Tianjin, as a major coastal city in China, many economic construction planning parks and engineering construction projects have relied on the special advantages of it. The relative sea level has brought huge hidden danger to the economic and social development of Tianjin. And, land subsidence is the most important factor that influences relative sea level rise. Research analyzed Radarsat-2(2012-2016) and Sentinel-1(2016-2018) through PS-InSAR. And the results indicated that the subsidence rate of the southern plain of Tianjin slowed down as a whole, however, the annual average maximum subsidence rate was still more than 100mm/a. In addition, Wuqing and Jinghai sedimentary areas as well as several subsidence centers have been formed, and the settlement scope tends to expand to the east coast. By establishing a regular grid of land subsidence and groundwater to construct a geo-weighted regression model (GWR), it is found that Wuqing sedimentary area as a whole is positively correlated with TCA. While for Jinghai sedimentary area, there is a spatial difference in terms of TCA and SCA. According to the relative sea level change, it can be predicted that the natural coastline of Tianjin will recede by about 28 km 2 in 5 years and 87 km 2 in 20 years. Based on the above research results, this paper integrates land subsidence, groundwater, land classification status and other related factors, and uses machine learning method (XGBoost) to evaluate Tianjin’s urban safety as well as analyze high-risk areas and main contributing factors. From the perspective of earth system science, this paper analyzes the potential risks of seawater inundation and urban security caused by the superposition of sea level rise and coastal plain land subsidence, so as to improve the ability of coastal areas to resist disasters.

Expansive soil is a kind of special soil with soil particles mainly composed of hydrophilic minerals, and has significant deformation characteristics of water absorption expansion and water loss shrinkage. This characteristic often brings great harm to engineering construction. Relying on the foundation engineering of the bridge on the expansive soil slope of the Jiangxi-Huaihe River, this paper studies the effects of slope excavation and rainfall on the horizontal deformation of the bridge foundation by using temperature simulation and humidity fields and numerical simulation methods. The research results show that during the excavation process, the bridge foundation will produce a horizontal displacement pointing to the top of the slope, and the rainfall after excavation will cause the horizontal displacement of the bridge foundation to decrease and gradually develop in the opposite direction. During the excavation process, the rebound of slope excavation is the main factor affecting the horizontal displacement of the bridge foundation. Under short-term rainfall conditions, the hygroscopic expansion of the slope soil becomes the main influencing factor. Under extreme rainfall conditions, the main cause of the horizontal deformation of the bridge foundation is The influencing factors are transformed into the reduction of the soil weight of the slope and the strength of the soil material.

Rod structures are widely used in mechanical engineering as connecting and transmission links for structural elements of a wide variety of machines and mechanisms. During operation, they are subject-ed to variable mechanical and thermal influences, which create a complex stress-strain state in structur-al elements, depending on their temperature, and affecting their strength and reliability. Therefore, the determination of the thermally stressed state of rod structures, taking into account their mechanical properties (in particular, elasticity and thermal conductivity) is one of the topical scientific and tech-nical problems. Here, spatially one-dimensional unsteady boundary value problems (BVPs) of uncoupled ther-moelasticity are considered, which can be used to study various bar structures. This model describes well thermodynamic processes at low strain rates and here a unified technique is proposed for solving various BVPs typical of practical applications. Problems of determining the thermally stressed state of a thermoelastic rod using a model of uncoupled thermoelasticity are considered. Generalized solutions of non-stationary and stationary direct and semi-inverse BVPs under the action of power and heat sources of various types are con-structed on the basis of the method of generalized functions. Acting sources can also be specified by singular generalized functions, under different boundary conditions at the ends of the rod. Con-sidered are shock elastic waves that arise in such structures under the action of shock loads. Regu-lar integral representations of generalized solutions are obtained, which give an analytical solution to the stated BVPs.

