Калькулирование себестоимости продукции и учет затрат на предприятии АО «Алмалыкский ГМК»

Объектом исследования данной дипломной работы является хозяйственная деятельность предприятия АО "Алмалыкский ГМК" ЦРМЗ. Предметом исследования данной работы являются методы учета затрат и калькулирования себестоимости продукции предприятия.The Object of study of this thesis is the economic activity of the enterprise JSC "Almalyksky GMK" CRMZ. The subject of this study is the methods of cost accounting and costing of production costs of the enterprise

Time response of oxygen optodes on profiling platforms and its dependence on flow speed and temperature

The time response behavior of Aanderaa optodes model 3830, 4330, and 4330F, as well as a Sea-Bird SBE63 optode and a JFE Alec Co. Rinko dissolved oxygen sensor was analyzed both in the laboratory and in the field. The main factor for the time response is the dynamic regime, i.e., the water flow around the sensor that influences the boundary layer’s dynamics. Response times can be drastically reduced if the sensors are pumped. Laboratory experiments under different dynamic conditions showed a close to linear relation between response time and temperature. Application of a diffusion model including a stagnant boundary layer revealed that molecular diffusion determines the temperature behavior, and that the boundary layer thickness was temperature independent. Moreover, field experiments matched the laboratory findings, with the profiling speed and mode of attachment being of prime importance. The time response was characterized for typical deployments on shipboard CTDs, gliders, and floats, and tools are presented to predict the response time as well as to quantify the effect on the data for a given water mass profile. Finally, the problem of inverse filtering optode data to recover some of the information lost by their time response is addressed

Excitons in InGaAs Quantum Dots without Electron Wetting Layer States

The Stranski-Krastanov (SK) growth-mode facilitates the self-assembly of quantum dots (QDs) using lattice-mismatched semiconductors, for instance InAs and GaAs. SK QDs are defect-free and can be embedded in heterostructures and nano-engineered devices. InAs QDs are excellent photon emitters: QD-excitons, electron-hole bound pairs, are exploited as emitters of high quality single photons for quantum communication. One significant drawback of the SK-mode is the wetting layer (WL). The WL results in a continuum rather close in energy to the QD-confined-states. The WL-states lead to unwanted scattering and dephasing processes of QD-excitons. Here, we report that a slight modification to the SK-growth-protocol of InAs on GaAs -- we add a monolayer of AlAs following InAs QD formation -- results in a radical change to the QD-excitons. Extensive characterisation demonstrates that this additional layer eliminates the WL-continuum for electrons enabling the creation of highly charged excitons where up to six electrons occupy the same QD. Single QDs grown with this protocol exhibit optical linewidths matching those of the very best SK QDs making them an attractive alternative to standard InGaAs QDs

Independent operation of two waveguide-integrated quantum emitters

We demonstrate the resonant excitation of two quantum dots in a photonic integrated circuit for on-chip single-photon generation in multiple spatial modes. The two quantum dots are electrically tuned to the same emission wavelength using a pair of isolated $p$-$i$-$n$ junctions and excited by a resonant pump laser via dual-mode waveguides. We demonstrate two-photon quantum interference visibility of $(79\pm2)\%$ under continuous-wave excitation of narrow-linewidth quantum dots. Our work solves an outstanding challenge in quantum photonics by realizing the key enabling functionality of how to scale-up deterministic single-photon sources.Comment: 7 pages 3 figures, Supplementary materials 7 pages 9 figure

The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metastatic cancer cells. In order to improve the prognosis of patients with bone metastases this cycle must be broken. Radium-223 dichloride (radium-223), the first targeted alpha therapy (TAT) approved, is an osteomimetic radionuclide that is incorporated into bone metastases where its high-linear energy transfer alpha radiation disrupts both the activity of bone cells and cancer cells. Therefore, radium-223 treatment has been shown preclinically to directly affect cancer cells in both osteolytic breast cancer and osteoblastic prostate cancer bone metastases as well as to inhibit the differentiation of osteoblasts and osteoclasts. Clinical studies have demonstrated an increase in survival in patients with metastatic castration-resistant prostate cancer. Due to the effectiveness and low toxicity of radium-223, several novel combination treatment strategies are currently eliciting considerable research interest

