Complexity of determining exact tolerances for min-max combinatorial optimization problems

Suppose that we are given an instance of a combinatorial optimization problemwith min-max objective along with an optimal solution for it. Let the cost of asingle element be varied. We refer to the range of values of the element’s costfor which the given optimal solution remains optimal as its exact tolerance. Inthis paper we examine the problem of determining the exact tolerance of eachelement in combinatorial optimization problems with min-max objectives. Weshow that under very weak assumptions, the exact tolerance of each elementcan be determined in polynomial time if and only if the original optimizationproblem can be solved in polynomial time

Antiangiogenic Therapy for Patients with Recurrent and Newly Diagnosed Malignant Gliomas

Malignant gliomas have a poor prognosis despite advances in diagnosis and therapy. Although postoperative temozolomide and radiotherapy improve overall survival in glioblastoma patients, most patients experience a recurrence. The prognosis of recurrent malignant gliomas is dismal, and more effective therapeutic strategies are clearly needed. Antiangiogenesis is currently considered an attractive targeting therapy for malignant gliomas due to its important role in tumor growth. Clinical trials using bevacizumab have been performed for recurrent glioblastoma, and these studies have shown promising response rates along with progression-free survival. Based on the encouraging results, bevacizumab was approved by the FDA for the treatment of recurrent glioblastoma. In addition, bevacizumab has shown to be effective for recurrent anaplastic gliomas. Large phase III studies are currently ongoing to demonstrate the efficacy and safety of the addition of bevacizumab to temozolomide and radiotherapy for newly diagnosed glioblastoma. In contrast, several other antiangiogenic drugs have also been used in clinical trials. However, previous studies have not shown whether antiangiogenesis improves the overall survival of malignant gliomas. Specific severe side effects, difficult assessment of response, and lack of rational predictive markers are challenging problems. Further studies are warranted to establish the optimized antiangiogenesis therapy for malignant gliomas

From 2D conformal to 4D self-dual theories: quaternionic analyticity

It is shown that self-dual theories generalize to four dimensions both the conformal and analytic aspects of two-dimensional conformal field theories. In the harmonic space language there appear several ways to extend complex analyticity (natural in two dimensions) to quaternionic analyticity (natural in four dimensions). To be analytic, conformal transformations should be realized on $CP^3$, which appears as the coset of the complexified conformal group modulo its maximal parabolic subgroup. In this language one visualizes the twistor correspondence of Penrose and Ward and consistently formulates the analyticity of Fueter.Comment: 24 pages, LaTe

Selective substitution in orbital domains of a low doped manganite : an investigation from Griffiths phenomenon and modification of glassy features

An effort is made to study the contrast in magnetic behavior resulting from minimal disorder introduced by substitution of 2.5% Ga or Al in Mn-site of La${_{0.9}}$Sr$_{0.1}$MnO${_3}$. It is considered that Ga or Al selectively creates disorder within the orbital domains or on its walls, causing enhancement of Griffiths phase (GP) singularity for the former and disappearance of it in the later case. It is shown that Ga replaces Mn$^{3+}$ which is considered to be concentrated within the domains, whereas Al replaces Mn$^{4+}$ which is segregated on the hole-rich walls, without causing any significant effect on structure or ferromagnetic transition temperatures. Thus, it is presumed that the effect of disorder created by Ga extend across the bulk of the domain having correlation over similar length-scale resulting in enhancement of GP phenomenon. On the contrary, effect of disorder created by Al remains restricted to the walls resulting in the modification of the dynamics arising from the domain walls and suppresses the GP. Moreover contrasting features are observed in the low temperature region of the compounds; a re-entrant spin glass like behavior is observed in the Ga doped sample, while the observed characteristics for the Al doped sample is ascribed only to modified domain wall dynamics with the absence of any glassy phase. Distinctive features in third order susceptibility measurements reveals that the magnetic ground state of the entire series comprises of orbital domain states. These observations bring out the role of the nature of disorder on GP phenomenon and also reconfirms the character of self-organization in low-doped manganites

Evaluation of Groundwater potential Zones using RS and GIS Application in Malattar watershed, Tamil Nadu, India

Groundwater is one of the major sources of water both in the semi-arid and arid regions like Tamil Nadu, India. It is of fundamental importance to any social or economic development. In recent decades, as surface water supplies have been depleted or contaminated and hence more attention has been given to groundwater resources. The advances in the technology especially in the field of remote sensing satellite technology, geophysics, etc. have resulted in enormous increase in the extraction of groundwater. The reservoirs and tanks of the surface water body mainly depending on rainfall.  Due to various reasons the capacity of these structures is also reduced. Hence the storage conditions of these structures are poor during monsoon seasons. In many parts of the state, the declination of groundwater level is a major concern because of continuous pumping of groundwater and poor storage in tanks and reservoirs. Variation of temperature, wind velocity, sunshine hours and evapotranspiration were analyzed. Seasonal average rainfall for 46 years was used to analyze spatial distribution. Geomorphology, land use and lineaments derived from satellite data and geology and soil prepared from district resource maps. Depth to bed rock and weathered rock derived from geophysical survey data to evaluate aquifer thickness. Groundwater potential zonation map was generated using Geographical Information system (GIS) by integration of various thematic maps in the Malattar watershe

