Modulation of Restriction Enzyme PvuII Activity by Metal ion Cofactors

Metal ions like Ca2+, Mn2+, Tb3+, Eu3+ etc., can bind at the active site and have varying effects on the enzymatic activity. In a crystal structure with DNA, two Ca2+ ions were bound to the active site of each PvuII monomer, and the metals share the ligands. Ca2+ ions promote DNA binding and not cleavage in many nucleases. We explored the role of Mg2+ and Ca2+ binding at the metal binding sites of PvuII to elucidate the role of each metal site. We monitored the cleavage kinetics of PvuII in presence of mixed metals. The cleavage kinetics data for Ca2+ and Mg2+ set were modeled using parameters from previous studies on PvuII. Our global analysis on single turnover cleavage kinetics datasets show best fit to a model in which mixed metal species are formed and active. The cleavage rate constants for the mixed metal species ranged from 0.01-0.08 sec-1, which is similar to the rate when only one metal is bound. From earlier work in our lab, Tb3+ was shown to have a tight (2 µM) binding site and a weak binding site in PvuII. The difference in affinity allows one site to be filled with Tb3+ and the other with another metal. Indirect Tb3+ luminescence spectroscopy of the Tb3+ bound to enzyme in presence of other metals indicates that Ca2+ and Mn2+ displace Tb3+ from the enzyme. This was observed by the decrease in the luminescence intensity of E-Tb3+ complex with the addition of Ca2+/Mn2+ ions. Under similar conditions, the addition of Mg2+ ions to the E-Tb3+ complex results in an increase in the signal observed. This indicates the formation of the mixed species E-Tb3+-Mg2+. No enzymatic activity was detected for the enzyme with the addition of Mg2+ to the E-Tb3+ complex, whereas with the addition of Mn2+ ions there was detectable activity. The observed activity with Mn2+ ion was due to the displacement of Tb3+ ions from the active site, forming the active EMn2+Mn2+ species. Although the E-Mg2+-Tb3+ species is catalytically inactive, it does bind the DNA as confirmed by fluorescence anisotropy using nonhydrolyzable phosphoramidate DNA

MODEL OF HOSPITAL COST-EFFECTIVENESS

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. A fost elaborat un model de cost-eficacitate pentru Spitalul Raional din Moldova. Modelul a inclus intrare și ieșire. Obiectivul a fost crearea unui model de rentabilitate și evaluarea cost-eficienței spitalului timp de un an. Material și metode. Sondajul a implicat 5 054 de pacienți tratați în 2018. Au fost incluse 12 luni în model. Pentru fiecare lună au fost calculate cheltuielile financiare ale tratării pacienților. A fost efectuată o analiză a corelației între numărul de pacienți tratați și costul pe pacient. Rezultate. Rezultatele studiului au arătat că, spitalul a avut o eficiență economică negativă în 2018. Au fost identificate lunile aprilie, ianuarie, august, decembrie, octombrie, septembrie, noiembrie care au prezentat eficiență economică negativă. Au fost identificate lunile februarie, martie, mai, iunie, iulie care au demonstrat eficiență economică pozitivă. Analiza corelației a fost efectuată utilizând MedCalc Software Ltd, Ostend, Belgia, 2022. Coeficientul de corelație a fost egal r xy = „-“ 0,7995. Nivelul de semnificație a corelației a fost p = 0,0018. Concluzii. Astfel, cu cât sunt mai mulți pacienți tratați pe an, cu atât costul per pacient este mai mic. A fost dezvoltat un model de cost-eficacitate. Este prezentat cost-eficacității spitalului pentru un an.Background. A cost-effectiveness model for District Hospital in Moldova has been developed. The model included the input and output. Objective was to create a model for cost-effectiveness and evaluate the hospital cost-effectiveness for one year. Material and Methods. The survey involved 5 054 patients treated in 2018. There were 12 months that was included in the model. For each month, the financial expenses of treating patients were calculated. A correlation analysis was carried out between the number of treated patients and the cost per patient. Results. The results of study showed that, the hospital had a negative economic efficiency in 2018. Months April, January, August, December, October, September, November was identified that showed the negative economic efficiency. Months February, March, May, June, July was identified that showed the positive economic efficiency. Correlation analysis was performed using the MedCalc Software Ltd, Ostend, Belgium, 2022. The correlation coefficient was equal r xy = „-“ 0.7995. The significance level of correlation was p = 0,0018. Conclusion. Thus, the more treated patients per year, the lower the cost per patient. A cost-effectiveness model was developed. The hospital cost-effectiveness for one year is presented

