Suggestions for changes in the production of a part "revolver trigger"

Studie pojednává o technologii výroby součásti „spoušť revolveru“. Finální sestavou je krátká ruční palná zbraň ALFA Steel a její modelové řady společnosti ALFA-PROJ spol. s r.o. V úvodu se studie zabývá spouští a její technologičností. Následuje seznámení s průběhem výroby podle současného technologického postupu a jejími nedostatky. Byla zjištěna hlavní příčina výrobní nepřesnosti a provedla se analýza návrhů změn včetně úpravy technologického postupu. Na základě experimentu se v technické kontrole měřily rozměry na poskytnutých vzorcích odlitků navržené výroby. V experimentu se ověřovaly i rozměry spouští vyrobených současnou výrobou. Výsledky naměřených hodnot se navzájem porovnaly a na základě shody produktů vyhodnotily. V konečné fázi studie se porovnaly výrobní náklady na práci jednoho kusu spouště s nově navrženou technologií.The study deals with production technology of “revolver trigger“. Final assembly is short firearm ALFA Steel and its model series of ALFA-PROJ, Ltd company. Introduction submits an explanation of trigger technology suitability. The following analysis describes current manufacturing process, which has manufacturing inaccuracy problem. Furthermore rootcause of manufacturing inaccuracy was determined and analysis of suggestions for changes (including modifications of technological process) was realized. Based on experiment dimensions were measured on provided samples of suggest production in Technical Control Department. Dimensions of triggers manufactured by current production were verified during the experiment too. Results were compared according to the rejects of production. In the final phase of the study manufacturing labor costs were compared for the one piece of trigger with the new suggested technology.

Mono-\u3cem\u3eN\u3c/em\u3e-acyl-2,6-diaminopimelic Acid Derivatives: Analysis by Electromigration and Spectroscopic Methods and Examination of Enzyme Inhibitory Activity

Thirteen mono-N-acyl derivatives of 2,6-diaminopimelic acid (DAP)—new potential inhibitors of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18)—were analyzed and characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopies and two capillary electromigration methods: capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC). Structural features of DAP derivatives were characterized by IR and NMR spectroscopies, whereas CZE and MEKC were applied to evaluate their purity and to investigate their electromigration properties. Effective electrophoretic mobilities of these compounds were determined by CZE in acidic and alkaline background electrolytes (BGEs) and by MEKC in acidic and alkaline BGEs containing a pseudostationary phase of anionic detergent sodium dodecyl sulfate (SDS) or cationic detergent cetyltrimethylammonium bromide (CTAB). The best separation of DAP derivatives, including diastereomers of some of them, was achieved by MEKC in an acidic BGE (500 mM acetic acid [pH 2.54] and 60 mM SDS). All DAP derivatives were examined for their ability to inhibit catalytic activity of DapE from Haemophilus influenzae (HiDapE) and ArgE from Escherichia coli (EcArgE). None of these DAP derivatives worked as an effective inhibitor of HiDapE, but one derivative—N-fumaryl, Me-ester-DAP—was found to be a moderate inhibitor of EcArgE, thereby providing a promising lead structure for further studies on ArgE inhibitors

Insulin-like Growth Factor 1 Analogs Clicked in the C Domain : Chemical Synthesis and Biological Activities

Human insulin-like growth factor 1 (IGF-1) is a 70 amino acid protein hormone, with key impact on growth, development, and lifespan. The physiological and clinical importance of IGF-1 prompted challenging chemical and biological trials toward the development of its analogs as molecular tools for the IGF-1 receptor (IGF1-R) studies and as new therapeutics. Here, we report a new method for the total chemical synthesis of IGF-1 analogs, which entails the solid-phase synthesis of two IGF-1 precursor chains that is followed by the CuI-catalyzed azide-alkyne cycloaddition ligation and by biomimetic formation of a native pattern of disulfides. The connection of the two IGF-1 precursor chains by the triazole-containing moieties, and variation of its neighboring sequences (Arg36 and Arg37), was tolerated in IGF-1R binding and its activation. These new synthetic IGF-1 analogs are unique examples of disulfide bonds' rich proteins with intra main-chain triazole links. The methodology reported here also presents a convenient synthetic platform for the design and production of new analogs of this important human hormone with non-standard protein modifications

The efficiency of insulin production and its content in insulin-expressing model β-cells correlate with their Zn 2+ levels : Zn 2+ levels in β-cells

