The role and regulation of CD1d in normal and pathological B cells

This work provides novel insights into the intersection between two critical areas of immunology, the CD1d-invariant NKT (iNKT) axis and B cells. CD1d is a non-polymorphic, MHC class I-like molecule, which presents phospho- and glycosphingo-lipid antigens to a subset of CD1d-restricted T cells called iNKT cells. CD1d is expressed on a variety of antigen presenting cells and the CD1d-iNKT cell axis regulates nearly all aspects of the innate and adaptive immune response. Expression of CD1d on B cells allows these cells to form cognate interactions with iNKT cells. Emerging evidence suggests, however, that expression of CD1d on B cells is variable, both on “normal” B cells during humoral immune responses, and also on “pathological” B cells in certain B cell disorders. In this work, I investigate in detail the expression of CD1d on B cells across a range of conditions. Using both human and murine germinal centre (GC) B cells as a model for normal B cells, I show for the first time that CD1d expression changes dynamically, both at the surface protein and transcriptional level. CD1d falls to a nadir as a naïve B cell enters the GC, and subsequently rises again in post GC B cells. I then provide evidence that the loss of CD1d expression is paralleled in pathological B cells, specifically in Epstein-Barr Virus infection of B cells and the plasma cell disorder Multiple Myeloma. In these conditions, CD1d is again downregulated at both the surface and transcriptional level. Having established that CD1d expression is lost in certain scenarios, I attempt to elucidate the biological significance of this downregulation. I approach this aim by attempting to constitutively express CD1d in murine GC B cells, and subsequently assessing the GC reaction. Constitutive expression of CD1d is achieved by two distinct methods, either by using adoptive transfer of Cd1d1 transduced haematopoietic stem cells or by using a CD1d transgenic mouse model. I show that both of these approaches represent a feasible way to constitutively express CD1d in murine GC B cells, but cannot establish a definitive biological role for CD1d downregulation in murine GC B cells. Finally, I investigate the transcriptional mechanisms governing the downregulation of CD1d, in either normal or pathological B cells. By analysing GC and MM B cells, I provide the first evidence that both retinoic acid signalling and bivalent chromatin domains act as a dual regulatory mechanism of CD1d. These findings demonstrate a new concept in the field of MM biology, specifically that MM B cells (like lymphomas) are able to “hijack” physiological pathways for disease propagation. Although previous work has highlighted the ability of all-trans retinoic acid (ATRA) alone to increase CD1d expression, this uncovering of a dual mechanism provides the rationale to use both ATRA and the polycomb-repressive complex inhibitor GSK343 to restore CD1d expression. I show that this is a more effective strategy than ATRA alone in increasing CD1d expression. Although this will need to be validated in further in vivo models, this ability to further increase CD1d expression may be of great therapeutic importance in the emerging field of tumour immunotherapy.Open Acces

Analyzing and evaluating the energy efficiency based on multi-5G small cells with a mm-waves in the next generation cellular networks

This paper evaluates the impact of multi-5G small cell systems on the energy efficiency (EE) in a Fifth Generation (5G) of cellular networks. Both the proposed model and the analysis of the EE in this study take into account (i) the path losses, fading, and shadowing that affect the received signal at the user equipment (UE) within the same cell, and (ii) the interference effects of adjacent cells. In addition, the concepts of new technologies such as large MIMO in millimeter range communication have also been considered. The simulation results show that the interference from adjacent cells can degrade the EE of a multi-cell cellular network. With the high interference the number of bits that will be transferred per joule of energy is 1.29 Mb/J with a 0.25 GHz bandwidth and 16 transmit antennas. While, with a 1 GHz bandwidth the transfer rate increases to 5.17 Mb/J. Whereas, with 64 transmit antennas the EE improved to 5.17 Mb/J with a 0.25 GHz BW and 20.70 Mb/J with a 1 GHz BW. These results provide insight into the impact of the number of antennas in millimeter range communication and the interference from adjacent cells on achieving real gains in the EE of multi-5G small cells cellular network

Machine Learning Algorithms for Smart Data Analysis in Internet of Things Environment: Taxonomies and Research Trends

Machine learning techniques will contribution towards making Internet of Things (IoT) symmetric applications among the most significant sources of new data in the future. In this context, network systems are endowed with the capacity to access varieties of experimental symmetric data across a plethora of network devices, study the data information, obtain knowledge, and make informed decisions based on the dataset at its disposal. This study is limited to supervised and unsupervised machine learning (ML) techniques, regarded as the bedrock of the IoT smart data analysis. This study includes reviews and discussions of substantial issues related to supervised and unsupervised machine learning techniques, highlighting the advantages and limitations of each algorithm, and discusses the research trends and recommendations for further study

Cranial electrostimulation improves slow wave sleep in collegiate population: a polysomnographic study

