[Thermal Environment Evolution and Response Mechanism of Urban Sprawl Based on Multi-source Data].

Improving the urban thermal environment and improving the quality of human settlements are important prerequisites for creating ecologically livable cities. The current research on the relationship between urban expansion and the thermal environment is mostly based on remote sensing data, and the application of multi-source data is weak. Here, we selected the Xi'an metropolitan core area, measured the urban expansion and temporal and spatial evolution of the thermal environment based on Landsat remote sensing images in 2010 and 2020, and used multi-source data, such as interest points and the Baidu thermal index, to study the response mechanism of the urban thermal environment through geoscience statistical analysis methods.

Variable-heavy (VH) families influencing IgA1&2 engagement to the antigen, FcαRI and superantigen proteins G, A, and L.

Interest in IgA as an alternative antibody format has increased over the years with much remaining to be investigated in relation to interactions with immune cells. Considering the recent whole antibody investigations showing significant distal effects between the variable (V) and constant (C)- regions that can be mitigated by the hinge regions of both human IgA subtypes A1 and A2, we performed an in-depth mechanistic investigation using a panel of 28 IgA1s and A2s of both Trastuzumab and Pertuzumab models. FcαRI binding were found to be mitigated by the differing glycosylation patterns in IgA1 and 2 with contributions from the CDRs.

More Than Meets the Kappa for Antibody Superantigen Protein L (PpL).

Immunoglobulin superantigens play an important role in affinity purification of antibodies and the microbiota-immune axis at mucosal areas. Based on current understanding, Protein A (SpA), Protein G (SpG) and Protein L (PpL) are thought to only bind specific regions of human antibodies, allowing for selective purification of antibody isotypes and chains. Clinically, these superantigens are often classified as toxins and increase the virulence of the producing pathogen through unspecific interactions with immune proteins.

Augmenting recombinant antibody production in HEK293E cells: optimizing transfection and culture parameters.

Background: Optimizing recombinant antibody production is important for cost-effective therapeutics and diagnostics. With impact on commercialization, higher productivity beyond laboratory scales is highly sought, where efficient production can also accelerate antibody characterizations and investigations.

Methods: Investigating HEK293E cells for mammalian antibody production, various transfection and culture parameters were systematically analyzed for antibody light chain production before evaluating them for whole antibody production.

Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen.

The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common mechanism may underlie both the TCR and IgE nickel binding. Focusing on Trastuzumab and Pertuzumab IgE variants as serendipitous investigation models, we found Ni-NTA interactions independent of Her2 binding to be due to glutamine stretches.

Sagacity in antibody humanization for therapeutics, diagnostics and research purposes: considerations of antibody elements and their roles.

The humanization of antibodies for therapeutics is a critical process that can determine the success of antibody drug development. However, the science underpinning this process remains elusive with different laboratories having very different methods. Well-funded laboratories can afford automated high-throughput screening methods to derive their best binder utilizing a very expensive initial set of equipment affordable only to a few.

Essentially Leading Antibody Production: An Investigation of Amino Acids, Myeloma, and Natural V-Region Signal Peptides in Producing Pertuzumab and Trastuzumab Variants.

Boosting the production of recombinant therapeutic antibodies is crucial in both academic and industry settings. In this work, we investigated the usage of varying signal peptides by antibody V-genes and their roles in recombinant transient production, systematically comparing myeloma and the native signal peptides of both heavy and light chains in 168 antibody permutation variants. We found that amino acids count and types (essential or non-essential) were important factors in a logistic regression equation model for predicting transient co-transfection protein production rates.

An Alternative HIV-1 Non-Nucleoside Reverse Transcriptase Inhibition Mechanism: Targeting the p51 Subunit.

The ongoing development of drug resistance in HIV continues to push for the need of alternative drug targets in inhibiting HIV. One such target is the Reverse transcriptase (RT) enzyme which is unique and critical in the viral life cycle-a rational target that is likely to have less off-target effects in humans. Serendipitously, we found two chemical scaffolds from the National Cancer Institute (NCI) Diversity Set V that inhibited HIV-1 RT catalytic activity.

