Eric Sembrat's Test Bonanza

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The DNA mismatch repair system is critical for accurate DNA replication.  This system is highly conserved across organisms ranging from bacteria to humans reflecting the importance of minimizing genomic defects during cell division. The mismatch repair protein MutS has been identified the key factor that detects base-base mismatches and insertion-deletion mismatches in double stranded DNA and signals for their repair.  Despite intense study, a temporally resolved understanding of the molecular details of the MutS:DNA interactions during mismatch repair initiation has been difficult to obtain because these transient interactions occur within an overwhelming background of properly matched DNA basepairs.

We used single molecule fluorescence resonance energy transfer (smFRET) to characterize conformational changes in MutS as it scans homoduplex DNA, recognizes mismatches, activates to a sliding clamp, and interacts with downstream proteins in the repair signaling pathway. We found a series of sequential conformational changes that provide a mechanistic picture of: i) dynamic DNA bending by MutS, ii) concomitant conformational changes within MutS itself, iii) motion of MutS scanning along DNA, iv) ATP binding states that commit MutS:mismatch DNA complexes to convert to sliding states used in signaling, and v) the modulation of these MutS behaviors by other regulatory factors.

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PLEASE NOTE: This is a WEBINAR

The displacement of a liquid by an air bubble is a generic two-phase flow that underpins applications as diverse as microfluidics, thin-film coating, enhanced oil recovery, and biomechanics of the lungs. I will present two intriguing examples of such flows where, firstly, oscillations in the shape of propagating bubbles are induced by a simple change in tube geometry, and secondly, flexible vessel boundaries that enable streamwise variations of the channel depth suppress viscous fingering instability.

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Cosmic rays have been observed on Earth with energies in excess of 10^20 eV. Because cosmic rays are charged particles and are bent by galactic magnetic fields, the origin of these particles has remained a mystery. Gamma-ray bursts are one of a few astronomical sources containing an environment capable of accelerating charged particles to the energies observed. In addition, gamma-ray bursts are the leading candidate due to the fact that the total aggregate power observed in gamma-ray bursts and ultra high energy cosmic rays are the same order of magnitude. Neutrinos can only be created by hadronic interactions, so an observation of neutrinos in coincidence with a gamma-ray burst would provide compelling evidence that hadrons are accelerated in gamma-ray burst fireballs and hence the origin of cosmic rays. Using the IceCube Neutrino Observatory in its 40 string configuration, a stacked search was performed to look for the simultaneous occurrence of muon neutrinos with 117 gamma-ray bursts. No evidence for neutrino emission was found, placing a 90% upper limit 0.82 of the predicted neutrino fluence.

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For many investigations like astronomical observations in various electromagnetic windows, atmospheric and high altitude research, it is necessary to reach the top of the atmosphere. Balloons have been used as a carrier for a long time. The Tata Institute of Fundamental Research has conducted regular balloon flights for over 60 years and operates the National Balloon Facility in Hyderabad. This facility has been used by Indian and international groups for a variety of investigations. Balloons provide a cost effective means for space research by a small group of scientists. I will talk about the adventures of ballooning with special reference to the flights conducted by TIFR. I will show slides of various aspects of the fabrication, launch and recovery operations and also show some of the instruments flown. I'll briefly talk about long duration flights. I'll conclude by showing a short video clip.

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 PLEASE NOTE: This is a WEBINAR

More than 125 years ago Osborne Reynolds launched the quantitative study of turbulent transition as he sought to understand the conditions under which fluid flowing through a pipe would be laminar or turbulent. Since laminar and turbulent flow have vastly different drag laws, this question is as important now as it was in Reynolds' day.  Reynolds understood how one should define ``the real critical value'' for the fluid velocity beyond which turbulence can persist indefinitely.  He also appreciated the difficulty in obtaining this value.  For years this critical Reynolds number, as we now call it, has been the subject of study, controversy, and uncertainty. Now, more than a century after Reynolds pioneering work, we know that the onset of turbulence in shear flows is properly understood as a statistical phase transition.  How turbulence first develops in these flows is more closely related to the onset of an infectious disease than to, for example, the onset of oscillation in the flow past a body or the onset of motion in a fluid layer heated from below.  Through the statistical analysis of large samples of individual decay and proliferation events, we at last have an accurate estimate of the real critical Reynolds number for the onset of turbulence in pipe flow, and with it, an understanding of the nature of transitional turbulence.

