gebhart/patrepeval huggingface dataset:
Molecular mechanisms of necrosis in glioblastoma: The role of glutamate excitotoxicity (2009)

Glioblastomas continue to rank among the most lethal primary human tumors. Despite treatment with the most rigorous surgical interventions along with the most optimal chemotherapeutic and radiation regimens, the median survival is just 12-15 mo for patients with glioblastoma. Among the histological hallmarks of glioblastoma, necrosis has been demonstrated to be a powerful predictor of poor patient prognosis. Over the years, there have been many advances in our understanding of the molecular mechanisms underlying glioblastoma formation, yet the mechanisms that lead to tumor necrosis remain unclear. One pathway that may lead to necrosis in glioblastoma involves the neurotransmitter, glutamate, which has been shown to accumulate in the peritumoral fluid as a result of decreased cellular uptake by glioblastoma cells. This accumulation leads to subsequent glutamate excitotoxicity and probable necrosis through a massive elevation of intracellular Ca(2+) and reduction in cellular ATP levels. We propose that a pathway involving tumor necrosis factor-alpha (TNFalpha), astrocyte-elevated gene-1 (AEG-1) and nuclear factor-kappaB (NFkappaB) leads to decreased glutamate uptake through coordinated downregulation of the excitatory amino acid transporter 2 (EAAT2), the glutamate transporter responsible for the majority of glutamate uptake in the human brain. In addition, we suggest that AEG-1 signaling, loss of phosphatase and tensin homolog (PTEN), and ionotropic glutamate receptor activity lead to AKT pathway activation, which results in nutrient overconsumption and necrosis. Together, these pathways provide a new perspective on glioblastoma necrosis involving the process of glutamate excitotoxicity. Future research should address the components of these molecular pathways in order to better understand the mechanism of necrosis in glioblastoma and to begin to develop targeted therapies that may improve patient prognosis in the future.
Self-Assembled Colloidal Superparticles from Nanorods (2012)

Colloidal superparticles are nanoparticle assemblies in the form of colloidal particles. The assembly of nanoscopic objects into mesoscopic or macroscopic complex architectures allows bottom-up fabrication of functional materials. We report that the self-assembly of cadmium selenide-cadmium sulfide (CdSe-CdS) core-shell semiconductor nanorods, mediated by shape and structural anisotropy, produces mesoscopic colloidal superparticles having multiple well-defined supercrystalline domains. Moreover, functionality-based anisotropic interactions between these CdSe-CdS nanorods can be kinetically introduced during the self-assembly and, in turn, yield single-domain, needle-like superparticles with parallel alignment of constituent nanorods. Unidirectional patterning of these mesoscopic needle-like superparticles gives rise to the lateral alignment of CdSe-CdS nanorods into macroscopic, uniform, freestanding polymer films that exhibit strong photoluminescence with a striking anisotropy, enabling their use as downconversion phosphors to create polarized light-emitting diodes.
HSV-1-Based Vectors for Gene Therapy of Neurological Diseases and Brain Tumors: Part I. HSV-1 Structure, Replication and Pathogenesis (1999)

The design of effective gene therapy strategies for brain tumors and other neurological disorders relies on the understanding of genetic and pathophysiological alterations associated with the disease, on the biological characteristics of the target tissue, and on the development of safe vectors and expression systems to achieve efficient, targeted and regulated, therapeutic gene expression. The herpes simplex virus type 1 (HSV-1) virion is one of the most efficient of all current gene transfer vehicles with regard to nuclear gene delivery in central nervous system-derived cells including brain tumors. HSV-1-related research over the past decades has provided excellent insight into the structure and function of this virus, which, in turn, facilitated the design of innovative vector systems. Here, we review aspects of HSV-1 structure, replication and pathogenesis, which are relevant for the engineering of HSV-1-based vectors.
Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses. (2003)

Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia naïve mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOM/rF-CEA/ TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity.
Chemically prepared magnetic nanoparticles (2004)

Nanotechnology has spurred efforts to design and produce nanoscale components for incorporation into devices. Magnetic nanoparticles are an important class of functional materials, possessing unique magnetic properties due to their reduced size (below 100 nm) with potential for use in devices with reduced dimensions. Recent advances in processing by chemical synthesis and the characterisation of magnetic nanoparticles are the focus of this review. Emphasis has been placed on the various solution chemistry techniques used to synthesise particles, including: precipitation, borohydride reduction, hydrothermal, reverse micelles, polyol, sol–gel, thermolysis, photolysis, sonolysis, multisynthesis processing and electrochemical techniques. The challenges and methods for examining the structural, morphological, and magnetic properties of these materials are described.
Polymeric nanotherapeutics: clinical development and advances in stealth functionalization strategies (2013)

