Measurements of Protein-Protein Interactions by Size Exclusion Chromatography

A method is presented for determining second virial coefficients B_2 of protein solutions from retention time measurements in size exclusion chromatography (SEC). We determine B_2 by analyzing the concentration dependance of the chromatographic partition coefficient. We show the ability of this method to track the evolution of B_2 from positive to negative values in lysozyme and bovine serum albumin solutions. Our SEC results agree quantitatively with data obtained by light scattering.Comment: 18 pages including 1 table and 5 figure

Mathematical formulation to predict the harmonics of the superconducting Large Hadron Collider magnets. II. Dynamic field changes and scaling laws

A superconducting particle accelerator like the LHC (Large Hadron Collider) at CERN, can only be controlled well if the effects of the magnetic field multipoles on the beam are compensated. The demands on a control system solely based on beam feedback may be too high for the requirements to be reached at the specified bandwidth and accuracy. Therefore, we designed a suitable field description for the LHC (FIDEL) as part of the machine control baseline to act as a feed-forward magnetic field prediction system. FIDEL consists of a physical and empirical parametric field model based on magnetic measurements at warm and in cryogenic conditions. The performance of FIDEL is particularly critical at injection when the field decays, and in the initial part of the acceleration when the field snaps back. These dynamic components are both current and time dependent and are not reproducible from cycle to cycle since they also depend on the magnet powering history. In this paper a qualitative and quantitative description of the dynamic field behavior substantiated by a set of scaling laws is presented.peer-reviewe

Self-interaction chromatography as a tool for optimizing conditions for membrane protein crystallization

The second virial coefficient, or B value, is a measurement of how well a protein interacts with itself in solution. These interactions can lead to protein crystallization or precipitation, depending on their strength, with a narrow range of B values (the `crystallization slot') being known to promote crystallization. A convenient method of determining the B value is by self-interaction chromatography. This paper describes how the light-harvesting complex 1-reaction centre core complex from Allochromatium vinosum yielded single straight-edged crystals after iterative cycles of self-interaction chromatography and crystallization. This process allowed the rapid screening of small molecules and detergents as crystallization additives. Here, a description is given of how self-interaction chromatography has been utilized to improve the crystallization conditions of a membrane protein

Development and demonstration of next generation technology for Nb_3Sn accelerator magnets with lower cost, improved performance uniformity, and higher operating point in the 12-14 T range

The scope of the proposal outlined in this white paper is the development and demonstration of the technology needed for next generation of Nb_3Sn accelerator magnets in the 12-14 T range. The main goal is to cut magnet cold-mass cost by a factor 2 or higher with respect to the Nb_3Sn magnets produced by the US Accelerator Upgrade Project (AUP) for the High-Luminosity Large Hadron Collider (HL-LHC). This goal will be achieved by significant reduction of labor hours, higher operating point, and improved performance uniformity. A key factor will be automation that will be achieved through industry involvement and benefitting from the experience gained in US national laboratories through the production of the AUP magnets. This partnership will enable the development of a technology that will be easily transferable to industry for mid- and large-scale production of Nb_3Sn accelerator magnets in the 12-14 T range. This step is essential to enable next generation of colliders such as the FNAL-proposed Muon Collider, FCC and other HEP hadron colliders. This is a Directed R&D where direction is given by the field range and industry involvement for high-automation and industry-ready technology. The plan includes ten milestones, to be achieved in 6-8 years at the cost of 5-7 $M/year.Comment: White Paper for Snowmass 2022, 8 pages, 2 tables, 1 figur

