gebhart/patrepeval huggingface dataset:
Biochemistry and Biophysics of HIV-1 gp41 - Membrane Interactions and Implications for HIV-1 Envelope Protein Mediated Viral-Cell Fusion and Fusion Inhibitor Design (2011)

Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.
Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium. (1992)

Parathyroid hormone (PTH), a major regulator of mineral ion metabolism, and PTH-related peptide (PTHrP), which causes hypercalcemia in some cancer patients, stimulate multiple signals (cAMP, inositol phosphates, and calcium) probably by activating common receptors in bone and kidney. Using expression cloning, we have isolated a cDNA clone encoding rat bone PTH/PTHrP receptor from rat osteosarcoma (ROS 17/2.8) cells. The rat bone PTH/PTHrP receptor is 78% identical to the opossum kidney receptor; this identity indicates striking conservation of this receptor across distant mammalian species. Additionally, the rat bone PTH/PTHrP receptor has significant homology to the secretin and calcitonin receptors but not to any other G protein-linked receptor. When expressed in COS cells, a single cDNA clone, expressing either rat bone or opossum kidney PTH/PTHrP receptor, mediates PTH and PTHrP stimulation of both adenylate cyclase and phospholipase C. These properties could explain the diversity of PTH action without the need to postulate other receptor subtypes.
C‐peptide in the natural history of type 1 diabetes (2009)

Type 1 diabetes is diagnosed when the patient's endogenous insulin secretion decreases to a level which results in hyperglycemia. After diagnosis, insulin secretion continues to decline. As a reference for clinical trials trying to preserve endogenous beta-cell function in patients with recently diagnosed type 1 diabetes, in this short review I attempt to summarize the natural history of endogenous beta-cell function after the diagnosis of type 1 diabetes.
Morphologic, immunologic, and cytogenetic classification of acute myeloid leukemia and myelodysplastic syndrome in childhood: a report from the Childrens Cancer Group. (1996)

The purposes of this report are to reaffirm concordance difficulties with the acute myeloid leukemia (AML) French-American-British (FAB) classification, to present the frequency of previously delineated AML syndromes in pediatric patients and to describe additional characteristic AML profiles utilizing composite morphologic, cytogenetic and immunophenotypic data. Profiles of 124 children with acute myeloid leukemia (AML) and 13 children with myelodysplastic syndrome entered on the Childrens Cancer Group (CCG) pilot study CCG-2861 were examined. Concordance between institutions and reviewers for FAB designation was 65%. Discordance was found principally between M1 and M2, M2 and M4, and M4 and M5. In 49% of marrow specimens, leukemic blasts expressed at least one T lineage-related antigen; 24% expressed the B lineage-related antigen CD19. CDw14 correlated with FAB M4 or M5 morphology and was the only surface antigen associated with a specific FAB subtype. Normal karyotypes were found for 15% of the 75 children with satisfactory karyotype preparations. Recurring aberrations, found in 76% of children, included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), rearrangements of band 11q23, t(6;9) (p23;q34), trisomy 8 and monosomy 7. Results from this pilot study and from the current CCG randomized trial correlating morphology, immunophenotyping and cytogenetics, will help to classify AML into unique subgroups with differing clinical consequences or therapy requirements.
Sequential administration of augmentation strategies in treatment-resistant obsessive-compulsive disorder (1996)

Given that an important proportion of patients with obsessive-compulsive disorder (OCD) fail to respond adequately to serotonin (5-HT) reuptake inhibitors (SRI), augmentation strategies aimed at enhancing further 5-HT transmission by different mechanisms were attempted sequentially in 13 SRI-resistant patients. Addition of the 5-HT1A l beta-adrenergic antagonist pindolol did not alter OCD symptomatology but produced a rapid improvement of depressive symptoms. The 5-HT1A agonist buspirone as well as 5-hydroxytryptophan, the immediate precursor of 5-HT, added to the SRI-pindolol regimen, were not effective in attenuating the intensity of OCD. Tryptophan, added to the SRI-pindolol regimen, produced a significant improvement after 4 weeks, with further amelioration after 6 weeks (36% decrease of the Yale-Brown Obsessive Compulsive Score), which was maintained with treatment prolongation.
Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression. (2001)

