Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT). We carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosourea (ENU), aiming to identify potential therapeutic entry points. Here we report the isolation of 106 founder animals that show suppression of Mecp2-null traits from screening 3,177 Mecp2/Y genomes. Using exome sequencing, genetic crosses and association analysis, we identify 33 candidate genes in 30 of the suppressor lines. A network analysis shows that 61% of the candidate genes cluster into the functional categories of transcriptional repression, chromatin modification or DNA repair, delineating a pathway relationship with MECP2. Many mutations lie in genes that are predicted to modulate synaptic signaling or lipid homeostasis. Surprisingly, mutations in genes that function in the DNA damage response (DDR) also improve symptoms in Mecp2/Y mice. The combinatorial effects of multiple loci can be resolved by employing association analysis. One line, which was previously reported to carry a suppressor mutation in a gene required for cholesterol synthesis, Sqle, carries a second mutation in retinoblastoma binding protein 8 (Rbbp8 or CtIP), which regulates a DDR choice in double stranded break (DSB) repair. Cells from Mecp2/Y mice have increased DSBs, so this finding suggests that the balance between homology directed repair and non-homologous end joining is important for neuronal cells. In this and other lines, the presence of two suppressor mutations confers better symptom improvement than one locus alone, suggesting that combination therapies could be effective in RTT.


Observations of sea surface temperature (SST), sea level pressure (SLP), surface wind, and outgoing longwave radiation (OLR) show that the El Nino-Southern Oscillation (ENSO) displays western Pacific anomaly patterns in addition to eastern Pacific anomaly patterns. During the warm phase of ENSO, warm SST and low SLP anomalies in the equatorial eastern Pacific and low OLR anomalies in the equatorial central Pacific are accompanied by cold SST and high SLP anomalies in the off-equatorial western Pacific and high OLR anomalies in the off-equatorial far western Pacific. Also, while the zonal wind anomalies over the equatorial central Pacific are westerly, those over the equatorial far western Pacific are easterly. The nearly out-of-phase behavior between the eastern and western tropical Pacific is also observed during the cold phase of ENSO, but with anomalies of opposite sign. These western Pacific interannual anomaly patterns are robust features of ENSO, independent of data sets. It is argued that equatorial easterly (westerly) wind anomalies over the far western Pacific during the warm (cold) phase of ENSO are initiated by off-equatorial western Pacific cold (warm) SST anomalies, and that these winds are important for the evolution of ENSO. An atmosphere model is employed to demonstrate that small off-equatorial western Pacific cold (warm) SST anomalies (compared to those in the east) are sufficient to produce equatorial easterly (westerly) wind anomalies as observed over the far western Pacific. The coupled ocean-atmosphere model of Zebiak and Cane is then modified to investigate the evolution of the western Pacific interannual anomaly patterns in a coupled ocean-atmosphere system, by including a meridional structure to the subsurface temperature parameterization in the western Pacific. The modified model produces both western and eastern Pacific interannual anomaly patterns.


Background: CAR-T immunotherapy has shown remarkable promising results for relapsed/ refractory (R/R) acute lymphoblastic leukemia (ALL). However, CD19-targeted CAR T cell therapy for R/R ALL has a relapse rate of approximately 50% at 1 year after CART therapy, and the most common mechanism of relapse is due to CD19 antigen loss or decreased target expression on the surfaces of the lymphoblastic leukemia cells. Potential approaches to overcome this challenge include engineering CAR T cells to achieve multispecificity and to respond to lower expression levels of target antigens by dual target CAR T strategies.
 Objective: In order to evaluate the efficacy and safety of CD19/CD22 dual target CAR T cells for R/R ALL patients to determine if targeting multiple antigens can prevent treatment failure and improve response rates and durability of response.
 Method: A novel CAR T cells with tandem targeting CD19 and CD22 antigens and a third generation CAR construct of CD28 and OX40 co-stimulatory domains were administered to 23 patients with R/R ALL with a median age of 24(6-56)years. High-risk patients were enrolled in this cohort, including 10 with BCR-ABL+ALL (6 of 10 with T 315I mutation), 4 with TP53 mutation, 2 with Ph-like ALL and 3 with relapsed ALL post allo-HSCT. The patients received a single infusion of CAR T cells with dose escalation schedule:10%--30%--60%. The median infusion dose of CAR T cells was 1 (0.5- 2.5) ×107cells/kg.
 Results: The median follow-up was 9 (3.5-20) months. The day 28 CR/CRi rate was 100% with21/22 (95.5%) molecular remission. Six-month OS was 94.4% and RFS was 76.9%. One-year OS was 57.2% and RFS was 67.3%. One-year OS of high tumor burden (BM blast> 30%)(15/22) and low tumor burden(BM blast≤30%)(7/22) was 47.5% and 75% respectively (p>0.05). The 1-year OS of the CAR T- to- allo-HSCT group(14/22) was better than that of the non-transplant group(8/22) (OS 72.9% vs. 26.7%, p = 0.116). The cumulative relapse rate of 6 months and 1 year were 23.1% and 32.7% respectively. The overall incidence of CRS were 91% included 22.7%grade III CRS ,4.5% grade IV CRS and 0% severe CRES. Only one patient presented MAH syndrome and was cured with low dose dexamethasone. There was no CAR T-related death.
 Conclusions: The tandem CD19/CD22 dual target CAR T cells therapy is a safe and high efficacy treatment for R/R ALL patients. It is possible that multi-targeted CAR-T cell therapy may overcome this resistance mechanism and improve clinical outcomes.

 No relevant conflicts of interest to declare.


During an earthquake, soils filter and send out the shaking to the building and simultaneously it has the role of bearing the building vibrations and transmitting them back to the ground. In other words, the ground and the building interact with each other. Hence, soil-structure interaction (SSI) is a key parameter that affects the performance of buildings during the earthquakes and is worth to be taken into consideration. Columns are one of the most crucial elements in RC buildings that play an important role in stability of the building and must be able to dissipate energy under seismic loads. Recent earthquakes showed that formation of plastic hinges in columns is still possible as a result of strong ground motion, despite the application of strong column-weak beam concept, as recommended by various design codes. Energy is dissipated through the plastic deformation of specific zones at the end of a member without affecting the rest of the structure. The formation of a plastic hinge in an RC column in regions that experience inelastic actions depends on the column details as well as soil-structure interaction (SSI). In this paper, 854 different scenarios have been analyzed by inelastic time-history analyses to predict the nonlinear behavior of RC columns considering soil-structure interaction (SSI). The effects of axial load, height over depth ratio, main period of soil and structure as well as different characteristics of earthquakes, are evaluated analytically by finite element methods and the results are compared with corresponding experimental data. Findings from this study provide a simple expression to estimate plastic hinge length of RC columns including soil-structure interaction.


The spectral impurities of the EG and G 25-kCi /sup 60/Co source were determined by using a 1-mCi mockup source. The mockup source was identical in construction to the 25-kCi source and was identically mounted. The spectrum of the mockup source was measured by using a 3 x 3 inch NaI detector and a multichannel analyzer. Measurements were made with and without a graded Z filter. ''Pure'' /sup 60/Co spectra, i.e., spectra free of scattered impurities, were used to subtract out the direct 1.17- and 1.33-MeV lines from the mockup spectra to leave only impurities. Several checks on the resulting impurity spectra indicated that a conservative estimate on their accuracy is +- 20%. A large fraction of the total number of x rays was found to be due to spectral impurities which caused the average energy of the spectra to be appreciably degraded. The average energy of the filtered spectra is 1.105 +- 0.020 MeV, while that of the unfiltered spectrum is 0.937 +- 0.020 MeV.


We provide two case studies in the application of ideas drawn from conversation analysis to the design of technologies that enhance the experience of human conversation. We first present a case study of the design of an electronic guidebook, focusing on how conversation analytic principles played a role in the design process. We then discuss how the guidebook project has inspired our continuing work in social, mobile audio spaces. In particular, we describe some as yet unrealized concepts for adaptive audio spaces.


We read with interest the article by Pfeilschifter et al. on the safety of thrombolysis with dabigatran (DB) in a mouse model of experimental stroke. The authors have shown that recombinant tissue plasminogen activator (rt-PA) might be safe with DB at clinically significant serum concentrations of DB. But it remains unclear as to what were the actual DB levels in the mouse population at the time when rt-PA was administered. Further routinely measured anticoagulant parameters such as activated partial thromboplastin time (aPTT) and international normalized ratio are not reported at the time when rt-PA was given. Although thrombin time is a reliable marker for DB activity, it is not widely available, thus limiting its use. DB has a nonlinear relationship with aPTT. The primary utility of aPTT is in its negative predictive value, as a normal aPTT suggests little anticoagulant activity. Whether rt-PA would have been safe with a normal aPTT in this experimental model remains unknown.


xDNA and yDNA are new classes of synthetic nucleic acids characterized by having base-pairs with one of the bases larger than the natural congeners. Here these larger bases are called x- and y-bases. We recently investigated and reported the structural and electronic properties of the x-bases (Fuentes-Cabrera et al. J. Phys. Chem. B 2005, 109, 21135-21139). Here we extend this study by investigating the structure and electronic properties of the y-bases. These studies are framed within our interest that xDNA and yDNA could function as nanowires, for they could have smaller HOMO-LUMO gaps than natural DNA. The limited amount of experimental structural data in these synthetic duplexes makes it necessary to first understand smaller models and, subsequently, to use that information to build larger models. In this paper, we report the results on the chemical and electronic structure of the y-bases. In particular, we predict that the y-bases have smaller HOMO-LUMO gaps than their natural congeners, which is an encouraging result for it indicates that yDNA could have a smaller HOMO-LUMO gap than natural DNA. Also, we predict that the y-bases are less planar than the natural ones. Particularly interesting are our results corresponding to yG. Our studies show that yG is unstable because it is less aromatic and has a Coulombic repulsion that involves the amino group, as compared with a more stable tautomer. However, yG has a very small HOMO-LUMO gap, the smallest of all the size-expanded bases we have considered. The results of this study provide useful information that may allow the synthesis of an yG-mimic that is stable and has a small HOMO-LUMO gap.


