Additional Contacts Research Articles

Deep Brain Stimulation: When to Test Directional?

Directional deep brain stimulation (DBS) allows for steering of the stimulation field, but extensive and time-consuming testing of all segmented contacts is necessary to identify the possible benefit of steering. It is therefore important to determine under which circumstances directional current steering is advantageous. Fifty two Parkinson's disease patients implanted in the STN with a directional DBS system underwent a standardized monopolar programming session 5 to 9 months after implantation. Individual contacts were tested for a potential advantage of directional stimulation. Results were used to build a prediction model for the selection of ring levels that would benefit from directional stimulation. On average, there was no significant difference in therapeutic window between ring-level contact and best directional contact. However, according to our standardized protocol, 35% of the contacts and 66% of patients had a larger therapeutic window under directional stimulation compared to ring-mode. The segmented contacts warranting directional current steering could be predicted with a sensitivity of 79% and a specificity of 57%. To reduce time required for DBS programming, we recommend additional directional contact testing initially only on ring-level contacts with a therapeutic window of less than 2.0 mA.

Recognition of γ-subunit by β-subunit. Stabilization of the GTP-bound state of translation initiation factor 2 in archaea and eukaryotes

Eukaryotic and archaeal translation initiation factor 2 (e/aIF2) functions as a heterotrimeric complex. It consists of three subunits (α,β, γ). The α- and β-subunits are linked to the γ-subunit by hydrogen bonds and van der Waals interactions, but do not contact each other. Although the main functions of the factor are performed by the γ-subunit reliable formation of αγ- and βγ-complexes is necessary for its proper functioning. In this work, we made mutations in the recognition part of the βγ interface and showed that both in eukaryotes and archaea, the hydrophobic effect plays a decisive role in the recognition of subunits. The shape and properties of the hollow on the surface of the γ-subunit facilitates the transition of the disordered recognition part of the β-subunit into the α-helix containing approximately the same number of residues in archaea and eukaryotes. In addition, based on the newly obtained data, it was concluded that in archaea and eukaryotes, the transition of the γ-subunit to the active state leads to additional contact between its switch 1 and the C-terminal part of the β-subunit, which stabilizes the helical conformation of the switch.

Structural and Spectroscopic Studies of Steric and Electronic Substituent Effects in a Series of Magnesium Aminodiboranates Mg[(BH3)2NMeR]2.

The magnesium N,N-dimethylaminodiboranate compound Mg[(BH3)2NMe2]2, the most volatile compound of magnesium known, serves as an excellent chemical vapor deposition (CVD) precursor for the growth of thin films such as the dielectric material MgO. To explore how the thermal stability and physical properties of magnesium aminodiboranates depend on the steric and electronic properties of the nitrogen-bound substituents, we have made a series of analogues of Mg[(BH3)2NMe2]2, in which one of the two methyl substituents on nitrogen is replaced with an ethyl, iso-propyl, or tert-butyl group. In the crystal structure of Mg[(BH3)2NMe(t-Bu)]2, the magnesium center is coordinated to two chelating (BH3)2NMe(t-Bu) ligands, each of which binds in a κ2,κ2 fashion so that the magnesium center forms eight Mg-H contacts. Unlike Mg[(BH3)2NMe2]2, however, which has a linear N···Mg···N angle and is an isolated molecule in the solid state, the N···Mg···N angle in Mg[(BH3)2NMe(t-Bu)]2 is distinctly nonlinear (149.9°) because hydrogen atoms of BH3 groups of nearby molecules form two additional Mg-H contacts with the magnesium center. When the complexes are heated in toluene solution, the (BH3)2NMeR- groups reversibly undergo B-N bond cleavage (with concomitant migration of a hydrogen atom) to release the aminoborane BH2═NMeR and form magnesium borohydride, Mg(BH4)2. For the methyl, ethyl, and iso-propyl derivatives, the equilibrium strongly favors Mg[(BH3)2NMeR]2. In contrast, for the tert-butyl derivative, the equilibrium strongly favors BH2═NMe(t-Bu) and Mg(BH4)2. The results suggest that more strongly electron-donating groups slightly strengthen the B-N bonds and disfavor B-N bond cleavage, provided that the groups are not too large. In contrast, sterically bulky ligands disfavor B-N bond reformation, thus promoting the dissociative equilibrium that involves B-N bond cleavage. Interestingly, the rates at which the complexes approach equilibrium depend only weakly on the nature of the R group, at least within the series studied. These findings are relevant to the potential use of magnesium aminodiboranates as CVD precursors to the superconducting phase MgB2.