Long-circulating polymeric nanotherapeutics have garnered increasing interest in research and in the clinic owing to their ability to improve the solubility and pharmacokinetics of therapeutic cargoes. Modulation of carrier properties promises more effective drug localization at the disease sites and can lead to enhanced drug safety and efficacy. In the present review, we highlight the current development of polymeric nanotherapeutics in the clinic. In light of the importance of stealth properties in therapeutic nanoparticles, we also review the advances in stealth functionalization strategies and examine the performance of different stealth polymers in the literature. In addition, we discuss the recent development of biologically inspired "self" nanoparticles, which present a differing stealth concept from conventional approaches.
Umbilical Cord Blood Cells (2009)

The umbilical cord of a healthy neonate contains within it a multipotential treatment for a myriad of diseases and injuries. What was once tossed into the biohazard waste without a second thought is now known to be a goldmine of antigenically immature cells that rival the use of bone marrow for reconstitution of blood lineages. Umbilical cord blood (UCB) is emerging as an effective and feasible clinical treatment as its availability increases and benefits are realized. Basic science research has demonstrated a broad therapeutic capacity ranging from cell replacement to cell protection and anti-inflammation in a number of animal disease and injury models. UCB is easily obtained with no harm to infant or mother and can be stored at cryogenic temperatures with relatively little loss of cells upon thaw. The heterogeneous mononuclear fraction has been identified and characterized and transplanted both locally and systemically to treat animal models of stroke, myocardial infarction, Amytrophic Lateral Sclerosis, San Filippo, spinal cord injury, traumatic brain injury, and age-related neurodegeneration, among others. In the pages to follow, we share protocols for the identification and research use of the mononuclear cell fraction of UCB.
Allergen-derived long peptide immunotherapy down-regulates specific IgE response and protects from anaphylaxis (2000)

To evaluate a long peptide-based allergy vaccine in a murine model, CBA/J mice were sensitized with low dose alum-adsorbed phospholipase A2 (PLA2), a major bee venom allergen. Presensitized mice were treated by daily i.p. injections of a mixture of three long overlapping peptides (44- to 60-mer) spanning the entire PLA2 molecule (100 microg/peptide) for 6 consecutive days. This therapeutic approach induced a sharp drop in PLA2-specific IgE, an increase in specific IgG2a, and a marked T cell hyporesponsiveness. T cell cytokine secretion was characterized by a shift from a Th2 to a Th1 profile. Prophylactic treatment of naive mice with long peptides prior to sensitization with PLA2 induced a comparable modulation of B and T cell responses. Upon i.p. challenge with native PLA2, presensitized mice treated with the long peptide mixture were fully protected from anaphylaxis. This indicated that allergen-derived long overlapping peptides were safe and able to modulate an established Th2 response or to prevent its development. Furthermore, long peptide-based immunotherapy provided clinical protection against anaphylaxis, thus appearing as a promising approach of the therapy of allergic diseases.
Adaptive coding and modulation in MIMO OFDMA systems (2008)

Adaptive coding and modulation are well known techniques for enhancing the performance of systems transmitting over quasi-static fading channels. Especially their application in OFDM based systems promises gains in spectral efficiency. In former work we presented an efficient method for the joint optimization of code rate and modulation formats if rate-compatible punctured codewords are mapped onto sub-symbols with heterogeneous channel quality and modulation formats. In this paper, we demonstrate the application of our scheme to MIMO techniques. More specifically, we investigate non-orthogonal spatial multiplexing schemes in bit-interleaved coded OFDM systems. The techniques are evaluated within the context of the OFDMA/TDMA system designed within the EU FP6 Integrated Project WINNER.
Effect of inspiratory pressure support on the arousal response to CO2 in sleeping dogs (1995)