In this paper, we introduce a new traveling wave with a buffer zone, which is approached by an asymmetric credit migration model with fixed migration boundary. The asymptotic behavior of the solution of the model is discussed. By constructing two sets of sub and super solutions sequences, it is proved that the solution of the credit rating migration model approaches the new traveling wave with buffer zone as time goes to infinite in a direction. Additionally, some numerical results are presented.

The [3+2] cycloaddition (32CA) reactions of N-methyl-C-(2-furyl) nitrone with maleimide derivatives have been studied in gas phase, ethanol and acetonitrile solvents within the Molecular Electron Density Theory (MEDT) framework at the B3LYP-D3/6-31G(d) level. Topological analysis classifies the nitrone as a zwitter-ionic (zw-) three atom component (TAC) associated with high energy barrier, while the high global electron density transfer (GEDT) decreases the requested energy cost for the rupture of the olefinic double bond of the maleimide derivatives and consequently decreases the activation barrier. Computations show that these 32CA reactions follow a one-step mechanism with highly asynchronous bond formation, while no new covalent bonds are formed at the transition states (TSs). Moreover, strongly repulsive non-covalent interactions at the endo TSs are found, presumably leading to their energetic destabilization relative to the exo ones. The predicted exo-selectivity agrees well with the experimental findings. Inclusion of solvent effects increases the activation energy, in particular for the endo TSs. Also, the influence of temperature was investigated at 289.15 K, 298.15 K and 393.15 K.

Deborah D. Rupert1, Marah N. Kays2,, Olivia R. Negris3,#, Beatrix B. Thompson4,#, Marla L. Clayman5, Lisa J. Mordell6, Tricia R. Pendergrast7, Rakhee K. Bhayani8, Eve Bloomgarden9,#, Shikha Jain10,** to whom correspondence should be addressed# authors contributed equallyMedical Scientist Training Program, State of New York Stony Brook University, Stony Brook, NYKansas City University, Kansas City, MORush Medical College, Chicago, ILDepartment of Obstetrics and Gynecology, Yale University, New Haven, CTCenter for Healthcare Organization and Implementation Research, Veterans Affairs Bedford Healthcare System, Bedford, MAStritch School of Medicine, Loyola University, Chicago, ILNorthwestern University Feinberg School of Medicine, Chicago, ILDepartment of Medicine, Washington University School of Medicine, St Louis, MODivision of Endocrinology, NorthShore University Health System, Chicago, ILDivision of Hematology and Oncology, University of Illinois at Chicago, Chicago, IL

A search has been conducted, employing ab initio molecular orbital theory, for potential tetrel-bonded complexes between the fluorinated methanes methyl fluoride, difluoromethane and fluoroform, and the related hydrides ammonia, water, hydrogen fluoride, phosphine, hydrogen sulfide and hydrogen chloride. Eleven such complexes have been identified, six containing CH3F and five CH2F2. The complexes are typically less strongly bound than their hydrogen-bonded counterparts, and the interaction energies vary in a consistent way with the periodic trend of the electron donors. The intermolecular separations and changes of the relevant intramolecular bond lengths, the wavenumber shifts of the critical vibrational modes, and the extents of charge transfer for the atoms most closely involved in the interactions correlate, by and large, with the strengths of interaction.

The phenomena in which an extra electron is removed from a negative ion is called photo-detachment. Photo-detachment is important phenomena, used to find the structure of anions, particulary to find the electron affinities. In this paper, we present theoretically the induced efffects in the photo-detached of tri-atomic anion H3 near hard reflecting wall or surface. For the photo-detachment process, a Z-polarized coherent source of radiations (laser) is used to kick electrons from H3 like anion in the domain of a hard reflecting surface. Imaging method is adopted to derive the generalized detached electron wave, differential cross-section and the total cross-section Analytically. Numerical solutions (simulations) for total electron flux and the total cross-section is also presented. In the electron flux, shows visible oscillation and hence the induced effect of surface in the interference. It is depicted that the reflecting hard wall strongly affects the flux and total photo-detachment cross-section

TITLE: Letter to the Editor: Impact of antimicrobial selection for prophylaxis of left ventricular assist device surgical infections.ARTICLE TYPE: letter to the editorCORRESPONDENCE: 1. SYED ABDUL REHMAN SHAHContact; +92 3350238188 Email; arshah321@gmail.comInstitute: Dow University of Health Sciences, karachiAddress; H#2 G#50/4/2/2 Umar bungalows A Rehman street garden east Karachi

Background: Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. Methods: We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. Results: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared to pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared to pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. Conclusion: We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings have implications for future vaccination strategies and possibly cross-reactive T cell immunity.

