gebhart/patrepeval huggingface dataset:
Microfluidics Based Point‐of‐Care Diagnostics (2017)

Point-of-care (POC) diagnostic devices have been predicted to provide a boon in health care especially in the diagnosis and detection of diseases. POC devices have been found to have many advantages like a rapid and precise response, portability, low cost, and non-requirement of specialized equipment. The major objective of a POC diagnostic research is to develop a chip-based, self-containing miniaturized device that can be used to examine different analytes in complex samples. Further, the integration of microfluidics (MF) with advanced biosensor technologies is likely to result in improved POC diagnostics. This paper presents the overview of the different materials (glass, silicon, polymer, paper) and techniques for the fabrication of MF based POC devices along with their wide range of biosensor applications. Besides this, the authors have presented in brief the challenges that MF is currently facing along with possible solutions that may result in the availability of the accessible, reliable, and cost-efficient technology. The development of these devices requires the combination of developed MF components into POC devices that are user-friendly, sensitive, stable, accurate, low cost, and minimally invasive. These MF based POC devices have tremendous potential in providing improved healthcare including easy monitoring, early detection of disease, and increased personalization.
Efficient Palladium‐Catalyzed Coupling of Aryl Chlorides and Tosylates with Terminal Alkynes: Use of a Copper Cocatalyst Inhibits the Reaction (2003)

Less catalyst, lower temperature, and greater generality are the advantages of the new general protocol over those previously described for the palladium-catalyzed coupling of aryl chlorides and alkynes (see scheme). Better results are obtained without a copper cocatalyst, which has been found to inhibit product formation in the coupling reaction of aryl chlorides with terminal alkynes.
The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition (2012)

Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors.
Ester and Amide Derivatives of the Nonsteroidal Antiinflammatory Drug, Indomethacin, as Selective Cyclooxygenase-2 Inhibitors (2000)

Recent studies from our laboratory have shown that derivatization of the carboxylate moiety in substrate analogue inhibitors, such as 5,8,11,14-eicosatetraynoic acid, and in nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin and meclofenamic acid, results in the generation of potent and selective cyclooxygenase-2 (COX-2) inhibitors (Kalgutkar et al. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 925-930). This paper summarizes details of the structure-activity studies involved in the transformation of the arylacetic acid NSAID, indomethacin, into a COX-2-selective inhibitor. Many of the structurally diverse indomethacin esters and amides inhibited purified human COX-2 with ICo5 values in the low-nanomolar range but did not inhibit ovine COX-1 activity at concentrations as high as 66 microM. Primary and secondary amide analogues of indomethacin were more potent as COX-2 inhibitors than the corresponding tertiary amides. Replacement of the 4-chlorobenzoyl group in indomethacin esters or amides with the 4-bromobenzyl functionality or hydrogen afforded inactive compounds. Likewise, exchanging the 2-methyl group on the indole ring in the ester and amide series with a hydrogen also generated inactive compounds. Inhibition kinetics revealed that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Conversion of indomethacin into ester and amide derivatives provides a facile strategy for generating highly selective COX-2 inhibitors and eliminating the gastrointestinal side effects of the parent compound.
Effects of glycosylation on protein conformation and amide proton exchange rates in RNase B (1992)

Assignment of most of the proton NMR resonances of bovine pancreatic RNase B has been achieved using standard NMR techniques and by comparison with the published assignments for RNase A. A comparison of the NMR spectra of RNase B with RNase A shows that glycosylation of the enzyme has little overall effect on the conformation of the protein in solution. Comparisons of hydrogen-deuterium solvent exchange rates for the NH protons of RNase A and RNase B were made using two-dimensional 1H correlation spectroscopy. In the case of the glycosylated enzyme the exchange rates decreased for the NH protons of residues 9-14, 23-24, 32, 34-35, 39-40, 43-44, 48-49, 60, 71, 75-76, 80, 83-85, 100-101, 107, 111 and 122, relative to the unglycosylated RNase A. These results are consistent with the presence of the oligosaccharide inducing enhanced global dynamic stability and consequent changes to the unfolding equilibrium of the enzyme. The enhanced stability is observed not only for residues in the vicinity of the glycosylation site, asparagine-34, but also at residues remote from this site, as much as 30 A away.
Attenuation properties of optical waveguides with a metal boundary (1973)

