gebhart/patrepeval huggingface dataset:
A novel anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis and tumor growth (2003)

The goal of our study was to raise monoclonal antibodies (mAbs) against endothelial cell-surface proteins specific for tumor vasculature. Here, we describe the generation and intensive characterization of mAb AA98, including its functional properties and its antigen identification. In our study, an enhanced mAb AA98 immunoreactivity was observed on stimulated human umbilical vein endothelial cells (HUVECs). In addition, mAb AA98 showed remarkably restricted immunoreactivity against intratumoral neovasculature compared with blood vessels of normal tissues. We identified the AA98 antigen as human CD146, an adhesion molecule belonging to the immunoglobulin superfamily. Data from in vitro experiments imply structural and signaling functions for endothelial CD146; however, the role of CD146 in vivo is largely unknown. Here, we show that mAb AA98 displays antiangiogenic properties in vitro and in vivo. Proliferation and migration of HUVECs were inhibited by mAb AA98 as was angiogenesis in chicken chorioallantoic membrane (CAM) assays and tumor growth in 3 xenografted human tumor models in mice. Our data provide new insights into the function of CD146 on endothelial cells, validate CD146 as a novel target for antiangiogenic agents, and demonstrate that mAb AA98 has potential as a diagnostic and therapeutic agent in vascular and cancer biology.
Structure-Guided Design of Selective Inhibitors of Neuronal Nitric Oxide Synthase (2013)

Nitric oxide synthases (NOSs) comprise three closely related isoforms that catalyze the oxidation of L-arginine to L-citrulline and the important second messenger nitric oxide (NO). Pharmacological selective inhibition of neuronal NOS (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. Here, we present a structure-guided, selective nNOS inhibitor design based on the crystal structure of lead compound 1 in nNOS. The best inhibitor, 7, exhibited low nanomolar inhibitory potency and good isoform selectivities (nNOS over eNOS and iNOS are 472-fold and 239-fold, respectively). Consistent with the good selectivity, 7 binds to nNOS and eNOS with different binding modes. The distinctly different binding modes of 7, driven by the critical residue Asp597 in nNOS, offers compelling insight to explain its isozyme selectivity, which should guide future drug design programs.
Methods and Mechanisms for Cross-Electrophile Coupling of Csp2 Halides with Alkyl Electrophiles (2015)

Cross-electrophile coupling, the cross-coupling of two different electrophiles, avoids the need for preformed carbon nucleophiles, but development of general methods has lagged behind cross-coupling and C-H functionalization. A central reason for this slow development is the challenge of selectively coupling two substrates that are alike in reactivity. This Account describes the discovery of generally cross-selective reactions of aryl halides and acyl halides with alkyl halides, the mechanistic studies that illuminated the underlying principles of these reactions, and the use of these fundamental principles in the rational design of new cross-electrophile coupling reactions. Although the coupling of two different electrophiles under reducing conditions often leads primarily to symmetric dimers, the subtle differences in reactivity of aryl halides and alkyl halides with nickel catalysts allowed for generally cross-selective coupling reactions. These conditions could also be extended to the coupling of acyl halides with alkyl halides. These reactions are exceptionally functional group tolerant and can be assembled on the benchtop. A combination of stoichiometric and catalytic studies on the mechanism of these reactions revealed an unusual radical-chain mechanism and suggests that selectivity arises from (1) the preference of nickel(0) for oxidative addition to aryl halides and acyl halides over alkyl halides and (2) the greater propensity of alkyl halides to form free radicals. Bipyridine-ligated arylnickel intermediates react with alkyl radicals to efficiently form, after reductive elimination, new C-C bonds. Finally, the resulting nickel(I) species is proposed to regenerate an alkyl radical to carry the chain. Examples of new reactions designed using these principles include carbonylative coupling of aryl halides with alkyl halides to form ketones, arylation of epoxides to form β-aryl alcohols, and coupling of benzyl sulfonate esters with aryl halides to form diarylmethanes. Arylnickel(II) intermediates can insert carbon monoxide to form acylnickel(II) intermediates that react with alkyl halides to form ketones, demonstrating the connection between the mechanisms of reactions of aryl halides and acid chlorides with alkyl halides. The low reactivity of epoxides with nickel can be overcome by the use of either titanium or iodide cocatalysis to facilitate radical generation and this can also be extended to enantioselective arylation of meso-epoxides. The high reactivity of benzyl bromide with nickel, which leads to the formation of bibenzyl in attempted reactions with bromobenzene, can be overcome by using a benzyl mesylate along with cobalt phthalocyanine cocatalysis to convert the mesylate into an alkyl radical.
EFNS guidelines on neurostimulation therapy for neuropathic pain (2007)

Pharmacological relief of neuropathic pain is often insufficient. Electrical neurostimulation is efficacious in chronic neuropathic pain and other neurological diseases. European Federation of Neurological Societies (EFNS) launched a Task Force to evaluate the evidence for these techniques and to produce relevant recommendations. We searched the literature from 1968 to 2006, looking for neurostimulation in neuropathic pain conditions, and classified the trials according to the EFNS scheme of evidence for therapeutic interventions. Spinal cord stimulation (SCS) is efficacious in failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) type I (level B recommendation). High-frequency transcutaneous electrical nerve stimulation (TENS) may be better than placebo (level C) although worse than electro-acupuncture (level B). One kind of repetitive transcranial magnetic stimulation (rTMS) has transient efficacy in central and peripheral neuropathic pains (level B). Motor cortex stimulation (MCS) is efficacious in central post-stroke and facial pain (level C). Deep brain stimulation (DBS) should only be performed in experienced centres. Evidence for implanted peripheral stimulations is inadequate. TENS and r-TMS are non-invasive and suitable as preliminary or add-on therapies. Further controlled trials are warranted for SCS in conditions other than failed back surgery syndrome and CRPS and for MCS and DBS in general. These chronically implanted techniques provide satisfactory pain relief in many patients, including those resistant to medication or other means.
Differentiation of Transplanted Microencapsulated Fetal Pancreatic Cells (2007)

This study demonstrates that fetal pancreatic cells differentiate and function normally when placed within barium alginate microcapsules and transplanted.
Hash-Based Motion Modeling in Wyner-Ziv Video Coding (2007)

Generally, distributed video coding (DVC) schemes perform motion estimation at the decoder side, without the current frame being available. In order to generate the side-information reliably, one solution consists in allocating a limited bit budget to send a hash of the current frame. At the decoder, this auxiliary hash is used to perform motion estimation. This paper studies the accuracy of hash-based motion estimation and compares it to conventional encoder-side motion estimation. We show that, at low rates, the very limited bit-budget of the hash does not ensure a reliable motion estimation, while at medium to high rates the motion accuracy is comparable with the finite precision used to represent motion vectors. Then, we derive the rate-distortion characteristic, which combines the cost of encoding the hash and the prediction residuals after decoder-side motion compensation. We show that, at high rates, hash-based motion modeling can virtually achieve the same coding efficiency as motion-compensated predictive coding. Instead, at medium-to-low rates we observe a significant coding loss. Experimental results on real video sequences validate the results of the proposed model.
Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas. (1987)

We have previously reported the isolation of a human breast cancer cell line resistant to doxorubicin (adriamycin; AdrR MCF-7 cells) that has also developed the phenotype of multidrug resistance (MDR). MDR in this cell line is associated with increased expression of mdr (P glycoprotein) gene sequences. The development of MDR in AdrR MCF-7 cells is also associated with changes in the expression of several phase I and phase II drug-detoxifying enzymes. These changes are remarkably similar to those associated with development of xenobiotic resistance in rat hyperplastic liver nodules, a well-studied model system of chemical carcinogenesis. Using an mdr-encoded cDNA sequence isolated from AdrR MCF-7 cells, we have examined the expression of mdr sequences in rat livers under a variety of experimental conditions. The expression of mdr increased 3-fold in regenerating liver. It was also elevated (3- to 12-fold) in several different samples of rat hyperplastic nodules and in four of five hepatomas that developed in this system. This suggests that overexpression of mdr, a gene previously associated with resistance to antineoplastic agents, may also be involved in the development of resistance to xenobiotics in rat hyperplastic nodules. In addition, although the acute administration of 2-acetylaminofluorene induced an 8-fold increase in hepatic mdr-encoded RNA, performance of a partial hepatectomy either before or after administration of 2-acetylaminofluorene resulted in a greater than 80-fold increase in mdr gene expression over that in normal untreated livers. This represents an important in vivo model system in which to study the acute regulation of this drug resistance gene.
Health care expenditures for people with diabetes mellitus, 1992. (1994)

