3,206 research outputs found
GENO PROTECTIVE AND ANTI-APOPTOTIC EFFECT OF GREEN TEA AGAINST PERINATAL LIPOPOLYSACCHARIDE-EXPOSURE INDUCED LIVER TOXICITY IN RAT NEWBORNS
published_or_final_versio
A Variational Method in Out of Equilibrium Physical Systems
A variational principle is further developed for out of equilibrium dynamical
systems by using the concept of maximum entropy. With this new formulation it
is obtained a set of two first-order differential equations, revealing the same
formal symplectic structure shared by classical mechanics, fluid mechanics and
thermodynamics. In particular, it is obtained an extended equation of motion
for a rotating dynamical system, from where it emerges a kind of topological
torsion current of the form , with and
denoting components of the vector potential (gravitational or/and
electromagnetic) and is the angular velocity of the accelerated frame.
In addition, it is derived a special form of Umov-Poynting's theorem for
rotating gravito-electromagnetic systems, and obtained a general condition of
equilibrium for a rotating plasma. The variational method is then applied to
clarify the working mechanism of some particular devices, such as the Bennett
pinch and vacuum arcs, to calculate the power extraction from an hurricane, and
to discuss the effect of transport angular momentum on the radiactive heating
of planetary atmospheres. This development is seen to be advantageous and opens
options for systematic improvements.Comment: 22 pages, 1 figure, submitted to review, added one referenc
A mutate-and-map protocol for inferring base pairs in structured RNA
Chemical mapping is a widespread technique for structural analysis of nucleic
acids in which a molecule's reactivity to different probes is quantified at
single-nucleotide resolution and used to constrain structural modeling. This
experimental framework has been extensively revisited in the past decade with
new strategies for high-throughput read-outs, chemical modification, and rapid
data analysis. Recently, we have coupled the technique to high-throughput
mutagenesis. Point mutations of a base-paired nucleotide can lead to exposure
of not only that nucleotide but also its interaction partner. Carrying out the
mutation and mapping for the entire system gives an experimental approximation
of the molecules contact map. Here, we give our in-house protocol for this
mutate-and-map strategy, based on 96-well capillary electrophoresis, and we
provide practical tips on interpreting the data to infer nucleic acid
structure.Comment: 22 pages, 5 figure
Microscopic Realization of the Kerr/CFT Correspondence
Supersymmetric M/string compactifications to five dimensions contain BPS
black string solutions with magnetic graviphoton charge P and near-horizon
geometries which are quotients of AdS_3 x S^2. The holographic duals are
typically known 2D CFTs with central charges c_L=c_R=6P^3 for large P. These
same 5D compactifications also contain non-BPS but extreme Kerr-Newman black
hole solutions with SU(2)_L spin J_L and electric graviphoton charge Q obeying
Q^3 \leq J_L^2. It is shown that in the maximally charged limit Q^3 -> J_L^2,
the near-horizon geometry coincides precisely with the right-moving temperature
T_R=0 limit of the black string with magnetic charge P=J_L^{1/3}. The known
dual of the latter is identified as the c_L=c_R=6J_L CFT predicted by the
Kerr/CFT correspondence. Moreover, at linear order away from maximality, one
finds a T_R \neq 0 quotient of the AdS_3 factor of the black string solution
and the associated thermal CFT entropy reproduces the linearly sub-maximal
Kerr-Newman entropy. Beyond linear order, for general Q^3<J_L^2, one has a
finite-temperature quotient of a warped deformation of the magnetic string
geometry. The corresponding dual deformation of the magnetic string CFT
potentially supplies, for the general case, the c_L=c_R=6J_L CFT predicted by
Kerr/CFT.Comment: 18 pages, no figure
Amyloid β-peptide directly induces spontaneous calcium transients, delayed intercellular calcium waves and gliosis in rat cortical astrocytes
The contribution of astrocytes to the pathophysiology of AD (Alzheimer's disease) and the molecular and signalling mechanisms that potentially underlie them are still very poorly understood. However, there is mounting evidence that calcium dysregulation in astrocytes may be playing a key role. Intercellular calcium waves in astrocyte networks in vitro can be mechanically induced after Aβ (amyloid β-peptide) treatment, and spontaneously forming intercellular calcium waves have recently been shown in vivo in an APP (amyloid precursor protein)/PS1 (presenilin 1) Alzheimer's transgenic mouse model. However, spontaneous intercellular calcium transients and waves have not been observed in vitro in isolated astrocyte cultures in response to direct Aβ stimulation in the absence of potentially confounding signalling from other cell types. Here, we show that Aβ alone at relatively low concentrations is directly able to induce intracellular calcium transients and spontaneous intercellular calcium waves in isolated astrocytes in purified cultures, raising the possibility of a potential direct effect of Aβ exposure on astrocytes in vivo in the Alzheimer's brain. Waves did not occur immediately after Aβ treatment, but were delayed by many minutes before spontaneously forming, suggesting that intracellular signalling mechanisms required sufficient time to activate before intercellular effects at the network level become evident. Furthermore, the dynamics of intercellular calcium waves were heterogeneous, with distinct radial or longitudinal propagation orientations. Lastly, we also show that changes in the expression levels of the intermediate filament proteins GFAP (glial fibrillary acidic protein) and S100B are affected by Aβ-induced calcium changes differently, with GFAP being more dependent on calcium levels than S100B
Holography for chiral scale-invariant models
Deformation of any d-dimensional conformal field theory by a constant null
source for a vector operator of dimension (d + z -1) is exactly marginal with
respect to anisotropic scale invariance, of dynamical exponent z. The
holographic duals to such deformations are AdS plane waves, with z=2 being the
Schrodinger geometry. In this paper we explore holography for such chiral
scale-invariant models. The special case of z=0 can be realized with gravity
coupled to a scalar, and is of particular interest since it is related to a
Lifshitz theory with dynamical exponent two upon dimensional reduction. We show
however that the corresponding reduction of the dual field theory is along a
null circle, and thus the Lifshitz theory arises upon discrete light cone
quantization of an anisotropic scale invariant field theory.Comment: 62 pages; v2, published version, minor improvements and references
adde
Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide
Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28–81 years), male 81%, Child–Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0–9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways
A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes
Aim
We assessed the safety of ustekinumab (a monoclonal antibody used in psoriasis to target the IL-12 and IL-23 pathways) in a small cohort of recent-onset (<100 days of diagnosis) adults with type 1 diabetes (T1D) by conducting a pilot open-label dose-finding and mechanistic study (NCT02117765) at the University of British Columbia.
Methods
We sequentially enrolled 20 participants into four subcutaneous dosing cohorts: i) 45mg loading-weeks 0/4/16, ii) 45mg maintenance-weeks 0/4/16/28/40, iii) 90mg loading-weeks 0/4/16 and iv) 90mg maintenance-weeks 0/4/16/28/40. The primary endpoint was safety as assessed by an independent data and safety monitoring board (DSMB) but we also measured mixed meal tolerance test C-peptide, insulin use/kg, and HbA1c. Immunophenotyping was performed to assess immune cell subsets and islet antigen-specific T cell responses.
Results
Although several adverse events were reported, only two (bacterial vaginosis and hallucinations) were thought to be possibly related to drug administration by the study investigators. At 1 year, the 90mg maintenance dosing cohort had the smallest mean decline in C-peptide AUC (0.1pmol/mL). Immunophenotyping showed that ustekinumab reduced the percentage of circulating Th17, Th1 and Th17.1 cells and proinsulin-specific T cells that secreted IFN-γ and IL-17A.
Conclusion
Ustekinumab was deemed safe to progress to efficacy studies by the DSMB at doses used to treat psoriasis in adults with T1D. A 90mg maintenance dosing schedule reduced proinsulin-specific IFN-γ and IL-17A-producing T cells. Further studies are warranted to determine if ustekinumab can prevent C-peptide AUC decline and induce a clinical response
- …