Attenuation coefficients have been measured at 6328 Å in liquid waveguides bounded on one side by a metal wall. Provided that the measurements be made on selected samples meeting certain criterions, Ohmic boundary absorption is found to depend on mode order N as (N + 1)2 and waveguide thickness w as w−3, in agreement with theory.
Multinational federations in comparative perspective (2007)

Since federation involves a combination of elements of ‘self-rule’ for the
constituent units for certain purposes and ‘shared rule’ through common
institutions for certain other purposes, it will be the contention of this
chapter that the form which each of these two aspects takes in an individual
multinational federation has a crucial bearing on its relative effectiveness.
Thus, the mere adoption of federation or not does not give the full picture.
The organization of ‘self-rule’ for the constituent units may take a variety of
forms, and the particular form has a direct effect upon the effective operation
of a multinational federation. Similarly, ‘shared rule’ in the common institutions may take a variety of institutional forms and processes, and these too
significantly affect the operation of a multinational federation.
Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue (2021)

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19).
A Potent New Class of Reductively Activated Peptide Gene Delivery Agents (2000)

A new class of peptide gene delivery agents were developed by inserting multiple cysteine residues into short (dp 20) synthetic peptides. Substitution of one to four cysteine residues for lysine residues in Cys-Trp-Lys(18) resulted in low molecular weight DNA condensing peptides that spontaneously oxidize after binding to plasmid DNA to form interpeptide disulfide bonds. The stability of cross-linked peptide DNA condensates increased in proportion to the number of cysteines incorporated into the peptide. Disulfide bond formation led to a decrease in particle size relative to control peptide DNA condensates and prevented dissociation of peptide DNA condensates in concentrated sodium chloride. Cross-linked peptide DNA condensates were 5-60-fold more potent at mediating gene expression in HepG2 and COS 7 cells relative to uncross-linked peptide DNA condensates. The enhanced gene expression was dependent on the number of cysteine residues incorporated, with a peptide containing two cysteines mediating maximal gene expression. Cross-linking peptides caused elevated gene expression without increasing DNA uptake by cells, suggesting a mechanism involving intracellular release of DNA triggered by disulfide bond reduction. The results establish cross-linking peptides as a novel class of potent gene delivery agents that enhance gene expression through a new mechanism of action.
Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases (2000)

Therapy targeting the VEGFR-2 inhibited tumor growth in a murine model of colon carcinoma liver metastasis. Surprisingly, this therapy did not only inhibit angiogenesis but also led to endothelial cell death. These findings suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for tumor endothelial cells in liver metastases from colon carcinoma.
Differential Regulation of Raf-1, A-Raf, and B-Raf by Oncogenic Ras and Tyrosine Kinases (1997)

It has previously been shown that maximal activation of Raf-1 is produced by synergistic signals from oncogenic Ras and activated tyrosine kinases. This synergy arises because Ras-GTP translocates Raf-1 to the plasma membrane where it becomes phosphorylated on tyrosine residues 340 and 341 by membrane-bound tyrosine kinases (Marais, R., Light, Y., Paterson, H. F., and Marshall, C. J. (1995) EMBO J. 14, 3136-3145). We have examined whether the other two members of the Raf family, A-Raf and B-Raf, are regulated in a similar way to Raf-1. A-Raf behaves like Raf-1, being weakly activated by oncogenic Ras more strongly activated by oncogenic Src, and these signals synergize to give maximal activation. B-Raf by contrast is strongly activated by oncogenic Ras alone and is not activated by oncogenic Src. These results show that maximal activation of B-Raf merely requires signals that generate Ras-GTP, whereas activation of Raf-1 and A-Raf requires Ras-GTP together with signals that lead to their tyrosine phosphorylation. B-Raf may therefore be the primary target of oncogenic Ras.
A review of dielectric optical metasurfaces for wavefront control (2018)

During the past few years, metasurfaces have been used to demonstrate optical elements and systems with capabilities that surpass those of conventional diffractive optics. Here, we review some of these recent developments, with a focus on dielectric structures for shaping optical wavefronts. We discuss the mechanisms for achieving steep phase gradients with high efficiency, simultaneous polarization and phase control, controlling the chromatic dispersion, and controlling the angular response. Then, we review applications in imaging, conformal optics, tunable devices, and optical systems. We conclude with an outlook on future potentials and challenges that need to be overcome.
Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis (2013)

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.
Single channel properties of lysenin measured in artificial lipid bilayers and their applications to biomolecule detection (2010)

