gebhart/patrepeval huggingface dataset:
Gradient index metamaterials (2005)

Metamaterials--artificially structured materials with tailored electromagnetic response--can be designed to have properties difficult or impossible to achieve with traditional materials fabrication methods. Here we present a structured metamaterial, based on conducting split ring resonators (SRRs), which has an effective index of refraction with a constant spatial gradient. We experimentally confirm the gradient by measuring the deflection of a microwave beam by a planar slab of the composite metamaterial over a range of microwave frequencies. The gradient index metamaterial may prove an advantageous alternative approach to the development of gradient index lenses and similar optics, especially at higher frequencies. In particular, the gradient index metamaterial we propose may be suited for terahertz applications, where the magnetic resonant response of SRRs has recently been demonstrated.
Heregulin ameliorates the dystrophic phenotype in mdx mice (2004)

Duchenne's muscular dystrophy (DMD) is a fatal neuromuscular disease caused by absence of dystrophin. Utrophin is a chromosome 6-encoded dystrophin-related protein (DRP), sharing functional motifs with dystrophin. Utrophin's ability to compensate for dystrophin during development and when transgenically overexpressed has provided an important impetus for identifying activators of utrophin expression. The utrophin promoter A is transcriptionally regulated in part by heregulin-mediated, extracellular signal-related kinase-dependent activation of the GABP(alpha/beta) transcription factor complex. Therefore, this pathway offers a potential mechanism to modulate utrophin expression in muscle. We tested the ability of heregulin to improve the dystrophic phenotype in the mdx mouse model of DMD. Intraperitoneal injections of a small peptide encoding the epidermal growth factor-like region of heregulin ectodomain for 3 months in vivo resulted in up-regulation of utrophin, a marked improvement in the mechanical properties of muscle as evidenced by resistance to eccentric contraction mediated damage, and a reduction of muscle pathology. The amelioration of dystrophic phenotype by heregulin-mediated utrophin up-regulation offers a pharmacological therapeutic modality and obviates many of the toxicity and delivery issues associated with viral vector-based gene therapy for DMD.
Identification of a Novel Bone Morphogenetic Protein-responsive Gene That May Function as a Noncoding RNA (1998)

Bone morphogenetic proteins (BMPs)/osteogenic proteins (OPs), members of the transforming growth factor-beta superfamily, have a wide variety of effects on many cell types including osteoblasts and chondroblasts, and play critical roles in embryonic development. BMPs transduce their effects through binding to two different types of serine/threonine kinase receptors, type I and type II. Signaling by these receptors is mediated by the recently identified Smad proteins. Despite the rapid progress in understanding of the signaling mechanism downstream of BMP receptors, the target genes of BMPs are poorly understood in mammals. Here we identified a novel gene, termed BMP/OP-responsive gene (BORG), in C2C12 mouse myoblast cell line which trans-differentiates into osteoblastic cells in response to BMPs. Expression of BORG was dramatically induced in C2C12 cells by the treatment with BMP-2 or OP-1 within 2 h and peaked at 12-24 h, whereas transforming growth factor-beta had a minimal effect. BMP-dependent expression of BORG was also detected in other cell types which are known to respond to BMPs, suggesting that BORG is a common target gene of BMPs. Cloning and sequence analysis of BORG cDNA and the genomic clones revealed that, unexpectedly, the transcript of BORG lacks any extensive open reading frames and contains a cluster of multiple interspersed repetitive sequences in its middle part. The unusual structural features suggested that BORG may function as a noncoding RNA, although it is spliced and polyadenylated as authentic protein-coding mRNAs. Together with the observation that transfection of antisense oligonucleotides of BORG partially inhibited BMP-induced differentiation in C2C12 cells, it is possible that a new class of RNA molecules may have certain roles in the differentiation process induced by BMPs.
Photoconductivity from PbS-nanocrystal∕semiconducting polymer composites for solution-processible, quantum-size tunableinfrared photodetectors (2004)