OBJECTIVE
This meta-analysis compares the feasibility, safety and clinical outcome of long-term therapy with topotecan vs. standard treatment duration in patients with recurrent ovarian cancer.

MATERIALS AND METHODS
Data of 523 patients from five clinical trials were reviewed and retrospectively allocated into two groups. Those patients who received 6 or fewer courses were compared to those with 7 or more courses of intravenous topotecan. Response rates, overall survival and toxicity profiles were compared between these groups.

RESULTS
One hundred and fifty-two (29%) patients received 7 or more courses and 371 patients (71%) received up to 6 courses of topotecan. Hematological toxicity was significant but similar in both treatment groups and was not cumulative. Non-hematological toxicity was generally mild. Eighty-seven (17%) patients responded to topotecan treatment, 66 of these patients received 7 or more courses of therapy. In total, 14 patients experienced their initial response at or after course 6 of therapy. Within the subset of patients with response or disease stabilization at course 6, those who stopped treatment at course 6 for reasons other than progressive disease or adverse events had a median survival of 83.6 weeks and those who continued treatment for longer than 6 courses had a significantly longer median survival of 107.0 weeks.

CONCLUSION
Chemotherapy with 7 or more courses of topotecan in recurrent ovarian cancer is feasible with no evidence of cumulative toxicity. The results of this retrospective analysis suggest a potential for late response and a survival benefit for those patients without disease progression who continue topotecan therapy beyond 6 cycles of treatment.


Aim: This study was an attempt at investigating the variation in growth and morphology of primary avian chondrocyte and neural cell cultures established under standard laboratory conditions. Methods: For establishing chondrocyte cultures, the tibia were dissected from chick embryos that were 12 (E12), 14 (E14) and 15 (E15) days old. For the neural cell culture initiation, the two lobes of the forebrain were dissected from chick embryos that were 4 (E4), 8 (E8) and 12 (E12) days old. The final characterization of the cells was performed by H&E and CFV staining. Results: In the chondrocyte cultures, two forms of morphology were observed which is reversible in process.The primary variation evaluated in chondrocytes cultures was the effect of the media on the state of the cells. Based on whether the cells were cultured in DMEM or MEM, there was a difference in the transformation of the attached cells from the differentiated to de-differentiated forms. The primary variation examined in neuron cultures was the embryonic age of the tissue and the effect that it had on the proliferation and neurite formation of the cells. E8 embryo neural cells cultures result in well-developed cells with neurite formation along with axonal and dendritic outgrowths with highly complex interconnections between them. Conclusion: Ultimately, this study demonstrated the composition of culture media had an effect on the morphological appearance of the chondrocytes, as well as, confirmed that the culture of primary neurons is best performed using cells from an E8 embryo.


Abstract : Advances in technology and evolution of doctrine provide grounds to review commonly-held assumptions about the level at which combined arms warfare begins. This thesis examines the platoon equipped with the Bradley Infantry Fighting Vehicle to determine if combined arms warfare has devolved to find its current roots at platoon level. This study accomplishes three objectives. First, for background it provides a brief history of the evolution of combined arms. Second, it focuses on aspects of maneuver theory, organization, combat experience, doctrine, and weapons technology to support the conclusion that the contemporary Bradley infantry platoon is the starting point for combined arms warfare. Third, this study contends that the devolution of combined arms warfare is a fundamental process that can be understood only with reference to full context. That is, a consideration of dynamics peculiar to the Bradley platoon is only part of the picture. For the process to make sense, it must account for larger external fundamental, including the interaction over time among technology, doctrine, theory, organization, and experience.


Background: Dental wastes are one of the environmental issues due to toxic and pathogenic agents such as pathological wastes, pharmaceutical and chemical etc have particular sensitivity. The aim of this study was to determine the dental waste management and related factors in the city of Ilam. Methods: In this cross-sectional study, the studied community was all the sixteen dental clinics in Ilam. Five samples of each clinic per week (Saturday, Sunday and Wednesday) were selected. Thereafter waste sample was manually separated into 36 components and were weighed using a laboratory scale with an accuracy of 0.01 g. Each component was weighed five times and the mean value obtained for each component was considered. Production per capita was calculated for each person. Data were analyzed using descriptive statistics, SPSS and Excel software. Results: The per capita percent for infectious waste section was 51%. The average of infectious waste is 201.13 g. The per capita percent for chemical, pharmaceutical waste section was 36% with an average of 142.48 g. The per capita percent for toxicity section was 13% in the dental clinics with the weighted average of 48.78 g. According to the results of the checklist, further dental clinics have been poorly managed. Conclusion: According to the presence of various materials and different components with different characteristics in the dental wastes, the optimal management of this type of wastes should be carried out based on the specific characteristics, which include programs to reduce waste production, segregation,


Background: The relationship between shift work and cardiovascular disease is controversial.
Objectives: The present study aimed to assess the relationship between shift work and arterial age and to identify predictors of early arterial aging.
Methods/Study Design: A total of 61 workers, 77% working in 2 or more shifts, underwent arteriography. Arterial age (AA), brachial and aortic augmentation index (Aix Brach and Aix Ao) and pulse wave velocity (PWV) were assessed. The participants were questioned about smoking habits, cardiovascular family and personal history, physical work and number of shifts.
Results/Findings: Aix Brach was: -40±29 %, AixAo: 16±1.71%, PWV: 8.06±1.44 m/s, AA: 41±15 years. The number of shifts was significantly associated with Aix Brach (p<0.01) and Aix Ao (p<0.01) (Multiple R=0.875, F<0.01); PWV (p<0.01) and AA (p=0.0001) (Multiple R=0.922, F<0.01). Multiple regression analysis revealed significant associations between arterial age and smoking (p=0.0008), positive cardiovascular family history (p=0.023) and physical work (p=0.0029) (Multiple R=0.758, F<0.01). Early arterial aging was more likely in shift workers compared to the other participants (OR=1.189, 95%CI=0.346-4.089).
Conclusion: Shift work, smoking, positive cardiovascular family history and physical work predict early arterial aging.


Background: Patients with psychiatric disorders can be vulnerable to oral diseases due to the adverse effects of medications and disease per se. The aim of this study is to assess oral health status, self-perceived dental needs, and barriers to utilization of dental services along with evaluation of intervention urgency among psychiatric patients. Materials and Methods: In this cross-sectional study, 165 individuals were examined at the psychiatric outpatient department of a tertiary care center. Clinical examination [dentition status and community periodontal index (CPI) modified] was done according to the World Health Organization Basic Oral Health Surveys, 2013. Other information was collected by direct interview and all the data were recorded on a prestructured, validated pro forma. Data were analyzed using SPSS Software. The statistical significance was determined by analysis of variance (ANOVA) and level of significance was set at P < 0.05. Results: Although decayed, missing, and filled teeth (DMFT) and CPI-modified scores increased with increase in duration of illness, the difference was not statistically significant. Evaluation of self-reported attributes revealed that the majority of the individuals had reported dental pain (34.6%) as their dental problem, 39.6% visit dentist only when there is a dental problem, and 41.7% did not felt any need to visit dentist. The ANOVA of DMFT in relation to duration of illness (P > 0.062) and CPI-modified scores (P > 0.078) were not statistically significant. Although when intervention urgency was evaluated, 70.3% needed prompt treatment depending on their oral health assessment. Conclusion: The findings of this study suggest that oral health concerns of this marginalized section of the population are unrecognized and should be given prominence by psychiatrists.


G ATA4 is localised on human chromosome 8p23.1-p22 and codes for a zinc finger transcription factor. Mice lacking Gata4 suffer from defective ventral morphogenesis and heart tube formation.1,2 This factor therefore targets various genes important for heart development and basic cardiac function. Recently, three GATA4 mutations have been detected in families with congenital heart disease.3,4 A mutation affecting a residue next to the C-terminal zinc finger has been identified in family members with atrial septal defects, and resulted in the disruption of a physical interaction between Gata4 and TBX5.3 There is growing evidence that the two zinc fingers of Gata4 display distinct functions so as to facilitate protein–DNA and protein–protein interactions.

To further our understanding of the specific role of GATA4 in human congenital heart disease, we searched for mutations in the sequences coding for the zinc fingers in diseased heart tissues of 68 patients with complex heart malformations, encompassing atrial (ASD), ventricular (VSD), and atrioventricular septal defects (AVSD). These patients mostly died in early infancy as a result of the severity of the cardiac abnormalities. We isolated genomic DNA from the formalin fixed malformed hearts, amplified exons 3 and 4 from DNA fragments of about 2 kb, and carried out double strand direct sequencing. Mutations were confirmed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) or cloning and subsequent sequencing to separate alleles (fig 1A–F).

 Figure 1
 Analysis of GATA4 mutations in malformed human hearts. (A) DNA was isolated from the affected tissues of 68 formalin fixed hearts with complex cardiac malformations. (B) Genomic DNA was about 2 kb and 50 ng was used for polymerase chain reaction (PCR). (C) Exons 3 and 4 of GATA4 were amplified to analyse mutations affecting the two zinc fingers; arrows show exon 4 fragments; −/+ depicts negative and …


Ecotourism has experienced rapid growth because of global concerns regarding sustainability. However, significant differences are observed between the theory and practice of ecotourism management, especially in Southeast Asian countries. This study reviews the management of ecotourism in five countries (Malaysia, Thailand, Vietnam, Laos, and Cambodia) by comparing the theoretical definition with the practical operations in each country. The goal of this study is to investigate the cause of the gap between the theoretical definition and the practical operation of ecotourism. This study also addresses critical issues regarding national ecotourism policy and the practical implementation of ecotourism-based products in each country. This study would be of interest to national policymakers and researchers to study, plan, and improve their ecotourism development strategies. The results suggest that the main reason for the gap in the ecotourism operations of these countries is the lack of communication and cooperation between policymakers and other tourism stakeholders. The government is significant in leading ecotourism development, and an official and national ecotourism strategy is required in planning and operating ecotourism. However, consistency in policy and the attitude of the government will increase the competitive power of ecotourism. The assistance of non-government organizations is not a long-term strategy for ecotourism development, and less-developed countries like Vietnam should attempt to use the resources of its administrative government system, similar to the Tambon Administrative Organization of Thailand, to develop a suitable policy for ecotourism management in the long-term.


