gebhart/patrepeval huggingface dataset:
Cyclodextrins (2008)

beta-cyclodextrin (beta-CD) and other cyclodextrins (CDs) have utility for solubilizing and stabilizing drugs; however, some are nephrotoxic when administered parenterally. A number of workers have attempted to identify, prepare, and evaluate various CD derivatives with superior inclusion complexation and maximal in vivo safety for various biomedical uses. A systematic study led to SBE-beta-CD (Captisol), a polyanionic variably substituted sulfobutyl ether of beta-CD, as a non-nephrotoxic derivative and HP-beta-CD, a modified CD developed by Janssen. SBE-beta-CD and HP-beta-CD have undergone extensive safety studies and are currently used in six products approved by the Food and Drug Administration (four for Captisol and two for HP-beta-CD). They are also in use in numerous clinical and preclinical studies. This article will focus on the issues that led to the development of these two CDs, their safety, characterization, and applications, and especially their ability to improve drug delivery. SBE-beta-CD interacts very well with neutral drugs to facilitate solubility and chemical stability, and because of its polyanionic nature, it interacts particularly well with cationic drugs. Complexes between SBE-beta-CD and HP-beta-CD and various drugs have been shown to rapidly dissociate after parenteral drug administration, to have no tissue-irritating effects after intramuscular dosing, and to result in superior oral bioavailability of poorly water-soluble drugs. The pharmacokinetics, tissue distribution, and cellular effects of some representative CDs, including SBE-beta-CD and HP-beta-CD, are reviewed. The safety profiles of CDs are discussed, with emphasis on the biological effects of some CDs on the gastrointestinal tract, kidney, and reproduction and development and the carcinogenic potential of CDs. In addition, human experience with CD derivatives, specifically SBE-beta-CD and HP-beta-CD, indicates that these two CDs are well tolerated in humans and have no adverse effects on the kidneys or other organs following either oral or intravenous administration.
The cost of health care for children and adults with sickle cell disease (2009)

Although sickle cell disease (SCD) is marked by high utilization of medical resources, the full cost of care for patients with SCD, including care not directly related to SCD, is unknown. The purpose of this study was to estimate the total cost of medical care for a population of children and adults with SCD. We used data from individuals diagnosed with SCD enrolled in the Florida Medicaid program during 2001-2005 to estimate total, SCD-related, and non-SCD-related cost per patient-month based on patient age at the time of health care use. Across the 4,294 patient samples, total health care costs generally rose with age, from $892 to $2,562 per patient-month in the 0-9- and 50-64-year age groups, respectively. Average cost per patient-month was $1,389. Overall, 51.8% of care was directly related to SCD, the majority of which (80.5%) was associated with inpatient hospitalizations. Notably, non-SCD-related costs were substantially higher than those reported for the general US population. These results suggest a discounted (3% discount rate) lifetime cost of care averaging $460,151 per patient with SCD. Interventions designed to prevent SCD complications and avoid hospitalizations may reduce the significant economic burden of the disease.
Chemopreventive Strategies Using NSAIDs and COX-2 Inhibitors (2003)

The chemopreventive efficacy of NSAIDs against colorectal cancer has been established. Also, NSAIDs may decrease the incidence of carcinomas of the esophagus, stomach, breast, lung, prostate, urinary bladder and ovary. The clinical use of these agents is limited to patients with familial adenomatous polyposis (FAP), which may benefit from chemopreventive treatment with sulindac or the selective COX-2 inhibitor celecoxib. The mechanism of chemoprevention by NSDAIDs is still a matter of debate. COX-2 inhibition explains at least part of the observed effects, however, other targets have been proposed. The effect of NSAIDs is incomplete and molecular mechanisms related to resistance need to be studied. Also, more effective chemopreventive regimens are needed; combination therapy appears attractive, potentially increasing efficacy and decreasing toxicity. This review discusses molecular and clinical aspects of chemoprevention of the adenomacarcinoma sequence with NSAIDs or COX-2 inhibitors.
Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells (2001)

The use of Cre/loxP recombination in mammalian cells has expanded rapidly. We describe here that Cre expression in cultured mammalian cells may result in a markedly reduced proliferation and that this effect is dependent on the endonuclease activity of Cre. Chromosome analysis after Cre expression revealed numerous chromosomal aberrations and an increased number of sister chromatid exchanges. Titration experiments in mouse embryo fibroblasts with a ligand-regulatable Cre-ER(T) show that toxicity is dependent on the level of Cre activity. Prolonged, low levels of Cre activity permit recombination without concomitant toxicity. This urges for a careful titration of Cre activity in conditional gene modification in mammalian cells.
Detection of von Willebrand Disorder and Identification of Qualitative von Willebrand Factor Defects (2000)

Two von Willebrand factor (vWF):collagen binding (activity) assay (CBA) kit methods are commercially available. A monoclonal antibody (MAB)-based enzyme-linked immunosorbent assay (ELISA) system reported to correlate with a standard vWF:ristocetin cofactor (RCof) assay is also commercially available. It is marketed as a vWF:Activity assay and is available in 2 assay version formats. In the present study, these 4 vWF-activity options were compared directly with in-house vWF:CBA ELISAs for their ability to detect von Willebrand disease (vWD) and identify qualitative vWF defects. The 2 MAB-based systems detected vWD but could not specifically identify qualitative vWF defects, although the recently modified Mark II kit was more effective for the latter compared with the original Mark I kit. All vWF:CBA methods, including in-house and commercial, also effectively detected vWD but differed in their ability to identify qualitative vWF defects. Effectiveness was highest using the in-house reference vWF:CBA (using a type I/III collagen mix product from equine tendon), the Gradipore vWF:CBA (also uses equine tendon-derived collagen), or the in-house vWF:CBA methods using type III human collagen at a relatively low concentration (1 or 3 micrograms/mL, without covalent linkage). The IMMUNO vWF:CBA seemed to be the least effective among the vWF:CBA methods for detection of qualitative vWF defects.
Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett’s oesophagus (2002)

MCE helps visually identify areas with IM and HGD having specific patterns but not patients with LGD (appear similar to IM). MCE may be a useful clinical tool for the increased detection of patients with IM as well as for surveillance of patients for the detection of HGD. If these preliminary results are validated, MCE would help identify high yield areas, potentially eliminating the need for random biopsies.
Design of Piezoresistive MEMS-Based Accelerometer for Integration with Wireless Sensing Unit for Structural Monitoring (2003)

The use of advanced embedded system technologies such as microelectromechanical system (MEMS) sensors and wireless communications hold great promise for measuring the response of civil structures to ambient and external disturbances. In this paper, the design of a high-performance, planar piezoresistive MEMS accelerometer is discussed in detail. The piezoresistive accelerometer possesses superior performance characteristics including low noise densities when measuring local structural responses characterized by high-frequency content. A low-cost wireless sensing unit, designed for automated structural monitoring, is utilized to record and wirelessly transmit measurements obtained by the piezoresistive accelerometer. To validate the performance of the wireless monitoring system including the interfaced piezoresistive accelerometer, a five degrees-of-freedom laboratory test structure is utilized.
Sketching and Composing Widgets for 3D Manipulation (2008)

Abstract We present an interface for 3D object manipulation in which standard transformation tools are replaced with transient 3D widgets invoked by sketching context‐dependent strokes. The widgets are automatically aligned to axes and planes determined by the user's stroke. Sketched pivot‐points further expand the interaction vocabulary. Using gestural commands, these basic elements can be assembled into dynamic, user‐constructed 3D transformation systems. We supplement precise widget interaction with techniques for coarse object positioning and snapping. Our approach, which is implemented within a broader sketch‐based modeling system, also integrates an underlying “widget history” to enable the fluid transfer of widgets between objects. An evaluation indicates that users familiar with 3D manipulation concepts can be taught how to efficiently use our system in under an hour.
Iron Homeostasis during Cystic Fibrosis Pulmonary Exacerbation (2012)

Hypoferremia is a salient characteristic of CFPE that improves with waning inflammation. Despite antibiotic treatment, many patients remain hypoferremic and anemic because of ineffective erythropoiesis.
Substitution of Asparagine for Arginine 347 of Recombinant Factor Xa Markedly Reduces Factor Va Binding (2000)