Although growth factors and extracellular matrix (ECM) are recognized as important contributors to breast epithelial growth, morphogenesis, hormone responsiveness, and neoplastic progression, the influence of functional interactions between breast stromal and epithelial cells on these processes has not been defined. Using a novel three-dimensional cell-cell interaction model, we have compared the abilities of different mesenchymal cell types, including breast fibroblasts derived from reduction mammoplasty and tumor tissues, and human umbilical endothelial cells (HUVECs) to induce three-dimensional morphogenesis and growth of normal MCF10A and preneoplastic MCF10AT1-EIII8 (referred as EIII8) human breast epithelial cells. Our data demonstrate a requirement for organspecific fibroblasts in the induction of epithelial morphogenesis. Whereas inclusion of normal reduction mammoplasty fibroblasts inhibit or retard morphological conversion and growth of MCF10A and EIII8 cells, respectively, tumor-derived breast fibroblasts evoke ductal-alveolar morphogenesis of both MCF10A and EIII8 cells. The growth and morphogenesis inhibitory effects of normal fibroblasts remain even in the presence of estrogen because they are able to suppress the estrogen-induced growth of EIII8 cells, whereas tumor fibroblasts support and maintain estrogen responsiveness of EIII8 cells. The inductive morphogenic effects of tumor fibroblasts on EIII8 cells is further augmented by the inclusion of HUVECs because these cocultures undergo a dramatic increase in proliferation and branching ductal-alveolar morphogenesis that is accompanied by an increase in invasion, degradation of coincident ECM, and expression of MMP-9. Therefore, tumor fibroblasts confer morphogenic and mitogenic induction of epithelial cells, and further enhancement of growth and progression requires active angiogenesis. These data illustrate the importance of structural and functional interactions between breast stromal and epithelial cells in the regulation of breast epithelial growth and progression.
Quantification of two different types of apolipoprotein A-I containing lipoprotein particles in plasma by enzyme-linked differential-antibody immunosorbent assay. (1987)

We describe a method for measuring apolipoprotein A-I (ApoA-I) associated and unassociated with apolipoprotein A-II (ApoA-II) in plasma. To directly determine associated ApoA-I, we coated microtiter plates with antibody to ApoA-II, blocked the nonspecific binding sites, and incubated the plate with plasma, immobilizing the lipoprotein particles containing both ApoA-II and ApoA-I. The unbound constituents of plasma were washed away, peroxidase-labeled antibody to ApoA-I was added, the plate rewashed, peroxidase substrate added, and the resulting color measured. ApoA-I unassociated with ApoA-II was evaluated by subtracting the concentration of associated ApoA-I from the total ApoA-I concentration. The method is specific, rapid, and precise. Within- and between-assay CVs were 5.6 and 9.8%, respectively. Analytical recovery of ApoA-I was 94%. The average normolipidemic concentration of ApoA-I associated with ApoA-II in 50 women was 790 mg/L; in 50 men, it was 788 mg/L. The corresponding values for unassociated ApoA-I were 644, 577 mg/L. Both lipoprotein forms of ApoA-I were detected in all major density classes, but were most abundant in high-density lipoproteins. The technique is applicable to measurement of any two apolipoproteins that occur in both associated and unassociated forms in plasma.
Therapeutic Potential of Mesenchymal Stem Cells in Regenerative Medicine (2013)

Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expanded in vitro. Moreover, their ability to modulate immune responses makes them an even more attractive candidate for regenerative medicine as allogeneic transplant of these cells is feasible without a substantial risk of immune rejection. MSCs secrete various immunomodulatory molecules which provide a regenerative microenvironment for a variety of injured tissues or organ to limit the damage and to increase self-regulated tissue regeneration. Autologous/allogeneic MSCs delivered via the bloodstream augment the titers of MSCs that are drawn to sites of tissue injury and can accelerate the tissue repair process. MSCs are currently being tested for their potential use in cell and gene therapy for a number of human debilitating diseases and genetic disorders. This paper summarizes the current clinical and nonclinical data for the use of MSCs in tissue repair and potential therapeutic role in various diseases.
Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men. (2009)