The aim of the present study was to test the hypothesis that afferent mechanoreceptor stimuli from the respiratory muscles contribute to the arousal response to CO2 from both non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. We studied three dogs implanted with electromyographic (EMG) electrodes in the costal diaphragm and transversus abdominis muscles. During sleep, the animals were exposed to supplemental CO2 in O2 to maintain a constant level of end-tidal PCO2 (50 Torr for NREM, 56 Torr for REM) and breathed either spontaneously (SB) or with inspiratory pressure support (IPS). The arousal response was quantified as the time from initiation of CO2 administration to arousal. EMG activity of the costal diaphragm on IPS was decreased to approximately 70% (P < 0.01) of that during SB trials for both NREM and REM, whereas EMG activity of the transversus abdominis muscles did not differ between SB and IPS for either sleep state. The mean time to arousal was increased during NREM from 128.3 +/- 24.7 s (SB) to 216.8 +/- 38.7 s (IPS) (P < 0.025) and was increased during REM from 144.9 +/- 26.1 s (SB) to 219.0 +/- 23.8 s (IPS) (P < 0.001). In summary, in support of our hypothesis, we found that suppression of inspiratory muscle activity, without augmented expiratory muscle activity, delayed the arousal response to hypercapnia during both NREM and REM sleep.
A novel LIF‐CE method for the separation of hyaluronan‐ and chondroitin sulfate‐derived disaccharides: Application to structural and quantitative analyses of human plasma low‐ and high‐charged chondroitin sulfate isomers (2007)

The report describes a rapid and simple CE method using LIF detection for the analysis of unsaturated disaccharides obtained from enzymatic depolymerization of plasma chondroitin sulfate (CS) isomers. The disaccharide reducing groups were labeled with 2-aminoacridone (AMAC). The fluorotagged products can be separated by reversed-polarity CE using a sodium acetate buffer, pH 3.8, in the presence of 0.05% methylcellulose. The choice of the appropriate electrophoretic conditions was performed after a deep analysis of the most important parameters affecting analyte separation. In particular, the effect of both run buffer concentration and pH on resolution, efficiency, migration times, and peak area was evaluated. The selected electrophoretic conditions allowed us to separate the CS isomers-derived Delta-disaccharides in less than 12 min, also resolving the nonsulfated disaccharides released from CS isomers from those released from hyaluronan (HA). Moreover, these conditions gave a good reproducibility of both the migration times (CV%, 0.25) and the peak areas (CV%, 1.4). Intra- and interassay CV were 5.37 and 7.23%, respectively, and analytical recovery was about 86%. The applicability of the above method to the quantitative and structural disaccharide analyses of plasma CS isomers was investigated. Data obtained from 44 healthy human subjects were compared with those obtained by a fluorophore-assisted carbohydrate electrophoresis (FACE) reference assay, by using the Passing and Bablok regression and Bland-Altman tests. The developed method could represent a good tool for an ultrasensitive analysis of CS isomers in biological samples from different sources, particularly when samples are available in very low amounts.
Spatial restriction of α4 integrin phosphorylation regulates lamellipodial stability and α4β1-dependent cell migration (2003)

Integrins coordinate spatial signaling events essential for cell polarity and directed migration. Such signals from alpha4 integrins regulate cell migration in development and in leukocyte trafficking. Here, we report that efficient alpha4-mediated migration requires spatial control of alpha4 phosphorylation by protein kinase A, and hence localized inhibition of binding of the signaling adaptor, paxillin, to the integrin. In migrating cells, phosphorylated alpha4 accumulated along the leading edge. Blocking alpha4 phosphorylation by mutagenesis or by inhibition of protein kinase A drastically reduced alpha4-dependent migration and lamellipodial stability. alpha4 phosphorylation blocks paxillin binding in vitro; we now find that paxillin and phospho-alpha4 were in distinct clusters at the leading edge of migrating cells, whereas unphosphorylated alpha4 and paxillin colocalized along the lateral edges of those cells. Furthermore, enforced paxillin association with alpha4 inhibits migration and reduced lamellipodial stability. These results show that topographically specific integrin phosphorylation can control cell migration and polarization by spatial segregation of adaptor protein binding.
Steric Control of Conductivity in Highly Conjugated Polythiophenes (2001)

A series of 4-alkylidene-, 4-alkyl-, and 4,4‘-dialkyl-substituted 4H-[5,1-b;1,5-b‘]cyclopentabithiophenes was designed in which the substituents in position 4 occupy well-defined areas in the space around the bithiophene unit to evaluate the effects played by their steric properties on the electrical conductivity of the materials resulting from anodic polymerization. The geometry of all the monomers was either inferred from X-ray diffractometric analysis or calculated through molecular modeling techniques. The polymers were prepared under identical experimental conditions and characterized by CV, IR, and UV−vis spectroscopy and in situ conductivity. Various types of molecular descriptors were utilized to create QSPR models, which demonstrated a good relationship between the molecular structure of the monomers and the conductivity of the corresponding polymers.
Urinary C-type natriuretic peptide excretion: a potential novel biomarker for renal fibrosis during aging (2011)