A Genetically Encoded Dark-to-Bright Biosensor for Visualisation of Granzyme-Mediated Cytotoxicity

Granzyme B (GZMB) is a key enzyme released by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells to induce apoptosis in target cells. We designed a novel fluorogenic biosensor which is able to assess GZMB activity in a specific and sensitive manner. This cleavage-responsive sensor for T cell activity level (CRSTAL) is based on a fluorescent protein that is only activated upon cleavage by GZMB or caspase-8. CRSTAL was tested in stable cell lines and demonstrated a strong and long-lasting fluorescence signal upon induction with GZMB. It can detect GZMB activity not only by overexpression of GZMB in target cells but also following transfer of GZMB and perforin from effector cells during cytotoxicity. This feature has significant implications for cancer immunotherapy, particularly in monitoring the efficacy of chimeric antigen receptor (CAR)-T cells. CAR-T cells are a promising therapy option for various cancer types, but monitoring their activity in vivo is challenging. The development of biosensors like CRSTAL provides a valuable tool for monitoring of CAR-T cell activity. In summary, CRSTAL is a highly sensitive biosensor that can detect GZMB activity in target cells, providing a means for evaluating the cytotoxic activity of immune cells and monitoring T cell activity in real time.Deutsche Forschungsgemeinschaf

Allosteric MEK1/2 Inhibitor Refametinib (BAY 86-9766) in Combination with Sorafenib Exhibits Antitumor Activity in Preclinical Murine and Rat Models of Hepatocellular Carcinoma

OBJECTIVE: The objectives of the study were to evaluate the allosteric mitogen-activated protein kinase kinase (MEK) inhibitor BAY 86-9766 in monotherapy and in combination with sorafenib in orthotopic and subcutaneous hepatocellular carcinoma (HCC) models with different underlying etiologies in two species. DESIGN: Antiproliferative potential of BAY 86-9766 and synergistic effects with sorafenib were studied in several HCC cell lines. Relevant pathway signaling was studied in MH3924a cells. For in vivo testing, the HCC cells were implanted subcutaneously or orthotopically. Survival and mode of action (MoA) were analyzed. RESULTS: BAY 86-9766 exhibited potent antiproliferative activity in HCC cell lines with half-maximal inhibitory concentration values ranging from 33 to 762 nM. BAY 86-9766 was strongly synergistic with sorafenib in suppressing tumor cell proliferation and inhibiting phosphorylation of the extracellular signal-regulated kinase (ERK). BAY 86-9766 prolonged survival in Hep3B xenografts, murine Hepa129 allografts, and MH3924A rat allografts. Additionally, tumor growth, ascites formation, and serum alpha-fetoprotein levels were reduced. Synergistic effects in combination with sorafenib were shown in Huh-7, Hep3B xenografts, and MH3924A allografts. On the signaling pathway level, the combination of BAY 86-9766 and sorafenib led to inhibition of the upregulatory feedback loop toward MEK phosphorylation observed after BAY 86-9766 monotreatment. With regard to the underlying MoA, inhibition of ERK phosphorylation, tumor cell proliferation, and microvessel density was observed in vivo. CONCLUSION: BAY 86-9766 shows potent single-agent antitumor activity and acts synergistically in combination with sorafenib in preclinical HCC models. These results support the ongoing clinical development of BAY 86-9766 and sorafenib in advanced HCC

A coherent spin-photon interface with waveguide induced cycling transitions

Solid-state quantum dots are promising candidates for efficient light-matter interfaces connecting internal spin degrees of freedom to the states of emitted photons. However, selection rules prevent the combination of efficient spin control and optical cyclicity in this platform. By utilizing a photonic crystal waveguide we here experimentally demonstrate optical cyclicity up to $\approx15$ through photonic state engineering while achieving high fidelity spin initialization and coherent optical spin control. These capabilities pave the way towards scalable multi-photon entanglement generation and on-chip spin-photon gates.Comment: 5 pages, 4 figure