gebhart/patrepeval huggingface dataset:
Surface acoustic wave methods to determine the anisotropic elastic properties of thin films* (2001)

We have developed experimental and analytical methods to measure the anisotropic elastic properties of thin supported films. In this approach, surface acoustic waves (SAWs) were generated using a line-focused laser. Waves with frequency components up to 400 MHz were detected by a Michelson interferometer. Dispersion relations for the SAW phase velocity were calculated from displacement waveforms acquired with source-detector separations of 5-15 mm. To determine film properties from the dispersion relations, we developed a new inversion algorithm based on the delta-function representation of the fully anisotropic, elastodynamic Green function for wave propagation. Our methods were first applied to an elastically isotropic aluminium film on an isotropic fused silica substrate. The results show the validity of our methods and were in good agreement with literature values. The results also illustrate various aspects of measurement uncertainty. The same SAW methods were used to examine a series of titanium nitride films on single-crystalline silicon wafers. The inversion results assuming orthotropic elastic symmetry indicated that c11 increased and c13 decreased with increasing film thickness. Values for the film thickness determined by our analysis were in good agreement with destructive measurements of the actual thicknesses.
The heat-shock response: regulation and function of heat-shock proteins and molecular chaperones. (1997)

Exposure of cells to stresses such as heat shock, oxidant injury and heavy metals causes an imbalance in protein metabolism which challenges the cell to respond rapidly, yet precisely, to minimize the deleterious effects of environmental and physiological stress. The heat-shock response, through the activation of HSFs, results in the elevated expression of heat-shock genes and the concomitant synthesis of HSPs and molecular chaperones. Molecular chaperones function in a variety of protein biosynthetic events and protect proteins from the deleterious effects of acute or chronic stress by stabilizing and refolding protein-folding intermediates or facilitating protein degradation. The accumulation of misfolded proteins has also become a central issue to diseases of protein folding, including sickle cell haemoglobin, cystic fibrosis and prion diseases, in addition to complex multifactorial diseases such as bacterial and viral infections, myocardial ischaemia, neurodegenerative diseases and cancer.
A Feasibility Study of a Capacitive Biosensor for Direct Detection of DNA Hybridization (1999)

This preliminary study was performed to prove the feasibility of a direct capacitive DNA biosensor for detection of nucleic acids. Two different methods for immobilization of the oligonucleotide probes were used. The first type of sensor was composed of a gold rod with a self-assembled monolayer of a 26-base long oligonucleotide probe, modified with an SH-group at the 5′-end. Coverage studies showed that only around 20% of the surface was covered, probably due to the bulky nature of the probes. Hybridization studies performed in a flow-through cell showed selectivity towards a DNA sample containing single stranded fragments of cytomegalo virus (CMV) possessing a complementary sequence. As few as 25 molecules could be detected at sample concentrations of 0.2attomolar with an injection volume of 250 μL. Controls with fragments of double-stranded CMV and single-stranded hepatitis B virus and tyrosinase mRNA gave all lower responses. The other type of sensor was modified by covalent immobilization of a phosphorylated 8-base long oligonucleotide probe to a self-assembled monolayer of cysteamine. This biosensor also showed selectivity against single stranded fragments of CMV and also in this case as few as 25 molecules could be detected.
Routine evaluation of the nonradiometric BACTEC NR 660 system (1986)

The present study compares the sensitivity, accuracy, and practicability of a nonradiometric blood culture system with those of the standard blood culture system in use in our laboratory. A total of 1,080 sets of four blood cultures bottles were compared, giving 143 positive aerobic-medium associations and 139 positive anaerobic-medium associations. The conventional system recovered 171 isolates, whereas the BACTEC NR 660 system (Johnston Laboratories, Towson, Md.) recovered 155 isolated. There were no significant differences in total isolates with either system (P more than 0.05). The BACTEC NR 660 system recovered a slightly lower number of Serratia marcescens and Streptococcus faecalis but a higher number of Pneumococcus spp. The mean detection times were 55.9 h with the conventional system and 31.6 h with the BACTEC NR 660 system (P less than 0.001). Our results demonstrate that the BACTEC NR 660 system is suitable for routine use.
Attempts at Automatic Detection of Railway Head Edges from Images and Laser Data (2012)