Effect of contact force on pulsed field ablation lesions in porcine cardiac tissue.

Contact force has been used to titrate lesion formation for radiofrequency ablation. Pulsed field ablation (PFA) is a field-based ablation technology for which limited evidence on the impact of contact force on lesion size is available. Porcine hearts (n = 6) were perfused using a modified Langendorff set-up. A prototype focal PFA catheter attached to a force gauge was held perpendicular to the epicardium and lowered until contact was made. Contact force was recorded during each PFA delivery. Matured lesions were cross-sectioned, stained, and the lesion dimensions measured. A total of 82 lesions were evaluated with contact forces between 1.3and 48.6 g. Mean lesion depth was 4.8 ± 0.9 mm (standard deviation), mean lesion width was 9.1 ± 1.3 mm, and mean lesion volume was 217.0 ± 96.6 mm3 . Linear regression curves showed an increase of only 0.01 mm in depth (depth = 0.01 × contact force + 4.41, R2 = 0.05), 0.03 mm in width (width = 0.03 × contact force + 8.26, R2 = 0.13) for each additional gramof contact force, and 2.20 mm3 in volume (volume = 2.20 × contact force + 162, R2 = 0.10). Increasing contact force using a bipolar, biphasic focal PFA system has minimal effects on acute lesion dimensions in an isolated porcine heart model and achieving tissue contact is more important than the force with which that contact is made.

Influence of the structure of the coat protein N-terminal segment in potato virus X and alternanthera mosaic virus on the structure and physico-chemical properties of virions

The amino acid sequences of coat proteins (CPs) of potexviruses such as potato virus X (PVX) and alternanthera mosaic virus (AltMV) share about 40% sequence identity. However, the N-terminal CP domains of these virions differ both in length (the N-terminal CP domain of PVX is longer by 28 residues, ∆N = 28), and in amino acid sequence. In this work, we determined the effect of the N-terminal CP domain on the structure and physicochemical properties of the entire PVX and AltMV virions. It was shown that the melting point of PVX samples is 10-12°C higher than that of AltMV preparations; the circular dichroism spectra of these viruses also differ significantly. Spatial alignment of the existing high-resolution potexvirus CP structures showed that the RMSD value between Cα-atoms was the largest for the N-terminal domains of the two compared models. From computer simulations the ∆N-terminal CP domain of PVX is completely disordered. According to synchrotron small-angle X-ray scattering (SAXS) data, the structure of CP of PVX and AltMV virions differs, in particular, CP PVX has a larger size of crystallinity regions and, therefore, is more ordered. Using SAXS, virion diameters and helix parameters in solution are calculated. The influence of the conformation and localization of the N-terminal domain of PVX CP relative to the surface of the virion on its structure was revealed. Presumably, the increased thermal stability of PVX virions compared to AltMV is provided by the elongated N-terminal domains (ΔN = 28), which ensures additional contact between the adjacent CP subunits in the PVX virion.

Limiting the Spread of Multidrug-Resistant Bacteria in Low-to-Middle-Income Countries: One Size Does Not Fit All.

The spread of multidrug-resistant organisms (MDRO) is associated with additional costs as well as higher morbidity and mortality rates. Risk factors related to the spread of MDRO can be classified into four categories: bacterial, host-related, organizational, and epidemiological. Faced with the severity of the MDRO predicament and its individual and collective consequences, many scientific societies have developed recommendations to help healthcare teams control the spread of MDROs. These international recommendations include a series of control measures based on surveillance cultures and the application of barrier measures, ranging from patients' being isolated in single rooms, to the reinforcement of hand hygiene and implementation of additional contact precautions, to the cohorting of colonized patients in a dedicated unit with or without a dedicated staff. In addition, most policies include the application of an antimicrobial stewardship program. Applying international policies to control the spread of MDROs presents several challenges, particularly in low-to-middle-income countries (LMICs). Through a review of the literature, this work evaluates the real risks of dissemination linked to MDROs and proposes an alternative policy that caters to the means of LMICs. Indeed, sufficient evidence exists to support the theory that high compliance with hand hygiene and antimicrobial stewardship reduces the risk of MDRO transmission. LMICs would therefore be better off adopting such low-cost policies without necessarily having to implement costly isolation protocols or impose additional contact precautions.

