gebhart/patrepeval huggingface dataset:
Review article: oral, modified‐release mesalazine formulations — proprietary versus generic (2003)

Products containing mesalazine have been used in the treatment of inflammatory bowel disease for many years. Many of the oral, modified-release products are reaching the point of patent expiration, and it is expected that several new 'generic' versions will be developed. As mesalazine acts topically, the drug needs to be available at the site of inflammation to be effective. For this reason, the currently available products have been developed with individual formulations so that physicians have a choice when matching the different release profiles to the site and extent of disease. As such, the current guidelines state that oral, delayed-release mesalazine formulations are not interchangeable and should be prescribed by their proprietary (brand) name. The standard regulatory assessment process for generic or 'copy' products, using systemic bioequivalence data, does not appear to be sufficient when evaluating topically acting, oral, modified-release products. We therefore recommend that the regulatory bodies should require that new, oral mesalazine products should be assessed by a combination of dissolution, bioequivalence and (a minimum of one) adequately powered, comparative trial to determine therapeutic equivalence. Of most importance here is that the assessment of new modified-release products is sufficiently rigorous to allow patients and physicians to be confident in their use.
A new mtDNA mutation in the tRNA(Lys) gene associated with myoclonic epilepsy and ragged-red fibers (MERRF). (1992)

Myoclonic epilepsy with ragged-red fibers (MERRF) has been associated with an A--G transition at mtDNA nt 8344, within a conserved region of the tRNA(Lys) gene. Although the 8344 mutation is highly prevalent in patients with MERRF, it is not observed in 10%-20% of the cases, suggesting genetic heterogeneity. We have sequenced the tRNA(Lys) gene of five MERRF patients lacking the common 8344 mutation. One of these showed a novel T-->C transition at nucleotide position 8356, disrupting a highly conserved base pair in the T psi C stem. The mutant mtDNA population was essentially homoplasmic in muscle but was heteroplasmic in blood (47%). Neither 20 patients with other mitochondrial diseases nor 25 controls carried this mutation. These findings suggest that tRNA(Lys) alterations may play a specific role in the pathogenesis of MERRF syndrome.
India - Building capacities for public private partnerships (2006)

This report concentrate on projects where private investment has been made, and where the government is either the purchaser of services under the project, or where it provides a financial contribution through direct investment or through risk bearing. The main sectors of focus are transportation (ports, airports, roads, and rail), water and sanitation and other urban infrastructure (solid waste management, light rail, bus terminals).
New anti-mycobacterial hydantoins. (1980)

Ten 1-(4-substituted-thiazol-2-yl)hydantoins have been synthesized. Some of them have shown antitubercular activity against Mycobacterium smegmatis.
CYP450 and Its Implications in the Clinical Use of Antipsychotic Drugs (2015)

Polypharmacy implies a high potential for drug-drug interactions. The capacity of the cytochrome P450 enzyme system involved in the metabolism of psychoactive drugs differs greatly, which leads to variable drug elimination rates and inter-subject differences in serum drug concentrations. Polymorphisms in genes coding for CYP450 enzymes contribute to this inter-subject variability. Therapeutic response and adverse effects vary among patients treated with the same dose of a certain drug. Polypharmacy, comorbidity and the use of certain substances (grapefruit juice, caffeine and tobacco) increase the chances of clinically relevant interactions in a psychotic patient. Choosing drugs with low interaction potential seems to be the best strategy to prevent clinically relevant interactions particularly in elderly, polymedicated, oncologic and HIV patients.
Noninvasive Evaluation of Active Lower Gastrointestinal Bleeding: Comparison Between Contrast-Enhanced MDCT and 99mTc-Labeled RBC Scintigraphy (2008)

Contrast-enhanced MDCT and (99m)Tc-labeled RBC scanning show significant disagreement for evaluation of active lower gastrointestinal bleeding. Contrast-enhanced MDCT appears effective for detection and localization in cases of active lower gastrointestinal bleeding in which hemorrhage is active at the time of CT.
Nanoparticles Comprising a Mixed Monolayer for Specific Bindings with Biomolecules (2004)