Patients with Sjögren's syndrome (SS) in association with either Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) or Sclerodactyly were tested for HLA-A, B and Dr antigens and the phenotypes of the 4th component of complement (CA). Significant associations were identified between HLA-Bw62, Dr4, C4B2.9, C4A8 and females with SS-RA. The MHC antigen frequencies noted for secondary Sjögren's syndrome differed from those reported for their respective primary diseases and the implications of these observations are discussed.


In this text I offer a narrative reflection, as a teacher-traveler, on my live(d) experiences in a sometimes (always already) violent world. Preoccupied with the possibilities of the work of mourning, in the first two movements I draw on stories of my time teaching in China at the dawn of this millennium to tell tales of tragedy, terror, and tension that provoked strange pedagogical moments. I reflect on the difficulties and passions of live(d) pedagogies that crack open curri/culum to tarry with/in these provocative, generative spaces as places for mourning and connection, ambivalence and ambiguity. During the 3rd movement I join Butler's questioning of 'what counts as a grievable life' as I attempt a textual encounter with an (un)grievable 'other'. I ask: How might recognition of lives/deaths through the act of inscription and collective mourning be related to understanding human connection? In a pedagogical refrain, I draw Derrida into my conversation with feminist theory to ask seriously about the pedagogical potential of tarrying with/in mourning, particularly for peace education that prioritizes an awareness of human connection. What are the transformative possibilities of returning again to mourning? I conclude with a call from peace educators and other emerging epistemologies that challenge us to think differently about human connection in our pedagogical work. Above all this text is a provocation in/to difficult spaces of mourning and pedagogical movement.


The excretion of naltrexone and its primary metabolite 6,beta-naltrexol in breast milk from a 30-year-old lactating opiate addict undergoing oral naltrexone pharmacotherapy (5 mg/d) was studied. Concentrations of naltrexone and 6,beta-naltrexol in serial milk and plasma samples taken over a 19.3-hour period of a dose interval at steady state were measured by gas chromatography. The calculated infant dose relative to the maternal weight was 0.03% for naltrexone and 0.83% (as naltrexone equivalents) for 6,beta-naltrexol. Total relative infant dose estimated for the complete 24-hour dose interval was 1.06%. Her 6-week-old breastfed infant was healthy, achieving expected milestones, and showed no adverse effects. Only 6,beta-naltrexol was detected in infant plasma and at a very low concentration of 1.1 micro g/L. Use of naltrexone during breastfeeding should be undertaken only after an individual risk benefit analysis.


In direct drive inertial confinement fusion, the residual speckle pattern remaining after beam smoothing plays an important role in the seeding of instabilities at the ablation front. We have used an x-ray laser as an XUV backlighter to characterize the imprinted modulation in thin foils for smoothing by random phase plate and spectral dispersion at both 0.35 pm and 0.53 pm irradiation, and induced spatial incoherence at 0.53 pm irradiation. We also demonstrate measurements of the modulation due to a single mode optical imprint generated by a narrow slit interference pattern, and modification of the imprint with a superposed smooth irradiation to study time dependence of the imprinting process. 8 refs., 10 figs.


BACKGROUND
Obesity has been recognized as a risk factor in the development and recurrence of breast cancer and is also associated with poor prognostic outcomes. This systematic review and network meta-analysis aimed to identify the most effective exercise, physical activity, and dietary interventions to reduce fat mass, body fat percentage and body weight as well as potentially increase lean mass in women diagnosed with or at high risk of breast cancer.

METHODS
A systematic search of databases was performed up to May 2022. Eligible randomized controlled trials examined the effects of exercise, physical activity and/or dietary interventions on fat mass and lean mass in women diagnosed with or at high risk of breast cancer. A random-effects network meta-analysis was conducted to determine the effects of different interventions across outcomes when sufficient studies were available.

RESULTS
Eighty-four studies (n = 6428) were included in this review. Caloric restriction and combined exercise + caloric restriction significantly reduced fat mass (range, -3.9 to -3.7 kg) and body weight (range, -5.3 to -4.7 kg), whereas physical activity + caloric restriction significantly reduced body fat percentage (-2.4%; 95% confidence interval [CI], -3.4% to -13%) and body mass index (-2.2 kg × m-2 ; 95% CI, -3.0 to -1.4 kg × m-2 ) in breast cancer patients. Resistance exercise was the most effective intervention to increase lean mass (0.7 kg; 95% CI, 0.5-1.0 kg) in breast cancer patients.

CONCLUSION
Multimodal exercise and diet programs were the most effective interventions to reduce fat mass, body fat percentage, and body weight and increase and/or preserve lean mass.


Lane detection in complex road scenes is still a challenging task due to poor lighting conditions, interference of irrelevant road markings or signs, etc. To solve the problem of lane detection in the various complex road scenes, we proposed a geometric attention-aware network (GAAN) for lane detection. The proposed GAAN adopted a multi-task branch architecture, and used the attention information propagation (AIP) module to perform communication between branches, then the geometric attention-aware (GAA) module was used to complete feature fusion. In order to verify the lane detection effect of the proposed model in this paper, the experiments were conducted on the CULane dataset, TuSimple dataset, and BDD100K dataset. The experimental results show that our method performs well compared with the current excellent lane line detection networks.


Indico, CERN's popular open-source tool for event management, is in widespread use among facilities that make up the HEP community. It is extensible through a robust plugin architecture that provides features such as search and video conferencing integration. In 2018, Indico version 2 was released with many notable improvements, but without a full-featured search functionality that could be implemented easily outside of CERN. At both Fermi and Brookhaven National Laboratories, the user community viewed the lack of this popular feature as a significant impediment to deployment of the new software. In the meantime, CERN embarked upon a major redesign of their core search service, one that would also necessitate a rewrite of the Indico search interface. Seeing this pressing need, the two US labs decided to collaborate, with assistance from the CERN development team, on a project to develop the requisite search functionality for the larger user community. The resulting design exploits the simplified schema defined in the new CERN Search micro-service, based on Invenio and Elasticsearch, while still providing a flexible path to implementation for alternative backend search services. It is intended to provide a software package that can be installed easily and used out of the box, by anyone at any site. This paper will discuss the design choices and architectural challenges, and provide an overview of the deployment and use of these new plugins.


Operational Program of
Competitiveness and Internationalization (POCI), Lisbon
Operational Program, with support from the European
Regional Development Fund (FEDER), and the Foundation
for Science and Technology I. P, with support from the State
Budget – OE, under project no. 016893, entitle
"Development of Auxetic Fibrous Composite for Personal
Protection (POCI-01-0145-FEDER-016893 and
PTDC/CTM-POL/5814/2014)


Abstract.
 TREMADOCIAN TRILOBITES FROM DARK SHALE FACIES OF THE ALFARCITO MEMBER (SANTA ROSITA FORMATION), QUEBRADA DE MOYA, JUJUY, ARGENTINA. The Quebrada de Moya constitutes a distinctive locality of the Santa Rosita Formation (uppermost Furongian—lowermost Ordovician) in the Quebrada de Humahuaca (Sierra de Tilcara, Cordillera Oriental of Jujuy, Argentina). The trilobites Leptoplastides marianus (Hoek), Parabolinella sp., Hapalopleura acantha Malanca and Brandán, and Asaphellus sp. are described from the dark shale facies of the upper part of the Alfarcito Member. A grainstone interstratified in the mudstones contains a low-diversity conodont assemblage of the Cordylodus angulatus Zone (lower Tremadocian). The Ordovician age of the section is confirmed, in addition, by the record of the graptolite Rhabdinopora flabelliformis ssp. in a sandstone underlying the studied levels. The dark shales accumulated by suspension fall-out during periods of maximum flooding, in a reducing, distal offshore marine environment. The trilobite fauna is largely dominated by L. marianus. The upper part of the Alfarcito Member does not show dark facies in other sectors of the Sierra de Tilcara. The sedimentologic characters of the section described, the low diversity of the conodont assemblage, and the scarcity of agnostoid trilobites may be indicative of a partial isolation of the basin.


Purpose – This research was aimed at showing the impact of a teaching strategy called the Quantum Teaching Strategy on students' academic achievements in two school subjects, namely in Bahasa Indonesia and Science, in comparison to that experienced through classes using a conventional teaching strategy.This research also examined the role of self-esteem on the students' academic achievements in both the subjects in inclusive schools in Indonesia.Methodology – This research was a quasi-experimental study on two intact groups of sixth graders of two different inclusive schools.The sample was assigned through multi-staged cluster sampling from 78 elementary schools in 15 sub-district areas.The data on student academic achievements was collected by means of tests, while the data on self-esteem were obtained through a questionnaire. T-test was used to analyze the different impacts of the Quantum Teaching Strategy and conventional teaching strategy on the academic achievements of students, while ANCOVA was applied to determine whether the students' self-esteem influenced their academic achievements in Bahasa Indonesia and Science.
Findings – The t-test showed that the Quantum Teaching Strategy had a better impact on both Bahasa Indonesia and Science achievements as compared to the conventional teaching strategy.
Significance – Findings of this study can be used as a guide for planning and using Quantum Teaching Strategy in teaching and learning Bahasa Indonesia and Science in inclusive schools.


The collagenase produced by mesenchymal cells has been thought to have a great importance in the pathophysiology of connective tissue metabolism and prolongation of chronic inflammation. The factors, such as IL-1 and PMN factor, released by inflammatory cells have been known to induce mesenchymal cells to produce collagenase. In the present study, the collagenase activity of the nasal secretions were estimated using FITC-labelled collagens as substrates. The factor, enhancing the fibroblasts to produce collagenase, was also isolated from nasal secretions and partially characterized. The fibroblasts used in the present study were cultured with explant of the sections of nasal polyp obtained from a patient with chronic sinusitis. The collagenase activity in nasal secretions from patients with chronic sinusitis was high, whereas that of allergic nasal secretions was extremely low. Furthermore, the collagenase productions of nasal polyp-derived fibroblasts were enhanced by the extracts of nasal secretions from patients with chronic sinusitis. Crude extracts of nasal secretions were fractionated by ammonium sulfate precipitation. The active materials precipitated by 50% to 80% ammonium sulfate were further purified by Sephadex G-75 gel chromatography. The molecular weight determination of the active fraction checked by HPLC utilizing for TSK 2,000 SW gel column indicates 20,000 daltons for the active materials. However, the collagenase production of human microvascular endothelial cells derived from nasal mucosa was not enhanced by this factor. Although either the origin or the nature was not confirmed, the factor was considered to relate to the prolongation of chronic inflammation in the nasal and paranasal sinus pathology. Analysis of these factors will expected to establish methods for new therapeutics in chronic inflammation.


