50175 research outputs found
Sort by
XRCC2 Regulates Replication Fork Progression during dNTP Alterations
No full textRAD51 paralogs are essential for maintenance of genomic integrity through protection of stalled replication forks and homology-directed repair (HDR) of double-strand breaks. Here, we find that a subset of RAD51 paralogs, XRCC2 (FANCU) and its binding partner RAD51D, restrain active DNA synthesis during dinucleotide triphosphate (dNTP) alterations in a manner independent of HDR. The absence of XRCC2 is associated with increased levels of RRM2, the regulatory subunit of ribonucleotide reductase (RNR), and concomitantly high nucleotide pools, leading to unrestrained fork progression and accumulation of DNA damage during dNTP alterations. Mechanistically, this function is independent of redox signaling and RAD51-mediated fork reversal and is regulated by ataxia-telangiectasia and Rad3-related (ATR) signaling through phosphorylation of XRCC2 (Ser247). Together, these findings identify roles of RAD51 paralogs in the control of replication fork progression and maintenance of genome stability during nucleotide pool alterations
Development of an integrated haptic system for simulating upper gastrointestinal endoscopy
No full textVirtual reality together with haptics offers immersive and flexible platforms for training doctors in medical procedures. In this paper, we present mechanical design, control, integration, and user-studies of a virtual reality-based haptic simulator for Upper Gastrointestinal (GI) endoscopy. The design overcomes some of the limitations of the existing systems. First, there is an extra degree of freedom for simulating junctions controlled by sphincter muscles in addition to translational and rotational degrees of freedom along and about the axis of the endoscope-tube. Second, the force-feedback is continuous over a longer range in all three degrees of freedom. Third, multiple insertions and removals of the tube are made possible with a magnetically actuated snap-fit mechanism. A Dynamics based feed-forward control algorithm is developed and characterized for fidelity and transparency. The system provides continuous force up to 11 N in the axial direction and continuous torque up to 255 mN.m about the axial direction. The haptic device is integrated with a physics-based Virtual Reality (VR) interface. Furthermore, an immersion study was conducted using the integrated system with a cohort of novice and experienced clinicians. The haptic response and virtual model were rated high and improvements were suggested for graphical visualization and physical arrangement
Rewiring of one carbon metabolism in Salmonella serves as an excellent live vaccine against systemic salmonellosis
No full textLive attenuated vaccines are superior to the killed or subunit vaccines. We designed a Salmonella Typhimurium strain by deleting folD gene (encoding methylenetetrahydrofolate dehydrogenasecy-clohydrolase) in the presence of a heterologous fhu gene (encoding formyltetrahydrofolate synthetase) and tested its vaccine potential under stringent conditions of lethal and sub-lethal challenges with virulent Salmonella in the murine model. The efficacy of the vaccine in conferring protection against Salmonella infection was determined in a wide range of host conditions of systemic infection, corresponding to human young adults, neonates, geriatric age and, importantly, to the immune compromised state of pregnancy. The standardized vaccination regime comprised a primary dose of 10(4) CFU/animal followed by a booster dose of 10(2) CFU/animal on day 7. Challenge with the virulent pathogen was done at day 7 post-administration of the booster. Subsequently, the mortality, morbidity, systemic colonization, antibody response and cytokine profiling were determined. The vaccinated cohort showed a strong protection against virulent pathogen in all models tested. The serum anti-Salmonella antibody titers and cytokine levels were significantly higher in the vaccinated cohort compared to the mock vaccinated cohort. Thus, we report the development and validation of a live attenuated vaccine candidate conferring excellent protection against Salmonellosis and typhoid fever. (C) 2018 Elsevier Ltd. All rights reserved
Single and Multi-dimensional Integrated optic Photon sources for Quantum communication
No full textWe present an on-chip nonlinear optics based correlated and higher dimensional state photon source using silicon hybrid materials. The four-wave mixing process occurring in a ring resonator is used to generate a frequency comb of signal and idler wavelengths corresponding to different resonant wavelengths around the pump resonance. The frequency comb based four-wave mixing process is used to generate higher-dimensional entangled photon pairs. The individual comb lines, into which the correlated photon pairs could be generated leads to higher dimensional entanglement. The ability to generate higher dimensional photon states is advantageous to pack more information for high data rate quantum communication and information processing applications
A comparative study of wave dispersion between discrete and continuum linear bond-based peridynamics systems: 1D framework
No full textWave dispersion behavior is compared between discrete and continuum systems of a linear bond-based peridynamic bar. Numerical dispersion is known to be prominent in the discrete system, by which, classical behavior is not captured at lower wave-numbers. Using spectral analysis of motion, in this paper, a possibility of absence of numerical dispersion is demonstrated. (C) 2018 Elsevier Ltd. All rights reserved
Towards Improving Data Center Utilisation by Reducing Fragmentation