This work presents a strategy of using mixed monolayer protected nanoparticles for specific interactions with target biological molecules. The mixed monolayer is composed of a shielding component and a capture component. The shielding component utilizes ethylene glycol oligomers to prevent nonspecific binding with biomolecules. The capture component is chosen to specifically interact with the target of interest, such as a protein molecule. Such a concept was demonstrated by two synthetic systems. The first one is gold nanoparticles protected by a mixed monolayer of tri(ethylene glycol) thiol (EG(3)-SH) and tiopronin (Tp), which was prepared by a one-step synthesis. Surface chemical composition studies using (1)H NMR spectroscopy revealed that the reactivity of EG(3)-SH is 3 times as high as that of Tp in the nanoparticle formation. Gel electrophoresis analysis identified a critical ratio of (EG(3)-S-)/Tp on the nanoparticle surface above which no nonspecific binding occurred. By further derivatizing Tp into a biotin group, we synthesized Au(-S-EG(3))(n)/Tp-biotin particles that bind specifically to streptavidin with negligible nonspecific binding. The second system is gold nanoparticles protected by a mixed monolayer of EG(3)-SH and glutathione (GSH). By controlling the feeding ratio of EG(3)-SH and GSH, we made Au(-S-EG(3))(n)/GSH particles that bind specifically to gultathione-S-transferase (GST) with negligible nonspecific binding.
Therapeutic Advantage of Pretargeted Radioimmunotherapy Using a Recombinant Bispecific Antibody in a Human Colon Cancer Xenograft (2005)

Pretargeting increases the amount of radioactivity delivered to colorectal tumors sufficiently to improve the therapeutic index and responses as compared with conventional radioimmunotherapy.
<title>Interstitial laser coagulation of the prostate: experimental studies</title> (1991)

A percutaneous, low power, interstitial method of controlled tissue coagulation by laser light has been developed and assessed as a possible alternative to existing therapy for benign and malignant prostatic disease. For prostate cancer this technique may be of importance when the tumor volume is small and well defined, particularly as these tumors can increasingly be identified by transrectal ultrasound (TRUS) and are unlikely to have metastasised. The possibility therefore arises of destruction of such small lesions in situ, thereby avoiding the need for radical surgery or radiotherapy. Using the male beagle prostate model, one or more 150-400 micron fibers was implanted within the substance of the prostate through which a Yttrium Aluminum Garnet (YAG) laser energy could be transmitted. Using long exposures and lower powers than used in routine endoscopic laser therapy, well-defined areas of coagulative necrosis could be created without extensive tissue charring or damage to the fiber. For an energy dose of 1000J a lesion approximately 1 cm in diameter results at four days. The ultrasound scanning methods can detect the fiber(s) and the area(s) of coagulation. At 6/52 months following treatment, healing was by fibrosis or cystic degeneration. There were no ill effects on the subjects following coagulation of the prostate. Multiple fiber experiments produced larger volume lesions relevant to more extensive cancer or for the coagulation of benign adenomatous hyperplasia causing outflow symptoms. Ultrasound guided clinical treatments in patients with cutaneous metastases or hepatic and pancreatic tumors have confirmed the experimental results so far obtained. The technique may prove of value for the destruction of early, small, focal tumors of the prostate and for the treatment of moderate benign enlargement. Clinical trial for both benign and malignant disease has commenced.
Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response (2014)

Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer therapies, as it compromises treatment and drives malignant progression. This review seeks to clarify the oxygen levels that are pertinent to this issue. It is argued that normoxia (20% oxygen) is an extremely poor comparator for "physoxia", i.e. the much lower levels of oxygen universally found in normal tissues, which averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it should be recognized that the median oxygenation in untreated tumours is significantly much lower, falling between approximately 0.3% and 4.2% oxygen, with most tumours exhibiting median oxygen levels <2%. This is partially dependent on the tissue of origin, and it is notable that many prostate and pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even further, often unrecognized, changes in tumour oxygenation that may vary longitudinally, increasing or decreasing during treatment in ways that are not always predictable. Studies that fail to take cognizance of the actual physiological levels of oxygen in tissues (approximately 5%) and tumours (approximately 1%) may fail to identify the real circumstances driving tumour response to treatment and/or malignant progression. This can be of particular importance in genetic studies in vitro when comparison to human tumours is required.
Endocytosis and the recycling of plasma membrane. (1983)