Enclomiphene (Androxal), in development by Repros Therapeutics Inc, is a non-steroidal estrogen receptor antagonist that promotes gonadotropin-dependent testosterone secretion by the testes. Enclomiphene constitutes the trans-stereoisomer of clomiphene citrate, a drug that has been widely prescribed for several decades for the treatment of female ovulatory dysfunction. Because of the antagonistic effects of enclomiphene, the drug has the potential to increase serum testosterone levels in men with secondary hypogonadism by restoring physiological endogenous testosterone secretion while maintaining testicular volume and, potentially, spermatogenesis. In clinical trials conducted to date, enclomiphene demonstrated significant efficacy in the physiological restoration of testosterone levels in males with secondary hypogonadism. The compound also exhibited an unanticipated favorable effect on fasting plasma glucose; this result has been accompanied by rapidly accumulating evidence from other researchers for a bidirectional relationship between low serum testosterone and obesity/metabolic syndrome (syndrome X) in men. Short-term clinical safety data for enclomiphene have been satisfactory and equivalent to safety data for testosterone gels and placebo. Enclomiphene demonstrates promise in the management of secondary hypogonadism associated with obesity, metabolic syndrome and, possibly, infertility, and should undergo placebo-controlled, randomized clinical trials for these indications.
Spatial frequency response of color image sensors: Bayer color filters and Foveon X3 (2004)

We compared the Spatial Frequency Response (SFR) of image sensors that use the Bayer color filter pattern and Foveon X3 technology for color image capture. Sensors for both consumer and professional cameras were tested. The results show that the SFR for Foveon X3 sensors is up to 2.4x better. In addition to the standard SFR method, we also applied the SFR method using a red/blue edge. In this case, the X3 SFR was 3-5x higher than that for Bayer filter pattern devices.
Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B) (1996)

Sanfilippo B syndrome is caused by a deficiency of alpha-N-acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N-acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.
Leptin Modulates both Resorption and Formation while Preventing Disuse-Induced Bone Loss in Tail-Suspended Female Rats (2005)

In vitro studies have demonstrated leptin-positive effects on the osteoblast lineage and negative effects on osteoclastogenesis. Therefore, we tested the hypothesis that leptin may prevent tail-suspension-induced bone loss characterized by an uncoupling pattern of bone remodeling, through both mechanisms. Female rats were randomly tail-suspended or not and treated either with ip administration of leptin or vehicle for 3, 7, and 14 d. As measured by dual energy x-ray absorptiometry, tail-suspension induced a progressive decrease in tibia-metaphysis bone mineral density, which was prevented by leptin. Histomorphometry showed that this was related to the prevention of the transient increase in osteoclast number observed with suspension at d 7. These effects could be mediated by the receptor activator of nuclear factor kappaB-ligand (RANKL)/osteoprotegerin (OPG) pathway since we observed using direct RT-PCR, a suspension-induced increase in RANKL gene expression in proximal tibia at d 3, which was counterbalanced by leptin administration with a similar 3-fold increase in OPG expression and a RANKL to OPG ratio close to nonsuspended conditions. In addition, leptin prevented the decrease in bone formation rate induced by tail-suspension at d 14. The latter could be related to the role of leptin in mediating the reciprocal differentiation between adipocytes and osteoblasts, because leptin concurrently blunted the disuse-induced increase in bone marrow adipogenesis. In summary, these data suggest that peripheral administration of leptin could prevent disuse-induced bone loss through, first, a major inhibitory effect on bone resorption and, second, a delayed effect preventing the decrease in bone formation.
The Complete Gene Sequence of Titin, Expression of an Unusual ≈700-kDa Titin Isoform, and Its Interaction With Obscurin Identify a Novel Z-Line to I-Band Linking System (2001)

Titin is a giant vertebrate striated muscle protein with critical importance for myofibril elasticity and structural integrity. We show here that the complete sequence of the human titin gene contains 363 exons, which together code for 38 138 residues (4200 kDa). In its central I-band region, 47 novel PEVK exons were found, which contribute to titin's extensible spring properties. Additionally, 3 unique I-band titin exons were identified (named novex-1 to -3). Novex-3 functions as an alternative titin C-terminus. The novex-3 titin isoform is approximately 700 kDa in size and spans from Z1-Z2 (titin's N-terminus) to novex-3 (C-terminal exon). Novex-3 titin specifically interacts with obscurin, a 721-kDa myofibrillar protein composed of 57 Ig/FN3 domains, followed by one IQ, SH3, DH, and a PH domain at its C-terminus. The obscurin domains Ig48/Ig49 bind to novex-3 titin and target to the Z-line region when expressed as a GFP fusion protein in live cardiac myocytes. Immunoelectron microscopy detected the C-terminal Ig48/Ig49 obscurin epitope near the Z-line edge. The distance from the Z-line varied with sarcomere length, suggesting that the novex-3 titin/obscurin complex forms an elastic Z-disc to I-band linking system. This system could link together calcium-dependent, SH3-, and GTPase-regulated signaling pathways in close proximity to the Z-disc, a structure increasingly implicated in the restructuring of sarcomeres during cardiomyopathies.
Sketching images eyes-free (2002)