Prognostic factors for anastomotic insufficiency in elective colorectal surgery

Introduction: Anastomotic insufficiency is a severe, potentially fatal complication of colorectal surgery. Its frequency, according to different authors, reaches up to 20%. It is related to two main types of risk factors: associated with the patient and associated with the therapeutic approach.Aim: The aim of the study is to determine prognostic factors for anastomotic insufficiency. The collected data from patients operated on for a period of 5 years (2013-2017) in the Second Surgery Clinic, Alexandrovska University Hospital, Sofia, were analyzed.Materials and Methods: A total of 158 patients undergoing elective colorectal surgery have been retrospectively included. These on emergency, non-proven malignancies and with preoperative haemotransfusion were excluded from the study. All patients were evaluated by age, gender, BMI, ASA score, Charlson Comorbidity Score, localization, TNM stage and histological type. The surgical approach and the method of resection were determined. The postoperative period and complications were classified according to the Clavien-Dindo scale. The number of leukocytes, platelets, RDW, CRP and albumin were examined preoperatively, and on the day 1 and day 4, in the early postoperative period.Results: The average age of the patients was 67 (29-87). Of these, 100 (63.3%) were men, and 58 (36.7%) are women. The mean BMI was 27.1 (23-33). A total of  78.9% of the operated patients weree in TNM stage II and III. Histologically, 77.8% were moderately differentiated adenocarcinomas. The mean Charlson Comorbidity Score for the sample was 7.1 (range: 2-13), and the ASA score was 3 (2-4). The rectum was the most common localization - 40.1%, followed by right colon 22.8%, and the sigmoid colon 20.9%. Over the review period, most resections were conventional, with only 15.2% laparoscopic approach. The operations performed were right hemicolectomy - 36 (22.8%), left hemicolectomy -15 (9.5%), segmental resection - 38 (24.1%), total colectomy - 4 (2.5%) resection of the rectum - 44 (27.9%), and other - 21 (13.3%). In 12 (7.6 %) of the patients insufficiency was reported between day 2 and day 3, postoperatively. Five of them were treated conservatively and the other six were reoperated. Seven of the insufficiencies were after anterior resection of the rectum, 2 were after left hemicolectomy, 1 after resection of the sigmoid colon, one was after right hemicolectomy, which had been treated conservatively. The mean postoperative period of patients with insufficiency was 22 days (range: 9-45). For patients without complications, the postoperative period was 9.4 days (range: 4-21) and there was a strict statistical difference (P <0.05). All patients experienced an increase in leukocyte counts postoperatively, albumin drop, increased CRP and ESR. The mean platelet counts depended on the presence of insuffiency.Conclusion: The anterior resection, which is associated with technically more difficult anastomosis and neoadjuvant radiotherapy is a potential risk factor for anastomotic insufficiency. The use of blood parameters in the postoperative period allows early diagnosis of the complication and possible change of the therapeutic strategy

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Spatial Extent of Charge Repulsion Regulates Assembly Pathways for Lysozyme Amyloid Fibrils

Formation of large protein fibrils with a characteristic cross β-sheet architecture is the key indicator for a wide variety of systemic and neurodegenerative amyloid diseases. Recent experiments have strongly implicated oligomeric intermediates, transiently formed during fibril assembly, as critical contributors to cellular toxicity in amyloid diseases. At the same time, amyloid fibril assembly can proceed along different assembly pathways that might or might not involve such oligomeric intermediates. Elucidating the mechanisms that determine whether fibril formation proceeds along non-oligomeric or oligomeric pathways, therefore, is important not just for understanding amyloid fibril assembly at the molecular level but also for developing new targets for intervening with fibril formation. We have investigated fibril formation by hen egg white lysozyme, an enzyme for which human variants underlie non-neuropathic amyloidosis. Using a combination of static and dynamic light scattering, atomic force microscopy and circular dichroism, we find that amyloidogenic lysozyme monomers switch between three different assembly pathways: from monomeric to oligomeric fibril assembly and, eventually, disordered precipitation as the ionic strength of the solution increases. Fibril assembly only occurred under conditions of net repulsion among the amyloidogenic monomers while net attraction caused precipitation. The transition from monomeric to oligomeric fibril assembly, in turn, occurred as salt-mediated charge screening reduced repulsion among individual charged residues on the same monomer. We suggest a model of amyloid fibril formation in which repulsive charge interactions are a prerequisite for ordered fibril assembly. Furthermore, the spatial extent of non-specific charge screening selects between monomeric and oligomeric assembly pathways by affecting which subset of denatured states can form suitable intermolecular bonds and by altering the energetic and entropic requirements for the initial intermediates emerging along the monomeric vs. oligomeric assembly path

Measurement of the Ratio of b Quark Production Cross Sections in Antiproton-Proton Collisions at 630 GeV and 1800 GeV

We report a measurement of the ratio of the bottom quark production cross section in antiproton-proton collisions at 630 GeV to 1800 GeV using bottom quarks with transverse momenta greater than 10.75 GeV identified through their semileptonic decays and long lifetimes. The measured ratio sigma(630)/sigma(1800) = 0.171 +/- .024 +/- .012 is in good agreement with next-to-leading order (NLO) quantum chromodynamics (QCD)

A Model for Fuzzy Logic Assessment of Real Estate Investment Risks

Assessing the real estate investment risks is a major issue for the responsible management and the sustainable regional development. The paper proposes a fuzzy logic model for complex estimation of the real estate investment risks, based on the available information sources and the expert knowledge. The fuzzy logic model is designed as a hierarchical system that includes several variables. This model is intended to be implemented as a Web service in a cloud computing environment as a next natural step for increasing the span and efficiency of real estate manager activitie