The purpose of this report is to estimate diabetes prevalence and annual health care costs for people with diabetes in 1992, compare average annual costs for diabetics and nondiabetics, and estimate the portion of total U.S. health care expenditures incurred by people with the disease. Data from the 1987 National Medical Expenditure Survey were used to estimate diabetes prevalence and health care expenditures for diabetics in 1992. Diabetics were identified based on self-reports of a physician diagnosis of diabetes, a history of taking diabetic medications, or an encounter with the health care system specifically related to diabetes. Identified diabetics were classified as confirmed if they had a history of taking diabetic medications, had a diabetes-specific encounter with the health care system, or purchased diabetic equipment. Estimates of diabetes prevalence and health care expenditures were calculated separately for identified and confirmed diabetics using the National Medical Expenditure Survey database. Total health care expenditures included costs associated with inpatient hospital care, outpatient hospital care, office visits to a physician or other provider, emergency room visits, home health care, prescription drugs, dental care, and durable medical equipment purchases. We estimate that percapita annual health care expenditures in 1992 were more than three times greater for diabetics ($9,493) than for nondiabetics ($2,604). Percapita expenditures for confirmed diabetics ($11,157) were more than four times greater than for nondiabetics. In 1992, diabetics constituted 4.5% of the U.S. population but accounted for 14.6% of total U.S. health care expenditures ($105 billion). Confirmed diabetics constituted 3.1% of the U.S. population but accounted for 11.9% of total U.S. health care expenditures ($85 billion). This study found that health care expenditures for people with diabetes constituted about one in seven health care dollars spent in 1992. Health care reform and insurers should take note of these findings and structure benefit packages to promote care likely to reduce the costs of caring for diabetics.
Distribution of Modular Sums and the Security of the Server Aided Exponentiation (2001)

We obtain some uniformity of distribution results for the values of modular sums of the form $$\sum\limits_{j = 1}^n {a_j x_j } \left( {\bmod M} \right)\left( {x_1 , \ldots ,x_n } \right) \in \beta $$ where M ≥ 1 is an integer, a1,…, an are elements of the residue ring modulo M, selected unformly at random, and β is an arbitrary set of n-dimensional integer vectors. In some partial cases, for very special sets β, some results of this kind have been known, however our estimates are more precise and more general. Our technique is based on fairly simple properties of exponential sums. We also give cryptographic applications of some of these results. In particular, we consider an extension of a pseudo-random number generator due to V. Boyko, M. Peinado and R Venkatesan, and establish the security of some discrete logarithm based signature schemes making use of this generator (in both its original and extended forms). One of these schemes, which uses precomputation is well known. The other scheme which uses server aided computation, seems to be new. We show that for a certain choice of parameters one can guarantee an essential speed-up of both of these schemes without compromising the security (compared to the traditional discrete logarithm based signature scheme).
Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease (2013)

