Investigations on Aspergillus fumigatus double-stranded RNAs and their effects on the fungus

The aim of this research was to assess the incidence of dsRNA mycoviruses in the opportunistic human pathogenic fungus Aspergillus fumigatus, where previously no dsRNA viruses had been reported and to investigate the effects of any dsRNAs on the growth and pathogenicity of the fungus. Thus far 366 isolates (clinical and environmental) have been screened, 24 of which posses dsRNA elements. Successful efforts were made to completely characterise the two dsRNA segments of the isolate 88, partitivirus to obtain novel sequence information. Fungal viruses or mycoviruses are widespread and they usually infect their hosts persistently without any detectable phenotypic effects. They have been however linked with both hypovirulence and hypervirulence but are normally cryptic. To obtain information on the effect of the dsRNAs on their respective hosts, efforts were made to ‘cure’ isolate 88 of its dsRNA infection by cycloheximide treatment. However, following cycloheximide treatment, a sensitive reverse transcription polymerase chain reaction (RT-PCR) amplification assay showed that the dsRNA elements, whilst being reduced in amount, were not eliminated completely and that high levels of cycloheximide also interfered with spore production, pigmentation and overall growth of the isolate. In further experiments attempts were made to mobilise the dsRNAs from 4 isolates viz. A-56, A-54, A-78 and isolate 88 into isolate Af-273y, which is hygromycin resistant and yellow in colour, by hyphal tip fusion, protoplast fusion and protoplast transfection with purified virus. Protoplast fusion and viral transfection experiments were successful for some isolates, as assessed by the RT-PCR assay and small scale extractions of nucleic acids. Subsequently comparative growth experiments by radial growth assay and mycelial weight measurements between isolate Af-273y and Af-273y transfected with isolate 88 partitivirus in essentially the same genetic background were performed. These experiments showed that the partitivirus infection resulted in a sectored phenotype and significantly lowered the growth of the fungus. All efforts to initiate the molecular characterisation of uncharacterised dsRNA elements found in isolates A-54, A-78 and isolate-66 have thus far proven unsuccessful but a new approach (cDNA library construction) is proposed for the characterisation of these dsRNAs

A comprehensive computational mutation structurefunction approach for determining potential drug target sites in poliovirus 2A protease

Purpose: To investigate a computational approach for analysing the structure-function relationship of poliovirus 2A protease using various bioinformatics tools. Methods: The three-dimensional structure of 2Apro was modelled and analyzed using the crystal structure of coxsakievirus B4 as a template to understand the function of this protein. Structural validation programs, VADAR and QMEAN, were used to verify the 2Apro model. Analysis of protein stability changes in poliovirus 2A protease-mutated sequences using various servers was also performed. Furthermore, mutation pattern, intrinsic disorder regions (IDRs), hydrophobic regions, drug binding sites (DBS) and subcellular localization were identified. Results: Hydrophobicity results confirmed the suitability and reliability of 2A protease as a potential drug target. Less IDRs were observed in the protein. Moreover, the results showed the presence of various important drug binding targets among conserved regions of the protease. The predicted drug binding sites indicate their suitability for the inhibition and development of anti-viral drugs against poliovirus 2A protease. Conclusion: The current study resulted in the detection of important ligand interactions with respect to the binding site of the targeted protein. Thus, these compounds may be potent drug candidates and their potency may be increased against poliovirus 2A protease with relatively simple structural changes. Keywords: 2A Protease, Computational analysis, Drug binding sites, Intrinsic disorder regions, Hydrophobicit

