Modeling of the Division Point of Different Propagation Mechanisms in the Near-Region Within Arched Tunnels

An accurate characterization of the near-region propagation of radio waves inside tunnels is of practical importance for the design and planning of advanced communication systems. However, there has been no consensus yet on the propagation mechanism in this region. Some authors claim that the propagation mechanism follows the free space model, others intend to interpret it by the multi-mode waveguide model. This paper clarifies the situation in the near-region of arched tunnels by analytical modeling of the division point between the two propagation mechanisms. The procedure is based on the combination of the propagation theory and the three-dimensional solid geometry. Three groups of measurements are employed to verify the model in different tunnels at different frequencies. Furthermore, simplified models for the division point in five specific application situations are derived to facilitate the use of the model. The results in this paper could help to deepen the insight into the propagation mechanism within tunnel environments

New perspectives for pharmacological chaperoning treatment in methylmalonic aciduria cblB type

Methylmalonic aciduria cblB type (MMA cblB) is caused by the impairment of ATP:cob(I)alamin adenosyltransferase (ATR), the enzyme responsible for the synthesis of adenosylcobalamin (AdoCbl) from cob(I)alamin. No definitive treatment is available for patients with this condition and novel therapeutic strategies are therefore much needed. Recently, we described a proof-of-concept regarding the use of pharmacological chaperones as a treatment. This work describes the effect of two potential pharmacological chaperones - compound V (N-{[(4-chlorophenyl)carbamothioyl]amino}-2-phenylacetamide) and compound VI (4-(4-(4-fluorophenyl)-5-methyl-1H-pyrazol-3-yl)benzene-1,3-diol) - on six ATR mutants, including the most common, p.Arg186Trp. Comprehensive functional analysis identified destabilizing (p.Arg186Gln, p.Arg190Cys, p.Arg190His, p.Arg191Gln and p.Glu193Lys) and oligomerization (p.Arg186Trp and p.Arg191Gln) mutations. In a cellular model overexpressing the destabilizing/oligomerization mutations, compounds V and VI had a positive effect on the stability and activity of all ATR variants. When provided in combination with hydroxocobalamin a more positive effect was obtained than with the compounds alone, even in mutations previously described as B12 non-responsive. In addition, a normal oligomerization profile was recovered after treatment of the p.Arg186Trp mutant with both compounds. These promising results confirm MMA cblB type as a conformational disorder and hence, pharmacological chaperones as a new therapeutic option alone or in combination with hydroxocobalamin for many patients with MMA cblBThis work was supported by Instituto de Salud Carlos III and (grant PI13/01239) plus grants from the Fundación Isabel Gemio and Obra Social de La Caixa to BP; the Research Council of Norway [nr. 185181 to AM], The KG Jebsen Foundation, and NovoSeeds (Novo Nordisk). AG was supported by a Ramón y Cajal grant from the Ministerio de Ciencia y Tecnología. This work was supported also by the European Regional Development Fund (PI13/01239

Channel Capacities for Different Antenna Arrays with Various Transmitting Angles in Tunnels

[[abstract]]This paper focuses on the research of channel capacity of multiple-input multipleoutput (MIMO) system with different transmitting angles in straight and curvy tunnels.Araytracing technique is developed to calculate channel frequency responses for tunnels, and the channel frequency response is further used to calculate corresponding channel capacity. The channel capacities are calculated based on the realistic environment. The channel capacities of MIMO long term evolution system using spatial and polar antenna arrays by different transmitting angles are computed. Numerical results show that, The channel capacity for transmitting angle at 15◦ is largest compared to the other angles in the tunnels. Moreover, the channel capacity of polar array is better than that of spatial array both in the straight and curvy tunnels. Besides, the channel capacity for the tunnels with traffic is larger than that without traffic. Finally, it isworth noting that in these cases the presentwork provides not only comparative information but also quantitative information on the performance reduction.[[notice]]補正完畢[[incitationindex]]SC

A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Objective: We evaluated ibrutinib, a once-daily inhibitor of Bruton's tyrosine kinase, combined with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma who had received 1-3 prior therapies. Methods: This was a phase 2, single-arm, open-label, multicentre study (NCT02902965). The primary endpoint was progression-free survival (PFS). Results: Seventy-six patients were enrolled; 74 received ≥1 dose of study treatment. After median follow-up of 19.6 months, median PFS was 8.5 months (95% CI: 6.2-10.8); median overall survival was not reached. Overall response rate was 57% (95% CI: 45-68), and median duration of response was 9.5 months (95% CI: 6.9-10.6). Grade 3/4 AEs occurred in 73% of patients and fatal AEs occurred in 15% of patients. Incidence of major haemorrhage was 5%; one patient died from cerebral haemorrhage. After an observed increased incidence of serious (42%) and fatal (11%) infections, enrolment was suspended to implement risk-minimisation measures. The safety profile was otherwise consistent with known safety profiles of the individual drugs. Conclusion: Ibrutinib combined with bortezomib and dexamethasone elicited clinical responses. However, efficacy assessments conducted at potential restart of enrolment indicated that the targeted PFS could not be reached with additional patient enrolment, and the study was terminated

Microabrasion in tooth enamel discoloration defects: three cases with long-term follow-ups

Superficial irregularities and certain intrinsic stains on the dental enamel surfaces can be resolved by enamel microabrasion, however, treatment for such defects need to be confined to the outermost regions of the enamel surface. Dental bleaching and resin-based composite repair are also often useful for certain situations for tooth color corrections. This article presented and discussed the indications and limitations of enamel microabrasion treatment. Three case reports treated by enamel microabrasion were also presented after 11, 20 and 23 years of follow-ups

The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets