gebhart/patrepeval huggingface dataset:
Derivatives of 2-mercaptobenzenesulphonamide. XI. Synthesis and some pharmacological properties of 2-(2-[2-(3,4,5-trimethoxybenzamido)ethylthio] benzenesulphonyl) guanidines. (1993)

Tree methods of synthesis of 2-(2-[2-(3,4,5-trimethoxybenzamido)ethylthio] benzenesulphonyl)guanidines (IVa-b, Va-XIVa, VIII-XII) are described. The results of preliminary pharmacological examinations such as acute toxicity and influence on circulatory system of compound [IVb, VIa, XIa-XIVa] and substrates [IIIc-f] are presented. Some structure-activity relationship is discussed.
KIT as a Therapeutic Target in Metastatic Melanoma (2011)

Among patients with advanced melanoma harboring KIT alterations, treatment with imatinib mesylate results in significant clinical responses in a subset of patients. Responses may be limited to tumors harboring KIT alterations of proven functional relevance. Trial Registration clinicaltrials.gov Identifier: NCT00470470.
Nuclear localization of proteasomes participates in stress-inducible resistance of solid tumor cells to topoisomerase II-directed drugs. (2002)

Physiological cell conditions of solid tumors, such as glucose starvation and hypoxia,induce cellular resistance to topoisomerase II-directed drugs. Here, we show that the induction of drug resistance is mediated by nuclear accumulation of proteasomes, large multicatalytic protease complexes. We found that the nuclear proteasome accumulation during glucose starvation was attenuated by stable expression of a mutant type of proteasome subunit, XAPC7, that lacked the nuclear localization signal (NLS). It is important that the expression of NLS-defective XAPC7 also diminished the induction of resistance to etoposide and doxorubicin, typical topoisomerase II-directed drugs. Under normal conditions, however, the NLS-defective XAPC7 had little effect on either nuclear proteasome distribution or etoposide sensitivity. Our findings demonstrate that stress-induced nuclear proteasome accumulation occurs through up-regulation of the NLS-dependent transport. Inhibition of the nuclear proteasome accumulation can be a novel approach to circumventing resistance to topoisomerase II-directed drugs.
A new method for studying gradient-induced neutrophil desensitization based on an open microfluidic chamber (2009)

During inflammation neutrophils rapidly migrate to the site of tissue damage or infection by following complex gradients of bacterial peptides and host-derived chemokines. The efficiency and speed of neutrophil migration is critically dependent upon the ability of neutrophils to sense new gradients and utilize only those that provide the most direct path to the damaged or infected site. Receptor desensitization plays an important role in migration efficiency and is most commonly studied using bath application of chemotactic factor solutions instead of presenting cells with gradients analogous to those they would experience in vivo. Here we describe a new method for examining gradient-induced neutrophil desensitization using a previously-developed open-chamber microfluidic gradient generator.
Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development (2013)

Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.
Acetyl Groups in Native Glucomannan from Easter Lily Bulbs (1974)

Journal Article Acetyl Groups in Native Glucomannan from Easter Lily Bulbs Get access Tomoaki Matsuo, Tomoaki Matsuo Department of Agricultural Chemistry, Shizuoka University, Shizuoka, Japan Present address: Department of Horticulture, Faculty of Agriculture, Kagoshima University, Kagoshima 890 Japan. Search for other works by this author on: Oxford Academic Google Scholar Takashi Mizuno Takashi Mizuno Department of Agricultural Chemistry, Shizuoka University, Shizuoka, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 38, Issue 2, 1 February 1974, Pages 465–466, https://doi.org/10.1080/00021369.1974.10861176 Published: 01 February 1974 Article history Received: 17 August 1973 Published: 01 February 1974
The equiangular spiral antenna (1959)

