A document by Yasmine Elsherif. Click on the document to view its contents.

Polycatenane gels have attracted extensive attention due to their high degree of freedom and mobility. However, the synthesis of poly[2]catenane gels reported to date all rely on the polymer as the backbone. Herein, we prepared poly[2]catenane gels based on entirely sequential assembly of small molecules. Monomer M1 with two unclosed rings was first prepared, which self-assembled to form supramolecular polymers(SPs) via hydrogen bonding and π-π interactions. Upon adding small molecule monomers M2 and M3 with aldehyde groups, ring closing of SPs occurred due to the amino groups in the SPs reacted with M2 to form imine bonds. In addition, M3, which has twice the number of aldehyde groups as M2, enabled SPs to ring-close, causing the proceeding of crosslinking process at the same time. Thus linear SPs were transformed into poly[2]catenane gel networks. Due to the presence of hydrogen bonds in the poly[2]catenane gel, the gel also possessed stimulus responsiveness and self-healing properties.

The Chinese hamster ovary (CHO) cell is a fibroblast-like cell that produces proteins with post-translational modifications similar to human glycosylation. It is widely used in the production of recombinant therapeutic proteins and monoclonal antibodies. Culturing CHO cells typically requires the addition of a certain proportion of fetal bovine serum (FBS) to maintain cell proliferation and passaging. However, serum is characterized by its complex composition, batch-to-batch variability, high cost, and potential risk of exogenous contaminants such as mycoplasma and viruses, which impact the purity and safety of the synthesized proteins. Therefore, search for serum alternatives and development of serum-free media for CHO-based protein biomanufacturing are of great significance. This review systematically summarizes the application advantages of CHO cells and strategies for high-density expression. It highlights the developmental trends of serum substitutes from human platelet lysates to animal-free extracts and microbial-derived substances and elucidates the mechanisms by which these substitutes enhance CHO cell culture performance and recombinant protein production, aiming to provide theoretical guidance for exploring novel serum alternatives and developing serum-free media for CHO cells.

Background and Purpose: Hyoscine butylbromide (HBB) has a low oral (PO) bioavailability. Further, limited data on its activity on non-gastrointestinal (GI) smooth muscle spasms after oral dosing are available, meaning its effect outside the GI tract has been questioned. This pharmacokinetic/pharmacodynamic (PK/PD) study, conducted using female rats, aims to cover this gap. Experimental Approach: PK study: HBB and atropine (comparator) were administered PO and IV to rats, and concentrations in plasma, and colon, uterus and urinary bladder (CUB) were measured. PD study-1: Concentration–response (C-R) curves of HBB and atropine (10-9–10-4M) were obtained for carbachol (CCH)-induced (10-5 M) pre-contracted CUB; PD study-2: CUB were pre-incubated with HBB and atropine at maximum concentrations (Cmax) from PK study, and CCH C-R curves (10-9–10-4 M) were obtained; PD study-3: HBB and atropine were administered PO and IV to rats as for PK study, CUB were collected at 0.5 h (IV) and 4 h (PO), and CCH C-R curves (10-9–10-4 M) were obtained. Key Results: PO HBB showed higher Cmax in CUB (192.5, 3.70 and 1.85 ng∙g-1, respectively) than plasma (0.008 ng∙mL-1). HBB and atropine reduced (concentration dependently) CCH-induced contractions in CUB. PO HBB showed highest spasmolytic activity in colon (40%), followed by uterus (30%) and urinary bladder (10%). Conclusion and Implications: This is the first comparative study investigating PO and IV HBB and atropine in GI and non-GI tissues. Despite low bioavailability, PO HBB accumulates and exerts spasmolytic effects outside the GI tract.