We report photoconductivity at infrared wavelengths, 975–1300nm, from a polymer∕nanocrystal quantum dot composite. Biased films of the conjugated polymer poly[2-methoxy-5-(2′-ethylhexyloxy-p-phenylenevinylene)] (MEH-PPV) sensitized with PbS nanocrystals (∼5nm diameter) demonstrate photocurrent at wavelengths beyond the response of the polymer and corresponding to the absorption of the nanocrystals. The photocurrent is attributed to absorption in the nanocrystals with subsequent hole transfer to the polymer and had an internal quantum efficiency of ∼5×10−6to∼10−5charges∕photon at 5V bias.
Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82 (1995)

Previously, we have shown that CD81 and CD82, two members of the transmembrane 4 superfamily, form multimolecular membrane complexes by associating with each other and with CD4 or CD8 in T cells. In the present study, we further analyzed the molecular basis of the CD4 association with CD81 and CD82 by co-precipitation experiments. First, we examined the regions of CD4 involved in the association with CD81 and CD82 by employing chimeric proteins generated from CD4 and CD2. It was confirmed that CD4, but not CD2, was capable of binding with CD81 and CD82 in transfected cells. We found that the cytoplasmic region of CD4 was sufficient for the chimeric proteins to co-precipitate CD81, while both the cytoplasmic and extracellular regions of CD4 were required for them to efficiently co-precipitate CD82. We next found, by using truncated CD4 lacking the C-terminal 31 amino acids or mutated CD4 with the cysteine residues at 394 and 397 replaced by serine, that the p56lck binding site or the covalent modification with palmitic acid was not necessary for CD4 to associate with CD81 and CD82. Finally, we found that the binding of p56lck to CD4 strongly inhibited its association with CD81 and CD82. It is, therefore, suggested that CD4 exists at least in two physical states, one associated with p56lck and another associated with CD81 and CD82 in the absence or uncoupling of p56lck.
Effect of haemodialysis on plasma ADH levels, plasma renin activity and plasma aldosterone levels in patients with end-stage renal disease (1985)

Changes in plasma ADH levels and plasma aldosterone levels (PA) were studied in patients with end-stage renal disease (N = 40). The patients were divided into two groups according to their plasma renin activity (PRA) into a low renin (LR, n = 9) and a high renin group (HR, n = 31). The metabolic clearance rate (MCR) of plasma ADH was also investigated in 4 patients and 5 normal volunteers. Additionally, it was examined whether plasma ADH, aldosterone and renin were permeable through the dialysis membrane. Pre- and post-dialysis plasma ADH levels in LR were similar to those in the HR group. However, pre- and post-dialysis PA in the HR group were significantly greater than those in the LR group. Post-dialysis PRA was significantly increased in HR compared to pre-dialysis, but not in LR. Pre- and post-dialysis plasma osmolality was increased in both groups, but effective plasma osmolality (EPosm) was within the normal range. There was a significant correlation between EPosm and plasma ADH level both before and after haemodialysis, but the majority of the abnormally high values of ADH compared to the normal values was found within the normal range of EPosm. The patients exhibited high blood pressure and a rise in body weight, and haemodialysis caused a significant fall in body weight and blood pressure in both groups. MCR of ADH was significantly lower in the patients than that in normal subjects. Plasma ADH proved to be permeable through the dialysis membrane in all cases, but aldosterone in only a few cases. Renin was not permeable.
Glycolysis and growth rate in normal and in hexokinase-transfected NIH-3T3 cells. (1994)

The glycolytic enzyme hexokinase plays a key role in regulating cell energy metabolism. Its activity has been associated with cell growth rate and, notably, with neoplastic transformation. NIH-3T3 cells were transfected with a tumor hexokinase cDNA. The transfected cells showed increased hexokinase amount and activity, mainly located in the particulate cellular fraction, increased glycolytic rate evaluated as lactate production, and, finally, enhanced growth rate. These data may suggest that high hexokinase activity might be not merely the consequence of peculiar metabolic demands by actively replicating normal or cancer cells, but also a modification able per se to drive, at least partially, a more intense mitotic activity.
Individualized quality of life, standardized quality of life, and distress in patients undergoing a phase I trial of the novel therapeutic Reolysin (reovirus). (2005)

Individualized QL is easy to assess in seriously ill cancer patients, provides useful information relative to each individual, and is related to standard QL measures. Repeated assessment of individualized QL of patients in Phase I trials would be a useful addition to the research.
Adhesion behavior of rat lymphocytes to poly(ether)–poly(amino acid) block and graft copolymers (1986)

Block and graft copolymers consisting of poly(ether) and poly(amino acid) were synthesized, and adhesion behavior of rat lymphocytes to the surface of the film made from these copolymers was analyzed by the microsphere column method. Poly(ethylene glycol) (PEG) and poly(benzyl L-glutamate) (PBLG) were used as poly(ether) and poly(amino acid), respectively. Adhesion behavior of lymphocytes was found to depend on the content and chain length of the components in these copolymers.
A phase I study of BAY 43–9006 and gefitinib in patients with refractory or recurrent non-small-cell lung cancer (NSCLC) (2005)

3067 Background: Preclinical data in the A549 NSCLC xenograft model show that BAY 43–9006 (BAY) a dual-action Raf kinase and VEGFR inhibitor does not antagonize the effect of gefitinib. This phase I, single-center study was conducted to assess the safety and efficacy of this combination in patients (pts) with refractory or recurrent NSCLC. Methods: The dosing schedule was in two parts; part A, presented here, was to determine the optimal dose of BAY for use in part B, in which pharmacokinetic and pharmacodynamic parameters will be measured in 20 pts. Tumor response was assessed by RECIST. Results: 12 pts were treated (M:F = 6:6; median age 63 [range 46–78] years; ECOG status 0:1:2 = 5:6:1; number of prior systemic anti-cancer regimens 0:1:2:missing = 3:4:2:3). The first 6 pts received gefitinib 250 mg po qd with BAY 200 mg po bid, and the second 6 patients received gefitinib 250 mg po qd with BAY 400 mg po bid. The most common drug-related AEs were fatigue (75% of pts), diarrhea (75%) alanine aminotransferase (ALT; 58%), aspartate aminotransferase (AST; 42%), rash/desquamation (42%) and anorexia (42%), and were predominantly grade 1–2. Drug-related serious AEs were seen in 3 pts (diarrhea and ALT at BAY 200 mg bid, and dyspnea at BAY 400 mg bid). 1 (8%) partial response was achieved by a pt receiving BAY 200 mg bid and 8 (67%) pts had stable disease (SD) as best response (3 at BAY 200 mg bid, and 5 at 400 mg bid). Three patients died from disease progression and 4 are still on treatment. Conclusions: This study is the first to combine the novel targeted agent BAY with gefitinib. This combination was well-tolerated and led to tumor regression or SD in 9 of 12 pts. BAY 400 mg po bid combined with gefitinib 250 mg po qd is recommended for Part B of this study, which has accrued 7 patients. Results from part B will also be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer
A pilot tolerability and efficacy trial of sodium oxybate in ethanol‐responsive movement disorders (2005)

Sodium oxybate is currently approved in the United States exclusively for the treatment of cataplexy in narcoleptic patients. In a prior article published in this journal, we reported a patient with severe posthypoxic myoclonus whose myoclonus improved with ethanol and also with treatment with sodium oxybate. We extend this preliminary observation to five other patients with ethanol-responsive movement disorders in an open-label, dose-titration, add-on, 8-week trial. All five patients (one with severe alcohol-responsive posthypoxic myoclonus, two with epsilon-sarcoglycan-linked myoclonus-dystonia, and two with essential tremor) experienced improvement from baseline of 50% or greater as measured by blinded videotape review. Tolerability was satisfactory, with dose-dependent sedation as the most common side effect. Further studies of this drug in hyperkinetic movement disorders are warranted.
Mechanistic and Structural Analysis of a Family 31 α-Glycosidase and Its Glycosyl-enzyme Intermediate (2004)

We have determined the first structure of a family 31 alpha-glycosidase, that of YicI from Escherichia coli, both free and trapped as a 5-fluoroxylopyranosyl-enzyme intermediate via reaction with 5-fluoro-alpha-D-xylopyranosyl fluoride. Our 2.2-A resolution structure shows an intimately associated hexamer with structural elements from several monomers converging at each of the six active sites. Our kinetic and mass spectrometry analyses verified several of the features observed in our structural data, including a covalent linkage from the carboxylate side chain of the identified nucleophile Asp(416) to C-1 of the sugar ring. Structure-based sequence comparison of YicI with the mammalian alpha-glucosidases lysosomal alpha-glucosidase and sucrase-isomaltase predicts a high level of structural similarity and provides a foundation for understanding the various mutations of these enzymes that elicit human disease.
High operational stability of electrophosphorescent devices (2002)