Herein we describe a recombinant factor X (fX) with a single substitution at position 347 (fXR347N). Activated fXR347N had a reduced affinity for factor Va (fVa), although the catalytic impact of fVa binding remained intact. The mutation was selective as demonstrated by normal activation and inhibition, except in the presence of subsaturating heparin where the rate of inhibition by antithrombin III (ATIII) was 15% of normal. The reactivity of fXaR347N toward prothrombin was equivalent to wild-type fXa (fXaWT) in the absence of fVa and phospholipid. Addition (without phospholipid) of fVa dramatically increased the catalytic efficiency of fXaWT toward prothrombin but had a negligible effect on fXaR347N. On addition of phosphatidylcholine:phosphatidylserine (PC:PS, 3:1) vesicles, fXaR347Ndisplayed an increased catalytic activity in response to fVa, but the apparent affinity for fVa on the phospholipid surface was 5-20-fold lower than that of fXaWT. On an activated platelet surface, however, fXaWT and fXaR347N activated prothrombin similarly. In a competitive binding assay that measures the displacement of radiolabeled fXa from fVa on a phospholipid surface, fXaR347N was approximately 10-fold less effective than fXaWT. Substitution of fXa at position 347 selectively attenuates the interaction between fXa and fVa without affecting its catalytic activity.
Myelodysplastic syndromes: A practical approach to diagnosis and treatment (2010)

The myelodysplastic syndromes (MDS) are clonal bone marrow disorders that lead to underproduction of normal blood cells. The consequent cytopenias result in infections and bleeding complications. MDS transform to acute myeloid leukemia in one-third of patients. The number of diagnoses has exploded in the past decade as a result of increased recognition and understanding of the disease and the aging of the population. New therapies can extend life. MDS are now considered the most common form of leukemia, and in some cases deserve immediate intervention. This review describes common presentations of MDS, optimal diagnostic approaches, and therapies for lower-and higher-risk disease.
Protective effects of an anti‐melanocortin‐4 receptor scFv derivative in lipopolysaccharide‐induced cachexia in rats (2012)

The pharmacological profile of scFv 1E8a suggests its potential value in the treatment of cachexia or anorexia.
The actions of bismuth in the treatment of Helicobacter pylori infection (1997)

Bismuth salts have been used in medicine for over three centuries, particularly in the treatment of dyspepsia. Commonly used agents include colloidal bismuth subcitrate (CBS), bismuth subsalicylate (BSS) and the newer ranitidine bismuth citrate (RBC). These are safe drugs which exert local effects on the gastroduodenal mucosa. Gastric mucosal levels of bismuth exceed the concentrations required to kill Helicobacter pylori in vitro. The mechanisms of actions of bismuth on gastrointestinal pathogens including H. pylori are complex and include inhibition of protein and cell wall synthesis, membrane function and ATP synthesis. Adherence of H. pylori to surface epithelial cells is also impaired. Bismuth monotherapy is effective in vivo to suppress H. pylori but cure rates are low. CBS, BSS and RBC have synergistic activity with one or two antibiotics and are effective in eradicating H. pylori. CBS and RBC also exert other effects on the mucosa including cytoprotective and ulcer healing properties. In addition, RBC is effective in inhibiting gastric acid secretion.
Optically induced coherent transport far aboveTcin underdopedYBa2Cu3O6+δ (2014)

We report on a photoinduced transient state of ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{2}$O${}_{6+\ensuremath{\delta}}$ in which transport perpendicular to the Cu-O planes becomes highly coherent. This effect is achieved by excitation with mid-infrared optical pulses, tuned to the resonant frequency of apical oxygen vibrations, which modulate both lattice and electronic properties. Below the superconducting transition temperature ${T}_{c}$, the equilibrium signatures of superconducting interlayer coupling are enhanced. Most strikingly, the optical excitation induces a new reflectivity edge at higher frequency than the equilibrium Josephson plasma resonance, with a concomitant enhancement of the low-frequency imaginary conductivity ${\ensuremath{\sigma}}_{2}(\ensuremath{\omega})$. Above ${T}_{c}$, the incoherent equilibrium conductivity becomes highly coherent, with the appearance of a reflectivity edge and a positive ${\ensuremath{\sigma}}_{2}(\ensuremath{\omega})$ that increases with decreasing frequency. These features are observed up to room temperature in ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{2}$O${}_{6.45}$ and ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{2}$O${}_{6.5.}$ The data above ${T}_{c}$ can be fitted by hypothesizing that the light establishes a transient superconducting state over only a fraction of the solid, with a lifetime of a few picoseconds. Non-superconducting transport could also explain these observations, although one would have to assume transient carrier mobilities near 10${}^{4}$ cm${}^{2}$/V sec at 100 K, with a density of charge carriers similar to the below-${T}_{c}$ superfluid density. Our results are indicative of highly unconventional nonequilibrium physics and open new prospects for optical control of complex solids.
Selective recovery of foreign gene transcripts as virus-like particles in TMV-infected transgenic tobaccos (1988)