Inside-Out Design of Zinc-Binding Proteins with Non-Native Backbones.

The de novo design of functional proteins requires specification of tertiary structure and incorporation of molecular binding sites. Here, we develop an inside-out design strategy in the molecular modeling program Rosetta that begins with amino acid side chains from one or two α-helices making well-defined contacts with a ligand. A full-sized protein is then built around the ligand by adding additional helices that promote the formation of a protein core and allow additional contacts with the ligand. The protocol was tested by designing 12 zinc-binding proteins, each with 4-5 helices. Four of the designs were folded and bound to zinc with equilibrium dissociation constants varying between 95 nM and 1.1 μM. The design with the tightest affinity for zinc, N12, adopts a unique conformation in the folded state as assessed with nuclear magnetic resonance (NMR) and the design model closely matches (backbone root-mean-square deviation (RMSD) < 1 Å) an AlphaFold model of the sequence. Retrospective analysis with AlphaFold suggests that the sequences of many of the failed designs did not encode the desired tertiary packing.

X-ray Molecular Structures of 23 N1-4-Nitrophenyl, 2,4-Dinitrophenyl, and 2,4,6-Trinitrophenyl-2-pyrazolines

Herein, we present a complete crystallographic study of three series of N1-aryl substituted-2-pyrazolines, the aryl group being 4-nitrophenyl (series 1), 2,4-dinitrophenyl (series 2), and 2,4,6-trinitrophenyl (series 3). The structural features, bond distances and angles as well as torsions for each single compound will be described and comparatively discussed with data for related heterocycles found in the Cambridge Structural Database (2020.2.0). A deeper look at the data has been achieved to know the influence of the substituents on the molecular structures. In the crystals of compounds with stereogenic centers at positions 4 and 5, the presence of both enantiomers has been encountered in 12 cases out of 14 that include a literature result. Finally, molecular packings in all series have been analyzed reaching the conclusion that they follow several patterns depending on the existence or not, and the type of intermolecular interactions. A general pattern has been observed which implies a certain tendency of the molecules to arrange into chains, whose additional contacts could extend the dimensionality of the network.

Molecular dynamics studies of CED-4/CED-9/EGL-1 ternary complex reveal CED-4 release mechanism in the linear apoptotic pathway of Caenorhabditis elegans.

Many steps in programmed cell death are evolutionarily conserved across different species. The Caenorhabditis elegans proteins CED-9, CED-4 and EGL-1 involved in apoptosis are respectively homologous to anti-apoptotic Bcl-2 proteins, Apaf-1 and the "BH3-only" pro-apototic proteins in mammals. In the linear apoptotic pathway of C. elegans, EGL-1 binding to CED-9 leads to the release of CED-4 from CED-9/CED-4 complex. The molecular events leading to this process are not clearly elucidated. While the structures of CED-9 apo, CED-9/EGL-1 and CED-9/CED-4 complexes are known, the CED-9/CED-4/EGL-1 ternary complex structure is not yet determined. In this work, we modeled this ternary complex and performed molecular dynamics simulations of six different systems involving CED-9. CED-9 displays differential dynamics depending upon whether it is bound to CED-4 and/or EGL-1. CED-4 exists as an asymmetric dimer (CED4a and CED4b) in CED-9/CED-4 complex. CED-4a exhibits higher conformational flexibility when simulated without CED-4b. Principal Component Analysis revealed that the direction of CED-4a's winged-helix domain motion differs in the ternary complex. Upon EGL-1 binding, majority of non-covalent interactions involving CARD domain in the CED-4a-CED-9 interface have weakened and only half of the contacts found in the crystal structure between α/β domain of CED4a and CED-9 are found to be stable. Additional stable contacts in the ternary complex and differential dynamics indicate that winged-helix domain may play a key role in CED-4a's dissociation from CED-9. This study has provided a molecular level understanding of potential intermediate states that are likely to occur when CED-4a is released from CED-9.