[No abstract available]
A novel latent membrane 2 transcript expressed in Epstein-Barr virus–positive NK- and T-cell lymphoproliferative disease encodes a target for cellular immunotherapy (2010)

Therapeutic targeting of virus-encoded proteins using cellular immunotherapy has proved successful for Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. However, the more limited repertoire and immunogenicity of EBV-encoded proteins in other malignancies such as Hodgkin lymphoma and extranodal natural killer (NK)/T lymphoma has been more challenging to target. The immunosubdominant latent membrane protein 2 (LMP2) is considered the optimal target in such Latency II tumors, although data relating to its expression in T/NK malignancies are limited. In addressing the validity of LMP2 as an immunotherapeutic target we found that LMP2-specific effector CD8(+) T cells recognized and killed EBV-positive NK- and T-cell tumor lines, despite an apparent absence of LMP2A protein and barely detectable levels of LMP2 transcripts from the conventional LMP2A and LMP2B promoters. We resolved this paradox by identifying in these lines a novel LMP2 mRNA, initiated from within the EBV terminal repeats and containing downstream, epitope-encoding exons. This same mRNA was also highly expressed in primary (extra-nodal) NK/T lymphoma tissue, with virtually undetectable levels of conventional LMP2A/B transcripts. Expression of this novel transcript in T/NK-cell lymphoproliferative diseases validates LMP2 as an attractive target for cellular immunotherapy and implicates this truncated LMP2 protein in NK- and T-cell lymphomagenesis. This study is registered at clinicaltrials.gov as NCT00062868.
Annular electron beam with virtual cathode in a coaxial diode with magnetic insulation (2014)

Accumulation of electrons in course of transportation of tubular high-current electron beam in a coaxial diode with magnetic insulation was studied in the situation of counterstream electron motion occurring due to the formation of a virtual cathode. Accumulation of electrons in these flows is accompanied by gradual increase in their relative energy spread and simultaneous decrease in the maximum kinetic energy. The process is described analytically and confirmed in numerical modeling. The theory is an extension of the known theory of coaxial magnetically insulated diode (based on the conservation of axial component of the generalized momentum) taking into account the spread of electron energies. The numerical modeling employed the KARAT electromagnetic PiC-code. Experiments were performed using high-current electron accelerator SINUS-7 (pulsewidth 50 ns) in the range of diode voltages 350—800 kV, magnetic fields 8—24 kOe, electron beam currents 2—12 kA. A gradual increase of potential of the electron beam between the explosive-emission cathode and the virtual cathode was observed, which accompanies accumulation of circulating electrons as predicted in theory.
Phase I/II Study of Oncolytic Herpes Simplex Virus NV1020 in Patients with Extensively Pretreated Refractory Colorectal Cancer Metastatic to the Liver (2010)

This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via weekly hepatic artery infusion, followed by two or more cycles of conventional chemotherapy. Phase I included cohorts receiving 3 × 10(6), 1 × 10(7), 3 × 10(7), and 1 × 10(8) plaque-forming units (PFU)/dose to determine the optimal biological dose (OBD) for phase II. Blind independent computed tomography scan review was based on RECIST (response evaluation criteria in solid tumors) to assess hepatic tumor response. Phase I and II enrolled 13 and 19 patients, respectively. Patients experienced transient mild-moderate febrile reactions after each NV1020 infusion. Grade 3/4 virus-related toxicity was limited to transient lymphopenia in two patients. NV1020 shedding was not detected. Simultaneous cytokine and grade 1 coagulation perturbations were dose-limiting at 1 × 10(8) PFU/dose, considered the OBD. All 22 OBD patients had previously received 5-fluorouracil; most had received oxaliplatin or irinotecan (50% had both), many with at least one targeted agent. After NV1020 administration, 50% showed stable disease. The best overall tumor control rate after chemotherapy was 68% (1 partial response, 14 stable disease); this did not correlate with baseline variables or chemotherapy. Median time to progression was 6.4 months (95% confidence interval: 2, 8.9); median overall survival was 11.8 months (95% confidence interval: 8.3, 20.7). One-year survival was 47.2%. We conclude that NV1020 stabilizes liver metastases with minimal toxicity in mCRC. It may resensitize metastases to salvage chemotherapy and extend overall survival. A randomized phase II/III trial now appears justified.
Encapsulation for Flexible Electronic Devices (2011)