In this paper a look is taken at how the use of implant technology can be used to either increase the range of the abilities of a human and/or diminish the effects of a neural illness, such as Parkinson's Disease. The key element is the need for a clear interface linking the human brain directly with a computer. The area of interest here is the use of implant technology, particularly where a connection is made between technology and the human brain and/or nervous system. Pilot tests and experimentation are invariably carried out apriori to investigate the eventual possibilities before human subjects are themselves involved. Some of the more pertinent animal studies are discussed here. The paper goes on to describe human experimentation, in particular that carried out by the author himself, which led to him receiving a neural implant which linked his nervous system bi-directionally with the internet. With this in place neural signals were transmitted to various technological devices to directly control them. In particular, feedback to the brain was obtained from the fingertips of a robot hand and ultrasonic (extra) sensory input. A view is taken as to the prospects for the future, both in the near term as a therapeutic device and in the long term as a form of enhancement.


The possibility of controlling the processes of filamentation and generation of a supercontinuum during propagation of a high-power femtosecond laser pulse in air is investigated. Using a numerical simulation, it is shown that the initial phase modulation of the pulse results in a shift of the beginning of the filament from the output aperture of the laser system and in a significant increase in the filament length. The efficiency of the generation of the short-wavelength part of the supercontinuum in a pulse with a negative phase modulation is more than two orders of magnitude higher than for a pulse with a limited spectrum.


Individuals with diabetes mellitus (DM) have a considerably elevated risk of developing serious health problems including cardiovascular disease (CVD). Long‐term elevated levels of blood glucose in nondiabetic individuals may also be associated with increased risk of CVD. The aim of this study was to investigate the relationships between glycated haemoglobin A1c (HbA1c) and CVD, DM and all‐cause mortality.


The relationship between activism and social research constitutes a longstanding source of debate. In the mental health and disability fields, this tension has specific connotations: User-survivor activism is premised on the priority of first-hand experience over detached, 'objective' knowledge. Personal experience is the foundation for the specific and irreplaceable perspective that users and survivors bring upon issues of interest. Considering this, how do user/survivor activist groups relate and collaborate with academically oriented researchers who lack a first-person encounter with psychiatry? Drawing on my participant observer role in a user-led activist group in Chile and through three 'reflexive vignettes', in this paper, I retrospectively trace how my interests and presence were received, negotiated and contested by users and non-users in the field. The findings describe three episodes in which my own status - and that of others participating 'in the name of research' - was interrogated. Although the group was open to anyone, boundaries emerged in response to specific demands from external agents interested in participating. A sense of 'personal connection' with the aims and nature of the group was one of those boundaries. In parallel, professional members had their own way of signalling their legitimacy, usually through a self-critical, anti-professional and anti-academic attitude. Doubts about my commitment to the group emerged as fieldwork progressed. The vignettes map the tensions that I experienced, the efforts I made to navigate them and the way they affected my disposition towards the group. The article argues that researcher's reflexivity towards their own situation constitutes a primary source of information in the context of emergent, user-led advocacy efforts. Attention to how these groups accept and/or resist academic agendas provide insights into the solidarities and affinities that shape activist efforts. More than a pre-defined, 'ethico-political' disposition what's required from researchers interested in this field is reflexivity to navigate the interface between academia and activism, honesty about the limits of academia and openness towards the contingent outcomes of an encounter with activism.


The reliability and validity of six self-report physical activity measures were assessed in Latino adults. Validity was assessed by caltrac activity monitors, 'significant others', and construct analyses. Vigorous activity measures had higher reliability and validity (e.g. r > 0.40, P < 0.05) than moderate intensity measures. Though measures varied in their validity, the use of standard physical activity measures with Latinos was supported, and recommendations for specific measures were provided.


The natural sources of radiation represent the cause of the minimal contamination of the environment, including air, water, soil and generate the level of radioactivity detected in vegetal or animal food, under normal conditions. Of artificial radio nuclides which pollute the environment and food, the object of this study is 134 Caesium and 137 Caesium (134 Cs and 137 Cs), both because of their particularity to own a chemical structure similar to potassium (K + ), the prevalence in food of animal origin and total and rapid solubility in the body, and because of the usual measurements made in our country in order to detect the levels of radioactive contamination of food, aiming mainly the two mentioned isotopes of Caesium (134 Caesium and 137 Caesium). Given the fact that the eggs and egg products are not included in Romania in a strategic plan for monitoring the level of radioactive pollution, this study in dynamics, aims at recording the level of the two isotopes of Caesium, in the mentioned food products and at verifying if the detected values, are according to the rules laid down by the national and international norms. Thus, the comparative evaluation of the radioactive pollution in a year was aimed, at eggs collected from hens grown in particular, extensive, traditional system, compared to the eggs collected in the same period of time, in trade, from authorised units, from hens exploited in intensive system.


This paper aims to cover the philosophy of science or the religious Islamic epistemology through Bediuzzaman Said Nursi's thought carried out with the fraternization of natural sciences with the religious sciences, to strengthen the truths arranged on modern advanced scientific beliefs and spiritual alignments for development, for guiding and enlightening the modern-day youth. The cautious use of freedom and its protection with clear definition on the liberty limits was narrated by Bediuzzaman Said Nursi's Risale-i Nur (1910 – 1950), provided the desired the celestial and modern facts to right channelize with the determination to validate the evidences for Islam's assurance for religious revival. Reasoning the ignorance in individuals and exploitation of supremacy for rigid unsophisticated ideals of moral values, Bediuzzaman Said Nursi's prospered on the issue of the Islamic world from the oubliettes of inexperience and deficiency; with the spirit and liberal thought, that a superior demand on learning can place the society obsessed for development by protection from the onslaught which could disturb relationships for personal advantage, exclusive treatment and disenchanted extravaganza. Appeals to normalize the leadership character for materialism and the interest in properties have historically been connected to evolution, methodical substantiation of knowledge, and excellent protection for socio-economic expansion. To overcome numerous hindrances and sustained teaching with understandings of Islam, education needed to inspire erudition method towards development across all societies. Bediuzzaman Said Nursi's solid propagandizing's laid the foundation to peace and harmony do not use any force and avoid any disruption turned out to be effective, when it shared character and spiritual instruction. Core temperament and consciousness in its truthful real form will exhibit the quality of humankind, therefore and reveal facts about themselves.


The relevance of this study is due to the importance of expanding children's passion in reading through the project "Learning Station Community" (LSC). It is important that children are motivated by a genuine desire or need to read. The reading process is done pleasurably and the books provided are the colorful books with an interesting story to attract the children desire to read. This study applied the qualitative method and the data collected based on a combination of field research and interviews with children. As the results, this study found that by providing a comfortable place to learn, creating a pleasant reading environment and talk to children about what they do and do not like to read can boost their desire to read. The children admitted that they were amused to read the book in the mini library provided by the Learning Station Community since the environment in the library is designed casually and comfortable to learn. Additionally, children argued that reading books with friends is a greater delight than reading alone at home. Hence, the project of Learning Station Community is a great project to create situational interest and to encourage children's passion in reading.


This volume contains the presentations and round-table discussions of the 12th meeting of the Club Jules Gonin in March 1980. There are more than 50 articles covering many aspects of diseases of the choroid, the retina, and the vitreous. Some of the contributions, in the meantime, have been published in other journals. Two of the sessions were dedicated to retinal pathology, one to vitreous surgery, one to microsurgery of retinal detachment, and one to diabetic retinopathy. This is, indeed, a diversified set of topics, and, sometimes, it gets a little heavy for somebody who is not an expert in the particular field. The round-table discussions make fascinating reading (the one on the macula will be published independently in Ophthalmologica ). This book should be of great interest to the growing number of experts on the retina and the vitreous.


A 61-year-old man was admitted to our hospital because of a left lung cancer. The chest x-ray film showed an irregular mass in the left upper lung field and the ill-defined left upper mediastinal border. A large portion of the aorta seen in the CT section above the aortic arch was understood to be aortic elongation. When a left pneumonectomy was performed, a saccular aneurysm of the distal aortic arch was found and resected under partial aortic clamping. Following the aneurysmectomy mediastinal dissection was performed in the normal way. The patient recovered uneventfully. The pathological specimens showed a pT2N1M0 squamous cell carcinoma with obstructive pneumonia and an arteriosclerotic aneurysm. There was no report of lung cancer associated with aneurysm of the thoracic aorta. In a patient with left lung cancer obliterating the left upper mediastinal border (the "silhouette sign") the aortic arch should be closely examined by MRI and/or angiography.