A circularly polarized antenna is described which makes possible bandwidths that a few years ago were considered to be impossible. The design of the antenna is based upon the simple fundamental principle that if the shape of the antenna were such that it could be specified entirely by angles, its performance would be independent of wavelength. Since all such shapes extend to infinity it is necessary to specify at least one length for an antenna of finite size. The one length in this antenna, the arm length, need only be of the order of one wavelength at the lowest frequency of operation to obtain operation essentially independent of frequency, and the geometry of the antenna allows this arm length to be spiraled into a maximum diameter of one half wavelength or less. Antennas have been constructed that have an essentially constant radiation pattern and input impedance over bandwidths greater than 20 to 1.
Applied Photographic Optics Imaging Systems for Photography, Film and Video (1989)

"Applied Photographic Optics Imaging Systems for Photography, Film and Video." The Journal of Photographic Science, 37(1), p. 29
Ribo-gnome: The Big World of Small RNAs (2005)

Small RNA guides--microRNAs, small interfering RNAs, and repeat-associated small interfering RNAs, 21 to 30 nucleotides in length--shape diverse cellular pathways, from chromosome architecture to stem cell maintenance. Fifteen years after the discovery of RNA silencing, we are only just beginning to understand the depth and complexity of how these RNAs regulate gene expression and to consider their role in shaping the evolutionary history of higher eukaryotes.
The Heparin/Heparan Sulfate 2-O-Sulfatase from Flavobacterium heparinum (2003)

Heparan sulfate glycosaminoglycans are structurally complex polysaccharides critically engaged in a wide range of cell and tissue functions. Any structure-based approach to study their respective biological functions is facilitated by the use of select heparan sulfate glycosaminoglycan-degrading enzymes with unique substrate specificities. We recently reported of one such enzyme, the Delta4,5-glycuronidase cloned from Flavobacterium heparinum and recombinantly expressed in Escherichia coli (Myette, J. R., Shriver, Z., Kiziltepe, T., McLean, M. W., Venkataraman, G., and Sasisekharan, R. (2002) Biochemistry 41, 7424-7434). In this study, we likewise report the molecular cloning of the 2-O-sulfatase from the same bacterium and its recombinant expression as a soluble, highly active enzyme. At the protein level, the flavobacterial 2-O-sulfatase possesses considerable sequence homology to other members of a large sulfatase family, especially within its amino terminus, where the highly conserved sulfatase domain is located. Within this domain, we have identified by sequence homology the critical active site cysteine predicted to be chemically modified as a formylglycine in vivo. We also present a characterization of the biochemical properties of the enzyme as it relates to optimal in vitro reaction conditions and a kinetic description of its substrate specificity. In particular, we demonstrate that in addition to the fact that the enzyme exclusively hydrolyzes the sulfate at the 2-O-position of the uronic acid, it also exhibits a kinetic preference for highly sulfated glucosamines within each disaccharide unit, especially those possessing a 6-O-sulfate. The sulfatase also displays a clear kinetic preference for disaccharides with beta1-->4 linkages but is able, nevertheless, to hydrolyze unsaturated, 2-O-sulfated chondroitin disaccharides. Finally, we describe the substrate-product relationship of the 2-O-sulfatase to the Delta4,5-glycuronidase and the analytical value of using both of these enzymes in tandem for elucidating heparin/heparan sulfate composition.
Induction of antitumor immunity using bone marrow-generated dendritic cells (1996)

We have previously shown that bone marrow-generated dendritic cells (DC) pulsed with a class I-restricted peptide are potent inducers of CD8+ CTL. In the present study we have investigated whether bone marrow-generated DC are capable of inducing antitumor immunity. We show that a single immunization with DC pulsed with OVA peptide was highly effective in eliciting a protective immune response against a challenge with tumor cells expressing the OVA gene (E.G7-OVA), more so than immunization with irradiated E.G7-OVA cells, OVA peptide-pulsed RMA-S cells, or free OVA peptide mixed with adjuvant. The addition of free OVA protein to day 4 or day 7 bone marrow cultures, but not to day 9 mature DC, was also effective in eliciting CTL and engendering antitumor immunity, but was less effective than peptide-pulsed DC. Induction of CTL and antitumor immunity by bone marrow-generated DC pulsed with the class I-restricted OVA peptide correlated with the expression of syngeneic MHC class II molecules on the DC. This and the fact that induction of tumor immunity was dependent on CD4+ T cells suggest that in vivo priming of CTL and induction of antitumor immunity by bone marrow-generated DC also require the presentation of MHC class II-restricted epitopes and activation of CD4+ T cells. This observation has potentially important implications to the use of peptide-pulsed DC in clinical immunotherapy.
Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment (1999)

In older patients with MCI, hippocampal atrophy determined by premorbid MRI-based volume measurements is predictive of subsequent conversion to AD.
Modeling Prosodic Features With Joint Factor Analysis for Speaker Verification (2007)

In this paper, we introduce the use of continuous prosodic features for speaker recognition, and we show how they can be modeled using joint factor analysis. Similar features have been successfully used in language identification. These prosodic features are pitch and energy contours spanning a syllable-like unit. They are extracted using a basis consisting of Legendre polynomials. Since the feature vectors are continuous (rather than discrete), they can be modeled using a standard Gaussian mixture model (GMM). Furthermore, speaker and session variability effects can be modeled in the same way as in conventional joint factor analysis. We find that the best results are obtained when we use the information about the pitch, energy, and the duration of the unit all together. Testing on the core condition of NIST 2006 speaker recognition evaluation data gives an equal error rate of 16.6% and 14.6%, with prosodic features alone, for all trials and English-only trials, respectively. When the prosodic system is fused with a state-of-the-art cepstral joint factor analysis system, we obtain a relative improvement of 8% (all trials) and 12% (English only) compared to the cepstral system alone.
Self-expanding endovascular graft: an experimental study in dogs (1988)

An arterial endovascular graft was constructed by wrapping an expandable nylon mesh around a framework of Gianturco self-expanding metallic stents. The devices were passed through a 12-French Teflon catheter and positioned in the normal abdominal aorta of five dogs, two of which also had a device placed in an external iliac artery. At follow-up (1-6 months), all grafts remained patent, even though slight luminal narrowing due to neointimal encasement was noted. Histologically, all grafts were covered by neointimal proliferation at the time of removal. The graft material expanded with the stents, resulting in a tight fit between the graft and the vessel wall. Side branches narrowed but remained open because of the size of the nylon mesh. No migration of the grafts equipped with a barbed lead stent was noted. Expandable nylon mesh can be used as an endovascular graft material when wrapped around a framework of self-expanding stents. The resulting device can be easily delivered via transcatheter techniques, and once placed in a vessel, the nylon acts as a support for neointimal encasement, which forms a new vascular lumen.
Automated Statistical Analysis of Protein Abundance Ratios from Data Generated by Stable-Isotope Dilution and Tandem Mass Spectrometry (2003)

We describe an algorithm for the automated statistical analysis of protein abundance ratios (ASAPRatio) of proteins contained in two samples. Proteins are labeled with distinct stable-isotope tags and fragmented, and the tagged peptide fragments are separated by liquid chromatography (LC) and analyzed by electrospray ionization (ESI) tandem mass spectrometry (MS/MS). The algorithm utilizes the signals recorded for the different isotopic forms of peptides of identical sequence and numerical and statistical methods, such as Savitzky-Golay smoothing filters, statistics for weighted samples, and Dixon's test for outliers, to evaluate protein abundance ratios and their associated errors. The algorithm also provides a statistical assessment to distinguish proteins of significant abundance changes from a population of proteins of unchanged abundance. To evaluate its performance, two sets of LC-ESI-MS/MS data were analyzed by the ASAPRatio algorithm without human intervention, and the data were related to the expected and manually validated values. The utility of the ASAPRatio program was clearly demonstrated by its speed and the accuracy of the generated protein abundance ratios and by its capability to identify specific core components of the RNA polymerase II transcription complex within a high background of copurifying proteins.
Determinate state convolutional codes (1993)

A determinate state convolutional code is formed from a conventional convolutional code by pruning away some of the possible state transitions in the decoding trellis. This staged power transfer proves to be an extremely efficient way of enhancing the performance of a concatenated coding system. The authors analyze the decoding complexity and free distances of these new codes, determine some important statistical properties of the decoder output, and provide simulation results for performance at the low signal-to-noise ratios where a real communications system would operate. Several concise, practical examples are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Unlocking a Caged Lysosomal Protein from a Polymeric Nanogel with a pH Trigger (2014)

A polymeric nanogel has been used to sequester and turn off a lysosomal protein, acid α-glucosidase (GAA). The nanogel contains a β-thiopropionate cross-linker, which endows the nanogel with pH-sensitivity. While encapsulation of the enzyme fully turns off its activity, approximately 75% of the activity is recovered upon reducing the pH to 5.0. The recovered activity is ascribed to pH-induced degradation of the β-thiopropionate cross-linker causing the swelling of the nanogel and ultimately causing the release of the enzyme. We envision that strategies for sequestering protein molecules and releasing them at lysosomal pH might open up new directions for therapeutic treatment of lysosomal storage diseases.
Gene and Protein Expression Profiling of Human Ovarian Cancer Cells Treated with the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin (2007)

The promising antitumor activity of 17-allylamino-17-demethoxygeldanamycin (17AAG) results from inhibition of the molecular chaperone heat shock protein 90 (HSP90) and subsequent degradation of multiple oncogenic client proteins. Gene expression microarray and proteomic analysis were used to profile molecular changes in the A2780 human ovarian cancer cell line treated with 17AAG. Comparison of results with an inactive analogue and an alternative HSP90 inhibitor radicicol indicated that increased expression of HSP72, HSC70, HSP27, HSP47, and HSP90beta at the mRNA level were on-target effects of 17AAG. HSP27 protein levels were increased in tumor biopsies following treatment of patients with 17AAG. A group of MYC-regulated mRNAs was decreased by 17AAG. Of particular interest and novelty were changes in expression of chromatin-associated proteins. Expression of the heterochromatin protein 1 was increased, and expression of the histone acetyltransferase 1 and the histone arginine methyltransferase PRMT5 was decreased by 17AAG. PRMT5 was shown to be a novel HSP90-binding partner and potential client protein. Cellular protein acetylation was reduced by 17AAG, which was shown to have an antagonistic interaction on cell proliferation with the histone deacetylase inhibitor trichostatin A. This mRNA and protein expression analysis has provided new insights into the complex molecular pharmacology of 17AAG and suggested new genes and proteins that may be involved in response to the drug or be potential biomarkers of drug action.
Cross-Reactive Neuraminidase Antibodies Afford Partial Protection against H5N1 in Mice and Are Present in Unexposed Humans (2007)

These data reveal that humoral immunity elicited by huN1 can partially protect against H5N1 infection in a mammalian host. Our results suggest that a portion of the human population could have some degree of resistance to H5N1 influenza, with the possibility that this could be induced or enhanced through immunization with seasonal influenza vaccines.
Compression and direct manipulation of complex blendshape models (2011)

We present a method to compress complex blendshape models and thereby enable interactive, hardware-accelerated animation of these models. Facial blendshape models in production are typically large in terms of both the resolution of the model and the number of target shapes. They are represented by a single huge blendshape matrix, whose size presents a storage burden and prevents real-time processing. To address this problem, we present a new matrix compression scheme based on a hierarchically semi-separable (HSS) representation with matrix block reordering. The compressed data are also suitable for parallel processing. An efficient GPU implementation provides very fast feedback of the resulting animation. Compared with the original data, our technique leads to a huge improvement in both storage and processing efficiency without incurring any visual artifacts. As an application, we introduce an extended version of the direct manipulation method to control a large number of facial blendshapes efficiently and intuitively.
A Software System for Interventional Magnetic Resonance Image-Guided Prostate Brachytherapy (2000)