When it comes to software-intensive systems, system logs play a crucial role in Azures. Logs capture the system’s status and major occurrences at crucial times in time. The utility of log entries for data analysis and machine learning is severely limited due to their ad hoc, unstructured, and uncoordinated creation. Particularly in a DevOps setting, activities in data automation pipelines, visualizations, and analytics are prone to frequent disruptions due to uncontrolled change in log data format. Using a comprehensive case study at a top telecommunications firm as a foundation, this article outlines the primary obstacles faced by current methods of creating, storing, and overseeing the development of system logs data for sophisticated, big, software-intensive systems. Secondly, we provide a solution that is designed for machine learning and avoids the aforementioned problems when it comes to creating and controlling the development of log information in a Microsoft Azure DevOps environment. Third, we validate the strategy by conducting expert interviews, which prove that it solves the difficulties and challenges that have been identified. As a result, ML models that are fine-tuned for a certain dataset may rapidly become insufficient. Due to modifications to the characteristics and input data, a model that was once quite accurate may become inaccurate over time. Consequently, it is common to need distributed learning that incorporates dynamic model selection. Such a selection process involves replacing underperforming models with new ones, even if the old ones were fine-tuned for the previous data. It is possible to enhance the general accuracy of a set of ML models by using the famous Ensemble ML (EML) technique. There are a number of drawbacks to EML that should be considered. These include the lengthy model-building process, significant risks of overfitting, extensive training dataset requirements, costly processing resources, and the need for continual training. This research presents a new cloud-based approach to autonomous ML model tweaking and selection that outperforms current approaches in terms of automation of both model construction and selection. Prior to the automatic construction of focused supervised learning models, we employ unsupervised learning to get a deeper understanding of the data space. Specifically, we use a novel autoscaling technique to generate and assess ML algorithm instantiations on the fly, and we build a Cloud DevOps framework for autotuning with selection using container orchestration and communications between containers. Datasets pertaining to cloud network security are used to illustrate the suggested technique and tool.

A document by Gail Budhu. Click on the document to view its contents.

Covid-19 demanded new ways of working. In this paper, we present the experience of the Vaxi Taxi, a community-orientated model of care developed when Emergency Medical Services (EMS) pivoted in response to the Covid-19 pandemic, converting its ambulances into mobile vaccination units in the Western Cape, South Africa. Using a five-year long embedded research approach, we drew on traditions of organizational ethnography and critical action research. Data collection included documenting observations and reflections in a research diary during implementation. In addition, in-depth interviews, focus group discussions and a series of sensemaking discussions with academic research team members were done. Our analysis draws on the Everyday Health Systems Resilience framework (EHSR) which understands resilience as an emergent process underpinned by system capacities (cognitive, behavioral and contextual) that can be nurtured through response to stress and shock. Responses take the form of absorptive, adaptive or transformative strategies. We consider the Vaxi Taxi as adaptive resilience strategy that nurtured system capacities which may have transformative potential in future. For health practitioners, it highlights the value of creative problem-solving to generate ‘slack in the system’ and creating ‘spaces of unlearning’ in supporting adaptive strategies. However, the experience also highlighted that the relational work to support meaningful community relationships that enable trust take time. Routine EMS operations don’t support this trust building, and this requires alternative approaches. Finally, the paper represents a rare empirical example of an adaptive response to crisis tracked over time, and thus offers globally relevant lessons to the still-small EHSR literature.

In a previous study, conversational turns assessed on 43 infants using LENA technology at 18 months were found to predict socioemotional competencies at 30 months, controlling for their initial levels, child vocalizations, mother‘s warmth, and cumulative social risk. Using cross-lagged analysis, it was found that the direction was more likely to go from turns at 18 months to socioemotional competencies at 30 months, than the opposite. In this follow-up study, we examine the contribution of conversational turns at 30 months to socioemotional development of 33 children during school age (four years later, at 77 months of age). Using hierarchical regressions, we found that conversational turns at 30 months explained between 14.4% and 20.3% of variance in socioemotional development at 77 months.

