gebhart/patrepeval huggingface dataset:
Macrophage Responses to Silica Nanoparticles are Highly Conserved Across Particle Sizes (2008)

Concerns about the potential adverse health effects of engineered nanoparticles stems in part from the possibility that some materials display unique chemical and physical properties at nanoscales which could exacerbate their biological activity. However, studies that have assessed the effect of particle size across a comprehensive set of biological responses have not been reported. Using a macrophage cell model, we demonstrate that the ability of unopsonized amorphous silica particles to stimulate inflammatory protein secretion and induce macrophage cytotoxicity scales closely with the total administered particle surface area across a wide range of particle diameters (7-500 nm). Whole genome microarray analysis of the early gene expression changes induced by 10- and 500-nm particles showed that the magnitude of change for the majority of genes affected correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were particle size-specific were also identified. However, the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Direct comparison of the cell processes represented in the 10- and 500-nm particle gene sets using gene set enrichment analysis revealed that among 1009 total biological processes, none were statistically enriched in one particle size group over the other. The key mechanisms involved in silica nanoparticle-mediated gene regulation and cytotoxicity have yet to be established. However, our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Production of a recombinant vaccine candidate against Burkholderia pseudomallei exploiting the bacterial N-glycosylation machinery (2014)

Vaccines developing immune responses toward surface carbohydrates conjugated to proteins are effective in preventing infection and death by bacterial pathogens. Traditional production of these vaccines utilizes complex synthetic chemistry to acquire and conjugate the glycan to a protein. However, glycoproteins produced by bacterial protein glycosylation systems are significantly easier to produce, and could possible be used as vaccine candidates. In this work, we functionally expressed the Burkholderia pseudomallei O polysaccharide (OPS II), the Campylobacter jejuni oligosaccharyltransferase (OTase), and a suitable glycoprotein (AcrA) in a designer E. coli strain with a higher efficiency for production of glycoconjugates. We were able to produce and purify the OPS II-AcrA glycoconjugate, and MS analysis confirmed correct glycan was produced and attached. We observed the attachment of the O-acetylated deoxyhexose directly to the acceptor protein, which expands the range of substrates utilized by the OTase PglB. Injection of the glycoprotein into mice generated an IgG immune response against B. pseudomallei, and this response was partially protective against an intranasal challenge. Our experiments show that bacterial engineered glycoconjugates can be utilized as vaccine candidates against B. pseudomallei. Additionally, our new E. coli strain SDB1 is more efficient in glycoprotein production, and could have additional applications in the future.
A Systematic Approach to Building High Performance Software-Based CRC Generators (2005)

A framework for designing a family of novel fast CRC generation algorithms is presented. Our algorithms can ideally read arbitrarily large amounts of data at a time, while optimizing their memory requirement to meet the constraints of specific computer architectures. In addition, our algorithms can be implemented in software using commodity processors instead of specialized parallel circuits. We use this framework to design two efficient algorithms that run in the popular Intel IA32 processor architecture. First, a 'slicing-by-4' algorithm doubles the performance of existing software-based, table-driven CRC implementations based on the Sarwate (August 1988) algorithm while using a 4K cache footprint. Second, a 'slicing-by-8' algorithm triples the performance of existing software-based CRC implementations while using an 8K cache footprint.
Herb–Drug Interactions in Oncology: Focus on Mechanisms of Induction (2006)

An increasing number of cancer patients are using complementary and alternative medicines (CAM) in combination with their conventional chemotherapeutic treatment. Considering the narrow therapeutic window of oncolytic drugs, this CAM use increases the risk of clinically relevant herb-anticancer drug interactions. Such a relevant interaction is that of St. John's wort with the anticancer drugs irinotecan and imatinib. It is, however, estimated that CAM-anticancer drug interactions are responsible for substantially more unexpected toxicities of chemotherapeutic drugs and possible undertreatment seen in cancer patients. Induction of drug-metabolizing enzymes and ATP-binding cassette drug transporters can be one of the mechanisms behind CAM-anticancer drug interactions. Induction will often lead to therapeutic failure because of lower plasma levels of the anticancer drugs, and will easily go unrecognized in cancer treatment, where therapeutic failure is common. Recently identified nuclear receptors, such as the pregnane X receptor, the constitutive androstane receptor, and the vitamin D-binding receptor, play an important role in the induction of metabolizing enzymes and drug transporters. This knowledge has already been an aid in the identification of some CAM probably capable of causing interactions with anticancer drugs: kava-kava, vitamin E, quercetin, ginseng, garlic, beta-carotene, and echinacea. Evidently, more research is necessary to prevent therapeutic failure and toxicity in cancer patients and to establish guidelines for CAM use.
Balanced expression of single subunits in a multisubunit protein, achieved by cell fusion of individual transfectants (2002)