Single channel currents of lysenin were measured using artificial lipid bilayers formed on a glass micropipette tip. The single channel conductance for KCl, NaCl, CaCl(2), and Trimethylammonium-Cl were 474 ± 87, 537 ± 66, 210 ± 14, and 274 ± 10 pS, respectively, while the permeability ratio P(Na)/P(Cl) was 5.8. By adding poly(deoxy adenine) or poly(L-lysine) to one side of the bilayer, channel currents were influenced when membrane voltages were applied to pass the charged molecules through the channel pores. Current inhibition process was concentration-dependent with applied DNA. As the current fluctuations of α-hemolysin channels is often cited as the detector in a molecular sensor, these results suggest that by monitoring channel current changes, the lysenin channel has possibilities to detect interactions between it and certain biomolecules by its current fluctuations.
Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins. (1994)

Protein kinase C (PKC) translocates from the soluble to the cell particulate fraction on activation. Intracellular receptors that bind activated PKC in the particulate fraction have been implicated by a number of studies. Previous work identified 30- to 36-kDa proteins in the particulate fraction of heart and brain that bound activated PKC in a specific and saturable manner. These proteins were termed receptors for activated C-kinase, or RACKs. In the following study, we describe the cloning of a cDNA encoding a 36-kDa protein (RACK1) that fulfills the criteria for RACKs. (i) RACK1 bound PKC in the presence of PKC activators, but not in their absence. (ii) PKC binding to the recombinant RACK1 was not inhibited by a pseudosubstrate peptide or by a substrate peptide derived from the pseudosubstrate sequence, indicating that the binding did not reflect simply PKC association with its substrate. (iii) Binding of PKC to RACK1 was saturable and specific; two other protein kinases did not bind to RACK1. (iv) RACK1 contains two short sequences homologous to a PKC binding sequence previously identified in annexin I and in the brain PKC inhibitor KCIP. Peptides derived from these sequences inhibited PKC binding to RACK1. Finally, RACK1 is a homolog of the beta subunit of G proteins, which were recently implicated in membrane anchorage of the beta-adrenergic receptor kinase [Pitcher, J., Inglese, L., Higgins, J. B., Arriza, J. A., Casey, P. J., Kim, C., Benovic, J. L., Kwatra, M. M., Caron, M. G. & Lefkowitz, R. J. (1992) Science 257, 1264-1267]. Our in vitro data suggest a role for RACK1 in PKC-mediated signaling.
Bigtable: a distributed storage system for structured data (2006)

Bigtable is a distributed storage system for managing structured data that is designed to scale to a very large size: petabytes of data across thousands of commodity servers. Many projects at Google store data in Bigtable, including web indexing, Google Earth, and Google Finance. These applications place very different demands on Bigtable, both in terms of data size (from URLs to web pages to satellite imagery) and latency requirements (from backend bulk processing to real-time data serving). Despite these varied demands, Bigtable has successfully provided a flexible, high-performance solution for all of these Google products. In this paper we describe the simple data model provided by Bigtable, which gives clients dynamic control over data layout and format, and we describe the design and implementation of Bigtable.
Single base mutations in the human androgen receptor gene causing complete androgen insensitivity: rapid detection by a modified denaturing gradient gel electrophoresis technique. (1992)

Mutations of the human androgen receptor (AR) gene impair normal sexual differentiation and development in karyotypic males, resulting in a spectrum of external genital phenotypes ranging from complete female to nearly complete male. Identification and characterization of these mutations can provide valuable information regarding the functional importance of specific amino acids of the AR. To screen for point mutations in the AR gene underlying the phenotypic abnormalities in the androgen insensitivity syndrome (AIS), the eight exons of the AR gene were amplified from genomic DNA using the polymerase chain reaction (PCR) and analyzed by denaturing gradient gel electrophoresis. A computer program, MELTMAP, was used to identify optimum sequences for denaturing gradient gel electrophoresis, and mutation detection sensitivity was enhanced by forming heteroduplexes between control and subject PCR products to create base mismatches. In seven families with complete AIS, single base mutations were found in the region of the AR gene encoding the steroid-binding domain of the receptor. The mutations that converted amino acid 774 from Arg to His and amino acid 864 from Asp to Gly were recreated using site-directed mutagenesis and the mutant ARs expressed in COS 7 and CV1 cells. In both cases, abnormalities of androgen binding and transcriptional activation were consistent with the observed sex phenotype. These results together with others reported previously demonstrate that single amino acid changes within the region encoded by exons D to H of the AR gene can alter androgen binding and are a common cause of complete androgen resistance. The strategy used herein, employing denaturing gradient gel analysis of heteroduplex PCR products, provides a valuable aid to rapid detection of single base mutations in AIS.
Distributed Spatial Data Aggregation and Dilution Based on Hashing and Relational Algebra in Wireless Sensor Networks (2005)

