gebhart/patrepeval huggingface dataset:
High doses of siRNAs induce eri-1 and adar-1 gene expression and reduce the efficiency of RNA interference in the mouse (2005)

RNAi (RNA interference) is a gene-silencing mechanism that is conserved in evolution from worm to human and has been a powerful tool for gene functional research. It has been clear that the RNAi effect triggered by endogenous or exogenous siRNAs (small interfering RNAs) is transient and dose-dependent. However, there is little information on the regulation of RNAi. Recently, some proteins that regulate the RNA-silencing machinery have been identified. We have observed in previous work that the expression of target genes rebounds after being suppressed for a period of time by siRNAs. In the present study, we used secretory hepatitis B virus surface antigen gene as a reporter and compared its expression level in cell culture and mice challenged by different doses of siRNAs. A quicker and higher rebound of gene expression was observed in mice tail-vein-injected with higher doses of siRNA, and the rebound was associated with an increase in the mRNA level of meri-1 (mouse enhanced RNAi) and adar-1 (adenosine deaminase acting on RNA) genes encoding an exonuclease and RNA-specific adenosine deaminase respectively. Down-regulation of meri-1 by RNAi enhanced the sensitivity and efficiency of siRNA in inhibiting the expression of hepatitis B virus surface antigen. These results indicate that RNAi machinery may be under negative regulation, through the induction of a series of genes coding for destabilizing enzymes, by siRNAs introduced into the cell, and also suggest that a suitable amount of siRNA should be used for research or therapeutic applications.
Structural evolution of toll-like receptor 7/8 agonists from imidazoquinolines to imidazoles (2021)

Several synthetic heterocyclic small molecules like imiquimod, resiquimod, CL097, CL075, bromopirone, tilorone, loxoribine and isatoribine demonstrated TLR7/8 agonistic activity and relatively modest structural changes in such molecules result in major variation in the TLR7 and/or TLR8 activity. A strict dependency of the electronic configuration of the heterocyclic system was also observed to influence the agonistic activity. In the present review, an evolution of imidazole based TLR7/8 agonist from imidazoquinoline based scaffold is delineated along with the elaboration of detailed structure activity relationship (SAR) in each chemotype. The structural and activity details of not only the active compounds but also the related inactive compounds are included to better understand the SAR. TLR7/8 agonists are emerging as promising vaccine adjuvant candidates and the present SAR and structural information will provide a road map towards the identification of more potent and appropriate candidates for further drug discovery.
An image processing architecture and a motion control method for an autonomous vehicle (2003)

Describes the vision based road boundary extraction method and the trajectory control method. The authors have developed a real-time Hough transform module using the original algorithm. They improved the quadratic prediction model to the two-state prediction model for the trajectory control. They assumed that the road considered for this type of car would be highways defined by the Road Structure Standard in Japan.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Proteomics: from hypothesis to quantitative assay on a single platform. Guidelines for developing MRM assays using ion trap mass spectrometers (2008)

High-throughput HPLC-mass spectrometry (HPLC-MS) is routinely used to profile biological samples for potential protein markers of disease, drug efficacy and toxicity. The discovery technology has advanced to the point where translating hypotheses from proteomic profiling studies into clinical use is the bottleneck to realizing the full potential of these approaches. The first step in this translation is the development and analytical validation of a higher throughput assay with improved sensitivity and selectivity relative to typical profiling assays. Multiple reaction monitoring (MRM) assays are an attractive approach for this stage of biomarker development given their improved sensitivity and specificity, the speed at which the assays can be developed and the quantitative nature of the assay. While the profiling assays are performed with ion trap mass spectrometers, MRM assays are traditionally developed in quadrupole-based mass spectrometers. Development of MRM assays from the same instrument used in the profiling analysis enables a seamless and rapid transition from hypothesis generation to validation. This report provides guidelines for rapidly developing an MRM assay using the same mass spectrometry platform used for profiling experiments (typically ion traps) and reviews methodological and analytical validation considerations. The analytical validation guidelines presented are drawn from existing practices on immunological assays and are applicable to any mass spectrometry platform technology.
<title>Synthesis of axially disubstituted octakis-alkoxy-germanium(IV) phthalocyanines</title> (1994)