Model de cost-eficacitate a spitalului

Background. A cost-effectiveness model for District Hospital in Moldova has been developed. The model included the input and output. Objective was to create a model for cost-effectiveness and evaluate the hospital cost-effectiveness for one year. Material and Methods. The survey involved 5 054 patients treated in 2018. There were 12 months that was included in the model. For each month, the financial expenses of treating patients were calculated. A correlation analysis was carried out between the number of treated patients and the cost per patient. Results. The results of study showed that, the hospital had a negative economic efficiency in 2018. Months April, January, August, December, October, September, November was identified that showed the negative economic efficiency. Months February, March, May, June, July was identified that showed the positive economic efficiency. Correlation analysis was performed using the MedCalc Software Ltd, Ostend, Belgium, 2022. The correlation coefficient was equal rxy = „-“ 0.7995. The significance level of correlation was p = 0,0018. Conclusion. Thus, the more treated patients per year, the lower the cost per patient. A cost-effectiveness model was developed. The hospital cost-effectiveness for one year is presented.Introducere. A fost elaborat un model de cost-eficacitate pentru Spitalul Raional din Moldova. Modelul a inclus intrare și ieșire. Obiectivul a fost crearea unui model de rentabilitate și evaluarea cost-eficienței spitalului timp de un an. Material și metode. Sondajul a implicat 5 054 de pacienți tratați în 2018. Au fost incluse 12 luni în model. Pentru fiecare lună au fost calculate cheltuielile financiare ale tratării pacienților. A fost efectuată o analiză a corelației între numărul de pacienți tratați și costul pe pacient. Rezultate. Rezultatele studiului au arătat că, spitalul a avut o eficiență economică negativă în 2018. Au fost identificate lunile aprilie, ianuarie, august, decembrie, octombrie, septembrie, noiembrie care au prezentat eficiență economică negativă. Au fost identificate lunile februarie, martie, mai, iunie, iulie care au demonstrat eficiență economică pozitivă. Analiza corelației a fost efectuată utilizând MedCalc Software Ltd, Ostend, Belgia, 2022. Coeficientul de corelație a fost egal rxy = „-“ 0,7995. Nivelul de semnificație a corelației a fost p = 0,0018. Concluzii. Astfel, cu cât sunt mai mulți pacienți tratați pe an, cu atât costul per pacient este mai mic. A fost dezvoltat un model de cost-eficacitate. Este prezentat cost-eficacității spitalului pentru un an

A macro-micro system architecture analysis framework applied to Smart Grid meter data management systems by Sooraj Prasannan.

Thesis (S.M. in System Design and Management)--Massachusetts Institute of Technology, Engineering Systems Division, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 109-111).This thesis proposes a framework for architectural analysis of a system at the Macro and Micro levels. The framework consists of two phases -- Formulation and Analysis. Formulation is made up of three steps -- Identifying the System Boundary, Identifying the Object-Process System levels using the Object-Process Methodology (OPM) and then creating the Dependency Matrix using a Design Structure Matrix (DSM). Analysis is composed of two steps -- Macro-Level and Micro-Level Analysis. Macro-Level analysis identifies the system modules and their interdependencies based on the OPM and DSM clustering analysis and Visibility-Dependency Signature Analysis. The Micro-Level analysis identifies the central components in the system based on the connectivity metrics of Indegree centrality, Outdegeree centrality, Visibility and Dependency. The conclusions are drawn based on simultaneously interpreting the results derived from the Macro-Level and Micro-Level Analysis. Macro-Analysis is vital in terms of comprehending system scalability and functionality. The modules and their interactions influence the scalability of the system while the absence of certain modules within a system might indicate missing system functionality. Micro-Analysis classifies the components in the system based on connectivity and can be used to guide redesign/design efforts. Understanding how the redesign of a particular node will affect the entire system helps in planning and implementation. On the other hand, design Modification/enhancement of nodes with low connectivity can be achieved without affecting the performance or architecture of the entire system. Identifying the highly central nodes also helps the system architect understand whether the system has enough redundancy built in to withstand the failure of the central nodes. Potential system bottlenecks can also be identified by using the micro-level analysis. The proposed framework is applied to two industry leading Smart Grid Meter Data Management Systems. Meter Data Management Systems are the central repository of meter data in the Smart Grid Information Technology Layer. Exponential growth is expected in managing electrical meter data and technology firms are very interested in finding ways to leverage the Smart Information Technology market. The thesis compares the two Meter Data Management System architectures, and proposes a generic Meter Data Management System by combining the strengths of the two architectures while identifying areas of collaboration between firms to leverage this generic architecture.S.M.in System Design and Managemen

