160 research outputs found
Профессор С. С. Сулакшин (1919-2011)
Ушел из жизни основатель кафедры бурения скважин, доктор технических наук, профессор, Заслуженный деятель науки и техники Российской Федерации, Лауреат премии Совета Министров СССР, Почётный разведчик недр, Отличник разведки недр, Почётный академик АЕН РФ, "Почетный работник профессионального образования Российской Федерации" - Степан Степанович Сулакшин
Psychological disorders and personality characteristics of with gastro-esophageal reflux disease
Background: Gastro-esophageal reflux disease (GERD) can be traced back to disorders of the gastro-esophageal junction but several psychological factors interact to affect treatment outcomes. There is sparse literature from India regarding psychological co-morbidity and personality characteristics in patients with GERD.Aim and Objectives: To study the co-morbid psychological disorders and personality profiles in patients suffering from GERD.Methods: Two hundred patients with GERD-related symptoms were randomly screened for psychological disorders and personality characteristics using 30-item General Health Questionnaire (GHQ) and Sixteen Personality Factor Questionnaire (16PF) respectively. Patients who screened positive for presence of co-morbid psychological disorders were further interviewed using Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID-1) to find out the type of psychological disorder. Results:The prevalenceofpsychological co-morbidity in patients with GERD-related symptoms in our sample was foundto be 40%. Major depressive disorder was the most common psychological disorder found co-morbid in these patients. Alcohol dependence was significantly observed in males; while in females, major depressive disorder and generalized anxiety disorder was more commonly seen. Regarding personality characteristics, a higher degree of neuroticism and risk-taking attitudes was found in patients of GERD with associated psychological co-morbidity Conclusions:This study suggests that the management of GERD may include psychological evaluations and possibly interventions in standard treatment protocols.
Alternatives to antibiotics-a pipeline portfolio review
Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future.</p
Motor neuronopathy with dropped hands and downbeat nystagmus: A distinctive disorder? A case report
BACKGROUND: Eye movements are clinically normal in most patients with motor neuron disorders until late in the disease course. Rare patients are reported to show slow vertical saccades, impaired smooth pursuit, and gaze-evoked nystagmus. We report clinical and oculomotor findings in three patients with motor neuronopathy and downbeat nystagmus, a classic sign of vestibulocerebellar disease. CASE PRESENTATION: All patients had clinical and electrodiagnostic features of anterior horn cell disease. Involvement of finger and wrist extensors predominated, causing finger and wrist drop. Bulbar or respiratory dysfunction did not occur. All three had clinically evident downbeat nystagmus worse on lateral and downgaze, confirmed on eye movement recordings using the magnetic search coil technique in two patients. Additional oculomotor findings included alternating skew deviation and intermittent horizontal saccadic oscillations, in one patient each. One patient had mild cerebellar atrophy, while the other two had no cerebellar or brainstem abnormality on neuroimaging. The disorder is slowly progressive, with survival up to 30 years from the time of onset. CONCLUSION: The combination of motor neuronopathy, characterized by early and prominent wrist and finger extensor weakness, and downbeat nystagmus with or without other cerebellar eye movement abnormalities may represent a novel motor neuron syndrome
Topics on modular Galois representations modulo prime powers
This article surveys modularity, level raising and level lowering questions for two-dimensional representations modulo prime powers of the absolute Galois group of the rational numbers. It contributes some new results and describes algorithms and a database of modular forms orbits and higher congruences
Partially glycosylated dendrimers block MD-2 and prevent TLR4-MD-2-LPS complex mediated cytokine responses.
