Adenoid cystic carcinoma: emerging role of translocations and gene fusions.

Adenoid cystic carcinoma (ACC), the second most common salivary gland malignancy, is notorious for poor prognosis, which reflects the propensity of ACC to progress to clinically advanced metastatic disease. Due to high long-term mortality and lack of effective systemic treatment, the slow-growing but aggressive ACC poses a particular challenge in head and neck oncology. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to the ACC development have been recognized. Although the specific chromosomal translocations resulting in MYB-NFIB fusions provide insight into the ACC pathogenesis and represent attractive diagnostic and therapeutic targets, their clinical significance is unclear, and a substantial subset of ACCs do not harbor the MYB-NFIB translocation. Strategies based on detection of newly described genetic events (such as MYB activating super-enhancer translocations and alterations affecting another member of MYB transcription factor family-MYBL1) offer new hope for improved risk assessment, therapeutic intervention and tumor surveillance. However, the impact of these approaches is still limited by an incomplete understanding of the ACC biology, and the manner by which these alterations initiate and drive ACC remains to be delineated. This manuscript summarizes the current status of gene fusions and other driver genetic alterations in ACC pathogenesis and discusses new therapeutic strategies stemming from the current research

A new strategy to improve proactive route updates in mobile ad hoc networks

This paper presents two new route update strategies for performing proactive route discovery in mobile ad hoc networks (MANETs). The first strategy is referred to as minimum displacement update routing (MDUR). In this strategy, the rate at which route updates are sent into the network is controlled by how often a node changes its location by a required distance. The second strategy is called minimum topology change update (MTCU). In this strategy, the route updating rate is proportional to the level of topology change each node experiences. We implemented MDUR and MTCU on top of the fisheye state routing (FSR) protocol and investigated their performance by simulation. The simulations were performed in a number of different scenarios, with varied network mobility, density, traffic, and boundary. Our results indicate that both MDUR and MTCU produce significantly lower levels of control overhead than FSR and achieve higher levels of throughput as the density and the level of traffic in the network are increased

Two complex orthogonal space-time codes for eight transmit antennas

Two new constructions of complex orthogonal space-time block codes of order 8 based on the theory of amicable orthogonal designs are presented and their performance compared with that of the standard code of order 8. These new codes are suitable for multi-modulation schemes where the performance can be sacrificed for a higher throughput

Zespół pieczenia jamy ustnej

  Zespół pieczenia jamy ustnej (BMS) jest idiopatyczną jednostką chorobową manifestującą się jako długotrwałe uczucie piekącego, palącego lub kłującego bólu w obrębie błon śluzowych jamy ustnej, najczęściej języka. Dolegliwościom bólowym często towarzyszą zaburzenia smaku, uczucie suchości jamy ustnej oraz nieprawidłowości psychiatryczne. Mimo że jest to stosunkowo częste schorzenie, szczególnie w przypadku kobiet w wieku pomenopauzalnym, a jego obraz kliniczny opisuje się w literaturze medycznej od niemal 150 lat, BMS nadal stanowi mało znany problem diagnostyczny i terapeutyczny. Trudności napotykane w praktyce klinicznej są w dużej mierze wynikiem słabo poznanej, wieloczynnikowej etiologii schorzenia, nieobecnością żadnych nieprawidłowości w zakresie morfologii błon śluzowych jamy ustnej oraz niedostatkiem randomizowanych badań weryfikujących skuteczność postępowania leczniczego. Celem tego artykułu jest przybliżenie czytelnikom typowego obrazu klinicznego BMS, ukazanie znaczenia diagnostyki różnicowej zespołu oraz przedstawienie aktualnych danych dotyczących dostępnych sposobów terapii. Znajomość powyższych kwestii przez lekarzy różnych specjalności jest kluczowa dla poprawy jakości życia pacjentów cierpiących na BMS.