Hemimegalencephaly with intractable epilepsy: A case report

Isolated Hemimegalencephaly (iHME) is a rare form of congenital malformation of cortical development.It is characterized by enlargement of all or part of one cerebral hemisphere. It typically presents with intractable seizures, mental retardation, developmental delay, contralateral hemiparesis and hemianopia. The patient was a five and half month\u27s old baby girl who presented first with focal seizures at 10th day of life. No other physical or behavioral abnormality was noted. However, Initial EEG showed excessive sharp EEG transients more over the right hemisphere, repeated EEG showed spikes, polyspikes, sharps and slow wave discharges predominately over right hemisphere. MRI brain showed asymmetric enlargement of the right cerebral hemisphere, suggestive of hemimegalencephaly. Initial treatment with anti-epileptics was successful in controlling the seizures but later on the seizures became intractable even on polytherapy. Identification of this and similar cases of iHME can help us better understand this disorder and its associated symptoms and eventually help us develop better treatment options for it

Losartan associated anaphylaxis and angioneurotic oedema

A case of anaphylaxis and angioedema induced by angiotensin II receptor blocker (ARB), losartan is reported. A 37 years old hypertensive female presented to the Emergency Department with swelling over the face especially the lips, urticarial rash all over the body, and dyspnoea within an hour of losartan administration. She did not have any previous history of drug allergies. The patient was managed with epinephrine. Although angioneurotic oedema and anaphylaxis are well documented adverse effects of angiotensin converting enzyme (ACE) inhibitors, very few cases of these adverse reactions with ARBs have been reported in medical literature

Biased Over-the-Air Federated Learning under Wireless Heterogeneity

Recently, Over-the-Air (OTA) computation has emerged as a promising federated learning (FL) paradigm that leverages the waveform superposition properties of the wireless channel to realize fast model updates. Prior work focused on the OTA device ``pre-scaler" design under \emph{homogeneous} wireless conditions, in which devices experience the same average path loss, resulting in zero-bias solutions. Yet, zero-bias designs are limited by the device with the worst average path loss and hence may perform poorly in \emph{heterogeneous} wireless settings. In this scenario, there may be a benefit in designing \emph{biased} solutions, in exchange for a lower variance in the model updates. To optimize this trade-off, we study the design of OTA device pre-scalers by focusing on the OTA-FL convergence. We derive an upper bound on the model ``optimality error", which explicitly captures the effect of bias and variance in terms of the choice of the pre-scalers. Based on this bound, we identify two solutions of interest: minimum noise variance, and minimum noise variance zero-bias solutions. Numerical evaluations show that using OTA device pre-scalers that minimize the variance of FL updates, while allowing a small bias, can provide high gains over existing schemes.Comment: Accepted at IEEE International Conference on Communications (ICC), 202

Doing Taxes Better: Simplify, Open and Grow Economy

Taxes have been the cornerstone of IMF-led adjustment programs for Pakistan for over four decades. During this period, long term growth and productivity have declined while the tax policy has become more contentious and fragmented. Measures multiply as unrealistic targets are chased with mini budgets every quarter. The following arose from a high-level conference arranged by PIDE to outline future directions in tax policy

Dynamic Compression Plate: A useful procedure for sub-trochanteric femur fracture with osteopetrosis.

Introduction: Osteopetrosis is an un common disease. It is of infantile and adult type. With adult type osteopetrosis, bones are vulnerable to fracture even with minimal injury. As there is increased bone density and small medullary canal, therefore, these fractures are challenging for orthopedic surgeons.Objective: To evaluate the results of Dynamic Compression Plate (DCP) for the fixation of sub-trochanteric fractures of femur with osteopetrosis in term of union malunion, non-union and post-operative infection.Methodology: This prospective study was conducted in the department of Orthopedic surgery at Muhammad Medical College Mirpur Khas from March 2015 to February 2017. Patients, with sub-trochanteric fractures of femur having osteopetrosis, between the age of 20-60 years of either gender were included in this study. All fractures were fixed with DCP. Post-operatively patients were mobilized with crutches in 1st week, followed by partial weight bearing in 3rd week and full weight bearing in 6 weeks.Results: Union of fractures occur in 98 %patients. Mal union in one patient and nonunion in one patient. Post-operative infection was observed in one patient.Conclusion: This study shows management of sub trochanteric fractures of femur in patients with osteopetrosis are best treated with DCP with little or no complications.Key words: Osteopetrosis, sub trochanteric fractures, DCP