THE GREAT DIVERGENCE IN THE ANTHROPOCENE

The purpose of this paper is to make explicit and explore in detail some of the implicit assumptions that informed my book, Why Europe Grew Rich and Asia Did Not: Global Economic Divergence, 1600-1850. While the theoretical and methodological perspectives that inform the work are laid out in the introduction and conclusion of the book, why these frameworks were chosen is not elaborated upon. The emergence and impact of the Anthropocene, the new epoch which our planet has entered, are essential to the arguments of the book and in my opinion worth elucidation. The Anthropocene is a scientific category. The concept emerged from within the community of Earth System scholars and refers to a new epoch that followed the Holocene and in which “humans constitute the dominant driver of change to the Earth System.” The power of humanity to transform our planet demands a rethinking of historical practices and priorities. By making explicit the implicit assumptions of my work this paper represents a contribution to that rethinking

Spontaneous pneumoperitoneum associated with colonic pseudo-obstruction

Pneumoperitoneum is almost always pathognomonic of a perforated abdominal viscus requiring urgent surgical intervention. Spontaneous or non-surgical pneumoperitoneum is a rare clinical condition arising secondary to abdominal, thoracic, gynaecologic or idiopathic causes. In addition to good clinical judgement, an important component in the management process is to rule out other causes of pneumoperitoneum by performing appropriate investigations. We describe a 60-year-old man who presented with clinical features of pseudo-obstruction, following an injury to his back which was compounded by hypokalaemia. Roentgenography revealed massive pneumoperitoneum and colonic distension. As there were no overt clinical features of peritonitis, the patient was managed conservatively with parenteral nutrition and close observation. A water-soluble contrast enema and computed tomography of the abdomen were of no help in identifying the cause of his pneumoperitoneum but were helpful in eliminating the presence of hollow viscus perforation or an obvious inflammatory focus. The aetiology of pneumoperitoneum in our patient was most likely due to dissection of air through the distended colonic wall, secondary to large bowel pseudo-obstruction. The diagnosis of spontaneous or non-surgical pneumoperitoneum is one of exclusion and we stress the importance of relying on clinical parameters when managing such patients conservatively

A successful case of rescue encerclage in the mid trimester taken upto term: a case report

Cervical encerclage has been used to treat repeated second trimester pregnancy losses. Rescue cerclage is done in cases of advanced cervical dilatation with membranes protruding into the vagina. If done correctly after proper patient selection, it can successfully prolong a nonviable pregnancy to viability. Here, we present a case report of a multiparous lady with advanced cervical dilatation at 22 weeks who had a successful rescue cerclage where the pregnancy was taken upto 38 weeks