Environmental DNA (eDNA) analyses are powerful for describing marine biodiversity but must be optimized for their effective use in routine monitoring. To maximize eDNA detection probabilities of sparsely distributed populations, water samples are usually concentrated from larger volumes and filtered using fine-pore membranes, often a significant cost-time bottleneck in the workflow. This study aimed to streamline eDNA sampling by investigating plankton net versus bucket sampling, direct versus sequential filtration including self-preserving filters. Biodiversity was assessed using metabarcoding of the small ribosomal subunit (18S rRNA) and mitochondrial cytochrome c oxidase I (COI) genes. Multi-species detection probabilities were estimated for each workflow using a probabilistic occupancy modelling approach. Significant workflow-related differences in biodiversity metrics were reported. Highest amplicon sequence variant (ASV) richness was attained by the bucket sampling combined with self-preserving filters, comprising a large portion of micro-plankton. Less diversity but more metazoan taxa were captured in the net samples combined with 5 µm pore size filters. Pre-filtered 1.2 µm samples yielded few or no unique ASVs. The highest average (~32%) metazoan detection probabilities in the 5 µm pore size net samples confirmed the effectiveness of pre-concentrating plankton for biodiversity screening. These results contribute to streamlining eDNA sampling protocols for uptake and implementation in marine biodiversity research and surveillance.

Background and Purpose: The acquired resistance to PARP inhibitors (PARPi) caused by point mutations in PARP1 protein is hard to overcome through current strategies. In order to explore modalities to conquer resistance and identify patients who are most likely to benefit from PARP1-targeted therapy, we developed a proteolysis-targeted-chimaera (PROTAC) to degrade mutant PARP1 in p53-mutant TNBC. Experimental Approach: Based on analysis of the resistant mutations, we attempted to use PROTAC strategy to increase the sensitivity of cells expressing PARPi-resistant proteins that identified from patients. The antineoplastic activity of our synthetic degrader was evaluated in multiple human cell lines, as well as the xenograft model with p53 mutation. The proteomics subsequently was used to reveal the potential mechanism of the degrader. Ferroptosis, as main mechanism, was assayed via detecting SLC7A11 signaling, glutathione and lipid peroxidation. Besides, according to genetic alteration analysis from patients, three common p53 mutations were selected to assess PARP1-related cell death. Key Results: We developed a PROTAC termed “NN3”, and this compound could trigger ubiquitination and proteasome-mediated PARP1 degradation. Interestingly, compared with other reported PARP1 degraders, NN3 has a unique antitumor mechanism and it promote ferroptosis effectively via decreasing the SLC7A11/GPX4 pathway in HR-proficient TNBC cells, whether or not these cells express drug resistance-related PARP1 mutations. More importantly, NN3 showed potent activity and low toxicity in vivo studies on mutant-p53 TNBC. Conclusion and Implications: We identify PROTAC-mediated degradation of PARP1 as a novel strategy against PARPi resistance and a paradigm for targeting mutant-p53 cancers by inducing ferroptosis.

