal Service. A single network learns the entire recognition operation, going from the normalized image of the character to the final classification.
Biomimetic Peptide Surfaces That Regulate Adhesion, Spreading, Cytoskeletal Organization, and Mineralization of the Matrix Deposited by Osteoblast-like Cells (1999)

In an effort to regulate mammalian cell behavior in contact with solid material surfaces, we have functionalized surfaces with different ratios of both the putative cell binding (-Arg-Gly-Asp-) domain and a consensus heparan-binding domain. The peptide sequences -Arg-Gly-Asp- (-RGD-) and -Phe-His-Arg-Arg-Ile-Lys-Ala- (-FHRRIKA-) or mixtures of the two in the ratios of 75:25 (mimetic peptide surface I), 25:75 (mimetic peptide surface II), and 50:50 (mimetic peptide surface III) were immobilized on model surfaces using a heterobifunctional cross-linker to link the peptide(s) to amine-functionalized quartz surfaces. Contact angle measurements, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy were used to confirm the chemistry, thickness of the overlayers, and surface density of immobilized peptides ( approximately 4-6 pmol/cm2). The degree of rat calvaria osteoblast-like cell spreading, focal contact formation, cytoskeletal organization, proliferation, and mineralization of the extracellular matrix (ECM) on model biomaterial surfaces was examined. Mimetic peptide surface II (MPS II) and MPS III supported the highest degree of cell spreading (p < 0.05), following 4 h of incubation, compared to MPS I, homogeneous -RGD-, and homogeneous -FHRRIKA- grafted surfaces. Furthermore, MPS I, MPS II, MPS III, and homogeneous -RGD- surfaces promoted the formation of focal contacts and stress fibers by attached bone cells. The strength of bone cell detachment following 30 min of incubation was significantly higher (p < 0.05) on MPS II surfaces compared to homogeneous -RGD- and -FHRRIKA-. However, the degree of cell proliferation on the peptide surfaces were not significantly different from each other (p > 0.1). Following 24 d in culture, the areas of mineralized ECM formed on MPS II and MPS III surfaces were significantly (p < 0.05) larger than those of other surfaces. These results demonstrate that utilizing peptide sequences incorporating both cell- and heparin-adhesive motifs can enhance the degree of cell surface interactions and influence the long-term formation of mineralized ECM in vitro.
Materials for protein delivery in tissue engineering (1998)

The ability of protein agents to modulate cellular behaviors, such as motility, proliferation, adhesion and function, is the subject of intense research; new therapies involving proteins will likely result. Unfortunately, many proteins have short half-lives and the potential for toxicity after systemic delivery, so traditional routes of administration are not appropriate. Alternate methods for sustained delivery of these agents to the desired cells and tissues in biologically active conformations and concentrations are necessary. Techniques similar to those long used in the controlled delivery of drugs have been used to administer certain growth factors to cells and tissues; although clinical success has been limited to date, studies in animal models suggest the potential for tremendous advances in the near future. This review outlines the basic technology of controlled protein delivery using polymeric materials, and discusses some of the techniques under investigation for the efficient administration of proteins in tissue engineering.
Subdiaphragmatic vagotomy suppresses endotoxin-induced activation of hypothalamic corticotropin-releasing hormone neurons and ACTH secretion (1995)

In order to assess the possibility that endotoxin-induced activation of the hypothalamus-pituitary-adrenal (HPA) axis is mediated by vagal afferents, we studied the effects of transection of the vagal nerves on endotoxin-induced Fos expression in hypothalamic corticotropin-releasing hormone (CRH) neurons and plasma ACTH and corticosterone responses. Groups of rats were subjected to sham surgery, complete subdiaphragmatic vagotomy (SVGX), or selective transection of the hepatic branch (HVGX). Two weeks after surgery, endotoxin or saline was injected i.p. and rats were sacrificed by decapitation two hours later. SVGX blocked or attenuated the ACTH response to 20 and 250 micrograms/kg endotoxin, respectively. HVGX did not suppress the ACTH response to either endotoxin dose. In addition, corticosterone responses were not affected by SVGX or HVGX. The endotoxin-induced Fos expression in CRH neurons was suppressed in SVGX, but not in HVGX animals. These observations lead us to postulate that the CRH and ACTH responses to a low dose of endotoxin are mediated by vagal afferents. The responses to a high dose of endotoxin involve additional neuronal or humoral pathways.
Low cost, portable detection of gold nanoparticle‐labeled microfluidic immunoassay with camera cell phone (2009)

This paper describes the use of camera cell phone to detect the gold nanoparticle-labeled immunoassay results on microfluidic chip. On-chip heterogeneous immunoassay between anti-human IgG and human IgG (hIgG) was performed and the results were amplified by gold nanoparticle-enhanced silver staining to transform the nano-scale probe into detectable silver precipitation film. The detection results obtained by camera phone showed good correlation with the concentration of hIgG. This detection scheme is simple, low cost and easy to use and has significant promise for portable diagnosis and point of care testing on microfluidic platform.
Integrated Printed Circuit Board Device for Cell Lysis and Nucleic Acid Extraction (2012)

Preparation of raw, untreated biological samples remains a major challenge in microfluidics. We present a novel microfluidic device based on the integration of printed circuit boards and an isotachophoresis assay for sample preparation of nucleic acids from biological samples. The device has integrated resistive heaters and temperature sensors as well as a 70 μm × 300 μm × 3.7 cm microfluidic channel connecting two 15 μL reservoirs. We demonstrated this device by extracting pathogenic nucleic acids from 1 μL dispensed volume of whole blood spiked with Plasmodium falciparum. We dispensed whole blood directly onto an on-chip reservoir, and the system's integrated heaters simultaneously lysed and mixed the sample. We used isotachophoresis to extract the nucleic acids into a secondary buffer via isotachophoresis. We analyzed the convective mixing action with micro particle image velocimetry (micro-PIV) and verified the purity and amount of extracted nucleic acids using off-chip quantitative polymerase chain reaction (PCR). We achieved a clinically relevant limit of detection of 500 parasites per microliter. The system has no moving parts, and the process is potentially compatible with a wide range of on-chip hybridization or amplification assays.
SPECTROPHOTOMETRIC IDENTITY OF THE ENERGY TRANSFER CHROMOPHORES IN RENILLA AND AEQUOREA GREEN‐FLUORESCENT PROTEINS (1980)

Abstract— Spectral properties of guanidine‐denaturated and pronase‐digested green‐fluorescent proteins (GFP) from two species of bioluminescent coelenterates have been investigated. Spectrophotometric titrations of Renilla and Aequorea GFP, following denaturation in 6 M guanidine HCl at elevated temperature, revealed identical absorption peaks in acid (383–384 nm) and in alkali (447–448 nm) and a single isosbestic point in the visible region at 405 nm. Both proteins exhibited a spectrophotometric pK. of 8.1 in guanidine ‐HCl. Pronase digestion of the heat‐denaturated GFP's generated a methanol‐soluble blue‐fluorescent peptide with identical fluorescence emission spectra (λ max = 430 nm, uncorrected; φ f1 = 0.003) for both coelenterate species. These data suggest that the large absorption differences between native Renilla and Aequorea GFP molecules result from unique protein environments imported to a common chromophore.