Evaluation of thyroid profile in patients with abnormal uterine bleeding

INTRODUCTION: Large majority of patients present to the gynaecology OPD with complaints associated with abnormal uterine bleeding. Abnormal uterine bleeding can be with or without any organic cause. Dysfunctional uterine bleeding (DUB) is abnormal bleeding from uterine cavity without any pelvic pathology. This study was conducted to evaluate the thyroid profile in patients having abnormal uterine bleeding from puberty to premenopausal age group. AIM AND OBJECTIVES: i. To evaluate and compare the levels of T3, T4, and TSH in patients with abnormal uterine bleeding and controls. ii. To evaluate and compare the levels of T3, T4, and TSH in patients with abnormal uterine bleeding presenting with different menstrual patterns. MATERIALS AND METHODS: This study carried out in the department of Obstertics and Gyneology, SMIMS, Kulasekhram. Total 60 patients were selected and divided in to two groups. Group-I serves as controls (Without AUB), Group-II serves as cases (With AUB). All these patients were subjected to routine investigations and T3, T4, and TSH estimated. Statistical analysis was done by using SPSS (16.0) software version. RESULTS: In the present study thyroid dysfunction was found in 26% of patients with AUB. Of these 23% were hypothyroid and 3% were hyperthyroid the rest of the 74% were euthyroid. The commonest menstrual pattern seen among the patients with thyroid dysfunction was menorrhagia followed by polymenorrhagia. CONCLUSION: The study results showed that thyroid dysfunction was highly prevalent in patients presenting with AUB. Failure to evaluate the thyroid status may risk chance for missing the etiology and leads to inadvertent management. Therefore thyroid profile should form an integral part in the evaluation of all patients presenting with AUB

Neutrophil-lymphocyte ratio as a marker of disease severity and exacerbation in COPD

INTRODUCTION: Since the burden of COPD is increasing day by day and is a leading cause of mortality, it is important to have a prognostic marker for COPD. The well-known prognostic marker for COPD is the BODE score which includes 1) BMI 2) Degree OF Obstruction 3) Dyspnoea Scale 4) Exercise Capacity. Since the calculation Of BODE score is cumbersome and is not possible in sick patients, it is important to have a simple prognostic marker like Neutrophil- Lymphocyte Ratio(NLR) which can be easily obtained from a routine complete blood count which correlates well with that of BODE score. AIMS AND OBJECTIVES: 1.To assess whether Neutrophil-to-Lymphocyte ratio can be used to assess the severity of disease by comparing it with BODE score in COPD 2. To assess whether the Neutrophil Lymphocyte ratio is higher in COPD exacerbation compared to patients with stable COPD MATERIALS & METHODS: This analytical cross-sectional study is to be conducted among 80 patients which includes 30 patients who attend the emergency department of Gov.Rajaji Hospital, Madurai in a state of COPD Acute exacerbation and 50 Stable COPD patients who attend the OPD for followup. METHODOLOGY: A detailed history including duration of illness, smoking history, packyears and any past medical history was taken. Degree of dyspnoea was assessed using Modified Medical Research Council (MMRC) dyspnoea scale. Body mass index(BMI) calculated. Pulmonary function tests were done including FEV1/FVC and Post-bronchodilator FEV1.Peripheral blood samples were collected from all patients within 24hours of admission which includes total count, differential count of neutrophils and lymphocytes. Neutrophil-tolymphocyte ratio was calculated by dividing absolute neutrophil count by absolute lymphocyte count .BODE score was calculated in the stable COPD group. RESULTS: COPD is more prevalent among smokers and male sex.Low BMI is a risk factor for severe disease.NLR correlated with the severity of airflow obstruction.NLR has a positive correlation with mMRC scale. NLR correlated inversely with 6-minute walk distance. Thus,NLR correlated inversely with BMI,FEV1%,6-minute walk distance and has a positive correlation with mMRC scale. NLR correlated with the disease severity as it has positive correlation with BODE score. NLR was significantly higher in COPD exacerbation compared to patients with stable COPD CONCLUSION: NLR correlates well with the disease severity in stable COPD as compared to BODE score. So, it should be used as a routine prognostic marker of mortality in all patients with COPD.NLR can be used as a marker of COPD exacerbations

Ruptured ectopic pregnancy presenting as an irreducible inguinal hernia

An inguinal hernia that suddenly becomes irreducible may be secondary to a variety of other underlying conditions which can occasionally mislead the attending surgeon. Benign, inflammatory or neoplastic processes, as well as surgical emergencies such as intraperitoneal or retroperitoneal haemorrhage, have all been previously reported to mimic an inguinal hernia that suddenly becomes irreducible with or without clinical features of strangulation. We add an additional interesting presentation to this list in the form of a ruptured ectopic pregnancy, which is the first such case reported in the literature. A swelling in the groin may be much more complicated than it seems on superficial consideration and good clinical acumen is constantly required in managing such cases if a satisfactory outcome without any morbidity is to be expected