A deflection study of steel-polypropylene gear pair using finite element analysis

Polymer gears deflect significantly more than metal gears, affecting the kinematics of the gear during the engagement. Even though the applied load is within the material’s elastic limit, the induced deformation causes an extended contact between the gear tooth, resulting in abnormal wear and noise. In this work, a finite element investigation is done on the deflection induced in the driven polypropylene gear by the driver steel gear. It was observed that the gear tooth deflection causes extended contact both before and after engagement. Moreover, a contact was observed on the coast side of the meshing gear tooth. The coast side contact begins before the theoretical start of the meshing cycle, continues through the pitch point, and extends beyond the end of the meshing cycle. The coast side contact was recorded at the driven gear tooth on the path of approach and the driven gear tooth on the path of recess, respectively. The coast side and drive side lines of actions are perpendicular to one another. Because of the additional coast side contact, the roll angle increases by 19.2% and 34.2% in the path of approach and recess regions, respectively. Furthermore, due to the gear tooth’s coast side contact, the meshing gear’s contact stress exceeded the proportional limit.

Effect of the Coat Protein N-Terminal Domain Structure on the Structure and Physicochemical Properties of Virions of Potato Virus X and Alternanthera Mosaic Virus

The amino acid sequences of the coat proteins (CPs) of the potexviruses potato virus X (PVX) and alternanthera mosaic virus (AltMV) share ~40% identity. The N-terminal domains of these proteins differ in the amino acid sequence and the presence of the N-terminal fragment of 28 residues (ΔN peptide) in the PVX CP. Here, we determined the effect of the N-terminal domain on the structure and physicochemical properties of PVX and AltMV virions. The circular dichroism spectra of these viruses differed significantly, and the melting point of PVX virions was 10-12°C higher than that of AltMV virions. Alignment of the existing high-resolution 3D structures of the potexviral CPs showed that the RMSD value between the Cα-atoms was the largest for the N-terminal domains of the two compared models. Based on the computer modeling, the ΔN peptide of the PVX CP is fully disordered. According to the synchrotron small-angle X-ray scattering (SAXS) data, the structure of CPs from the PVX and AltMV virions differ; in particular, the PVX CP has a larger portion of crystalline regions and, therefore, is more ordered. Based on the SAXS data, the diameters of the PVX and AltMV virions and helix parameters in solution were calculated. The influence of the conformation of the PVX CP N-terminal domain and its position relative to the virion surface on the virion structure was investigated. Presumably, an increased thermal stability of PVX virions vs. AltMV is provided by the extended N-terminal domain (ΔN peptide, 28 amino acid residues), which forms additional contacts between the adjacent CP subunits in the PVX virion.

Hydrogen-bonding enables two-dimensional metal/semiconductor tunable contacts approaching the quantum limit and the modified Schottky-Mott limit simultaneously.

Achieving efficient electrical contacts in two-dimensional (2D) semiconductors is increasingly critical with the continuous scaling down of transistors. van der Waals (vdW) contacts with weak Fermi-level pinning are still hindered by the additional contact resistance due to weak interlayer coupling. Here, based on first-principles, we propose to exploit hydrogen-bonding interactions to intrinsically overcome the inherent vdW gap. Various metal/semiconductor heterojunctions with hydroxyl-terminated MXenes as the metal electrode demonstrate clean Ohmic contacts with ultralow contact resistance approaching the quantum limit via strong hydrogen-bonding of O-H⋯X (X = N, O, S, Se, etc.) at the interface. Hydrogen-bonding contacts are further shown to be an advantageous approach to achieve near-perfect N-type contacts for emerging 2D nitride, oxide, halide, and chalcogenide semiconductors that can simultaneously approach the modified Schottky-Mott limit. We finally discuss the general design concepts for hydrogen-bonding contacts, demonstrating their potential to go beyond vdW contacts in achieving ideal electrical contacts in 2D semiconductors.