Vanishing white matter disease is a genetic leukoencephalopathy caused by mutations in eukaryotic translation initiation factor 2B. Patients experience a slowly progressive neurological deterioration with episodes of rapid clinical worsening triggered by stress. The disease may occur at any age and leads to early death. Characteristic neuropathological findings include cystic degeneration of the white matter with feeble, if any, reactive gliosis, dysmorphic astrocytes and paucity of myelin despite an increase in oligodendrocytic density. These features have been linked to a maturation defect of astrocytes and oligodendrocytes. However, the nature of the link between glial immaturity and the observed neuropathological features is unclear. We hypothesized that the defects in maturation and function of astrocytes and oligodendrocytes are related. Brain tissue of seven patients with genetically proven vanishing white matter disease was investigated using immunohistochemistry, western blotting, quantitative polymerase chain reaction and size exclusion chromatography. The results were compared with those obtained from normal brain tissue of age-matched controls, from chronic demyelinated multiple sclerosis lesions and from other genetic and acquired white matter disorders. We found that the white matter of patients with vanishing white matter disease is enriched in CD44-expressing astrocyte precursor cells and accumulates the glycosaminoglycan hyaluronan. Hyaluronan is a major component of the extracellular matrix, and CD44 is a hyaluronan receptor. We found that a high molecular weight form of hyaluronan is overabundant, especially in the most severely affected areas. Comparison between the more severely affected frontal white matter and the relatively spared cerebellum confirms that high molecular weight hyaluronan accumulation is more pronounced in the frontal white matter than in the cerebellum. High molecular weight hyaluronan is known to inhibit astrocyte and oligodendrocyte precursor maturation and can explain the arrested glial progenitor maturation observed in vanishing white matter disease. In conclusion, high molecular weight species of hyaluronan accumulate in the white matter of patients with vanishing white matter disease, and by inhibiting glial maturation and proper function, they may be a major determinant of the white matter pathology and lack of repair.
The Use of Monoclonal Antibodies to Define Levels of Cystatin C in Normal Human Serum (1989)

We established four hybridoma cell lines which secreted monoclonal antibodies against human cystatin C. These monoclonal antibodies were of IgA(kappa), IgG2a(lambda), IgG1(kappa), and IgG1(lambda) isotypes, respectively. The association constants (Ka) of the three IgG monoclonal antibodies ranged from 3.6 x 10(9) M-1 to 7.3 x 10(10) M-1. An ELISA technique for the measurement of cystatin C was established by using one of these monoclonal antibodies. The assay procedure was highly specific, sensitive, and reproducible. The lower detectable limit of cystatin C by this procedure was 1.9 ng/ml. The level of cystatin C in normal human serum was 1.16 +/- 0.91 micrograms/ml (mean +/- S.D., n = 274).
Theoretical and computational aspects of 2-D inverse profiling (2001)

The authors discuss two techniques for solving two-dimensional (2D) inverse scattering problems by parameterizing the scattering configuration, and determining the optimum value of the parameters by minimizing a cost function involving the known scattered-field data. The computation of the fields in each estimated configuration is considered as an auxiliary problem. To improve the efficiency of these computations, the CGFFT iterative scheme is combined with a special extrapolation procedure that is valid for problems with a varying physical parameter such as frequency, angle of incidence, or contrast. Further, they analyze the dynamic range and the resolution of linearized schemes. To obtain an acceptable resolution for an object with a large contrast with respect to the surrounding medium, multiple-frequency information is used. Finally, the availability of a fast-forward solver was an incentive to consider nonlinear optimization. In particular, the authors use a quasi-Newton algorithm at only twice the computational cost of the distorted-wave Born iterative scheme.
Aripiprazole in Children with Attention-Deficit/Hyperactivity Disorder (2007)

Although this was a brief pilot study with a small sample size, in this cohort, APZ led to clinical benefit in reducing ADHD symptoms and improving overall functioning. Of note, cognitive functioning did not appear to be negatively impacted by APZ treatment.
Intrinsic Sensor Noise Features for Forensic Analysis on Scanners and Scanned Images (2009)

