Design of Project Template for a Building Company

Import 19/10/2011Diplomová práce s názvem „Návrh projektové šablony pro stavební firmu“ je zaměřena na tvorbu projektové šablony pro stavební firmu Ritmex s.r.o., oblast rodinné domy. V první části jsou shromážděna teoretická východiska týkající se daného tématu a popsány základní pojmy a vymezení projektového řízení. Dále je zde popsána metodologie zpracování. Ve druhé části je analýza současného stavu. Třetí část obsahuje samotnou aplikaci teoretických poznatků a návrh projektové šablony pro stavbu rodinného domu, včetně ukázky užití. V samotném závěru je obsažen návrh na další postup a využití této šablony.The diploma disertation called „Design of Project Template for a Builidng Company“ is focused on creating project templates for building Ritmex Company Ltd., the area of the family houses. In the first part is collected theoretical background concerning the topic and describes the basic concepts and definition of the project management. There is also the methodology described processing. The second part is an analysis of the current situation. The third part contains the actual application of theoretical knowledge and project templates proposal to build a house, including examples of use. In conclusion, it is drafting proposals for further action and use of this template.157 - Katedra systémového inženýrstvívelmi dobř

Statistical static timing analysis of nonzero clock skew circuit

As microprocessor and ASIC manufacturers continue to push the limits of transistor sizing into the sub-100nm regime, variations in the manufacturing process lead to increased uncertainty about the exact geometry and performance of the resulting devices. Traditional corner-based Static Timing Analysis (STA) assumes worst-case values for process parameters such as transistor channel length and threshold voltage when verifying integrated circuit timing performance. This has become unrea-sonably pessimistic and causes over-design that degrades full-chip performance, wastes engineering effort, and erodes profits while providing negligible yield improvement. Recently, Statistical Static Timing Analysis (SSTA) methods, which model process variations statistically as probability distribution functions (PDFs) rather than deterministically, have emerged to more accurately portray integrated circuit performance. This analysis has been thoroughly performed on traditional zero clock skew circuits where the synchronizing clock signal is assumed to arrive in phase with respect to each register. However, designers will often schedule the clock skew to different registers in order to decrease the minimum clock period of the entire circuit. Clock skew scheduling (CSS) imparts very different timing constraints that are based, in part, on the topology of the circuit. In this thesis, SSTA is applied to nonzero clock skew circuits in order to determine the accuracy improvement relative to their zero skew counterparts, and also to assess how the results of skew scheduling might be impacted with more accurate statistical modeling. For 99.7% timing yield (3 variation), SSTA is observed to improve the accuracy, and therefore increase the timing margin, of nonzero clock skew circuits by up to 2.5x, and on average by 1.3x, the amount seen by zero skew circuits.M.S., Computer Engineering -- Drexel University, 200

Molecular detection of Human Papillomavirus genotype-16&-18 in tissues from patients with prostate cancer and benign prostatic hyperplasia

Background: High oncogenic-risk genotypes of human Papillomavirus (HPV) infect a wide range of human cells, including prostate tissue that give rise to benign prostatic hyperplasia and prostatic adenocarcinomas. Objectives: This study aimed to detect DNA of HPV genotype-16 &18 using in situ hybridization technique in prostatic tissues from benign prostatic hyperplasia and prostatic adenocarcinomas, and elucidate the association between these HPV genotypes and prostatic carcinogenesis. Patients and methods: Forty-eight (48) formalin-fixed, paraffin embedded prostatic tissue blocks were obtained ,among them (28) tissue biopsies from prostatic carcinoma with different grades and (20) benign prostate hyperplastic tissue blocks as well as (10) apparently normal prostate tissue autopsies which were collected from the archives of Forensic Medicine Institute / Baghdad and used as prostate healthy control groups. Detection and genotyping of HPV was done by highly sensitive in situ hybridization technique. Results: The signals of in situ hybridization reactions of both HPV-16 and HPV-18 in prostate cancer cases in the present study was 25% (7 / 28) whereas in BPH, HPV-16 was detected in 45 %( 9 /20) and HPV-18 was presented in 35 %( 7/ 20). Neither HPV-16 nor HPV-18 was detected in the apparently healthy control group.The percentages of HPV 16 and HPV18 were increasing with advancing of grade of prostate cancer. Conclusion: Our results indicate that the oncogenic HPV-16 might contribute to the development of subset of prostate tumors. In addition, HPV16&18 might have a crucial role in progression of the prostate cancer and benign prostatic hyperplasi

SOX2: Not always eye malformations. Severe genital but no major ocular anomalies in a female patient with the recurrent c.70del20 variant

SOX2 variants have been identified in multiple patients with severe ocular anomalies and pituitary dysfunction, in addition to various systemic features. We investigated a 26-year-old female patient suffering from spastic paraparesis, hypoplasia of corpus callosum, hypogonadotropic hypogonadism (HH) and intellectual disability, who was monitored for over 20 years, allowing a detailed genotype-phenotype correlation along time. Whole exome sequencing on the patient and her relatives identified a de novo SOX2 c.70del20 variant, which has been frequently reported in individuals with SOX2-related anophthalmia. Importantly, our patient lacked major ocular phenotype but showed vaginal agenesis, a feature never reported before. Although the involvement of male urogenital tract (cryptorchidism, hypospadias, small penis), is a well known consequence of SOX2 variants, their effect on the female genitalia has never been properly addressed, even considering the paradoxical female excess of SOX2 cases in the literature. Our findings emphasize the importance of testing for SOX2 variants in individuals with HH and genital anomalies even though anophthalmia or microphthalmia are not observed. Moreover, our case strengthens the role of SOX2 as a master regulator of female gonadal differentiation, as widely demonstrated for other SOX genes related to 46, XX sex reversal, such as SOX3 and SOX9

Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes

Here the authors characterize structural variations (SVs) in a cohort of individuals with complex genomic rearrangements, identifying breakpoints by employing short- and long-read genome sequencing and investigate their impact on gene expression and the three-dimensional chromatin architecture. They find breakpoints are enriched in inactive regions and can result in chromatin domain fusions.Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements

De novo unbalanced translocations have a complex history/aetiology

We investigated 52 cases of de novo unbalanced translocations, consisting in a terminally deleted or inverted-duplicated deleted (inv-dup del) 46th chromosome to which the distal portion of another chromosome or its opposite end was transposed. Array CGH, whole-genome sequencing, qPCR, FISH, and trio genotyping were applied. A biparental origin of the deletion and duplication was detected in 6 cases, whereas in 46, both imbalances have the same parental origin. Moreover, the duplicated region was of maternal origin in more than half of the cases, with 25% of them showing two maternal and one paternal haplotype. In all these cases, maternal age was increased. These findings indicate that the primary driver for the occurrence of the de novo unbalanced translocations is a maternal meiotic non-disjunction, followed by partial trisomy rescue of the supernumerary chromosome present in the trisomic zygote. In contrast, asymmetric breakage of a dicentric chromosome, originated either at the meiosis or postzygotically, in which the two resulting chromosomes, one being deleted and the other one inv-dup del, are repaired by telomere capture, appears at the basis of all inv-dup del translocations. Notably, this mechanism also fits with the origin of some simple translocations in which the duplicated region was of paternal origin. In all cases, the signature at the translocation junctions was that of non-homologous end joining (NHEJ) rather than non-allelic homologous recombination (NAHR). Our data imply that there is no risk of recurrence in the following pregnancies for any of the de novo unbalanced translocations we discuss here

Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes

Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements