Study of the post-translational modifications of histone H4 by Fourier transform ion cyclotron resonance mass spectrometry.

Post-translational modification (PTM) of proteins is known to be a method by which protein function can be regulated. The addition of selected chemical groups at specific amino acid residues can act as a switch by which the function of a modified protein can be attenuated. Histones are a group of proteins which are found in the nucleus of eukaryotic cells and interact with DNA, providing it with a structural foundation upon which the chromosome is built. Histone proteins have numerous sequence variants and are known to be extensively post-translationally modified in a dynamic manner. These modifications have a direct effect on the interacting DNA resulting in increasing or decreasing levels of gene transcription. Advancements in analytical instrumentation, when coupled to high resolution separation techniques permit the analysis of increasingly complex biological mixtures. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) offers unrivalled mass resolving power and mass measurement accuracy, allowing the detailed study of mixtures of intact proteins and their post-translational modifications. These features have been exploited to provide a global view of the PTMs of histone proteins. The work contained within this thesis is a study, by FT-ICR MS, of the modifications of one of the most extensively modified histone proteins; histone H4. Firstly, the modifications of histone H4 were examined after treatment with a potent histone deacetylase inhibitor across several cell lines. The cell lines chosen showed a varying response to treatment with the inhibitor. From the cell lines tested, two which responded differently were further interrogated to elucidate the order in which acetylation occurs in the N-terminal region. Secondly, the modifications of histone H4 were analyzed after exposure to lactic acid over multiple treatment times. Lactic acid is a metabolic by-product, and is of interest when considering the Warburg effect and its role in tumorigenesis. Exposure of cells to levels of lactic acid which can be present under anaerobic conditions (i.e. during intense exercise) showed that lactate is able to inhibit histone de-acetylation. The resulting increase in hyper-acetylated forms of histone H4 could be potentially linked to increased gene expression, a typical observation in tumorigenic cells. Finally, using a mouse model for the neurological condition Rett Syndrome, the posttranslational modifications of histone H4 were investigated. The primary cause of Rett Syndrome is mutation of the DNA binding protein methyl CpG binding protein 2 (MeCP2). MeCP2 has been associated with multiple intracellular functions, one of which is chromatin remodelling. The work carried out showed a link between MeCP2 mutation and tri-methylation of histone H4. In addition, the tri-methylation was not solely identified through the presence of tri-methylated fragments in fragmentation mass spectra. Interestingly, the neutral loss of a methylene group was observed extensively during fragmentation of tri-methylated species. This unreported phenomenon made interpretation of spectra difficult; however, ultimately served as a useful marker for this modification

Vector Autoregressive Integrating Moving Average (Varima) Model of COVID-19 Pandemic and Oil Price

Purpose: A coronavirus associated with severe respiratory syndrome has created Coronavirus Disease 2019 (COVID-19), a highly contagious illness that affects the entire world population. On the other hand, COVID-19 is having a direct impact on human life because of its proliferation. So, the study's goal is to forecast and analyze the impact of the COVID-19 pandemic and the oil price utilizing multiple time series analysis methods (VARIMA model).   Theoretical framework: Recent literature has reported that the multivariate time series is robust model for forecasting and analyzing dynamic relationship between series, while the univariate ARIMA model has been generalized to include vector variables, that is an extension of its capabilities. The VAR (p) model analyzes the interdependence between two or more series but does not take into account the impact of shocks at various time variable delays.   Design/methodology/approach: This study uses VARMA (p, q) model which links a set of variables to their prior iterations as well as those of other variables and shocks to those same variables. Sample data concerning the COVID-19 pandemic and oil price was globally provided. It contains daily observations of them variables for the years 2020-2022.   Findings: The best model is VARIMA (2,1,2), and the results shown that the oil price is not only influenced by itself but also influenced by the Covid-19 pandemic. Moreover, the standard error grows over time of the forecast.   Research, Practical & Social implications: The best model is sound for short-term forecasting but unstable for long-term forecasting. Future researchers can integrate factors across areas. Include tourism demand and industry variables in modeling.   Originality/value: Collecting COVID-19 pandemic data and oil price series in a modern model that is a multivariate time series model with a high predicted level of model accuracy between these variables in order to predict and analyze the effects between them series and estimate the interaction between these two series with the most recent data is the value of this study, and then offers merchants the chance to comprehend the forecasting of oil price throughout the covid-19 effects as well as the associated risks

COMPARATIVE ULTRASONOGRAPHIC MEASUREMENT OF RENAL SIZE AND ITS CORRELATION WITH AGE, GENDER, AND BODY MASS INDEX IN NORMAL SUBJECTS IN SULAIMANI REGION

Background: The renal size of a population is a very useful diagnostic parameter in the practice of medicine. Since the renal size is affected by various factors, it is necessary to first determine the normal value. Objective:The aim of this study is to provide an estimation of renal size in normal subjects in Sulaimani Teaching Hospital, and to study its relation with age, gender, and body mass index (BMI) using ultrasonography. Therefore, this provides a standard data for our locality as we are deficient of them. Method:A cross sectional descriptive study was conducted in Sulaimani Teaching Hospital during the period of June 2013 to February 2014. 450 random volunteer person were included in the study aging between 18 - 96 years, without any known renal diseases.The total sample of the study were 450 person. 239 person (53%) were females, while 211 person (47%) were males. The mean of the right renal size in males was 76553.9947 mm3, while the mean of the left renal size was 94493.9mm3. In females, the mean of the right renal size was 68324.0292mm3, while the mean of the left renal size was 84150.43264mm3. Mean renal size for the right kidney was 72210.9842 mm3,While the mean renal size for the left kidney was 89031.0296 mm3. Results:There was a positive correlation between the size of the right and left kidney, with the left kidney size which is larger. There was also a positive correlation between renal size and age, as renal size increased with age till the 5th decade of life. While the male renal size was greater than the female renal size with the same age group, there was a positive correlation between renal size and body mass index (BMI)

Transfusion-related acute lung injury in a paediatric intensive care unit of Pakistan

Background: Transfusion-Related Acute Lung Injury (TRALI) is a major cause of transfusionrelated morbidity and mortality in the intensive care unit setting. There is a paucity of such data from Pakistan. The purpose of this study is to assess the incidence and outcome of TRALI in critically ill children admitted in a pediatric intensive care unit (PICU) of Pakistan.Methods: This is a retrospective cohort study of all critically ill or injured children who developed TRALI or possible TRALI after blood transfusion based on Canadian Conference Consensus criteria in a closed multidisciplinary-cardiothoracic PICU from January 2012 to June 2016. The demographic, pertinent clinical data, transfusion-related variables and outcome of all cases of TRALI were recorded.Results: Of total 2975 admissions in the PICU during study period, 35.8% (1066) received 5124 blood components. Eleven cases developed TRALI in our cohort. The incidence of TRALI was 1.03% per patient transfused and 0.19% (19/100,000 per blood product transfused). Median age was 8 (range 1-14) yr., 70 % (n=8) were male. Mean PRISM-III score was 16.3±6.7. Mean time interval for onset of TRALI was 2.73±1.67 hr. The postoperative cardiac surgical and hematology-oncology patients were most common categories (63.6%). Plasma and platelets were the most commomly identified trigger of TRALI. The case-specific mortality was 63.6% and the overall mortality was 10.7% (p\u3c0.0001).Conclusions: The incidence of TRALI in critically ill children is low, but is associated with high mortality. Critically ill children with high PRISM-III score, postoperative cardiac surgical and hematology-oncology patients are often affected by TRALI

Enhancement of machinability by workpiece preheating in end milling of Ti-6Al-4V

Purpose: The main objective of this paper is to investigate the effect of workpiece preheating with high frequency induction heating on improvement of machinability of Ti-6Al-4V during end milling using PVD TiAlN coated inserts. Tool life, cutting force and vibration were investigated during the experiments. Design/methodology/approach: End milling tests were conducted on Vertical Machining Centre (VMC ZPS, Model: MCFV 1060 with quarter immersion cutting. Titanium based alloy Ti-6Al-4V bar was used as the work-piece. Machining was performed with a 20 mm diameter end-mill tool holder (R390-020B20-11M) fitted with one insert. PVD TiAlN coated carbide inserts (R390-11 T3 08E-ML 2030) were used in the experiments. All of the experiments were run at room temperature and preheated conditions. The preheated temperature was maintained at 420ºC and no phase change of the workpiece in preheating was ensured from the phase diagram of Ti-6Al-4V. High frequency induction heating was utilized to run the preheated machining. Findings: Preheating helps in substantially increasing tool life and in lowering down the cutting force value, lowering the amplitude of vibration and dynamic forces. Practical implications: The cost of machining Ti-6Al-4V is extremely high because of the relatively low machining speed and short tool life. Therefore, improving the machinability of Ti-6Al-4V is a research topic of much interest, with a number of approaches reported with varied results, such as, cryogenic cutting, highpressure coolant, rotary-tool, and minimum quantity lubrication (MQL). Originality/value: A new approach of induction preheating to overcome the difficulties in machining of Ti-6Al-4V is presented in this paper. In preheated machining, high frequency induction heating is used as an external heat source to soften the work material surface layer in order to decrease its tensile strength and strain hardening. An experimental study has been performed to assess the effect of workpiece preheating using induction heating system to enhance the machinability of Ti-6Al-4V. The preheating temperature was maintained below the phase change temperature of Ti-6Al-4V

The Incidence, Risk Factors and Diagnosis of Ventilator Associated Penumonia.

Background: The critically ill patient is at risk of developing intensive care acquired infection, with the lungs being especially vulnerable. Ventilator associated pneumonia (VAP) occurring after two days of mechanical ventilation and it is the most nosocomial infection seen in the intensive care unit .The establishment of an accurate diagnosis of ventilator associated pneumonia remains problematic and yet there is still no accepted "gold standard" for the diagnosis. Patients& Methods: This is a cross section study for 328 patients admitted to intensive care unit at medical city teaching hospital. Full history, physical examination and investigation were done after 48 hours of admission according to clinical pulmonary infection score using clinical criteria (body temperature, WBC count, oxygenation, chest radiography and tracheal aspiration).Arterial blood gases were taken for all patients. Results: 40 patients developed ventilation associated pneumonia out of 328 patients (12.19%) treated intensive care unit. Most patients who developed pneumonia were at extreme of age and there was no association between the disease and gender. The presence of risk factors like invasive mechanical ventilation (97.5%) nasogastric intubation (90%), tracheostomy (75%), post-operative (30%),insertion of urinary catheter (75%) unconscious patients (57.5%) and vomiting (27.5%) were found as an important risk factors .Gram negative bacteria was the most frequently observed especially pseudomonas aeruginosa (40%) klebsiella (15%).. Conclusion: ventilator associated pneumonia is an important cause of mortality. The clinical pulmonary infection score was found to be the reliable method for diagnosis of ventilator associated pneumonia. There is general agreement that rapid initiation of appropriate antimicrobial therapy will improve the outcome

Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression

Chemical inhibitors of histone deacetylase (HDAC) activity are used as experimental tools to induce histone hyperacetylation and deregulate gene transcription, but it is not known whether the inhibition of HDACs plays any part in the normal physiological regulation of transcription. Using both in vitro and in vivo assays, we show that lactate, which accumulates when glycolysis exceeds the cell’s aerobic metabolic capacity, is an endogenous HDAC inhibitor, deregulating transcription in an HDAC-dependent manner. Lactate is a relatively weak inhibitor (IC(50) 40 mM) compared to the established inhibitors trichostatin A and butyrate, but the genes deregulated overlap significantly with those affected by low concentrations of the more potent inhibitors. HDAC inhibition causes significant up and downregulation of genes, but genes that are associated with HDAC proteins are more likely to be upregulated and less likely to be downregulated than would be expected. Our results suggest that the primary effect of HDAC inhibition by endogenous short-chain fatty acids like lactate is to promote gene expression at genes associated with HDAC proteins. Therefore, we propose that lactate may be an important transcriptional regulator, linking the metabolic state of the cell to gene transcription

Determination of Carbamate and Organophosphorus Pesticides in Vegetable Samples and the Efficiency of Gamma-Radiation in Their Removal

In the present study, the residual pesticide levels were determined in eggplants (Solanummelongena)

Evaluation of Children’s Anthropometric Measures in Rural and Urban Areas for Ergonomic Application

The prominent issue of the mismatches of children’s body dimensions with school furniture has made people realize the essential factors of providing ergonomic furniture. By evaluating rural and urban areas, school furniture can be designed for both areas based on their anthropometrics, thereby combating mismatches. This quantitative study focused on four regions in Malaysia. A total sample of 2,400 primary school children from seven to eleven years old from both rural and urban schools was evaluated. Six anthropometric aspects were measured: stature, subscapular height, shoulder breadth, hip width, buttock popliteal length, and popliteal height. The measurements were evaluated using SPSS, with which T-tests were performed, to evaluate the anthropometric differences between each province. Each region showed different results when its rural and urban areas were compared. This reveals that anthropometrics are different in certain areas, even when they are in the same country. The importance of knowing such matters will help to ease the sizing of products (such as furniture) based on location, hence, making ergonomic products possible

Zinc removal from wastewater using hydrogel modified biochar

In this study, hydrogel-(rice husk) biochar composite (HBC-RH) was prepared using acrylamide (AAm) as monomer, with N.N’-methylenebisacrylamide (MBA) as crosslinker, ammonium persulfate (APS) as initiator and rice husk biochar (RHB). The synthesized hydrogel-(rice husk) biochar composite was characterized for swelling capacity andthen utilized for the removal of zinc from wastewater. The optimum batch experimental conditions for this study were determined by evaluating the effect of solution pH, adsorbent dosage, adsorbate initial concentration and contact time. Langmuir isotherm best fitted the HBC-RH sorption of Zinc whereas the kinetic data were best described by pseudo second-order. The maximum monolayer sorption capacity of HBC-RH for zinc was 35.75mg/g