Introduction
 Extensive genomic characterization of multiple myeloma has identified subtypes with prognostic and therapeutic implications. In contrast, less is known about the myeloma epigenome. One challenge that has hindered epigenetic studies are assays amenable to biobanked specimens. Here, we sought to determine whether ATAC-seq and RNA-seq of myeloma cells from cryopreserved bone marrow aspirates recapitulated those from fresh samples and used this approach to investigate enhancers of myeloma oncogenes.
 Methods
 Consent and collection of specimens followed approved Institutional Review Board protocols. Mononuclear cells were enrichment by Ficoll gradient centrifugation and were either cryopreserved in 10% DMSO and RPMI media with 10% FBS or used to isolate viable CD138+CD38+ myeloma cells. RNA-seq used the mRNA HyperPrep kit (Kapa Biosystems) with RNA from 50,000 cells. ATAC-seq used the Tn5 transposase (Illumina) on 20,000 cells. Sequencing was performed on an HiSeq 4000 (Illumina). Sequencing data were quality and adapter trimmed using Trim Galore! And mapped to the GRCh37 genome using STAR (RNA-seq) or bowtie2 (ATAC-seq). MACS2 was used to determine chromatin accessible regions and R was used for downstream analyses. H3K27ac ChIP-seq from Jin et al. (Blood, 2018) were downloaded from the European nucleotide archive (PRJEB25605). RNA-seq from CoMMpass (NCT01454297) were downloaded from dbGaP phs000748.v7.p4. Enhancer RNAs were interrogated in intergenic regions excluding 500 bp upstream of TSSs and 5 kb downstream of transcription termination sites to avoid contamination from exonic mRNAs or intronic pre-mRNAs.
 Results
 We compared RNA-seq and ATAC-seq data from myeloma cells isolated from fresh bone marrow aspirates to those cryopreserved for up to 6 months from the same aspirate. RNA-seq and ATAC-seq data from fresh and frozen samples from the same aspirate were highly correlated with each other but distinct from other samples as depicted by principal component analysis (Fig. A,B). Inspection of CCND1 showed high levels of RNA in two patients and this was consistent in both fresh and frozen specimens as well as with FISH results indicating a t(11;14) translocation in these samples (Fig. C). Similarly, fresh and frozen specimens from the same patient showed consistent expression for CCND2 and MYC and these data corresponded with chromatin accessibility found near these genes (Fig. D, see regions shaded in gray).
 Based on these results we expanded our analysis to include 8 biobanked specimens, which identified 91,632 regions of chromatin accessibility that were enriched around plasma cell lineage genes such as IRF4, CD38, SLAMF7, and IGH. Chromatin accessibility often predicted proximal gene expression and this was especially pronounced for regions enriched for histone 3 lysine 27 acetylation (H3K27ac) - a mark of enhancers. Active enhancers are sometimes demarcated by enhancer RNAs (eRNAs) observable in RNA-seq data, thus we queried intergenic regions marked by chromatin accessibility and H3K27ac for eRNAs using RNA-seq data on 768 myeloma specimens from the CoMMpass study. This identified transcription at 4,729 of 13,452 potential regions. eRNA expression was highly correlated with proximal gene expression. To illustrate this point, we performed t-SNE clustering based on mRNA and eRNA expression and color-coded each sample by myeloma gene expression subtype (Fig. E). Interestingly, this identified several regions highly correlated with oncogene expression between myeloma subtypes. For example, an enhancer ~154 kb upstream of CCND2 was uniquely transcribed in the MAF subtype (Fig. F) and this was highly correlated with CCND2 expression (Fig. G).
 Conclusions
 Cryopreservation of myeloma bone marrow aspirates allows isolation and analysis of biobanked samples that produce RNA-seq and ATAC-seq data that are highly congruent with those obtained from fresh samples and this represents a strategy for retrospective genomic and epigenomic studies. Chromatin accessibility analysis identified distinct enhancer elements regulating oncogenes in myeloma subtypes providing mechanistic insight into myeloma pathology.
 Figure 1

 Lin: Amgen: Current Employment, Current equity holder in publicly-traded company. Hofmeister:Bristol Myers Squibb: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Nektar: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Oncopeptides: Honoraria; Oncolytics Biotech: Research Funding; Imbrium: Honoraria; Karyopharm: Honoraria, Research Funding. Nooka:Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Adaptive Technologies: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria. Lonial:GSK: Consultancy, Honoraria, Other: Personal fees; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding; Takeda: Consultancy, Other: Personal fees, Research Funding; Novartis: Consultancy, Honoraria, Other: Personal fees; Janssen: Consultancy, Honoraria, Other: Personal fees, Research Funding; Merck: Consultancy, Honoraria, Other: Personal fees; JUNO Therapeutics: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Honoraria; Onyx: Honoraria; Genentech: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy, Honoraria, Other: Personal fees; Sanofi: Consultancy; Abbvie: Consultancy. Boise:AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech: Membership on an entity's Board of Directors or advisory committees.


A process for producing an antimicrobial medical instrument, characterized by comprising: an adhesion step of adhering an solvent containing an antimicrobial agent, which is produced by dispersing particles of the antimicrobial agent in a mixed solution comprising a first solvent and a second solvent having different boiling points from each other, onto the surface of at least a part of a medical instrument which is to be inserted into the body; and a drying step of drying the antimicrobial-agent-containing solvent adhered onto the surface of the medical instrument.


COVID-19 develops certain neurological symptoms, the molecular pathophysiology of which is obscure. In the present study, two networks were constructed and their hub-bottleneck and driver nodes were evaluated to consider them as 'target genes' followed by identifying 'candidate genes' and their associations with neurological phenotypes of COVID-19. A tripartite network was first constructed using literature-based neurological symptoms of COVID-19 as input. The target genes evaluated therefrom were then used as query genes to identify the co-expressed genes from the RNA-sequence data of the frontal cortex of COVID-19 patients using pair-wise mutual information to genes. A 'combined gene network' (CGN) was constructed with 189 genes selected from TN and 225 genes co-expressed in COVID-19. Total 44 'target genes' evaluated from both networks and their connecting genes in respective networks were analyzed functionally by measuring pair-wise 'semantic similarity scores' (SSS) and finding Enrichr annotation terms against a set of genes. A new integrated 'weighted harmonic mean score' was formulated using SSS and STRING-based 'combined score' to select 21 gene-pairs among 'target genes' that provided 21 'candidate genes' with their properties as 'indispensable driver nodes' of CGN. Finally, six pairs providing seven prevalent candidate genes (ADAM10, ADAM17, AKT1, CTNNB1, ESR1, PIK3CA, FGFR1) exhibited direct linkage with the neurological phenotypes under tumour/cancer, cellular signalling, neurodegeneration and neurodevelopmental diseases. The other phenotypes under behaviour/cognitive and motor dysfunctions showed indirect associations with the former genes through other candidate genes. The pathophysiology of 'prevalent candidate genes' has been discussed for better interpretation of neurological manifestation in COVID-19.


Asay (2018) criticizes our contention that psychologists do best to adhere to a substantive theory of correspondence truth. He argues that deflationary theory can serve the same purposes as correspondence theory. In the present article we argue that (a) scientific realism, broadly construed, requires a version of correspondence theory and (b) contrary to Asay's suggestion, correspondence theory does have important additional resources over deflationary accounts in its ability to support generalizations over classes of true sentences.


The current paper summarizes recent findings on management approaches that reduce feather pecking in laying hens. Results from epidemiological studies as well as studies on single factors have been taken into account, from the period of 2005 up till now and older studies have been included where relevant. Feather pecking in laying hens is still a major problem and because of the development of an increasing number of flocks housed in non-cage systems and a possible future ban on beak trimming in some countries it is important to define effective management strategies. In general, recent studies provide additional evidence for factors associated with an increased or reduced risk for feather pecking compared with earlier work in this field. It has been confirmed that the rearing period is very important to prevent feather pecking in the laying phase. Management factors associated with a reduced risk for severe feather pecking are a reduced stocking density, diets with increased fibre contents, mash instead of pelleted feed, reduced light intensity, presence of good quality substrate, access to attractive outdoor runs and providing environmental enrichment to stimulate foraging and exploration behaviour. As feather pecking is a multifactorial problem, the interaction between management factors and between management and the genetic background of the bird is important and an area for further research. In addition, the transfer of knowledge from scientific studies to commercial practice an issue that should receive attention.


Purpose: To report the prevalence of plateau iris in patients with primary angle closure glaucoma (PACG), in North India. Materials and Methods: The patients with PACG, attending the glaucoma services at a tertiary care center in North India were included in the study. All patients had undergone Nd-YAG laser peripheral iridotomy at least four weeks prior to inclusion in the study. Four weeks prior to inclusion in the study, none of the patients had used pilocarpine. Ultrasound Biomicroscopy (UBM) images were qualitatively evaluated and plateau iris configuration was defined in an eye if the following criteria were fulfilled in two or more quadrants: anteriorly directed ciliary process supporting the peripheral iris, steep rise of iris root from its point of insertion followed by a downward angulation from the corneoscleral wall, absent ciliary sulcus, and iridotrabecular contact in the same quadrant. Results: One hundred and one eyes were included in the study. There were 63 (62.4%) females and 38 (37.6%) males. The mean age of the patients was 57.8 ± 9.5 years (range: 42 to 78 years). The mean axial length in the study population was 22.2 ± 1.1 mm. The mean spherical equivalent refraction was 0.06 ± 1.12 D. The mean intraocular pressure was 18.5 ± 4.7 mmHg (range: 12 – 24 mmHg). Twenty-nine (28.7%) subjects were diagnosed with plateau iris on the basis of above-defined criteria. Of the 29 eyes, 18 (62.1%) subjects had plateau iris in two quadrants, nine (31.03%) in three quadrants, and two (6.8%) had this configuration in all the four quadrants. Conclusions: Approximately 30% of the eyes with PACG had plateau iris on UBM. Plateau iris was very often the cause for residual angle closure following laser peripheral iridotomy in Indian eyes with PACG.


In this paper, the leaky-mode theory is applied to take into account for the dielectric losses in millimetre waveband inhomogeneous leaky-wave antennas. A practical dielectric-filled cosine-tapered periodic leaky-wave antenna working in the 45 GHz band is studied, showing how the desired sidelobes level and directivity are spoilt due to the effect of the losses. An iterative procedure is used to correct the negative effects of the losses in the radiation patterns of the leaky-wave structure. It is also shown the practical limits of the proposed correction approach. The leaky-mode theory is applied for the first time to compensate the losses in a practical leaky-wave antenna in hybrid waveguide printed circuit technology. This leaky-mode theory is validated with full-wave three-dimensional finite element method simulations of the designed antenna.


