Quality Control in the Production of Offensive Rifles

Import 05/08/2014Diplomová práce se zabývá rozborem současného stavu kontroly jakosti ve výrobě útočných pušek za účelem zvyšování spolehlivosti a přesnosti těchto zbraní. V této práci je uveden popis útočných pušek a rozbor technických požadavků na tyto zbraňové systémy z pohledu zajištění spolehlivosti a přesnosti. Součástí této diplomové práce je samostatný dokument, ve kterém je navržen způsob kontroly součástí, které mají vliv na spolehlivou funkci zbraně. Součástí samostatného dokumentu diplomové práce je i praktické ověření návrhu včetně vyhodnocení. Praktické ověření proběhlo pomocí porovnání závadovosti, srovnáním rozptylového obrazce a změřením funkčního diagramu zbraně.The Issue of this Master Thesis is analysis of the current state of the quality control in production of assault rifles for the purpose of improving the reliability and accuracy of these weapons. This Thesis describes assault rifles and analysis of technical requirements for these weapons systems from the perspective of reliability and accuracy. Part of this Thesis is a separate document, which proposes a method to control of components that affect the reliable operation of weapon. Part of this Separate document is also practical proposal validation, including evaluation. Practical verification was carried out by comparing of failure rates, comparing the scattering pattern and measuring the functional diagram weapons.346 - Katedra obrábění a montáževýborn

Determination of Requirements for an Assault Rifle

Import 03/08/2012Bakalářská práce se zabývá analýzou bojové činnosti vojáka u různých druhů vojsk za účelem specifikace jeho potřeb na útočnou pušku. Zpracovává návrh dotazníku umožňujícího analýzu požadavků na útočnou pušku dle různých hledisek. V bakalářské práci je navržen způsob provedení a vyhodnocení průzkumu u zvolených skupin vojáků a odborníků. Na základě vyhodnocení provedeného průzkumu formuluje a definuje základní požadavky na moderní útočnou pušku. Součástí bakalářské práce je přehled historického vývoje útočné pušky u vybraných armád.The Bachelor thesis deals with the analysis of combat operations of a soldier acting in different forces, specifying his/her needs of an assault rifle. It elaborates a questionnaire proposal providing an analysis of requirements for an assault rifle in different views. In the Bachelor thesis, there is a facture proposed and survey results at selected groups of soldiers and experts. On the basis of survey results conducted, the thesis formulates and defines basic requirements for a modern assault rifle. Another part of the Bachelor thesis is the historical development review of an assault rifle at selected armies.340 - Katedra výrobních strojů a konstruovánívýborn

A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).

BackgroundOfranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.MethodsThis pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).ResultsEnrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91-1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3-5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction.ConclusionsIn this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results.Clinical trials registrationNCT02511405

N-3 polyunsaturated fatty acid and neuroinflammation in aging and Alzheimer's disease

The innate immune system of the brain is mainly composed of microglial cells, which play a key role in the maintenance of synapses and the protection of neurons against noxious agents or lesions owing to their phagocytic activity. In the healthy brain, microglia are highly motile and strongly interact with neurons either by physical contact, induction of oxidative stress or through specific mediators, such as chemokines and cytokines. In response to inflammatory insult however, microglial cells get activated and produce inflammatory cytokines. The action of cytokines on specific receptors expressed in the brain triggers the development of sickness behavior and altered cognitive and emotional processes. The effects are acute and reversible as normal behavior is restored once the synthesis of inflammatory brain cytokines returns to baseline after a few hours. However, in pathological situations, these cytokines may reach toxic levels and have irreversible consequences such as neuronal death, as observed in neurodegenerative disorders such as Alzheimer’s disease. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients and fundamental components of neuronal and glial cell membranes. They accumulate in the brain during the perinatal period in a dietary supply-dependent fashion. Their brain levels may diminish with age, but can be increased by diets enriched in n-3 PUFAs. Changes in the immune profile have been associated with n-3 PUFAs intake in humans and animal models. Therefore, the increasing exposure of the population to diets low in n-3 PUFAs could contribute to the deleterious effects of the chronic activation of microglia in the brain