Stick boundary conditions and rotational velocity auto-correlation functions for colloidal particles in a coarse-grained representation of the solvent

We show how to implement stick boundary conditions for a spherical colloid in a solvent that is coarse-grained by the method of stochastic rotation dynamics. This allows us to measure colloidal rotational velocity auto-correlation functions by direct computer simulation. We find quantitative agreement with Enskog theory for short times and with hydrodynamic mode-coupling theory for longer times. For aqueous colloidal suspensions, the Enskog contribution to the rotational friction is larger than the hydrodynamic one when the colloidal radius drops below 35nm.Comment: new version with some minor change

Psychosocial aspects of closed- and open-loop insulin delivery: closing the loop in adults with Type 1 diabetes in the home setting.

AIMS: To explore the psychosocial experiences of closed-loop technology and to compare ratings of closed- and open-loop technology for adults with Type 1 diabetes taking part in a randomized crossover study. METHODS: Adults (aged > 18 years) on insulin pump therapy were recruited to receive a first phase of either real-time continuous glucose monitoring with overnight closed-loop or real-time continuous glucose monitoring alone (open-loop) followed by a second phase of the alternative treatment in random order, at home for 4 weeks, unsupervised. Participants were invited to share their views in semi-structured interviews. The impact of the closed-loop technology, positive and negative aspects of living with the device overnight, along with the hopes and anxieties of the participants, were explored. RESULTS: The participants in the trial were 24 adults with a mean (sd) age of 43 (12) years, of whom 54% were men. The mean (range) interview duration was 26 (12-46) min. Content and thematic analysis showed the following key positive themes: improved blood glucose control (n = 16); reassurance/reduced worry (n = 16); improved overnight control leading to improved daily functioning and diabetes control (n = 16); and improved sleep (n = 8). The key negative themes were: technical difficulties (n = 24); intrusiveness of alarms (n = 13); and size of equipment (n = 7). Of the 24 participant, 20 would recommend the closed-loop technology. CONCLUSIONS: Closed-loop therapy has positive effects when it works in freeing participants from the demands of self-management. The downside was technical difficulties, particularly concerning the pump and 'connectivity', which it is hoped will improve. Future research should continue to explore the acceptability of the closed-loop system as a realistic therapy option, taking account of user concerns as new systems are designed. Failure to do this may reduce the eventual utility of new systems.Diabetes UKThis is the accepted manuscript. The final version is available at http://dx.doi.org/10.1111/dme.12706

Protein Shape Sampled by Ion Mobility Mass Spectrometry Consistently Improves Protein Structure Prediction

Ion mobility (IM) mass spectrometry provides structural information about protein shape and size in the form of an orientationally-averaged collision cross-section (CCSIM). While IM data have been used with various computational methods, they have not yet been utilized to predict monomeric protein structure from sequence. Here, we show that IM data can significantly improve protein structure determination using the modelling suite Rosetta. We develop the Rosetta Projection Approximation using Rough Circular Shapes (PARCS) algorithm that allows for fast and accurate prediction of CCSIM from structure. Following successful testing of the PARCS algorithm, we use an integrative modelling approach to utilize IM data for protein structure prediction. Additionally, we propose a confidence metric that identifies near native models in the absence of a known structure. The results of this study demonstrate the ability of IM data to consistently improve protein structure prediction

Mid-infrared frequency comb spanning an octave based on an Er fiber laser and difference-frequency generation

We describe a coherent mid-infrared continuum source with 700 cm-1 usable bandwidth, readily tuned within 600 - 2500 cm-1 (4 - 17 \mum) and thus covering much of the infrared "fingerprint" molecular vibration region. It is based on nonlinear frequency conversion in GaSe using a compact commercial 100-fs-pulsed Er fiber laser system providing two amplified near-infrared beams, one of them broadened by a nonlinear optical fiber. The resulting collimated mid-infrared continuum beam of 1 mW quasi-cw power represents a coherent infrared frequency comb with zero carrier-envelope phase, containing about 500,000 modes that are exact multiples of the pulse repetition rate of 40 MHz. The beam's diffraction-limited performance enables long-distance spectroscopic probing as well as maximal focusability for classical and ultraresolving near-field microscopies. Applications are foreseen also in studies of transient chemical phenomena even at ultrafast pump-probe scale, and in high-resolution gas spectroscopy for e.g. breath analysis.Comment: 8 pages, 2 figures revised version, added reference