Highly responsive and rapid hydrogen peroxide-triggered degradation of polycaprolactone nanoparticles.

We synthesized an oxidation-responsive polycaprolactone (O-PCL) bearing pendant arylboronic esters as H2O2-responsive motifs. H2O2 induces fast depolymerization of O-PCL within days. Nanoparticles formulated from O-PCL disintegrate and release payload in response to concentrations of H2O2 (50 μM) that are relevant to human disease.

The quantification of antibody elements and receptors subunit expression using qPCR: The design of VH, VL, CH, CL, FcR subunits primers for a more holistic view of the immune system.

The expression levels of immunoglobulin elements and their receptors are important markers for health and disease. Within the immunoglobulin locus, the constant regions and the variable region families are associated with certain pathologies, yet a holistic view of the interaction between the expressions of the multiple genes remain to be fully characterized. There is thus an important need to quantify antibody elements, their receptors and the receptor subunits in blood (PBMC cDNA) for both screening and detailed studies of such associations.

Structure-guided development of purine amide, hydroxamate, and amidoxime for the inhibition of non-small cell lung cancer.

An 8-oxopurine-6-carboxamide compound (1a) was previously identified as an inhibitor of non-small cell lung cancer (NSCLC). In this study, more than 30 purine-6-carboxamide derivatives with variations at the C2, N7, C8, and N9 positions were synthesized to investigate the structure-activity relationship as a basis for the construction of an advanced pharmacophore model. This model suggests that purine-6-hydroxamate and purine-6-amidoxime analogs could form more hydrogen bonds with a target protein to enhance the inhibitory activities against H1975 cells.

Role of the IgE variable heavy chain in FcεRIα and superantigen binding in allergy and immunotherapy.

Background: Variable heavy chain (VH) family frameworks (FWRs) have been reported to affect antibody receptor and superantigen binding; however, such effects in IgE remain largely unknown. Given that VH family biases have been previously reported in IgE of certain allergies, there is a need to investigate this phenomenon for biotechnological and therapeutic purposes.

Objective: We sought to investigate the effects of VH families on IgE interaction with FcεRIα, anti-IgE omalizumab, antigen, and superantigen protein A (spA) by using the pertuzumab and trastuzumab IgE models.

Caries-related risk factors of obesity among 18-year-old adolescents in Hong Kong: a cross-sectional study nested in a cohort study.

Background: Socio-economic status, health awareness, and dietary habits have been reported as common risk factors of dental caries and obesity. The present study aimed to explore shared mediators between caries and obesity and to estimate the effects of caries-related factors on adiposity.

Methods: This was a cross-sectional study among adolescents aged 18 years.

Longitudinal association between obesity and periodontal diseases among secondary school students in Hong Kong: a prospective cohort study.

Background: There is no consensus opinion regarding the association between obesity and periodontal diseases among children and adolescents in the literature.

Methods: A prospective observational cohort study was conducted in a Hong Kong cohort at age 12, 15 and 18. CPI and various obesity indices including BMI, WC, WHR, WHtR, and TRSKF were recorded during each wave of data collection.

Author Correction: The effects of Antibody Engineering CH and CL in Trastuzumab and Pertuzumab recombinant models: Impact on antibody production and antigen-binding.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Allosteric Effects between the Antibody Constant and Variable Regions: A Study of IgA Fc Mutations on Antigen Binding.

Therapeutic antibodies have shifted the paradigm of disease treatments from small molecules to biologics, especially in cancer therapy. Despite the increasing number of antibody candidates, much remains unknown about the antibody and how its various regions interact. Recent findings showed that the antibody constant region can govern localization effects that are useful in reducing side effects due to systemic circulation by the commonly used IgG isotypes.

