gebhart/patrepeval huggingface dataset:
Gene Therapy-Mediated Modulation of Immune Processes in the Central Nervous System (2003)

Selective interference with immune processes in the central nervous system (CNS) is a very difficult task because of the limitations associated with the delivery of immuno modulatory molecules across the blood brain barrier. Systemic administration of immune-mediators, either by conventional routes or by intramuscularly or intravenous gene therapy, is hampered by severe side effects and alters immune-system functions also in peripheral organs. To overcome these problems, different gene therapy strategies have been developed to deliver immuno modulatory molecules directly within the central nervous system. The use of engineered CNS antigen-specific circulating cells as selective delivery vehicles, the direct injection of gene vectors into the brain parenchyma, or also the ependymal route, have been proposed as possible alternative gene therapy protocols to selectively interfere with immuno-pathological processes in the CNS. We will review the use of these CNS-targeted gene therapy protocols for the treatment of experimental autoimmune encephalomyelitis (EAE), the prototypical experimental immune-mediated disease of the CNS, and therefore discuss the relevance of these results for the therapy of multiple sclerosis (MS) the most common, immune-mediated, demyelinating disease of the CNS in humans.
Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study (1991)

A potent, synthetic cannabinoid was radiolabeled and used to characterize and precisely localize cannabinoid receptors in slide-mounted sections of rat brain and pituitary. Assay conditions for 3H-CP55,940 binding in Tris-HCl buffer with 5% BSA were optimized, association and dissociation rate constants determined, and the equilibrium dissociation constant (Kd) calculated (21 nM by liquid scintillation counting, 5.2 nM by quantitative autoradiography). The results of competition studies, using several synthetic cannabinoids, add to prior data showing enantioselectivity of binding and correlation of in vitro potencies with potencies in biological assays of cannabinoid actions. Inhibition of binding by guanine nucleotides was selective and profound: Nonhydrolyzable analogs of GTP and GDP inhibited binding by greater than 90%, and GMP and the nonhydrolyzable ATP analog showed no inhibition. Autoradiography showed great heterogeneity of binding in patterns of labeling that closely conform to cytoarchitectural and functional domains. Very dense 3H-CP55,940 binding is localized to the basal ganglia (lateral caudate-putamen, globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata), cerebellar molecular layer, innermost layers of the olfactory bulb, and portions of the hippocampal formation (CA3 and dentate gyrus molecular layer). Moderately dense binding is found throughout the remaining forebrain. Sparse binding characterizes the brain stem and spinal cord. Densitometry confirmed the quantitative heterogeneity of cannabinoid receptors (10 nM 3H-CP55,940 binding ranged in density from 6.3 pmol/mg protein in the substantia nigra pars reticulata to 0.15 pmol/mg protein in the anterior lobe of the pituitary). The results suggest that the presently characterized cannabinoid receptor mediates physiological and behavioral effects of natural and synthetic cannabinoids, because it is strongly coupled to guanine nucleotide regulatory proteins and is discretely localized to cortical, basal ganglia, and cerebellar structures involved with cognition and movement.
Follow-up colonoscopy in patients with colorectal adenomatous polyps. (1987)

Forty-four asymptomatic patients with adenomatous colorectal polyps were followed by repeated colonoscopies and subsequent removal of new polyps. The median follow-up time was 34 months (range, 4 to 131 months). Twenty-six patients (59 percent) developed new adenomatous polyps. The recurrence rate was 69 percent in patients with multiple polyps compared with 54 percent in patients with a single polyp. The location of new polyps was in the same colonic segment in 81 percent of the patients, but not at the same site in the colon where a previous polyp had been removed. The histopathology and size of new polyps compared with the initial polyps showed a significant improvement in histopathology toward more benign polyps (P less than 0.02) and smaller polyps (P less than 0.001). In patients who initially had single adenomatous polyps, new polyp(s) were diagnosed after a mean time of 23 months compared with 13.5 months in patients with two or more adenomatous polyps initially. Patients with atypia in initial polyp(s) developed new polyp(s) after a mean time of 11 months compared with 23 months in patients without atypia. The mean time from a colon with no polyps to the diagnosis of a new adenomatous polyp less than 5 mm in size was 11.5 months, which was a statistically significant shorter time than the 19.4 months observed for the development of polyps 5 mm or larger.
Building Flexible and Extensible Web Applications with Lua (2020)

