gebhart/patrepeval huggingface dataset:
Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells (2006)

Smooth muscle formation and function are critical in development and postnatal life. Hence, studies aimed at better understanding SMC differentiation are of great importance. Here, we report that multipotent adult progenitor cells (MAPCs) isolated from rat, murine, porcine, and human bone marrow demonstrate the potential to differentiate into cells with an SMC-like phenotype and function. TGF-beta1 alone or combined with PDGF-BB in serum-free medium induces a temporally correct expression of transcripts and proteins consistent with smooth muscle development. Furthermore, SMCs derived from MAPCs (MAPC-SMCs) demonstrated functional L-type calcium channels. MAPC-SMCs entrapped in fibrin vascular molds became circumferentially aligned and generated force in response to KCl, the L-type channel opener FPL64176, or the SMC agonists 5-HT and ET-1, and exhibited complete relaxation in response to the Rho-kinase inhibitor Y-27632. Cyclic distention (5% circumferential strain) for 3 weeks increased responses by 2- to 3-fold, consistent with what occurred in neonatal SMCs. These results provide evidence that MAPC-SMCs are phenotypically and functionally similar to neonatal SMCs and that the in vitro MAPC-SMC differentiation system may be an ideal model for the study of SMC development. Moreover, MAPC-SMCs may lend themselves to tissue engineering applications.
Beneficial effects of long-term selective endothelin type A receptor blockade in canine experimental heart failure (1998)

Our results suggest that endothelin-1 plays a role in the hemodynamic perturbations in canine pacing-induced cardiomyopathy. The favourable hemodynamic effects without concomitant aggravation of neurohormonal activation suggests that ETA receptor blockade may be beneficial in the treatment of heart failure.
Cyclobenzaprine drug assay and cyclobenzaprine-excipient interaction study by chromatography, thermal and spectral analysis. (2017)

The present study was carried out to investigate the compatibility of Cyclobenzaprine hydrochloride, a muscle relaxant and antidepressant with different pharmaceutical excipients. The study involved storing drug-excipient blends (200 mg) with 20% added moisture in closed glass vials at 100°c for 24 hours. A LC method was developed and validated for determination of cyclobenzaprine. The mobile phase consists of potassium dihydrogen phosphate buffer (20 mM, pH 3.0): methanol with flow rate 1.2 mL/min and UV detection at 289 nm. A good linearity was obtained with concentration ranging from 5-50 µg/mL. The HPLC study showed, drug interacts with some commonly used pharmaceutical excipients. The results were fairly good in agreement with the cyclobenzaprine hydrochloride-excipient interaction analysis, obtained from DSC, FTIR and UV-DRS. The HPLC method was validated as per ICH guidelines and applied for quality control of bulk and formulation of cyclobenzaprine hydrochloride.
D-dimer antigen: current concepts and future prospects (2008)

The D-dimer antigen is a unique marker of fibrin degradation that is formed by the sequential action of 3 enzymes: thrombin, factor XIIIa, and plasmin. First, thrombin cleaves fibrinogen producing fibrin monomers, which polymerize and serve as a template for factor XIIIa and plasmin formation. Second, thrombin activates plasma factor XIII bound to fibrin polymers to produce the active transglutaminase, factor XIIIa. Factor XIIIa catalyzes the formation of covalent bonds between D-domains in the polymerized fibrin. Finally, plasmin degrades the crosslinked fibrin to release fibrin degradation products and expose the D-dimer antigen. D-dimer antigen can exist on fibrin degradation products derived from soluble fibrin before its incorporation into a fibrin gel, or after the fibrin clot has been degraded by plasmin. The clinical utility of D-dimer measurement has been established in some scenarios, most notably for the exclusion of VTE. This article consists of 2 sections: in the first, the dynamics of D-dimer antigen formation is discussed and an overview of commercially available D-dimer assays is provided. The second section reviews available evidence for the clinical utilization of D-dimer antigen measurement in VTE, as well as emerging areas of D-dimer utilization as a marker of coagulation activation in other clinical settings.
Unique sequence specificity of topoisomerase II DNA cleavage stimulation and DNA binding mode of streptonigrin. (1994)

Streptonigrin stimulated unique intensity patterns of topoisomerase II-mediated DNA cleavage in agarose and sequencing gels with no similarity to those of doxorubicin, VM-26,4'(9-acridinylamino)-methanesulfon-m-anisidide, genistein, and mitoxantrone. Surprisingly, a statistical analysis of 60 sites stimulated by streptonigrin in SV40 and pBR322 DNAs showed that the drug required the dinucleotide 5'-TA-3' from 2- to 3-positions at the DNA cleavage site. Streptonigrin did not intercalate into the double helix; however, a positive value of the reduced linear dichroism indicated that indeed the drug interacted with the DNA. An angle of 45 degrees was found between the major drug and local DNA axes, suggesting a minor groove binding mode. Moreover, a DNA winding assay showed that streptonigrin may tighten the helical twist of DNA, similar to the known minor groove binder distamycin. Drug competition for receptor site binding was then evaluated by drug combination in the cleavage reaction. DNA cleavage intensity patterns were altered only with the streptonigrin/mitoxantrone combination, suggesting that the two compounds may compete for ternary complex formation. The results indicate that streptonigrin may bind to the DNA in a manner similar to that of minor groove binders and that its pharmacophore, possibly different from other topoisomerase II inhibitors, may be an important determinant of its unique sequence position specificity.
Direct Huffman coding and decoding using the table of code-lengths (2004)

A new Huffman coding and decoding technique is presented. There is no need to construct a full size Huffman table in this technique; instead, the symbols are encoded directly from the table of code-lengths. For decoding purposes a new Condensed Huffman Table (CHT) is also introduced. It is shown that by employing this technique both encoding and decoding operations become significantly faster, and the memory consumption also becomes much smaller compared to the normal Huffman coding/decoding.
Polymer-Assisted Dispersion of Single-Walled Carbon Nanotubes in Alcohols and Applicability toward Carbon Nanotube/Sol−Gel Composite Formation (2004)

Single-walled carbon nanotubes (SWCNTs) were directly dispersed into various alcohols by sonicating the nanotubes in the presence of poly(4-vinylpyridine) (P4VP). Depending upon the alcohol, it was possible to disperse up to 0.3 g of SWCNTs per liter of alcohol using only 0.6 g of P4VP, and with solution stability greater than 6 weeks. Scanning electron microscopy of "bucky" paper prepared from the polymer-treated nanotubes revealed reduced bundle size compared to the corresponding untreated nanotube paper. Additionally, the applicability of the dispersion system in the formation of SWCNT/silica composites is demonstrated.
Radiation force imaging of viscoelastic properties with reduced artifacts (2003)

It is well-known that changes in the mechanical properties of tissues are correlated with the presence of disease. In the eye, for example, the vitreous body undergoes dramatic changes in mechanical properties during age-related degradation. These changes may play a significant role in the formation of retinal detachment or other vitreoretinal diseases. We previously presented a noninvasive method called kinetic acoustic vitreoretial examination (KAVE), which may be used to detect these mechanical changes. KAVE uses acoustic radiation force as a means to produce small, localized displacements within the tissues. Returning echoes are processed using ultrasonic motion tracking so that the response of the tissue to the induced force can be evaluated. By repeating this process at a number of locations, images depicting viscoelastic properties of tissues can be formed. Through the combination of appropriate mechanical modeling and signal processing, we are able to generate images of parameters such as relative mass, relative elasticity, and relative viscosity. These parameters are called relative because they depend on the force applied, which is typically unknown. In this paper, we present new force-free images depicting the time constant tau, the damping ratio xi, and the natural frequency omega of the phantom material. These images are significant in that they lack the artifacts common in the relative property images. Experiments were conducted on a set of three acrylamide-based phantoms with varying gel concentrations. We present images depicting B-mode echogenicity, maximum radiation force-induced displacement, relative material parameters, and force-free characteristics of the series of phantoms. The presented force-free images depict mechanical properties without artifacts from local force variation due to acoustic reflection, refraction, and attenuation. Force-free images should prove particularly useful for in vivo imaging through inhomogeneous tissues.
StackGhost: Hardware facilitated stack protection (2001)

Conventional security exploits have relied on overwriting the saved return pointer on the stack to hijack the path of execution. Under Sun Microsystem &amp;apos;s Sparc processor architecture, we were able to implement a kernel modification to transparently and automatically guard applications&amp;apos; return pointers. Our implementation called StackGhost under OpenBSD 2.8 acts as a ghost in the machine. StackGhost advances exploit prevention in that it protects every application run on the system without their knowledge nor does it require their source or binary modification. We will document several of the methods devised to preserve the sanctity of the system and will explore the performance ramifications of StackGhost. 1
Thraustochytrid as a potential source of carotenoids (2003)