Estimation of the frequency of isoform–genotype discrepancies at the apolipoprotein E locus in heterozygotes for the isoforms

Estimates of the impact of apolipoprotein E (apo E) alleles coding for the three common isoforms on plasma lipid levels assume genetic homogeneity among the genotype classes. To test this assumption, we have determined the apo E genotype at the two common polymorphic sites (amino acids 112 and 158) by DNA amplification and hybridisation with allele‐specific oligoprobes, in 195 unrelated Caucasian participants of the Rochester Family Heart Study previously classified as heterozygotes by isoelectric focusing (IEF). Fourteen discordant samples were initially detected. Repeat typing of these samples by both methods resolved nine discrepancies and analysis of additional blood samples from the remaining five individuals eliminated a further four discrepancies. The only truly discordant allele was found in a female subject who had an E3 isoform with the common E2 (Cys 112 , Cys 158 ) genotype. Transmission of this allele from the mother was demonstrated. From these results, we estimate the frequency of discrepancies between isoforms and common genotypes to be 0.25% in this population. Allele misclassification was caused by poor amplification of the DNA in six samples and superimposition of glycosylated and nonglycosylated apo E isoforms on isoelectric focusing gels in five samples. We conclude that the assumption of genetic homogeneity among genotype classes is valid and that misclassification due to technical difficulties is more frequent than true discordancies. © 1992 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101763/1/1370090403_ftp.pd

Controlling Adult Stem Cell Behavior Using Nanodiamond-Reinforced Hydrogel: Implication in Bone Regeneration Therapy

Nanodiamonds (NDs) have attracted considerable attention as drug delivery nanocarriers due to their low cytotoxicity and facile surface functionalization. Given these features, NDs have been recently investigated for the fabrication of nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a three-dimensional scaffold for drug delivery and stem cell-guided bone regeneration. We investigated the effect of different concentration of NDs on the physical and mechanical properties of the GelMA hydrogel network. The inclusion of NDs increased the network stiffness, which in turn augmented the traction forces generated by human adipose stem cells (hASCs). We also tested the ability of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated gene expression, cell area, and focal adhesion number in hASCs. Moreover, the integration of the ND-Dex complex within GelMA hydrogels allowed a higher retention of Dex over time, resulting in significantly increased alkaline phosphatase activity and calcium deposition of encapsulated hASCs. These results suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to develop a novel platform for bone tissue engineering

Fabrication of a Double-Cross-Linked Interpenetrating Polymeric Network (IPN) Hydrogel Surface Modified with Polydopamine to Modulate the Osteogenic Differentiation of Adipose-Derived Stem Cells

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials and Interfaces, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acsami.8b05200.Hydrogel surface properties can be modified to form bioactive interfaces to modulate the osteogenic differentiation of stem cells. In this work, a hydrogel made of gelatin methacrylamide (GelMA) and alginate was designed and tested as a scaffold to control stem-cell osteogenic differentiation. The hydrogel’s surface was treated with polydopamine (pDA) to create an adhesive layer for the adsorption of the osteoinductive drug dexamethasone (Dex). The presence of the pDA coating enhanced Dex adsorption and retention over 21 days. This effect resulted in a delay in the osteogenic differentiation of hASCs cultured on the hydrogel treated with a pDA layer

Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair: In Vitro and In Vivo Analysis

Introduction Stem cell-based therapies represent a valid approach to restore cardiac function due to their beneficial effect in reducing scar area formation and promoting angiogenesis. However, their translation into the clinic is limited by the poor differentiation and inability to secrete sufficient therapeutic factors. To address this issue, several strategies such as genetic modification and biophysical pre-conditioning have been used to enhance the efficacy of stem cells for cardiac tissue repair. Methods In this study, a biomimetic approach was used to mimic the natural mechanical stimulation of the myocardium tissue. Specifically, human adipose-derived stem cells (hASCs) were cultured on a thin gelatin methacrylamide (GelMA) hydrogel disc and placed on top of a beating cardiomyocyte layer. qPCR studies and metatranscriptomic analysis of hASCs gene expression were investigated to confirm the correlation between mechanical stimuli and cardiomyogenic differentiation. In vivo intramyocardial delivery of pre-conditioned hASCs was carried out to evaluate their efficacy to restore cardiac function in mice hearts post-myocardial infarction. Results The cyclic strain generated by cardiomyocytes significantly upregulated the expression of both mechanotransduction and cardiomyogenic genes in hASCs as compared to the static control group. The inherent angiogenic secretion profile of hASCs was not hindered by the mechanical stimulation provided by the designed biomimetic system. Finally, in vivo analysis confirmed the regenerative potential of the pre-conditioned hASCs by displaying a significant improvement in cardiac function and enhanced angiogenesis in the peri-infarct region. Conclusion Overall, these findings indicate that cyclic strain provided by the designed biomimetic system is an essential stimulant for hASCs cardiomyogenic differentiation, and therefore can be a potential solution to improve stem-cell based efficacy for cardiovascular repair