The World Wide Web is in constant renovation, with new technologies emerging every day. Most of these technologies are still incipient, and there are few de facto standards for this &amp;quot;new Web&amp;quot;. There is a need for tools that can run with current standard support, but which are flexible and extensible enough to be eventually ported to new APIs and to incorporate new technologies. On the other hand, many Web developers cannot keep pace with the fast track of Web technologies. Therefore, it is important for new tools to be simple enough to be mastered quickly by the average programmer. This paper presents CGILua, a Web development tool that matches these requirements. The paper also discusses why this tool is being adopted in many commercial and academic projects, focusing on issues such as exibility, extensibility, simplicity, and portability.
The efficacy of local infiltration of triamcinolone acetonide with lignocaine compared with lignocaine alone in the treatment of postherpetic neuralgia. (2005)

Locally infiltrated injection triamcinolone acetonide with lignocaine was significantly more effective than injection lignocaine alone in the treatment of postherpetic neuralgia both at 6 and 12 weeks follow-up.
Inhibition of Neuronal Nitric-oxide Synthase by Calcium/ Calmodulin-dependent Protein Kinase IIα through Ser847 Phosphorylation in NG108-15 Neuronal Cells (2000)

We have previously demonstrated that phosphorylation of neuronal nitric-oxide synthase (nNOS) at Ser(847) by Ca(2+)/calmodulin-dependent protein kinases (CaM kinases) attenuates the catalytic activity of the enzyme in vitro (Hayashi Y., Nishio M., Naito Y., Yokokura H., Nimura Y., Hidaka H., and Watanabe Y. (1999) J. Biol. Chem. 274, 20597-20602). In the present study we determined that CaM kinase IIalpha (CaM-K IIalpha) can directly phosphorylate nNOS on Ser(847), leading to a reduction of nNOS activity in cells. The phosphorylation abilities of purified CaM kinase Ialpha (CaM-K Ialpha), CaM-K IIalpha, and CaM-kinase IV (CaM-K IV) on Ser(847) were analyzed using the synthetic peptide nNOS-(836-859) (Glu-Glu-Arg-Lys-Ser-Tyr-Lys-Val-Arg-Phe-Asn-Ser-Val-Ser-Ser-Tyr-Ser- Asp-Ser-Arg-Lys-Ser-Ser-Gly) from nNOS as substrate. The relative V(max)/K(m) ratios of CaM kinases for nNOS-(836-859) were found to be as follows: CaM-K IIalpha, 100; CaM-K Ialpha, 54.5; CaM-K IV, 9.1. Co-transfection of constitutively active CaM-K IIalpha1-274 but not inactive CaM-K IIalpha1-274, generated by mutation of Lys(42) to Ala, with nNOS into NG108-15 cells, resulted in increased Ser(847) phosphorylation in the presence of okadaic acid, an inhibitor of protein phosphatase (PP)1 and PP2A, with a concomitant inhibition of NOS enzyme activity. In addition, this latter decrease could be reversed by treatment with exogenous PP2A. Cells expressing mutant nNOS (S847A) proved resistant to phosphorylation and a decrease of NOS activity. Thus, our results indicate that Ca(2+) triggers cross-talk signal transduction between CaM kinase and NO and CaM-K IIalpha phosphorylating nNOS on Ser(847), which in turn decreases the gaseous second messenger NO in neuronal cells.
Affibody‐Functionalized Gold–Silica Nanoparticles for Raman Molecular Imaging of the Epidermal Growth Factor Receptor (2011)

The affibody functionalization of fluorescent surface-enhanced Raman scattering gold-silica nanoparticles as multimodal contrast agents for molecular imaging specific to epidermal growth factor receptor (EGFR) is reported. This nanoparticle bioconjugate reports EGFR-positive A431 tumors with a signal nearly 35-fold higher than EGFR-negative MDA-435S tumors. The low-level EGFR expression in adjacent healthy tissue is 7-fold lower than in the positive tumors. Validation via competitive inhibition reduces the signal by a factor of six, and independent measurement of EGFR via flow cytometry correlates at R(2) = 0.92.
Deep Boosting (2014)

We present a new ensemble learning algorithm, DeepBoost, which can use as base classifiers a hypothesis set containing deep decision trees, or members of other rich or complex families, and succeed in achieving high accuracy without over-fitting the data. The key to the success of the algorithm is a capacity-conscious criterion for the selection of the hypotheses. We give new data-dependent learning bounds for convex ensembles expressed in terms of the Rademacher complexities of the sub-families composing the base classifier set, and the mixture weight assigned to each sub-family. Our algorithm directly benefits from these guarantees since it seeks to minimize the corresponding learning bound. We give a full description of our algorithm, including the details of its derivation, and report the results of several experiments showing that its performance compares favorably to that of AdaBoost and Logistic Regression and their L1-regularized variants.
Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review (2000)

Large, well designed epidemiological studies focusing on well defined end points taking into account relevant confounders and with particular emphasis on exposure characterisation are ideally needed to confirm or refute these preliminary findings. In practice, these studies may be impracticable, partly due to the cost involved, but this is an issue that can be put right--for example, by use of subsets of the population in the design of exposure models. The studies should also reflect differences of culture and water treatment in different parts of the world. To identify the specific components that may be of aetiological concern and hence to fit the most appropriate exposure model with which to investigate human exposure to chlorinated DBPs, further detailed toxicological assessments of the mixture of byproducts commonly found in drinking water are also needed.
Immunological and virological interactions in patients receiving passive immunotherapy with HIV-1 neutralizing monoclonal antibodies. (1994)

Mouse monoclonal antibodies with high human immunodeficiency virus type 1 (HIV-1) neutralizing titers were used for passive immunotherapy of eleven late-state HIV-infected patients. In five patients the serum level of the core protein p24 decreased, while in five cases it remained unchanged. The level of viral RNA in plasma as measured by quantitative polymerase chain reaction (PCR) decreased in four cases, was stable in another four, and increased in three cases. An anti-mouse (HAMA) response developed in eight patients and anti-idiotypic antibodies appeared in six. Immune complexes that formed in patient sera during the treatment were shown to contain mostly envelope glycoprotein gp120 which decreased in nine of the eleven treated patients toward the end of treatment. Antibodies inhibiting gp120 binding to CD4 became detectable or increased in six patients during immunotherapy. Serology of the HIV-1 V3 region was studied for both the HIV-1 IIIB and MN strains with no or very small changes in titer or avidity after treatment. No change in neutralizing titers to strain HTLVIIIB was observed in serum samples collected before and after treatment was terminated. In nine of the eleven patients stimulation of the T lymphocytes to proliferate in vitro when activated by phytohemagglutinin (PHA) was shown to be increased compared to before treatment. Increased T-cell proliferation was also noted with several antigens such as HIV-1 recombinant antigens, cytomegalovirus (CMV), tetanus toxoid (TT), and purified protein derivate of mycobacterium tuberculosis (PPD). These findings indicate a decreased total gp120 content in serum, permitting better T-cell activation.
Immunization Therapy for Alzheimer Disease: A Comprehensive Review of Active Immunization Strategies (2010)

Based on the amyloid cascade hypothesis, various strategies targeting amyloid β protein (Aβ) have been invented for prevention and treatment of Alzheimer disease (AD). Active and passive immunizations with Aβ and Aβ antibodies successfully reduced AD pathology and improved cognitive functions in an AD mouse model. However, active immunization with AN-1792, a mixture of Aβ1-42 peptide and adjuvant QS21 induced autoimmune encephalitis in humans. Surprisingly, although AN-1792 cleared senile plaque amyloid, it showed no benefit in humans. It is speculated that AN-1792 failed in deleting more toxic forms of Aβ such as oligomers and intracellular Aβ, suggesting that newly developing vaccines should delete these toxic molecules. Since T cell epitopes exist mainly in the C-terminal portion of Aβ, vaccines using shorter N-terminal peptides are under development. In addition, since T helper 1 (Th1) immune responses activate encephalitogenic T cells and induce continuous inflammation in the central nervous system, vaccines inducing Th2 immune responses seem to be more promising. These are N-terminal short Aβ peptides with Th2 adjuvant or Th2-stimulating molecules, DNA vaccines, recombinant viral vector vaccines, recombinant vegetables and others. Improvement of vaccines will be also achieved by the administration method, because Th2 immune responses are mainly induced by mucosal or trans-cutaneous immunizations. Here I review recent progress in active immunization strategies for AD.
Loss of constitutional heterozygosity in colorectal tumors from patients with familial polyposis coli and those with nonpolyposis colorectal carcinoma. (1989)

Familial polyposis coli (FPC) is an autosomal dominant tumorigenic disorder, the major gene of which is mapped to chromosome 5q. We searched for a gene loss in colorectal tumors from FPC patients, as related to tumorigenesis by inactivation of tumor suppression genes, using restriction fragment length polymorphism analysis. The findings were compared with those in the case of nonpolyposis colorectal carcinomas (NPCC). We examined specimens from 39 FPC patients, including 21 adenocarcinomas and 49 adenomas, and 23 colorectal carcinomas from 22 NPCC patients. For this, we used 53 polymorphic DNA markers on all autosomes. Frequent loss of heterozygosity in colorectal carcinoma from FPC patients was observed on chromosomes 5 (24%), 14 (20%), 17 (31%), 18 (40%), and 22 (35%) and also on chromosomes 5 (32%), 14 (30%), 17 (27%), 18 (20%), and 22 (19%) in NPCC. Although loss of heterozygosity in adenoma from FPC patients was observed on nine chromosomes, the frequencies were less than 7%. As we fractionated tumors only macroscopically, actual frequencies of loss of heterozygosity are probably somewhat higher. However, these results do suggest that tumor suppression genes for colorectal carcinoma may locate on chromosomes 5, 14, 17, 18, and 22 and that they may play a critical role in carcinogenesis in both FPC and NPCC patients.
Blocking UV‐Induced eIF2α Phosphorylation with Small Molecule Inhibitors of GCN2 (2009)

The eIF2alpha kinase general control non-depressible 2 integrates translation initiation rates to amino acid availability. General control non-depressible 2 also regulates translation initiation during synaptic plasticity and GCN2(-/-) mice show improved memory compared with wild-type mice with a reduced threshold for triggering late long-term potentiation. This property suggests that inhibiting general control non-depressible 2 function might represent a therapeutic avenue for improving memory. We screened for general control non-depressible 2 inhibitors using a small library of known kinase inhibitors and ATP-analogs and identified three compounds--indirubin-3'-monoxime, SP600125 and a SyK inhibitor with activity against general control non-depressible 2. All three compounds inhibit the ability of general control non-depressible 2 to phosphorylate eIF2alphain vitro as well as in vivo following UV-treatment of mouse embryonic fibroblasts. Using computer-assisted modeling, we modeled the binding of the inhibitors in the ATP-binding site of general control non-depressible 2. This work provides the molecular basis for undertaking structure-activity relationships of these compounds in order to develop specific inhibitors of general control non-depressible 2.
A 60-ns 4-Mbit CMOS DRAM with built-in selftest function (1987)

A 4-Mb CMOS DRAM measuring 6.9/spl times/16.11 mm/SUP 2/ has been fabricated using a 0.9-/spl mu/m twin-tub CMOS, triple-poly, single-metal process technology. N-channel depletion-type trench cells, 2.5/spl times/5.5 /spl mu/m/SUP 2/ each, are incorporated in a p-well. A novel built-in selftest (BIST) function which enables a simultaneous and automatic test of all the memory devices on a board is introduced to reduce the RAM testing time in a system. This function is effective for system maintenance and a daily start-up test even in a relatively small system. A high-speed low-power 4-Mb CMOS DRAM with 60-ns access time, 50-mA active current, and 200-/spl mu/A standby current is realized by widening the DQ line bus which connects the sense amplifiers with DQ buffers, thereby reducing the parasitic capacitance of the DQ lines.
Protein Phosphatase 2A and Phosphoprotein SET Regulate Androgen Production by P450c17 (2003)

Cytochrome P450c17 catalyzes 17 alpha-hydroxylation needed for cortisol synthesis and 17,20 lyase activity needed to produce sex steroids. Serine phosphorylation of P450c17 specifically increases 17,20 lyase activity, but the physiological factors regulating this effect remain unknown. Treating human adrenal NCI-H295A cells with the phosphatase inhibitors okadaic acid, fostriecin, and cantharidin increased 17,20 lyase activity, suggesting involvement of protein phosphatase 2A (PP2A) or 4 (PP4). PP2A but not PP4 inhibited 17,20 lyase activity in microsomes from cultured cells, but neither affected 17 alpha-hydroxylation. Inhibition of 17,20 lyase activity by PP2A was concentration-dependent, could be inhibited by okadaic acid, and was restored by endogenous protein kinases. PP2A but not PP4 coimmunoprecipitated with P450c17, and suppression of PP2A by small interfering RNA increased 17,20 lyase activity. Phosphoprotein SET found in adrenals inhibited PP2A, but not PP4, and fostered 17,20 lyase activity. The identification of PP2A and SET as post-translational regulators of androgen biosynthesis suggests potential additional mechanisms contributing to adrenarche and hyperandrogenic disorders such as polycystic ovary syndrome.
Microarchitectures for Managing Chip Revenues under Process Variations (2008)

