Higgs Couplings in NonCommutative Standard Model

We consider the Higgs and Yukawa parts of the Non-Commutative Standard Model (NCSM). We explore the NC-action to give all Feynman rules for couplings of the Higgs boson to electro-weak gauge fields and fermions.Comment: 26 page

Phosphodiester hydrolysis computed for cluster models of enzymatic active sites

Computation of phosphodiester hydrolysis in different models with one or two metal ions, representing typical active site architectures of nucleases, reveals an associative mechanism to be favorable in all of the cases studied in this work. Direct attack of the nucleophilic water molecule with proton transfer to the phosphate group is facilitated by an extra positive charge as provided by a metal ion located at the attack site or a positively charged histidine residue, whereas no such contribution can be observed on leaving group departure. A major catalytic effect is found by proton transfer from the nucleophilic water molecule to a histidine–aspartate cluster. Attack of the thus generated hydroxide ion on the phosphate group is just sufficiently stabilized by the metal ions to allow subsequent P–O bond dissociation

A Mechanistic Study Of The Enzymatic Excision Mechanism In AP Endonuclease (APE1)

DNA with an abasic site is a cyto-toxic intermediate in the base excision repair (BER) pathway that is handled by the enzyme Apuridinic/Apyrimidinic endonuclease (APE1) [99, 56, 168, 90]. Several kinetics and thermodynamics aspects of the mechanism by which the APE1 enzyme processes its abasic DNA substrate have been discussed in this thesis. APE1 is an endonuclease that is it cleaves the DNA backbone at a non-terminal site, here at the abasic site. To obtain eminent insight about the catalytic role of amino acid residues and magnesium ions which are representatively recognized in active sites of endonuclease enzymes, quantum mechanical calculations of reaction pathways based on various cluster models mimicking such active sites of endonuclease enzymes have been performed and subsequently discussed in section 4. In this light our results underline the importance of an enzymatic active site architecture in the catalytic reaction, given the substrate is properly positioned. As a side-effect, we were able to evaluate the semi empirical method DFTB3/3OB [132] by comparison of reaction pathways calculating in different cluster models with the same reaction pathways calculations on the DFT level of theory (B3LYP/6- 31G(d,p)). Comparison of the obtained mechanisms and barriers obtained by DFT and DFTB for the minimalistic (cluster) models may nominate DFTB with reasonable accuracy and computational cost as a potential candidate for quantum method in hybrid QM/MM (quantum mechanics/molecular mechanics) approaches for phosphodiester hydrolysis in an enzymatic environment. However in the “reductionist approach” employed to evaluate multiple plausible types of reaction mechanism, the protein’s flexibility and heterogeneous electrostatic environment of protein residues is not taken into account. To enable reaction pathway caculations of the DNA cleavage mechanism in the full APE1 enzyme a model of a reaction-competent APE1-DNA reactant complex has been built, based on available crystal structure data and mutagenesis experiments from the literature [168, 133, 99, 92]. To remedy the lack of lucid information about structural details of APE1/DNA substrate bounded to Mg2+ ion molecular dynamic simulation together with pKa calculations for important amino acid residues in the active-site of the enzyme have been carried out (see section 5). To investigate the potential effect of metal ion binding on the stabilization of the active site in the Ape1-DNA substrate complex, the number and position of the metal ion(s) have been varied and single point mutations of vital active-site residues in the substrate complex of Ape1-DNA have been simulated. Taken together, the most likely model for an Ape1-DNA substrate complex has one Mg2+-ion located at binding site D and His309 