Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterizing the 3D Stress-Strain Behavior of Sandy Soils: A Neuro-Mechanistic Approach

An adaptive feod-back backpropagation artificial neural network (ANN) approach is used in this study along with proven mechanics-based knowledge/concepts to characterize the complex 3D monotonic stress-strain behavior of a sandy soil. To accomplish this objective, four consecutive modeling stages were conducted. In the first stage, mechanics-based knowledge relating to the cause and effect process (i.e., stress-strain) was used to design an appropriate general purpose stress-controlled ANN model. In the second stage, the designed model with appropriate input categories dictated by mechanics-based knowledge was trained and tested on 3D monotonic stress-strain experimental data of a sandy soil. in the third stage, statistical and graphical accuracy outcomes on training and testing stress-strain responses were used to arrive at the optimal neuro-mechanistic based model. In the last stage, the selected neuro-mechanistic based model is combined with appropriate mechanics-based concepts to create a hybrid neuro-mechanistic simulator (NMS). The developed NMS was found efficient in characterizing the 3D monotonic stressstrain behavior of Canadian River sand subjected to both shear and Hydrostatic Compression (HC) loading stress paths. Consequently, NMS can easily be used to simulate in real time any desired monotonic deformational behavior for given stress path and known initial stress and strain conditions. Introduction During the last decades, many investigations have focused on developing ANN-based constitutive models for geomaterials. Ghaboussi et al. (1991) modeled the constitutive behavior of plain concrete in biaxial monotonic as well as uniaxial cyclic loading conditions using standard ANN-backpropagation method and utilizing the one-point scheme data representation. Accuracy of the prediction for the biaxial monotonic case was better than the uniaxial cyclic loading case. Moreover, it was found that the larger the number of cycles used in training, the better the ANN model i Associate Prof., Dept. ofCiv. Engrg. , Kansas State Univ., Manhattan, KS 66506. 2 Graduate Research Assistant, Dept. of Cir. Engrg. , Kansas State Univ., Manhattan, KS 66506.
Comparative glycomics of leukocyte glycosaminoglycans

Glycosaminoglycans (GAGs) vary widely in disaccharide and oligosaccharide content in a tissue‐specific manner. Nonetheless, there are common structural features, such as the presence of highly sulfated non‐reducing end domains on heparan sulfate (HS) chains. Less clear are the patterns of expression of GAGs on specific cell types. Leukocytes are known to express GAGs primarily of the chondroitin sulfate (CS) type. However, little is known regarding the properties and structures of the GAG chains, their variability among normal subjects, and changes in structure associated with disease conditions. We isolated peripheral blood leukocyte populations from four human donors and extracted GAGs. We determined the relative and absolute disaccharide abundances for HS and CS GAGs classes using size exclusion chromatography‐mass spectrometry (SEC‐MS). We found that all leukocytes express HS chains with a level of sulfation that is more similar to heparin than to organ‐derived HS. The levels of HS expression follows the trend T cells/B cells > monocytes/natural killer cells > polymorphonuclear leukocytes (PMNs). In addition, CS abundances were considerably higher than total HS but varied considerably in a leukocyte cell type‐specific manner. Levels of CS were higher for myeloid lineage cells (PMNs and monocytes) than for lymphoid cells (B, T and natural killer (NK) cells). This information establishes the range of GAG structures expressed on normal leukocytes and is necessary for subsequent inquiry into disease conditions.
The substrate oxidation mechanism of pyranose 2‐oxidase and other related enzymes in the glucose–methanol–choline superfamily

Enzymes in the glucose–methanol–choline (GMC) oxidoreductase superfamily catalyze the oxidation of an alcohol moiety to the corresponding aldehyde. In this review, the current understanding of the sugar oxidation mechanism in the reaction of pyranose 2‐oxidase (P2O) is highlighted and compared with that of other enzymes in the GMC family for which structural and mechanistic information is available, including glucose oxidase, choline oxidase, cholesterol oxidase, cellobiose dehydrogenase, aryl‐alcohol oxidase, and pyridoxine 4‐oxidase. Other enzymes in the family that have been newly discovered or for which less information is available are also discussed. A large primary kinetic isotope effect was observed for the flavin reduction when 2‐d‐d‐glucose was used as a substrate, but no solvent kinetic isotope effect was detected for the flavin reduction step. The reaction of P2O is consistent with a hydride transfer mechanism in which there is stepwise formation of d‐glucose alkoxide prior to the hydride transfer. Site‐directed mutagenesis of P2O and pH‐dependence studies indicated that His548 is a catalytic base that facilitates the deprotonation of C2–OH in d‐glucose. This finding agrees with the current mechanistic model for aryl‐alcohol oxidase, glucose oxidase, cellobiose dehydrogenase, methanol oxidase, and pyridoxine 4‐oxidase, but is different from that of cholesterol oxidase and choline oxidase. Although all of the GMC enzymes share similar structural folding and use the hydride transfer mechanism for flavin reduction, they appear to have subtle differences in the fine‐tuned details of how they catalyze substrate oxidation.
Alignment between Lean Principles and Practices and Worker Safety Behavior

AbstractAlignment and synergy between the areas of lean construction and safety management are expected because all near misses and injury incidents represent waste from the lean perspective. This paper describes a research study of lean and safety principles and practices with regards to worker behavior and safety practices. Specifically, the study aimed to investigate the extent of alignment between lean construction principles/practices and worker behaviors associated with construction safety. To conduct the study, the researchers used a multistep process involving a comprehensive literature review, document content analyses by an expert panel, and a survey of industry practitioners knowledgeable about lean construction. The findings support the perspective that many similarities exist between the application and impacts of lean and safety principles and practices. Lean practitioners surveyed believe that implementation of the last planner system as a lean practice is most beneficial to the following s.
Engineering RNA‐binding proteins for biology

RNA‐binding proteins play essential roles in the regulation of gene expression. Many have modular structures and combine relatively few common domains in various arrangements to recognize RNA sequences and/or structures. Recent progress in engineering the specificity of the PUF class RNA‐binding proteins has shown that RNA‐binding domains may be combined with various effector or functional domains to regulate the metabolism of targeted RNAs. Designer RNA‐binding proteins with tailored sequence specificity will provide valuable tools for biochemical research as well as potential therapeutic applications. In this review, we discuss the suitability of various RNA‐binding domains for engineering RNA‐binding specificity, based on the structural basis for their recognition. We also compare various protein engineering and design methods applied to RNA‐binding proteins, and discuss future applications of these proteins.
Improved pregnancy outcomes in women exposed to malaria with high antibody levels against Plasmodium falciparum.

BACKGROUND Antibodies against VAR2CSA, the Plasmodium falciparum variant surface antigen that binds placental chondroitin sulfate A, have been suggested to mediate protection against malaria in pregnancy but also to be markers of infection. Here, we aimed to identify clinically relevant antibody responses, taking into consideration variations in parasite exposure and human immunodeficiency virus type 1 (HIV) infection status. METHODS Levels of immunoglobulin G (IgG) against placental and pediatric isolates, VAR2CSA (DBL2X, DBL3X, DBL5ε, and DBL6ε domains), and other blood-stage antigens (DBLγ, DBLα, MSP119, AMA1, and EBA175) were measured in plasma specimens from 293 pregnant Mozambican women at delivery. Associations between antibody responses, factors influencing malaria exposure, HIV infection status, and pregnancy outcomes were assessed. RESULTS Maternal antibodies were affected by placental infection, parity, season, and neighborhood of residence. HIV infection modified these associations and attenuated the parity-dependent increase in IgG level. High levels of antibody against AMA1, DBL3X, DBL6ε, placental isolates, and pediatric isolates were associated with increased weight and gestational age of newborns (P ≤ .036) among women with malaria episodes during pregnancy. CONCLUSIONS Antiparasite IgGs in women at delivery are affected by HIV infection, as well as by variations in the exposure to P. falciparum. Heterogeneity of malaria transmission needs to be considered to identify IgGs against VAR2CSA and other parasite antigens associated with improved pregnancy outcomes.
Possibilities of improving the function and esthetic appearance of finger stumps using the method of osseointegration

