Involvement of the matrix proteins SPARC and osteopontin in the dynamic interaction between tumour and host cells

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonOsteoblasts are highly active cells that are responsible for secreting bone forming components such as collagen type I and matricellular proteins that mediate collagen deposition and mineralisation. SPARC and osteopontin are matricellular proteins that are involved in bone regulation and cell-matrix interactions and are also upregulated in metastatic disease. Secretion of these proteins results in changes to the stromal environment that includes cell migration, angiogenesis, matrix degradation, matrix deposition, bone mineralisation and bone resorption. Signalling pathways not only lead to the expression of target proteins, but also have immediate early effects, for example, on cell adhesion. We asked if the ERK 1 and 2 module of the MAPK pathway was involved in the intracellular trafficking of SPARC and Osteopontin. Membrane trafficking is an essential process that ensures newly synthesised proteins pass from their site of synthesis to the extracellular environment. Using an inhibitor of ERK 1 and 2 activation (U0126), as well as siRNA directed against ERK 1 or 2 individually, a change in intracellular localisation of SPARC and osteopontin was observed in cells treated with U0126 and siRNA against ERK 2 alone, likely in or around the Golgi apparatus. Consistent with the observation above, analysis of protein secretion showed that there was a reduction of total protein secreted (30% reduction) when ERK 1 and 2 activation was prevented together or knock down of ERK 2 alone. A mechanism is proposed where ERK 2 is likely activating a substrate that is allowing SPARC and osteopontin to continue along the secretory pathway. This directly implicates ERK 2 as an important regulator of matricellular protein secretion in osteoblasts. In cancer, Ras mutations can lead to permanent activation of the MAPK pathway leading to cancer cell proliferation and survival, however, we propose another mechanism important in metastasis whereby ERK 2 activation is manipulated to facilitate secretion of matricellular proteins which can then mediate changes to the stromal environment that allow the tumour to metastasise successfully

Financial Leverage and its Relationship to Prediction of Financial Failure an Experimental Analytical Study of a Sample of Iraqi Private Banking Sector Banks for the Period 2014-2022

The survival, continuity and growth of business organizations, whether they are productive or service, such as financial institutions, including (banks) in their environments, is attributed to the extent of their success or failure in their commercial activities due to the dynamic and evolving environment produced by globalization, as well as the policies related to financial liberalization and openness, so it has become imperative for the managements of those banks to It works to face these financial challenges and risks, represented by the increase in its fixed costs in its productive activities, as well as the lack of funds necessary to meet its obligations towards its creditors, which forces it to take the right decisions to enhance its financial position, including the use of financial leverage to rely on public debt funds in its business to achieve its successes by entering investment projects and generating Profits for their owners to cover their fixed costs and pay their dues to creditors, and it is no secret that the process of expanding the debt without well-studied plans will lead to bankruptcy and then to its financial failure soon, and the process of predicting the financial failure of financial institutions is necessary due to the benefits it achieves that make benefiting from these effects The negative and economic effects of these challenges as a warning bell for the work of the departments of those banks.Among those methods and means taken by its departments is the use of the Altman (1968) model, which adopted the mathematical formula (z-score) through its application to some financial ratios. The study relied on conducting two processes of analysis and testing on the Bank of Baghdad of the Iraqi private banking sector for the purpose of determining the extent of its success, survival, growth and continuity in its work environment or failure. It included the financial and statistical analyzes of its data for the period from (2014-2022). After completing the two analyzes and testing, a number of conclusions were drawn up, the most prominent of which was the existence of a good significant relationship between the two variables (financial leverage and prediction of financial failure). The study came out with it, perhaps the most important of which are two basic aspects: the first is the need for banks to adopt plans that work to cover their credit activities in an efficient manner that works to make the most of their assets and that they do not use financial leverage except within certain limits (when exposed to financial hardship) that would reduce their fixed costs and generate It has profits to cover the resulting interests of loans and advances and to obtain profits for its permanence and growth in the work environment, and if it expands in the public debt, it will lead to failure, and the second is that its plans include using the aforementioned model to know the strength or weakness of its credit position to be remedied