To establish stable cell lines that produce recombinant multisubunit proteins, it is usually necessary to cotransfect cells with several independent gene constructs. Here, we show that a stepwise fusion of individually transfected cells, results in a fused cell-line that secretes a complete multisubunit protein. Functional expression of recombinant multisubunit proteins may require a defined expression ratio between each protein subunit. The cell-fusion technology described allows a predefined expression level of each subunit. Using SIgA as a model protein we demonstrate that the majority of the fused cells inherit the molar expression ratio of the parental transfected cells. These results indicate that simplified screening of clones expressing the expected subunit ratios may be possible using the cell-fusion technology. This technology may therefore be an alternative to generic transfection methods for the establishment of cells that produce multiprotein complexes such as antibodies, receptors, ion channels and other multisubunit proteins.
Metabolism of the calcium antagonist, mibefradil (POSICORTM, Ro 40-5967). Part III. Comparative pharmacokinetics of mibefradil and its major metabolites in rat, marmoset, cynomolgus monkey and man (1997)

1. The metabolism of mibefradil has been examined in rat, marmoset, cynomolgus monkey and man after single and multiple oral administration. 2. Metabolites typically represent between 50 and 80% of the circulating drug-related material after single oral doses of mibefradil to man, rat and marmoset. They arise by a combination of enzymatic processes: cytochrome P450-mediated oxidation at saturated and unsaturated carbon atoms, cytochrome P450-catalysed dealkylation and hydrolysis of the ester side-chain. 3. Plasma levels of mibefradil in the cynomolgus monkey are extremely low as a result of very efficient first-pass hydrolysis of its side-chain to give the corresponding alcohol. Steady-state concentrations of this metabolite are comparable with those of the parent drug in man and marmoset, but are relatively low in rat plasma. 4. Hydroxylation at the benzylic carbon of the tetrahydronaphthyl ring leads to further important metabolites in primates, whereas the products of O- and N-demethylation are found in small amounts in all four species. 5. Estimates of the exposure of the various species to the principal metabolites indicate that the choice of the rat, marmoset and cynomolgus monkey for the toxicological assessment of mibefradil was appropriate.
Interlaminar Connections in the Neocortex (2002)

This review summarizes the local circuit, interlaminar connections in adult mammalian neocortex. These were first demonstrated with anatomical techniques, which indicate some of the exquisite spatial precision present in the circuitry. Details, such as the class(es) of neurons targeted by some of these projections, have begun to be added in studies that combine paired/triple intracellular recordings with dye-filling of connected neurons. Clear patterns are emerging from these studies, with 'forward' projections from layer 4 to 3 and from 3 to 5 targeting both selected pyramidal cells and interneurons, while 'back' projections from layer 5 to 3 and from 3 to 4 target only interneurons. To place these data in a wider context, the major afferent inputs to and efferent outputs from each of the layers are discussed first.
Directional perfect absorption using deep subwavelength low-permittivity films (2014)

We experimentally demonstrate single beam directional perfect absorption (to within experimental accuracy) of $p$-polarized light in the near-infrared using unpatterned, deep subwavelength films of indium tin oxide (ITO) on Ag. The experimental perfect absorption occurs slightly above the epsilon-near-zero (ENZ) frequency of ITO, where the permittivity is less than 1 in magnitude. Remarkably, we obtain perfect absorption for films whose thickness is as low as \ensuremath{\sim}1/50th of the operating free-space wavelength and whose single pass attenuation is only \ensuremath{\sim}5%. We further derive simple analytical conditions for perfect absorption in the subwavelength-film regime that reveal the constraints that the thin layer permittivity must satisfy if perfect absorption is to be achieved. Then, to get a physical insight on the perfect absorption properties, we analyze the eigenmodes of the layered structure by computing both the real-frequency/complex-wavenumber and the complex-frequency/real-wavenumber modal dispersion diagrams. These analyses allow us to attribute the experimental perfect absorption condition to the crossover between bound and leaky behavior of one eigenmode of the layered structure. Both modal methods show that perfect absorption occurs at a frequency slightly larger than the ENZ frequency, in agreement with experimental results, and both methods predict a second perfect absorption condition at higher frequencies, attributed to another crossover between bound and leaky behavior of the same eigenmode. Our results greatly expand the list of materials that can be considered for use as ultrathin perfect absorbers and provide a methodology for the design of absorbing systems at any desired frequency.
Orthogonal Synthesis of Xeno Nucleic Acids (2016)