The CH/pi interaction energies between benzene and halomethanes (CH(2)Cl(2) and CHCl(3)) were accurately determined. Two-color ionization spectroscopy was applied to the benzene-CH(2)Cl(2) and -CHCl(3) clusters, and the binding energies in the neutral ground state, i.e. the CH/pi interaction energies in these model cluster systems, were precisely evaluated on the basis of the dissociation threshold measurements of the clusters in the cationic state and the ionization potential value of the bare molecule. The experimentally determined interaction energies were 3.8 +/- 0.2 and 5.2 +/- 0.2 kcal mol(-1) for benzene-CH(2)Cl(2) and -CHCl(3) respectively, and the remarkable enhancement of the CH/pi interaction energy with chlorine-substitution was quantitatively confirmed. The experimental interaction energies were well reproduced by the high-level ab initio calculations. The theoretical calculations clarified the unique nature of the activation of the CH/pi interaction by the chlorine-substitution.


We report the observation of a controlled Landau-Zener transition (LZT) in Rydberg atoms by breaking the symmetry of the underlying Hamiltonian. For a nonhydrogenic Rydberg atom inside a changing electric (F) field, a LZT occurs between the avoided crossing energy levels of neighboring Rydberg states only for a sufficiently high changing rate. If a transverse magnetic (B) field is applied as we implement, the atomic level symmetry is broken, which causes the Stark manifolds denoted by a different |m| (m is the magnetic quantum number) to interact with each other. The mixed state levels end up pushing the adiabatically repelled target states closer and additionally they serve as stepping stones for the sequential LZTs between the neighboring sublevels. Such a feature significantly decreases the changing rate required for an efficient LZT inside a pure electric field. We report experimental observations that support the above scenario. It opens a versatile approach for engineering a controlled LZT in more general systems.


In this paper we propose a class of financial market models which are based on telegraph processes with alternating tendencies and jumps. It is assumed that the jumps have random sizes and that they occur when the tendencies are switching. These models are typically incomplete, but the set of equivalent martingale measures can be described in detail. We provide additional suggestions which permit arbitrage-free option prices as well as hedging strategies to be obtained.


The usefulness of newly device hybrid artificial liver system was evaluated in anhepatic dogs. The artificial liver module was composed of 60 to 80gm. primary cultured canine (Beagle) hepatocytes which were attached to 200 borocillicate glass plates. Total hepatectomy were done through cavo-caval and porto-caval shunt method using Anthron catheter to 14 dogs. Dogs were divided into following three groups. Group I; no treatment (n = 6) Group II; plasma perfusion (n = 4) Group III; treated with the artificial liver systems (n = 4) The survival times were 21.3 +/- 5.6, 27.8 +/- 4.0, and 55.0 +/- 11.3 hours in group I, II, and III, respectively. The longest survival time was 65 hours in one of group III dogs. APTT levels in group I and II increased more than 100 sec. within 24 hours. On the other hand it was maintained within 50 sec. during 54 hours treatment in group III. Ammonia levels in group I and II extremely increased over 2000ng/dl. In group III, it was less than 400ng/dl for 54 hours. Plasma amino acid levels in group I and II (Glutamine, Arginine, AAA) revealed significantly higher than in group III at 18 hours after operation. It is concluded that the newly device hybrid artificial liver system was useful for in vivo liver support.


Cherns. Lesley 1979 01 15: The environmental significance of Lingula in the Ludlow Series of the Welsh Borderland and Wales. Lethaia. Vol. 12. pp. 35–46, Oslo. ISSN 0024–1164.

The inarticulate brachiopod Lingula is commonly regarded as an indicator of very nearshore environments, particularly when found in monospecific assemblages. However, neither of the two common species in the Lower Leintwardine Beds, L. lewisii and L. lata. which occur commonly in such associations, have distributions indicative of such an environment. Their Occurrence correlates closely with the Leintwardinian palaeogeography. The former species is concentrated in shelf areas, the latter is confined to the basin; the two distributions overlap little. Individuals of both species are found articulated and perpendicular to the bedding, apparently in situ. Hence, the species may be inferred to have equivalent, infaunal modes of life comparable to living representatives of the family. The basinal distribution of L. lara is an original feature. The depth of the actively subsiding basin was relatively great, judging from sedimentological and palaeogeographical evidence. Therefore, L. lata was a species adapted to 'deep-water' environments. The lingulid distributions, reviewed against the concept of brachiopod depth-related communities previously defined for the Ludlow show the latter to be inapplicable in the Leintwardinian. The depth significance postulated for the recurrent species associations typical of the shelf sequences cannot be accepted.


There are millions of people in the world who do not get enough to eat, and millions more who may get enough (or even too many) calories but nevertheless suffer from poor nutrition. In a 2005 report, the World Health Organization (2005) assessed chronic disease (such as cardiovascular disease, stroke, and diabetes) as a major challenge for public health worldwide and listed an unhealthy diet as a major factor contributing to chronic diseases. As discussed in two recent review articles in The Plant Cell, research in plant biochemistry and molecular biology could make significant contributions to improving the availability of nutritious plant-based foods. Martin et al. (2011) focus on the identification and measurement of phytonutrients in plant-based foods and assessing the impact of individual phytonutrients on disease. In particular, they discuss the potential for development of near-isogenic foods that differ only in the content of specific phytonutrients to investigate their nutritional properties. Using a variety of approaches, including traditional plant breeding and metabolic engineering, it may be possible to produce a variety of fruits, vegetables, and other plant-based food products that are enriched in particular phytonutrients and assess their abilities to mitigate chronic disease. For example, they discuss the development of a high anthocyanin purple tomato (see figure), which was shown to extend the life of cancer-prone mice (Butelli et al., 2008). Traka and Mithen (pages 2483–2497) emphasize the challenge of identifying plant metabolites whose manipulation might have a significant effect on mitigating chronic disease. They provide a critical assessment of three major sources of evidence used to support a role of dietary plant secondary metabolites in the prevention of chronic disease: epidemiological studies, the use of animal and cell models, and human intervention studies. They provide a good overview of these approaches and their limitations and conclude with a section outlining opportunities for plant scientists. They stress the need for human intervention studies to provide evidence for health benefits of plant-derived dietary components and echo Martin et al. on the value of developing near-isogenic genotypes of common foods that vary in specific phytochemicals for use in human studies. These review articles make a strong case for more plant scientists becoming involved in research on human health and working together with nutritionists, experimental medics, clinicians, and epidemiologists to bring more nutritional foods to the table and reduce the impact of chronic disease on human populations. Watch for more articles on Plant Science and Human Health and Nutrition in The Plant Cell review section in the coming year.


Solving the structure of an antibody-antigen complex gives atomic level information of the interactions between an antibody and its antigen, but such structures are expensive and hard to obtain. Alternative experimental sources include epitope mapping and binning experiments which can be used as a surrogate to identify key interacting residues. However, their resolution is usually not sufficient to identify if two antibodies have identical interactions. Computational approaches to this problem have so far been based on the premise that antibodies with similar sequences behave similarly. Such approaches will fail to identify sequence-distant antibodies that target the same epitope. We present Ab-Ligity, a structure-based similarity measure tailored to antibody-antigen interfaces. Using predicted paratopes on model antibody structures, we assessed its ability to identify those antibodies that target highly similar epitopes. Most antibodies adopting similar binding modes can be identified from sequence similarity alone, using methods such as clonotyping. In the challenging subset of antibodies whose sequences differ significantly, Ab-Ligity is still able to predict antibodies that would bind to highly similar epitopes (precision of 0.95 and recall of 0.69). We compared Ab-Ligity's performance to an existing tool for comparing general protein interfaces, InterComp, and showed improved performance on antibody cases alongside a significant speed-up. These results suggest that Ab-Ligity will allow the identification of diverse (sequence-dissimilar) antibodies that bind to the same epitopes from large datasets such as immune repertoires. The tool is available at http://opig.stats.ox.ac.uk/resources.


Geographic Object-based Image Analysis (GEOBIA) is increasingly used to process high-spatial resolution imagery, with applications ranging from single species detection to habitat and land cover mapping. Image segmentation plays a key role in GEOBIA workflows, allowing to partition images into homogenous and mutually exclusive regions. Nonetheless, segmentation techniques require a robust parameterization to achieve the best results. Frequently, inappropriate parameterization leads to sub-optimal results and difficulties in comparing distinct methods. Here, we present an approach based on Genetic Algorithms (GA) to optimize image segmentation parameters by using the performance scores from object-based classification, thus allowing to assess the adequacy of a segmented image in relation to the classification problem. This approach was implemented in a new R package called SegOptim, in which several segmentation algorithms are interfaced, mostly from open-source software (GRASS GIS, Orfeo Toolbox, RSGISLib, SAGA GIS, TerraLib), but also from proprietary software (ESRI ArcGIS). SegOptim also provides access to several machine-learning classification algorithms currently available in R, including Gradient Boosted Modelling, Support Vector Machines, and Random Forest. We tested our approach using very-high to high spatial resolution images collected from an Unmanned Aerial Vehicle (0.03 – 0.10 m), WorldView-2 (2 m), RapidEye (5 m) and Sentinel-2 (10 – 20 m) in six different test sites located in northern Portugal with varying environmental conditions and for different purposes, including invasive species detection and land cover mapping. The results highlight the added value of our novel comparison of image segmentation and classification algorithms. Overall classification performances (assessed through cross-validation with the Kappa index) ranged from 0.85 to 1.00. Pilot-tests show that our GA-based approach is capable of providing sound results for optimizing the parameters of different segmentation algorithms, with benefits for classification accuracy and for comparison across techniques. We also verified that no particular combination of an image segmentation and a classification algorithm is suited for all the tasks/objectives. Consequently, it is crucial to compare and optimize available methods to understand which one is more suited for a certain objective. Our approach allows a closer integration between the segmentation and classification stages, which is of high importance for GEOBIA workflows. The results from our tests confirm that this integration has benefits for comparing and optimizing both processes. We discuss some limitations of the SegOptim approach (and potential solutions) as well as a future roadmap to expand its current functionalities.


