Miracle-dz/UniFAR-FTUs huggingface dataset:
Multicenter Phase II Study of Whole-Body and Intracranial Activity With Ceritinib in Patients With ALK-Rearranged Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib: Results From ASCEND-2.

PURPOSE Phase I data (ASCEND-1) showed ceritinib efficacy in patients with ALK-rearranged non-small-cell lung cancer (NSCLC), regardless of brain metastases status and with or without prior therapy with an inhibitor of the ALK protein. Data are presented from a phase II trial (ASCEND-2) in which ceritinib efficacy and safety were evaluated in patients who had ALK-rearranged NSCLC previously treated with at least one platinum-based chemotherapy and who had experienced progression during crizotinib treatment as their last prior therapy. PATIENTS AND METHODS Patients with advanced ALK-rearranged NSCLC, including those with asymptomatic or neurologically stable baseline brain metastases, received oral ceritinib 750 mg/d. Whole-body and intracranial responses were investigator assessed (according to RECIST version 1.1). Patient-reported outcomes were evaluated with the Lung Cancer Symptom Scale and European Organisation for Research and Treatment of Cancer surveys (the core-30 and the 13-item lung cancer-specific quality-of-life questionnaires). RESULTS All 140 patients enrolled had received two or more previous treatment regimens, and all patients had received crizotinib. The median duration of exposure and the follow-up time with ceritinib were 8.8 months (range, 0.1 to 19.4 months) and 11.3 months (range, 0.1 to 18.9 months), respectively. Investigator-assessed overall response rate was 38.6% (95% CI, 30.5% to 47.2%). Secondary end points, all investigator assessed, included disease control rate (77.1%; 95% CI, 69.3% to 83.8%), time to response (median, 1.8 months; range, 1.6 to 5.6 months), duration of response (median, 9.7 months; 95% CI, 7.1 to 11.1 months), and progression-free survival (median, 5.7 months; 95% CI, 5.4 to 7.6 months). Of 100 patients with baseline brain metastases, 20 had active target lesions at baseline; investigator-assessed intracranial overall response rate was 45.0% (95% CI, 23.1% to 68.5%). The most common adverse events (majority, grade 1 or 2) for all treated patients were nausea (81.4%), diarrhea (80.0%), and vomiting (62.9%). Patient-reported outcomes showed a trend toward improved symptom burden. The global quality-of-life score was maintained during treatment. CONCLUSION Consistent with its activity in ASCEND-1, ceritinib treatment provided clinically meaningful and durable responses with manageable tolerability in chemotherapy- and crizotinib-pretreated patients, including those with brain metastases.
The US “Twin Deficits”: A Reappraisal

Une importante littérature empirique a analysé, depuis le milieu des années 80, la relation entre les déficits budgétaires et commerciaux des Etats-Unis, sans jamais atteindre un consensus. Deux éléments peu-vent être pris en compte pour expliquer ces résultats contradictoires. La comparaison des données à niveau par rapport aux données stationnarisées a un impact sur les conclusions. On remarque, à côté de cela, que le lien entre les exportations nettes et le solde budgétaire des Etats-Unis, stationnarisés ou non, est instable. Ce manque de robustesse peut venir de changements dans la contribution relative des chocs de demande et d’oñre dans l’économie américaine : les chocs de demande génèrent généralement une corrélation positive entre les déficits commerciaux et fiscaux, tandis que les chocs d’offre impliquent une corrélation négative entre les deux séries. Afín de contrôler la relevance empirique de cette intuition, nous avons employé un modèle RBC standard. Avec différents taux estimés de volatilité des chocs d’offre et de demande, le modèle répond aux changements de corrélation entre la balance commerciale et fiscale des Etats-Unis pour chaque sous-exemple, exceptés les années 90.
Incremental bit rates in FDD networks for LTE advanced over LTE