Background: The changes in ventricular repolarization after cardiac resynchronization therapy (CRT) are poorly understood. Objective: Address this knowledge gap using a multimodality approach including electrocardiographic and echocardiographic measurements in patients and using patient-specific computational modeling. Methods: In 33 patients electrocardiographic and echocardiographic measurements were performed before and at various intervals after CRT, both during CRT-ON and temporary CRT-OFF. T-wave area was calculated from vectorcardiograms, reconstructed from the 12-lead ECG. Computer simulations were performed using a patient-specific eikonal model of cardiac activation with spatially varying action potential duration (APD) and repolarization rate, fit to a patient’s ECG. Results: During CRT-ON T-wave area diminished within a day and remained stable thereafter, whereas QT-interval did not change significantly. During CRT-OFF T-wave area doubled within 5 days of CRT, while QT-interval and peak-to-end T-wave interval hardly changed. Left ventricular (LV) ejection fraction did not significantly increase before 1 month of CRT. Computer simulations indicated that the increase in T-wave area during CRT-OFF can be explained by changes in APD following chronic CRT that are opposite to the change in CRT-induced activation time. These APD changes were associated with a reduction in LV dispersion in repolarization during chronic CRT. Conclusions: T-wave area during CRT-OFF is a sensitive marker for adaptations in ventricular repolarization during chronic CRT that may include a reduction in LV dispersion of repolarization.

Time series classification (TSC) is an important and challenging problem in data mining. Time series data sets are an important basis for this research and are widely used in baseline verification of various algorithm models. Aiming at the problem that there are few domestic data sets and the current TSC data set is relatively old, a new data set for TSC task is established based on the average price data of concrete in major cities in China, which provides new data support for the research of TSC algorithm. We made use of the data center of Oriental Fortune to disclose the sample data of the average price of concrete from 2013-10-23 to 2021-01-20, created 730 autoregression-based series data sets by using sliding windows of different lengths, and then selected the appropriate sliding window length through machine learning model verification, finally, convolutional neural network (CNN) and long and short memory (LSTM) network, which are good at processing temporal features, are used to verify the data and prove the validity of the dataset. The dataset is freely available at https://gitee.com/lq2012/tsc-dataset.

Background: In order to determine tolerance development in hen’s egg (HE) allergic children, international guidelines recommend an oral food challenge after 6-24 months. This study aimed to assess whether parents follow this advice and factors that influence their decision. Methods: A follow-up of 158 challenge-proven HE allergic children was performed. Families who did not come to a rechallenge were contacted by phone and a standardized survey relating to the current allergy status was conducted. Logistic regression models were used to assess the effect of clinical and laboratory characteristics on the reevaluation of the allergy status. Results: 35% of the HE-allergic children conducted a rechallenge in a hospital, 27% continued avoiding HE without reevaluation and 11% performed a “home-testing” with HE. The odds ratio for patients to test for HE tolerance at home instead of in a hospital increased 7.94 times (CI:2.31-27.31) for every decrease in the severity score at the initial challenge, and 3.24 times (CI:1.26-8.33) for every decrease of the baseline specific IgE CAP-class. Tolerance of heated HE prior to reevaluation was most frequent in the home-tested (100%) and was more frequent in patients, who continued avoidance (68%) compared to those, who were rechallenged (44%). Conclusions: Our data suggest an association between reaction severity as well as specific IgE levels at initial food challenge and the choice of families whether and how to evaluate natural tolerance development in their HE-allergic child. Individualized management may be needed in order to achieve safe and effective medical care for these patients.

The Matchmaker Exchange (MME) launched in 2015 to provide a robust mechanism to discover novel disease-gene relationships. This federated network connects databases holding relevant data, where two or more users are looking for a match for the same gene (two-sided matchmaking). The number of unique genes present across MME has steadily increased; there are currently >13,520 unique genes (~68% of all protein coding genes) connected across MME’s nodes, GeneMatcher, DECIPHER, PhenomeCentral, MyGene2, seqr, Initiative on Rare and Undiagnosed Disease, PatientMatcher, and the RD-Connect Genome-Phenome Analysis Platform. The dataset accessible across MME includes more than 120,000 cases from over 12,000 contributors in 98 countries. Discovery of potential new disease-gene relationships occurs daily and international collaborations are moving these connections forward to publication. Expansion of data sharing into routine clinical practice has ensured access to discovery for even more individuals with undiagnosed rare genetic disease. MME supports connections to the literature (PubCaseFinder) and to human and model organism resources (Monarch Initiative) and scientists (ModelMatcher). Efforts are underway to explore additional approaches to matchmaking where there is only one querier (one-sided matchmaking). Genomic matchmaking has proven its utility over the past 7 years and will continue to facilitate discoveries in years to come.