Flexible electronic devices are influenced by mechanical impacts or bending. This mechanical stress can damage brittle inorganic thin-film layers. One way to improve the stability of such devices is to encapsulate them. For this reason, we encapsulate brittle inorganic materials in our thin-film transistors (TFTs) on flexible polyimide (Kapton) substrates by gluing a second patterned flexible polyimide substrate on top. The developed encapsulation method has the advantages of low process temperatures and micrometer alignment between features on the two substrates and does not damage any thin-film device layer. We are able to bend encapsulated TFTs down to a radius of 125 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\mu\hbox{m}$</tex></formula> without loss of functionality. At this bending radius, the saturation mobility decreases by 3%, and the threshold voltage shifts by 0.2 V. Compared with nonencapsulated TFTs, we decrease the bending radius before the devices fail by an order of magnitude.
An architecture for a mobile OSI mail access system (1989)

An architecture and implementation which support an interface to the X.400 mail environment using the full open-systems communications protocols for a portable computer are described. The implementation is designed to be used over a cellular radio telephone network. The portable computer is used to implement the user agent interface of the CCITT X.413 (1988) message store. A full set of security facilities, designed for use with interpersonal messaging (IPM), is included in the architecture. A number of important issues are discussed regarding the placement and management of keys for the IPM security, as well as authentication between the user and the portable computer and between the user agent and the message store. To support the use of the CCITT message-store model, it was necessary to implement a full protocol stack for open systems interconnection on the portable computer. The design and the author's experiences are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer (2005)

Cannabinoids, the active components of Cannabis sativa Linnaeus (marijuana) and their derivatives have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects and tumor regression. Here we show that expression levels of both cannabinoid receptors, CB1 and CB2, are significantly higher in CA-human papillomavirus-10 (virally transformed cells derived from adenocarcinoma of human prostate tissue), and other human prostate cells LNCaP, DUI45, PC3, and CWR22Rnu1 than in human prostate epithelial and PZ-HPV-7 (virally transformed cells derived from normal human prostate tissue) cells. WIN-55,212-2 (mixed CB1/CB2 agonist) treatment with androgen-responsive LNCaP cells resulted in a dose- (1-10 micromol/L) and time-dependent (24-48 hours) inhibition of cell growth, blocking of CB1 and CB2 receptors by their antagonists SR141716 (CB1) and SR144528 (CB2) significantly prevented this effect. Extending this observation, we found that WIN-55,212-2 treatment with LNCaP resulted in a dose- (1-10 micromol/L) and time-dependent (24-72 hours) induction of apoptosis (a), decrease in protein and mRNA expression of androgen receptor (b), decrease in intracellular protein and mRNA expression of prostate-specific antigen (c), decrease in secreted prostate-specific antigen levels (d), and decrease in protein expression of proliferation cell nuclear antigen and vascular endothelial growth factor (e). Our results suggest that WIN-55,212-2 or other non-habit-forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer.
Increased Release of Interleukin-1 Beta, Interleukin-6, and Tumor Necrosis Factor-Alpha by Bronchoalveolar Cells Lavaged From Involved Sites in Pulmonary Tuberculosis (1996)

Mycobacterium tuberculosis and its components have been shown to stimulate mononuclear phagocytes in vitro to release interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Animal models of tuberculosis (TB) also demonstrate the presence of cytokines in granulomas. We hypothesized that bronchoalveolar lavage (BAL) cells from patients with pulmonary TB would have increased spontaneous release of IL-1 beta, IL-6, and TNF-alpha and would have a concomitant alveolitis. We performed BAL on 26 patients with active TB and on six normal volunteers. BAL fluid from radiographically involved and uninvolved sites was evaluated separately for cell types and the spontaneous release of cytokines. The alveolar inflammation in involved sites was characterized by an increase in lymphocytes (miliary TB, 38 +/- 10%; involved sites, 22 +/- 4%; uninvolved sites, 13 +/- 2%; normal, 5 +/- 2%) and neutrophils (involved sites, 21 +/- 7%; uninvolved sites, 3 +/- 2%). There was a significant increase in the spontaneous release of IL-1 beta (501 +/- 280 pg/ml), TNF-alpha (782 +/- 165 pg/ml), and IL-6 (473 +/- 157 pg/ml) from involved sites of TB patients that was 5- to 20-fold greater than uninvolved sites, normal controls, or miliary TB. Northern analysis revealed increased gene expression of IL-1 beta, TNF-alpha, and IL-6 from the involved sites from two patients with TB compared with two negative controls. We conclude that BAL cells, especially alveolar macrophages, are activated in the alveolar inflammation of active TB and spontaneously release increased quantities of IL-1 beta, IL-6, and TNF-alpha, and that these cytokines are likely to be involved in directing granuloma formation and control of M. tuberculosis infection.
Efficient collision detection for animation and robotics (1993)

We present efficient algorithms for collision detection and contact determination between geometric models, described by linear or curved boundaries, undergoing rigid motion. The heart of our collision detection algorithm is a simple and fast incremental method to compute the distance between two convex polyhedra. It utilizes convexity to establish some local applicability criteria for verifying the closest features. A preprocessing procedure is used to subdivide each feature's neighboring features to a constant size and thus guarantee expected constant running time for each test. The expected constant time performance is an attribute from exploiting the geometric coherence and locality. Let n be the total number of features, the expected run time is between o(#) and 0(n) depending on the shape, if no special initialization is done. This technique can be used for dynamic collision detection, planning in three-dimensional space, physical simulation, and other robotics problems. The set of models we consider includes polyhedra and objects with surfaces described by rational spline patches or piecewise algebraic functions. We use the expected constant time distance computation algorithm for collision detection between convex polyhedral objects and extend it using a hierarchical representation to distance measurement between non-convex polytopes. Next, we use global algebraic methods for solving polynomial equations and the hierarchical description to devise efficient algorithms for arbitrary curved objects. We also describe two different approaches to reduce the frequency of collision detection from pairwise comparisons in an environment with n moving objects. One of them is to use a priority queue sorted by a lower bound on time to collision; the other uses an overlap test on bounding boxes. Finally, we present an opportunistic global path planner algorithm which uses the incremental distance computation algorithm to trace out a one-dimensional skeleton for the purpose of robot motion planning. The performance of the distance computation and collision detection algorithms attests their promise for real-time dynamic simulations as well as applications in a computer generated virtual environment
Synthesis of 3-Sulfonylamino Quinolines from 1-(2-Aminophenyl) Propargyl Alcohols through a Ag(I)-Catalyzed Hydroamination, (2 + 3) Cycloaddition, and an Unusual Strain-Driven Ring Expansion (2015)

We describe herein a silver-catalyzed conversion of 1-(2-aminophenyl)-propargyl alcohols to 4-substituted 3-tosylaminoquinolines using TsN3 as an amino surrogate. Controlled reactions reveal the pathway consisting of Ag(I)-catalyzed 5-exo-dig cyclization, catalyst-free (2 + 3) cycloaddition, and ring-expansive rearrangement via nitrogen expulsion. As a support study, we show that the cyclic enamines in similar conditions produce amidines via a C-C bond migration.
Synthesis of a heteropolytungstate and its use in outer-sphere redox kinetics. An inorganic chemistry laboratory experiment (1992)

An inorganic chemistry experiment has been developed combining two topics usually included in inorganic chemistry: heteropoly ions and mechanisms of oxidation-reduction reactions of transition metal ions.