A short origin-of-assembly sequence (OAS) located in the 30kDa movement protein gene, about 1.0kb from the 3'-end of the common strain of tobacco mosaic virus (TMV) RNA, nucleates encapsidation of the 6395-nucleotide-long genome by TMV coat protein in vitro, and presumably also in vivo. Single-stranded RNAs containing a foreign reporter gene sequence and the TMV OAS at their 5' - and 3' -ends, respectively, can be synthesized in vitro from recombinant SP6-transcription plasmids and will assemble spontaneously in vitro to form TMV-like 'pseudovirus' particles. In this paper, we show that foreign gene transcripts derived from the nuclear DNA of plants transformed by Agrobacterium tumefaciens, and which contain the TMV OAS, can be assembled into stable 'pseudovirus' particles in vivo during a systemic infection by TMV (helper). This is the first report of structural complementation between a heritable function bestowed on a transgenic plant and an infecting virus. As a route to protect, accumulate and recover a specific mRNA in vivo, in transgenic plant cells, this novel approach may find wider applications in developmental plant molecular biology.
Correction of Hypertriglyceridemia and Impaired Fat Tolerance in Lipoprotein Lipase–Deficient Mice by Adenovirus-Mediated Expression of Human Lipoprotein Lipase (1997)

Humans homozygous or heterozygous for mutations in the lipoprotein lipase (LPL) gene demonstrate significant disturbances in plasma lipoproteins, including raised triglyceride (TG) and reduced HDL cholesterol levels. In this study we explored the feasibility of adenovirus-mediated gene replacement therapy for LPL deficiency. A total of 5 x 10(9) plaque-forming units (pfu) of an E1/E3-deleted adenovirus expressing either human LPL (Ad-LPL) or the bacterial beta-galactosidase gene (Ad-LacZ) as a control were administered to mice heterozygous for targeted disruption in the LPL gene (n = 57). Peak expression of total postheparin plasma LPL activity was observed at day 7 in Ad-LPL mice versus Ad-LacZ controls (834 +/- 133 vs 313 +/- 89 mU/mL, P < .01), and correlated with human-specific LPL activity (522 +/- 219 mU/mL) and mass (9214 +/- 782 ng/mL), a change that was significant to 14 and 42 days, respectively. At day 7, plasma TGs were significantly reduced relative to Ad-LacZ mice (0.17 +/- 0.07 vs 1.90 +/- 0.89 mmol/L, P < .01) but returned to endogenous levels by day 42. Ectopic liver expression of human LPL was confirmed by in situ hybridization analysis and from raised LPL activity and mass in liver homogenates. Analysis of plasma lipoprotein composition revealed a marked decrease in VLDL-derived TGs. Severely impaired oral and intravenous fat-load tolerance in LPL-deficient mice was subsequently corrected after Ad-LPL administration and closely paralleled that observed in wild-type mice. These findings suggest that liver-targeted adenovirus-mediated LPL gene transfer offers an effective means for transient correction of altered lipoprotein metabolism and impaired fat tolerance due to LPL deficiency.
Expression of nerve growth factor mRNA and its translation products in the anagen hair follicle (2000)

The cellular localization of NGF mRNA and its translation products have been identified in ovine hair follicles. NGF mRNA was detected in the proliferating cells of the follicle bulb and differentiating cells of the suprabulbar region, but was absent from the outer root sheath. Western analysis revealed the presence of a 73 kDa NGF prohormone in extracts of ovine flank skin, but the mature 13 kDa NGF was absent. Immunohistochemical analysis with antibodies specific to mouse NGF and a pro-NGF specific domain localized the NGF prohormone to outer root sheath cells in the upper bulb region of the follicle, adjacent to the zone of keratinization. Antibody binding was also associated with the luminal epithelium of the apocrine sweat gland and the pilary canal of the follicle at its junction with the epidermis. These observations, together with the reported presence of high- and low-affinity NGF receptors in the follicle, implicate the NGF prohormone-responsive neuronal system in the regulation of hair growth.
Adsorption Behavior of Linear and Cyclic Genetically Engineered Platinum Binding Peptides (2007)

