Exploring the Connection between Sequence and Coordinated Gene Activity for Adjacent Promoter Pairs

Proper control of gene expression is necessary, yet it\u27s unclear how regulatory elements interact with only correct genes in the genome. One possibility is that the specialized regulatory regions immediately surrounding transcription start sites, known as promoters, dictate the ability to interact with nearby regulatory elements. If true, we expect genes with similar promoter sequences to be co-expressed, and those with dissimilar promoters to have differential expression. We determined co-expression indices for all adjacent promoters in D. melanogaster using data from several sources, including bi-hourly embryonic time-course data generated by modENCODE(Nature 459:927), a complete life-cycle time-course from RAMPAGE profiling (Genome Res. 23:169), and GRO-seq-derived promoter activity data for cultured S2 cells (Cell Rep. 2:1025). We then used an alignment-free sequence similarity measure (“N2”) to calculate relatedness scores for every adjacent promoter pair and tested for correlation between sequence relatedness and co-expression index. Distances between paired promoters were also tested for correlation with co-expression. Resulting analyses of the RAMPAGE dataset showed a positive trend between co-expression and sequence similarity among a small subset of adjacent promoters as compared to randomized data. No correlation appeared for the majority of pairs overall. A smaller minority of modENCODE data showed similar positive correlation. This disparity was likely due to the longer and higher resolution time-course of the RAMPAGE dataset. The co-expressed groups of promoters from S2 cells did not vary substantially from dissimilarly expressed pairs in terms of their sequence similarity. Although these analyses failed to reveal a strong connection between promoter sequence and coordinated gene activity, other metrics may provide better insight. We are continuing to evaluate other sequence similarity measures, for instance whether discrete sets of core promoter motifs (rather than entire promoter sequences) are adequate in classifying similarities in promoter activity

Exploring the Connection between Sequence and Coordinated Gene Activity for Adjacent Promoter Pairs

Proper control of gene expression is necessary, yet it\u27s unclear how regulatory elements interact with only correct genes in the genome. One possibility is that the specialized regulatory regions immediately surrounding transcription start sites, known as promoters, dictate the ability to interact with nearby regulatory elements. If true, we expect genes with similar promoter sequences to be co-expressed, and those with dissimilar promoters to have differential expression. We determined co-expression indices for all adjacent promoters in D. melanogaster using data from several sources, including bi-hourly embryonic time-course data generated by modENCODE(Nature 459:927), a complete life-cycle time-course from RAMPAGE profiling (Genome Res. 23:169), and GRO-seq-derived promoter activity data for cultured S2 cells (Cell Rep. 2:1025). We then used an alignment-free sequence similarity measure (“N2”) to calculate relatedness scores for every adjacent promoter pair and tested for correlation between sequence relatedness and co-expression index. Distances between paired promoters were also tested for correlation with co-expression. Resulting analyses of the RAMPAGE dataset showed a positive trend between co-expression and sequence similarity among a small subset of adjacent promoters as compared to randomized data. No correlation appeared for the majority of pairs overall. A smaller minority of modENCODE data showed similar positive correlation. This disparity was likely due to the longer and higher resolution time-course of the RAMPAGE dataset. The co-expressed groups of promoters from S2 cells did not vary substantially from dissimilarly expressed pairs in terms of their sequence similarity. Although these analyses failed to reveal a strong connection between promoter sequence and coordinated gene activity, other metrics may provide better insight. We are continuing to evaluate other sequence similarity measures, for instance whether discrete sets of core promoter motifs (rather than entire promoter sequences) are adequate in classifying similarities in promoter activity

Optimizing Deep Learning Models For Raspberry Pi

Deep learning models have become increasingly popular for a wide range of applications, including computer vision, natural language processing, and speech recognition. However, these models typically require large amounts of computational resources, making them challenging to run on low-power devices such as the Raspberry Pi. One approach to addressing this challenge is to use pruning techniques to reduce the size of the deep learning models. Pruning involves removing unimportant weights and connections from the model, resulting in a smaller and more efficient model. Pruning can be done during training or after the model has been trained. Another approach is to optimize the deep learning models specifically for the Raspberry Pi architecture. This can include optimizing the model's architecture and parameters to take advantage of the Raspberry Pi's hardware capabilities, such as its CPU and GPU. Additionally, the model can be optimized for energy efficiency by minimizing the amount of computation required. Pruning and optimizing deep learning models for the Raspberry Pi can help overcome the computational and energy constraints of low-power devices, making it possible to run deep learning models on a wider range of devices. In the following sections, we will explore these approaches in more detail and discuss their effectiveness for optimizing deep learning models for the Raspberry Pi