Electrophosphorescent devices with fac-tris(2-phenylpyridine)iridium as the green emitting dopant have been fabricated with a variety of hole and exciton blocking materials. A device with aluminum(III)bis(2-methyl-8-quinolinato)4-phenylphenolate (BAlq) demonstrates an efficiency of 19 cd/A with a projected operational lifetime of 10 000 h, operated at an initial brightness of 500 cd/m2; or 50 000 h normalized to 100 cd/m2. An orange-red electrophosphorescent device with iridium(III) bis(2-phenylquinolyl-N,C2′)acetylacetonate as the dopant emitter and BAlq as the hole blocker demonstrates a maximum efficiency of 17.6 cd/A with a projected operational lifetime of 5000 h at an initial brightness of 300 cd/m2; or 15 000 h normalized to 100 cd/m2. The average voltage increase for both devices is &amp;lt;0.3 mV/h. The device operational lifetime is found to be inversely proportional to the initial brightness, typical of fluorescent organic light emitting devices.
The Subsystems Approach to Genome Annotation and its Use in the Project to Annotate 1000 Genomes (2005)

The release of the 1000th complete microbial genome will occur in the next two to three years. In anticipation of this milestone, the Fellowship for Interpretation of Genomes (FIG) launched the Project to Annotate 1000 Genomes. The project is built around the principle that the key to improved accuracy in high-throughput annotation technology is to have experts annotate single subsystems over the complete collection of genomes, rather than having an annotation expert attempt to annotate all of the genes in a single genome. Using the subsystems approach, all of the genes implementing the subsystem are analyzed by an expert in that subsystem. An annotation environment was created where populated subsystems are curated and projected to new genomes. A portable notion of a populated subsystem was defined, and tools developed for exchanging and curating these objects. Tools were also developed to resolve conflicts between populated subsystems. The SEED is the first annotation environment that supports this model of annotation. Here, we describe the subsystem approach, and offer the first release of our growing library of populated subsystems. The initial release of data includes 180 177 distinct proteins with 2133 distinct functional roles. This data comes from 173 subsystems and 383 different organisms.
Real‐time evidence of surface modification at polystyrene lattices by poloxamine 908 in the presence of serum: in vivo conversion of macrophage‐prone nanoparticles to stealth entities by poloxamine 908 (2003)

Intravenously injected polystyrene nanoparticles, which are prone to rapid sequestration by professional phagocytes, are converted to stealth entities by prior bolus intravenous injection of poloxamine 908. This behaviour is not due to alteration in macrophage phagocytic activity. Laser Doppler anemometry and surface plasmon resonance were used to unravel the mechanisms fundamental to generation of such stealth entities in vivo by poloxamine 908. Electrophoretic mobility of poloxamine pre-coated monodisperse polystyrene nanoparticles in serum, which behave as stealth entities in vivo, was similar to that of uncoated nanoparticles incubated in poloxamine pre-treated serum. This observation supported the notion that poloxamine in serum can modify the surface of nanoparticles with similar topography to that of stealth poloxamine pre-coated particles, i.e. with polyoxyethylene chains projected from the surface. Surface plasmon resonance optical phenomenon was used for real-time monitoring of protein-poloxamine interactions and adsorption at the polystyrene interface. It was found that poloxamine can not only adsorb to a serum-modified surface but in addition poloxamine in serum can form macromolecular complexes with high affinity for adsorption to a polystyrene lattice. A role for serum albumin in surface modification of nanoparticles by poloxamine 908 is also identified. Hence, our biophysical observations correlate precisely with the in vivo longevity of uncoated polystyrene nanoparticles in poloxamine pre-treated rats. This rational and sensitive biophysical approach has unravelled the probable mechanism fundamental to generation of stealth entities in vivo and therefore has application in the design and nano-engineering of stealth colloidal carriers for optimal biological performance.
Cationic Vectors in Ocular Drug Delivery (2004)