Insulin is produced and stored inside the pancreatic β-cell secretory granules, where it is assumed to form Zn 2+ -stabilized oligomers. However, the actual storage forms of this hormone and the impact of zinc ions on insulin production in vivo are not known. Our initial X-ray fluorescence experiment on granules from native Langerhans islets and insulinoma-derived INS-1E cells revealed a considerable difference in the zinc content. This led our further investigation to evaluate the impact of the intra-granular Zn 2+ levels on the production and storage of insulin in different model β-cells. Here, we systematically compared zinc and insulin contents in the permanent INS-1E and BRIN-BD11 β-cells and in the native rat pancreatic islets by flow cytometry, confocal microscopy, immunoblotting, specific messenger RNA (mRNA) and total insulin analysis. These studies revealed an impaired insulin production in the permanent β-cell lines with the diminished intracellular zinc content. The drop in insulin and Zn 2+ levels was paralleled by a lower expression of ZnT8 zinc transporter mRNA and hampered proinsulin processing/folding in both permanent cell lines. To summarize, we showed that the disruption of zinc homeostasis in the model β-cells correlated with their impaired insulin and ZnT8 production. This indicates a need for in-depth fundamental research about the role of zinc in insulin production and storage

Two-dimensional electrophoretic comparison of metastatic and non-metastatic human breast tumors using in vitro cultured epithelial cells derived from the cancer tissues

<p>Abstract</p> <p>Background</p> <p>Breast carcinomas represent a heterogeneous group of tumors diverse in behavior, outcome, and response to therapy. Identification of proteins resembling the tumor biology can improve the diagnosis, prediction, treatment selection, and targeting of therapy. Since the beginning of the post-genomic era, the focus of molecular biology gradually moved from genomes to proteins and proteomes and to their functionality. Proteomics can potentially capture dynamic changes in protein expression integrating both genetic and epigenetic influences.</p> <p>Methods</p> <p>We prepared primary cultures of epithelial cells from 23 breast cancer tissue samples and performed comparative proteomic analysis. Seven patients developed distant metastases within three-year follow-up. These samples were included into a metastase-positive group, the others formed a metastase-negative group. Two-dimensional electrophoretical (2-DE) gels in pH range 4–7 were prepared. Spot densities in 2-DE protein maps were subjected to statistical analyses (R/maanova package) and data-mining analysis (GUHA). For identification of proteins in selected spots, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed.</p> <p>Results</p> <p>Three protein spots were significantly altered between the metastatic and non-metastatic groups. The correlations were proven at the 0.05 significance level. Nucleophosmin was increased in the group with metastases. The levels of 2,3-trans-enoyl-CoA isomerase and glutathione peroxidase 1 were decreased.</p> <p>Conclusion</p> <p>We have performed an extensive proteomic study of mammary epithelial cells from breast cancer patients. We have found differentially expressed proteins between the samples from metastase-positive and metastase-negative patient groups.</p

Criminal activity in connection with public procurement

Autor se v práci zabývá právní úpravou trestných činů souvisejících se zadáváním veřejných zakázek, a to zejména těch, které se této problematiky přímo týkají. Primárně jsou tedy analyzována ustanovení § 248 odst. 2 alinea 2, § 256 a § 257 trestního zákoníku. Po stručném historickém úvodu do problematiky práce popisuje některé instituty právní úpravy veřejných zakázek, jakož i některé pro trestní odpovědnost podstatné novinky této nové právní úpravy. V hlavní části práce pak autor podrobně analyzuje tři výše uvedené skutkové podstaty se zaměřením na aktuální rozhodovací praxi českých soudů s uvedením praktických příkladů trestněprávních jednání, ke kterým na úseku veřejných zakázek obvykle dochází. Autor se dále zaměřuje také na některé další trestné činy, které jsou v praxi, ať už častěji či spíše výjimečně, také páchány v souvislosti s veřejnými zakázkami, byť s nimi na rozdíl od třech výše uvedených trestných činů primárně nesouvisejí. Autor též podrobně analyzoval veškerou dostupnou judikaturu k trestným činům podle ustanovení § 248 odst. 2 alinea 2 a § 257 trestního zákoníku za období účinnosti současného trestního zákoníku, neboť s ohledem na nepříliš konkrétně vymezené skutkové podstaty v kombinaci s relativní vzácností těchto trestných činů je v některých případech velmi těžké dostatečně...The author analyses the existing legislation regarding crime related to public procurement, focusing on those that directly relate to public procurement. The primary objective of this thesis is a thorough analysis of sections 248 paragraph 2 alinea 2, section 256 and section 257 of the Czech criminal code. Following a brief historical introduction this thesis describes some of the important legal instruments present in the new law regulating public procurement, emphasising the new ones that may have a strong impact on criminal liability. The main part of the thesis then analyses the three aforementioned crimes, putting emphasis on the recent decisions of the Czech courts in this matter. The author also provides practical examples of criminal conduct related to public procurement. The author also focuses on some other crimes that may not be directly related to public procurement, but are in practice more or less often committed in relation to public procurement or together with the three aforementioned crimes. The author has also carried out a detailed analysis of the available case-law related to the crimes described in sections 248 paragraph 2 alinea 2 and 257 of the Czech criminal code in a time period between its entry into force up to the date of submitting this thesis. The reason for this...Department of Criminal LawKatedra trestního právaFaculty of LawPrávnická fakult

