gebhart/patrepeval huggingface dataset:
Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism (1999)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson's disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-ribose) polymerase (PARP), which catalyzes the attachment of ADP ribose units from NAD to nuclear proteins after DNA damage, are dramatically spared from MPTP neurotoxicity. MPTP potently activates PARP exclusively in vulnerable dopamine containing neurons of the substantia nigra. MPTP elicits a novel pattern of poly(ADP-ribosyl)ation of nuclear proteins that completely depends on neuronally derived nitric oxide. Thus, NO, DNA damage, and PARP activation play a critical role in MPTP-induced parkinsonism and suggest that inhibitors of PARP may have protective benefit in the treatment of Parkinson's disease.
Overexpression of EphA2, MMP‐9, and MVD‐CD34 in hepatocellular carcinoma: Implications for tumor progression and prognosis (2009)

Overexpressions of EphA2 and MMP-9 relate to tumor progression, metastasis, and prognosis in HCC. The present study suggests that EphA2 is associated with key mediators of angiogenesis and invasion.
A glucose-responsive controlled release of insulin system based on enzyme multilayers-coated mesoporous silica particles (2011)

A novel glucose-responsive controlled release of insulin system is constructed through coating enzyme multilayers on mesoporous silica particles (MSPs). The MSPs serve as the drug reservoir, and the enzyme multilayers cross-linked with glutaraldehyde act as a valve to control the release of insulin in response to the external glucose level.
Preparation and Properties of Alpha(1)-Proteinase InhibitorConcentrate from Human Plasma (1985)

Alpha(1)-proteinase inhibitor (a,-PI) has been prepared as a concentrate in quantities large enough for clinical testing of its safety and efficacy in the treatment of emphysema and other disorders. The α(1)-PI was purified from Cohn fraction IV-1 paste by polyethylene glycol precipitation and DEAE-Sepharose chromatography. The methods used in the purification are gentle and the resulting product behaves almost identically to the α(1)-PI from plasma. The protein has been heat treated (60°C, 10 h) to lower the risk of transmission of plasma-borne diseases. This resulted in some aggregation of the protein, but did not cause the generation of new antigenic sites. Half-life studies in animals showed that the protein behaved normally (catabolic t(1,2) of 68 h).
Equine Herpesvirus 1 Gene 12 Can Substitute for vmw65 in the Growth of Herpes Simplex Virus (HSV) Type 1, Allowing the Generation of Optimized Cell Lines for the Propagation of HSV Vectors with Multiple Immediate-Early Gene Defects (1999)

Herpes simplex virus (HSV) has often been suggested for development as a vector, particularly for the nervous system. Considerable evidence has shown that for use of HSV as a vector, immediate-early (IE) gene expression must be minimized or abolished, otherwise such vectors are likely to be highly cytotoxic. Mutations of vmw65 which abolish IE promoter transactivating activity may also be included to reduce IE gene expression generally. However, when vmw65 mutations are combined with an IE gene deletion, such viruses are hard to propagate, even on cells which otherwise complement the IE gene deletion effectively. We have found that vmw65 mutants can be effectively grown on cell lines expressing equine herpesvirus 1 gene 12, a non-HSV homologue of vmw65 with little sequence similarity to its HSV counterpart. This prevents repair by homologous recombination of vmw65 mutations in the virus, which would occur if mutations were complemented by vmw65 itself. The gene 12 protein is not packaged into HSV virions, which is important if viruses grown on such cells are to be used as vectors. These results not only further strengthen the evidence for direct functional homology between and similar modes of action of the two proteins but have allowed the generation of gene 12-containing cell lines in which ICP4 and ICP27 expression is induced by virus infection (probably by ICP0) and which give efficient growth of viruses deficient in ICP27, ICP4, and vmw65 (the viruses also have ICP34.5/ORFP deleted). Efficient growth of such viruses has not previously been possible. As these viruses are highly deficient in IE gene expression generally, such virus-cell line combinations may provide an alternative to HSV vectors with deletions of all four of the regulatory IE genes which, for optimal growth, require cell lines containing all four IE genes but which are hard to generate due to the intrinsic cytotoxicity of each of the proteins.
Diversity transform for fading channels (1996)

This paper investigates a transform that provides diversity to words of symbols transmitted over fading channels. This diversity transform (DRT) does not alter the distance between the input words nor the bandwidth or the information rate. The transform is based on an orthonormal transform and thus increases the channel alphabet. A considerable diversity gain is achieved over Rayleigh fading channel with perfect channel state information (CSI) and interleaving. The transform performances are evaluated both analytically and by simulation, and optimal transforms are determined for specific channels. Finally, a simple nonoptimal decoding scheme is developed, which provides a powerful and practical technique to transfer information over fading channels with or without coding.
Microarray‐based CGH detects chromosomal mosaicism not revealed by conventional cytogenetics (2007)

Somatic chromosomal mosaicism is a well-established cause for birth defects, mental retardation, and, in some instances, specific genetic syndromes. We have developed a clinically validated, targeted BAC clone array as a platform for comparative genomic hybridization (aCGH) to enable detection of a wide range of pathologic copy number changes in DNA. It is designed to provide high sensitivity to detect well-characterized submicroscopic micro-deletion and duplication disorders while at the same time minimizing detection of variation of uncertain clinical significance. In the course of studying 2,585 samples submitted to our clinical laboratory, chromosomal mosaicism was detected in 12 patient samples; 10 of these cases were reported to have had a normal blood chromosome analysis. This enhanced ability of aCGH to detect mosaicism missed by routine chromosome analysis may be due to some combination of testing multiple cell lineages and/or failure of cytogenetically abnormal T lymphocytes to respond to mitogens. This suggests that aCGH may detect somatic chromosomal mosaicism that would be missed by conventional cytogenetics.
An alternate construction of an access-optimal regenerating code with optimal sub-packetization level (2015)

Given the scale of today's distributed storage systems, the failure of an individual node is a common phenomenon. Various metrics have been proposed to measure the efficacy of the repair of a failed node, such as the amount of data download needed to repair (also known as the repair bandwidth), the amount of data accessed at the helper nodes, and the number of helper nodes contacted. Clearly, the amount of data accessed can never be smaller than the repair bandwidth. In the case of a help-by-transfer code, the amount of data accessed is equal to the repair bandwidth. It follows that a help-by-transfer code possessing optimal repair bandwidth is access optimal. The focus of the present paper is on help-by-transfer codes that employ minimum possible bandwidth to repair the systematic nodes and are thus access optimal for the repair of a systematic node. The zigzag construction by Tamo et al. in which both systematic and parity nodes are repaired is access optimal. But the sub-packetization level required is r <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k</sup> where r is the number of parities and k is the number of systematic nodes. To date, the best known achievable sub-packetization level for access-optimal codes is r <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k/r</sup> in a MISER-code-based construction by Cadambe et al. in which only the systematic nodes are repaired and where the location of symbols transmitted by a helper node depends only on the failed node and is the same for all helper nodes. Under this set-up, it turns out that this sub-packetization level cannot be improved upon. In the present paper, we present an alternate construction under the same setup, of an access-optimal code repairing systematic nodes, that is inspired by the zigzag code construction and that also achieves a sub-packetization level of r <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k/r</sup> .
Impact of betel quid, tobacco and alcohol on three-stage disease natural history of oral leukoplakia and cancer: implication for prevention of oral cancer (2004)

The natural history of the three-stage process from normal, oral leukoplakia to oral cancer in relation to betel quid chewing, smoking and drinking is rarely addressed. The aim of this study was to simultaneously quantify the effects of three risk factors on occurrence of oral leukoplakia and malignant transformation to oral cancer. A hospital-based case-control study design derived from three retrospective cohorts from 1988 to 1998 was conducted. A total of 74 oral cancer patients, 164 patients with oral leukoplakia and 187 controls were interviewed to collect information on their betel chewing, smoking and drinking habits. The effects of the three risk factors on the progression rates of the three-stage disease process were estimated using the three-state Markov model. Subjects who chewed betel quid were at greater risk of leukoplakia (adjusted odds ratio (OR) 17.7 (9.03-34.5)) but there was no significant effect on malignant transformation (OR 1.04 (0.61-1.76)). Smoking played a major role in the onset of leukoplakia (OR 4.26 (2.21-8.23)) but a minor role in malignant transformation (OR 1.36 (0.69-2.68)). Alcohol was positively associated with malignant transformation (OR 2.37 (1.47-3.82)) but unrelated to occurrence of leukoplakia (OR 0.76 (0.04-1.43)). We concluded that smoking and betel quid were two significant risk factors for the occurrence of leukoplakia, whereas alcohol was significantly responsible for malignant transformation.
Development of engineered magnetic materials for antenna applications. (2005)

Antennas and planar antenna arrays were designed and fabricated employing new engineered magnetic materials exhibiting properties electromagnetically superior to the existing state of the art. Aggressively miniaturized patch antennas on a reactive impedance surface exhibits high performance characteristics including bandwidth, miniaturization, gain, and efficiency. The Embedded Circuit Spiral Resonator is a new metamaterial providing enhancement of both tunable permeability and permittivity. The Embedded Circuit Spiral Resonator provides excellent performance as an insulator in its electromagnetic band-gap region. The band-gap region of the Embedded Circuit Spiral Resonator acts as an effective insulator to suppress coupling between densely packed array elements. The suppression of coupling between densely packed array elements enables the development of densely packed superdirective arrays, which is demonstrated experimentally. To validate the material properties of these newly developed materials, new material characterization techniques were developed including the Frequency Extended Perturbation Method, and the Hybrid Measurement Technique. These techniques provide the ability to characterize low-loss magnetic materials in the microwave region.
Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 (1991)

Vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1) are adhesive proteins induced on endothelium by cytokines. We examined the contribution of these adhesive proteins to human peripheral blood monocyte adherence to endothelium using transfected Chinese hamster ovary (CHO) cells stably expressing these proteins and monoclonal antibodies (MoAbs) to ELAM-1, VCAM-1, or CD49d/CD29 (VLA-4), the leukocyte receptor for VCAM-1. Monocytes bound to CHO cells transfected with cDNA of ELAM-1 or VCAM-1. Binding to ELAM-1 was inhibited by MoAb to ELAM-1 and binding to VCAM-1 was inhibited by MoAb to VCAM-1 or the alpha-chain of very late activation antigen-4 (VLA-4) (CD49d). Additive inhibition of adherence to unstimulated human umbilical vein endothelium (HUVE) was observed when monocytes were pretreated with both MoAb to CD49d and MoAb to CD18, the common beta-chain of the leukocyte beta 2 integrin receptors. Adherence of monocytes to HUVE stimulated by recombinant human tumor necrosis factor-alpha was not reduced by MoAbs to CD18, CD49d, or ELAM-1 when used singly, but combinations of these MoAbs produced significant inhibition. We conclude that multiple receptor-ligand systems are involved in monocyte adherence to endothelium.
Engineering a Hyperthermophilic Archaeon for Temperature-Dependent Product Formation (2012)

Extremely thermostable enzymes from microorganisms that grow near or above the boiling point of water are already used in biotechnology. However, the use of hyperthermophilic microorganisms themselves for biotechnological applications has been limited by the lack of their genetic accessibility. Recently, a genetic system for Pyrococcus furiosus, which grows optimally near 100°C, was developed in our laboratory. In this study, we present the first heterologous protein expression system for a microorganism that grows optimally at 100°C, a first step towards the potential expression of genes involved in biomass degradation or biofuel production in hyperthermophiles. Moreover, we developed the first system for specific gene induction in P. furiosus. As the cold shock promoter for protein expression used in this study is activated at suboptimal growth temperatures of P. furiosus, it is a powerful genetic tool for protein expression with minimal interference of the host's metabolism and without the need for chemical inducers.
Embryonic stem cell-derived tissues are immunogenic but their inherent immune privilege promotes the induction of tolerance (2007)