Despite extensive research in the field, the major problem in the ocular drug delivery domain still is rapid precorneal drug loss and poor corneal permeability. One of the approaches recently developed is the drug incorporation into cationic submicronic vectors which exploit the negative charges present at the corneal surface for increased residence time and penetration. This review will focus on the formulation of three main representative cationic colloids developed for ophthalmic delivery: liposomes, emulsions and nanoparticles (NP). Parameters such as choice of the vector type and size, nature of the cationic molecule, pH and ionic strength of the external phase and characteristics of the encapsulated drug will be discussed with accent on the relevance of the positive charge.
Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys (2013)

Adeno-associated virus (AAV) vectors delivered through the systemic circulation successfully transduce various target tissues in animal models. However, similar attempts in humans have been hampered by the high prevalence of neutralizing antibodies to AAV, which completely block vector transduction. We show in both mouse and nonhuman primate models that addition of empty capsid to the final vector formulation can, in a dose-dependent manner, adsorb these antibodies, even at high titers, thus overcoming their inhibitory effect. To further enhance the safety of the approach, we mutated the receptor binding site of AAV2 to generate an empty capsid mutant that can adsorb antibodies but cannot enter a target cell. Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery.
Antisense Expression of Protein Kinase Cα Inhibits the Growth and Tumorigenicity of Human Glioblastoma Cells (1994)

To investigate the role of protein kinase C (PKC) in the growth of astrocytic brain tumors, human glioblastoma cell line U-87 was stably transfected with the antisense complementary deoxyribonucleic acid encoding PKC alpha. The effect of selectively down-regulating the alpha isoform on other PKC isoforms, as well as serum-dependent proliferation and in vivo tumorigenicity, was determined. U-87 cells expressed high levels of PKC alpha and lesser amounts of the gamma, epsilon, and zeta isoforms, and a similar PKC isoform pattern was observed in two other human glioblastoma cell lines. Expression of the antisense PKC alpha complementary deoxyribonucleic acid resulted in no detectable PKC alpha by immunoblotting and a 95% reduction in total Ca2+/phospholipid-dependent PKC activity. U-87 cells expressing antisense PKC alpha exhibited an increase in doubling time in vitro, less serum-dependent growth, and reduced sensitivity to a selective PKC inhibitor, Ro 31-8220. The transplantation of U-87 cells expressing antisense PKC alpha into nude mice resulted in no tumor formation. These observations suggest that the inhibition of PKC alpha may be an important chemotherapeutic target for arresting the growth of glioblastomas.
p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway (2010)

p66Shc, a promoter of apoptosis, modulates oxidative stress response and cellular survival, but its role in the progression of diabetic nephropathy is relatively unknown. In this study, mechanisms by which p66Shc modulates high-glucose (HG)- or angiotensin (ANG) II-induced mitochondrial dysfunction were investigated in renal proximal tubular cells (HK-2 cells). Expression of p66Shc and its phosphorylated form (p-p66Shc, serine residue 36) and apoptosis were notably increased in renal tubules of diabetic mice, suggesting an increased reactive oxygen species production. In vitro, HG and ANG II led to an increased expression of total and p-p66Shc in HK-2 cells. These changes were accompanied with increased production of mitochondrial H(2)O(2), reduced mitochondrial membrane potential, increased translocation of mitochondrial cytochrome c from mitochondria into cytosol, upregulation of the expression of caspase-9, and ultimately reduced cell survival. Overexpression of a dominant-negative Ser36 mutant p66Shc (p66ShcS36A) or treatment of p66Shc- or PKC-β-short interfering RNAs partially reversed these changes. Treatment of HK-2 cells with HG and ANG II also increased the protein-protein association between p-p66Shc and Pin1, an isomerase, in the cytosol, and with cytochrome c in the mitochondria. These interactions were partially disrupted with the treatment of PKC-β inhibitor or Pin1-short interfering RNA. These data suggest that p66Shc mediates HG- and ANG II-induced mitochondrial dysfunctions via PKC-β and Pin1-dependent pathways in renal tubular cells.
Stress-Induced Structural Transitions in DNA and Proteins (2000)

The ability to manipulate, stretch and twist biomolecules opens the way to an understanding of their structural transitions. We review some of the recently discovered stress-induced structural transitions in DNA as well as the application of single molecule manipulation techniques to DNA unzipping and to the study of protein folding/unfolding transitions.