Relevance The work deals with the challenging problems of improving the function and aesthetic appearance of the finger stumps using a surgical technology of osseointegration. Purpose To present preliminary results of osseointegration with the use of titanium implants and exoprostheses for finger stumps. Material and methods Osseointegration was performed in order to improve the function and aesthetic appearance of 17 phalangeal finger stumps in 8 patients at the age of 15 to 57 years who underwent treatment at the FSBI RISC for RTO of the RF ministry of health in 2014. Results Osseointegration that was assessed with clinical and radiographic methods, bench tests, and DASH scale resulted in positive short-term outcomes. Conclusion Osseointegrated finger prostheses for defects at the phalangeal level improve hand functions and appearance within a short period of time. The method of osseointegration is strategically important for management of large limb segment amputations and high levels of truncation. It is relevant to develop domestic implants that will optimize treatment terms, its results, and further prosthetic application.
Natural history of anal vs oral HPV infection in HIV-infected men and women.

BACKGROUND Human immunodeficiency virus (HIV)-infected individuals are at greater risk for human papillomavirus (HPV)-associated anal than oropharyngeal cancers. The prevalence of anal vs oral HPV infections is higher in this population, but whether this is explained by higher incidence or persistence is unknown. METHODS Oral rinse and anal swab samples were collected semiannually from 404 HIV-infected adults in Baltimore, Maryland. Samples were tested for 37 HPV types using PGMY09/11 primers and reverse line-blot hybridization. Risk factors for HPV persistence were explored using adjusted Wei-Lin-Weissfeld models. RESULTS The prevalence (84% vs 28%), incidence (145 vs 31 per 1000 person-months), and 12-month persistence (54% vs 29%) were higher for anal vs oral HPV infections, respectively (each P < .001). Heterosexual men had lower incidence of anal HPV than men who have sex with men and women, but a higher incidence of oral HPV infection (test of interaction P < 0.001). In adjusted analyses, risk factors for HPV persistence included prevalent vs incident (adjusted hazard ratio [aHR] = 4.0; 95% confidence interval [CI], 3.5-4.8) and anal vs oral HPV infections (aHR = 1.5; 95% CI, 1.2-1.9). CONCLUSIONS The higher incidence and persistence of anal vs oral HPV infections likely contributes to the higher burden of anal as compared to oral HPV-associated cancers in HIV-infected individuals.
Broadly protective protein-based pneumococcal vaccine composed of pneumolysin toxoid-CbpA peptide recombinant fusion protein.

BACKGROUND Pneumococcus, meningococcus, and Haemophilus influenzae cause a similar spectrum of infections in the ear, lung, blood, and brain. They share cross-reactive antigens that bind to the laminin receptor of the blood-brain barrier as a molecular basis for neurotropism, and this step in pathogenesis was addressed in vaccine design. METHODS Biologically active peptides derived from choline-binding protein A (CbpA) of pneumococcus were identified and then genetically fused to L460D pneumolysoid. The fusion construct was tested for vaccine efficacy in mouse models of nasopharyngeal carriage, otitis media, pneumonia, sepsis, and meningitis. RESULTS The CbpA peptide-L460D pneumolysoid fusion protein was more broadly immunogenic than pneumolysoid alone, and antibodies were active in vitro against Streptococcus pneumoniae, Neisseria meningitidis, and H. influenzae. Passive and active immunization protected mice from pneumococcal carriage, otitis media, pneumonia, bacteremia, meningitis, and meningococcal sepsis. CONCLUSIONS The CbpA peptide-L460D pneumolysoid fusion protein was broadly protective against pneumococcal infection, with the potential for additional protection against other meningeal pathogens.
Progress and challenges in RSV prophylaxis and vaccine development.