Renal aging is characterized by structural changes in the kidney including fibrosis, which contributes to the increased risk of kidney and cardiac failure in the elderly. Studies involving healthy kidney donors demonstrated subclinical age-related nephropathy on renal biopsy that was not detected by standard diagnostic tests. Thus there is a high-priority need for novel noninvasive biomarkers to detect the presence of preclinical age-associated renal structural and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective properties and is present in the kidney; however, its modulation during aging remains undefined. We assessed circulating and urinary CNP in a Fischer rat model of experimental aging and also determined renal structural and functional adaptations to the aging process. Histological and electron microscopic analysis demonstrated significant renal fibrosis, glomerular basement membrane thickening, and mesangial matrix expansion with aging. While plasma CNP levels progressively declined with aging, urinary CNP excretion increased, along with the ratio of urinary to plasma CNP, which preceded significant elevations in proteinuria and blood pressure. Also, CNP immunoreactivity was increased in the distal and proximal tubules in both the aging rat and aging human kidneys. Our findings provide evidence that urinary CNP and its ratio to plasma CNP may represent a novel biomarker for early age-mediated renal structural alterations, particularly fibrosis. Thus urinary CNP could potentially aid in identifying subjects with preclinical structural changes before the onset of symptoms and disease, allowing for the initiation of strategies designed to prevent the progression of chronic kidney disease particularly in the aging population.
Characterization of front and back Si-SiO/sub 2/ interfaces in thick- and thin-film silicon-on-insulator MOS structures by the charge-pumping technique (1989)

It is shown that the charge-pumping technique can be successfully applied to SOI structures, directly providing important and reliable information about the quality of both front- and back-gate interfaces. The possibility of performing measurements on a transistor level makes direct correlation with other MOS characteristics and material parameters possible. In particular, the ability of this technique to perform measurements on thin-film transistors and to separate the information from front and back gates makes it indispensable for characterization of advanced SOI CMOS structures. Although the technique was demonstrated only on 5- mu m channel length devices, it has sufficient sensitivity to be applicable to transistors of micrometer and submicrometer dimensions. Charge-pumping measurements on laser-recrystallized SOI MOSFETs showed that the front interface is only slightly deteriorated compared to that of bulk MOSFET devices, while the back interface is of a substantially lower quality, with about 10 times higher interface trap densities.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Neisseria lactamica Protects against Experimental Meningococcal Infection (2002)

Immunological and epidemiological evidence suggests that the development of natural immunity to meningococcal disease results from colonization of the nasopharynx by commensal Neisseria spp., particularly with N. lactamica. We report here that immunization with N. lactamica killed whole cells, outer membrane vesicles, or outer membrane protein (OMP) pools and protected mice against lethal challenge by a number of diverse serogroup B and C meningococcal isolates in a model of bacteremic infection. Sera raised to N. lactamica killed whole cells, OMPs, or protein pools were found to cross-react with meningococcal isolates of a diverse range of genotypes and phenotypes. The results confirm the potential of N. lactamica to form the basis of a vaccine against meningococcal disease.
Causes and consequences of DNA hypomethylation in human cancer (2005)

While specific genes are hypermethylated in the genome of cancer cells, overall methylcytosine content is often decreased as a consequence of hypomethylation affecting many repetitive sequences. Hypomethylation is also observed at a number of single-copy genes. While global hypomethylation is highly prevalent across all cancer types, it often displays considerable specificity with regard to tumor type, tumor stage, and sequences affected. Following an overview of hypomethylation alterations in various cancers, this review focuses on 3 hypotheses. First, hypomethylation at a single-copy gene may occur as a 2-step process, in which selection for gene function follows upon random hypo methylation. In this fashion, hypomethylation facilitates the adaptation of cancer cells to the ever-changing tumor tissue microenvironment, particularly during metastasis. Second, the development of global hypomethylation is intimately linked to chromatin restructuring and nuclear disorganization in cancer cells, reflected in a large number of changes in histone-modifying enzymes and other chromatin regulators. Third, DNA hypomethylation may occur at least partly as a consequence of cell cycle deregulation disturbing the coordination between DNA replication and activity of DNA methyltransferases. Finally, because of their relation to tumor progression and metastasis, DNA hypomethylation markers may be particularly useful to classify cancer and predict their clinical course.
The quantitative proteomic response of Synechocystis sp. PCC6803 to phosphate acclimation (2013)

This acclimation response bears strong similarity to the previously reported response to nitrogen deprivation within Synechocystis sp. PCC 6803. However, it also demonstrates some characteristics of desiccation stress, such as the regulation of fatty acids and increased abundance of rehydrin in the 3% Pi culture.