Although human embryonic stem (ES) cells may one day provide a renewable source of tissues for cell replacement therapy (CRT), histoincompatibility remains a significant barrier to their clinical application. Current estimates suggest that surprisingly few cell lines may be required to facilitate rudimentary tissue matching. Nevertheless, the degree of disparity between donor and recipient that may prove acceptable, and the extent of matching that is therefore required, remain unknown. To address this issue using a mouse model of CRT, we have derived a panel of ES cell lines that differ from CBA/Ca recipients at defined genetic loci. Here, we show that even expression of minor histocompatibility (mH) antigens is sufficient to provoke acute rejection of tissues differentiated from ES cells. Nevertheless, despite their immunogenicity in vivo, transplantation tolerance may be readily established by using minimal host conditioning with nondepleting monoclonal antibodies specific for the T cell coreceptors, CD4 and CD8. This propensity for tolerance could be attributed to the paucity of professional antigen-presenting cells and the expression of transforming growth factor (TGF)-beta(2). Together, these factors contribute to a state of acquired immune privilege that favors the polarization of infiltrating T cells toward a regulatory phenotype. Although the natural privileged status of ES cell-derived tissues is, therefore, insufficient to overcome even mH barriers, our findings suggest it may be harnessed effectively for the induction of dominant tolerance with minimal therapeutic intervention.
Adverse Balance of Nitric Oxide/Peroxynitrite in the Dysfunctional Endothelium Can be Reversed by Statins (2007)

Vascular endothelial dysfunction is a complex phenomenon that might be caused by a deficiency of nitric oxide (NO) and an overproduction of peroxynitrite (ONOO-). This study used a nanotechnological approach to monitor the in vitro effect of statins on the [NO]/[ONOO-] balance in normal and dysfunctional endothelial cells. NO and (ONOO-) were measured by electrochemical nanosensors in a single human umbilical vein endothelial cell (HUVEC) treated with atorvastatin or simvastatin for 24 hours in the presence or absence of 50 microg/mL oxidized-LDL. An imbalance between [NO]/[ONOO-] concentrations was used as an indicator of endothelial dysfunction and correlated with endothelial nitric oxide synthase (eNOS) expression. Ox-LDL induced dysfunction of the endothelium by uncoupling eNOS. NO concentration decreased from 300 +/- 12 to 146 +/- 8 nmol/L and (ONOO-) increased from 200 +/- 9 to 360 +/- 13 nmol/L. The [NO]/[ONOO-] balance decreased from 1.50 +/- 0.04 (control) to 0.40 +/- 0.03 for cells co-incubated with ox-LDL. Treatment with statins reversed eNOS uncoupling, induced by oxidized-LDL and significantly increased the [NO]/[ONOO-] balance to 1.2 +/- 0.1. These results demonstrate that statins can restore endothelial function by increasing eNOS expression, decreasing eNOS uncoupling, reducing the (ONOO-) level (nitroxidative stress), and shifting the [NO]/[ONOO-] balance towards NO.
Crystal structure, at 2.6-A resolution, of the Streptomyces lividans xylanase A, a member of the F family of beta-1,4-D-glycanases. (1994)

The crystal structure of the 32-kDa catalytic domain of the Streptomyces lividans xylanase A was solved by molecular isomorphous replacement methods and subsequently refined at 2.6-A resolution to a conventional crystallographic R factor of 0.21. This is the first successful structure determination of a member of the F family of endo-beta-1,4-D-glycanases. Unlike the recently determined xylanases of the G family (Wakarchuk, W. W., Campbell, R. L., Sung, W. L., Davoodi, J., and Yaguchi, M. (1994) Protein Sci. 3, 467-475), where the catalytic domains have a unique beta-sheet structure, the 32-kDa domain of the S. lividans xylanase A is folded into a complete (alpha/beta)8 barrel, the first such fold observed among beta-1,4-D-glycanases. The active site is located at the carbonyl end of the beta barrel. The crystal structure supports the earlier assignment of Glu-128 and Glu-236 as the catalytic amino acids (Moreau, A., Roberge, M., Manin, C., Shareck, F., Kluepfel, D., and Morosoli, R. (1994) Biochem. J., in press).
Dual-Mode EPR Study of Mn(III) Salen and the Mn(III) Salen-Catalyzed Epoxidation of cis-β-Methylstyrene (2001)

Dual-mode electron paramagnetic resonance (EPR), in which an oscillating magnetic field is alternately applied parallel or perpendicular to the static magnetic field, is a valuable technique for studying both half-integer and integer electron spin systems and is particularly useful for studying transition metals involved in redox chemistry. We have applied this technique to the characterization of the Mn(III) salen (salen = N,N'-ethylene bis(salicylideneaminato)) complex [(R,R)-(-)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III)], with an S = 2 integer electron spin system. Furthermore, we have used dual-mode EPR to study the Mn salen complex during the Mn(III) salen-catalyzed epoxidation of cis-beta-methylstyrene. Our study shows that the additives N-methylmorpholine N-oxide (NMO) and 4-phenylpyridine-N-oxide (4-PPNO), which are used to improve epoxidation yields and enantioselection, bind to the Mn(III) center prior to the epoxidation reaction, as evidenced by the alteration of the Mn(III) parallel mode EPR signal. With these additives as ligands, the axial zero-field splitting values and (55)Mn hyperfine splitting of the parallel mode signal are indicative of an axially elongated octahedral geometry about the Mn(III) center. Since the dual-mode EPR technique allows the observation of both integer and half-integer electron spin systems, Mn oxidation states of II, III, IV, and potentially V can be observed in the same sample as well as any radical intermediates or Mn(III,IV) dinuclear clusters formed during the Mn(III) salen-catalyzed epoxidation reaction. Indeed, our study revealed the formation of a Mn(III,IV) dinuclear cluster in direct correlation with expoxide formation. In addition to showing the possible reaction intermediates, dual-mode EPR offers insight into the mechanism of catalyst degradation and formation of unwanted byproducts. The dual-mode technique may therefore prove valuable for elucidating the mechanism of Mn(III) salen catalyzed reactions and ultimately for designing optimum catalytic conditions (solvents, oxidants, and additives such as NMO or 4-PPNO).
Gene selection and classification from microarray data using kernel machine (2004)

The discrimination of cancer patients (including subtypes) based on gene expression data is a critical problem with clinical ramifications. Central to solving this problem is the issue of how to extract the most relevant genes from the several thousand genes on a typical microarray. Here, we propose a methodology that can effectively select an informative subset of genes and classify the subtypes (or patients) of disease using the selected genes. We employ a kernel machine, kernel Fisher discriminant analysis (KFDA), for discrimination and use the derivatives of the kernel function to perform gene selection. Using a modified form of KFDA in the minimum squared error (MSE) sense and the gradients of the kernel functions, we construct an effective gene selection criterion. We assess the performance of the proposed methodology by applying it to three gene expression datasets: leukemia dataset, breast cancer dataset and colon cancer dataset. Using a few informative genes, the proposed method accurately and reliably classified cancer subtypes (or patients). Also, through a comparison study, we verify the reliability of the gene selection and discrimination results.
Corticosteroids and medroxyprogesterone acetate inhibit the induction of E-selectin on the vascular endothelium by MDA-MB-231 breast cancer cells. (1996)

The vascular endothelium plays a critical role in cancer metastasis by directing circulating cancer cells into extravascular tissues and by expressing cell adhesion molecules. The authors investigated the interaction between breast cancer cells and vascular endothelial cells in the expression of E-selectin, and the effect of corticosteroids or medroxyprogesterone acetate (MPA) on such interaction. An MDA-MB-231 cell line, derived from human breast cancer induced E-selectin on the cell surface of human umbilical vascular endothelial cells. This induction was enhanced with a supplement of mononuclear cells of peripheral blood added to the culture medium. Corticosteroids and MPA blocked the induction of E-selectin proportional to concentration. Anti-IL-1 beta, but not anti-IL1 alpha or- TNF a, antibodies blocked induction. These findings suggest that MDA-MB-231 cells induce expression of E-selectin on vascular endothelium by releasing IL-1 beta directly or indirectly, but this induction is blocked by corticosteroids and MPA. Corticosteroids and MPA may inhibit cancer metastasis by blocking E-selectin expression on the vascular endothelium.