Upper Limit on the Cosmic Gamma-Ray Burst Rate from High Energy Diffuse Neutrino Background

We derive upper limits on the ratio $f_{GRB/CCSN}(z) \equiv R_{GRB}(z)/R_{CCSN}(z) \equiv f_{GRB/CCSN}(0)(1+z)^\alpha$, the ratio of the rate, $R_{GRB}$, of long-duration Gamma Ray Bursts (GRBs) to the rate, $R_{CCSN}$, of core-collapse supernovae (CCSNe) in the Universe ($z$ being the cosmological redshift and $\alpha\geq 0$), by using the upper limit on the diffuse TeV--PeV neutrino background given by the AMANDA-II experiment in the South Pole, under the assumption that GRBs are sources of TeV--PeV neutrinos produced from decay of charged pions produced in $p\gamma$ interaction of protons accelerated to ultrahigh energies at internal shocks within GRB jets. For the assumed ``concordance model'' of cosmic star formation rate, $R_{SF}$, with $R_{CCSN}(z) \propto R_{SF}(z)$, our conservative upper limits are $f_{GRB/CCSN}(0)\leq 5.0\times10^{-3}$ for $\alpha=0$, and $f_{GRB/CCSN}(0)\leq 1.1\times10^{-3}$ for $\alpha=2$, for example. These limits are already comparable to (and, for $\alpha\geq 1$ already more restrictive than) the current upper limit on this ratio inferred from other astronomical considerations, thus providing a useful independent probe of and constraint on the CCSN-GRB connection. Non-detection of a diffuse TeV--PeV neutrino background by the up-coming IceCube detector in the South pole after three years of operation, for example, will bring down the upper limit on $f_{GRB/CCSN}(0)$ to below few $\times10^{-5}$ level, while a detection will confirm the hypothesis of proton acceleration to ultrahigh energies in GRBs and will potentially also yield the true rate of occurrence of these events in the Universe.Comment: Two references added, an overall constant numerical factor corrected, Figures and relevant portions of abstract and main text slightly changed, main conclusions unchanged, 18 pages Latex with 4 Figures, version accepted for publication in PR

An unedited 1.1 kb mitochondrial orfB gene transcript in the Wild Abortive Cytoplasmic Male Sterility (WA-CMS) system of Oryza sativa L. subsp. indica

<p>Abstract</p> <p>Background</p> <p>The application of hybrid rice technology has significantly increased global rice production during the last three decades. Approximately 90% of the commercially cultivated rice hybrids have been derived through three-line breeding involving the use of WA-CMS lines. It is believed that during the 21^stcentury, hybrid rice technology will make significant contributions to ensure global food security. This study examined the poorly understood molecular basis of the WA-CMS system in rice.</p> <p>Results</p> <p>RFLPs were detected for <it>atp6 </it>and <it>orfB </it>genes in sterile and fertile rice lines, with one copy of each in the mt-genome. The RNA profile was identical in both lines for <it>atp6</it>, but an additional longer <it>orfB </it>transcript was identified in sterile lines. 5' RACE analysis of the long <it>orfB </it>transcript revealed it was 370 bp longer than the normal transcript, with no indication it was chimeric when compared to the genomic DNA sequence. cDNA clones of the longer <it>orfB </it>transcript in sterile lines were sequenced and the transcript was determined unedited. Sterile lines were crossed with the restorer and maintainer lines, and fertile and sterile F₁hybrids were respectively generated. Both hybrids contained two types of <it>orfB </it>transcripts. However, the long transcript underwent editing in the fertile F₁hybrids and remained unedited in the sterile lines. Additionally, the editing of the 1.1 kb <it>orfB </it>transcript co-segregated with fertility restoring alleles in a segregating population of F₂progeny; and the presence of unedited long <it>orfB </it>transcripts was detected in the sterile plants from the F₂segregating population.</p> <p>Conclusion</p> <p>This study helped to assign plausible operative factors responsible for male-sterility in the WA cytoplasm of rice. A new point of departure to dissect the mechanisms governing the CMS-WA system in rice has been identified, which can be applied to further harness the opportunities afforded by hybrid vigor in rice.</p