in protonated form. At the D site, the metal ion may play a catalytic role in leaving group departure. This scenario allows Tyr171 and His309 to form hydrogen-bonds to the phosphate group that may help DNA binding as well as stabilizing a pentacovalent transition state/intermediate. Asn212 acts in properly positioning the nucleophile which can then transfer a proton to Asp210. A combined QM/MM approach wherein the active site was treated quantum mechanically and the remaining enzyme classically empowered us to investigate the enzymatic reaction pathways of phosphodiester backbone cleavage by APE1 enzyme and enabled us to depict a more realistic picture of the enzyme’s functions in abasic DNA cleavage (see section 6). Opposed to the “reductionist approach”, the QM/MM approach is accurate enough and computationally efficient to gain electronic level insight into the chemical reaction while taking the protein environment explicitly into account and as such allowed the contribution of individual residues in the enzyme environment to be quantified. To find the energetically most favorable pathway for phosphate hydrolysis catalyzed by APE1 enzyme, several possible reaction mechanisms were initially explored by potential energy calculations. As dynamical effects are important in the reaction progress, free energy calculations have subsequently been performed on selected pathways (based on their potential energy profile). According to our QM/MM calculated enzymatic reaction pathways of phosphodiester backbone cleavage by the APE1 enzyme, the dissociative type of mechanism is the most favorable pathway. Herein an important role is played by a metal ligated water molecule that donates a proton to the leaving group while the cleaved sugar backbone migrates toward the Mg2+ ion. This allows a water molecule, activated by proton transfer to Asp210, to attack the phosphorous atom of abasic DNA as nucleophile. The APE1 enzyme as an indispensable key player in BER has been discussed in atomic resolution in this thesis, Our efforts promote the understanding of catalytic and dynamical features of the APE1 enzyme in the abasic DNA cleavage mechanism, including effects of pH and single-site mutations. The detailed insight thus gained may be helpful in designing inhibitors for APE1 as a potential drug target in cancer chemotherapy.Abasische DNA ist ein cytotoxisches Intermediat des Basenexizions Reparaturmechanismus (BER), welches durch das Enzym apuridinische/apyrimidinische Endonuklease (APE1) [99, 56, 168, 90] weiter prozessiert wird. In dieser These wurden verschiedene kinetische und thermodynamische Aspekte des Mechanismus, durch welchen APE1 Enzyme ihr abasisches DNA Substrat umwandeln, diskutiert. APE1 ist eine Endonuklease, welche das DNA Rückgrat an nicht-terminaler Position spaltet, in diesem Fall an der abasischen Position. Um tiefere Einsicht in die katalytische Funktion von Aminosäure-Seitenketten und Magnesiumionen, welche representativ für das aktive Zentrum von Endonukleasen stehen, zu erhalten, wurden quantummechanische Berechnungen von Reaktionswegen basierend auf verschiedenen Cluster-Modellen, die das aktive Zentrum von Endonukleasen imitieren, durchgeführt und nachfolgend im Abschnitt 4 diskutiert. In diesem Licht unterstreichen unsere Ergebnisse die Relevanz der Architektur des aktiven Zentrums für die katalytische Reaktion, vorausgesetzt das Substrat ist korrekt positioniert. Als Nebeneffekt waren wir in der Lage die semi-empirische Methode DFTB3/3OB durch den Vergleich von Reaktionswegen berechnet in verschiedenen Cluster-Modellen mit gleichen Reaktionsweg-Parametern auf DFT -Level zu evaluieren (B3LYP/6-31G(d,p)). Der Vergleich, der durch DFT und DFTB erhaltenen Mechanismen und Barrieren für die minimalistischen (Cluster) Modelle, nominiert DFTB [132] mit angemessener Genauigkeit und Rechenkosten als potentiellen Kandidaten für quantummechanische Methoden in hybrid QM/MM (Quantummechaniken/ Molekulare Mechaniken) Ansätzen für Phosphodiester-Hydrolyse in enzymatischer Umbegung. Jedoch wird im oft verwendeten „reduktionistischen Ansatz“ zur Evaluierung multipler plausibler Formen von Reaktions-Mechanismen die Fexibilität des Proteins und die heterogene elektrostatische Umgebung der Protein-Seitenketten nicht berücksichtigt. Um Reaktionsweg-Berechnungen des DNASpaltungs-Mechanismus im gesamten APE1 Enzym zu ermöglichen, wurde ein Modell eines Reaktionskompetenten APE1-DNA Edukt-Komplexes gebaut, basierend auf den in der Literatur [168, 133, 99, 92]. vorhandenen Krystallstrukturdaten und Mutagenesis-Experimenten. Um den Fehlen von Informationen über strukturelle Details von APE1/DNA-Substrat gebunden an Mg2+ Ionen entgegenzuwirken, wurden Moleküldynamik-Simulationen zusammen mit pKa Berechnungen für wichtige Aminosäure-Seitenketten im aktiven Zentrum durchgeführt (siehe Abschnitt 5). Zur Untersuchung des potentiellen Effekts der Bindung von Metallionen auf die Stabilisierung des aktiven Zentrum im APE1-DNA Substratkomplex wurde die Anzahl und Position der Metallionen variiert und Punktmutationen wesentlicher Seitenketten des Substratkomplex von APE1-DNA simuliert. Detailierte Analyse dieser Simulationen versorgte uns mit angemessenen Statistiken und Informationen über strukturelle Details des aktiven Zentrums von APE1. Zusammenfassend beiinhalted das wahrscheinlichste Modell für den APE1-DNA Substratkomplex ein Mg2+-Ion lokalisiert an der Bindungsstelle D sowie ein His309 in protonierter Form. And der D Bindungsstelle könnte das Metallion eine katalytische Rolle bei der Abspaltung der Abgangsgruppe einnehmen. Dieses Szenario erlaubt Tyr171 und His309 Wasserstoffbrücken zu den Phosphatgruppen zu formen, welche bei der DNA-Bindung sowie bei der Stabilisierung eines pentakovalenten Überganszustands/ Intermediates behilflich sein könnten. Asn212 spielt bei der korrekten Positionierung des Substrats eine Rolle, welches dann ein Proton auf Asp210 übertragen kann. Ein kombinierter QM/MM Ansatz, in welchem das aktive Zentrum quantummechanisch und das übrige Enzym klassisch betrachtet wurde, ermöglichte uns die enzymatischen Reaktionswege der Phosphodiesterrückgrat-Spaltung durch APE1 zu untersuchen und befähigte uns zu einer realistischeren Abbildung der enzymatischen Funtkionen der abasischen DNA Spaltung (siehe Abschnitt 6). Im Gegensatz zum „reduktionistischen Ansatz“ ist der QM/MM Ansatz präzise genug und rechentechnisch effizient um auf elektorischem Level Einsicht in chemische Reaktionen bei explizieter Berücksichtigung der Proteinumgebung zu erhalten und erlaubt als dieses die Quantifizierung der Beiträge individueller Seitenketten der Enzym-Umgebung. Um den engergetisch favorisierten Reaktionsweg für Phosphathydrolyse katalysiert durch APE1-Enzyme zu indentifizieren, wurden mehrere Reaktionsmechanismen initial durch Potentialenergie-Berechnungen untersucht. Aufgrund der Wichtigkeit dynamischer Effekte für den Reaktionsprozess wurden Berechnungen mit freier Energie stückweise an ausgewählten Reaktionswegen durchgeführt (basierend auf ihrem potentiellen Energieprofil). Zufolge unserer durch QM/MM berechneten enzymatischen Reaktionswege der Phosphodiester RückgratSpaltung durch APE1 Enzyme ist der dissoziative Mechanismus der favorisierte Reaktionsweg. In diesem wird eine wichtige Rolle durch ein Metalliganden gebundenes Wasser-Molekül eingenommen, welches Protonen an die Abgangsgruppe überträgt während das gespaltene Zucker-Rückgrat in Richtung des Mg2+ Ions wandert. Das erlaubt einem Wasser-Molekül, aktiviert durch durch Protonentransfer zu Asp210, als Nukleophil das Phosphoratom der abasischen DNA anzugreifen. Das APE1-Enzym wurde in dieser Thesis als ein unverzichtbarer Schlüsselspieler des BER mit atomarer Auflösung diskutiert. Unsere Bemühungen fördern das Verständnis der katalytischen und dynamischen Eigenschaften des APE1 Enzyms im abasischen DNA Spaltungs-Mechanismus unter Einbeziehung von Effekten durch pH und Punktmutationen. Der hierdurch erhaltene Einblick könnte für das Design von Inhibitoren für APE1 als potentielles Ziel für Therapeutika in der Chemotherapie hilfreich sein