As transistor feature sizes continue to shrink intothe sub-90nm range and beyond, the effects of process variationson critical path delay and chip yields have amplified. A commonconcept to remedy the effects of variation is speed-binning, bywhich chips from a single batch are rated by a discrete range offrequencies and sold at different prices. In this paper, we discussstrategies to modify the number of chips in different bins andhence enhance the profits obtained from them. Particularly, wepropose a scheme that introduces a small Substitute Cacheassociated with each cache way to replicate the data elementsthat will be stored in the high latency lines. Assuming a fixedpricing model, this method increases the revenue by as much as13.8% without any impact on the performance of the chips.
Synthesis of programmable integrases (2009)

Accurate modification of the 3 billion-base-pair human genome requires tools with exceptional sequence specificity. Here, we describe a general strategy for the design of enzymes that target a single site within the genome. We generated chimeric zinc finger recombinases with cooperative DNA-binding and catalytic specificities that integrate transgenes with >98% accuracy into the human genome. These modular recombinases can be reprogrammed: New combinations of zinc finger domains and serine recombinase catalytic domains generate novel enzymes with distinct substrate sequence specificities. Because of their accuracy and versatility, the recombinases/integrases reported in this work are suitable for a wide variety of applications in biological research, medicine, and biotechnology where accurate delivery of DNA is desired.
Blood vessel maturation in a 3‐dimensional spheroidal coculture model: direct contact with smooth muscle cells regulates endothelial cell quiescence and abrogates VEGF responsiveness (2001)

Paracrine interactions between endothelial cells (EC) and mural cells act as critical regulators of vessel wall assembly, vessel maturation and define a plasticity window for vascular remodeling. The present study was aimed at studying blood vessel maturation processes in a novel 3-dimensional spheroidal coculture system of EC and smooth muscle cells (SMC). Coculture spheroids differentiate spontaneously in a calcium-dependent manner to organize into a core of SMC and a surface layer of EC, thus mimicking the physiological assembly of blood vessels with surface lining EC and underlying mural cells. Coculture of EC with SMC induces a mature, quiescent EC phenotype as evidenced by 1) a significant increase in the number of junctional complexes of the EC surface layer, 2) a down-regulation of PDGF-B expression by cocultured EC, and 3) an increased resistance of EC to undergo apoptosis. Furthermore, EC cocultured with SMC become refractory to stimulation with VEGF (lack of CD34 expression on VEGF stimulation; inability to form capillary-like sprouts in a VEGF-dependent manner in a 3-dimensional in gel angiogenesis assay). In contrast, costimulation with VEGF and Ang-2 induced sprouting angiogenesis originating from coculture spheroids consistent with a model of Ang-2-mediated vessel destabilization resulting in VEGF responsiveness. Ang-2 on its own was able to stimulate endothelial cells in the absence of Ang-1 producing SMC, inducing lateral sheet migration as well as in gel sprouting angiogenesis. Taken together, the data establish the spheroidal EC/SMC system as a powerful cell culture model to study paracrine interactions in the vessel wall and provide functional evidence for smooth muscle cell-mediated quiescence effects on endothelial cells.
<title>Practical video indexing and retrieval system</title> (1998)

We integrated a practical digital video database system based on language and image analysis with components from digital video processing, still image search, information retrieval, closed captioning processing. The attempt is to utilize the multiple modalities of information in video and implement data fusion among the multiple modalities; image information, speech/dialog information, closed captioning information, sound track information such as music, gunfire, explosion, caption information, motion information, temporal information. Effort is made to allow access video contents at different levels including video program level, scene level, shot level, and object level. Approaches of browsing, subject-based classification, and random retrieving are available to gain access to the contents.