Abstract The more and more high resolution of aerial and ground images, as well as high density of laser data cause that they are more and more widely applied in many engineering projects. Given the current technical parameters, it is also possible to map railway infrastructure not only from the ground level but also from airborne locations (photogrammetry, laser scanning). Testing the usefulness of those data in obtaining information about railway infrastructure, and in particular, in detecting rail heads has been a subject of research of this paper authors. The paper presents results of experiments, consisting in verification of existing solutions and testing own algorithms for an automatic extraction of railway rail heads. The tested algorithms of object detecting and locating produced preliminary, satisfying results. The authors believe it to be reasonable to continue their research work.
Hydrodynamic Limb Vein Injection of Adeno-Associated Virus Serotype 8 Vector Carrying Canine Myostatin Propeptide Gene into Normal Dogs Enhances Muscle Growth (2009)

Inhibition or blockade of myostatin, a negative growth factor of skeletal muscle, enhances muscle growth and therefore is considered a promising strategy for the treatment of muscle-wasting diseases such as the muscular dystrophies. Previously, we showed that myostatin blockade in both normal and dystrophin-deficient mdx mice by systemic delivery of the myostatin propeptide (MPRO) gene by an adeno-associated virus serotype 8 (AAV8) vector could enhance muscle growth and ameliorate dystrophic lesions. Here, we further investigate whether the muscle growth effect of myostatin blockade can be achieved in dogs by gene transfer. First, we cloned the canine MPRO gene, packaged it in the AAV8 vector, and showed robust muscle-enhancing effects after systemic delivery into neonatal mice. This vector was then further tested in two 3-month-old normal dogs (weighing 9.7 and 6.3 kg). The vector was delivered to one limb by hydrodynamic vein injection, and the contralateral limb served as a control. The delivery procedure was safe, without discernible adverse effects. AAV vector DNA and MPRO gene expression were detected by quantitative polymerase chain reaction, Western blotting, and immunofluorescence staining of muscle biopsies. Overexpression of MPRO resulted in enhanced muscle growth without a cytotoxic T lymphocytic immune response, as evidenced by larger myofibers in multiple muscles, increased muscle volume determined by magnetic resonance imaging, and the lack of CD4+ and CD8+ T cell infiltration in the vector-injected limbs. Our preliminary study thus supports further investigation of this therapeutic strategy in the dystrophin-deficient golden retriever muscular dystrophy dog model.
Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer's disease neurons: implications for mitochondrial dysfunction and neuronal damage (2012)

We recently reported increased mitochondrial fission and decreased fusion, increased amyloid beta (Aβ) interaction with the mitochondrial fission protein Drp1, increased mitochondrial fragmentation, impaired axonal transport of mitochondria and synaptic degeneration in neurons affected by AD. In the present study, we extended our previous investigations to determine whether phosphorylated tau interacts with Drp1 and to elucidate mitochondrial damage in the progression of AD. We also investigated GTPase activity, which is critical for mitochondrial fragmentation, in postmortem brain tissues from patients with AD and brain tissues from APP, APP/PS1 and 3XTg.AD mice. Using co-immunoprecipitation and immunofluorescence analyses, for the first time, we demonstrated the physical interaction between phosphorylated tau and Drp1. Mitochondrial fission-linked GTPase activity was significantly elevated in the postmortem frontal cortex tissues from AD patients and cortical tissues from APP, APP/PS1 and 3XTg.AD mice. On the basis of these findings, we conclude that Drp1 interacts with Aβ and phosphorylated tau, likely leading to excessive mitochondrial fragmentation, and mitochondrial and synaptic deficiencies, ultimately possibly leading to neuronal damage and cognitive decline. Treatment designed to reduce the expression of Drp1, Aβ and/or phosphorylated tau may decrease the interaction between Drp1 and phosphorylated tau and the interaction between Drp1 and Aβ, conferring protection to neurons from toxic insults of excessive Drp1, Aβ and/or phosphorylated tau.
Rational design of a chimeric toxin: an intramolecular location for the insertion of transforming growth factor .alpha. within Pseudomonas exotoxin as a targeting ligand (1992)