Abstract Thraustochytrids, marine protists whose dominant genera are Thraustochytrium and Schizochytrium , belong to the kingdom Chromista and are known as an industrial source of DHA. We describe here that thraustochytrid strain KH105, isolated as a DHA producer, also accumulates significant levels of β‐carotene and xanthophylls including canthaxanthin and astaxanthin. A4‐d cultivation using a medium composed of 10% glucose and less than 0.3% of nitrogen sources in a half‐concentration of seawater gave an astaxanthin production up to 6.1 mg/L, and canthaxanthin content reached more than 10 mg/L under conditions where a higher concentration of nitrogen sources (6%) was employed. It might be advantageous in mass production systems for these carotenoids to be extracted readily by simply suspending the cells with organic solvents such as acetone and chloroform. Analyses on the morphological and life history features of the KH105 strain revealed that it belongs to the genus Schizochytrium . This particular species of thraustochytrids is thus considered to be a promising source of xanthophylls as well as DHA for use in the food industry.
Document understanding for a Broad Class of Documents (2001)

We present a document analysis system able to assign logical labels and extract reading order in a broad set of documents. All information sources, from geometric features and spatial relations to the textual features and content are employed in the analysis. To deal effectively with these information sources, we define a document representation general and flexible enough to represent complex documents. To handle such a broad document class, it uses generic document knowledge only. The generic document knowledge used is identified explicitly. Our system integrates components based on computer vision, artificial intelligence, and natural language processing techniques. Experimental results for each component and for the entire system are presented. The performance of the system is good, especially when considering the
Integrated genomic analyses of ovarian carcinoma (2011)

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.
A frequency-domain video transcoder for dynamic bit-rate reduction of MPEG-2 bit streams (1998)

Many of the forthcoming video services and multimedia applications are expected to use preencoded video for storage and transmission. Video transcoding is intended to provide transmission flexibility to preencoded bit streams by dynamically adjusting the bit rate of these bit streams according to new bandwidth constraints that were unknown at the time of encoding. In this paper, we propose a drift-free MPEG-2 video transcoder, working entirely in the frequency domain. The various modes of motion compensation (MC) defined in MPEG-2 are implemented in the discrete cosine transform (DCT) domain at reduced computational complexity. By using approximate matrices to compute the MC-DCT blocks, we show that computational complexity can be reduced by 81% compared with the pixel domain approach. Moreover, by using a Lagrangian rate-distortion optimization for bit reallocation, we show that optimal transcoding of high-quality bit streams can produce better picture quality than that obtained by directly encoding the uncompressed video at the same bit rates using a nonoptimized Test Model 5 (TM5) encoder.
Nitric Oxide Mediates IL-1β-Induced Islet Dysfunction and Destruction: Prevention by Dexamethasone (1993)

Nitric oxide has recently been implicated as a cellular molecule that mediates interleukin-1 beta (IL-1 beta)-induced inhibition of glucose-stimulated insulin secretion by islets of Langerhans. In this study evidence is presented which demonstrates that islets contain both the cytokine inducible and the constitutive isoforms of nitric oxide synthase as determined by NADPH diaphorase staining and immunohistochemical localization. Untreated islets contain NADPH diaphorase activity, and the intensity of NADPH diaphorase staining is dramatically increased after culture for 18 hrs with IL-1 beta. Both control and IL-1 beta-induced NADPH diaphorase staining of islets is inhibited by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (NMMA). Importantly, approximately 60-70% of islet cells stained positive for NADPH diaphorase (under both IL-1 beta treated and control conditions), suggesting that a subset of islet cells contain nitric oxide synthase. The beta-cell appears to be the endocrine cell type which contains constitutive nitric oxide synthase as demonstrated by immunohistochemical co-localization of constitutive nitric oxide synthase and insulin. IL-1 beta is believed to stimulate the expression of cytokine inducible nitric oxide synthase because the synthetic glucocorticoid, dexamethasone, prevents IL-1 beta induced inhibition of glucose stimulated insulin secretion and cGMP accumulation by islets. Both dexamethasone, and the nitric oxide synthase inhibitors NMMA and aminoguanidine also prevent IL-1 beta induced islet degeneration. These results indicate that nitric oxide produced by the inducible isoform of nitric oxide synthase mediates cytokine induced islet dysfunction and destruction, and that the beta-cell is the islet endocrine cellular source of constitutive nitric oxide synthase.
The Gold Nanorod-Biology Interface: From Proteins to Cells to Tissue (2013)

Gold nanorods absorb and scatter light strongly in the near-infrared portion of the electromagnetic spectrum, making them ideal tissue contrast agents for imaging techniques such as optical coherence tomography (OCT). Strong interactions occur at the nano-bio interface, such as proteins binding to gold nanorods forming a 'corona.' To fulfill the promise of nanorods for applications such as contrast agents, we must better understand the intrinsic interactions of these nanomaterials with biological systems at the molecular, cellular and tissue level. In this paper, we briefly review the nanorod-protein interface. We then present some new fast relaxation imaging (FReI) measurements of how the presence of strongly-absorbing gold nanorods affects protein binding and folding, taking into account inner filter effects and the strong quenching effect of nanorods on fluorescent-labeled proteins. Next we show that two-photon photoluminescence of the gold nanorods can be used to image the nanorods in tissue constructs, allowing us to independently study their tissue distribution so they can be used successfully as contrast agents in optical coherence microscopy.
An overview and analysis of 3D WSI (2002)