Haploidentical Hematopoietic Stem-Cell Transplantation in Adults

Haploidentical hematopoietic stem-cell transplantation is an alternative transplant strategy for patients without an HLA-matched donor. Still, only half of patients who might benefit from transplantation are able to find an HLA-matched related or unrelated donor. Haploidentical donor is readily available for many patients in need of immediate stem-cell transplantation. Historical experience with haploidentical stem-cell transplantation has been characterised by a high rejection rate, graft-versus-host disease, and transplant-related mortality. Important advances have been made in this field during the last 20 years. Many drawbacks of haploidentical transplants such as graft failure and significant GVHD have been overcome due to the development of new extensive T cell depletion methods with mega dose stem-cell administration. However, prolonged immune deficiency and an increased relapse rate remain unresolved problems of T cell depletion. New approaches such as partial ex vivo or in vivo alloreactive T cell depletion and posttransplant cell therapy will allow to improve immune reconstitution in haploidentical transplants. Results of unmanipulated stem-cell transplantation with using ATG and combined immunosuppression in mismatched/haploidentical transplant setting are promising. This paper focuses on recent advances in haploidentical hematopoietic stem-cell transplantation for hematologic malignancies

KIR genotype and haplotype repertoire in Kuwaiti healthy donors, hematopoietic cell transplant recipients and healthy family members

The gene complex located on chromosome 19q13.4 encodes the Killer-cell Immunoglobulin-like Receptors (KIRs), which exhibit remarkable polymorphism in both gene content and sequences. Further, the repertoire of KIR genes varies within and between populations, creating a diverse pool of KIR genotypes. This study was carried out to characterize KIR genotypes and haplotypes among 379 Arab Kuwaiti individuals including 60 subjects from 20 trio families, 49 hematopoietic cell transplantation (HCT) recipients and 270 healthy Kuwaiti volunteer HCT donors. KIR Genotyping was performed by a combination of reverse sequence specific oligonucleotide probes (rSSO) and/or Real Time PCR. The frequencies of KIR genes in 270 healthy Kuwaiti volunteer donors were compared to previously reported frequencies in other populations. In addition, we compared the differences in KIR repertoire of patients and healthy donors to investigate the reproducibility of previously reported significant differences between patients with hematological malignancies and healthy donors. The observed frequencies in our cohort volunteer HCT donors was comparable to those reported in neighboring Arab populations. The activating genes KIR2DS1, KIR2DS5 and KIR3DS1 and the inhibitory gene KIR2DL5 were significantly more frequent in patients compared to healthy donors, however, none of the previously reported differences were reproducible in our Kuwaiti cohort. This report is the first description of KIR gene carrier frequency and haplotype characterization in a fairly large cohort of the Kuwaiti population, which may have implications in KIR based HCT donor selection strategies.We thank Amanda Willis and Shawna Kennedy from Baylor University Medical Center for assisting in the initial analysis of KIR genotyping data. We are very grateful for Basil Khuder, the bioinformatics scientist at Phoenix Children's Hospital for imputing the missing KIR gene carrier frequency required to generate the PCA graphical representation. This research was supported by a grant from the Kuwait Foundation for the Advancement of Sciences, Kuwait (P116-13MC-08) and Research Core Facility of the Health Sciences Center (RCF - Grant No: SRUL02/13), Kuwait University, Kuwait.Scopu

Elucidating the effects of reaction time on the physicochemical characterization of valorized synthesized alumina

Aluminum waste-can management in Malaysia has recently become a serious environmental and public health issue, particularly in metropolitan areas. This has prompted the need to valorize these waste-cans into value-added products using the most economical and environmentally friendly techniques. In this study, the sol–gel technique was used to synthesize high-quality alumina from the aluminum waste-cans collected. From this method, the observed peaks of the synthesized alumina were identified as diaspore (α-AlO(OH)), boehmite (γ-AlO(OH)), aluminum oxide, or gamma-alumina (γ-Al2O3 ) crystalline structure and corundum. The morphological configuration, microstructure, and functional group properties of the synthesized alumina were evaluated. All the synthesized alumina exhibited a non-spherical shape and appeared to have hexagonal-like shape particles. Moreover, the XRD patterns of the synthesized alumina AL-6-30 and AL-12-30 exhibited a small angle (1–10◦ ) with no XRD peak, which indicated a mesoporous pore structure with no long-range order. The overall results of γ-alumina synthesized from the aluminum waste-cans showed an optimal condition in producing a highly structured γ-alumina with excellent surface-area characteristics. The synthesized alumina exhibited stronger and highly crystalline functional characteristics almost comparable with the commercially available brands on the market

A cross cultural study of gender differences in omnichannel retailing contexts

This research examines gender difference in omnichannel experience in modern shopping malls, combining personal, physical and virtual encounters. It proposes a new theoretical model: the gender-based shopping mall omnichannel experience model. Data was collected using 1139 questionnaires completed by millennial shoppers in the United Kingdom and United Arab Emirates. Data was analysed using partial least squares. The results showed a shift in males shopping behaviour as they pay more attention to peer interaction on social platforms, service excellence, convenience, diversity and personalisation in shopping malls than female shoppers, while aesthetics and privacy are more important for female shoppers

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe