Specification And Mechanical Verification Of Performance Profiles Of Software Components

Software performance predictability is vital to a system design and unpredictable performance is a leading cause of software failure. The emphasis of this dissertation is on verification that component-based software performs as specified. Performance profiles (specifications) depend on functional specifications and are necessary for all components for modular verification. Modular verification process is scalable because it uses profiles as contracts and allows verification of a single component in isolation with the assumption that any underlying component would have already been verified or will be verified to meet its specifications independently. This dissertation presents an integration of performance specification (profiles) with functional specifications within a single language. It contains a mechanizable and modular proof system to verify the performance bounds of reusable software components built reusing other components. The proof system forms the basis for a prototype verification condition (VC) generator. Experimentation with the VC generator illustrates that software component performance can be formally specified and verified. This dissertation discusses only duration (timing) aspect of performance, but the results can be extended to include space constraints

Effect of D-chiro-inositol on hormonal parameters and insulin resistance in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder among women of reproductive age, characterized by hormonal imbalance and insulin resistance. D-chiro-inositol, a naturally occurring inositol isomer, has been suggested as a potential treatment option for PCOS. This study aimed to investigate the effects of D-chiro-inositol supplementation on hormonal parameters, and insulin resistance in women with PCOS. Methods: This randomized controlled study was conducted among 60 women of PCOS with insulin resistance, who were assigned to either Group A (D-chiro-inositol) or Group B (placebo) for 12 weeks. S. FSH, LH, S. total testosterone, fasting blood glucose, fasting insulin, and insulin resistance (HOMA-IR) were measured at baseline and after 12 weeks of treatment. Statistical analyses were performed using SPSS version 23.0 for Windows. Results: After 12 weeks of treatment, significant reductions in serum luteinizing hormone, serum total testosterone, fasting insulin, and HOMA-IR were observed in the D-chiro-inositol group compared to the placebo group. However, no significant changes were observed in fasting blood glucose levels. D-chiro-inositol was well-tolerated, with no significant differences in side effects between the two groups. Conclusions: D-chiro-inositol supplementation for 12 weeks significantly improved hormonal parameters, and insulin resistance in women with PCOS. The treatment was well-tolerated, suggesting that D-chiro-inositol can be an effective therapeutic option for patients with PCOS

Effect of estradiol valerate on endometrial thickness in polycystic ovary syndrome having ovulation induction with letrozole

Background: PCOS is a common endocrine disorder in women of reproductive age. Letrozole is an orally active aromatase inhibitor and as effective as chlomiphene citrate for induction of ovulation. Estrogen is important in the regeneration and growth of the endometrium prior to ovulation prepare the tissue to respond to progesterone post ovulation in PCOS patients. Aim of the study was to assess the effects of estradiol valerate on endometrial thickness in PCOS having ovulation induction with letrozole. Methods: This randomized controlled study was conducted in the department of reproductive endocrinology and infertility, BSMMU, Dhaka, with 1 year duration. A total 80 diagnosed cases of PCOS patients with subfertility were included in this study. Among them 40 patients received letrozole and estradiol valerate and 40 patients received letrozole and placebo. Results: On day 8, mean endometrial thickness was not statistically significant between two groups (p=0.436). On day of triggering, mean endometrial thickness was significantly higher in intervention group 9.2±1.4 mm than control group 8.2±1.4 mm (p=0.004). Mean changes of endometrial thickness on day of triggering compared with on day 8 was significantly higher in intervention group 3.2±1.5 mm than control group 2.5±1.6 mm (p=0.043). Pregnancy rate was higher in intervention group 13 (38.2%) than control group 8 (22.2%) with relative risk 1.72, 95% CI (0.82-3.63%), that was not statistically significant between two groups (p=0.144). Conclusions: Mean changes of endometrial thickness on day of triggering were significantly higher in intervention group than control group. The pregnancy rate achieved with letrozole+estradiol valerate combination was higher than that achieved with letrozole and placebo group

β-Catenin Promotes the Differentiation of Epidermal Langerhans Dendritic Cells

The epithelial signaling protein and transcriptional regulator β-catenin has recently been implicated in hematopoietic dendritic cell (DC) differentiation as well as in DC-mediated tolerance. We here observed that epidermal Langerhans cells (LCs) but not interstitial/dermal DCs express detectable β-catenin. LCs are unique among the DC family members in that LC networks critically depend on epithelial adhesion molecules as well as on the cytokine transforming growth factor-β1 (TGF-β1). However, despite the important functions of LCs in the immune system, the molecular mechanisms governing LC differentiation and maintenance remain poorly defined. We found that TGF-β1 induces β-catenin in progenitor cells undergoing LC differentiation and that β-catenin promotes LC differentiation. Vitamin D, another epidermal signal, enhanced TGF-β1-mediated β-catenin induction and promoted the expression of multiple epithelial genes by LCs. Moreover, full-length vitamin D receptor (VDR) promoted, whereas a truncated VDR diminished, the positive effects of ectopic β-catenin on LC differentiation. Therefore, we here identified β-catenin as a positive regulator of LC differentiation in response to TGF-β1 and identified a functional interaction between β-catenin and VDR in these cells

Transcriptional regulation of Langerhans cell differentiation

Das zytokin TGF-beta1 induziert die in-vitro differenzierung von Langerhans zellen (LC) aus CD34+ hämatopoietischen vorläuferzellen. LCs bilden netzwerke in der epidermis, welche durch TGF-beta1 aufrechterhalten werden. Jene molekularen mechanismen “downstream” von TGF-beta1 welche für LC differenzierung und LC netzwerk-formierung verantwortlich sind blieben bisher weitgehend unerforscht. Diese fragen wurden in der vorliegenden doktorarbeit untersucht. Wir fanden dass TGF-beta1 LC differenzierung via aktivierung des ALK3 rezeptors sowie der nachgeschalteten transkriptionsfaktoren SMAD1/5/8 induziert. Andererseits führt die aktivierung des klassischen ALK5-SMAD2/3 signalweges zur Inhibition von LC differenzierung sowie zur Inhibition der maturierung/aktivierung von LCs. Passend zu diesen befunden kam es durch zugabe des proteins BMP-7, einem bekannten selektiven aktivator von ALK3 (aber nicht von ALK5), zur induktion von LC differenzierung. In weiteren analysen fanden wir dass das protein beta-catenin (beta-catenin) durch TGF-beta1 in LC Vorläuferzellen induziert wird und dass beta-catenin LC differenzierung fördert. Zusätlich konnten wir zeigen dass vitamin-D, ein hormon welches in der epidermis vorkommt, die beta-catenin- und TGF-beta1-abhängige LC differenzierung fördert. Zusätzlich werden epitheliale adhesionsmoleküle an der oberfläche von LCs durch vitamin-D hochreguliert. Weiters kooperiert vitamin-D/vitamin-D receptor mit beta-catenin während der LC differenzierung. Andere unteruchungen ergaben dass die epithelialen charakteristika von LCs zugunsten eines motilen phänotyps nach deren aktivierung verloren gehen und dass dies mit der hochregulierung des oberflächenproteins N-cadherin sowie der transkriptionsfaktoren ZEB1/ZEB2 einhergeht. Zusammenfassend fanden wir dass LC differenzierung durch einen TGF-beta1-abhängigen signalweg: TGF-beta1-ALK3-beta-catenin induziert wird und dass andererseits eine aktivierung von ALK5 die aufrechterhaltung eines unreifen epithelialen LC phänotyps bewirkt.Transforming growth factor beta 1 (TGF-beta1) induces Langerhans cell (LC) differentiation from CD34+ hematopoietic progenitor cells (HPCs). LCs form tight networks in the epidermis that critically depend on TGF-beta1-mediated inhibition of LC activation. However, the underlying mechanisms of TGF-beta1 signaling during LC differentiation remain poorly understood. In this study, we aimed to study the transcriptional regulation of LC differentiation and to dissect the TGF-beta1 signaling pathway downstream of LC differentiation. We here identified that TGF-beta1 utilizes the type-I receptor ALK3-SMAD1/5/8 cascade for inducing LC differentiation from HPCs. Conversely, signaling via the classical TGF-β1 receptor ALK5-SMAD2/3 cascade impaired LC differentiation and maturation by blocking pro-inflammatory cytokine production. We also identified BMP-7, an activator of ALK2/3 but not ALK5, induces LC differentiation that is associated with the selective activation of SMAD1/5/8. Moreover, TGF-beta1 induced the epithelial signaling protein beta-catenin in progenitor cells undergoing LC differentiation and beta-catenin promotes LC differentiation. Vitamin D, another epidermal signal, enhanced TGF-beta1-mediated beta-catenin induction and promoted the expression of multiple epithelial genes by LCs. Moreover, full length vitamin D receptor (VDR) promoted, whereas a truncated VDR diminished the positive effects of ectopic beta-catenin on LC differentiation indicating a functional interaction among beta-catenin and VDR in these cells. On the other hand, during activation, LCs change from a sessile, adhesive phenotype to a motile phenotype by inducing mesenchymal genes like N-cadherin and transcriptional regulators ZEB1/ZEB2. We propose that TGF-beta1-ALK3-dependent induction of beta-catenin is critical for LC differentiation and that the TGF-beta1-ALK5 cascade preserves an immature epithelial resident LC phenotype.submitted by Nighat YasminAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. SpracheWien, Med. Univ., Diss., 2012OeB

Ethnotaxonomical Approach in the Identification of Useful Medicinal Flora of Tehsil Pindigheb (District Attock) Pakistan

researchThe presented research investigated the use of folk remedies among the people of Tehsil Pindigheb, District Attock of Pakistan. During the ethnobotanical survey, we documented indigenous knowledge and collected plant specimens which included medicinal plants. Through questionnaire, ethnomedicinal data was collected from key informants and local inhabitants in randomly selected villages. One hundred plant species belonging to 44 families were recorded as medicinal flora of the area. Due to construction of new housing colonies, modern agricultural practices and cultural changes within the community, the use of traditional knowledge and medicinal plant species are threatened day by day in the area. This study will provide help in future conservation strategies