Prepare and Study Some Mechanical and Electrical Properties of KAl(SO4)2.12H2O as Aqueous Solutions

Some of physical properties of  KAl(SO4)2.12H2O dissolves in distilled water had been studied at different concentrations (0.05% , 0.075% , 0.1% , 0.125 and 0.15 gm./ml) such as (mechanical and electrical properties), the mechanical properties  such as ultrasonic velocity had been measured by ultrasonic waves system at frequency 25 KHz, other mechanical properties had been calculated such as absorption coefficient of ultrasonic waves, relaxation time, relaxation amplitude, specific acoustic impedance, compressibility and bulk modules. The electrical properties such as electrical conductivity, molar conductivity and degree of dissociation were measured by conductivity meter, The results show that the specific acoustic impedance and bulk modules are increasing with the increase of the concentration , absorption coefficient of ultrasonic waves ,compressibility, relaxation time, relaxation amplitude and shear viscosity are decreasing with increase the concentration, also The results show that the conductivity is increasing with increase the concentration. Keywords: KAl(SO4)2.12H2O solution, Electrical properties, Mechanical properties, ultrasound technique.

Synthesis and crystal structure of poly{bis-(3-nitro-2,4-pentanediono)-copper(II)}, [Cu(NO2-acac)2]n

The organo-inorganic polymer, poly[{Cu(NO2-acac)2}3]n, has been prepared and its crystal structure was determined. The structure consists of a trimeric unit in which, acetylacetone ligated symmetrically to copper atoms that pose in the center of octahedrons. The three octahedral fragments of the trimer are linked to each other through nitro group. Crystal Data: C10H12CuN2O8, Mr = 351.76, triclinic, P-1 (No. 2), a = 5.8237(2) Å, b = 7.7963(3) Å, c = 7.8847(3) Å, α = 81.988(2)°, b = 75.294(2)°, γ = 72.217(2)°, V = 328.98(2) Å3, T = 143(2) K, Z = 1, Z' = 0.5, μ(Mo Kα) = 1.703, 3021 reflections measured, 1421 unique (Rint = 0.0156) which were used in all calculations. The final wR2 was 0.0686 (all data) and R1 was 0.0217 (I > 2σ (I))

The Effect of the Gardens of Knowledge Strategy on Cognitive Thinking and Scientific Skills for First Primary Grader in Sciences Subject

يهدف البحث الى التعرف على اثر استراتيجية حدائق المعرفة  في التفكير المعرفي  والمهارات  العلمية لتلاميذ الصف الاول الابتدائي في مادة العلوم. وضع الباحثون هدفان لتحقيق اجراءات البحث من خلال صياغة فرضيتين صفريتين بعد ان حدد الباحثون مجتمع البحث وعينته في تلاميذ الصف الاول الابتدائي ضمن تربية قضاء العزيزية في محافظة واسط ضمن مدرستين في العزيزية مدرسة العزيزية الابتدائية للبنين وتمثلت بالشعبة أ التي درست وفق استراتيجية حدائق المعرفة وهي تلاميذ المجموعة التجريبية, ومدرسة الرصافي الابتدائية  للبنين ممتثلة بالشعبة ب درست على وفق الطريقة الاعتيادية كما وأعد الباحثون اختبارين التفكير المعرفي وبلغت فقراته 20 فقرة من نوع الاختبار ذو بديلين واختبار المهارات العلمية والمؤلف من 15 فقرة للتجارب المعروضة واظهرت النتائج تفوق تلاميذ المجموعة التجريبية التي درست باستراتيجية حدائق المعرفة في التفكير المعرفي والمهارات العلمية في مادة العلوم لتلاميذ الصف الاول الابتدائي.  The research aims to identify the effect of the knowledge gardens strategy on the cognitive thinking and scientific skills of first-grade students in the science subject The researchers set two goals to achieve the research procedures by formulating two zero hypotheses after the researchers identified the research community and its sample in the first grade pupils within the education of the Al-Aziziyah district in Wasit governorate within two schools in Al-Aziziyah, Al-Azizia Primary School for Boys. The experimental, Al-Rusafi Primary School for Boys, complying with Division B, was studied according to the usual method. The researchers also prepared two cognitive thinking tests, with 20 items of the two-alternative test and the scientific skills test consisting of 15 items for the presented experiments. The results showed the superiority of the pupils of the experimental group that studied the strategy of knowledge gardens in thinking Cognitive and scientific skills in science for first-grade pupils

DDX3X suppresses the susceptibility of hindbrain lineages to medulloblastoma

DEAD-Box Helicase 3 X-Linked (DDX3X) is frequently mutated in the Wingless (WNT) and Sonic hedghog (SHH) subtypes of medulloblastoma—the commonest malignant childhood brain tumor, but whether DDX3X functions as a medulloblastoma oncogene or tumor suppressor gene is not known. Here, we show that Ddx3x regulates hindbrain patterning and development by controlling Hox gene expression and cell stress signaling. In mice predisposed to Wnt- or Shh medulloblastoma, Ddx3x sensed oncogenic stress and suppressed tumor formation. WNT and SHH medulloblastomas normally arise only in the lower and upper rhombic lips, respectively. Deletion of Ddx3x removed this lineage restriction, enabling both medulloblastoma subtypes to arise in either germinal zone. Thus, DDX3X is a medulloblastoma tumor suppressor that regulates hindbrain development and restricts the competence of cell lineages to form medulloblastoma subtypes

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The Critical Factors Influencing the Investment Decisions of Life and Health Insurance Companies

Amir A. Jassim is Professor of Finance and Business Law, School of Business and Administrative Sciences at California State University. Myron E. Hatcher is Professor of Information Systems and Decision Sciences, School of Business and Administrative Sciences at California State University

Early detection of left ventricular dysfunction in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor (Imatinib): using global longitudinal strain

Introduction: Early detection of left ventricular (LV) dysfunction and cardiotoxicity is among the documented side effects of numerous antineoplastic drugs including imatinib, which belongs to tyrosine kinase inhibitors (TKIs), administered for chronic myeloid leukemia (CML) treatment. Therefore, identification of patients at higher risk for developing LV dysfunction and cardiotoxicity would be a good strategy to reduce mortality rates. Method: This case-control study was conducted on patients with confirmed CML, taking imatinib, referred to Babylon Oncology Center in Marjan Medical City, Babil, Iraq, between January 5th and July 1st, 2019. To this end, a special questionnaire comprised of items about patients&rsquo; age, oncological and medical history of diabetes mellitus (DM), hypertension (HT), ischemic heart disease (IHD), cardiomyopathy (CMP), or heart failure (HF) along with measurement of weight, height, heart rate, and blood pressure as baseline information was employed. Echocardiographic examination was also done for case (i.e. patient) and control groups. Results: The mean age of the patients included in this study was 43.90(&plusmn;13.73) years, respectively with minimum and maximum patient age of 17 and 64 years. As well, there was no difference in diastolic function of echocardiographic readings during the study. However, a significant difference was observed between the mean values of S^ (cm/sec). Therefore, the systolic function could be evaluated by tissue Doppler imaging technique. There was correspondingly a significant reduction in global longitudinal strain (GLS) with preserved LV ejection fraction (LVEF). The GLS results also revealed that 60% of the patients (n=24) had normal GLS% (&le;-18%) and 40% of the cases (n=16) had impaired GLS% (&ge;-17%). Conclusion: GLS decline was observed in patients with CML receiving imatinib, compared with the control group, since they had fairly preserved or normal LVEF. Thus, GLS drop was detected&nbsp;&nbsp; without any significant reduction in EF