A series of new octakis-substituted Germanium-phthalocyanines for use in photodynamic therapy of tumors has been synthesized. Starting from 1,4-dialkoxy-2,3-dicyano-benzene the metal-free octakis-alkoxy-phthalocyanine 13 was prepared. The metallation to the corresponding octakis-alkoxy-GeCl<SUB>2</SUB>-phthalocyanine 15 was done with a GeCl<SUB>4</SUB>-DMF complex. Alkaline hydrolysis gave quantitatively the octakis-alkoxy-Ge(OH)<SUB>2</SUB>- phthalocyanine 16. By substitution of the hydroxy groups with alcohols, thiols and silanols the axially disubstituted phthalocyanines were obtained. The most important photophysical properties for PDT (Q-bands, singlet oxygen quantum yields and (Phi) <SUB>f</SUB>) are reported.
Curcumin Binding to DNA and RNA (2009)

Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical with a variety of biological activities. The ongoing research and clinical trials have proved that this natural phenolic compound has great and diverse pharmacological potencies. Beside its effective antioxidant, antiinflammatory, and antimicrobial/antiviral properties, curcumin is also considered as a cancer chemopreventive agent. While the antioxidant activity of curcumin is well documented, its interaction with DNA and RNA is not fully investigated. This study was designed to examine the interactions of curcumin with calf thymus DNA and yeast RNA in aqueous solution at physiological conditions, using constant DNA and RNA concentration (6.25 mM) and various curcumin/polynucleotide (phosphate) ratios of 1/120, 1/80, 1/40, 1/20, and 1/10. Fourier transform infrared (FTIR) and UV-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of curcumin-DNA and curcumin-RNA complexes in aqueous solution. Spectroscopic evidence showed that curcumin binds to the major and minor grooves of DNA duplex and to RNA bases as well as to the back bone phosphate group with overall binding constants of K(curcumin-DNA) = 4.255 x 10(4) M(-1) and K(curcumin-RNA) = 1.262 x 10(4) M(-1). Major DNA and RNA aggregation occurred at high pigment concentration. No conformational changes were observed upon curcumin interaction with these biopolymers; that is, DNA remains in the B, and RNA retains its A-family structure.
LPTO-03. IN-VITRO & IN-VIVO CULTURE OF PATIENT (PT) DERIVED CSF-CTCs IN LEPTOMENINGEAL DISEASE (LMDz) FROM MELANOMA TO IDENTIFY NOVEL TREATMENT STRATEGIES (2019)

Abstract BACKGROUND: Approximately 5% of melanoma pts develop LMDz. There are essentially no models of LMDz available for therapeutic development. Here we report, the in-vitro &amp; in-vivo culturing of CSF-CTCs. METHODS: CSF-CTCs were detected by the Veridex CellSearch® System. Cell-free DNA and cell-associated DNA were extracted, sequenced and profiled. Expanded ex-vivo CSF-CTCs were grown in-vitro and tested for drug sensitivity. CSF-CTCs were grown successfully in-vivo from 1 pt; labeled human Braf V600E WM164 cells were injected IT in as a control. RESULTS: CSF-CTCs: 12 LMDz pts and 8 melanoma pts without LMDz were studied. All but 1 LMDz pts (92%) had CSF-CTCs (avg: 2148.60; range 23 - 3055 CTCs/ml). In contrast, 3/8 (37%) melanoma Brain Mets pts without LMDz had CSF-CTCs but fewer of them (avg: 0.31; range 0.13 - 0.6 CTCs/ml CSF). CSF-CTCs Profile: These had BrafV600E (83%), and GNAQ Q209P &amp; NRAS Q61R in 1 pt each. Ex-vivo culture of CSF-CTCs and PDX model: After lengthy optimization of conditions we successfully expanded CSF-CTCs in-vitro (~25% of pts), and in-vivo in immunodeficient mice from 1 pt (~10% of samples). Ceritinib, used as a FAK inhibitor, with MEKi was effective in-vitro (p=3.17e-6) and prolonged survival in-vivo in LMDz (median survival: &amp;gt;32 days vs control: 18 days; p=7.81e-5). CONCLUSIONS: Though the sample size is small, this is the first report of the successful in-vitro &amp; in-vivo culture of CSF-CTCs from pts with LMDz. Single cell analysis to determine how representative these models are and further in-vivo testing are in progress.
Business Models for Insurance of Business Web Services (2011)

A new business—insurance on business Web services—is proposed. As more and more Web services will be developed to fulfill the ever increasing needs of e-Business, the e-marketplace for Web services will soon be established. However, the qualities of these business Web services are unknown without real experiences and users can hardly make decisions on service selection. We propose that insurance can help build trust in the market of Web services. In this chapter, we propose three insurance models for business Web services and enabling technologies, including quality description, reputation scheme, transaction analysis, etc. We believe that the insurance of business Web services will help service competition and hence boost the development of more and more business Web services, and the software industry at large.Request access from your librarian to read this chapter's full text.
Bacillus velezensis RC 218 as a biocontrol agent to reduce Fusarium head blight and deoxynivalenol accumulation: Genome sequencing and secondary metabolite cluster profiles (2016)

Bacillus subtilis RC 218 was originally isolated from wheat anthers as a potential antagonist of Fusarium graminearum, the causal agent of Fusarium head blight (FHB). It was demonstrated to have antagonist activity against the plant pathogen under in vitro and greenhouse assays. The current study extends characterizing B. subtilis RC 218 with a field study and genome sequencing. The field study demonstrated that B. subtilis RC 218 could reduce disease severity and the associated mycotoxin (deoxynivalenol) accumulation, under field conditions. The genome sequencing allowed us to accurately determine the taxonomy of the strain using a phylogenomic approach, which places it in the Bacillus velezensis clade. In addition, the draft genome allowed us to use bioinformatics to mine the genome for potential metabolites. The genome mining allowed us to identify 9 active secondary metabolites conserved by all B. velezensis strains and one additional secondary metabolite, the lantibiotic ericin, which is unique to this strain. This study represents the first confirmed production of ericin by a B. velezensis strain. The genome also allowed us to do a comparative genomics with its closest relatives and compare the secondary metabolite production of the publically available B. velezensis genomes. The results showed that the diversity in secondary metabolites of strains in the B. velezensis clade is driven by strains making different antibacterials.
Cryptographically secure shields (2014)

Probing attacks are serious threats on integrated circuits. Security products often include a protective layer called shield that acts like a digital fence. In this article, we demonstrate a new shield structure that is cryptographically secure. This shield is based on the newly proposed SIMON lightweight block cipher and independent mesh lines to ensure the security against probing attacks of the hardware located behind the shield. Such structure can be proven secure against state-of-the-art invasive attacks. For the first time in the open literature, we describe a chip designed with a digital shield, and give an extensive report of its cost, in terms of power, metal layer(s) to sacrifice and of logic (including the logic to connect it to the CPU). Also, we explain how “Through Silicon Vias” (TSV) technology can be used for the protection against both frontside and backside probing.
Development and Characterization of Eucalyptol Microemulsions for Topic Delivery of Curcumin (2011)

Microemulsions have received great attention for applications in transdermal drug delivery. The use of curcumin for treating various skin diseases like scleroderma, psoriasis, and skin cancer was extensively reported. The solubility of curcumin in various oils, surfactants, and cosurfactants was studied herein in order to find the optimal components for a transdermal delivery vehicle. Microemulsion systems composed of eucalyptol, polysorbate 80, ethanol, and water were developed as transdermal delivery vehicles for curcumin. Effects of the microemulsion composition on transdermal curcumin delivery were studied using Franz diffusion cells. The transdermal curcumin flux, permeability coefficient, and enhancement ratio were analyzed to evaluate the effects of eucalyptol/water ratios in the microemulsions. Pseudo-ternary phase diagrams of the eucalyptol microemulsions with various surfactant/cosurfactant ratios (1:1-1:3) were constructed to investigate their phase behaviors. Conductivity, interfacial tension, size, and viscosity data of the microemulsions were used to characterize the physicochemical properties of transdermal vehicles. The influence of the microemulsions on skin histology and on the delivery route was analyzed using hematoxylin/eosin staining and confocal laser scanning microscopy. In conclusion, microemulsions were successfully developed for transdermal curcumin delivery after screening various components and adjusting the oil/water ratios. The curcumin permeation rate of the microemulsion developed was 15.7-fold higher than that of the control (eucalyptol only). These results indicate that an eucalyptol microemulsion system is a promising tool for the percutaneous delivery of curcumin.
Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma (2017)

Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different driver mutants, including the serine/threonine-protein kinase B-raf (BRAF) inhibitor dabrafenib, which has exhibited promising efficacy for treating patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients carrying mutations that may be treated using targeted therapies is important. However, the methods of molecular detection presently applied in clinical practice, particularly detection of BRAF in NSCLC patients, require further investigation. Therefore, more sensitive and economic methods are required. The present study applied the competitive allele-specific TaqMan polymerase chain reaction (CastPCR) technology to the molecular detection of EGFR (del2235-2249, del2236-2250, T790M, L858R) and BRAF (V600E, G469A, D594G) mutations in 144 treatment-naive patients with lung adenocarcinoma, and analyzed the association between the mutation rates and patients' clinicopathological features. 51.4% (74/144) cases were identified harboring EGFR mutations. A total of 40.3% (58/144) patients carried sensitizing mutations (exon 19 deletion or L858R) and 14.6% (21/144) carried T790M mutations. 6.9% (10/144) mutation-positive patients were double-mutated. Total EGFR mutation rate was significantly increased in female compared with that of males (60.9 vs. 43.8%, P<0.05), in non-smokers compared with that of smokers (62.8 vs. 34.5%, P<0.05). In total, 8.3% (12/144) patients were identified with BRAF mutations. 16.7% were V600E (2/12) and 83.3% (10/12) were non-V600E mutants. Among the 10 non-V600E mutations, D594G accounted for 90.0% (9/10) and G469A accounted for 10.0% (1/10). Statistical analysis demonstrated that the BRAF mutation rate was not associated with any of the following clinicopathological features: Sex, age, smoking history, clinical stages, distant metastasis, differentiation degree, tumor size and regional lymph node metastasis (P≥0.05). CastPCR technology is a robust method with high sensitivity for the molecular detection of EGFR and BRAF mutations in clinical formalin-fixed paraffin-embedded samples.
Multiphoton crosslinking for biocompatible 3D printing of type I collagen (2015)

Multiphoton fabrication is a powerful technique for three-dimensional (3D) printing of structures at the microscale. Many polymers and proteins have been successfully structured and patterned using this method. Type I collagen comprises a large part of the extracellular matrix for most tissue types and is a widely used cellular scaffold material for tissue engineering. Current methods for creating collagen tissue scaffolds do not allow control of local geometry on a cellular scale. This means the environment experienced by cells may be made up of the native material but unrelated to native cellular-scale structure. In this study, we present a novel method to allow multiphoton crosslinking of type I collagen with flavin mononucleotide photosensitizer. The method detailed allows full 3D printing of crosslinked structures made from unmodified type I collagen and uses only demonstrated biocompatible materials. Resolution of 1 μm for both standing lines and high-aspect ratio gaps between structures is demonstrated and complex 3D structures are fabricated. This study demonstrates a means for 3D printing with one of the most widely used tissue scaffold materials. High-resolution, 3D control of the fabrication of collagen scaffolds will facilitate higher fidelity recreation of the native extracellular environment for engineered tissues.
Improved 68Ga-labelled truncated peptides targeting the neuropeptide Y1 receptor for cancer imaging by positron emission tomography (2016)