AbstractObjective: Current prostatic brachytherapy implant procedures use ultrasound imaging for geometric guidance during surgery, with pre-surgical planning based on ultrasound images and post-surgical dosimetry based on computed tomography (CT). This procedure suffers from the poor soft-tissue contrast of ultrasound and CT and problems inherent in the repositioning of the patient at surgery. We have designed and implemented an integrated real-time imaging and treatment-planning software system that combines the superior soft-tissue contrast of magnetic resonance (MR) images with the real-time acquisition of those images for localization, verification, and dosimetric purposes. The system permits the surgeon and patient to complete all phases of treatment in one setting.Materials and Methods: We utilize an intra-operative MR unit that permits real-time imaging and stereotactic localization during a surgical procedure. Our software system integrates with the unit and features (i) a calibration schema to calibrate the prostatic surgical implant template within the unit, (ii) full volumetric data acquisition of the prostate, (iii) interactive three-dimensional (3D) treatment planning with volumetric dose evaluation, and (iv) geometric and dosimetric feedback during the surgical procedure. We utilize a software architecture that uses mediators between the abstract data types, or objects. These mediators communicate state changes in individual objects (e.g., a change in a catheter position) to other objects (e.g., a dose-volume histogram) that depend on these changes. A consistent 3D representation of the treatment volumes allows interactive reconstruction of the volumes on arbitrary MR image sections and real-time dose computations.Results: We have successfully implemented the system clinically and have treated 143 patients (as of August 2000). The system supports four clinical phases. The first consists of calibrating the implant template with respect to the patient's anatomy and the MR unit. The second consists of acquiring a complete volumetric MR data set of the prostatic volume. The third consists of delineating the treatment volume (often a sub-volume of the prostate) and the dose-limiting critical volumes. These volumes are used in determining the surgical treatment plan based on catheter and seed placement in the prostate and a dosimetric evaluation of all volumes. The final phase consists of implanting the catheters with the radioactive seeds, where each catheter is imaged and compared to the planned position of the catheter, thus allowing a direct comparison, and possible adjustment, of the implanted versus planned catheter position.
Laser photostimulation of collagen production in healing rabbit achilles tendons (1998)

This study of laser photostimulation on tendon healing in rabbits suggests that such therapy facilitates collagen production in a manner that enhances tendon healing.
ChemInform Abstract: Synthesis and Pharmacological Characterization of a Conformationally Restrained Series of Indole‐2‐carboxylates [cf. (VI)] as in vivo Potent Glycine Antagonists. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Nothing but skin and bone (2006)

Skin and bone - what comes to mind at hearing this phrase? While certainly a metaphor for disease, it also defines two very different tissues, one a flexible and contiguous outer covering, the other a morphologically diverse hard tissue distributed at over 200 sites in the body. As the accompanying series of Reviews highlights, these tissues are indeed diverse, but there are also surprising similarities. Skin is the interface between the internal organs and the environment, and as such plays a crucial role in the body's defense mechanism. The skin and its many appendages are responsible for functions as diverse as epidermal barrier and defense, immune surveillance, UV protection, thermoregulation, sweating, lubrication, pigmentation, the sensations of pain and touch, and, importantly, the protection of various stem cell niches in the skin. Bone serves a number of purposes: it provides protection for vital organs, a lever for locomotion, a reservoir for calcium, and the site of adult hematopoiesis. The tissue is composed of osteoblasts, osteoclasts, and their individual precursors plus a complex mixture of mesenchymal, myeloid, and lymphoid cells in the marrow space. Finally, the endothelial microenvironment provides nutrition and is a conduit for the influx and emigration of cells that impact bone biology in several important ways. This Review series guides the reader through these various facets of 2 diverse, yet interdependent, tissues.