In this paper we describe one method of transforming a mouse-based graphical user interface into a navigable, grid-based auditory interface. We also report the results of an experiment that tested the effectiveness of a drawing tool for the blind called IC2D that uses this interaction style. The experiment included eight visually impaired participants and eight blindfolded sighted participants. The results show that auditory interpretation of graphics is an effective interface technique for visually impaired users. Further, the experiment demonstrates that visually impaired users can develop meaningful drawings when given adequate technological support.
Brønsted Acid−Base Ionic Liquids as Proton-Conducting Nonaqueous Electrolytes (2003)

A new series of Brønsted acid−base ionic liquids were derived from the controlled combination of a monoprotonic acid with an organic base under solvent-free conditions. Appropriate amounts of solid bis(trifluoromethanesulfonyl)amide (HTFSI) and solid imidazole (Im) were mixed at various molar ratios to have compositions varying from an equimolar salt to HTFSI- or Im-rich conditions. The mixture at equivalent molar ratio formed a protic neutral salt with a melting point of 73 °C, which was thermally stable at temperatures even above 300 °C. The melting points of other compositions were lower than those of the equimolar salt and Im or HTFSI, giving eutectics between the equimolar salt and HTFSI or Im. Some of the compositions with certain molar ratios of Im and HTFSI were liquid at room temperature. For Im excess compositions, the conductivity was found to increase with increasing Im mole fraction, and the 1H NMR chemical shift of the proton attached to the nitrogen atom of Im was shifted to a lower magnetic field. On the contrary, the conductivity decreased with increasing HTFSI mole fraction, and the 1H NMR chemical shift of the proton attached to the TFSI imide anion also shifted to a higher magnetic field. Self-diffusion coefficients, measured by pulsed-gradient spin−echo NMR (PGSE-NMR) methods in Im- or HTFSI-rich compositions, indicated that fast proton exchange reactions between the protonated Im cation and Im take place in excess Im. The proton conduction follows a combination of Grotthuss- and vehicle-type mechanisms. Direct current polarization measurements were used for the confirmation of proton conduction in Im-rich compositions. Furthermore, reduction of molecular oxygen could be observed at the interface between a Pt electrode and these ionic liquids. This introduces the Brønsted acid−base ionic liquid system as a new candidate for proton conductor such as a fuel cell electrolyte to operate under anhydrous conditions and at elevated temperature.
A new sensor for monitoring chest wall motion during high-frequency oscillatory ventilation (1999)

The recently developed technique of fibre optic respiratory plethysmography (FORP) has been modified to monitor the rapid, small amplitude movements of the chest wall during high-frequency oscillatory ventilation (HFOV). The FORP sensor is an expandable belt encircling the chest, in which is housed a fibre optic loop that alters its radius of curvature as a function of chest perimeter. These curvature changes cause variations in macrobending losses of light transmitted through the fibre, which are proportional to the chest perimeter. Dynamic measurement of transmitted light intensity can hence be used to monitor chest wall motion (CWM). For application to HFOV, the design of the FORP belt was altered to increase sensitivity and the materials were chosen to maximise macrobending effects induced by the CWM. FORP was tested in four piglets ventilated with HFOV, both in the normal and surfactant-deficient lung. Measurement of CWM was possible over the full range of tidal volumes and ventilation frequencies used during HFOV. In all cases, the measured frequency of the CWM fell within 3% of the applied ventilation frequency. In addition, the technique was sufficiently sensitive to detect changes in the amplitude of CWM in response to changes in applied tidal volume. It is anticipated that application of this new non-invasive measurement device will lead to an increased understanding of the dynamics of chest and abdominal wall motion during HFOV.
Terfenadine, a Nonsedating Antihistamine (1985)

Terfenadine is an antihistamine recently approved for use in the U.S. Terfenadine possesses a unique chemical structure when compared with other antihistamines. It is a selective inhibitor of H1-receptors with little or no anticholinergic, antiserotoninergic, or antiadrenergic effects. Comparative studies have shown that terfenadine is as effective as other antihistamines in the treatment of allergic rhinitis and other hypersensitivity conditions. This drug produces a minimal amount of central nervous system (CNS) depression, which is documented by studies demonstrating that terfenadine and its metabolites do not readily pass into the CNS and have little affinity for central H1-receptors. The lack of CNS depression and anticholinergic effects, and the long duration of action that allows twice-a-day dosing make terfenadine an attractive alternative to other antihistamines.