Micro-resonator soliton generated directly with a diode laser

An external-cavity diode laser is reported with ultralow noise, high power coupled to a fiber, and fast tunability. These characteristics enable the generation of an optical frequency comb in a silica micro-resonator with a single-soliton state. Neither an optical modulator nor an amplifier was used in the experiment. This demonstration greatly simplifies the soliton generation setup and represents a significant step forward to a fully integrated soliton comb system.Comment: 7 pages, 5 figure

Tumor-Targeted Synergistic Blockade of MAPK and PI3K from a Layer-by-Layer Nanoparticle

Purpose: Cross-talk and feedback between the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR cell signaling pathways is critical for tumor initiation, maintenance, and adaptive resistance to targeted therapy in a variety of solid tumors. Combined blockade of these pathways—horizontal blockade—is a promising therapeutic strategy; however, compounded dose-limiting toxicity of free small molecule inhibitor combinations is a significant barrier to its clinical application. Experimental Design: AZD6244 (selumetinib), an allosteric inhibitor of Mek1/2, and PX-866, a covalent inhibitor of PI3K, were co-encapsulated in a tumor-targeting nanoscale drug formulation—layer-by-layer (LbL) nanoparticles. Structure, size, and surface charge of the nanoscale formulations were characterized, in addition to in vitro cell entry, synergistic cell killing, and combined signal blockade. In vivo tumor targeting and therapy was investigated in breast tumor xenograft-bearing NCR nude mice by live animal fluorescence/bioluminescence imaging, Western blotting, serum cytokine analysis, and immunohistochemistry. Results: Combined MAPK and PI3K axis blockade from the nanoscale formulations (160 ± 20 nm, −40 ± 1 mV) was synergistically toxic toward triple-negative breast (MDA-MB-231) and RAS-mutant lung tumor cells (KP7B) in vitro, effects that were further enhanced upon encapsulation. In vivo, systemically administered LbL nanoparticles preferentially targeted subcutaneous MDA-MB-231 tumor xenografts, simultaneously blocked tumor-specific phosphorylation of the terminal kinases Erk and Akt, and elicited significant disease stabilization in the absence of dose-limiting hepatotoxic effects observed from the free drug combination. Mice receiving untargeted, but dual drug-loaded nanoparticles exhibited progressive disease. Conclusions: Tumor-targeting nanoscale drug formulations could provide a more safe and effective means to synergistically block MAPK and PI3K in the clinic.United States. Department of Defense (OCRP Teal Innovator Award)National Institutes of Health (U.S.) (Grant NIBIB 1F32EB017614-02)Misrock FoundationNational Science Foundation (U.S.)Swiss National Science FoundationDavid H. Koch Institute for Integrative Cancer Research at MIT (Support Grant P30-CA14051)National Cancer Institute (U.S.)National Science Foundation (U.S.) (Massachusetts Institute of Technology. Materials Research Science and Engineering Center. Shared Experimental Facilities Grant DMR-0819762)Breast Cancer Alliance (Exceptional Project Grant

Evaluating the impact of lane marking quality on the operation of Autonomous Vehicles

The quality of lane markings is pivotal for safe operations and efficient trajectory generations of connected and autonomous vehicles (AVs). However, most studies are devoted to enhancing in-vehicle detection systems and ignore the impact of faulty lane markings. An instrumented vehicle was employed to mimic the data input of an AV and real-world trials were conducted on (1) live motorways; and (2) a controlled motorway facility. From the live motorway data, causal factors affecting computer vision lane detection and classification algorithms were examined, and an enhanced lane classification algorithm was developed to overcome the limitations posed by poor lane markings. In the controlled motorway facility, experiments to modify the physical appearance of the lane markings were conducted to further test the performance of the developed algorithm. The detection rates of the developed lane classification algorithm were compared with the lane departure warning (LDW) system already implemented in the vehicle. Findings revealed that the LDW system is accurate over 95% and 54% of the time when lanes are faded by 50% and 75% respectively. Further testing on the quality of the lane markings was carried out virtually in such a way that the experiments were replicated in a simulation environment to (1) identify lane marking conditions that can be reliably adopted for safe operations of AVs, (2) estimate the effect of adverse weather and lighting conditions on road markings detection, and (3) address localization issues for AVs. Simulation results show that poor lane markings have a significant negative impact on AV safety, especially in inclement weather and poor light conditions inducing an increase in conflicts and delays. This can be compensated for if more sophisticated sensors are employed in AVs, and the operators of road networks develop lane-based digital road maps. Nicolette Formosa, Ph.D. https://orcid.org/0000-0002-2403-9984 [email protected], Mohammed Quddus, Ph.D. [email protected], Cheuk Ki Man, Ph.D. [email protected], Mohit Kumar Singh, Ph.D., Aff.M.ASCE https://orcid.org/0000-0001-7736-5583 [email protected], Craig Morton, Ph.D. [email protected], and Cansu Bahar Masera

Assessing temporary traffic management measures on a motorway: lane closures vs narrow lanes for connected and Autonomous Vehicles in roadworks

Connected and automated vehicles (CAVs) are being developed and designed to operate on existing roads. Their safe and efficient operation during roadworks, where traffic management measures are often introduced, is crucial. Two alternative measures are commonly applied during roadworks on motorways: (i) closing one or multiple lanes (ii) narrowing one or all lanes. The former can cause delays and increased emissions, while the latter can pose safety risks. This study uses a VISSIM-based traffic microsimulation to compare the effectiveness of these two strategies on traffic efficiency and safety, considering various market penetration rates (MPR) of CAVs. The model was calibrated and validated with the data collected from M1 motorway in the United Kingdom. Results show that average delays per vehicle-kilometre-travelled decreased from 102.7 to 2.5 s (with lane closure) and 23.6 to 0.6 s (with narrow lanes) with 0% and 100% CAV MPR, respectively. Moreover, safety in narrow lanes improved by 4.8 times compared to 1.5 times improvement in lane closure with a 100% CAV MPR; indicating that narrow lanes would result in better safety performance. These findings could assist transport authorities in designing temporary traffic management measure that results in better CAV performance when navigating through roadworks

An experiment and simulation study on developing algorithms for CAVs to navigate through roadworks

Navigating through roadworks represents one of the main sources of safety risk for Connected and Autonomous Vehicles (CAVs) due to the altered road layouts. The built-in base maps do not normally reflect these changes, causing CAVs to experience difficulties in sensing and trajectory generation. Therefore, the objective of this paper is to evaluate different collision-free trajectory generation for CAVs at roadworks to improve safety and traffic performance. Trajectory generation algorithms using lane-level dynamic maps were examined for: 1) CAVs rely on data from in-vehicle sensor only; and 2) CAVs receive additional information via a Smart Traffic Cone (STC) in advance regarding roadwork configurations. Experiments were conducted at a controlled motorway facility operated by National Highways (England) using a vehicle instrumented with a suite of sensors. Schematics of the roadworks scenario were translated into an integrated simulation platform consisting of a traffic microsimulation (VISSIM) to simulate traffic dynamics and a sub-microscopic simulator (PreScan) capable of simulating vehicle autonomy and connectivity. Results indicate that traffic conflicts and delays decrease by 40% and 3% respectively when CAVs receive additional information in advance (i.e., Scenario 2) compared to the other scenario. These findings would assist road network operators in developing ‘CAV-enabled roadworks’ and vehicle manufacturers in designing a vehicle-based ‘roadworks assist’ system

Genetic Screening of GJB2 and SLC26A4 in Korean Cochlear Implantees: Experience of Soree Ear Clinic

ObjectivesGenetic hearing loss is highly heterogeneous and more than 100 genes are predicted to cause this disorder in humans. In spite of this large genetic heterogeneity, mutations in SLC26A4 and GJB2 genes are primarily responsible for the major etiologies of genetic hearing loss among Koreans. The purpose of this study is to investigate the genetic cause of deafness in Korean cochlear implantees by performing a genetic screening of the SLC26A4 and GJB2 genes.MethodsThe study cohort included 421 unrelated Korean patients with sensorineural hearing loss (SNHL) and who had received cochlear implants (CI) at Soree Ear Clinic from July 2002 to December 2010. Among 421 CI patients, we studied 230 cases who had received the genetic screening for SLC26A4 or GJB2 genes. Written informed consent was obtained from all participants. All patients had severe to profound, bilateral hearing loss. For 56 patients who showed enlarged vestibular aqueduct on their computed tomography (CT) scan, we analyzed SLC26A4. For 174 CT negative patients, GJB2 gene was sequenced.ResultsFor the 56 SLC26A4 patients, 32 (57.1%) had two pathogenic recessive mutations in SLC26A4. A single recessive SLC26A4 mutation was identified in 14 patients (25%). H723R and IVS7-2A>G were the most commonly found mutations, accounting for 60.3% (47/78) and 30.8% (24/78) of the mutated alleles, respectively. For the 174 GJB2 patients, 20 patients (11.5%) had two pathogenic recessive mutations in GJB2. 235delC was the most common mutation, accounting for 43.0% (31/72) of mutant alleles.ConclusionThe two major genes, SLC26A4 and GJB2, contribute major causes of deafness in CI patients. Continuous studies are needed to identify new genes that can cause hearing loss to Korean CI patients

