Influence of Technological Process Parameters of Cargo Transportation on the Variable Component of the Total Costs

Ефективність процесу перевезення вантажів визначається його витратами, що залежать від параметрів транспортних технологій. Управління витратами є актуальною проблемою в умовах ринкових змін. Проаналізовано вплив параметрів технологічного процесу перевезення вантажів на змінну складову загальних витрат. В результаті отримано двофакторну регресійну модель визначення змінних витрат, в яку, в якості змінних, увійшли вантажопідйомність транспортного засобу і його питома витрата палива. Результати аналізу статистичних показників свідчать про її адекватність і можливість застосування на практиці.The efficiency of cargo transportation process is determined by its costs, which depend on the parameters of transport technologies. These include labor costs, the cost of spare parts, fuel and lubricants, repair and maintenance of roads and transport, the cost of building maintenance, taxes and others. It is common practice to divide the costs into those independent and dependent on the volume of production. The first group is referred to as variable costs, the second - to the fixed costs. Road freight transport variable costs are directly related to the implementation of the transport operation. Cost management is an urgent problem in the conditions of market transformations. Within the framework of the research the authors have analyzed the impact of transport technology parameters to the variable component of the total cost. The conducted analysis resulted in creating a two-factor regression model for determining the variable costs which include the vehicle load and its specific fuel consumption as variables. The results of the analysis of statistical indicators show its adequacy and possibility of applying in practice

Pirt, a Phosphoinositide-Binding Protein, Functions as a Regulatory Subunit of TRPV1

SummaryTransient receptor potential vanilloid 1 (TRPV1) is a molecular sensor of noxious heat and capsaicin. Its channel activity can be modulated by several mechanisms. Here we identify a membrane protein, Pirt, as a regulator of TRPV1. Pirt is expressed in most nociceptive neurons in the dorsal root ganglia (DRG) including TRPV1-positive cells. Pirt null mice show impaired responsiveness to noxious heat and capsaicin. Noxious heat- and capsaicin-sensitive currents in Pirt-deficient DRG neurons are significantly attenuated. Heterologous expression of Pirt strongly enhances TRPV1-mediated currents. Furthermore, the C terminus of Pirt binds to TRPV1 and several phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP2), and can potentiate TRPV1. The PIP2 binding is dependent on the cluster of basic residues in the Pirt C terminus and is crucial for Pirt regulation of TRPV1. Importantly, the enhancement of TRPV1 by PIP2 requires Pirt. Therefore, Pirt is a key component of the TRPV1 complex and positively regulates TRPV1 activity

Casimir force on interacting Bose-Einstein condensate

We have presented an analytic theory for the Casimir force on a Bose-Einstein condensate (BEC) which is confined between two parallel plates. We have considered Dirichlet boundary conditions for the condensate wave function as well as for the phonon field. We have shown that, the condensate wave function (which obeys the Gross-Pitaevskii equation) is responsible for the mean field part of Casimir force, which usually dominates over the quantum (fluctuations) part of the Casimir force.Comment: Accepted in Journal of Physics B: Atomic, Molecular and Optical Physic

Phase 3 KEYNOTE-042 Study: Pembrolizumab vs Platinum-Based Chemotherapy as 1l Therapy for Advanced NSCLC with a PD-L1 TPS ≥1%

First-line (1L) therapy with pembrolizumab in patients with metastatic NSCLC without targetable aberrations and programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% significantly improved the primary endpoint of PFS, and OS (secondary endpoint) compared to chemotherapy in the KEYNOTE-024 study. In KEYNOTE-042 (NCT02220894), we evaluated pembrolizumab vs chemotherapy at the lower PD-L1 TPS of ≥1%

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities

PS1 Phase 3 KEYNOTE-042 Study: Pembrolizumab vs Platinum-Based Chemotherapy as 1l Therapy for Advanced NSCLC with a PD-L1 TPS ≥1%

First-line (1L) therapy with pembrolizumab in patients with metastatic NSCLC without targetable aberrations and programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% significantly improved the primary endpoint of PFS, and OS (secondary endpoint) compared to chemotherapy in the KEYNOTE-024 study. In KEYNOTE-042 (NCT02220894), we evaluated pembrolizumab vs chemotherapy at the lower PD-L1 TPS of ≥1%

Pirt, a TRPV1 Modulator, Is Required for Histamine-Dependent and -Independent Itch

Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood. Recent work has begun to identify genes that contribute to detecting itch at the molecular level. Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation. Pirt−/− mice exhibit deficits in cellular and behavioral responses to various itch-inducing compounds, or pruritogens. Pirt contributes to both histaminergic and nonhistaminergic itch and, crucially, is involved in forms of itch that are both TRPV1-dependent and -independent. Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways

Raman and Mössbauer spectroscopic studies of tungsten doped Ni–Zn nano ferrite

In this study, tungsten substituted Ni-Zn nano ferrites of the composition Ni0.5Zn0.5WxFe2−xO4 with x = 0.0, 0.2, 0.4 have been synthesized by a co-precipitation method. The prepared samples were pre-sintered at 850 °C and then annealed at 1000 °C for 3 h each. The structural, morphological, optical and magnetic properties of these samples were studied by using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy (RS) and Mössbauer spectroscopy (MS). XRD revealed the formation of spinel single-phase structure with an average crystallite size of 53–60 nm. Fourier transform infrared spectroscopy show two prominent peaks primarily due to the tetrahedral and octahedral stretching vibrations in the range of 400–600 cm−1. Raman spectra indicate first order three Raman active modes; (A1 g + Eg + T2 g) at around 688, 475 and 326 cm−1. Mössbauer spectroscopy reveals that substitution of W3+ for Fe3+ cation results in reduction of total magnetic moment and consequently the net magnetization