Application of Economic Equity Value Added (EEVA) and True Value Added (TVA) in explaining of Modern models derived from Free Cash Flow (CVFCFF and CVFCFE)

Investors and financial managers nowadays expect through use of reliable measures to find out about real business profitability and performance. In response to this need, in recent years, financial experts, inside and outside the country, have tried a variety of performance metrics, including Cash Value Added (CVA), Created Shareholder Value (CSV), Shareholder Value Added (SVA), Residual Income (RI), Market Value Added (MVA), Economic Value Added (EVA), Adjusted Economic Value Added (AEVA), and Refined Economic Value Added (REVA), each of which conveying a different information content regarding company’s value and performance. To the same effect, the current study addresses two other economic performance indicators, namely True Value Added (TVA) and Equity Economic Value Added (EEVA), and their informational worth for CVFCFF and CVFCFE as the two new cash flow based valuation models in the automotive industry operating on Tehran Stock Exchange between 2005 and 2009. The results of the F-test performed in test of the hypotheses confirm significant association of the mentioned cash flow based evaluation models with TVA and EEVA. Keywords: EEVA, TVA, CVFCFF, CVFCF

A Comparison of Facial Emotion Recognition in Patients with Temporal Lobe Epilepsy and Non-epileptics

Abstract Introduction: Temporal lobe epilepsy (TLE) is related to the mesial temporal lobe structures such as the hippocampus, amygdala, and Parahippocampal gyrus. In patients with TLE, the amygdala complex is a component of the temporal lobe that is damaged. Previous studies on emotional processing have proven deficits due to amygdala damage in these patients. The present study compares the facial emotion recognition in patients with temporal lobe epilepsy and healthy controls. It was hypothesized that the TLE group have more dysfunctions than non- people with epilepsy. Methods: In this comparative study, 120 subjects, including 60 patients with a definite diagnosis of the temporal lobe and 60 non-epileptic individuals, were recruited using purposive sampling. The patient group was chosen from the Chamran hospital and Iranian Epilepsy Association, Tehran, Iran. The research data were collected by the Ekman computer test of facial emotion recognition. This test uses 36 images to measure the six basic emotions (i.e., happiness, disgust, anger, fear, sadness, and surprise); these images were adapted from the Ekman and Friesen series of images. The data were analyzed using multivariate analysis of variance by SPSS Statistics 19-IBM in two levels of response accuracy and reaction time in TLE patients and healthy individuals. Results: Data analysis showed a significant difference in the response accuracy of facial expressions of happiness, disgust, anger, fear, sadness, and surprise in patients with TLE (P < 0.01). Furthermore, recognizing emotions of fear, disgust, and anger in patients with TLE was more inadequate. When it came to the reaction time of emotion recognition, the TLE patients showed a higher functional impairment than the healthy group (P < 0.01). The reactions to fear and disgust were notably slower than other emotions. Conclusions: The results showed more inaccurate facial emotion recognition of fear, disgust, and anger inferred from facial expressions. Moreover, the reaction time response of facial emotion recognition for all six emotions was slower, compared to non-epileptics. Assessing the emotional recognition dysfunction through this measurement can facilitate recognizing the emotional deficiency regarding social communication in TLE patients. Psychological dysfunction can be a predictor of not a good response to the treatment, more frequency of seizures, and worse quality of life in these patients

The Angular Correlations in Top Quark Decays in Standard Model Extensions

The CMS collaboration at the CERN-LHC have searched for the $t$-channel single top quark production using the spin correlation of the $t$-channel. The signal extraction and cross section measurement relies on the angular distribution of the charged lepton in the top quark decays, the angle between the charged lepton momentum and top spin in the top rest frame. The behavior of the angular distribution is a distinct slope for the t-channel single top (signal) while it is flat for the backgrounds. In this letter we investigate the contributions which this spin correlation may receive from a two-Higgs doublet model, a top-color assisted technicolor (TC2) and the noncommutative extension of the Standard Model.Comment: 5 figure

Causes of Recurrent Urinary Tract Infection in Children on Prophylaxis

 Introduction: Urinary tract infection (UTI) is a common pediatric problem. It has been estimated that 8% of girls and 2% of boys suffer from UTI during childhood. So, prevention of scar formation in high risk children is very important. This study was performed to evaluate the causes of recurrent urinary tract infection in children on prophylaxis. Materials & Methods: This study was performed on 141 cases in 126 children with recurrent UTI. A questionnaire was prepared and data including sex, age, grade of vesicoureteral reflux, and antibiotic used for prophylaxis were collected. Results: The mean age of the patients was 46.6±41.1 months; 24 % of the participants were male and 76% were female. The most common predisposing factor of recurrent UTI was vesicoureteral reflux. E.coli was the microorganism responsible for most of the cases (85.5%). In 85.5% of the children, Co-trimoxazole was used as prophylaxis. Drug resistance was the most common reason of recurrence. Conclusions: We conclude that girls are at higher risk of recurrent infection and regarding the high prevalence of Co-trimoxazole resistance, administration of this drug should be limited and with caution. Keywords: Urinary tract infections; Vesico-Ureteral Reflux; Drug resistance; Chil

The Effects of Occupational Stress on Quality of Life and Associated Factors among Hospital Nurses in Iran

Nurses deal with many crises at work. It is obvious that being exposed to stress for long, results in severe physical and mental complications and affects individual is welfare. This study was aimed at determining the quality of life (QOL) of nurses and whether there is any relation between occupational stress and QOL. This analytical-descriptive cross sectional study was carried out in University hospitals of Zanjan, Iran. 241 nurses were sampled using proportional to size stratified method. The data were collected by means of Iranian version of the Short Form Health Survey (SF-36) and a questionnaire on demographic information and work factors. Occupational stress was measured by Toft Gray and Anderson’s tool. The questionnaires were filled by nurses themselves and the data were analyzed by Spearman’s Correlation test, Kruskal-Wallis and one-way ANOVA and Enter-method Regression with SPSS 16.0 software. The results showed a high level of occupational stress among nurses, which adversely affected their quality of life. According to the results QOL of male and female nurses differ with men having a higher QOL and less occupational stress. 2 work factors, satisfaction and others positive attitude towards nursing, affected all dimensions of QOL and occupational stress. There was no significant correlation between QOL or occupational stress and factors like position, shift, ward, experience, time off, overtime hours, interest in desertion and education. According to harmful effects of occupational stress on nurses, cognitive-behavioral interventions, learning coping strategies are proposed

Triglyceride to HDL cholesterol ratio and risk for gestational diabetes and birth of a large-for-gestational-age newborn

Background: Using oral glucose for glucose challenge test (GCT) and glucose tolerance test (GTT) is problematic, especially in early pregnancy when the pregnant woman is experiencing gastrointestinal complications. This research seeks to investigate the relationship between the ratio of Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) and the risk of gestational diabetes and large for gestational age (LGA) fetus for suggesting a more appropriate index for diagnosis of gestational diabetes. Methods: The present cross-sectional study investigated pregnant women visiting the Perinatal Clinic of Ayatollah Rouhani Hospital in Babol for prenatal care from September 2015-2016. The GCT was performed on these pregnant women at 24-28 weeks as a screening test and their lipid profile, including HDL-C and TG, was simultaneously assessed after eight to 14 hours of fasting. Results: Significant differences were observed between women with and without gestational diabetes in terms of mean triglyceride, HDL, LDL/HDL ratio, triglyceride/LDL ratio and triglyceride/HDL ratio. The cut-off point of TG/HDL in the GTT was 4.254 with a sensitivity of 79.07% and specificity of 78%. Conclusions: According to the results obtained, lipid profile can help predict the risk of gestational diabetes, especially TG/HDL ratio that has a high sensitivity to diagnose gestational diabetes, while, lipid indices could not predict birth of a LGA neonate

The efficacy of metacognitive therapy on emotional processing components of patients with functional dyspepsia: controlled clinical trial

Background: Functional dyspepsia is characterized by a set of symptoms in the upper gastrointestinal tract due to an underlying organic cause and is one of the common causes of patients ’visits to gastroenterologists. A few researches have been conducted on the effectiveness of psychotherapy with respect to the psychological components of these patients. Therefore, the purpose of this study is to investigate the effect of metacognitive therapy on emotional processing components of these patients. Materials and Methods: In this study, 40 patients with dyspeptic symptoms were recruited after medical examination by gastroenterologists, performing H. Pylori test and undergoing endoscopy. Moreover, 20 of the patients were randomly assigned to a group for metacognitive therapy and another 20 to the control group. The Baker's emotional processing questionnaire was used at pre-treatment, post-treatment and three months after treatment for evaluating changes in patients' emotional processing styles. Finally, repeated measures analysis of variance was employed for data analysis by using SPSS 19. Results: The research data that was obtained by repeated measures analysis of variance indicated statistically significant differences in three emotional processing scales in metacognitive therapy group compared to the control group at pre-treatment, post-treatment and three months after treatment. Conclusion: Compared to the control group, the metacognitive therapy of functional dyspepsia patients was more effective in the short- and long-term for coping with difficulty in emotional recognition and experience, difficulty in emotional control and expression as well as inadequate emotional processin