The Influence of the Factor of Providing Additional Contact Information by the Client on the Outcome of the Transaction in Telemarketing

The subject of the study is the search for the relationship between the provision of additional information by the client and the success of the transaction. The more information the client is willing to provide, the higher his interest in purchasing a product or service and the less likely it is to refuse after a preliminary agreement. Special attention is paid to the most common reasons for refusals, such as the inability to get through to the client, refusal dictated by close people, cases when the client changed his mind without explicitly stating the reason. Based on the methods of mathematical statistics, confirmations of the hypotheses put forward about the absence of a significant influence of the fact of providing additional contact information by the client on the outcome of transactions in general were obtained, but its significant influence in certain classes of refusals was confirmed. The importance of studying the model of making a purchase decision among the client's inner circle is substantiated. The novelty of the research lies in the detailed analysis of particular cases of failure and the mathematical justification of the hypotheses put forward. The main conclusion based on the results of the study is that additional information from the client is an intangible pledge that reinforces the desire to purchase a product or service. Additional information about another person indicates an evasion of responsibility or a hidden refusal. The results confirm the words said by psychologist Boris Mikhailovich Teplov that despite his individuality, a person is under the influence of society and acts in certain social conditions. It is necessary to analyze the client's refusal without interrupting the models of his interaction with other persons influencing the purchase decision.

Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells

The current study investigated the binding variations among the wilt type, Omicron sub-variants BA.2.75 and BA.5, using protein-protein docking, protein structural graphs (P SG), and molecular simulation methods. HADDOCK predicted docking scores and dissociation constant (KD) revealed tighter binding of these sub-variants in contrast to the WT. Further investigation revealed variations in the hub residues, protein sub-networks, and GlobalMetapath in these variants as compared to the WT. A very unusual dynamic for BA.2.75 and BA.5 was observed, and secondary structure transition can also be witnessed in the loops (44–505). The results show that the flexibility of these three loops is increased by the mutations as an allosteric effect and thus enhances the chances of bonding with the nearby residues to connect and form a stable connection. Furthermore, the additional hydrogen bonding contacts steer the robust binding of these variants in contrast to the wild type. The total binding free energy for the wild type was calculated to be –61.38 kcal/mol, while for BA.2.75 and BA.5 variants the T BE was calculated to be –70.42 kcal/mol and 69.78 kcal/mol, respectively. We observed that the binding of BA.2.75 is steered by the electrostatic interactions while the BA.5 additional contacts are due to the vdW (Van der Waal) energy. From these findings, it can be observed the Spike (S) protein is undergoing structural adjustments to bind efficiently to the hACE2 (human angiotensin-converting enzyme 2) receptor and, in turn, increase entry to the host cells. The current study will aid the development of structure-based drugs against these variants. Communicated by Ramaswamy H. Sarma

Discovery of potent 1,1-diarylthiogalactoside glycomimetic inhibitors of Pseudomonas aeruginosa LecA with antibiofilm properties

In this work, β-thiogalactoside mimetics bearing 1,1-diarylmethylene or benzophenone aglycons have been prepared and assayed for their affinity towards LecA, a lectin and virulence factor from Pseudomonas aeruginosa involved in bacterial adhesion and biofilm formation. The hit compound presents higher efficiency than previously described monovalent inhibitors and the crystal structure confirmed the occurrence of additional contacts between the aglycone and the protein surface. The highest affinity (160 nM) was obtained for a divalent ligand containing two galactosides. The monovalent high affinity compound (Kd = 1 μM) obtained through structure-activity relationship (SAR) showed efficient antibiofilm activity with no associated bactericidal activity.

1217. An outbreak of carbapenem-resistant Acinetobacter baumannii in an isolation ward for COVID-19 and successful outbreak control with infection control measures