Recently, phage and cell-surface display libraries have been adapted for genetically selecting short peptides for a variety of inorganic materials. Despite the enormous number of inorganic-binding peptides reported and their bionanotechnological utility as synthesizers and molecular linkers, there is still a limited understanding of molecular mechanisms of peptide recognition of and binding to solid materials. As part of our goal of genetically designing these peptides, understanding the binding kinetics and thermodynamics, and using the peptides as molecular erectors, in this report we discuss molecular structural constraints imposed upon the quantitative binding characteristics of peptides with an affinity for inorganics. Specifically, we use a high-affinity seven amino acid Pt-binding sequence, PTSTGQA, as we reported in earlier studies and build two constructs: one is a Cys-Cys constrained "loop" sequence (CPTSTGQAC) that mimics the domain used in the pIII tail sequence of the phage library construction, and the second is the linear form, a septapeptide, without the loop. Both sequences were analyzed for their adsorption behavior on Pt thin films by surface plasmon resonance (SPR) spectroscopy and for their conformational properties by circular dichroism (CD). We find that the cyclic peptide of the integral Pt-binding sequence possesses single or 1:1 Langmuir adsorption behavior and displays equilibrium and adsorption rate constants that are significantly larger than those obtained for the linear form. Conversely, the linear form exhibits biexponential Langmuir isotherm behavior with slower and weaker binding. Furthermore, the structure of the cyclic version was found to adopt a random coil molecular conformation, whereas the linear version adopts a polyproline type II conformation in equilibrium with the random coil. The 2,2,2-trifluoroethanol titration experiments indicate that TFE has a different effect on the secondary structures of the linear and cyclic versions of the Pt binding sequence. We conclude that the presence of the Cys-Cys restraint affects both the conformation and binding behavior of the integral Pt-binding septapeptide sequence and that the presence or absence of constraints could be used to tune the adsorption and structural features of inorganic binding peptide sequences.
The Plenacoustic Function and Its Sampling (2006)

The spatialization of the sound field in a room is studied, in particular the evolution of room impulse responses as a function of their spatial positions. It was observed that the multidimensional spectrum of the solution of the wave equation has an almost bandlimited character. Therefore, sampling and interpolation can easily be applied using signals on an array. The decay of the spectrum is studied on both temporal and spatial frequency axes. The influence of the decay on the performance of the interpolation is analyzed. Based on the support of the spectrum, the number and the spacing between the microphones is determined for the reconstruction of the sound pressure field up to a certain temporal frequency and with a certain reconstruction quality. The optimal sampling pattern for the microphone positions is given for the linear, planar and three-dimensional case. Existing techniques usually make use of room models to recreate the sound field present at some point in the space. The presented technique simply starts from the measurements of the sound pressure field in a finite number of positions and with this information the sound pressure field can be recreated at any spatial position. Finally, simulations and experimental results are presented and compared with the theory
Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224‐015, an inhibitor of the interleukin‐1β converting enzyme (1995)

1. The aim of this study was to determine whether a synthetic inhibitor of the interleukin-1 beta converting enzyme (ICE) displays oral activity in models of inflammation. 2. To this end, the ICE inhibitor, SDZ 224-015, was examined in rat paw oedema, pyrexia and nociception tests. 3. SDZ 224-015 (0.3-300 micrograms kg-1) potently reduced carrageenin-induced paw oedema, with an oral ED50 of approximately 25 micrograms kg-1. This effect was independent of endogenous glucocorticoid, as shown by retention of activity upon adrenalectomy. 4. Pyrexia induced by lipopolysaccharide (0.1 mg kg-1 s.c.) or by interleukin-1 beta (100 ng i.v.) was also reduced, over a similar dose-range to oedema (oral ED50s 11 micrograms kg-1 and 4 micrograms kg-1 respectively). 5. SDZ 224-015 (0.2-5 mg kg-1, p.o.) displayed analgesic activity in the Randall-Selitto yeast-inflamed paw pressure test, significant at a dose of 1 mg kg-1, p.o. 6. Thus, SDZ 224-015 has potent oral activity in several acute models for inflammation, suggesting that ICE inhibitors may constitute a novel type of anti-inflammatory agent.