Fractures in younger life are very common especially those involving the upper limb.
However, the causes of these fractures are poorly understood. The aim of this population
based case-control study was to evaluate the association of both bone dependent and
independent factors with upper limb fracture risk in children 9-16 years of age. Areal
(aBMD) and apparent (BMAD) bone mineral density were measured by dual energy Xray
absorptiometry (DXA). Skeletal age (SA) and metacarpal index (MI) was determined
by hand radiograph. Types and patterns of physical activity, risk taking and diet were
assessed by interview-administered questionnaires. Coordination was measured using the
8-point movement ABC. A total of 321 fracture cases and 321 randomly selected ageand
gender- matched controls were recruited. Fracture sites were as follow: hand: n=91,
wrist and forearm: n=190, upper arm: n=40. Conditional logistic regression analysis
showed wrist and forearm fracture risk was significantly associated with lumbar spine
BMAD (OR: 1.52/SD reduction, 95% CI 1.18-1.96), MI (OR: 1.43/SD reduction, 95% CI
1.14-2.20), light physical activity (OR: 0.81/unit, 95% CI 0.65-1.00), cola consumption
(OR: 1.43/category, 95% CI 1.08-1.88) but conclusions may be limited by sample size
considerations. Obesity or overweight was not associated with any fracture type. For total
fractures, there was a gender discordant effect of sports participation with an increased
fracture risk in boys and decreased fracture risk in girls which reached statistical
significance for total, contact, non-contact and high-risk sports participation as well as
four individual sports (soccer, cricket, surfing and swimming). In conclusion, both bone
dependent and independent factors are important determinants of upper limb fracture risk
in children. There is heterogeneity of cause for both gender and different fracture sites
that will necessitate different approaches to prevention.


On page 2793 in the 18 May 2017 issue, under "Disclosures," Laurie H. Sehn is incorrectly cited as the article's Associate Editor. Thomas L. Ortel should be cited as the Associate Editor with the disclosure, "Associate Editor Thomas L. Ortel served as an advisor or consultant for Instrumentation Laboratory."The publisher apologizes for this error. Also, in theAcknowledgments section on page 2799, the sentence "The assistance of Robin Cox and the Division of Pediatric Anesthesia at the Alberta Children's Hospital in facilitating the collection of control blood samples is gratefully acknowledged" is missing. The errors have been corrected in the online version, which now differs from the print version.


This paper argues that automated knowledge acquisition for diagnosis has had limited success in both failure-driven diagnosis and model-based diagnosis. The paper describes fault-based and model-based reasoning for diagnosis and surveys some of the approaches to knowledge acquisition in both areas. The Diagnostic Remodeller (DR) algorithm I am currently implementing for the automated generation of behavioural models from fault-based knowledge is presented. An example of fault-based knowledge from the Jet Engine Troubleshooting Assistant (JETA) is used to demonstrate how a behavioural model can be extracted


TFH cells have been identified as a new T helper subset specialized to regulate the development of effector and memory B cells and long-lived plasma cells. The interaction between TFH and B cells leads to the activation of B cells and germinal centers (GC) formation. Considering the importance of TFH for B cell antibody response, novel vaccine adjuvants and intranasal vaccines to boost TFH number or function may be an attractive vaccination strategy to enhance vaccine efficacy in humans. Adenotonsillar tissues are major parts of nasopharyngeal associated lymphoid tissues (NALT) and they are important in response to upper respiratory tract pathogens and intranasal vaccination. This PhD project investigated the frequencies of TFH in human NALT and PBMC in children and adults. The effects of CpG-DNA and live attenuated influenza vaccine (LAIV) on TFH in human NALT and the TFH-mediated B cell immunity to influenza virus were studied. The importance of the cytokine IL-21 and plasmacytoid dendritic cells (pDC) in TFH cell-mediated B cell antibody production was also investigated.
Adenotonsillar MNC and PBMC were isolated from adenotonsillar tissues and peripheral blood respectively. TFH (CD4+ CXCR5high ICOShigh) numbers and function were analysed by flowcytometry and intracellular cytokine staining. Purified TFH (CD4+ CXCR5hi) and non-TFH cells (CD4+ CXCR5-) were co-cultured with B cells in the presence of influenza virus antigen and CpG-DNA or of LAIV. Purified pDC were added to the TFH-B cell co-culture to study their importance in TFH -mediated B cell antibody production. Haemagglutinin (HA)-specific antibody production was analysed by ELISA and ELISpot assay. IL-21 receptor blocking by neutralization was used to study the importance of IL-21 in TFH-mediated B cell antibody production.
A prominent number of TFH were found in human NALT which were considerably higher than in PBMC. There was an age-associated difference in TFH numbers in NALT and BPMC, i.e. the mean TFH number was higher in children than in adults. TFH in NALT were shown to express high levels of IL-4, IL-10 and IL-21 and that were important for B cell antibody production. A good correlation between the numbers of GC B cell and TFH in NALT was seen. Co-culture of purified TFH but not non-TFH with B cells promoted antibody production. Stimulation of adenotonsillar MNC by CpG-DNA significantly increased TFH number and that was correlated with HA-specific antibody production following influenza antigen stimulation. Co-incubation of TFH-B cell with pDC enhanced the CpG-DNA-mediated antibody production. We also found that stimulation with LAIV significantly increased TFH number and that was correlated with HA-specific antibody production. Blocking the IL-21R significantly reduced the number of TFH that was correlated with a significant reduction of HA-specific antibody production.
Enhancing vaccine immunogenicity through modulation of TFH numbers or function in human NALT using immunological adjuvants such as CpG-DNA and through intranasal vaccination may be an effective vaccination strategy against respiratory pathogens.


Primary liver cancer comprises a diverse group of liver tumors. The heterogeneity of these tumors is seen as one of the obstacles to finding an effective therapy. The Hippo pathway, with its downstream transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), has a decisive role in the carcinogenesis of primary liver cancer. Therefore, we examined the expression pattern of YAP and TAZ in 141 patients with hepatocellular carcinoma keratin 19 positive (HCC K19+), hepatocellular carcinoma keratin 19 negative (HCC K19−), combined hepatocellular–cholangiocarcinoma carcinoma (cHCC-CCA), or cholangiocarcinoma (CCA). All cHCC-CCA and CCA patients showed high expression levels for YAP and TAZ, while only some patients of the HCC group were positive. Notably, we found that a histoscore of both markers is useful in the challenging diagnosis of cHCC-CCA. In addition, positivity for YAP and TAZ was observed in the hepatocellular and cholangiocellular components of cHCC-CCA, which suggests a single cell origin in cHCC-CCA. Within the K19− HCC group, our results demonstrate that the expression of YAP is a statistically significant predictor of poor prognosis when observed in the cytoplasm. Nuclear expression of TAZ is an even more specific and independent predictor of poor disease-free survival and overall survival of K19− HCC patients. Our results thus identify different levels of YAP/TAZ expression in various liver cancers that can be used for diagnostics.


Crocus sativus is the source of saffron, which is made from dried stigmas of the plant. It is a male-sterile triploid that ever since its origin has been propagated vegetatively. The mode of evolution and area of origin of saffron are matters of long-lasting debates. Here we analyzed chloroplast genomes, genotyping-by-sequencing (GBS) data, nuclear single-copy genes, and genome sizes to solve these controversial issues. We could place 99.3% of saffron GBS alleles in Crocus cartwrightianus, a species occurring in southern mainland Greece and on Aegean islands, identifying it as the sole progenitor of saffron. Phylogenetic and population assignment analyses together with chloroplast polymorphisms indicated the wild C. cartwrightianus population south of Athens as most similar to C. sativus. We conclude that the crop is an autotriploid that evolved in Attica by combining two different genotypes of C. cartwrightianus. Vegetative propagation prevented afterwards segregation of the favorable traits of saffron.


BACKGROUND: Computer vision syndrome is a group of eye and vision-related problems that result from prolonged computer use. The worldwide pandemic of coronavirus disease-2019 (COVID-19) lockdown has led to an increase in the digital screen exposure as jobs as well as academic learning have majorly shifted online. This has caused an increase in digital eye strain (DES) globally. The aims and objectives of this study were to compare the knowledge, attitude, and practices among medical and nonmedical professionals with regard to DES in a background of COVID-19 lockdown. MATERIALS AND METHODS: A cross-sectional, observational, online questionnaire-based research survey analysis was conducted among medical professionals with age- and sex-matched nonmedical professionals. Responses were collected over a week and analyzed. The level of significance was set at a P < 0.05. Statistical Package for the Social Sciences software version 23.0 was used for the result analysis. RESULTS: Our study included 353 (50.4%) medical and 347 (49.6%) nonmedical personnel. It was noted that 266 (75.4%) of medical professionals and 268 (77.2%) of nonmedical professionals experienced eye problems after prolonged digital screen exposure. A significant proportion of respondents experienced an increase in symptoms following COVID-19 lockdown with 140 (52.6%) being medical professionals and 163 (60.8%) nonmedical professionals (P = 0.015). CONCLUSIONS: DES is a preventable lifestyle-associated disorder. Awareness among the masses can reduce the adverse effects. Proper lighting, adequate viewing distance, voluntary blinking, and using lubricating eye drops are a few ways to reduce the chances of DES. Further studies are needed to formulate standardized guidelines for the management of DES.


The cuticle is important in the physiology of the vegetables because it acts as the first interaction between the plant and the environment. Structure and chemical composition cuticle varies across of plant developmental stages affecting it s funtion as protector barrier. In this work we studied chemistry composition of cuticular waxes during the ontogeny of 'Tommy Atkins', 'Kent' and 'Keitt' mango (Mangifera indica L.) fruits. Fruits were randomly sampled from an orchard at Navojoa, Sonora, Mexico. This study was done at two stages: during fruit growth and storage. A completely randomized design with three replications was used. Chemical composition of epicuticular e intracuticular waxes were measured in each sample. The major fraction present in the waxes of plants were identified and quantified : fatty acids, alkanes and fatty alcohols. GC-FID analysis, 15 compounds were identified alkanes (C18 to C33), 11 precursor fatty acids (C13 to C27) and fatty alcohols 9 compounds (C17 to C26). In the chemical composition of epicuticular waxes, distribution model of the fractions was similar among cultivars studied during the ontogeny. Cultivars showed differences in the proportion of the fractions and the concentration of the individual components. The relative composition of the fractions studied in epicuticular wax during fruit growth (values shown at 60 DPA), the largest proportion was alkanes (50-60%), followed by fatty acids (38-46% ) and a lesser proportion of fatty alcohols (2-4%). Significant differences between cultivars in the proportion of the fractions tested. In intracuticular wax fraction was predominant fatty acid (62-77%), followed by alkanes (21-35%) and alcohol (2-6%) during ontogeny of fruit. Palabras clave: Mangifera indica L., cera epicuticular, cera intracuticular, composicion quimica. CHEMICAL COMPOSITION OF THE CUTICULAR WAXES OF Mangifera indica L. FRUITS


Sweet potatoes, Ipomoea batatas (L.), infested with the sweetpotato weevil, Cylas formicarius elegantulus (Summers), were examined by radiography and ultrasound. No weevil life stage was clearly detected by radiographic methods. However, uninfested sweet potatoes and feeding tunnels in infested tuberous roots were clearly distinguishable. Thus, radiography could assist in the development of quarantine treatments. Ultrasound could not penetrate the root surface and did not produce an image.