Background：Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation surgery. Cryoballoon ablation (CBA), a traditional catheter ablation technique, enjoys widespread clinical application. In contrast, Pulsed field ablation (PFA) is a novel non thermal ablation technique for the treatment of atrial fibrillation (AF) patients, with safety comparable to traditional catheter ablation surgery. The present study aims to evaluate and compare the procedural efficiency and safety profiles of PFA and CBA in the management of AF. Methods：We performed a systematic search across PubMed, the Cochrane Library, and Embase databases, encompassing the literature up to February 2024, to inform our systematic review and meta-analysis. When assessing outcome indicators, the risk ratio (RR) and its corresponding 95% confidence interval (CI) were calculated for dichotomous variables. For continuous variables, the mean difference (MD) and the associated 95% CI were determined. In this scenario, a Relative Risk (RR) value less than 1 and a Mean Difference (MD) value less than 0 are deemed favorable for the PFA group. This could translate to a reduced likelihood of surgical complications or enhanced surgical performance within the PFA group. Results：In this analysis, nine observational studies encompassing 2,875 patients with AF were included. Among these, 38% (n=1105) were treated with PFA, while 62% (n=1,770) received CBA. The results indicated that PFA was associated with a significantly shorter surgical duration compared to CBA, with a mean difference (MD) of -10.49 minutes (95% CI [-15.50, -5.49]; p<0.0001). Nevertheless, no statistically significant differences were observed when comparing the two treatment cohorts concerning fluoroscopy time (MD 0.71; 95% CI [-0.45, 1.86]; p=0.23) and the recurrence of atrial arrhythmias during follow-up (RR 0.95; 95% CI 0.78-1.14; p=0.57).In terms of perioperative complications, the PFA group showed a significantly decreased risk of phrenic nerve palsy (RR 0.15; 95% CI 0.06-0.39; p<0.0001) and an increased risk of cardiac tamponade (RR 3.48; 95% CI 1.26-9.66; p=0.02) compared to the CBA group. No significant differences were noted between the PFA and CBA groups regarding the incidence of stroke/TIA (RR 0.99; 95% CI 0.30-3.22; p=0.99), Vascular access complication (RR 0.87; 95% CI 0.36-2.10; p=0.76), atrial esophageal fistula (RR 0.33; 0.01-8.13; p=0.50), and major or minor bleeding events (RR 0.39; 95% CI 0.09-1.74; p=0.22). Conclusions：Compared to CBA, PFA not only shortens surgical time but also shows non-inferiority regarding fluoroscopy time and the recurrence rate of atrial arrhythmias. Both PFA and CBA have distinct advantages concerning perioperative complications. This illustrates that PFA, while being effective, also preserves safety.

Background: Surgical site infection (SSI) is a frequent complication following emergency equine laparotomy. It negatively impacts equine welfare, increases treatment costs and is a hospital biosecurity risk justifying investigations of ways to reduce SSI incidence. Objectives: To determine if a sutured-on stent dressing for anaesthetic recovery reduces SSI in horses following emergency laparotomy. Study design: Randomised controlled trial. Methods: Eligible horses undergoing emergency exploratory laparotomy were enrolled. Horses were randomised to have a sutured-on stent dressing (intervention) or standard adhesive textile dressing (control) placed for incisional protection during anaesthetic recovery. Horses were followed up to 90 days postoperatively. Data were analysed according to intention-to-treat principles. Time to SSI (primary outcome) for each group was analysed using a Cox proportional hazard model. Secondary outcomes (SSI during hospitalisation, pyrexia during hospitalisation, days hospitalisation and incisional hernia formation at 90 days) were analysed using Chi-squared tests and a univariable logistic regression model (categorical data) or by comparing means between groups (continuous data). Results: The study included 352 horses (167 intervention group, 185 control group). SSI developed in 101 horses (28.7%) at a mean of 9.7 days (SD 4.6 days). Rate of SSI was not significantly different between intervention and control groups unadjusted (Hazard Ratio [HR] 0.83, 95% CI 0.56 - 1.23, P=0.36) or adjusted for variables significantly associated with rate of SSI (HR 0.88, 95% CI 0.59 – 1.30, P=0.51). There were no significant differences in secondary outcomes between intervention and control groups. Main limitations: This study was performed at a single centre and only evaluated incisional protection for anaesthetic recovery. Conclusions: Use of a sutured-on stent dressing for anaesthetic recovery did not reduce the rate of SSI compared to a textile adhesive dressing. Further RCT are required to investigate efficacy of other interventions on reduction of SSI following emergency laparotomy

Metabolomics plays a pivotal role in elucidating the intricate chemical communications in plant-microbe interactions. This comprehensive review explores how metabolomics has transformed our understanding by uncovering metabolic dynamics during pathogen infections, identifying metabolites crucial for plant resistance, and advancing metabolomics-driven breeding strategies for disease-resistant crops. The review underscores metabolomics' capacity to unveil the metabolic fingerprints of symbiotic relationships, emphasizing the pivotal role of signaling metabolites in these interactions. Furthermore, it discusses metabolomics' role in discovering novel bioactive compounds from endophytes and their potential applications in agriculture and biotechnology. By synthesizing recent advancements, this review provides a thorough exploration of metabolomics' transformative impact on deciphering chemical dialogues between plants and their microbial counterparts. This insight not only enhances our understanding of plant-microbe interactions but also lays the foundation for sustainable agricultural practices aimed at resilience and productivity.