HIV-1 and SARS-CoV-2: Patterns in the evolution of two pandemic pathogens

Humanity is currently facing the challenge of two devastating pandemics caused by two very different RNA viruses: HIV-1, which has been with us for decades, and SARS-CoV-2, which has swept the world in the course of a single year. The same evolutionary strategies that drive HIV-1 evolution are at play in SARS-CoV-2. Single nucleotide mutations, multi-base insertions and deletions, recombination, and variation in surface glycans all generate the variability that, guided by natural selection, enables both HIV-1’s extraordinary diversity and SARS-CoV-2’s slower pace of mutation accumulation. Even though SARS-CoV-2 diversity is more limited, recently emergent SARS-CoV-2 variants carry Spike mutations that have important phenotypic consequences in terms of both antibody resistance and enhanced infectivity. We review and compare how these mutational patterns manifest in these two distinct viruses to provide the variability that fuels their evolution by natural selection.Fil: Fischer, Will. Los Alamos National Laboratory; Estados Unidos. New Mexico Consortium; MéxicoFil: Giorgi, Elena E.. New Mexico Consortium; México. Los Alamos National Laboratory; Estados UnidosFil: Chakraborty, Srirupa. Center For Nonlinear Studies; Estados Unidos. Los Alamos National Laboratory; Estados UnidosFil: Nguyen, Kien. Los Alamos National Laboratory; Estados UnidosFil: Bhattacharya, Tanmoy. Los Alamos National Laboratory; Estados UnidosFil: Theiler, James. Los Alamos National Laboratory; Estados UnidosFil: Goloboff, Pablo Augusto. American Museum of Natural History; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Yoon, Hyejin. Los Alamos National Laboratory; Estados UnidosFil: Abfalterer, Werner. Los Alamos National Laboratory; Estados UnidosFil: Foley, Brian T.. Los Alamos National Laboratory; Estados UnidosFil: Tegally, Houriiyah. University Of Kwazulu-natal; SudáfricaFil: San, James Emmanuel. University Of Kwazulu-natal; SudáfricaFil: de Oliveira, Tulio. University of KwaZulu-Natal; SudáfricaFil: Gnanakaran, Sandrasegaram. Los Alamos National Laboratory; Estados UnidosFil: Korber, Bette. Los Alamos National Laboratory; Estados Unidos. New Mexico Consortium; Méxic

"The fruits of independence": Satyajit Ray, Indian nationhood and the spectre of empire

Challenging the longstanding consensus that Satyajit Ray's work is largely free of ideological concerns and notable only for its humanistic richness, this article shows with reference to representations of British colonialism and Indian nationhood that Ray's films and stories are marked deeply and consistently by a distinctively Bengali variety of liberalism. Drawn from an ongoing biographical project, it commences with an overview of the nationalist milieu in which Ray grew up and emphasizes the preoccupation with colonialism and nationalism that marked his earliest unfilmed scripts. It then shows with case studies of Kanchanjangha (1962), Charulata (1964), First Class Kamra (First-Class Compartment, 1981), Pratidwandi (The Adversary, 1970), Shatranj ke Khilari (The Chess Players, 1977), Agantuk (The Stranger, 1991) and Robertsoner Ruby (Robertson's Ruby, 1992) how Ray's mature work continued to combine a strongly anti-colonial viewpoint with a shifting perspective on Indian nationhood and an unequivocal commitment to cultural cosmopolitanism. Analysing how Ray articulated his ideological positions through the quintessentially liberal device of complexly staged debates that were apparently free, but in fact closed by the scenarist/director on ideologically specific notes, this article concludes that Ray's reputation as an all-forgiving, ‘everybody-has-his-reasons’ humanist is based on simplistic or even tendentious readings of his work

