structural insights into n terminal to c terminal interactions and implications for thermostability of a β α 8 triosephosphate isomerase barrel enzyme

Although several factors have been suggested to contribute to thermostability, the stabilization strategies used by proteins are still enigmatic. Studies on a recombinant xylanase from Bacilllus sp. NG-27 (RBSX), which has the ubiquitous (beta/alpha)(8)-triosephosphate isomerase barrel fold, showed that just a single mutation, V1L, although not located in any secondary structural element, markedly enhanced the stability from 70 degrees C to 75 degrees C without loss of catalytic activity. Conversely, the V1A mutation at the same position decreased the stability of the enzyme from 70 degrees C to 68 degrees C. To gain structural insights into how a single extreme N-terminus mutation can markedly influence the thermostability of the enzyme, we determined the crystal structure of RBSX and the two mutants. On the basis of computational analysis of their crystal structures, including residue interaction networks, we established a link between N-terminal to C-terminal contacts and RBSX thermostability. Our study reveals that augmenting N-terminal to C-terminal noncovalent interactions is associated with enhancement of the stability of the enzyme. In addition, we discuss several lines of evidence supporting a connection between N-terminal to C-terminal noncovalent interactions and protein stability in different proteins. We propose that the strategy of mutations at the termini could be exploited with a view to modulate stability without compromising enzymatic activity, or in general, protein function in diverse folds where N and C termini are in close proximity. Database The coordinates of RBSX, V1A and V1L have been deposited in the PDB database under the accession numbers 4QCE, 4QCF, and 4QDM, respectivel

All Optical Switch Using Indium-Tin-Oxide in a Diffracting Grating

A switch is defined as a component of electrical circuit that interrupts and diverts electrical current in a circuit, in order to regulate flow of power through a conductor. There are primarily two types of switches: mechanical and electrical. Mechanical switches require physical or manual contact for operation. Electrical switches function based on semiconductor properties of conducting current when doped with impurities. Transistors are essential and one of the most prevalent semiconductor switches in modern computing. A network composed of millions of transistors that work together to enable our computers to function effectively. Transistors only function at a given maximum speed, which is limited by the drift velocity of charge carriers between the junctions of a transistor. Now that there is a higher need for faster computing than ever before, engineers are about to reach a roadblock where we would not be able to pack more and transistors into the limited space available. There is a need for a different type of switch, one that is not limited by the speed of a charge carrier. This thesis proposes an all-optical switch, which operates by lasers instead of electrical signals, as an alternative to electrical switches. The primary purpose of an all-optical switch is logical switching similar to an electronic transistor. The all-optical switch proposed only works with lasers without relying on external stimulation for any operational step to achieve switching operation. Coupled-mode equations for high-contrast-gratings (HCGs) were solved in MATLAB to determine the grating dimensions that exhibit fano-resonance. The resulting gratings were modeled using the simulation software Lumerical FDTD in conjunction with non-linear optical medium Indium-tin-oxide (ITO), exploiting ITO’s property to undergo change in refractive index upon irradiation by light at epsilon-near-zero frequencies, to achieve the switching operation in the modeled nanostructure. It is shown that the proposed nanostructure can attenuate the incoming control signal (probe beam) and shifts its transmission curve by a band gap of ~6nm, on application of the excitation beam (pump beam) to a thin ITO layer incorporated into the structure. A detector calibrated to read the control signal will interpret this change in transmission as a logical zero. In conclusion, it is concluded that the nanostructure can act as an optical switch and perform logical switching in several hundered femtoseconds that puts the operational frequency of the conceptual nanostructure device in terahertz range

Atypically Large Arteriovenous Malformation: A Surgical Challenge

Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. The majority of AVMs involve the extremities, head and neck, and lungs. We report a case of a 20-year-old female with a large, high flow AVM at unusual location. The perforators of this malformation were originating directly from lumbar arteries, revealed by computed tomography angiography. In the absence of facilities of embolizing feeder vessels, such large AVM gave us a great surgical challenge in terms of dissection, raising the mass, ligating perforators, and avoiding skin loss

Emerging role of N- and C-terminal interactions in stabilizing (β/α)8 fold with special emphasis on Family 10 xylanases