Effect of VH-VL Families in Pertuzumab and Trastuzumab Recombinant Production, Her2 and FcγIIA Binding.

Many therapeutic antibodies are humanized from animal sources. In the humanization process, complementarity determining region grafting is tedious and highly prone to failure. With seven known VH families, and up to six known κ VL families, there are choices aplenty.

The effects of Antibody Engineering CH and CL in Trastuzumab and Pertuzumab recombinant models: Impact on antibody production and antigen-binding.

Current therapeutic antibodies such as Trastuzumab, are typically of the blood circulatory IgG1 class (Cκ/ CHγ1). Due to the binding to Her2 also present on normal cell surfaces, side effects such as cardiac failure can sometimes be associated with such targeted therapy. Using antibody isotype swapping, it may be possible to reduce systemic circulation through increased tissue localization, thereby minimising unwanted side effects.

Longitudinal Association between Obesity and Dental Caries in Adolescents.

Objective: To investigate the longitudinal association between obesity and dental caries among adolescents.

Study Design: The present cohort study was conducted among a random sample of 12-year-old adolescents in Hong Kong. Two rounds of follow-up were performed when the participants were aged 15 and 18 years.

The role of Antibody Vκ Framework 3 region towards Antigen binding: Effects on recombinant production and Protein L binding.

Antibody research has traditionally focused on heavy chains, often neglecting the important complementary role of light chains in antibody formation and secretion. In the light chain, the complementarity-determining region 3 (VL-CDR3) is specifically implicated in disease states. By modulating VL-CDR3 exposure on the scaffold through deletions in the framework region 3 (VL-FWR3), we further investigated the effects on secretion in recombinant production and antigen binding kinetics.

Structural analyses of 2015-updated drug-resistant mutations in HIV-1 protease: an implication of protease inhibitor cross-resistance.

Background: Strategies to control HIV for improving the quality of patient lives have been aided by the Highly Active Anti-Retroviral Therapy (HAART), which consists of a cocktail of inhibitors targeting key viral enzymes. Numerous new drugs have been developed over the past few decades but viral resistances to these drugs in the targeted viral enzymes are increasingly reported. Nonetheless the acquired mutations often reduce viral fitness and infectivity.

Discovery of a novel splice variant of Fcar (CD89) unravels sequence segments necessary for efficient secretion: A story of bad signal peptides and good ones that nevertheless do not make it.

The IgA receptor, Fcar (CD89) consists of 5 sequence segments: 2 segments (S1, S2) forming the potential signal peptide, 2 extracellular EC domains that include the IgA binding site, and the transmembrane and cytoplasmic tail (TM/C) region. Numerous Fcar splice variants have been reported with various combinations of the sequence segments mentioned above. Here, we report a novel splice variant termed variant APD isolated from a healthy volunteer that lacks only the IgA-binding EC1 domain.

Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin.

Microtubule targeting agents (MTAs) constitute a class of drugs for cancer treatment. Despite many MTAs have been proven to significantly improve the treatment outcomes of various malignancies, resistance has usually occurred. By selection from a two million entry chemical library based on the efficacy and safety, we identified purine-type compounds that were active against lung small cell lung cancer (NSCLC).

Anthropometric measurements and periodontal diseases in children and adolescents: a systematic review and meta-analysis.

The aim of this systematic review was to identify and summarize evidence of the association between anthropometric measurements and periodontal status in children and adolescents. We searched PubMed, Institute for Scientific Information Web of Knowledge, Cochrane Library, and 7 additional databases, following the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, up to December 2014. Observational studies reporting data on the association between anthropometric measurements and periodontal diseases in 2-18-y-old participants were included.

Fast reversible single-step method for enhanced band contrast of polyacrylamide gels for automated detection.

Staining SDS-PAGE is commonly used in protein analysis for many downstream characterization processes. Although staining and destaining protocols can be adjusted, they can be laborious, and faint bands often become false negatives. Similarly, these faint bands hinder automated software band detections that are necessary for quantitative analyses.