Computational modeling of structural dynamics and energetics of two allosteric proteins: Kinesins and Acetylcholine Receptors

To quote famous physicist and Nobel laureate, Dr. Richard Feynman, “…everything that living things do can be understood in terms of the jigglings and wigglings of atoms.” It is these jigglings and wigglings of atoms that form the focus of my dissertation, which studies the structural dynamics of two different allosteric proteins through computational simulations. Protein allostery is a field that has been investigated widely. But the structural details of how signals initiating at one site transmit through the network of residues in different proteins and result in the alteration of their functional states, still remains largely unresolved. Here, we independently study the kinesin motor protein and the neuromuscular acetylcholine receptor (nAChR) – both of which play crucial roles in cellular signaling. Kinesins are intracellular porters, carrying organelles, molecules and other cargo within the cell, while nAChRs are transmembrane receptors that aid in intercellular communication at nerve-to-muscle synapses. These two protein families are structurally and functionally very different, but both are allosteric in nature, with interesting protein dynamics that efficiently convert chemical energy to mechanical motions in order to perform their cellular functions. The total timescale of an entire allosteric transition is currently too long for complete all-atom molecular dynamics simulations. Thus, in this dissertation, for both the projects, we begin at different equilibrium states of the proteins and carry out comparative analyses of conformation and dynamics at those states, which aids in elucidating the structural and functional correlates for these systems. For the kinesin-microtubule (KIN-MT) system, we have built atomistic structure models for the key nucleotide-binding states of the kinesin-MT complex from lower resolution cryo-EM maps, by suitably modifying the MD potential with the EM map force. We have also studied ligand-protein (ADP/ATP-kinesin) interactions and predicted the sequence of structural changes in kinesin-MT complex during its conformational transitions between important biochemical states and pinpointed key contributing residues. Simultaneously, we have also characterized the transmitter binding sites of neuromuscular acetylcholine receptors and analyzed the energy asymmetries between the fetal and adult endplate receptors. Through large-scale simulations of the fetal and adult binding sites, we have come across compelling evidence of the structural causes that explain these asymmetries and were successful in identifying the minimum construct that is both necessary and sufficient to exchange the function between adult and fetal binding sites in AChRs. Our in silico models and predictions act as important tools to further guide mutational and functional experiments

Decrypting the Structural, Dynamic, and Energetic Basis of a Monomeric Kinesin Interacting with a Tubulin Dimer in Three ATPase States by All-Atom Molecular Dynamics Simulation

We have employed molecular dynamics (MD) simulation to investigate, with atomic details, the structural dynamics and energetics of three major ATPase states (ADP, APO, and ATP state) of a human kinesin-1 monomer in complex with a tubulin dimer. Starting from a recently solved crystal structure of ATP-like kinesin–tubulin complex by the Knossow lab, we have used flexible fitting of cryo-electron-microscopy maps to construct new structural models of the kinesin–tubulin complex in APO and ATP state, and then conducted extensive MD simulations (total 400 ns for each state), followed by flexibility analysis, principal component analysis, hydrogen bond analysis, and binding free energy analysis. Our modeling and simulation have revealed key nucleotide-dependent changes in the structure and flexibility of the nucleotide-binding pocket (featuring a highly flexible and open switch I in APO state) and the tubulin-binding site, and allosterically coupled motions driving the APO to ATP transition. In addition, our binding free energy analysis has identified a set of key residues involved in kinesin–tubulin binding. On the basis of our simulation, we have attempted to address several outstanding issues in kinesin study, including the possible roles of β-sheet twist and neck linker docking in regulating nucleotide release and binding, the structural mechanism of ADP release, and possible extension and shortening of α4 helix during the ATPase cycle. This study has provided a comprehensive structural and dynamic picture of kinesin’s major ATPase states, and offered promising targets for future mutational and functional studies to investigate the molecular mechanism of kinesin motors