A data aggregation and dilution scheme is introduced for the wireless sensor network, which can be perceived as a distributed relational database. A new algorithm that can run on tiny sensor nodes to aggregate or dilute the sensed data packets is developed. Two location based hash functions are also introduced to determine how the sensed data can be grouped or which sensors should be excluded from a query. Analytical models are provided for the performance evaluation. The numerical results show that our scheme can reduce the number of transmitted packets 50% on average compared to the case where aggregation or dilution is not used.
The nanosilica hazard: another variable entity (2010)

Silica nanoparticles (SNPs) are produced on an industrial scale and are an addition to a growing number of commercial products. SNPs also have great potential for a variety of diagnostic and therapeutic applications in medicine. Contrary to the well-studied crystalline micron-sized silica, relatively little information exists on the toxicity of its amorphous and nano-size forms. Because nanoparticles possess novel properties, kinetics and unusual bioactivity, their potential biological effects may differ greatly from those of micron-size bulk materials. In this review, we summarize the physico-chemical properties of the different nano-sized silica materials that can affect their interaction with biological systems, with a specific emphasis on inhalation exposure. We discuss recent in vitro and in vivo investigations into the toxicity of nanosilica, both crystalline and amorphous. Most of the in vitro studies of SNPs report results of cellular uptake, size- and dose-dependent cytotoxicity, increased reactive oxygen species levels and pro-inflammatory stimulation. Evidence from a limited number of in vivo studies demonstrates largely reversible lung inflammation, granuloma formation and focal emphysema, with no progressive lung fibrosis. Clearly, more research with standardized materials is needed to enable comparison of experimental data for the different forms of nanosilicas and to establish which physico-chemical properties are responsible for the observed toxicity of SNPs.
[Impact of micrometastasis in pathologically negative lymph node on staging and prognosis of non-small cell lung cancers]. (2002)

The detection of micrometastasis in the lymphnodes may serve as a supplement to the present staging system for lung cancer. Even though the prognosis of patients with micrometastasis being poorer than those without, micrometastasis in the lymph nodes should not be regarded as an independent prognostic factor.
Detection of DNA breaks in apoptotic cells utilizing the DNA binding domain of poly(ADP-ribose) polymerase with fluorescence microscopy (1997)

The DNA binding domain (DBD) of poly(ADP-ribose) polymerase (PARP) has proved to be a novel, highly sensitive probe for detecting DNA breaks in intact cells undergoing apoptosis. A recombinant peptide spanning the DNA binding domain of PARP was expressed, purified and used to detect DNA strand breaks in fixed cells. Fluorescence microscopy with this probe followed by detection with anti-PARP antisera initially revealed an increased binding following treatment of cells with DNA strand-breaking agents (such asN-methyl-N'-nitro-N-nitrosoguanidine) and, subsequently, using biotinylated PARP DBD, during the later stages of apoptosis in several cell systems, when internucleosomal strand breaks became evident. This procedure was found to be at least as sensitive and required fewer steps to detect DNA strand breaks than those utilizing Klenow incorporation of biotinylated nucleotides.
Highly efficient single-layer dendrimer light-emitting diodes with balanced charge transport (2003)

High-efficiency single-layer-solution-processed green light-emitting diodes based on a phosphorescent dendrimer are demonstrated. A peak external quantum efficiency of 10.4% (35 cd/A) was measured for a first generation fac-tris(2-phenylpyridine) iridium cored dendrimer when blended with 4,4′-bis(N-carbazolyl)biphenyl and electron transporting 1,3,5-tris(2-N-phenylbenzimidazolyl)benzene at 8.1 V. A maximum power efficiency of 12.8 lm/W was measured also at 8.1 V and 550 cd/m2. These results indicate that, by simple blending of bipolar and electron-transporting molecules, highly efficient light-emitting diodes can be made employing a very simple device structure.