Respiratory syncytial virus (RSV) is a respiratory tract pathogen that causes significant morbidity and mortality in children aged <5 years (most disease occurs at age <1 year) and is a major public health burden worldwide. More than 90% of children are infected at least once with RSV before the age of 2 years [1–3]. RSV accounts for approximately 70% of hospitalizations due to bronchiolitis [1, 4]. In the United States alone, the estimated healthcare costs associated with RSV hospitalizations exceed $950 million, making it a significant economic burden [5]. Further, the RSV burden is disproportionately greater in children aged <5 years living in developing countries [3]. RSV infection does not confer long-term protection, as reinfections occur throughout life, which poses a significant disease risk in individuals with cardiopulmonary disease, immunocompromised patients, and the elderly [7]. In the elderly, complications of RSV infection often result from exacerbation of underlying pulmonary and cardiac disease. [7]. A member of the Paramyxoviridae family, Pneumovirus genus, RSV exists as an enveloped virus containing a negative-sense, single-stranded RNA genome. The genome encodes for the following 11 proteins: nonstructural proteins (NS1, NS2, and M2-2), the viral nucleocapsid protein (N), phosphoprotein (P), matrix (M), RNA-dependent RNA polymerase (L), M2-1, and 3 surface glycoproteins (G [attachment], F [fusion], and SH [small hydrophobic]). There are 2 RSV major groups, A and B, and multiple genotypes within each group. The protective immune response to RSV infection is primarily directed against the 2 major surface viral glycoproteins, F and G. The F glycoprotein seems most important for induction of protective immunity and is associated with a high serum neutralizing antibody response as well as activation of CD14 and Toll-like receptor-4 (TLR-4) [8]. RSV F protein undergoes structural rearrangement during the fusion process. Antigenic sites on the postfusion form of the protein have been associated with a range of neutralizing activity. However, recent evidence suggests that most of the F protein–specific neutralizing antibodies in human sera are directed against the prefusion form of the RSV F protein. Thus, the antigenic nature of the RSV F protein may have important implications for prophylaxis and vaccine development [9]. The RSV G protein has been implicated in the pathogenesis of disease after primary infection and formalin-inactivated (FI-RSV)–enhanced disease [6]. The highest degree of antigenic diversity in RSV is found in the RSV G protein. This diversity may play an important role in viral pathogenesis by facilitating immune evasion. The ability of this protein to evade or inhibit the host immune response may complicate vaccine development. RSV binds to several surface ligands, including cellular glycosaminoglycans, CX3CR1 [10], ICAM-I [11], Annexin-II [12], and nucleolin [13].
Comparison of Quality and Output of Different Optimal Perimetric Testing Approaches in Children With Glaucoma

Importance There is limited evidence to support the development of guidance for visual field testing in children with glaucoma. Objective To compare different static and combined static/kinetic perimetry approaches in children with glaucoma. Design, Setting, and Participants Cross-sectional, observational study recruiting children prospectively between May 2013 and June 2015 at 2 tertiary specialist pediatric ophthalmology centers in London, England (Moorfields Eye Hospital and Great Ormond Street Hospital). The study included 65 children aged 5 to 15 years with glaucoma (108 affected eyes). Main Outcomes and Measures A comparison of test quality and outcomes for static and combined static/kinetic techniques, with respect to ability to quantify glaucomatous loss. Children performed perimetric assessments using Humphrey static (Swedish Interactive Thresholding Algorithm 24-2 FAST) and Octopus combined static tendency-oriented perimetry/kinetic perimetry (isopter V4e, III4e, or I4e) in a single sitting, using standardized clinical protocols, administered by a single examiner. Information was collected about test duration, completion, and quality (using automated reliability indices and our qualitative Examiner-Based Assessment of Reliability score). Perimetry outputs were scored using the Aulhorn and Karmeyer classification. One affected eye in 19 participants was retested with Swedish Interactive Thresholding Algorithm 24-2 FAST and 24-2 standard algorithms. Results Sixty-five children (33 girls [50.8%]), with a median age of 12 years (interquartile range, 9-14 years), were tested. Test quality (Examiner-Based Assessment of Reliability score) improved with increasing age for both Humphrey and Octopus strategies and were equivalent in children older than 10 years (McNemar test, &khgr;2 = 0.33; P = .56), but better-quality tests with Humphrey perimetry were achieved in younger children (McNemar test, &khgr;2 = 4.0; P = .05). Octopus and Humphrey static MD values worse than or equal to −6 dB showed disagreement (Bland-Altman, mean difference, −0.70; limit of agreement, −7.74 to 6.35) but were comparable when greater than this threshold (mean difference, −0.03; limit of agreement, −2.33 to 2.27). Visual field classification scores for static perimetry tests showed substantial agreement (linearly weighted &kgr;, 0.79; 95% CI, 0.65-0.93), although 25 of 80 (31%) were graded with a more severe defect for Octopus static perimetry. Of the 7 severe cases of visual field loss (grade 5), 5 had lower kinetic than static classification scores. Conclusions and Relevance A simple static perimetry approach potentially yields high-quality results in children younger than 10 years. For children older than 10 years, without penalizing quality, the addition of kinetic perimetry enabled measurement of far-peripheral sensitivity, which is particularly useful in children with severe visual field restriction.
Membrane remodeling capacity of a vesicle‐inducing glycosyltransferase

