Private orders for kindjal and shashka blades of the Kuban Cossack Host from Zlatoust arms factory in the late 19th and early 20th centuries

The article attempts to study and analyze private orders for kindjal and shashka blades of the Kuban Cossack Host in 1888-1904. The term “private orders” refers to orders made not by the Military Headquarters of the Kuban Cossack Host and the Main Artillery Department, but by regiment commanders, atamans of divisions and stanitsa, and individuals – cossacks and officers of the Kuban Cossack Host, as well as owners of jewelry workshops and stores selling uniforms and equipment for cossacks. The temporal borders of the study are determined by the fact that it was during this period that the practice of private orders became most common due to the reasons mentioned in the article. The sources explored in the article enable to assess the role of demand generated by Caucasian cossacks on the development of Kuban region economy. It also allows to supplement the understanding of activities of commercial enterprises which were engaged in the trade of uniforms and edged weapons to officers of the Kuban Cossack Host during this period. The information contained in explored documents makes it possible to study the practice of individual orders of blades from cossacks and officers in detail. The article also studies the orders of blades for the 1st Khopersky and 1st Kuban cavalry regiments of the Kuban Cossack Host

Influence of the instability of chip formation and preheating of work on tool life in maching high temperature resistant steel and titanium alloys

It has been established by experimental investigations that machining of high temperature resistant steel and titanium alloys with cemented carbide tools is accompanied with inherent instability of chip formation. This type of instability causes micro and macro chipping of the tool tip and consequently decreases tool life to a great extent. It has been also established that tool life can be greatly increased by preliminary heating of the work up to a certain optimum temperature, which varies with work and tool materials and conditions of cut

Investigation of the influence of chatter on tool wear

Experimental investigations have been carried out to determine the influence of chatter on cemented carbide tool wear in turning medium carbon steel. Conditions of stable cutting and those conducive to intensive chatter in the investigated range of cutting speed and other cutting conditions were established. Tool wear test performed under these two different conditions have facilitated to establish the typical nature of tool wear during chatter. Chatter leads to intensive wear of the flank surface due to additional rubbing of the same along the wavy cutting surface, formed during chatter. Besides chatter leads to lowering down of the values of chip-tool contact lengths due to a lower value of the coefficient of chip shrinkage. Consequently tool wear along the rake surface is less during chatter

Investigation of the physical causes of improved machinability of steel alloyed with calcium

Investigations have been carried out to determine the possibility of improving machinability of steel by alloying with calcium or other ingredients and also to explain the physi¬cal causes of improved machinability. Results of the experiments show that machina¬bility of steel can be raised several times without adversely affecting its physiomechanical properties. Causes of the improvement of machinability higher degree of hardening of the sulphides due to micro alloying with calcium. Hardened sulphides are ca¬pable of effectively resisting the movement of dislocations in the chip-tool plastic contact zones and as a result the percentage of the total work of plastic deformation spent in changing the internal energy of metal is much higher in the case of alloyed steel than that of the normal steel. And consequently the percentage of total work spent in raising the cutting temperature is much lower in the case of the alloyed steel. Relatively lower value of cutting temperature ultimately facilitates higher tool life, i.e. higher machinability of calcium alloyed steel

Biological assessment of robust noise models in microarray data analysis

Motivation: Although several recently proposed analysis packages for microarray data can cope with heavy-tailed noise, many applications rely on Gaussian assumptions. Gaussian noise models foster computational efficiency. This comes, however, at the expense of increased sensitivity to outlying observations. Assessing potential insufficiencies of Gaussian noise in microarray data analysis is thus important and of general interest