Molecular Analysis of Carbapenem and Aminoglycoside Resistance Genes in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Clinical Strains: A Challenge for Tertiary Care Hospitals

Carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) strains have become a global threat due to their remarkable capability to survive and disseminate successfully by the acquisition of resistance genes. As a result, the treatment strategies have been severely compromised. Due to the insufficient available data regarding P. aeruginosa resistance from Pakistan, we aimed to investigate the resistance mechanisms of 249 P. aeruginosa strains by antimicrobial susceptibility testing, polymerase chain reaction for the detection of carbapenemases, aminoglycoside resistance genes, extended-spectrum beta-lactamases (ESBLs), sequence typing and plasmid typing. Furthermore, we tested silver nanoparticles (AgNPs) to evaluate their in vitro sensitivity against antimicrobial-resistant P. aeruginosa strains. We observed higher resistance against antimicrobials in the general surgery ward, general medicine ward and wound samples. Phenotypic carbapenemase-producer strains comprised 80.7% (201/249) with 89.0% (179/201) demonstrating genes encoding carbapenemases: blaNDM-1 (32.96%), blaOXA48 (37.43%), blaIMP (7.26%), blaVIM (5.03%), blaKPC-2 (1.12%), blaNDM-1/blaOXA48 (13.97%), blaOXA-48/blaVIM (1.68%) and blaVIM/blaIMP (0.56%). Aminoglycoside-modifying enzyme genes and 16S rRNA methylase variants were detected in 43.8% (109/249) strains: aac(6′)-lb (12.8%), aac(3)-lla (12.0%), rmtB (21.1%), rmtC (11.0%), armA (12.8%), rmtD (4.6%), rmtF (6.4%), rmtB/aac(3)-lla (8.2%), rmtB/aac(6′)-lla (7.3%) and rmtB/armA (3.6%). In total, 43.0% (77/179) of the strains coharbored carbapenemases and aminoglycoside resistance genes with 83.1% resistant to at least 1 agent in 3 or more classes and 16.9% resistant to every class of antimicrobials tested. Thirteen sequence types (STs) were identified: ST235, ST277, ST234, ST170, ST381, ST175, ST1455, ST1963, ST313, ST207, ST664, ST357 and ST348. Plasmid replicon types IncFI, IncFII, IncA/C, IncL/M, IncN, IncX, IncR and IncFIIK and MOB types F11, F12, H121, P131 and P3 were detected. Meropenem/AgNPs and Amikacin/AgNPs showed enhanced antibacterial activity. We reported the coexistence of carbapenemases and aminoglycoside resistance genes among carbapenem-resistant P. aeruginosa with diverse clonal lineages from Pakistan. Furthermore, we highlighted AgNP’s potential role in handling future antimicrobial resistance concerns

Characterization of Genomic Diversity among Carbapenem-Resistant Escherichia coli Clinical Isolates and Antibacterial Efficacy of Silver Nanoparticles from Pakistan

The emergence of carbapenem-resistant Escherichia coli (E. coli) is considered an important threat to public health resulting in resistance accumulation due to antibiotics misuse and selection pressure. This warrants periodic efforts to investigate and develop strategies for infection control. A total of 184 carbapenem-resistant clinical strains of E. coli were characterized for resistance pattern, resistance genes, plasmids, sequence types and in vitro efficacy of silver nanoparticles (AgNPs). Carbapenem resistance was prevalent in E. coli isolated from female patients (64.7%), urine samples (40.8%) and surgical wards (32.1%). Polymyxin-B showed higher susceptibility. ESBLs and carbapenemases were produced in 179 and 119 isolates, respectively. Carbapenemase-encoding genes were observed among 104 strains with blaNDM-1 (45.1%), blaOXA-48 (27%), blaNDM-7 (3.8%), blaNDM-1/blaOXA-48 (15.4%), blaNDM-7/blaOXA-48 (2.9%), blaOXA-48/blaVIM (3.8%) and blaNDM-1/blaVIM (2%). ESBL resistance genes were detected in 147 isolates, namely blaSHV (24.9%), blaCTX-M (17.7%), blaTEM (4.8%), blaSHV/blaCTX-M (29.2%), blaSHV/blaTEM (15%) and blaCTX-M/blaTEM (8.8%). ST405 (44.4%) and ST131 (29.2%) were more frequent sequence types with ST101 (9.7%), ST10 (9.7%) and ST648 (7%). The replicon types IncFII, IncFIIK, IncA/C, IncN and IncL/M were detected. The combination of MEM/AgNPs remained effective against carbapenemase-positive E. coli. We reported genetically diverse E. coli strains coharboring carbapenemases/ESBLs from Pakistan. Moreover, this study highlights the enhanced antibacterial activity of MEM/AgNPs and may be used to manage bacterial infections