The crystal structure of the TLR4-MD-2-LPS complex responsible for triggering powerful pro-inflammatory cytokine responses has recently become available. Central to cell surface complex formation is binding of lipopolysaccharide (LPS) to soluble MD-2. We have previously shown, in biologically based experiments, that a generation 3.5 PAMAM dendrimer with 64 peripheral carboxylic acid groups acts as an antagonist of pro-inflammatory cytokine production after surface modification with 8 glucosamine molecules. We have also shown using molecular modelling approaches that this partially glycosylated dendrimer has the flexibility, cluster density, surface electrostatic charge, and hydrophilicity to make it a therapeutically useful antagonist of complex formation. These studies enabled the computational study of the interactions of the unmodified dendrimer, glucosamine, and of the partially glycosylated dendrimer with TLR4 and MD-2 using molecular docking and molecular dynamics techniques. They demonstrate that dendrimer glucosamine forms co-operative electrostatic interactions with residues lining the entrance to MD-2's hydrophobic pocket. Crucially, dendrimer glucosamine interferes with the electrostatic binding of: (i) the 4'phosphate on the di-glucosamine of LPS to Ser118 on MD-2; (ii) LPS to Lys91 on MD-2; (iii) the subsequent binding of TLR4 to Tyr102 on MD-2. This is followed by additional co-operative interactions between several of the dendrimer glucosamine's carboxylic acid branches and MD-2. Collectively, these interactions block the entry of the lipid chains of LPS into MD-2's hydrophobic pocket, and also prevent TLR4-MD-2-LPS complex formation. Our studies have therefore defined the first nonlipid-based synthetic MD-2 antagonist using both animal model-based studies of pro-inflammatory cytokine responses and molecular modelling studies of a whole dendrimer with its target protein. Using this approach, it should now be possible to computationally design additional macromolecular dendrimer based antagonists for other Toll Like Receptors. They could be useful for treating a spectrum of infectious, inflammatory and malignant diseases
In situ conjugation of dithiophenol maleimide polymers and oxytocin for stable and reversible polymer–peptide conjugates
The in situ one-pot synthesis of peptide–polymer bioconjugates is reported. Conjugation occurs efficiently without the need for purification of dithiophenol maleimide functionalized polymer as a disulfide bridging agent for the therapeutic oxytocin. Conjugation of polymers was demonstrated to be reversible and to significantly improve the solution stability of oxytocin
RAFT aqueous dispersion polymerization yields poly(ethylene glycol)-based diblock copolymer nano-objects with predictable single phase morphologies
A poly(ethylene glycol) (PEG) macromolecular chain transfer agent (macro-CTA) is prepared in high yield (>95%) with 97% dithiobenzoate chain-end functionality in a three-step synthesis starting from a monohydroxy PEG113 precursor. This PEG113-dithiobenzoate is then used for the reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Polymerizations conducted under optimized conditions at 50 °C led to high conversions as judged by 1H NMR spectroscopy and relatively low diblock copolymer polydispersities (Mw/Mn < 1.25) as judged by GPC. The latter technique also indicated good blocking efficiencies, since there was minimal PEG113 macro-CTA contamination. Systematic variation of the mean degree of polymerization of the core-forming PHPMA block allowed PEG113-PHPMAx diblock copolymer spheres, worms, or vesicles to be prepared at up to 17.5% w/w solids, as judged by dynamic light scattering and transmission electron microscopy studies. Small-angle X-ray scattering (SAXS) analysis revealed that more exotic oligolamellar vesicles were observed at 20% w/w solids when targeting highly asymmetric diblock compositions. Detailed analysis of SAXS curves indicated that the mean number of membranes per oligolamellar vesicle is approximately three. A PEG 113-PHPMAx phase diagram was constructed to enable the reproducible targeting of pure phases, as opposed to mixed morphologies (e.g., spheres plus worms or worms plus vesicles). This new RAFT PISA formulation is expected to be important for the rational and efficient synthesis of a wide range of biocompatible, thermo-responsive PEGylated diblock copolymer nano-objects for various biomedical applications
The Gravity Collective: A Search for the Electromagnetic Counterpart to the Neutron Star-Black Hole Merger GW190814
We present optical follow-up imaging obtained with the Katzman Automatic
Imaging Telescope, Las Cumbres Observatory Global Telescope Network, Nickel
Telescope, Swope Telescope, and Thacher Telescope of the LIGO/Virgo
gravitational wave (GW) signal from the neutron star-black hole (NSBH) merger
GW190814. We searched the GW190814 localization region (19 deg for the
90th percentile best localization), covering a total of 51 deg and 94.6%
of the two-dimensional localization region. Analyzing the properties of 189
transients that we consider as candidate counterparts to the NSBH merger,
including their localizations, discovery times from merger, optical spectra,
likely host-galaxy redshifts, and photometric evolution, we conclude that none
of these objects are likely to be associated with GW190814. Based on this
finding, we consider the likely optical properties of an electromagnetic
counterpart to GW190814, including possible kilonovae and short gamma-ray burst
afterglows. Using the joint limits from our follow-up imaging, we conclude that
a counterpart with an -band decline rate of 0.68 mag day, similar to
the kilonova AT 2017gfo, could peak at an absolute magnitude of at most
mag (50% confidence). Our data are not constraining for ''red'' kilonovae and
rule out ''blue'' kilonovae with (30% confidence). We
strongly rule out all known types of short gamma-ray burst afterglows with
viewing angles 17 assuming an initial jet opening angle of
and explosion energies and circumburst densities similar to
afterglows explored in the literature. Finally, we explore the possibility that
GW190814 merged in the disk of an active galactic nucleus, of which we find
four in the localization region, but we do not find any candidate counterparts
among these sources.Comment: 86 pages, 9 figure
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