To investigate the potential utility of Pseudomonas exotoxin (PE) in forming rationally designed chemotherapeutic agents, we inserted a cDNA encoding transforming growth factor alpha (TGF alpha) at several locations in a gene encoding a mutant full-length PE (PE4E) which does not bind to the PE receptor. After expression in Escherichia coli, we purified the chimeric toxins to near homogeneity and showed that they were specifically cytotoxic to human epidermoid, ovarian, colon, and hepatocellular carcinoma lines. Like the previously reported TGF alpha-PE40, one of the new molecules (TGF alpha-PE4E) contains the ligand at the amino terminus. Two additional chimeras (PE4E-TGF alpha and PE4E-TGF alpha-598-613) each contain TGF alpha inserted near the carboxyl terminus of PE. We show that preservation of the correct PE carboxyl-terminal amino acid sequence, REDLK, allows the toxins containing TGF alpha carboxyl inserts to retain significant cytotoxicity against target cells, since another molecule (PE4E-TGF alpha-ILK) containing a nonfunctional carboxyl-terminal sequence was over 100-fold less active. The chimeric toxins with TGF alpha had the same binding affinity for the EGF receptor whether the ligand occupied the amino or carboxyl position. Molecules with TGF alpha near the carboxyl position were consistently less active against target cells but also less toxic to mice than those with TGF alpha at the amino terminus, indicating both types of molecules might be therapeutically effective. Our results establish that a ligand can be placed near the carboxyl terminus of PE, within the portion of the toxin that translocates to the cytosol. The amino-terminal position in such molecules is then available for the placement of other targeting ligands.
Conversion of Thiols to Disulfides Using a Hexamethylenetetramine-Bromine Complex (2006)

Hexamethylenetetramine-bromine complex, a yellow-orange, very stable homogeneous solid, affects a mild and fairly general conversion of thiols to disulfides.
Microengineered Electrically Resettable Circuit Breaker (2004)

Electromechanical circuit breakers based on microelectromechanical systems (MEMS) structures are proposed, and initial prototypes are demonstrated. The devices use laterally moving thermal actuators to set and trip low resistance contacts. The actuators are fabricated from electroplated Ni, on Si substrates, with Au-Co contact layers. Trip currents of 300 mA are obtained, with contact resistances below 1 /spl Omega/. Rapid tripping (below 50 ms) is achieved, even for modest over-current levels, and sensitivity to ambient temperature is much less than for positive temperature coefficient (PTC) devices typically used for over-current protection in electronics applications. These MEMS devices offer an ultra-miniature, potentially low cost solution for circuit protection applications at low currents, where a high degree of system control is desired.
Transformer 2β homolog (Drosophila) (TRA2B) Regulates Protein Kinase C δI (PKCδI) Splice Variant Expression during 3T3L1 Preadipocyte Cell Cycle (2014)

Obesity is characterized by adipocyte hyperplasia and hypertrophy. We previously showed that PKCδ expression is dysregulated in obesity (Carter, G., Apostolatos, A., Patel, R., Mathur, A., Cooper, D., Murr, M., and Patel, N. A. (2013) ISRN Obes. 2013, 161345). Using 3T3L1 preadipocytes, we studied adipogenesis in vitro and showed that expression of PKCδ splice variants, PKCδI and PKCδII, have different expression patterns during adipogenesis (Patel, R., Apostolatos, A., Carter, G., Ajmo, J., Gali, M., Cooper, D. R., You, M., Bisht, K. S., and Patel, N. A. (2013) J. Biol. Chem. 288, 26834-26846). Here, we evaluated the role of PKCδI splice variant during adipogenesis. Our results indicate that PKCδI expression level is high in preadipocytes and decreasing PKCδI accelerated terminal differentiation. Our results indicate that PKCδI is required for mitotic clonal expansion of preadipocytes. We next evaluated the splice factor regulating the expression of PKCδI during 3T3L1 adipogenesis. Our results show TRA2B increased PKCδI expression. To investigate the molecular mechanism, we cloned a heterologous splicing PKCδ minigene and showed that inclusion of PKCδ exon 9 is increased by TRA2B. Using mutagenesis and a RNA-immunoprecipitation assay, we evaluated the binding of Tra2β on PKCδI exon 9 and show that its association is required for PKCδI splicing. These results provide a better understanding of the role of PKCδI in adipogenesis. Determination of this molecular mechanism of alternative splicing presents a novel therapeutic target in the management of obesity and its co-morbidities.
Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines (1995)