Expression of HSP70 and Its Relation with Other Cytokines in Human Middle Ear Effusion

ObjectivesWhile other cytokines are known to be associated with otitis media with effusion (OME), the involvement of heat shock protein 70 (HSP70) in middle ear effusion (MEE) is unknown. This study was undertaken to investigate the possibility of there being a HSP70 expression in human MEE and to determine its potential role as a cytokine in OME.MethodsThe levels of HSP70, tumor necrosis factor-alpha and interleukin-1beta were measured by enzyme-linked immunosorbent assay in the effusion of different groups of OME patient following collection of the MEE using our new collection system. The clinical characteristics of the OME patients and the MEE status were analyzed.ResultsHSP70 was expressed in all the types of MEE. The mucous and seromucous effusions showed higher HSP70 levels than that of the serous effusion. The HSP70 level was correlated with the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the effusions. The positive correlations between HSP70, TNF-α and IL-1β were statistically significant (P<0.05).ConclusionThe highly elevated level of HSP70 in the seromucous and mucous effusions implicates this protein in the chronicity of OME

Sentinel Lymph Node Radiolocalization with 99mTc Filtered Tin Colloid in Clinically Node-Negative Squamous Cell Carcinomas of the Oral Cavity

The objective of this study was to evaluate the feasibility of sentinel lymph node biopsy by using a radiotracer lymphatic mapping technique in patients with squamous cell carcinoma of the oral cavity, and the diagnostic value of this technique. We studied twenty patients with previously untreated squamous cell carcinomas of the oral cavity and N0 necks. After the peritumoral injection of 99mTc filtered tin colloid preop-eratively, lymphoscintigraphy and intraoperative mapping using a gamma detector were performed to localize sentinel nodes. An open biopsy of the sentinel node was followed by complete neck dissection. We identified the sentinel nodes in 19 of 20 patients (95.0%) by lymphoscintigraphy and in all (100%) by intraoperative gamma detector. In all cases, the status of the sentinel node accurately predicted the pathologic status of the neck with the false negative rate being 0%. The negative predictive value for the absence of cervical metastases was 100%. In conclusion, our radio-localization technique of sentinel nodes using 99mTc filtered tin colloid in N0 squamous cell carcinomas of the oral cavity is technically feasible and appears to accurately predict the presence of the occult metastatic disease

Desenvolvimento e modelagem de quadrirrotor: um estudo de caso

TCC (graduação) - Universidade Federal de Santa Catarina. Centro Tecnológico. Engenharia Elétrica.Este trabalho apresenta um estudo sobre o desenvolvimento e modelagem de um veículo quadrirrotor. Este documento acompanha o processo de desenvolvimento de uma dessas aeronaves, partindo de um estudo sobre as principais dinâmicas de voo e características desse tipo de sistema. No estudo é apresentado um processo de caracterização usando as diferentes componentes do aparelho, o que permitiu a modelagem e simulação do sistema. É proposto também uma solução para implementação e controle a partir desse modelo simulado

Detection of Sentinel Lymph Nodes in patients with Early Stage Cervical Cancer

The purpose of this study was to determine the feasibility of identifying the sentinel lymph nodes (SNs) as well as to evaluate factors that might influence the SN detection rate in patients with cervical cancer of the uterus. Eighty nine patients underwent intracervical injection of 1% isosulfan blue dye at the time of planned radical hysterectomy and lymphadenectomy between January 2003 and December 2003. With the visual detection of lymph nodes that stained blue, SNs were identified and removed separately. Then all patients underwent complete pelvic lymph node dissection and/or para-aortic lymph node dissection. SNs were identified in 51 of 89 (57.3%) patients. The most common site for SN detection was the external iliac area. Metastatic nodes were detected in 21 of 89 (23.5%) patients. One false negative SN was obtained. Successful SN detection was more likely in patients younger than 50 yr (p=0.02) and with a history of preoperative conization (p=0.05). However, stage, histological type, surgical procedure and neoadjuvant chemotherapy showed no significant difference for SN detection rate. Therefore, the identification of SNs with isosulfan blue dye is feasible and safe. The SN detection rate was high in patients younger than 50 yr or with a history of preoperative conization