CROSSTALK BETWEEN THE ER STRESS PATHWAY AND OSMOTIC STRESS IN S. CEREVISIAE

In Saccharomyces cerevisiae, the general stress response (GSR) protects cells from diverse stress conditions such as osmotic stress and heat stress, while the Unfolded Protein Response (UPR) is a protein folding stress signalling pathway which maintains homeostasis of the endoplasmic reticulum (ER). A mechanism of how and if at all the UPR integrates with other pathways is largely unknown. The focus of this thesis was to determine whether essential components of the UPR like the bZIP transcription factor Hac1p and the Rpd3p-Sin3p histone deacetylase integrated within osmotic stress and to identify a possible mechanism of such an integration event. Data from this thesis demonstrate that UPR components protect cells from hyperosmotic stress. Hac1p is a direct positive regulator of GSR genes. Rpd3p and Hac1p belong to the same pathway in activating GSR genes. Data also suggest that Hac1p does not contribute to the increase in nucleosomal histone acetylation levels after osmotic stress. The Gcn5 histone acetyltransferase contributes to the increase in histone acetylation observed after osmotic stress. The Rpd3p represses GSR genes in unstressed cells but also contributes to the activation of GSR genes after hyperosmotic shock. The Rpd3 large complex and not the small complex is involved regulating GSR gene expression. Subsequent investigation demonstrates that a possible mechanism by which the UPR contributes to the GSR gene activation is by the RNA polymerase II clearance at the GSR gene promoters

Pile-Up Mitigation using Attention

Particle production from secondary proton-proton collisions, commonly referred to as pile-up, impair the sensitivity of both new physics searches and precision measurements at LHC experiments. We propose a novel algorithm, PUMA, for identifying pile-up objects with the help of deep neural networks based on sparse transformers. These attention mechanisms were developed for natural language processing but have become popular in other applications. In a realistic detector simulation, our method outperforms classical benchmark algorithms for pile-up mitigation in key observables. It provides a perspective for mitigating the effects of pile-up in the high luminosity era of the LHC, where up to 200 proton-proton collisions are expected to occur simultaneously

Porcine Islet Cell Xenotransplantation

This article reviews the rationale, sources and preparation of pig islets for xenotransplantation. Pancreatic islet cell transplantation is an attractive alternative and an effective treatment option for type 1 diabetes, however, donor pancreas shortages prevent islet transplantation from being a widespread solution as the supply cannot possibly equal the demand. Porcine islet xenotransplantation has the potential to address these shortages, and recent preclinical and clinical trials show promising scientific support. Pig islets provide a readily available source for islet transplantation, with the recent trials in non-human primates (NHPs) demonstrating their potential to reverse diabetes. The risk of zoonosis can be reduced by designated pathogen-free breeding of the donor pigs, but porcine endogenous retroviruses (PERVs) which are integrated into the genome of all pigs, are especially difficult to eliminate. However, clinical trials have demonstrated an absence of PERV transmission with a significant reduction in the number of severe hypoglycemic episodes and up to 30% reduction in exogenous insulin doses. A number of methods are currently being tested to overcome the xenograft immune rejection. Some of these methods include the production of various transgenic pigs to better xenotransplantation efficiency and the encapsulation of islets to isolate them from the host immune system. Furthermore, ongoing research is also shedding light on factors such as the age and breed of the donor pig to determine the optimal islet quantity and function

Brute-Force Mapmaking with Compact Interferometers: A MITEoR Northern Sky Map from 128 MHz to 175 MHz

We present a new method for interferometric imaging that is ideal for the large fields of view and compact arrays common in 21 cm cosmology. We first demonstrate the method with the simulations for two very different low-frequency interferometers, the Murchison Widefield Array and the MIT Epoch of Reionization (MITEoR) experiment. We then apply the method to the MITEoR data set collected in 2013 July to obtain the first northern sky map from 128 to 175 MHz at ∼2° resolution and find an overall spectral index of −2.73 ± 0.11. The success of this imaging method bodes well for upcoming compact redundant low-frequency arrays such as Hydrogen Epoch of Reionization Array. Both the MITEoR interferometric data and the 150 MHz sky map are available at http://space.mit.edu/home/tegmark/omniscope.html.National Science Foundation (U.S.) (AST-0908848)National Science Foundation (U.S.) (AST-1105835)National Science Foundation (U.S.) (AST-1440343

Search for Pair-Produced Resonances Decaying to Quark Pairs in Proton-Proton Collisions at √s = 13 TeV

A general search for the pair production of resonances, each decaying to two quarks, is reported. The search is conducted separately for heavier resonances (masses above 400 GeV), where each of the four final-state quarks generates a hadronic jet resulting in a four-jet signature, and for lighter resonances (masses between 80 and 400 GeV), where the pair of quarks from each resonance is collimated and reconstructed as a single jet resulting in a two-jet signature. In addition, a b-tagged selection is applied to target resonances with a bottom quark in the final state. The analysis uses data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 35.9  fb⁻¹, from proton-proton collisions at a center-of-mass energy of 13 TeV. The mass spectra are analyzed for the presence of new resonances, and are found to be consistent with standard model expectations. The results are interpreted in the framework of R-parity-violating supersymmetry assuming the pair production of scalar top quarks decaying via the hadronic coupling λ′′312 or λ′′323 and upper limits on the cross section as a function of the top squark mass are set. These results probe a wider range of masses than previously explored at the LHC, and extend the top squark mass limits in the ˜t→qq′ scenario

Search for electroweak production of charginos and neutralinos in multilepton final states in proton-proton collisions at √s = 13 TeV

Results are presented from a search for the direct electroweak production of charginos and neutralinos in signatures with either two or more leptons (electrons or muons) of the same electric charge, or with three or more leptons, which can include up to two hadronically decaying tau leptons. The results are based on a sample of proton-proton collision data collected at s√=13 TeV, recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb⁻¹. The observed event yields are consistent with the expectations based on the standard model. The results are interpreted in simplified models of supersymmetry describing various scenarios for the production and decay of charginos and neutralinos. Depending on the model parameters chosen, mass values between 180 GeV and 1150 GeV are excluded at 95% CL. These results significantly extend the parameter space probed for these particles in searches at the LHC. In addition, results are presented in a form suitable for alternative theoretical interpretations