A document by Wanting Yang. Click on the document to view its contents.

Understanding microbial adaptation is crucial for predicting how soil carbon dynamics and global biogeochemical cycles will respond to climate change. This study employs the DEMENT model of microbial decomposition, along with empirical mutation and dispersal rates, to explore the roles of mutation and dispersal in adaptation of soil microbial populations to shifts in litter chemistry, changes that are anticipated with climate-driven vegetation dynamics. Following a change in litter chemistry, mutation generally allows for a higher rate of litter decomposition than dispersal, especially when dispersal predominantly introduces genotypes already present in the population. These findings challenge the common idea that mutation rates are too low to affect ecosystem processes on ecological timescales. These results demonstrate that evolutionary processes, such as mutation, can help maintain ecosystem functioning as the climate changes.

This paper presents an experimental study carried out to understand the behavior of rubberized concrete columns under axial loads, and numerically analyze the behavior of rubberized reinforced concrete (RRC) columns under cyclic loading. Experimental tests were carried out on twelve large-scale columns with square and circular cross sections, with replacement of fine aggregate at percentages with crumb rubber (CR) of 0%, 10%, and 15% under axial loading. Square RRC columns were examined by a finite element program (ABAQUS) under cyclic loading. The results of the experiments showed that the columns with crumb rubber had a lower load capacity than those without crumb rubber when exposed to axial loads. The obtained numerical results showed good agreement with the experimental results, indicating the ability of the numerical model to simulate the behavior of rubberized concrete columns under axial and cyclic loads. Moreover, the replacement of fine aggregate by 10% and 15% with crump rubber increases the lateral displacement and ductility of the column under cyclic loading. Rubber can be used in concrete columns with no significant effect on their ultimate strength or deformability. However, crumb rubber concrete (CRC) can delay and reduce the amount of damage occurring under cyclic loading.

This study describes the design of a transducer for bone conduction implants (BCIs) that combines a piezoelectric element and a displacement amplifier. To develop a displacement amplifier with the maximum possible amplification ratio, theoretical analysis was performed to derive the parameters that affect the amplification ratio. Parametric sweep analysis was conducted to calculate the amplification ratio according to changes in the various parameters. The resulting optimal displacement amplifier afforded the maximum amplification ratio when the beam thickness, depth, inclination angle, and length were 0.15 mm, 1.2 mm, 6.5°, and 4 mm, respectively. The displacement amplifier with these optimal parameter values amplified the piezoelectric element displacement by approximately 7.7-fold. Frequency characteristic analysis by weight was performed to derive a mechanical resonance location with frequency characteristics that appropriately compensated for hearing loss. As a result of this analysis, when a weight of 0.3 g was applied to the displacement amplifier, the mechanical resonance was that required for BCI transducers.

The validation of a bioanalytical method is essential to ascertain its suitability for a specific purpose and ensure the accuracy of its analytical outcomes, particularly within the pharmaceutical industry. The pseudovirion-based neutralization assay (PBNA) is considered the gold standard for detecting and quantifying neutralizing antibodies against human papillomavirus in the development of the disease-prevent vaccines. This paper introduces a modified high-throughput triple-color PBNA method designed to simultaneously detect the neutralizing antibodies against as many as 14 HPV types. The primary objective is to present a comprehensive validation of the triple-color PBNA method applicable to general vaccine immunogenicity assays. The results demonstrate good specificity, accuracy, precision, linearity, robustness, and applicability of the method. This innovative triple-color PBNA provides a high-throughput approach for large-scale immunogenicity assessments that vaccine developers might encounter, overcoming limitations of labor-intensive and complex nature associated with traditional neutralization assays. The research establishes a robust foundation and good guiding example for evaluating vaccine responses in both preclinical and clinical phases, offering valuable insights to the field.