Xylanases belong to an important class of industrial enzymes. Various xylanases have been purified and characterized from a plethora of organisms including bacteria, marine algae, plants, protozoans, insects, snails and crustaceans. Depending on the source, the enzymatic activity of xylanases varies considerably under various physico-chemical conditions such as temperature, pH, high salt and in the presence of proteases. Family 10 or glycosyl hydrolase 10 (GH10) xylanases are one of the well characterized and thoroughly studied classes of industrial enzymes. The TIM-barrel fold structure which is ubiquitous in nature is one of the characteristics of family 10 xylanases. Family 10 xylanases have been used as a “model system” due to their TIM-barrel fold to dissect and understand protein stability under various conditions. A better understanding of structure-stability-function relationships of family 10 xylanases allows one to apply these governing molecular rules to engineer other TIM-barrel fold proteins to improve their stability and retain function(s) under adverse conditions. In this review, we discuss the implications of N-and C-terminal interactions, observed in family 10 xylanases on protein stability under extreme conditions. The role of metal binding and aromatic clusters in protein stability is also discussed. Studying and understanding family 10 xylanase structure and function, can contribute to our protein engineering knowledge

Searches for Higgs boson production through decays of heavy resonances

The discovery of the Higgs boson has led to new possible signatures for heavy resonance searches at the LHC. Since then, search channels including at least one Higgs boson plus another particle have formed an important part of the program of new physics searches. In this report, the status of these searches by the CMS Collaboration is reviewed. Searches are discussed for resonances decaying to two Higgs bosons, a Higgs and a vector boson, or a Higgs boson and another new resonance, with proton-proton collision data collected at $\sqrt{s}=$ 13 TeV in the years 2016-2018. A combination of the results of these searches is presented together with constraints on different beyond-the-standard model scenarios, including scenarios with extended Higgs sectors, heavy vector bosons and extra dimensions. Studies are shown for the first time by CMS on the validity of the narrow-width approximation in searches for the resonant production of a pair of Higgs bosons. The potential for a discovery at the High Luminosity LHC is also discussed.The discovery of the Higgs boson has led to new possible signatures for heavy resonance searches at the LHC. Since then, search channels including at least one Higgs boson plus another particle have formed an important part of the program of new physics searches. In this report, the status of these searches by the CMS Collaboration is reviewed. Searches are discussed for resonances decaying to two Higgs bosons, a Higgs and a vector boson, or a Higgs boson and another new resonance, with proton-proton collision data collected at $\sqrt{s}$ = 13 TeV in the years 2016-2018. A combination of the results of these searches is presented together with constraints on different beyond-the-standard model scenarios, including scenarios with extended Higgs sectors, heavy vector bosons and extra dimensions. Studies are shown for the first time by CMS on the validity of the narrow-width approximation in searches for the resonant production of a pair of Higgs bosons. The potential for a discovery at the High Luminosity LHC is also discussed

Search for the Z boson decay to ττμμ\tau\tau\mu\mu in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe first search for the Z boson decay to $\tau\tau\mu\mu$ at the CERN LHC is presented, based on data collected by the CMS experiment at the LHC in proton-proton collisions at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb$^{-1}$. The data are compatible with the predicted background. For the first time, an upper limit at the 95% confidence level of 6.9 times the standard model expectation is placed on the ratio of the Z $\to$ $\tau\tau\mu\mu$ to Z $\to$ 4$\mu$ branching fractions. Limits are also placed on the six flavor-conserving four-lepton effective-field-theory operators involving two muons and two tau leptons, for the first time testing all such operators

Dark sector searches with the CMS experiment

International audienceAstrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report

Search for soft unclustered energy patterns in proton-proton collisions at 13 TeV

International audienceThe first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138 fb$^{-1}$ of proton-proton collision data at $\sqrt{s}$ = 13 TeV collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by Hidden Valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics. With no observed excess of events over the standard model expectation, limits are set on the cross section for production via gluon fusion of a scalar mediator with SUEP-like decays

Measurement of inclusive and differential cross sections for W+^+W−^- production in proton-proton collisions at s\sqrt{s} = 13.6 TeV

International audienceMeasurements at $\sqrt{s}$ = 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb$^{-1}$. Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavour and charge of the leptons, the number of jets, and number of jets originating from b quarks. An inclusive W$^+$W$^-$ production cross section of 125.7 $\pm$ 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For first time in proton-proton collisions, WW events with at least two reconstructed jets are studied and compared with recent theoretical predictions