No full textMany enterprise organizations, like large ecommerce platforms, are consolidating their ICT infrastructure on private clouds to harness cloud properties of scalability and elasticity. Administratively many of these cloud deployments use pre-defined VM sizes to ease effort of use and placement. With this sizing, workloads' requirements poorly match with the offered sizes leading to poor VM and host utilisations. This paper proposes alternate VM sizing approaches to overcome this and compares internal, external resource fragmentation in each case. To evaluate this, utilisation traces from the private cloud of Flipkart, having thousands of servers and VMs are used. Evaluations show that applications as well as host utilisation benefits accrue by customising VM sizes to application requirements. We also show how VM sizes and host configurations influence consolidation ratios and utilisation
Angular analysis of the decay B+ -> K+mu(+)mu(-) in proton-proton collisions at root s=8 TeV
No full textThe angular distribution of the flavor-changing neutral current decay B+ -> K+mu(+)mu(-) is studied in proton-proton collisions at a center-of-mass energy of 8 TeV. The analysis is based on data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 20.5 fb(-1). The forward-backward asymmetry A(FB) of the dimuon system and the contribution F-H from the pseudoscalar, scalar, and tensor amplitudes to the decay width are measured as a function of the dimuon mass squared. The measurements are consistent with the standard model expectations
‘Roshini’- Developing a DIY Rural Solar Light: utilizing products at End-of-Life (EoL) stage
No full textAccess to electricity (primarily for lighting) has
been a challenge in developing countries, especially for rural
areas. Further, hands-on DIY approaches in rural areas could
empower the youth in various vocational skills involving
sustainable design and energy-use, viz., Photovoltaics (PV),
energy-storage devices, smart-sensors, efficient lighting and
waste recycling. With these objectives in mind, a Do-it-yourself
(DIY) kit ‘Roshini’- aimed to provide a basic solar-based lighting
has been envisaged. The design also has provision for extended-
use of PV-panels by utilizing partially-degraded ones. The aim of
this study is to understand the challenges and benefits of DIY
based kits for affordable and reliable product-development and
dissemination in rural base-of-the-pyramid (BoP) households.
A preliminary study was conducted on a group of students
from Bengaluru city (Karnataka state) and Namakkal district
(Tamil Nadu state) to understand the ability of youth to acquire
the vocational skills of assembly, design, and learnings from a
DIY-kit prepared to impart a basic understanding of product
design and electronics design. The major benefits seen from this
DIY-oriented study is the design-learning and skill development
amongst the youth. With the idea of DIY, cost of assembly of the
product and associated environmental impacts are reduced.
In summary, this study helps us to learn the strengths and
weaknesses of DIY modules; and would provide us with
innovative pedagogical models for training and education of rural
youth and adolescent population . Furthermore, this DIY
approach can be extended to urban slums, street vendors and
womenfolk across the rural-urban divide to empower youth and
adults alike
Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition
No full textIn eukaryotic translation initiation, AUG recognition of the mRNA requires accommodation of Met-tRNA(i) in a `PIN' state, which is antagonized by the factor eIF1. eIF5 is a GTPase activating protein (GAP) of eIF2 that additionally promotes stringent AUG selection, but the molecular basis of its dual function was unknown. We present a cryo-electron microscopy (cryo-EM) reconstruction of a yeast 48S pre-initiation complex (PIC), at an overall resolution of 3.0 angstrom, featuring the N-terminal domain (NTD) of eIF5 bound to the 40S subunit at the location vacated by eIF1. eIF5 interacts with and allows a more accommodated orientation of Met-tRNAi. Substitutions of eIF5 residues involved in the eIF5-NTD/tRNAi interaction influenced initiation at near-cognate UUG codons in vivo, and the closed/open PIC conformation in vitro, consistent with direct stabilization of the codon:anticodon duplex by the wild-type eIF5-NTD. The present structure reveals the basis for a key role of eIF5 in start-codon selection
Divide and Grow: Capturing Huge Diversity in Crowd Images with Incrementally Growing CNN
No full textAutomated counting of people in crowd images is a challenging task. The major difficulty stems from the large diversity in the way people appear in crowds. In fact, features available for crowd discrimination largely depend on the crowd density to the extent that people are only seen as blobs in a highly dense scene. We tackle this problem with a growing CNN which can progressively increase its capacity to account for the wide variability seen in crowd scenes. Our model starts from a base CNN density regressor, which is trained in equivalence on all types of crowd images. In order to adapt with the huge diversity, we create two child regressors which are exact copies of the base CNN. A differential training procedure divides the dataset into two clusters and fine-tunes the child networks on their respective specialties. Consequently, without any hand-crafted criteria for forming specialties, the child regressors become experts on certain types of crowds. The child networks are again split recursively, creating two experts at every division. This hierarchical training leads to a CNN tree, where the child regressors are more fine experts than any of their parents. The leaf nodes are taken as the final experts and a classifier network is then trained to predict the correct specialty for a given test image patch. The proposed model achieves higher count accuracy on major crowd datasets. Further, we analyse the characteristics of specialties mined automatically by our method