A document by Mohamad El Moheb. Click on the document to view its contents.

In most countries, genetically modified microorganisms are not approved for use for fermentation in the food industry. Therefore, random mutagenesis and subsequent screening are performed to improve the productivities of valuable metabolites and enzymes as well as other specific functions in an industrial microbial strain. In addition, targeted gene knockout is performed by genetic recombination using its enzyme genes as selectable markers to maintain self-cloning status. However, random mutagenesis has a drawback as it does not guarantee improvement of the targeted function. Conversely, self-cloning is rarely used to breed an industrial microbial strain. This is probably because a self-cloning strain is similar to a genetically modified strain, as both undergo homologous recombination, although exogenous genes are not introduced. In this article, I discuss the usefulness of genome editing technology as a substitute for conventional techniques to breed filamentous fungal strains. This article particularly focusses on “genome co-editing,” a genome editing technology used for knocking out two genes concomitantly, as reported in Magnaporthe grisea and Aspergillus oryzae. Especially, when genome co-editing is applied to a target gene and a membrane transporter gene that aid the entry of toxic compounds into cells, the resulting clone can be categorized as an autotrophic and non-genetically modified clone. Such a clone should easily apply to industrial fermentation without being restricted by a genetically modified status. Genome co-editing will also be used to construct mutant strains with multiple target gene knockouts by eliminating multiple membrane transporter genes. This could substantially improve the productivities of valuable metabolites and enzymes in a stepwise manner. Thus, genome co-editing is considered a potentially powerful method to knock out single or multiple target genes that can contribute to the breeding of filamentous fungal strains in the food industry.

When confronted with a public health emergency, significant innovative treatment protocols can sometimes be discovered by medical doctors at the front lines based on repurposed medications. We propose a statistical framework for analyzing the case series of patients treated with such new protocols, that enables a comparison with our prior knowledge of expected outcomes, in the absence of treatment. The goal of the proposed methodology is not to provide a precise measurement of treatment efficacy, but to establish the existence of treatment efficacy,  in order to facilitate the binary decision of whether the treatment protocol should be adopted  on an emergency basis. The methodology consists of a frequentist component that compares a treatment group against the  probability of an adverse outcome in the absence of treatment, and calculates an efficacy threshold that has to be exceeded by this  probability, in order to control the corresponding $p$-value, and reject the null hypothesis. The  efficacy threshold is further adjusted with a Bayesian technique, in order to also control the false positive rate. A random selection bias threshold is then calculated from the efficacy threshold to control for random selection bias. Exceeding the efficacy threshold establishes the existence of treatment efficacy by the preponderance of evidence, and exceeding the more demanding random selection bias threshold establishes the existence of treatment efficacy by the clear and convincing evidentiary standard. The combined techniques are applied to case series of high-risk COVID-19 outpatients, that were treated using the early Zelenko protocol and the more enhanced McCullough protocol.

Type A aortic dissection (TAAD) is a life-threatening clinical emergency requiring timely surgical intervention. Concomitant with pregnancy at any stage, it adds an additional level of complexity which mandates careful planning for the management strategy that will yield the optimal outcomes. It is life-threatening pathology to both the mother and foetus, with mortality rates of up to 30% and 50% reported, respectively. Safe imaging modalities that do no expose the foetus to radiation and contrast are recommended to reach an accurate diagnosis. In addition, meticulous multi-disciplinary team planning is pivotal to ensure optimal outcomes are achieved through careful choice of surgical technique as well as strict control of medications. Although TAAD in pregnancy is associated with high mortality and morbidity to both the mother and her foetus, success in the treatment of this small subset of patients can certainly be achieved.