The oogenesis-flight syndrome reflects the temporal allocation of energy resources between dispersal / migration and reproduction and is a key concept in research on migratory behaviour in animals. In migratory butterflies, host plant abundance and quality may act as environmental cues to switch between the two states, but the mechanisms regulating this process are virtually unknown. Here, we used an experimental set-up to assess how variation in host plant abundance affected the activity of regulatory elements in the painted lady butterfly (Vanessa cardui), a model species for insect migratory behaviour studies. Chromatin immunoprecipitation (ChIP-seq) was used to evaluate histone tail modifications of H3K27ac and H3K4me3, as a proxy for regulatory activity. The results indicate that recently eclosed females that had access to host plants invested in reproduction at an earlier stage and that variation in host plant abundance triggered significant differences in regulatory element activity via histone tail acetylation. The functions of genes in the vicinity of differentially activated regions were primarily associated with metabolism, egg shell formation, female receptivity, muscle activity, pheromone binding and chromosome maintenance. Our results provide a first glimpse into the regulatory underpinnings of how females perceive the environment and allocate resources for either migration or reproduction and a starting point for more detailed understanding of the links between environmental variation, gene regulation and behaviour in butterflies.

Background : Studies have shown a high risk of interstitial lung disease after hospitalization with adenovirus (AdV) and a high risk of asthma after hospitalization with respiratory syncytial virus (RSV) Objective : To clarify to what extent children hospitalized with respiratory tract infection caused by AdV or RSV develop pulmonary disease Design : Register-based cohort study Methods : Data on infections with AdV and RSV were coupled to data on asthma, asthma medication bronchiectasia, and interstitial lung disease including bronchiolitis obliterans during a follow-up time of 15 – 20 years. An age-matched control group was also generated. The risks of subsequent lung disease and/or having received asthma medication and hazard ratios (HRs) for asthma between the index groups and the control group were computed Findings : In total 4704 children were included. Less than 5 cases of interstitial lung disease or bronchiectasia were found in any group. After hospitalization with AdV or RSV the risk of acquiring an asthma diagnosis or having received asthma medication during follow up was 29% and 65%, respectively for AdV, and 22% and 51%, respectively for RSV; corresponding to adjusted HRs of 2.16 (0.92-5.07), 2.60 (1.57-4.31), 2.87 (2.30-3.58), and 2.37 (2.07-2.71), respectively Conclusion : We could not confirm an increased risk of interstitial lung disease after infection with AdV. However, there is a considerable risk of asthma after hospitalization with AdV or RSV and with respect to RSV the risk is higher than previously reported as expressed by the fraction having received asthma medication during follow up

To avoid reaching lethal temperatures during periods of heat stress, plants may acclimate either their biochemical thermal tolerance, or leaf morphological and physiological characteristics to reduce leaf temperature (T leaf). While emerging evidence indicates that plants from warmer environments have a greater capacity to regulate T leaf, the extent of intraspecific variation and contribution of provenance is relatively unexplored. We tested whether upland and lowland provenances of four tropical tree species grown in a common garden differed in their thermal safety margins by measuring leaf thermal traits, midday leaf-to-air temperature differences (∆T leaf), and critical leaf temperature defined by chlorophyll fluorescence (T­ crit). Provenance variation was highly species- and trait- specific. Higher ∆T leaf and T­ crit were observed in the lowland provenance for Terminalia microcarpa, and in the upland provenance for Castanospermum australe, with no provenance differences observed in the other two species. Within-species covariation of T crit and ∆T leaf led to a convergence of thermal safety margins across provenances. These findings suggest that when grown under common conditions, lowland and upland provenances may not differ substantially in their vulnerability (defined here as thermal safety margin) to heat stress, despite differences in operating temperatures and T crit.

Title:

Objective: To evaluate the impact of twin dating by ultrasound-measured crown-rump length (CRL) of the larger (CRL-L), smaller (CRL-S) or mean twin measurement (CRL-M) on the rates of preterm birth (PTB) and detection of fetal growth restriction. Design: A cohort study. Setting: A tertiary fetal medicine centre (London, UK). Population or sample: All twin pregnancies between 1998 and 2023 who underwent ultrasound assessment of first trimester CRL and fetal growth. Methods: Data collection included CRL measurement, estimated fetal weight (EFW), pregnancy outcome and birthweight (BW) for each twin. Pregnancies were retrospectively re-dated by CRL-S, CRL-L and CRL-M. Main outcome measures: Small for gestational age (SGA) <10 th centile and PTB rates. Results: Of the 1129 twin pairs median CRL was 61mm (IQR:56.0-66.0) and 63mm (IQR:58.4-68.9) for the smaller and larger twin respectively with a mean discordance of 4.0%. Prenatal SGA diagnosis occurred in 19.8% and 23.1% of smaller twins when dated by CRL-S and CRL-L respectively. When pregnancies were dated by CRL-M versus CRL-S or CRL-L there was no difference in prenatal SGA diagnosis (p=0.275 and p=0.419); SGA at birth (p=0.132 and p=0.325); or PTB (p=1.00 and p=0.765 respectively). Conclusions: Dating by the smaller, larger or mean-twin CRL doesn’t significantly alter rates of extreme preterm birth, SGA detection or SGA birth. Dating by the mean twin CRL reduces stigmatisation of the smaller twin, alleviating parental anxiety, whilst retaining the utility of accurate gestational age assessment without impacting on clinical outcomes.

When approaching the common femoral artery (CFA), although arterial puncture is successful, inserting the sheath along the guidewire can sometimes prove challenging. This is particularly true in cases of severe CFA calcification, a history of multiple punctures due to chronic limb-threatening ischemia, or after CFA endarterectomy. Typically, attempts are made to

Carbon sequestration by application of organic materials and biochar in soil is an important strategy to increase soil organic carbon (SOC), but the stability of SOC, particularly humic substances (HS) vary with the types of organic material. Cotton straw and its derived compost and biochar were added with equivalent carbon content to soil and incubated for 180 days. The structural characteristics of humic acid (HA), fulvic acid (FA) and humin (Hu) were investigated using solid-state 13C nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The results showed that biochar treatment increased the aryl C of HA, FA, and Hu by 1.38%, 1.68%, and 10.46% compared to straw treatment and increased the aryl C of HA, FA, and Hu by 1.46%, 1.99% and 2.01% compared to compost treatment. The O-alkyl C of HA was 10.59% and 10.65% in high biochar/straw and biochar/compost ratios respectively, while it was 9.81% and 9.61% in low biochar/straw and biochar/compost ratios. In addition, the O-alkyl C of FA was 62.83% and 58.48% in high ratios of biochar/straw and biochar/compost, respectively, while it was 55.85% and 55.94% in low ratios of biochar/straw and biochar/compost. These results suggest that biochar is advantageous for aryl C formation of FA and Hu due to its high aryl C content, whereas straw or compost is advantageous for alkyl C formation of HA. The stability of aryl C and O-alkyl C of HA, FA, and Hu can be improved in soils by incorporating biochar in combination with straw or compost.

Background: Investigating and documenting novel mutations within inborn errors of immunity (IEIs) has demonstrably enriched our comprehension of disease causation. This encompasses elucidating the clinical and immunological presentations linked to specific gene alterations, ultimately leading to refined classification precision and, optimistically, improved treatment modalities. The present study aims to the profiles of patients within the Iranian IEI registry exhibiting mutations within the NFKB signaling pathway. Methods: Peripheral blood mononuclear cells were utilized for immunophenotyping of B and T lymphocyte subsets, and proliferation assays. Immunoblotting was employed to assess the expression levels of the corresponding protein in each patient harboring the respective variant. Results: The study cohort encompassed 17 patients: 8 with NFKB1 mutations, 5 with NFKB2 mutations, 3 with IKBKB mutations, and 1 with an IKBKG mutation. All NFKB1 and NFKB2 mutations presented as heterozygous, whereas IKBKB mutations were homozygous and the IKBKG mutation was hemizygous. The predominant clinical features included hypogammaglobulinemia and B cell subset disturbances, with T cell subsets and proliferation being normal in most, though not all, cases. Protein expression in patients generally mirrored healthy controls, except for two individuals harboring NFKB2 mutations. Conclusions: These findings provide novel IEI cases linked to NFKB pathway mutations. Comprehensive evaluation and functional analysis of novel mutations, confirming potential impacts on disease manifestation, also highlight the need for specialized care and further research within immunodeficiency disorders.