1160 Objectives Many human cancers express the neuropeptide Y1 receptor (Y1R), notably breast cancers. Limited success has been achieved for Y1R imaging agents due to the short biological half-life of the peptide, and truncated neuropeptide Y (NPY) analogues have not been successfully used for Y1R imaging to date. The goal of this study was to evaluate the possibility of using radiolabeled modified truncated NPY analogues to visualize Y1R expression in a preclinical model of Y1R-positive tumor.  Methods Truncated NPY analogues were synthesized using solid phase peptide synthesis. These peptides were derived from the sequence [Pro30, Tyr32, Leu34]NPY(28-36), also known as BVD15. Tyr-5 and Arg-6 were substituted with unnatural amino acids in order to enhance plasma stability while maintain the receptor binding affinity to Y1R. In addition, we substituted Leu-4 to Lys-4 in order to conjugate a DOTA chelator for 68Ga labeling, with or without a neutral or cationic linker. Four different peptides were evaluated. The receptor binding affinity and in vitro plasma stability of these compounds were evaluated. PET/CT imaging and biodistribution studies were performed using immune-compromised mice bearing HEK293T::WT and HEK293T::hY1R tumors. Results [Lys(DOTA)4, Bip5]BVD15 (CCZ01035), [Lys(Ahx-DOTA)4, Bip5]BVD15 (CCZ01053), and [Lys(Pip-DOTA)4, Bip5]BVD15 (CCZ01055) had good binding affinity to Y1R (Ki = 23.4 - 32.3 nM). However, the substitution of homoarginine for arginine at position 6 [Lys(DOTA)4, Har6]BVD15 (P05067) led to poor binding affinity (Ki > 1000 nM) and this compound was not further evaluated. CCZ01035, CCZ01053 and CCZ01055 were labeled with 68Ga with > 99% radiochemical purity with average decay-corrected radiochemical yields ranging from 42 – 69%. Their average specific activity were > 2.5 Ci / μmol (n = 3). [68Ga]CCZ01035 was very stable in vitro, with more than 95% of intact peptide after 1 h incubation in mouse plasma. The peptides with an Ahx or Pip linker had lower plasma stability in vitro. PET/CT imaging and biodistribution studies for 68Ga-labeled CCZ01053, CCZ01035 and CCZ01055 showed that the radioactivity had a predominant renal clearance. HEK293T::hY1R tumors were clearly visualized with minimal background activity with CCZ01035 and CCZ01055. [68Ga]CCZ01055 provided lower kidney accumulation and improved tumor visualization, with average uptake ratios of Y1R tumor to wild type tumor, blood and muscle of 3.87 ± 0.83, 4.12 ± 1.14 and 17.6 ± 4.64 %ID/g, respectively. Y1R tumor uptake with [68Ga]CCZ01055 was reduced with co-injection of 100 μg peptide YY, confirming the specificity of tumor accumulation was receptor mediated. Conclusions Key amino-acid substitutions combined with the use of a cationic linker on a modified DOTA-conjugated truncated NPY1R binding peptide allowed clear visualization of NPY1R expressing tumors. [68Ga]CCZ01055 is a promising imaging agent to visualize Y1R expressing cancers by positron emission tomography.
Micro-Bunched Beam Production at FAST for Narrow Band THz Generation Using a Slit-Mask (2018)

We discuss simulations and experiments on creating micro-bunch beams for generating narrow band THz radiation at the Fermilab Accelerator Science and Technology (FAST) facility. The low-energy electron beamline at FAST consists of a photoinjector-based RF gun, two L-band superconducting accelerating cavities, a chicane, and a beam dump. The electron bunches are lengthened with cavity phases set off-crest for better longitudinal separation and then micro-bunched with a slit-mask installed in the chicane. We carried out the experiments with 30 MeV electron beams and detected signals of the micro-bunching using a skew quadrupole magnet in the chicane. In this paper, the details of micro-bunch beam production, the detection of micro-bunching and comparison with simulations are described.
The power of withholding (2016)

William Trevor's Felicia's Journey is a literary work which reflects how individual lives bear the imprint of the political, economic and cultural narratives and histories of their places of origin. This chapter argues that the novel transcends simplistic paradigms and embraces a much broader picture of humanity and inhumanity. It is undeniable that historical conflicts between Ireland and Britain are a significant presence in Felicia's Journey. William Trevor possesses a mastery of narrative technique which has been recognised by readers and reviewers alike for almost fifty years. Thwarted communications, withheld information recur not just as a motif in Trevor's plots, but also of his narrative technique, as his deft and canny characterisation of Joseph Ambrose Hilditch exemplifies. Where transparency and intimacy typify his representation of the main female characters, Felicia and Miss Calligary, and their pasts, concealment, ambiguity and piecemeal disclosure create opaque perceptions of Hilditch's world.