A document by Sebastian Velasteguí. Click on the document to view its contents.

Laccases belong to a family of multicopper enzymes able to oxidize a broad spectrum of organic compounds. Despite the well-known property of laccases to carry out bleaching and degradation of industrial dyes and polyphenolic compounds, their industrial use is often limited by the high cost, low efficiency, or instability of these enzymes. To look for new microorganisms which produce laccases that are potentially suitable for industrial applications, we have isolated several fungal strains from a cave in northern Spain. Their phenotypic analysis on agar plates supplemented with ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) disclosed two laccase-positive strains. Further genotyping revealed that they belonged to the Gliomastix murorum and Conidiobolus thromboides species. The secretion of G. murorum and C. thromboides laccase-like enzymes was then confirmed by zymography. Further identification of these polypeptides by mass-spectroscopy revealed the nature of the laccases and made it possible to predict their functional domains and other features. In addition, plate assays revealed that the laccases secreted by both G. murorum and C. thromboides were capable of degrading industrial dyes (Congo Red, Indigo, and Eriochrome Black T). Homology modeling and substrate docking predicted the putative structure of the currently uncrystallized G. murorum enzyme as well as its amino acid residues potentially involved in interactions with these dyes. In summary, new biochemical and structural insights into decolorization mediated by G. murorum laccase as well as identification of laccase-like oxidase in C. thromboides point to a promising future for these enzymes in biotechnology.

Rationale The lung clearance index (LCI) is increasingly being used in the clinical surveillance of patients with cystic fibrosis (CF). However, there are limited data on long-term variability and clinically relevant changes in LCI during routine clinical surveillance. Objectives To evaluate long-term variability of LCI and propose a threshold for a clinically relevant change. Methods Children with CF aged 4-18 years performed LCI measurements every three months as part of routine clinical surveillance during 2011-2020 in two centers. The variability of LCI during periods of clinical stability was assessed using mixed-effects models and was used to identify thresholds for clinically relevant changes. Results Repeated LCI measurements of acceptable quality (N= 858) were available in 100 patients with CF. Variability of repeated LCI measurements over time expressed as coefficient of variation (CV%) was 7.4%. The upper limit of normal (ULN) for relative changes in LCI between visits was 19%. Conclusion We report the variability of LCI in children and adolescents with CF during routine clinical surveillance. According to our data, a change in LCI beyond 19% may be considered clinically relevant. These findings will help guide clinical decisions according to LCI changes.

By their paternal transmission, Y-chromosomal haplotypes are sensitive markers of population history and male-mediated introgression. Previous studies identified biallelic single-nucleotide variants in the SRY, ZFY, DDX3Y genes, which in domestic goats identified four major Y-chromosomal haplotypes Y1A, Y1B, Y2A and Y2B with a marked geographic partitioning. Here, we analyze whole-genome sequences of 386 domestic goats from 75 modern breeds and 7 wild goat species that were generated by the VarGoats goat genome project. Phylogenetic analyses indicated domestic haplogroups corresponding to Y1B, Y2A and Y2B, respectively, whereas Y1A is split into Y1AA and Y1AB. All five haplogroups were detected in 26 ancient DNA samples from southeast Europe or Asia. Haplotypes from present-day bezoars are not shared with domestic goats and are attached to deep nodes of the trees and networks. Haplogroup distributions for 180 domestic breeds indicate ancient paternal population bottlenecks and expansions during the migrations into northern Europe, eastern and southern Asia and Africa south of the Sahara. In addition, sharing of haplogroups indicates male-mediated introgressions, most notably an early gene flow from Asian goats into Madagascar and the crossbreeding that in the 19th century resulted in the popular Boer and Anglo-Nubian breeds. More recent introgressions are those from European goats into the native Korean goat population and from Boer goat into Uganda, Kenya, Tanzania, Malawi and Zimbabwe. This study illustrates the power of the Y-chromosomal variants for reconstructing the history of domestic species with a wide geographic range.