TRIB2 as a biomarker for diagnosis and progression of melanoma

Malignant melanoma is the most deadly form of skin cancer. There is a critical need to identify the patients that could be successfully treated by surgery alone and those that require adjuvant treatment. In this study, we demonstrate that the expression of tribbles2 (TRIB2) strongly correlates with both the presence and progression of melanocyte-derived malignancies. We examined the expression of TRIB2 in addition to 12 previously described melanoma biomarkers across three independent full genome microarray studies. TRIB2 expression was consistently and significantly increased in benign nevi and melanoma, and was highest in samples from patients with metastatic melanoma. The expression profiles for the 12 biomarkers were poorly conserved throughout these studies with only TYR, S100B and SPP1 showing consistently elevated expression in metastatic melanoma versus normal skin. Strikingly we confirmed these findings in 20 freshly obtained primary melanoma tissue samples from metastatic lesions where the expression of these biomarkers were evaluated revealing that TRIB2 expression correlated with disease stage and clinical prognosis. Our results suggest that TRIB2 is a meaningful biomarker reflecting diagnosis and progression of melanoma, as well as predicting clinical response to chemotherapy.Fundacao para a Ciencia e a Tecnologia (FCT) [PEst-OE/EQB/LA0023/2012, SFRH/BPD/84634/2012, SFRH/BPD/70718/2010]info:eu-repo/semantics/publishedVersio

CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion.

Fast amoeboid migration is critical for developmental processes and can be hijacked by cancer cells to enhance metastatic dissemination. This migratory behavior is tightly controlled by high levels of actomyosin contractility, but how it is coupled to other cytoskeletal components is poorly understood. Septins are increasingly recognized as novel cytoskeletal components, but details on their regulation and contribution to migration are lacking. Here, we show that the septin regulator Cdc42EP5 is consistently required for amoeboid melanoma cells to invade and migrate into collagen-rich matrices and locally invade and disseminate in vivo. Cdc42EP5 associates with actin structures, leading to increased actomyosin contractility and amoeboid migration. Cdc42EP5 affects these functions through SEPT9-dependent F-actin cross-linking, which enables the generation of F-actin bundles required for the sustained stabilization of highly contractile actomyosin structures. This study provides evidence that Cdc42EP5 is a regulator of cancer cell motility that coordinates actin and septin networks and describes a unique role for SEPT9 in melanoma invasion and metastasis

Mislocalization of the E3 Ligase, beta-Transducin Repeat-containing Protein 1 (beta-TrCP1), in Glioblastoma Uncouples Negative Feedback between the Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase 1 (PHLPP1) and Akt

The PH domain leucine-rich repeat protein phosphatase, PHLPP, plays a central role in controlling the amplitude of growth factor signaling by directly dephosphorylating and thereby inactivating Akt. The cellular levels of PHLPP1 have recently been shown to be enhanced by its substrate, activated Akt, via modulation of a phosphodegron recognized by the E3 ligase β-TrCP1, thus providing a negative feedback loop to tightly control cellular Akt output. Here we show that this feedback loop is lost in aggressive glioblastoma but not less aggressive astrocytoma. Overexpression and pharmacological studies reveal that loss of the feedback loop does not result from a defect in PHLPP1 protein or in the upstream kinases that control its phosphodegron. Rather, the defect arises from altered localization of β-TrCP1; in astrocytoma cell lines and in normal brain tissue the E3 ligase is predominantly cytoplasmic, whereas in glioblastoma cell lines and patient-derived tumor neurospheres, the E3 ligase is confined to the nucleus and thus spatially separated from PHLPP1, which is cytoplasmic. Restoring the localization of β-TrCP1 to the cytosol of glioblastoma cells rescues the ability of Akt to regulate PHLPP1 stability. Additionally, we show that the degradation of another β-TrCP1 substrate, β-catenin, is impaired and accumulates in the cytosol of glioblastoma cell lines. Our findings reveal that the cellular localization of β-TrCP1 is altered in glioblastoma, resulting in dysregulation of PHLPP1 and other substrates such as β-catenin

Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

<p>Abstract</p> <p>Background</p> <p>Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the <it>Xiphophorus </it>melanoma model system, a mutated version of the EGF receptor Xmrk (<it>Xiphophorus </it>melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation.</p> <p>Methods</p> <p>Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene <it>FOSL1 </it>was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.</p> <p>Results</p> <p>Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (<it>Fosl1</it>), early growth response 1 (<it>Egr1</it>), osteopontin (<it>Opn</it>), insulin-like growth factor binding protein 3 (<it>Igfbp3</it>), dual-specificity phosphatase 4 (<it>Dusp4</it>), and tumor-associated antigen L6 (<it>Taal6</it>). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that <it>FOSL1</it>, <it>OPN</it>, <it>IGFBP3</it>, <it>DUSP4</it>, and <it>TAAL6 </it>also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of <it>FOSL1 </it>in human melanoma cell lines reduced their proliferation and migration.</p> <p>Conclusion</p> <p>Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.</p