Long Term Evolution (LTE) Networks are being planned to be upgraded to LTE Advanced along with increasing availability of Release 10 User Equipment (UEs) and Spectrum Availability for Carrier Aggregation. LTE Advanced brings a major step increase in Down Link and Uplink Throughputs and related spectral efficiencies. This paper explains the evolution of Frequency Division Duplex (FDD) throughputs for different Channel Bandwidths. The maximum theoretical physical layer throughputs and expected actual application layer throughputs after removing the necessary overheads by different broadcast, signaling, synchronization & random access channels have been explained with an impact analysis thereof. Throughput gains for upcoming LTE Advanced deployments have been computed for Frame Structure Type 1 (FDD) for Channel Bandwidth of 1.4 MHz, 3MHz, 5 MHz, 10 MHz, 15 MHz and 20 MHz along with Carrier Aggregation of 2 & 5 Component Carriers. Impact of increasing Signaling Channels, retransmissions & code rate on throughputs has been explained so that the computations can be extended to any deployment scenario.
Ultrastructural studies of eight cases of fetal Tay-Sachs disease.

7 fetuses of 27 high risk pregnancies showed absence of hexosaminidase A and were aborted. In all 7 cases, biochemical examination of fetal tissue confirmed the diagnosis. In the brains of the Tay-Sachs disease fetuses electronmicroscopy showed an increase in G-M2 ganglioside and absence of hexosaminidase A. By 12 weeks gestation abnormal cytoplasmic inclusions were present in the spinal cord. By 22 weeks, ganglion cells of the retina and spinal ganglia showed alteration of cellular organelles and abnormal lipid material in the cytoplasm. Attempts at enzyme replacement were unseccessful.
Double-integrating-sphere system at the National Institute of Standards and Technology in support of measurement standards for the determination of optical properties of tissue-mimicking phantoms

Abstract. There is a need for a common reference point that will allow for the comparison of the optical properties of tissue-mimicking phantoms. After a brief review of the methods that have been used to measure the phantoms for a contextual backdrop to our approach, this paper reports on the establishment of a standardized double-integrating-sphere platform to measure absorption and reduced scattering coefficients of tissue-mimicking biomedical phantoms. The platform implements a user-friendly graphical user interface in which variations of experimental configurations and model-based analysis are implemented to compute the coefficients based on a modified inverse adding-doubling algorithm allowing a complete uncertainty evaluation. Repeatability and validation of the measurement results of solid phantoms are demonstrated for three samples of different thicknesses, d=5.08 mm, 7.09 mm, and 9.92 mm, with an absolute error estimate of 4.0% to 5.0% for the absorption coefficient and 11% to 12% for the reduced scattering coefficient (k=2). The results are in accordance with those provided by the manufacturer. Measurements with different polarization angles of the incident light are also presented, and the resulting optical properties were determined to be equivalent within the estimated uncertainties.
Low Cost Plastic Optical Fiber Pressure Sensor Embedded in Mattress for Vital Signal Monitoring

The aim of this paper is to report the design of a low-cost plastic optical fiber (POF) pressure sensor, embedded in a mattress. We report the design of a multipoint sensor, a cheap alternative to the most common fiber sensors. The sensor is implemented using Arduino board, standard LEDs for optical communication in POF (λ = 645 nm) and a silicon light sensor. The Super ESKA® plastic fibers were used to implement the fiber intensity sensor, arranged in a 4 × 4 matrix. During the breathing cycles, the force transmitted from the lungs to the thorax is in the order of tens of Newtons, and the respiration rate is of one breath every 2–5 s (0.2–0.5 Hz). The sensor has a resolution of force applied on a single point of 2.2–4.5%/N on the normalized voltage output, and a bandwidth of 10 Hz, it is then suitable to monitor the respiration movements. Another issue to be addressed is the presence of hysteresis over load cycles. The sensor was loaded cyclically to estimate the drift of the system, and the hysteresis was found to be negligible.
Transformational leadership takes Majan to the top of the class

Purpose – This paper aims to detail the human resource management practices that have helped Majan College, Oman, to win a string of prizes for total quality management.Design/methodology/approach – The paper outlines the characteristics of four main leadership styles – transformational, authoritarian, participative and delegative – and describes the benefits the college has gained by, in the main, practicing transformational leadership.Findings – The paper shows that, when transformational leadership is practiced, team members believe that their leaders care about them as people, rather than as a means to an end; leaders pay close attention to team members' need for achievement and personal growth, creating an environment in which team members feel that they are pursuing meaningful goals; and leaders gain credibility and respect by “walking the talk”. Practical implications – The paper provides useful information on the advantages and disadvantages of various leadership styles, when practiced in an academ.
TCAD simulation of interface traps related variability in bulk decananometer mosfets

Interface traps can introduce random variations in the drain current of MOSFETs, becoming a source of device variability. In this work, 2D and 3D TCAD simulations of devices with channel length in the decananometer range are carried out to analyze the impact of their spatial distribution on the drift of the threshold voltage. 2D simulations show that traps located close to the center of the channel lead to larger threshold voltage shifts. Moreover, as the non-uniformity increases, larger threshold voltages and variability are observed. 3D simulations indicate that this trend is only observed in large area devices, pointing out that the study of the variability of small area devices must be carried out through 3D simulations.
Bidirectional WDM-PON based on gain-saturated reflective semiconductor optical amplifiers

We propose a bidirectional wavelength-division-multiplexed passive optical network by employing gain-saturated reflective semiconductor optical amplifiers (RSOAs) for wavelength-independent optical network terminals. The fabricated RSOA module has the input saturation power less than -13 dBm and its saturated gain higher than 13 dB within the C-band for arbitrary polarization states. The upstream signals are generated by remodulating the downstream signals whose modulation amplitude is squeezed through gain-saturated RSOAs. We present experimental results on bidirectional transmission with 1.25 Gb/s for upstream and 2.5 Gb/s for downstream data rates over 20-km transmission distance.
The role of nuclear factor kappa B and nitric oxide interaction in heart remodelling

Hypertrophy of the myocardium is induced by haemodynamic and humoral alterations, which in turn stimulate the production of factors triggering protein synthesis, thus initiating myocardial growth. It has recently been documented that nuclear factor kappa B (NF-κB) represents a key factor that mediates both neurohormonal and proinflammatory signals leading finally to hypertrophic and/or fibrotic processes in the cardiovascular system. It was suggested that blockade of NF-κB may exert a protective effect against pathological myocardial growth. Recent data indicate that increased activity of NF-κB, besides its deleterious effects, leads to the increased production of nitric oxide, which as a result of its hypotensive and antigrowth activity exerts protection against the hypertrophic and proliferative processes. This ambivalent nature of NF-κB might limit the use of NF-κB inhibitors for therapeutic purposes and should evoke further studies to clarify unequivocally the nature of NF-κB inhibition in the haemodynamically overloaded circulation.
High volume rate 3-D ultrasound imaging using cross array based on synthetic transmit focusing

A high volume rate 3D ultrasound imaging method using a cross array based on synthetic transmit focusing is presented, in which an ultrasound wave is transmitted successively using each element of a 1D transmit array transducer placed along the elevation direction and the returning pulse echoes are received using all elements of an 1D receive array transducer placed along the lateral direction. On receiving, by employing the conventional dynamic focusing and synthetic transmit focusing methods along lateral and elevation directions, respectively, ultrasound waves can be focused effectively at all imaging points. In this paper, we also proposed a new real-time 3D imaging method using a cross array for improving transmit power and the elevational resolution, which uses linear wave fronts on transmit. Numerical analysis and computer simulation results show that proposed methods provide a volume image with dynamically focused beam pattern along both the lateral and the elevation directions with only 65 transmit-receive events. In particular, a linear-wave-front based method provides a uniform elevation beam width over large depth of field.
Managing for Conservation and Recreation: The Ningaloo Whale Shark Experience

The Western Australian Department of Environment and Conservation has statutory responsibility for conservation, and commercial and recreational aspects of the Ningaloo Whale Shark Experience. The whale shark experience participation rate had grown by 150% since 1995. In this paper, the ability of the existing management programme to balance ecological, social and economic factors is reviewed. The Department has established a statutory Code of Conduct which applied equally to commercial and recreational users when interacting with whale sharks. The Code of Conduct for Whale Shark Interaction was developed to provide for an acceptable impact on the wildlife and a safe visitor experience. A restricted licensing regime was applied. Studies conducted to date indicate that any significant impact on the whale shark population is unlikely as a result of the tourism interactions at Ningaloo. Social surveys indicate a high level of satisfaction with all aspects of the whale shark experience. An education programme was implemented to cater for industry needs and a local, national and international audience. At this time, the Ningaloo Whale Shark experience may effectively be described as an ecologically sustainable wildlife tourism industry managed by a government conservation department based on non-consumptive use of wildlife.
The beta2 but not alpha7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice.

