Status of the LHCb magnet system

The LHCb experiment focuses on the precision measurement of CP violation and rare decays in the B-meson system. It plans to operate with an average luminosity of $2\times 10^{32}$~cm$^{-2}$s$~^{-1}$, which should be obtained from the beginning of the LHC operation. The LHCb detector exploits the forward region of the pp collisions at the LHC collider. It requires a single-arm spectrometer for the separation and momentum measurement of the charged particles with a large dipole magnet of a free aperture of $\pm 300$~mrad horizontally and $\pm 250$~mrad vertically. The magnet is designed for a total integrated field of 4~Tm. The pole gap is 2.2 to 3.5~m vertically (the direction of the field) and 2.6 to 4.2~m horizontally. The overall length of the magnet (in beam direction) is 5~m and its total weight about 1500~t. The power dissipation in the aluminium coils will be 4.2~MW. The magnet yoke is constructed from low carbon steel plates of 100~mm thickness. The maximum weight of one plate does not exceed 25~t. The coils are wound from large hollow aluminium conductor of $50~{\rm mm}\times 50~{\rm mm}$ cross-section with a central cooling channel of 25~mm diameter for the pressurized demineralized water. Each of the two coils is composed of 15~monolayer pancakes of 15~turns per pancake. To reach good field quality the coils are bent by 45$^\circ$ towards the gap along the horizontal aperture of $\pm 300$~mrad and the pole pieces have large shims. The underlying magnet design, its present status and milestones will be reviewed

PD-0283: 4D dose accumulation for dose painting by numbers for lung cancer

In conventional radiotherapy of locally advanced lung cancer (LALC) doses levels are homogeneously delivered to the entire PTV, whereat dose escalation is restricted by normal tissue toxicity. Several studies have shown the geometrical correlation between high FDG uptake in a PET scan and tumour recurrence. This is the rationale for FDG-based local dose escalation, e.g. by dose prescription on the voxel values of a PET scan – dose painting by numbers (DPBN). The aim of this study is to investigate the robustness of the DPBN plans against tumour motio

Comprehensive CRISPR-Cas9 screens identify genetic determinants of drug responsiveness in multiple myeloma

The introduction of new drugs in the past years has substantially improved outcome in multiple myeloma (MM). However, the majority of patients eventually relapse and become resistant to one or multiple drugs. While the genetic landscape of relapsed/ resistant multiple myeloma has been elucidated, the causal relationship between relapse-specific gene mutations and the sensitivity to a given drug in MM has not systematically been evaluated. To determine the functional impact of gene mutations, we performed combined whole-exome sequencing (WES) of longitudinal patient samples with CRISPR-Cas9 drug resistance screens for lenalidomide, bortezomib, dexamethasone, and melphalan. WES of longitudinal samples from 16 MM patients identified a large number of mutations in each patient that were newly acquired or evolved from a small subclone (median 9, range 1-55), including recurrent mutations in TP53, DNAH5, and WSCD2. Focused CRISPR-Cas9 resistance screens against 170 relapse-specific mutations functionally linked 15 of them to drug resistance. These included cereblon E3 ligase complex members for lenalidomide, structural genes PCDHA5 and ANKMY2 for dexamethasone, RB1 and CDK2NC for bortezomib, and TP53 for melphalan. In contrast, inactivation of genes involved in the DNA damage repair pathway, including ATM, FANCA, RAD54B, and BRCC3, enhanced susceptibility to cytotoxic chemotherapy. Resistance patterns were highly drug specific with low overlap and highly correlated with the treatment-dependent clonal evolution in patients. The functional association of specific genetic alterations with drug sensitivity will help to personalize treatment of MM in the future

Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia

Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia

Модернизация ректификационной колонны разделения пропан-пропиленовой фракции

Объектом проектирования является ректификационная колонна непрерывного действия для разделения пропан пропиленовой фракции, а также конденсатора-холодильника для конденсации пропилена. Целью работы является расчет ректификационной колонны и конденсатора-холодильника. В ходе расчета колонны был составлен материальный баланс колонны, рассчитано оптимальное флегмовое число и оптимальное значение числа теоретических тарелок. Так же был выполнен конструктивно-механический расчет. Входе которого определили исполнительную марку стали ректификационной колонны, условия прочности и устойчивости, найдены значения толщины стенки цилиндрической обечайки, эллиптических днища и крышки. Произведен расчет штуцеров и фланцев. В технологическом расчете теплообменника был составлен тепловой баланс. РассчитаныThe design object is a continuous distillation column for the separation of propane propylene fraction, as well as a condenser-cooler for condensation of propylene. The aim of the work is to calculate the distillation column and condenser-refrigerator. During the calculation of the column, the material balance of the column was compiled, the optimal reflux ratio and the optimal value of the number of theoretical plates were calculated. A structural and mechanical calculation was also performed. The inlet of which the executive grade of the distillation column was determined, the strength and stability conditions, the wall thickness of the cylindrical shell, elliptical bottom and cover were found. Calculation of fittings and flanges. In the technological calculation of the heat exchanger,

Search for neutral charmless B decays at LEP

A search for rare charmless decays of \Bd and \Bs mesons has been performed in the exclusive channels \Bd_{(\mathrm s)}\ra\eta\eta, \Bd_{(\mathrm s)}\ra\eta\pio and \Bd_{(\mathrm s)}\ra\pio\pio. The data sample consisted of three million hadronic \Zo decays collected by the L3 experiment at LEP from 1991 through 1994. No candidate event has been observed and the following upper limits at 90\% confidence level on the branching ratios have been set \begin{displaymath} \mathrm{Br}(\Bd\ra\eta\eta)<4.1\times 10^{-4},\,\, \mathrm{Br}(\Bs\ra\eta\eta)<1.5\times 10^{-3},\,\, \end{displaymath} \begin{displaymath} \mathrm{Br}(\Bd\ra\eta\pio)<2.5\times 10^{-4},\,\, \mathrm{Br}(\Bs\ra\eta\pio)<1.0\times 10^{-3},\,\, \end{displaymath} \begin{displaymath} \mathrm{Br}(\Bd\ra\pio\pio)<6.0\times 10^{-5},\,\, \mathrm{Br}(\Bs\ra\pio\pio)<2.1\times 10^{-4}. \end{displaymath} These are the first experimental limits on \Bd\ra\eta\eta and on the \Bs neutral charmless modes