gebhart/patrepeval huggingface dataset:
Preclinical antitumor activity of nanoliposomal irinotecan (Nal-IRI, MM-398) and utilization as a foundation of front-line pancreatic cancer regimens. (2017)

336 Background: Nanoliposomal irinotecan (nal-IRI, MM-398) recently gained approval in combination with 5-fluorouracil/leucovorin (5-FU/LV) in post-gemcitabine metastatic pancreatic ductal adenocarcinoma (PDAC) based on the extended survival and manageable safety profile observed in the Phase 3 NAPOLI-1 trial. Preclinically, we have previously demonstrated the anti-tumor activity of nal-IRI with 5-FU and oxaliplatin, standard of care agents in first-line PDAC, and are currently investigating this combination in patients with previously untreated metastatic PDAC in a Phase 2 clinical trial (NCT02551991). Herein, we further evaluate nal-IRI as a potential backbone of first-line metastatic PDAC by assessing the preclinical anti-tumor activity of nal-IRI relative to, and in combination with, gemcitabine and nanoparticle albumin-bound-paclitaxel (nab-P). Methods: Nal-IRI tumor metabolite (CPT-11 and SN-38) levels were measured in mice treated with nal-IRI in combination with gemcitabine or nab-P. Anti-tumor activity and tolerability of nal-IRI, 5-FU, gemcitabine and nab-P monotherapies and combinations were evaluated using pancreatic cancer cell line (ASPC-1 and CFPAC-1)-derived xenograft models, as well as a panel of five patient-derived xenograft models. Results: Administration of gemcitabine or nab-P prior to or simultaneously with nal-IRI resulted in unchanged or increased nal-IRI deposition, as measured by tumor CPT-11 and SN-38 levels at 24 hours post-injection. Moreover, in both cell line-derived and patient-derived xenograft models of PDAC, nal-IRI monotherapy demonstrated comparable or improved anti-tumor activity relative to gemcitabine or nab-P monotherapies. Further, nal-IRI consistently improved tumor growth inhibition and survival when used in combination with either 5-FU, gemcitabine and/or nab-P, relative to the combination of gemcitabine plus nab-P. All treatments were well-tolerated in these preclinical models. Conclusions: These findings illustrate the compatibility and therapeutic potential of nal-IRI as a foundation of first-line PDAC combination regimens, and warrant clinical evaluation.
RefSeq microbial genomes database: new representation and annotation strategy (2013)

The source of the microbial genomic sequences in the RefSeq collection is the set of primary sequence records submitted to the International Nucleotide Sequence Database public archives. These can be accessed through the Entrez search and retrieval system at http://www.ncbi.nlm.nih.gov/genome. Next-generation sequencing has enabled researchers to perform genomic sequencing at rates that were unimaginable in the past. Microbial genomes can now be sequenced in a matter of hours, which has led to a significant increase in the number of assembled genomes deposited in the public archives. This huge increase in DNA sequence data presents new challenges for the annotation, analysis and visualization bioinformatics tools. New strategies have been developed for the annotation and representation of reference genomes and sequence variations derived from population studies and clinical outbreaks.
0.85 µm bottom-emitting vertical-cavity surface-emittinglaser diode arrays grown on AlGaAs substrates (1994)

The first 0.85 µm 8×8 bottom-emitting vertical-cavity surface-emitting laser diodes (VCSELs) have been grown on AlGaAs substrates. Their characteristics are the same as those of VCSELs grown on GaAs substrate. The authors have also fabricated 8×8 independently addressable VCSEL arrays which exhibited good lasing characteristics and uniform threshold current density.
Photodynamic Therapy Targeted to Pathogens (2004)