Abstract Background The superinfection of multidrug-resistant bacteria is an important complication in critically ill COVID-19 patients. An outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) occurred in an isolation ward for COVID-19. We performed an outbreak investigation, and successfully controlled the outbreak with the enhanced environmental cleaning and additional gowning and gloving. Methods This study analyzed all COVID-19 patients with CRAB in any specimen, who admitted to an isolation ward for COVID-19 of a tertiary hospital in South Korea from October to November 2021. Results During the outbreak period, a total of 23 patients with COVID-19 and CRAB were identified (Figure 1). Index case was 85-year old female patient who was referred from a long-term care facility. The mean age of cases was 72.9 and 14 (60.9%) patients were male. In most patients (91.3%), CRAB were identified in sputum culture, two were identified in blood culture at initial, and four patients were identified in sputum and blood culture at the same time. Most of the patients were applying high flow nasal cannula (26.1%) or mechanical ventilation (60.9%)(Table1). As shown in figure2, CRAB outbreak occurred mainly in the wards around the index case, and in particular, environmental culture was carried out in the area marked with a rectangle. CRAB was cultured on the floor, air inlet, air outlet, and window frame of the ward except for wards 3305 and 3319. Phenotypic antimicrobial resistance patterns of CRAB isolates from patients and environment were identical, and additional whole genome sequencing analyses are ongoing to find the clonality of isolates. We applied the infection control measures with the enhanced environmental cleaning using sodium hypochlorite(NaClO) 1000ppm and phenolic compounds more than twice a day, enhanced hand hygiene, and additional gowning and gloving over personal protective equipment (PPE) mandatory for COVID-19 on 29th October. No additional CRAB cases occurred since 2nd November 2021 for two weeks. Figure 1.Daily number of cases with carbapenem-resistant Acinetobacter baumannii during outbreak periodFigure 2.Floor plan of isolation ward with Acinetobacter baumannii outbreak Conclusion Even when PPEs and precautions for COVID-19 are applied to isolation wards for COVID-19, it is helpful for preventing transmission of multidrug-resistant bacteria to apply additional contact precautions and environmental cleaning. Disclosures All Authors: No reported disclosures.

1914. Characteristics of Hospital Onset SARS Cov-2 Infections Before and After the Emergence of The Highly Transmissible Variant B.1.1.529 In a Comprehensive Cancer Center

Abstract Background SARS-CoV-2 B.1.1.529 (Omicron) variant was first identified in November 2021 in South Africa and was notable for its increased transmissibility and rapid spread worldwide. In the United States, this variant led to a surge in COVID-19 cases by December 2021. As a result, we experienced a steep rise in cases among patients and employees at our institution starting December 22nd, 2021. Therefore, we compared the incidence and characteristics of hospital-onset COVID-19 (HO-COVID-19) in our cancer patients prior to and during the surge of the Omicron variant. Methods We identified HO-COVID-19, as per the CDC definition, from our infection control surveillance database, and additional contact tracing information was reviewed to determine the possible sources of HO-COVID-19. Whole-genome sequencing studies were conducted randomly on nasopharyngeal swabs of patients and employees who had COVID-19 during the study period. Results Twenty-six HO-COVID-19 infections were identified from the beginning of the pandemic (February 2020) through February 2022 (Table 1). Only 17 cases occurred over 22 months from the beginning of the pandemic through early December 2021 (Figure 1). These HO-COVID-19 occurred during the 3 COVID-19 surges that were epidemiologically attributed to the variants seen prior to Omicron. Among these 17 patients, 12 (70%) were symptomatic, 9 (53%) had a link to an infected employee, 7 (41%) died during their hospitalization (3 of the deaths were attributable to COVID-19), and 10 (59%) recovered and were discharged. Over 6 weeks (from December 22nd, 2021, through February 1st, 2022), 9 HO-COVID-19 were discovered during the Omicron variant surge (Figure 1). Six (67%) of these patients were symptomatic, 8 (89%) had a link to an infected employee, 2 (22%) died (1 death was attributed to COVID-19 ), and 7 (78%) recovered and were discharged. Table 1.Characteristics and demographics of patients with hospital-onset COVID-19.Abbreviation: PCR, polymerase chain reaction; HOCI, hospital-onset COVID-19 infections.Figure 1.Bar chart of nosocomial COVID-19 cases graphed against line graphs of COVID-19 infections diagnosed weekly among patient and employee at MD Anderson Cancer Center between March 2020 through February 2022 Conclusion The Omicron variant surge led to marked increases in HO-COVID-19 despite the continuous adoption of enhanced infection control practices, testing on admission, and daily symptoms screening of patients and employees. Disclosures Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.

Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro.

SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro). Polyprotein processing is essential yet incompletely understood. We studied Mpro-mediated processing of the nsp7-11 polyprotein, whose mature products include cofactors of the viral replicase, and identified the order of cleavages. Integrative modeling based on mass spectrometry (including hydrogen-deuterium exchange and cross-linking) and x-ray scattering yielded a nsp7-11 structural ensemble, demonstrating shared secondary structural elements with individual nsps. The pattern of cross-links and HDX footprint of the C145A Mpro and nsp7-11 complex demonstrate preferential binding of the enzyme active site to the polyprotein junction sites and additional transient contacts to help orient the enzyme on its substrate for cleavage. Last, proteolysis assays were used to characterize the effect of inhibitors/binders on Mpro processing/inhibition using the nsp7-11 polyprotein as substrate.

Monitoring of Dniester watershed pollution by reason of flooding and other environmental disasters

The work is about the solution of the scientific and practical task of substantiating the construction of geomodels of zones of probable flooding of the Dniester River on the basis of aerospace and contact measurements. In order to localize flooded areas and predict the dynamics of changes in geometric characteristics, natural and man-made factors that cause the rise of the groundwater level were analyzed. The main types of activity and load on the water resources of the Dniester basin are: residential and communal economy, industry, agriculture, including fisheries, hydropower and flood protection. Among the main cross-border problems typical for the Dniester River are: pollution by organic, biogenic and dangerous substances; hydromorphological changes; pollution by plastic and other household waste of the coastal strip of the river; spread of invasive species. The transboundary Dniester river is used for electricity generation. Dubossar hydroelectric power plant (HPP) (1954) in Moldova and Dnistrovsk HPP (1987) and Dnistrovsk HPP-2 (2000) in Ukraine were built on the river. Their activities led to hydromorphological changes of the river and its regulation.The main role in the pollution of the waters of the Dniester basin by biogenic substances on the territory of Ukraine and Moldova belongs to diffuse sources of agricultural origin. Water management activities and intensive chemicalization of agricultural land significantly affect the water quality of the Dniester River. The possibility of using available satellite images makes it possible to reduce the time and material costs of conducting additional contact measurements when determining zones of probable flooding, without reducing the accuracy of forecast parameters. The developed cartographic geomodels of areas of probable flooding make it possible to determine and visually assess the degree of flooding under different modes of operation of pressure horizons that have a hydraulic connection with groundwater.

Outcomes of a Community Engagement and Information Gathering Program to Support Telephone-Based COVID-19 Contact Tracing: Descriptive Analysis.

Contact tracing is an important public health tool for curbing the spread of infectious diseases. Effective and efficient contact tracing involves the rapid identification of individuals with infection and their exposed contacts and ensuring their isolation or quarantine, respectively. Manual contact tracing via telephone call and digital proximity app technology have been key strategies in mitigating the spread of COVID-19. However, many people are not reached for COVID-19 contact tracing due to missing telephone numbers or nonresponse to telephone calls. The New York City COVID-19 Trace program augmented the efforts of telephone-based contact tracers with information gatherers (IGs) to search and obtain telephone numbers or residential addresses, and community engagement specialists (CESs) made home visits to individuals that were not contacted via telephone calls. The aim of this study was to assess the contribution of information gathering and home visits to the yields of COVID-19 contact tracing in New York City. IGs looked for phone numbers or addresses when records were missing phone numbers to locate case-patients or contacts. CESs made home visits to case-patients and contacts with no phone numbers or those who were not reached by telephone-based tracers. Contact tracing management software was used to triage and queue assignments for the telephone-based tracers, IGs, and CESs. We measured the outcomes of contact tracing-related tasks performed by the IGs and CESs from July 2020 to June 2021. Of 659,484 cases and 861,566 contact records in the Trace system, 28% (185,485) of cases and 35% (303,550) of contacts were referred to IGs. IGs obtained new phone numbers for 33% (61,804) of case-patients and 11% (31,951) of contacts; 50% (31,019) of the case-patients and 46% (14,604) of the contacts with new phone numbers completed interviews; 25% (167,815) of case-patients and 8% (72,437) of contacts were referred to CESs. CESs attempted 80% (132,781) of case and 69% (49,846) of contact investigations, of which 47% (62,733) and 50% (25,015) respectively, completed interviews. An additional 12,192 contacts were identified following IG investigations and 13,507 following CES interventions. Gathering new or missing locating information and making home visits increased the number of case-patients and contacts interviewed for contact tracing and resulted in additional contacts. When possible, contact tracing programs should add information gathering and home visiting strategies to increase COVID-19 contact tracing coverage and yields as well as promote equity in the delivery of this public health intervention.