Left ventricular papillary muscle geometry is distorted in dilated non-ischemic hearts, and following anterior infarction caused by a wrap around left anterior descending artery occlusion. Loss of the apex creates a spherical left ventricular (LV) chamber, and subsequent dilation causes secondary mitral insufficiency by stretching the annulus, altering tethering of the chords and widening the dimension between the bases of papillary muscles to impair leaflet coaptation. This report will describe an intraventricular way to narrow the widened inter papillary muscle distance toward normal.


AbstractCuba sought international help in the 1960s from individuals, organisations, and countries that were sympathetic to the revolution in response to acts of aggression by the US government. We discuss the experiences of one such group of individuals, North Americans from Canada and the United States, who travelled to Cuba in the 1960s to live and work there. We show that the revolution benefited from their support in practical and symbolic ways. It politically socialised North Americans and imbued them with a revolutionary enthusiasm. This enthusiasm was tempered over time by recognition of the revolution's limitations. The story of these North Americans offers an insider perspective on the revolution in its early humanist phase and furthers an understanding of the New Left's views on Cuba in the 1960s. Data come from 28 qualitative interviews with North Americans who lived and worked in Cuba in the 1960s.Keywords: Cuba, Cuban revolution, New Left, North America, political socialisation, 1960sIntroductionThe Cuban revolution of 1959 was one of the most remarkable phenomena in the history of Latin America (Kaplan 2009). It represented one of the most profound social transformations ever seen in the Americas (Fagen 1969). Cuba transformed its political culture, socialised its economy, redistributed its wealth, and mobilised its population to address illiteracy, poor health, and other social and economic problems (Saney 2004). Optimism filled the air. There was hope that a more just society was possible.The United States responded to Cuba's revolutionary process with acts of aggression aimed at destroying the revolution and at isolating Cuba from the Western Hemisphere (Bolender 2010; Dominguez 1978). In response, Cuba sought international help where it could from individuals, organisations, and countries that were sympathetic to the revolution, including from North Americans.Thousands of persons from around the globe came to Cuba in the 1960s to view the revolution's accomplishments and support the revolutionary process, including North Americans from the US and Canada. A number of these North Americans were so impressed by what they observed, so attracted by the energy and excitement generated by the revolution, that they decided to stay, some for years, before they returned home, working as economic advisers, engineers, journalists, teachers, and translators. We discuss why they travelled to Cuba, their experiences on the island, and the meaning Cuba has had in their lives. Almost nothing has been written about these individuals. Our study is unique, because it analyses primary material gathered through qualitative interviews with Americans and Canadians who lived in Cuba for years, before they eventually returned home. Our account of North Americans on the island offers an insider perspective on the revolution in its early humanist phase and enhances an understanding of the New Left's views on Cuba in the 1960s (Radosh 1976).The story of these North Americans is important for a number of reasons. It demonstrates the significance for Cuba of a North American presence on the island in the 1960s. It also shows how the revolution politically socialised North Americans. Political socialisation here refers to exposure to political information and values and to the impact of this exposure on one's attitudes about politics and society (Merelman 1986). The revolution imbued North Americans with a revolutionary enthusiasm, which was tempered over time by recognition of the revolution's limitations. There are few descriptions of the impact of political socialisation on individuals living in Cuba in the 1960s (Lewis, Lewis and Rigdon 1978), although there is a considerable literature on the general process of political socialisation and efforts to transform revolutionary culture (Fagen 1969; Medin 1990; Rhoades 1979).MethodsWe used a snowball sampling technique (Goodman 1961) to recruit individuals for this study whereby one North American recruited another. …


We present a new mechanism for harmonic generation in magnetorheological (MR) fluids, which differs from the usual ones due to magnetic anisotropy existing in amorphous ferromagnetic materials. Based on thermodynamics, we derive the incremental magnetic susceptibility of the MR fluid which is partially situated in a nonuniform magnetic field, and further extract the desired harmonics analytically. By measuring such harmonics, it seems possible to monitor the structure of MR fluids.


The staff of the Pentagon Family Assistance Center was closely exposed to the intense grief experienced by those who had suddenly lost their loved ones following the crash of American Airlines Flight 77 into the Pentagon on September 11, 2001. In addition, some Pentagon Family Assistance Center workers were in the Pentagon when it was attacked, and others lost friends or colleagues in the event. A "Brief Education and Support" group intervention, designed to avoid the detailed exploration of traumatic experiences, was used to help workers recognize and understand their reactions to the event, and, as appropriate, to normalize those reactions. A second aim was to support positive coping and warn against problematic coping. The groups were characterized by much sharing of emotional and behavioral reactions to the work and to the Pentagon crash, and they were useful in prompting reflection on ways of coping. They appeared to offer one acceptable and effective way of educating emergency workers about their traumatic stress reactions, normalizing those reactions, and promoting adaptive coping.


Objective: Focusing on temporal associations between momentary (or state) loneliness, appraisal of social company, and being alone in daily life may help elucidate mechanisms that contribute to the development of prolonged (or trait) loneliness and major depressive disorder (MDD). We aim to examine if (a) a self-reinforcing loop between loneliness, negative appraisals of social company, and being alone in daily life may contribute to trait loneliness; (b) this possible self-reinforcing loop may also contribute to the development of MDD, by testing differences in temporal relationships between these social elements in participants who did or did not develop MDD during follow-up; and (c) any of these social elements at baseline predicted a MDD at follow-up. Methods: A female general population sample (n = 417) participated in an experience sampling method (ESM) study. Time-lagged analyses between loneliness, appraisal of social company, and being alone were examined at baseline, and their associations with the development of MDD during 20 months follow-up were investigated. Results: State loneliness was followed by an increase in negative appraisals of social company and a higher frequency of being alone. Further, negative appraisals of social company were associated with a higher frequency of being alone afterward. Only the latter was significant in the transition to MDD group. Trait loneliness predicted MDD during follow-up. Conclusions: Avoiding social contact after appraising company more negatively may contribute to the development of MDD.


The ROS1 receptor tyrosine kinase can be aberrantly activated by gene rearrangements that generate oncogenic ROS1 kinase fusions. ROS1 fusions have been detected in diverse adult and pediatric cancers including up to 2% of non-small cell lung cancers (NSCLC), 1-9% of cholangiocarcinomas, and 0.5-1% of gliomas and glioblastomas. There are over 50 known fusion partners of ROS1. Notable examples include CD74, EZR, SDC4, and SLC34A2 in NSCLC; GOPC exons 1-3 (short form or GOPC(S)) in cholangiocarcinoma; and GOPC exons 1-7 (long form or GOPC(L)) in glioblastoma. Crizotinib and entrectinib are FDA-approved ROS1 tyrosine kinase inhibitors (TKIs), but clinical emergence of ROS1 resistance mutations S1986F/Y, F2004C/I/V, L2026M, G2032R, and D2033N restricts their therapeutic utility. Due to the diversity of ROS1 fusion partners and kinase-domain mutations, development of novel ROS1 inhibitors that retain potency against fusion variants and resistance mutations would be beneficial to address these clinical needs.
 NVL-520 is a novel, brain-penetrant ROS1-selective inhibitor that exhibits preclinical activity against ROS1 alterations, including resistance mutations, while also sparing inhibition of TRKB. TRKB inhibition in the central nervous system has been implicated in adverse events observed with FDA-approved dual TRK/ROS1 inhibitor entrectinib and FDA-approved ALK inhibitor lorlatinib. We previously reported the activity of NVL-520 in several cell line and xenograft models bearing CD74-ROS1, EZR-ROS1, and SDC4-ROS1 fusions, with a wild-type kinase domain or a G2032R mutation. Here we report a broader comparative characterization of NVL-520 and other ROS1 inhibitors against a diverse set of ROS1 fusion partners and kinase-domain mutations.
 NVL-520 showed potent suppression of proliferation and/or ROS1 signaling in Ba/F3, NIH3T3, or human cancer cell lines expressing CD74-, EZR-, SLC34A2-, or GOPC(L)-ROS1 fusions. NVL-520 also retained potent inhibition of Ba/F3 cells expressing ROS1 fusions with F2004C, F2004V, G2101A, or G2032R mutations. To further demonstrate the broad activity of NVL-520, we utilized NIH3T3 cells expressing CD74- or EZR-ROS1 fusions with G2032R or F2004C mutations. NVL-520 robustly suppressed colony formation and downstream effector signaling in the ROS1 G2032R and F2004C resistance mutant context. Lastly, NVL-520 demonstrated inhibition of ROS1 signaling in a human glioblastoma cell line U118MG, which harbors the GOPC(L)-ROS1 fusion. In conclusion, the preclinical profile of NVL-520 supports its potential to address a medical need for patients with a diverse array of ROS1 fusion partners and kinase-domain mutations, both in NSCLC and in other cancers such as glioblastoma. NVL-520 is being evaluated in a Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC or other solid tumors (NCT05118789).
 Citation Format: Anupong Tangpeerachaikul, Clare Keddy, Katelyn Nicholson, Monika Davare, Henry E. Pelish. Preclinical activity of NVL-520 in ROS1-driven cancer models with diverse fusion partners and kinase-domain mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3336.