A large portion of digital images available today are acquired using digital cameras or scanners. While cameras provide digital reproduction of natural scenes, scanners are often used to capture hard-copy art in a more controlled environment. In this paper, new techniques for nonintrusive scanner forensics that utilize intrinsic sensor noise features are proposed to verify the source and integrity of digital scanned images. Scanning noise is analyzed from several aspects using only scanned image samples, including through image denoising, wavelet analysis, and neighborhood prediction, and then obtain statistical features from each characterization. Based on the proposed statistical features of scanning noise, a robust scanner identifier is constructed to determine the model/brand of the scanner used to capture a scanned image. Utilizing these noise features, we extend the scope of acquisition forensics to differentiating scanned images from camera-taken photographs and computer-generated graphics. The proposed noise features also enable tampering forensics to detect postprocessing operations on scanned images. Experimental results are presented to demonstrate the effectiveness of employing the proposed noise features for performing various forensic analysis on scanners and scanned images.
Kinetic Analysis of Tear Interference Images in Aqueous Tear Deficiency Dry Eye before and after Punctal Occlusion (2003)

In this study, kinetic analysis of tear interference images provided evidence that retardation of lipid spread is, but MGD is not, the main reason for the increased thickness of precorneal lipid film in the inferior cornea of eyes with ATD. As a result, lipid film is deficient in the superior cornea and unevenly distributed, further destabilizing the tear film. The fact that PO significantly improves lipid spread, evenness, and thickness suggests that the performance of lipid film is also dictated by the amount of aqueous tear fluid. These findings provide new insight into the interaction between the lipid film and the aqueous tear fluid.
Memory effect of polymer dispersed liquid crystal by hybridization with nanoclay (2009)

The electro-optical performances of polymer dispersed liquid crystal (PDLC) were investigated in the presence of organically modified clays. With the addition and increasing amount of modified clay, driving voltage and memory effect, viz. transparent state of the film after the electricity is off simultaneously increased due most likely to the increased viscosity. Among the two types of modifier, 4-(4-aminophenyl) benzonitrile having greater chemical affinity with LC than hexylamine, gave finer dispersion of clay in liquid crystal, greater viscosity, larger driving voltage and response time, and greater memory effect.
Transformation of the Methylotrophic Yeast Hansenula polymorpha (1986)

Summary: A mutant of Hansenula polymorpha defective in β-isopropylmalate dehydrogenase was isolated. It was transformed with YEp13, a shuttle vector containing the Saccharomyces cerevisiae LEU2 gene, either using the protoplasting method or by treatment with LiCl. Leu+ transformants were recovered at a frequency of 30-60 μg DNA)−1. The transformants were shown to contain an autonomously replicating plasmid by stability tests, hybridization experiments and by the recovery of YEp13 from transformed cells via transformation of Escherichia coli. YEp13 linearized by BamHI digestion was also effective in transformation; the linearized plasmid was shown to recircularize and replicate autonomously in the transformants.
Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. (1990)

Free radical-mediated oxidative damage has been implicated in tissue injury resulting from ischemia/reperfusion events. Global cortical ischemia/reperfusion injury to Mongolian gerbil brains was produced by transient occlusion of both common carotid arteries. Protein oxidation, as measured by protein carbonyl content, increased significantly during the reperfusion phase that followed 10 min of ischemia. The activity of glutamine synthetase, an enzyme known to be inactivated by metal-catalyzed oxidation reactions, decreased to 65% of control levels after 2 hr of reperfusion that followed 10 min of ischemia. We also report that the free radical spin trap N-tert-butyl-alpha-phenylnitrone [300 mg/kg (body weight)] administered 60 min before ischemia/reperfusion is initiated, partially prevents protein oxidation and protects from loss of glutamine synthetase activity. In addition, we report a N-tert-butyl-alpha-phenylnitrone-dependent nitroxide radical obtained in the lipid fraction of the ischemia/reperfusion-lesioned brains, but there was very little radical present in the comparable sham-operated control brains. These data strengthen the previous observation utilizing in vivo-trapping methods, that free radical flux is increased during the reperfusion phase of the ischemia-lesioned gerbil brain. The loss of glutamine synthetase would be expected to increase the levels of brain L-glutamate. Thus, the oxidative inactivation of glutamine synthetase may be a critical factor in the neurotoxicity produced after cerebral ischemia/reperfusion injury.