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial

Purpose: Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Methods: The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician’s choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. Results: In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P < 0.01) versus TPC; median OS was 10.0 and 4.8 months, respectively. Improvement in OS was observed in both poorer and better GPA prognostic groups. Survival rates at 12 months were 44.4% for EP versus 19.4% for TPC. Consistent with the overall BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). Conclusions: The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744)

Mixed-affinity binding in humans with 18-kDa translocator protein ligands

(11)C-PBR28 PET can detect the 18-kDa translocator protein (TSPO) expressed within macrophages. However, quantitative evaluation of the signal in brain tissue from donors with multiple sclerosis (MS) shows that PBR28 binds the TSPO with high affinity (binding affinity [K(i)], ~4 nM), low affinity (K(i), ~200 nM), or mixed affinity (2 sites with K(i), ~4 nM and ~300 nM). Our study tested whether similar binding behavior could be detected in brain tissue from donors with no history of neurologic disease, with TSPO-binding PET ligands other than (11)C-PBR28, for TSPO present in peripheral blood, and with human brain PET data acquired in vivo with (11)C-PBR28. METHODS: The affinity of TSPO ligands was measured in the human brain post-mortem from donors with a history of MS (n = 13), donors without any history of neurologic disease (n = 20), and in platelets from healthy volunteers (n = 13). Binding potential estimates from thirty-five (11)C-PBR28 PET scans from an independent sample of healthy volunteers were analyzed using a gaussian mixture model. RESULTS: Three binding affinity patterns were found in brains from subjects without neurologic disease in similar proportions to those reported previously from studies of MS brains. TSPO ligands showed substantial differences in affinity between subjects classified as high-affinity binders (HABs) and low-affinity binders (LABs). Differences in affinity between HABs and LABs are approximately 50-fold with PBR28, approximately 17-fold with PBR06, and approximately 4-fold with DAA1106, DPA713, and PBR111. Where differences in affinity between HABs and LABs were low (~4-fold), distinct affinities were not resolvable in binding curves for mixed-affinity binders (MABs), which appeared to express 1 class of sites with an affinity approximately equal to the mean of those for HABs and LABs. Mixed-affinity binding was detected in platelets from an independent sample (HAB, 69%; MAB, 31%), although LABs were not detected. Analysis of (11)C-PBR28 PET data was not inconsistent with the existence of distinct subpopulations of HABs, MABs, and LABs. CONCLUSION: With the exception of (11)C-PK11195, all TSPO PET ligands in current clinical application recognize HABs, LABs, and MABs in brain tissue in vitro. Knowledge of subjects’ binding patterns will be required to accurately quantify TSPO expression in vivo using PET

Down syndrome: Distribution of brain amyloid in mild cognitive impairment.

IntroductionDown syndrome (DS) is associated with a higher risk of dementia. We hypothesize that amyloid beta (Aβ) in specific brain regions differentiates mild cognitive impairment in DS (MCI-DS) and test these hypotheses using cross-sectional and longitudinal data.Methods18F-AV-45 (florbetapir) positron emission tomography (PET) data were collected to analyze amyloid burden in 58 participants clinically classified as cognitively stable (CS) or MCI-DS and 12 longitudinal CS participants.ResultsThe study confirmed our hypotheses of increased amyloid in inferior parietal, lateral occipital, and superior frontal regions as the main effects differentiating MCI-DS from the CS groups. The largest annualized amyloid increases in longitudinal CS data were in the rostral middle frontal, superior frontal, superior/middle temporal, and posterior cingulate cortices.DiscussionThis study helps us to understand amyloid in the MCI-DS transitional state between cognitively stable aging and frank dementia in DS. The spatial distribution of Aβ may be a reliable indicator of MCI-DS in DS