Photodynamic therapy (PDT) employs a non-toxic dye termed a photosensitizer (PS) together with low intensity visible light, which, in the presence of oxygen, produce cytotoxic species. PS can be targeted to its destination cell or tissue and, in addition, the irradiation can be spatially confined to the lesion giving PDT the advantage of dual selectivity. This promising approach can be used for various applications including microbial inactivation and the treatment of infections. Resistance to PDT has not been shown and multiantibiotic-resistant strains are as easily killed as naive strains. It is known that Gram (+) bacteria are more sensitive to PDT as compared to Gram (-) species. However, the use of cationic PS or agents that increase the permeability of the outer membrane allows for the effective killing of Gram (-) organisms. Some PS have an innate positive charge, but our approach is to link PS to a cationic molecular vehicle such as poly-L-lysine. This modification dramatically increases PS binding to and penetrating through the negatively charged bacterial permeability barrier. Due to focused light delivery the use of PDT is possible only for localized infections. Nonetheless numerous diseases can be treated. Selectivity of the PS for microbes over host cells, accurate delivery of the PS into the infected area, and PDT dose adjustment help minimize side effects and give PDT an advantage over conventional therapy. There are only a few reports about the use of antimicrobial PDT in animal models and clinical trials. We have used genetically modified bioluminescent bacteria to follow the effect of PDT in infected wounds, burns, and soft tissue infections in mice. Not only were bacteria infecting wounds, burns, and abscesses killed, but mice were saved from death due to sepsis and wound healing was improved.
Pengaruh Perluasan Merek terhadap Brand Image; Studi Empiris pada Merek Bodrex (Brand Extensions Influence on Brand Image:Empirical Study on Bodres's Brand) (2010)

Bodrex's manufacturer is attempting to use Bodrex brand success to enter flu and cough medicine category by releasing Bodrex Flu dan Batuk. The launching of Bodrex Flu dan Batuk will affect Bodrex's brand image. The objective of this research is to examine the influence of Bodrex Flu dan Batuk on Bodrex's brand image. This research was conducted in Yogyakarta using purposive sampling method on respondents that have been using Bodrex for 6 months. Data were collected by using questionnaire with Likert scale that measured initial brand image, category fit, image fit, consumers' attitude towards brand extension, innovative ness, and final brand image, Structural Equation Modeling (SEM) application was used to analyse data. Research result showed that brand extension has its effect on Bodrex's brand image, in which its final brand Image was affected significantly by consumers' attitude towards brand extension (t-value = 4.88) and Initial brand Image (t-value = 15.14). However, Initial brand Image (standardized solution = 0,88) has a larger role In final brand Image formation than consumers' attitude towards brand extension (standardized solution = 0.15). Consumers' attitude towards Bodrex's brand extension affected significantly by Image fit (t-value = 5.29), category fit (t¬value = 1.99) and Insignificantly by Initial brand Image (t-value = 0.49).
The anti-hepatitis B virus activities, cytotoxicities, and anabolic profiles of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (1992)

The anti-hepatitis B (anti-HBV) activities of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (2'-deoxy-3'-thia-5-fluorocytosine [FTC]) were studied by using an HBV-transfected cell line (HepG2 derivative 2.2.15, subclone P5A). The (-) isomer was found to be a potent inhibitor of viral replication, with an apparent 50% inhibitory concentration of 10 nM, while the (+) isomer was found to be considerably less active. Both isomers showed minimal toxicity to HepG2 cells (50% inhibitory concentration, > 200 microM) and showed minimal toxicity in the human bone marrow progenitor cell assay. In accord with the cellular antiviral activity data, the 5'-triphosphate of (-)-FTC inhibited viral DNA synthesis in an endogenous HBV DNA polymerase assay, while the 5'-triphosphate of the (+) isomer was inactive. Unphosphorylated (-)-FTC did not inhibit product formation in the endogenous assay, suggesting that the antiviral activity of the compound is dependent on anabolism to the 5'-triphosphate. Both (-)- and (+)-FTC were anabolized to the corresponding 5'-triphosphates in chronically HBV-infected HepG2 cells. The rate of accumulation and the steady-state concentration of the 5'-triphosphate of (-)-FTC were greater. Also, (-)-FTC was not a substrate for cytidine deaminase and, therefore, is not subject to deamination and conversion to an inactive uridine analog. The (+) isomer is, however, a good substrate for cytidine deaminase.
Pharmacokinetic study of anti-interleukin-6 (IL-6) therapy with monoclonal antibodies: enhancement of IL-6 clearance by cocktails of anti-IL-6 antibodies (1995)

The use of inhibiting cytokine-binding-proteins (CBPs) such as soluble cytokine receptors and anticytokine antibodies is considered for the treatment of cytokine-dependent diseases. The pleiotropic cytokine interleukin-6 (IL-6) is a target for immunointervention in numerous pathologic situations, including multiple myeloma, B-cell lymphoma, and rheumatoid arthritis. An antitumor response was obtained in the treatment of a patient with multiple myeloma. A controversial issue is to evaluate whether the carrier effect of the CBPs might limit their efficiency in blocking the target cytokine. We analyzed the pharmacokinetics of radiolabeled IL-6 in mice treated with various combinations of anti-IL-6 antibodies. We show that injection of one or two antibodies led to the stabilization of the cytokine. Conversely, simultaneous treatment with three anti-IL-6 antibodies, binding to three distinct epitopes, induced the rapid uptake of the trimeric immune complexes by the liver and the elimination of IL-6 from the central compartment. The use of cocktails of three antibodies binding simultaneously to a cytokine thus provides a new means of enhancing the clearance of the target molecule and should help in the design of antibody-based clinical trials by overcoming the problem of the accumulation of the cytokine in the form of monomeric immune complexes.
CHIN (community healthcare information network) provides vital healthcare linkages. (1994)

When the term "electronic data interchange" (EDI) was first introduced, it referred to purchase orders, electronic claims, and electronic remittance processing. Those EDI applications are becoming commonplace now, however, and new applications for EDI technology are being developed. Healthcare financial managers should expect that the electronic data highways used for claims traffic eventually will transport both financial and clinical information. These electronic exchanges will not only be between payers and providers but also between hospitals, laboratories, physicians, and allied health professionals. The name commonly given to this view of an electronically linked healthcare world is the community healthcare information network (CHIN).
Robust Docosahexaenoic Acid–Mediated Neuroprotection in a Rat Model of Transient, Focal Cerebral Ischemia (2009)

We conclude that DHA experimental therapy at low and medium doses improves neurologic and histologic outcomes after focal cerebral ischemia and might provide benefits in patients after ischemic stroke.
Functional analysis of plastid DNA replication origins in tobacco by targeted inactivation (2002)

Sequences described as chloroplast DNA replication origins were analysed in vivo by creating deletion and insertion mutants via plastid transformation in tobacco. Deletion of the described oriA sequence, which is located within the intron of the trnI gene, resulted in heteroplastomic transformants, when the selection marker was inserted within the intron. Removal of the complete intron sequence together with the oriA sequence, however, yielded homoplastomic transformants of normal phenotype, in which wild-type signals were no longer detectable through Southern analysis, thus bringing the role of the described oriA sequence for plastome replication into question. Similarly, deletion of sequence elements upstream of trnI, which have a possible ori function in Oenothera, did not show any effect in tobacco. The two copies of oriB, which are located at the very end of the plastome Inverted Repeats, were targeted with two different transformation vectors in a cotransformation approach. While in initial transformants integration of the selection marker could be detected at both sites, the transgene was found exclusively at one site or the other after additional rounds of regeneration. Whereas the copy of oriB in Inverted Repeat B could be completely deleted, targeting of the copy in Inverted Repeat A resulted in heteroplastomic lines, as the essential ycf1 gene was also affected. Due to the strong selection against cotransformants we conclude that at least one copy of the oriB sequence is essential for plastome replication, whereas replication appears possible without oriA elements.
Biochemical and aggregation analysis of Bence Jones proteins from different light chain diseases (2008)

Deposition of immunoglobulin light chains is a result of clonal proliferation of monoclonal plasma cells that secrete free immunoglobulin light chains, also called Bence Jones proteins (BJP). These BJP are present in circulation in large amounts and excreted in urine in various light chain diseases such as light chain amyloidosis (AL), light chain deposition disease (LCDD) and multiple myeloma (MM). BJP from patients with AL, LCDD and MM were purified from their urine and studies were performed to determine their secondary structure, thermodynamic stability and aggregate formation kinetics. Our results show that LCDD and MM proteins have the lowest free energy of folding while all proteins show similar melting temperatures. Incubation of the BJP at their melting temperature produced morphologically different aggregates: amyloid fibrils from the AL proteins, amorphous aggregates from the LCDD proteins and large spherical species from the MM proteins. The aggregates formed under in vitro conditions suggested that the various proteins derived from patients with different light chain diseases might follow different aggregation pathways.
Subtractive Patterning via Chemical Lift-Off Lithography (2012)

Conventional soft-lithography methods involving the transfer of molecular "inks" from polymeric stamps to substrates often encounter micrometer-scale resolution limits due to diffusion of the transferred molecules during printing. We report a "subtractive" stamping process in which silicone rubber stamps, activated by oxygen plasma, selectively remove hydroxyl-terminated alkanethiols from self-assembled monolayers (SAMs) on gold surfaces with high pattern fidelity. The covalent interactions formed at the stamp-substrate interface are sufficiently strong to remove not only alkanethiol molecules but also gold atoms from the substrate. A variety of high-resolution patterned features were fabricated, and stamps were cleaned and reused many times without feature deterioration. The remaining SAM acted as a resist for etching exposed gold features. Monolayer backfilling into the lift-off areas enabled patterned protein capture, and 40-nanometer chemical patterns were achieved.
High-Quality Manganese-Doped Zinc Sulfide Quantum Rods with Tunable Dual-Color and Multiphoton Emissions (2011)

We report a simple, fast and green phosphine-free colloidal chemistry to synthesize high-quality wurtzite-type Mn-doped ZnS quantum rods (QRs) with tunable diameters (1.6-5.6 nm), high aspect ratios (up to 50), variable Mn doping levels (0.18-1.60%), and high quantum yields (up to 45%). The electron paramagnetic resonance spectra with modeling reveal the successful doping of paramagnetic Mn(2+) ions in the host ZnS QRs. The Mn-doped ZnS QRs demonstrate tunable dual-color (orange and blue) emissions by tuning the doping levels and UV excitation wavelengths. The orange emission with long decay lifetime (3.3 ms) originates from the doped Mn(2+) states, while the blue emission with fast decay lifetime (0.31 ns) is attributed to the QR surface states. The bright two- and three-photon excitation upconversion luminescence from the Mn-doped ZnS QRs have been observed using tunable near-infrared femtosecond laser. Our strategy provides a versatile route to programmably control the optical properties of anisotropic semiconductor nanomaterials, which may create new opportunities for photonic devices and bioimaging applications.
A Genetically Encoded Bidentate, Metal‐Binding Amino Acid (2007)

A two-ring binder: To facilitate the design of metalloproteins, the bidentate, metal-binding amino acid bipyridylalanine (BpyAla) was genetically encoded in E. coli in response to the amber nonsense codon with high fidelity and yield. The incorporation of BpyAla requires a BpyAla-specific aminoacyl-tRNA synthetase, which was evolved in a stepwise fashion. The structural basis of selective recognition of BpyAla by this synthetase was also determined. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z703397_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Metastatic models of human cancer xenografted in the nude mouse: The importance of orthotopic transplantation (1994)

Metastatic model of human tumor xenografts have been developed using orthotopic transplantation of histologically intact tissue (onplantation) of lung, stomach, colon, pancreatic, prostate and bladder carcinomas. These models represent the entire process of the metastasis, consisting of local tumor growth, vascular and lymphatic invasion at the local site, flow in the vessels and lymphatic, extravasation at the metastatic organs, and seeding and growth at relevant metastatic sites. Orthotopically transplanted human small-cell lung carcinoma displayed a different chemosensitivity pattern compared with the subcutaneous transplanted model, suggesting different pharmacodynamics between the orthotopic lung and the ectopic subcutaneous sites. The intact-tissue orthotopic-onplantation model seems to be useful to study the mechanism of metastasis for discovery of antimetastatic agents and for the patient tumors and for this treatment design.
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice (2011)

This study identifies tau oligomers as an acutely toxic tau species in vivo, and suggests that tau oligomers induce neurodegeneration by affecting mitochondrial and synaptic function, both of which are early hallmarks in AD and other tauopathies. These results open new avenues for neuroprotective intervention strategies of tauopathies by targeting tau oligomers.
Design Considerations for a Real-Time Ocular Counterroll Instrument (1983)

A video-based technique for measuring the torsional movement of the eye (counterroll) by processing video images of the eyeball is presented. Spectral estimates show that most of the variance of the iris image is in the angular direction. It will be demonstrated that cross correlation between sequences that are obtained by circular sampling of the digitized image of the iris is sufficient to extract the counterroll information. Computation time for angular correlation is thus significantly reduced and real-time hardware implementation becomes feasible. As the result of a preprocessing step, we obtain the information about the horizontal and vertical movement of the eye and also the diameter of the pupil. To improve the measurement resolution, a fast second degree local least square interpolation of the cross-correlation function is used. Possible sources of error and the limitations of the algorithm will be studied. The results of the computer simulations made using the algorithm serve to experimentally confirm the error estimates. Application of the algorithm to photographically obtained image data from human subjects demonstrates its practicality on normal eyes. The system design for a device for measuring 3D movement of the eye will be discussed.
Phantom movements and pain An fMRI study in upper limb amputees (2001)

Using functional MRI, we investigated 14 upper limb amputees and seven healthy controls during the execution of hand and lip movements and imagined movements of the phantom limb or left hand. Only patients with phantom limb pain showed a shift of the lip representation into the deafferented primary motor and somatosensory hand areas during lip movements. Displacement of the lip representation in the primary motor and somatosensory cortex was positively correlated to the amount of phantom limb pain. Thalamic activation was only present during executed movements in the healthy controls. The cerebellum showed no evidence of reorganizational changes. In amputees, movement of the intact hand showed a level of activation similar to movement of the right dominant hand in the healthy controls. During imagination of moving the phantom hand, all patients showed significantly higher activation in the contralateral primary motor and somatosensory cortices compared with imagination of hand movements in the controls. In the patients with phantom limb pain but not the pain-free amputees, imagined movement of the phantom hand activated the neighbouring face area. These data suggest selective coactivation of the cortical hand and mouth areas in patients with phantom limb pain. This reorganizational change may be the neural correlate of phantom limb pain.
Novel electrochemical device for the detection of cholesterol or glucose (1993)

A thin-layer twin-electrode electrochemical cell in which the working and auxiliary electrodes are facing each other and which contains the appropriate enzyme and a mediator was used for the determination of cholesterol or glucose. A steady-state diffusion-controlled response was obtained for cholesterol whereas for glucose the response was limited by diffusion and kinetics. Simulation of the system showed that a steady-state response is obtained, in the absence of kinetic complications, after a time of 0.01 d2/Ds, where d is the distance between the two electrodes and D is the diffusion coefficient of the mediator. Linear plots of steady-state current versus concentration were obtained for cholesterol and glucose. The results were compared with those expected theoretically and a thin-layer capillary fill device is proposed.
Books in Spanish for Young Readers in School and Public Libraries: A Survey of Practices and Attitudes. (1987)

Enquete sur les attitudes et les pratiques des bibliotheques publiques et scolaires americaines concernant la selection, l'acquisition et l'utilisation des livres en espagnol pour enfants et adolescents
Acoustofluidics 5: Building microfluidic acoustic resonators (2012)

Acoustophoresis is getting more attention as an effective and gentle non-contact method of manipulating cells and particles in microfluidic systems. A key to a successful assembly of an acoustophoresis system is a proper design of the acoustic resonator where aspects of fabrication techniques, material choice, thickness matching of involved components, as well as strategies of actuation, all have to be considered. This tutorial covers some of the basics in designing and building microfluidic acoustic resonators and will hopefully be a comprehensive and advisory document to assist the interested reader in creating a successful acoustophoretic device.