Because the meningococcal transferrin receptor was shown to elicit bactericidal and protective antibodies in laboratory animals, we undertook a study of the protective role of each of the polypeptides within the Tbp1-Tbp2 complex. We developed a procedure to purify from Neisseria meningitidis B16B6 the two proteins in milligram amounts and raised specific antisera in rabbits and mice. Only antisera specific for Tbp2 displayed bactericidal activity against the parent strain. Mice immunized with purified Tbp2 survived a lethal challenge to a similar degree as animals immunized with the Tbp1-Tbp2 complex, demonstrating that Tbp2 played an important role in the protective activity observed with the complex. Both Tbp1- and Tbp2-specific antisera inhibited transferrin binding to the purified receptor in a solid-phase binding assay, suggesting that the antibodies were able to interact with the Tbp1 molecule only when it was removed from its membrane environment. Finally, Tbp2-specific immunoglobulins were able to lower the growth rate of the meningococci when human transferrin was their sole iron source. Therefore, in all four different systems tested, Tbp2 or antibodies specific for Tbp2 displayed biological characteristics close to those of the Tbp1-Tbp2 complex. This suggests that Tbp2 plays an important role in the protective activity of the complex, eliciting antibodies that are not only bactericidal but also inhibitory for meningococcal growth.
Effects of citrus limonoids on glutathione S-transferase activity in mice (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of citrus limonoids on glutathione S-transferase activity in miceLuke K. T. Lam, Ying Li, and Shin HasegawaCite this: J. Agric. Food Chem. 1989, 37, 4, 878–880Publication Date (Print):July 1, 1989Publication History Published online1 May 2002Published inissue 1 July 1989https://pubs.acs.org/doi/10.1021/jf00088a010https://doi.org/10.1021/jf00088a010research-articleACS PublicationsRequest reuse permissionsArticle Views467Altmetric-Citations90LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A Timing-Driven Soft-Macro Placement and Resynthesis Method in Interaction with Chip Floorplanning (1999)

In this paper, we present a complete chip design method which incorporates a soft-macro placement and resynthesis method in interaction with chip floorplanning for area and timing improvements. We present a performance-driven soft-macro clustering and placement method which preserves hardware descriptive language (HDL) design hierarchy to guide the soft-macro placement process. We develop a timing-driven design flow to exploit the interaction between HDL synthesis and physical design tasks. During each design iteration, we resynthesize soft macros with either a relaxed or a tightened timing constraint which is guided by the post-layout timing information. The goal is to produce area-efficient designs while satisfying the timing constraints. Experiments on a number of industrial designs ranging from 75-K to 230-K gates demonstrate that the proposed soft-macro clustering and placement method improves critical-path delays on an average of 22%. Furthermore, the results show that by effecti...
A Novel Antibacterial 8-Chloroquinolone with a Distorted Orientation of the N1-(5-Amino-2,4-difluorophenyl) Group (2003)

Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential. In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones. Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria. This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus. The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity. An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 Cl atom and the N-1 substituent. Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group. Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.
Modulation of DNA repair by pharmacological inhibitors of the PIKK protein kinase family (2012)

Modulation of DNA repair pathways in oncology has been an area of intense interest in the last decade, not least as a consequence of the promising clinical activity of poly(ADP-ribose) polymerase (PARP) inhibitors. In this review article, we highlight inhibitors of the phosphatidylinositol 3-kinase related kinase (PIKK) family as of potential interest in the treatment of cancer, both in combination with DNA-damaging therapies and as stand-alone agents.
Cost analysis of current therapies for limited coronary artery revascularization. (1997)

MIDCAB grafting provides a new surgical approach that is comparable in charges to catheter-based interventions. The technique markedly reduces length of stay and perioperative morbidity. The selection of medical or surgical limited coronary revascularization can now be based primarily on clinical outcomes without consideration for associated resource allocation.
Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability (2012)

Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts by using induced pluripotent stem cells (iPSCs). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent-resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the PI3K pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening.
Role of fibroblast activation in inducing interstitial fibrosis. (2001)

Tubulointerstitial fibrosis is an obligate finding in end-stage diseased kidneys. Renal fibrosis is defined as excessive matrix deposition that leads to tissue destruction and impairment of renal function. This process is often independent of the initial underlying disease and is not self-limited, in contrast to normal wound healing. Fibroblasts are the main effector cells in fibrogenesis, and mainly contribute to increased synthesis of matrix components. Increased matrix production is preceeded by massive proliferation of fibroblasts. The transformation from quiescent interstitial cells to proliferating and excessively matrix-producing cells has been termed fibroblast activation, which includes functional implications as well as phenotypic changes such as the expression of alpha-smooth muscle actin ("myofibroblasts"). Activation of fibroblasts typically occurs through four distinct mechanisms: stimulation by growth factors ("auto- and paracrine"), by direct cell-cell contacts, by extracellular matrix via integrins, and by environmental conditions such as hyperglycemia or hypoxia in renal disease. The crucial step though, that distinguishes wound healing from fibrosis, is the perpetuation of the activated state. The clarification of cellular events connected with fibrogenesis has led to new approaches for therapy. Direct targeting of fibroblasts, inhibition of matrix deposition and specific inhibition of fibroblast activation have proved successful in experimental models and thus may lead to new approaches in the treatment of progressive renal disease.