Objective: Sleep disturbance is quite prevalent among students, which leads to deleterious consequences on health. Cranial electrostimulation (CES) has been speculated to entrain cortical slow waves; therefore, we investigated the efficacy of cranial electrostimulation to improve slow wave sleep in collegiates. Methods: Twenty-eight students with Pittsburgh sleep quality index (PSQI) score >5 were randomly assigned into two groups: CES and control. Participants in CES group completed 60 minutes of CES intervention for 12 weeks with 100 µA microcurrent and 0.5 Hz frequency parameters during night. Pre- and post-intervention measures were taken for sleep architecture using over-night polysomnography (PSG) and sleep quality using PSQI. Participants were instructed to report to the laboratory at 10:00 p.m. and PSG was performed with electroencephalograms (EEG), chin electromyography (EMG) and bilateral electrooculogram (EOG) in place. Sleep stages were scored manually in accordance with the new AASM guidelines. PSG variables reported in the present study are sleep latency (SL), total sleep time (TST), percentage of N1, N2, N3, NREM (non-rapid eye movement), REM (rapid eye movement) and sleep efficiency (SE%). Results: After ascertaining the comparability of demographic and sleep variables at baseline for both the groups, a 2X2 mixed model ANOVA was employed. Significant between-group differences were obtained for N1% and N3% such that N1% decreased and N3% increased post CES. However, other PSG variables, along with PSQI score did not demonstrate statistically significant between-group difference. Discussion: The present study demonstrated that 12-weeks of CES improved N3% and reduced N1%. Future researches should be undertaken to build upon the findings of present study

Sixth Generation (6G)Wireless Networks: Vision, Research Activities, Challenges and Potential Solutions

The standardization activities of the fifth generation communications are clearly over and deployment has commenced globally. To sustain the competitive edge of wireless networks, industrial and academia synergy have begun to conceptualize the next generation of wireless communication systems (namely, sixth generation, (6G)) aimed at laying the foundation for the stratification of the communication needs of the 2030s. In support of this vision, this study highlights the most promising lines of research from the recent literature in common directions for the 6G project. Its core contribution involves exploring the critical issues and key potential features of 6G communications, including: (i) vision and key features; (ii) challenges and potential solutions; and (iii) research activities. These controversial research topics were profoundly examined in relation to the motivation of their various sub-domains to achieve a precise, concrete, and concise conclusion. Thus, this article will contribute significantly to opening new horizons for future research direction

Antimicrobial susceptibility patterns: a three-year surveillance study in a rehabilitation setting

Introduction: To analyze the susceptibility patterns in a rehabilitation center. Methods: This retrospective observational study was conducted between January 2011 and to January 2013 at Sultan Bin Abdulaziz Humanitarian City (SBAHC), Riyadh, Kingdom of Saudi Arabia. Number of the patients, specimen type, pathogen detected and antibiogram were entered in database for analysis using Inter System Track care software. Results: A total of 4525 isolates were available from 5148 patients. Most (74%) of the isolates were from urine samples and were due to Eschericia coli (49.8%), Enterococcus faecalis (15%) and (Proteous mirabilis(9.49%). Of all the isolates, Eschericia coli was the commonest (49.8%) Gram negative organism, while(Stahylococcus aureus was the commonest (51%) among Gram positive organisms. The most effective antibiotics against Pseudomonas aeroginosa were ciprofloxacin and gentamicin. Meropenem shows excellent activity against Gram negative bacteria. Methicillin resistant Staphylococcus aureus (MRSA) was susceptible to Vancomycin and Rifampicin in 97% and 85% cases. Conclusion: A high incidence of urinary tract infections caused by Eschericia coli, Enterococcus faecalisandProteous mirabilis was reported. Staphylococcus aureus was the commonest pathogen isolated from infected bed sores.Pan African Medical Journal 2016; 2

A randomised double-blind placebo-controlled trial of minocycline and/or Omega-3 fatty acids added to treatment as usual for At Risk Mental States (NAYAB): study protocol

Background The At Risk Mental State (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials that have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for ARMS that are available both in high, low and middle-income countries. Methods A six-month intervention study of minocycline and/or Omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. 320 consenting patients with capacity will be recruited from community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants to each study arm, and 236 will complete in total. We will determine whether the addition of minocycline and/or Omega-3 fatty acids to TAU attenuates rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy end-point is conversion to psychotic disorder at 12 months post study entry. Analysis will be by intention-to-treat, using analysis-of variance, chi-squared tests and adjusted odds ratios to assess between-group differences. Cox regression analyses will be used to analyse potential between-group differences in time-to-onset of psychosis. Discussion The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive are readily available in low/middle-income countries such as Pakistan, and if evidenced, may prove to be safe and effective for treating ARMS