Production technology of part barrel shroud

Studie pojednává o technologii výroby součásti plášť hlavně „ocel sport“ z tyčového polotovaru. Jedná se o součást finální sestavy krátké ruční palné zbraně – revolveru ALFA steel model Sport české společnosti ALFA - PROJ spol. s r.o. V úvodu rešerše je vysvětlena základní problematika strojního obrábění (historický vývoj strojního obrábění, vývoj nástrojových materiálů, frézování a obrábění děr). Dále předkládá vysvětlení k obecnému rozdělení zbraní a analýze technologičnosti pláště hlavně. Následující rozbor technologického postupu součásti charakterizuje postup výroby pláště hlavně ve výše uvedené společnosti. Poslední část studie poukazuje na možné návrhy zlepšení výroby a racionalizačních opatření.The study deals with technology of "sport steel" barrel shroud part made from a rod semi-product. It makes part of final assembly of a short firearm - ALFA steel revolver, Sport model, of ALFA - PROJ, Ltd. Czech company. Recherche introduction explains basic tooling (its history, tool material's development, milling and hole machining). Furthermore, it is submits an explanation to general arms division and analysis of barrel shroud technology suitability. The following technology process analysis describes the barrel shroud manufacturing process in the aforementioned company. Study's last part shows possible suggestions for manufacturing improvements and rationalizing measures.

Criminal activity in connection with public procurement

The author analyses the existing legislation regarding crime related to public procurement, focusing on those that directly relate to public procurement. The primary objective of this thesis is a thorough analysis of sections 248 paragraph 2 alinea 2, section 256 and section 257 of the Czech criminal code. Following a brief historical introduction this thesis describes some of the important legal instruments present in the new law regulating public procurement, emphasising the new ones that may have a strong impact on criminal liability. The main part of the thesis then analyses the three aforementioned crimes, putting emphasis on the recent decisions of the Czech courts in this matter. The author also provides practical examples of criminal conduct related to public procurement. The author also focuses on some other crimes that may not be directly related to public procurement, but are in practice more or less often committed in relation to public procurement or together with the three aforementioned crimes. The author has also carried out a detailed analysis of the available case-law related to the crimes described in sections 248 paragraph 2 alinea 2 and 257 of the Czech criminal code in a time period between its entry into force up to the date of submitting this thesis. The reason for this..

Interception and recording of telecommunications

AB S T R A C T W I R E T A P P I N G A N D R E C O R D I N G O F T E L E C O M M U N I C A T I O N T R A F F I C The author of this thesis analyzes the legal institutes related to secret surveillance of communication or the correspondent data. Those institutes are not only wiretapping and recording of telecommunication traffic according to section 88 TrŘ and capture of data on telecommunication traffic according to section 88a TrŘ, but also acoustic surveillance of private premises and capture of e-mail communication, which are according to the current legal framework realized via section § 158d paragraph 3 TrŘ - surveillance of persons and items. The core of this thesis is the analysis of the aforementioned institutes and the corresponding case law, both Czech and the ECHR case law. The thesis also evaluates the practices of the Czech law enforcement authorities based on the case law of the Supreme court in the special proceeding to evaluate the legality of some of the aforementioned institutes, which is also described in this thesis. The thesis also analyzes the legal framework for the international cooperation in criminal matters, which (due to the globalization and its effect on telecommunications) grows in importance. One chapter is dedicated to the analysis of the most prominent case law regarding the..

A CuAAC–Hydrazone–CuAAC Trifunctional Scaffold for the Solid-Phase Synthesis of Trimodal Compounds: Possibilities and Limitations

We present a trifunctional scaffold designed for the solid-phase synthesis of trimodal compounds. This scaffold holds two alkyne arms in a free and TIPS-protected form for consecutive CuAAC (copper(I)-catalyzed azide–alkyne cycloaddition), one Fmoc-protected hydrazide arm for reaction with aldehydes, and one carboxylic acid arm with CF2 groups for attachment to the resin and 19F-NMR quantification. This scaffold was attached to a resin and derivatized with model azides and aliphatic, electron-rich or electron-poor aromatic aldehydes. We identified several limitations of the scaffold caused by the instability of hydrazones in acidic conditions, in the presence of copper during CuAAC, and when copper accumulated in the resin. We successfully overcame these drawbacks by optimizing synthetic conditions for the derivatization of the scaffold with aromatic aldehydes. Overall, the new trifunctional scaffold combines CuAAC and hydrazone chemistries, offering a broader chemical space for the development of bioactive compounds