The author reviews the early trends in 3-D WSI (wafer scale integration) and examines recent breakthroughs in technology to assess the viability of 3-D. It is concluded that this option is rich with possibility for the designer. However, not every architecture can benefit equally from this packaging approach. An attempt is made to quantify this impact by computing an average wire-shortening effect from 3-D partitioning, but even this average improvement is pessimistic if the given architecture is such that the most critical paths can all be placed on the vertical wiring runs in the stack, depending on the vertical spacing of the wafers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Minimizing User Search Time in Menu Retrieval Systems (1985)

The optimal structuring of menu indexes in computerized information retrieval is examined. The number of alternatives per page that minimizes search time is determined as a function of the human and machine factors of search strategy, scanning time, key-press time, and computer response time. For a wide range of conditions, the optimal number of alternatives per page is in the range of from four to eight, with limiting integer values of three and four for exhaustive and self-terminating search, respectively.
Phase 1 studies assessing the safety, PK, and VEGF-modulating effects of PTC299, a novel VEGF expression inhibitor (2007)

3562 Background: VEGF expression is regulated posttranscriptionally through the 5’- and 3’- untranslated regions (UTRs) of its mRNA. PTC299 is a novel, orally bioavailable, small molecule that acts via the VEGF 5’-UTR to selectively inhibit tumor VEGF production. In multiple preclinical human tumor xenograft models, PTC299 reduces elevated human VEGF levels in tumor and in circulation, decreases tumor microvessel density, and substantially slows tumor growth. With cytotoxic agents or with other antiangiogenics, PTC299 enhances tumor growth delay. Methods: PTC299 safety in animal toxicology studies supported Phase 1 studies in healthy volunteers. The first study was a Phase 1 single-dose (SD) trial. The second study was a Phase 1, multiple-dose (MD) study assessing BID or TID dosing for 7 days. During dose escalations, 8 subjects (4 males, 4 females; 6 PTC299, 2 placebo) per cohort were randomized in a double-blind manner. A fed-fasting crossover was performed in 12 subjects (6 males, 6 females) in the SD study. Subjects underwent clinical observations, laboratory testing, and blood sampling for PK and circulating VEGF. Results: In the SD study, 52 subjects (age range 18–55 years) were enrolled (40 at 5 dose levels and 12 to assess food effects. In the MD study, 32 subjects (age range 31–78 years) were enrolled (24 to BID dosing and 8 to TID dosing). AEs included: headache, dizziness nausea, vomiting, and stomach discomfort (all Grade 1); and diarrhea (Grade 2). No bleeding, clotting, hypertension, or proteinuria occurred. C max and AUC increased proportional to dose. There was a ∼40% increase in the C max with food, but no change in AUC. Mean PTC299 C max and AUC increased by ∼2-fold over 7 days, exceeding target trough plasma concentrations active in xenograft models. A 2-compartment model describes the PK data. Circulating VEGF levels are being assayed. Conclusions: PTC299 is the first drug designed to modulate post-transcriptional control mechanisms to treat human disease. In these initial studies, PTC299 shows safety at plasma exposures associated with preclinical activity and can be taken without regard to food. Final clinical data on dose ranging, safety, PK, and circulating VEGF levels will be presented. Studies of PTC299 in patients with cancer are being initiated. No significant financial relationships to disclose.
Characterization of hotspots in a highly enhancing SERS substrate (2011)

Vapor deposition of silver and gold onto a porous anodized aluminum oxide template is shown to produce a SERS substrate with an average surface enhancement factor of 10(7)-10(8). The high level of enhancement is explored using a combination of dark-field Rayleigh scattering and Raman spectroscopy and imaging. The scattering spectrum of the surface indicates a Plasmon resonance at 633 nm and dark-field imaging shows a relatively uniform scattering intensity at this wavelength. These measurements are consistent with the uniform enhanced Raman intensity observed in Raman maps of the substrate. Scanning electron microscopy shows the surface exhibits heterogeneous nanostructures with diameters of approximately 100 nm, the size of the pores in the template. Our measurements indicate that interactions between adjacent structures forming junctions and crevices likely give rise to a high density of hotspots, which provide the extraordinary SERS enhancement. The advantage of substrates prepared in this way is the reproducibly dense distribution of hotspots across the surface, increasing the likelihood that an analyte will experience the largest enhancement.