Sequence-defined peptide triazole nucleic acids (PTzNA) were synthesized by means of a solid-phase orthogonal "AB+CD" iterative strategy. In this approach, AB and CD building blocks containing carboxylic acid (A), azide (B), alkyne (C), and primary amine (D) functions are assembled together by successive copper-catalyzed azide-alkyne cycloaddition (CuAAC) and acid-amine coupling steps. Different PTzNA genetic sequences were prepared using a library of eight building blocks (i.e., four AB and four CD building blocks).
Intrabodies targeting the Kaposi sarcoma–associated herpesvirus latency antigen inhibit viral persistence in lymphoma cells (2005)

Kaposi sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen-1 (LANA1) is essential for the maintenance and segregation of viral episomes in KSHV latently infected B cells. We report development of intracellular, rabbit-derived antibodies generated by phage display technology, which bind to N-terminal LANA1 epitopes and neutralize the chromosome-binding activity of LANA1. Although these cloned single-chain variable fragments (scFvs) show relatively low binding affinities for the LANA1 viral antigen in in vitro assays, they nonetheless outcompete KSHV-seropositive human sera for LANA1 epitope binding. In heterologous cells, intracellular intrabody expression inhibits LANA1-dependent plasmid maintenance of both an artificial plasmid containing KSHV LANA1 binding sequences and a bacterial artificial chromosome containing the entire KSHV genome. In KSHV naturally infected primary effusion lymphoma cells, intracellular intrabody expression causes a reduction or loss of the typical LANA1 punctate, nuclear pattern. This morphologically apparent LANA1 dispersion correlates to loss of viral episome by molecular analysis. These data suggest a novel approach to antiherpes viral therapy and confirm LANA1 is critical target for neutralization of KSHV viral latency.
Piecewise smooth surface reconstruction (1994)

We present a general method for automatic reconstruction of accurate, concise, piecewise smooth surface models from scattered range data. The method can be used in a variety of applications such as reverse engineering—the automatic generation of CAD models from physical objects. Novel aspects of the method are its ability to model surfaces of arbitrary topological type and to recover sharp features such as creases and corners. The method has proven to be effective, as demonstrated by a number of examples using both simulated and real data.
Transfer of Pantoea citrea, Pantoea punctata and Pantoea terrea to the genus Tatumella emend. as Tatumella citrea comb. nov., Tatumella punctata comb. nov. and Tatumella terrea comb. nov. and description of Tatumella morbirosei sp. nov. (2009)

Pantoea citrea, Pantoea punctata and Pantoea terrea were described for strains isolated from fruit and soil originating in Japan. These three 'Japanese' species have been shown to be phylogenetically distant from other species of the genus Pantoea. It has been observed previously that, using multilocus sequence analysis (MLSA), the 'Japanese' species consistently formed a distinct clade with an extended branch length, casting doubt on the inclusion of these species within the genus Pantoea. Furthermore, the 'Japanese' species are closely related to Tatumella ptyseos, strains of which originate from human clinical specimens. DNA-DNA hybridization and phenotypic tests confirmed the observed phylogenetic distance of P. citrea, P. punctata and P. terrea from the genus Pantoea and the affiliation of these species with Tatumella. In addition, strains causing pink disease of pineapple, identified previously as P. citrea , were shown to represent a separate species by using 16S rRNA gene sequence analysis, and MLSA and DNA-DNA hybridization data. The name Tatumella morbirosei sp. nov. with the type strain LMG 23360(T) (=BD 878(T)=NCPPB 4036(T)=CMC6(T)) is proposed to accommodate these strains. The new combinations Tatumella citrea (Kageyama et al. 1992) comb. nov. (type strain, SHS 2003(T)=ATCC 31623(T)=BD 875( T)=CCUG 30156(T)=CIP 105599(T)=DSM 13699(T)=JCM 8882(T)=LMG 22049(T)), Tatumella punctata (Kageyama et al. 1992) comb. nov. (type strain, SHS 2006(T)=ATCC 31626(T)=BD 876( T)=CCUG 30159(T)=CIP 105598(T)=DSM 13700(T)=JCM 8885(T)=LMG 22050(T)) and Tatumella terrea (Kageyama et al. 1992) comb. nov. (type strain, SHS 2008(T)=ATCC 31628(T)=BD 877(T)=CCUG 30161(T)=CIP 105600(T)=DSM 13701(T)=JCM 8887(T)=LMG 22051(T)) are proposed for P. citrea, P. punctata and P. terrea , respectively.
Ammonia in breath and emitted from skin (2013)

Ammonia concentrations in exhaled breath (eNH3) and skin gas of 20 healthy subjects were measured on-line with a commercial cavity ring-down spectrometer and compared to saliva pH and plasma ammonium ion (NH(+)4), urea and creatinine concentrations. Special attention was given to mouth, nose and skin sampling procedures and the accurate quantification of ammonia in humid gas samples. The obtained median concentrations were 688 parts per billion by volume (ppbv) for mouth-eNH3, 34 ppbv for nose-eNH3, and 21 ppbv for both mouth- and nose-eNH3 after an acidic mouth wash (MW). The median ammonia emission rate from the lower forearm was 0.3 ng cm(-2) min(-1). Statistically significant (p < 0.05) correlations between the breath, skin and plasma ammonia/ammonium concentrations were not found. However, mouth-eNH3 strongly (p < 0.001) correlated with saliva pH. This dependence was also observed in detailed measurements of the diurnal variation and the response of eNH3 to the acidic MW. It is concluded that eNH3 as such does not reflect plasma but saliva and airway mucus NH(+)4 concentrations and is affected by saliva and airway mucus pH. After normalization with saliva pH using the Henderson-Hasselbalch equation, mouth-eNH3 correlated with plasma NH(+)4, which points to saliva and plasma NH(+)4 being linked via hydrolysis of salivary urea.
INFORMATION SECURITY AND NEW TECHNOLOGY Potential Threats and Solutions (1994)

Abstract IS security professionals are faced with a stream of products and information technologies that create both new threats and the potential for new defenses. This article explores the impact of emerging technologies, including imaging and wireless communications, on information security.
Update on colorectal cancer. (2000)

An estimated 129,400 new cases of colorectal cancer occurred in the United States during 1999. The lifetime risk of developing this cancer is 2.5 to 5 percent in the general population but two to three times higher in persons who have a first-degree relative with colon cancer or an adenomatous polyp. Between 70 and 90 percent of colorectal cancers arise from adenomatous polyps, whereas only 10 to 30 percent arise from sessile adenomas. Tumors or polyps that develop proximal to the splenic flexure carry a poorer prognosis than those that arise more distally, in part because of delayed diagnosis secondary to later development of symptoms. The Dukes system is the classic staging method for colorectal cancer; the TNM staging system is more detailed and therefore more useful for surgical purposes. Although screening guidelines vary, most agree that colorectal cancer screening should begin at 50 years of age in patients without a personal or family history of colorectal cancer.
Single molecule measurements of channel proteins incorporated into biomimetic polymer membranes (2006)

Lipid bilayer membranes have been extensively utilized to examine membrane channel and pore proteins and are the subjects of study in their own right. There has been considerable recent interest in developing technologies to substitute or strengthen lipid bilayer membranes for a number of applications, including sensing or drug delivery. In particular, biomimetic amphiphilic block co-polymers have been shown to have the capacity to form membrane structures and to contain membrane proteins within them. In this work, we describe the creation of biomimetic membranes from a 5.7 nm thick tri-block co-polymer and the investigation of the effects of the polymer environment on incorporated channel proteins (α-haemolysin, OmpG, and alamethicin) with single molecule transport measurements. We found that the polymer membranes consistently have seal resistances of tens of GΩ and greater, and that the conductance of single channels is reduced by approximately 10% from that measured in diphytanoyl phosphatidylcholine lipid membranes, possibly as a result of increased cohesion of the polymer compared to lipid. The voltage gating ability and threshold voltages of voltage gated channels were also found to be very similar in the lipid and polymer environments.
Long-Term and Memory Immune Responses in Mice against Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus Glycoprotein Ectodomains (2012)

Although respiratory syncytial virus (RSV) is a significant human pathogen, no RSV vaccines are available. We have reported that a virus-like particle (VLP) RSV vaccine candidate stimulated, in mice, robust, protective anti-RSV glycoprotein T(H)1 biased immune responses without enhanced respiratory disease upon RSV challenge. We report here an analysis of long-term responses to these VLPs. BALB/c mice immunized, without adjuvant, with VLPs or with infectious RSV generated anti-F and anti-G protein serum antibody responses that were stable over 14 months. Neutralizing antibody titers stimulated by VLPs were robust and durable for 14 months, whereas those of RSV-immunized animals declined significantly by 3 months. F protein-specific antibody-secreting cells were detected in the bone marrows of VLP-immunized mice but not in the marrows of RSV-immunized mice. Adoptive transfer of enriched splenic B cells from VLP-immunized mice into immunodeficient rag(-/-) mice resulted in anti-F and anti-G protein serum IgG antibody responses, in recipient mice, that were protective upon RSV challenge. In contrast, transfer of splenic B cells from RSV-immunized mice produced no detectable serum antibody in the recipients, nor could these mice inhibit RSV replication upon virus challenge. Immunization with VLPs stimulated the formation of germinal center GL7(+) B cells in normal mice. VLP immunization of TCR βδ(-/-) T-cell-deficient mice did not induce anti-RSV IgG antibodies, results consistent with T-cell-dependent immune responses. These results demonstrate that VLPs are effective in stimulating long-lived RSV-specific, T-cell-dependent neutralizing antibody-secreting cells and RSV-specific memory responses.
An object attribute thresholding algorithm for document image binarization (2002)

Document image binarization is not a completely solved problem for unconstrained document images. Binarization algorithms, whether global or local, can easily fail on images with noisy or complex background, or poor contrast. The authors report preliminary results on a new approach to document image binarization, an algorithm based on gray scale histogram and run-length histogram analysis. Experimental results on unconstrained machine printed address blocks from the US letter mail stream show that over 99% of such address blocks can be correctly binarized.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis and Biological Evaluation of Fatty Acyl Ester Derivatives of (−)-2′,3′-Dideoxy-3′-thiacytidine (2012)

A number of fatty acyl derivatives of (-)-2',3'-dideoxy-3'-thiacytidine (lamivudine, 3TC, 1) were synthesized and evaluated for their anti-HIV activity. The monosubstituted 5'-O-fatty acyl derivatives of 3TC (EC(50) = 0.2-2.3 μM) were more potent than the corresponding monosubstituted N(4)-fatty acyl (EC(50) = 0.4-29.4 μM) and 5'-O-N(4)-disubstituted (EC(50) = 72.6 to >154.0 μM) derivatives of the nucleoside. 5'-O-Myristoyl (16) and 5'-O-12-azidododecanoyl derivatives (17) were found to be the most potent compounds (EC(50) = 0.2-0.9 μM) exhibiting at least 16-36-fold higher anti-HIV activity against cell-free virus than 1 (EC(50) = 11.4-32.7 μM). The EC(90) values for 16 against B-subtype and C-subtype clinical isolates were several folds lower than those of 1. The cellular uptake studies confirmed that compound 16 accumulated intracellularly after 1 h of incubation with CCRF-CEM cells and underwent intracellular hydrolysis. 5'-O-Fatty acyl derivatives of 1 showed significantly higher anti-HIV activity than the corresponding physical mixtures against the B-subtype virus.
Data-driven subtypes of major depressive disorder: a systematic review (2012)

The studies performed to date do not provide conclusive evidence for the existence of depressive symptom dimensions or symptomatic subtypes. The wide diversity of identified factors and classes might result either from the absence of patterns to be found, or from the theoretical and modeling choices preceding analysis.