RATIONALE Tobacco use is implicated in approximately 440,000 deaths per year, making it the leading cause of preventable death in the United States. Although it is generally recognized that tobacco use is correlated with a variety of health-related complications, many smokers are unsuccessful in their efforts to stop smoking using current cessation therapies. OBJECTIVES Given that nicotine is the addictive component of tobacco, successful smoking cessation therapies must address the various processes, including reward, which contribute to nicotine addiction. As such, determining the nicotinic receptor subtypes involved in nicotine reward is of utmost importance to understanding how nicotine addiction progresses. METHODS Conditioned place preference (CPP) in three-chamber conditioning boxes was performed. For antagonist studies, drug was given on all conditioning sessions 10 min before nicotine or saline injection and placement in the boxes. RESULTS We have demonstrated that a pretreatment with the alpha4beta2 subunit of the nicotinic acetylcholine receptor (nAChR) antagonist dihydro-beta-erythroidine (2.0 mg/kg, s.c.) blocked nicotine (0.5 mg/kg, s.c.) CPP in wild-type mice (C57BL/6 mice). In contrast, pretreatment with an antagonist of the alpha7 subunit of the nAChR, methyllycaconitine (MLA, 5.0 or 10.0 mg/kg, s.c.), had no effect on this behavior. Finally, we showed that mice lacking the beta2 subunit of the nAChR did not exhibit nicotine CPP while alpha7 knock-out mice did. CONCLUSION Taken together, these data suggest that the beta2 subunit of the nAChR is critically involved in nicotine reward as measured by CPP.
Effects of different repolishing techniques on colour change of provisional prosthetic materials.

UNLABELLED OBJECTIVES. To investigate repolishing effect of stained provisional prosthetic materials in vitro. METHODS. Thirty two cylindrical specimens (10 x 2 mm) were prepared for each of light-polymerized composites (Revotek LC, Rx-Create), bis-acryl composites (Structur Premium, Protemp Garant3, Luxatemp Fluorescence), methyl-methacrylate (UnifastTRAD) and ethyl-methacrylate (DentalonPlus) based provisional material using a mould. The specimens were divided into 4 groups (n=8) according to different repolishing techniques. The specimens were stored for 24 hours at 37 degrees C in distilled water, and then transferred into 4 different staining agents. The colour was measured with a spectrophotometer (Vita Easyshade) before exposure and after repolishing procedures, and colour changes (DeltaE) were calculated. STATISTICAL ANALYSIS three-way ANOVA, Tukey HSD post-hoc test (p<0.05). RESULTS. The influence of type of provisional material, polishing procedure, food colorants and combinations of them on colour change was significant (p<0.05). After the repolishing procedures, all the specimens stored in distilled water achieved an unnoticeable colour change (DeltaE<3.7), except Dentalon Plus, Rx Create, Unifast TRAD. A similar tendency was observed in artificial food colourant solution following subsequent repolishing of the specimens. As for the red wine, all repolished specimens attained unnoticeable colour change (DeltaE<3.7), except Dentalon Plus using Rx polishing paste, Enhance polishing set or repeated glazing procedure. CONCLUSION. Repolishing was found to be an effective way to improve aesthetic appearance for provisional prosthetic materials by partially removing staining observed on the surface of the restorations.
An evidence-based framework on community-centred approaches for health: England, UK

Abstract Community participation is a central concept for health promotion, covering a breadth of approaches, purposes and activities. This paper reports on a national knowledge translation project in England, UK, which resulted in a conceptual framework and typology of community-based approaches, published as national guidance. A key objective was to develop a conceptual framework linked to sources of evidence that could be used to support increased uptake of participatory methods across the health system. It was recognized that legitimacy of community participation was being undermined by a scattered evidence base, absence of a common terminology and low visibility of community practice. A scoping review, combined with stakeholder consultation, was undertaken and 168 review and conceptual publications were identified and a map produced. A ‘family of community-centred approaches for health and wellbeing’ was then produced as way of organizing the evidence and visually representing the range of intervention types. There are four main groups, with sub-categories: (i) strengthening communities, (ii) volunteer and peer roles, (iii) collaborations and partnerships and (iv) access to community resources. Each group is differentiated using key concepts and theoretical justifications around increasing equity, control and social connectedness. An open access bibliography is available to accompany the framework. The paper discusses the application of the family of community-centred approaches as a flexible planning tool for health promotion practice and its potential to be used as a framework for organizing and synthesizing evidence from a range of participatory methods.
Exocyst SEC3 and Phosphoinositides Define Sites of Exocytosis in Pollen Tube Initiation and Growth1[OPEN]

The SEC3 exocyst subunit serves as a landmark for secretory vesicles, and its localization and differential regulation by membrane lipids determine pollen tube initiation and polar growth. Polarized exocytosis is critical for pollen tube growth, but its localization and function are still under debate. The exocyst vesicle-tethering complex functions in polarized exocytosis. Here, we show that a sec3a exocyst subunit null mutant cannot be transmitted through the male gametophyte due to a defect in pollen tube growth. The green fluorescent protein (GFP)-SEC3a fusion protein is functional and accumulates at or proximal to the pollen tube tip plasma membrane. Partial complementation of sec3a resulted in the development of pollen with multiple tips, indicating that SEC3 is required to determine the site of pollen germination pore formation. Time-lapse imaging demonstrated that SEC3a and SEC8 were highly dynamic and that SEC3a localization on the apical plasma membrane predicts the direction of growth. At the tip, polar SEC3a domains coincided with cell wall deposition. Labeling of GFP-SEC3a-expressing pollen with the endocytic marker FM4-64 revealed the presence of subdomains on the apical membrane characterized by extensive exocytosis. In steady-state growing tobacco (Nicotiana tabacum) pollen tubes, SEC3a displayed amino-terminal Pleckstrin homology-like domain (SEC3a-N)-dependent subapical membrane localization. In agreement, SEC3a-N interacted with phosphoinositides in vitro and colocalized with a phosphatidylinositol 4,5-bisphosphate (PIP2) marker in pollen tubes. Correspondingly, molecular dynamics simulations indicated that SEC3a-N associates with the membrane by interacting with PIP2. However, the interaction with PIP2 is not required for polar localization and the function of SEC3a in Arabidopsis (Arabidopsis thaliana). Taken together, our findings indicate that SEC3a is a critical determinant of polar exocytosis during tip growth and suggest differential regulation of the exocytotic machinery depending on pollen tube growth modes.
Effects of moxonidine on corticocerebral blood flow under normal and ischemic conditions in conscious rabbits.

Hypertension associated with excessive liberation of circulating and tissue catecholamines is an independent risk factor for further cardiovascular complications and an important predictor of stroke. Moxonidine is a centrally acting anti-hypertensive drug with potent action on I1-imidazoline receptors. It inhibits catecholamine release and is therefore expected to exert an antiadrenergic effect at various levels in the regulation of the cardiovascular system. The aim of this study was to investigate the effect of moxonidine (0.025-0.1 mg/kg, i.v.) on the normal and unilateral carotid occlusion-induced impaired corticocerebral blood flow (cCBF) determined by hydrogen polarography, on mean arterial blood pressure (MABP) and heart rate (HR) in conscious rabbits. Moxonidine produced a reduction of MABP and HR. On the other hand, after administration of the drug, a significant increase in the normal and impaired cCBF was observed. Because the improvement in cCBF was conspicuous in both normal and ischemic conditions, moxonidine might be beneficial not only in the treatment of hypertension but also in the management of cerebral ischemia.