 

 

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Cancer continues to elude us. Metastasis, relapse and drug resistance are all still poorly understood and clinically insuperable. Evidently, the prevailing paradigms need to be re-examined and out-of-the-box ideas ought to be explored. Recently, has become acknowledged that transformative convergence of physical sciences with life sciences can bring forth new perspectives for addressing major questions and challenges relating to cancer. Drawing upon recent discoveries demonstrating the parallels between collective behaviors of bacteria and cancer, I will present a new picture of cancer as a society of smart communicating cells motivated by the realization of bacterial social intelligence. There is growing evidence that cancer cells, much like bacteria do, rely on advanced communication, social networking and cooperation to grow, spread within the body, colonize new organs, relapse and develop drug resistance. I will address the role of communication, cooperation and decision-making in bacterial collective navigation, swarming logistics and colony development. This will lead to a new picture of cancer cell migration, metastasis colonization and cell fate determination. I will reason that the new understanding calls for “cyber war” on cancer – the developments of drugs to target cancer communication and control.

“Bacterial linguistic communication and social intelligence”

http://www.cell.com/trends/microbiology/abstract/S0966-842X(04)00138-6

 
"Bacterial survival strategies suggest rethinking cancer cooperativity"

 http://www.cell.com/trends/microbiology/abstract/S0966-842X(12)00101-1

 

 

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Granular materials exhibit large spatial variations in their response to external loading, whether static or dynamic. As such, continuum models of properties such as the shear modulus and sound speed often fail. A promising alternative is to build an understanding of bulk behaviors from measurements at the particle scale, by analogy with the statistical mechanics of thermal systems. I will describe experiments in which we utilize photoelastic particles and piezo-embedded 'smart' particles to explore how two familiar properties -- temperature equilibration and densities of states -- might arise in this new context.

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Recent advancements in computational fluid dynamics have enabled researchers to efficiently explore problems that involve moving elastic boundaries immersed in fluids for problems such as cardiac fluid dynamics, fish swimming, and the movement of bacteria. These advances have also made modeling the interaction between a fluid and an electromechanical model of an elastic organ feasible. The tubular hearts of some ascidians and vertebrate embryos offers a relatively simple model organ for such a study. Blood is driven through the heart by either peristaltic contractions or valveless suction pumping through localized periodic contractions. Models considering only the fluid-structure interaction aspects of these hearts are insufficient to resolve the actual pumping mechanism. The electromechanical model presented here will integrate feedback between the conduction of action potentials, the contraction of muscles, the movement of tissues, and the resulting fluid motion.

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mso-bidi-font-style:italic">The problem of speciation and species aggregation on a neutral landscape, subject to random mutational fluctuations without selective drive, has been a focus of research since the seminal work of Kimura on genetic drift. This problem, which has received increased attention due to the recent development of a neutral ecological theory by Hubbell, bears comparison with mathematical problems such as percolation and branching and coalescing random walks. I will discuss an agent-based computational model in which clustering (speciation) occurs on a neutral phenotype landscape. This model corresponds to sympatric speciation: organisms cluster phenotypically, but are not spatially separated. Moreover, clustering occurs not only in the case of assortative mating, but also in the case of asexual fission (bacterial splitting). In contrast, clusters fail to form in a control case where organisms mate randomly. The population size and the number of clusters (species) undergo a critical phase transition, most likely of the directed percolation universality class, as the maximum mutation size is varied, and cluster size appears to undergo a percolation transition.

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Motile immune cells like neutrophils (the most abundant type of white blood cell) track down invading microbes by chemotaxis, keep hold of them by adhesion, and neutralize them by phagocytosis.  We integrate concepts and tools from immunobiology and biophysics to examine the mechanistic underpinnings of this amazing, cross-disciplinary feat.  Single-live-cell experiments using micropipette manipulation, optical tweezers, and a new type of horizontal atomic force microscope allow us to assess the nano-to-microscale ingredients of one-on-one encounters between human neutrophils and their targets (such as opsonized particles or pathogenic fungi and bacteria).  We dissect such encounters by examining separately the immunophysical roles of opsonization, chemotaxis, immune-cell priming, adhesion, and phagocytosis, as well as their vital interplay.  Providing a fresh view of the initiation of host-pathogen interactions, this approach demonstrates how the integration of essential physical insight with immunobiology allows us to define tighter constraints on possible explanations of cell and molecular behavior. 

Reference:

Heinrich, V., and C.-Y. Lee.  (2011).  Blurred line between chemotactic chase and phagocytic consumption:  An immunophysical, single-cell perspective.  Journal of Cell Science  124(18):3041-3051.

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