Intracellular vesicles are abundant in eukaryotic cells but absent in the Gram‐negative bacterium Escherichia coli. However, strong overexpression of a monotopic glycolipid‐synthesizing enzyme, monoglucosyldiacylglycerol synthase from Acholeplasma laidlawii (alMGS), leads to massive formation of vesicles in the cytoplasm of E. coli. More importantly, alMGS provides a model system for the regulation of membrane properties by membrane‐bound enzymes, which is critical for maintaining cellular integrity. Both phenomena depend on how alMGS binds to cell membranes, which is not well understood. Here, we carry out a comprehensive investigation of the membrane binding of alMGS by combining bioinformatics methods with extensive biochemical studies, structural modeling and molecular dynamics simulations. We find that alMGS binds to the membrane in a fairly upright manner, mainly by residues in the N‐terminal domain, and in a way that induces local enrichment of anionic lipids and a local curvature deformation. Furthermore, several alMGS variants resulting from substitution of residues in the membrane anchoring segment are still able to generate vesicles, regardless of enzymatic activity. These results clarify earlier theories about the driving forces for vesicle formation, and shed new light on the membrane binding properties and enzymatic mechanism of alMGS and related monotopic GT‐B fold glycosyltransferases.
Insertion of a 59 amino acid peptide in Salmonella Typhimurium membrane results in loss of virulence in mice

We demonstrated previously that expression of a single trans‐membrane region of the Δ12‐desaturase gene of Synechocystis sp. PCC 6803 in Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) altered the membrane physical state of this pathogen, induced a significant change in the pattern of mRNA transcription of major heat shock genes, and inhibited pathogen growth inside murine macrophages. In this study, we demonstrate that injection of the modified Salmonella strain [Stm(pBAD200)] into C57Bl6j mice is safe. Survival of mice was associated with bacterial clearance, an increased number of splenic leukocytes, and high levels of interleukin–12, interferon γ and tumor necrosis factor α in spleens as well as in sera. Furthermore, Stm(pBAD200)‐injected mice developed a Salmonella‐specific antibody and Th1‐like responses. Mice challenged with Stm(pBAD200) are protected from systemic infection with Salmonella wild‐type. Similarly, mice infected with Stm(pBAD200) by the oral route survived when challenged with an oral lethal dose of Salmonella wild‐type. The avirulent Stm(pBAD200) phenotype is associated with a remarkable change in the expression of the hilC, hilD, hilA, invF and phoP genes, among others, whose products are required for invasion and replication of Salmonella inside phagocytic cells. These data demonstrate the use of trans‐membrane peptides to generate attenuated strains, providing a potential novel strategy to develop vaccines for both animal and human use.
HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences.

BACKGROUND Drug resistance mutations (DRMs) can serve as distinct, nonpolymorphic markers for evaluating diversity of expressed HIV-1. We screened for DRMs during early-acute viremia and examined the diversity in reverse transcriptase (RT) relative to envelope (env) in cases of transmitted drug resistance. METHODS We evaluated 111 longitudinal plasma samples collected every 2-7 days from 15 individuals who seroconverted for HIV-1 infection in 1994-2000. The samples were screened with sensitive polymerase chain reaction assays for the commonly transmitted M41L and K70R mutations and for K65R, which was undetected by bulk sequencing. Mutation-positive samples were further characterized by clonal sequencing of RT and env V1-V3. RESULTS Drug resistance mutations were detected in 4 of 15 seroconverters at 5-50 days of viral nucleic acid expression; most mutations disappeared about the time of seroconversion. Clonal sequencing verified low-level K65R at frequencies of 0.4%-4.9%. In each case, K65R coexisted unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of 1.6%-23.0%. In one seroconverter, variants with M184V and nonnucleoside RT inhibitor mutations were also identified at first RNA expression. Each seroconverter displayed a homogeneous V1-V3 env population. CONCLUSIONS Reverse-transcriptase DRMs demonstrate that the breadth of variants in transmission may be greater than what is reflected in envelope sequences.