305 research outputs found
Provably Efficient Maximum Entropy Exploration
Suppose an agent is in a (possibly unknown) Markov Decision Process in the
absence of a reward signal, what might we hope that an agent can efficiently
learn to do? This work studies a broad class of objectives that are defined
solely as functions of the state-visitation frequencies that are induced by how
the agent behaves. For example, one natural, intrinsically defined, objective
problem is for the agent to learn a policy which induces a distribution over
state space that is as uniform as possible, which can be measured in an
entropic sense. We provide an efficient algorithm to optimize such such
intrinsically defined objectives, when given access to a black box planning
oracle (which is robust to function approximation). Furthermore, when
restricted to the tabular setting where we have sample based access to the MDP,
our proposed algorithm is provably efficient, both in terms of its sample and
computational complexities. Key to our algorithmic methodology is utilizing the
conditional gradient method (a.k.a. the Frank-Wolfe algorithm) which utilizes
an approximate MDP solver.Comment: Updated experiment results; minor revisions in writin
Online Control with Adversarial Disturbances
We study the control of a linear dynamical system with adversarial
disturbances (as opposed to statistical noise). The objective we consider is
one of regret: we desire an online control procedure that can do nearly as well
as that of a procedure that has full knowledge of the disturbances in
hindsight. Our main result is an efficient algorithm that provides nearly tight
regret bounds for this problem. From a technical standpoint, this work
generalizes upon previous work in two main aspects: our model allows for
adversarial noise in the dynamics, and allows for general convex costs
Many-body diagrammatic expansion in a Kohn-Sham basis: implications for Time-Dependent Density Functional Theory of excited states
We formulate diagrammatic rules for many-body perturbation theory which uses
Kohn-Sham (KS) Green's functions as basic propagators. The diagram technique
allows to study the properties of the dynamic nonlocal exchange-correlation
(xc) kernel . We show that the spatial non-locality of is
strongly frequency-dependent. In particular, in extended systems the
non-locality range diverges at the excitation energies. This divergency is
related to the discontinuity of the xc potential.Comment: 4 RevTeX pages including 3 eps figures, submitted to Phys. Rev. Lett;
revised version with new reference
Withaferin a alone and in combination with Cisplatin suppresses growth and metastasis of ovarian cancer by targeting putative cancer stem cells.
Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately within few months of initial treatment, tumor relapse occurs because of platinum-resistance. This is attributed to chemo-resistance of cancer stem cells (CSCs). Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs. Treatment of nude mice bearing orthotopic ovarian tumors generated by injecting human ovarian epithelial cancer cell line (A2780) with WFA and cisplatin (WFA) alone or in combination resulted in a 70 to 80% reduction in tumor growth and complete inhibition of metastasis to other organs compared to untreated controls. Histochemical and Western blot analysis of the tumors revealed that inclusion of WFA (2 mg/kg) resulted in a highly significant elimination of cells expressing CSC markers - CD44, CD24, CD34, CD117 and Oct4 and downregulation of Notch1, Hes1 and Hey1 genes. In contrast treatment of mice with CIS alone (6 mg/kg) had opposite effect on those cells. Increase in cells expressing CSC markers and Notch1 signaling pathway in tumors exposed to CIS may explain recurrence of cancer in patients treated with carboplatin and paclitaxel. Since, WFA alone or in combination with CIS eliminates putative CSCs, we conclude that WFA in combination with CIS may present more efficacious therapy for ovarian cancer
The progress made in determining the Mycobacterium tuberculosis structural proteome
Mycobacterium tuberculosis is a highly infectious pathogen that is still responsible for millions of deaths annually. Effectively treating this disease typically requires a course of antibiotics, most of which were developed decades ago. These drugs are, however, not effective against persistent tubercle bacilli and the emergence of drug-resistant stains threatens to make many of them obsolete. The identification of new drug targets, allowing the development of new potential drugs, is therefore imperative. Both proteomics and structural biology have important roles to play in this process, the former as a means of identifying promising drug targets and the latter allowing understanding of protein function and proteinâdrug interactions at atomic resolution. The determination of M. tuberculosis protein structures has been a goal of the scientific community for the last decade, who have aimed to supply a large amount of structural data that can be used in structure-based approaches for drug discovery and design. Only since the genome sequence of M. tuberculosis has been available has the determination of large numbers of tuberculosis protein structures been possible. Currently, the molecular structures of 8.5% of all the pathogen's protein-encoding ORFs have been determined. In this review, we look at the progress made in determining the M. tuberculosis structural proteome and the impact this has had on the development of potential new drugs, as well as the discovery of the function of crucial mycobaterial proteins
Orbital state and magnetic properties of LiV_2 O_4
LiV_2 O_4 is one of the most puzzling compounds among transition metal oxides
because of its heavy fermion like behavior at low temperatures. In this paper
we present results for the orbital state and magnetic properties of LiV_2 O_4
obtained from a combination of density functional theory within the local
density approximation and dynamical mean-field theory (DMFT). The DMFT
equations are solved by quantum Monte Carlo simulations. The trigonal crystal
field splits the V 3d orbitals such that the a_{1g} and e_{g}^{pi} orbitals
cross the Fermi level, with the former being slightly lower in energy and
narrower in bandwidth. In this situation, the d-d Coulomb interaction leads to
an almost localization of one electron per V ion in the a_{1g} orbital, while
the e_{g}^{pi} orbitals form relatively broad bands with 1/8 filling. 2The
theoretical high-temperature paramagnetic susceptibility chi(T) follows a
Curie-Weiss law with an effective paramagnetic moment p_{eff}=1.65 in agreement
with the experimental results.Comment: 11 pages, 10 figures, 2 table
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Epidemiology and risk factors of chronic kidney disease in India â results from the SEEK (Screening and Early Evaluation of Kidney Disease) study
Background: There is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually. Methods: We cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected. Results: The total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18â98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively. Conclusion: The prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies. It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India
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