The avian neck allows the head to perform a variety of tasks that would be carried out by the forelimbs in other vertebrates, as the forelimbs are primarily adapted for flight in birds. This has created a strong additional selection pressure on the cervical column and has resulted in the evolution of a vast array of neck morphologies throughout extant birds. This diversity is most evident in the large variation observed in vertebral counts of the neck, and the lack of known homology between species with differing cervical counts has hindered research into morphological variation of the avian cervical spine. The lack of quantitative assessment of this variation has stunted our understanding of how the neck became such an integral component of avian biology. Recent work has shown that Hox gene patterning is conserved within the neck across Aves and that five cervical regions exist within the avian spine, and homologous interspecific comparisons can now be made by comparing aspects of regional morphology. Iterating on previous work, this thesis uses 3D geometric morphometrics as a proxy to delineate and analyse these cervical regions within extant birds. Here I use a holistic approach to understand functional and ecological drivers in avian neck shape and length in a diverse selection of 52 specimens (46 species) of modern birds by combining three-dimensional geometric morphometrics with multivariate statistics and quantitative dissection as part of the following four objectives. The first objective sought to determine if patterns of cervical regionalisation exist within extant Aves by assessing the variation in regional vertebral counts and by using Phenotypic Trajectory Analysis to examine factors that affect morphological variation across the entire cervical spine. Results indicated that increases to cervical counts are not responsible for neck elongation in birds and that few ecological factors have a significant correlation with regional vertebral counts. Vertebral morphology across the entire cervical column only displays significant variation in birds with extreme cervical kinematics, such as carnivores. The second objective was to quantify the relationship between neck length, head mass, and body mass across extant birds. Neck length and head mass scale according to isometry. The relationship between neck length and head mass is also isometric and this indicates that neck length in birds is not as tightly constrained by head mass when compared to other vertebrates. Relative neck lengths are shorter in birds that locomote using powered flight and head mass is lower in terrestrial birds. This may indicate that powered flight is a constraint on cervical morphological variation. The third objective was to quantify factors affecting variation in the morphology and length of individual regions. Region lengths strongly correlated with neck length and this suggests that avian neck elongation is a product of increases to vertebral length rather than increases to vertebral counts, and that regions 2 and 5 are responsible for this elongation. Body mass and neck length were revealed to have the strongest correlation with morphological variation in regions across 4 out of 5 cervical regions. Only ecological factors associated with specialised cervical kinematics, i.e. adaptations to carnivory or aquatic foraging, displayed significant variation in regional vertebral morphology. The final objective was to quantify variation in avian muscle architecture and I found that muscle architecture and mass scaled predominantly according to positive allometry. Ecology has a weak correlation with muscle architecture and mass variation and may accommodate fast head strikes and adaptations to underwater foraging in certain taxa. Cranial muscles that support the head appear to be more morpho-functionally restricted, whilst caudal muscles display much more variation in architecture and mass. This thesis has shown that across multiple aspects of morphology, the avian cervical column is a generalised musculoskeletal system, only adapting to specialised patterns of cervical kinematics. The avian cervical column is often referred to as a surrogate arm due to its role in positioning the head to manipulate the environment in the stead of the forelimbs which are heavily adapted for flight and the generalised pattern of morphological variation recovered here supports the hypothesis that the avian neck is a surrogate arm. Future work is needed to be done in the wake of this thesis to ensure that more birds are sampled for their variation in muscle architecture, as well as undertaking projects that seek to quantify variation in avian cervical kinematics and patterns of intervertebral flexion.


: In this paper, we have analysed cells which are in the process of enucleation in mouse spleen. We have provided additional support for the hypothesis that erythroid cells can autonomously undergo enucleation. The presence of a constriction in the nucleus and in the plasma membrane during this process has bee confirmed. Microfilaments have been described for the first time in the cytoplasm of maturing erythroid cells. Their position during enucleation is suggestive of an active role for these elements in this process.


The spatio-temporal (ST) position information between local features plays an important role in action recognition task. To use the information, neighborhood-based features are built for describing local ST information around ST interest points. However, traditional methods of constructing neighborhood, such as sub-ST volumetric method and nearest-neighbor-based neighborhood method, ignore the orientation information of neighborhood. To make the neighborhood-based features more discriminative, we construct a novel, oriented neighborhood by imposing weights on the distance components. Specifically, in our scheme, firstly, local features are produced, and encoded by locality-constrained linear coding (LLC). Then, oriented neighborhoods are constructed by imposing weights on the distance components between features, and obtain single-scale oriented neighborhood features (SONFs). Next, multi-scale oriented neighborhood features (MONFs) are formed by concatenating SONFs. As a result, action video sequences are represented as a collection of MONFs. Finally, locality-constrained group sparse representation (LGSR) is used as classifier upon MONFs. Experimental results on the KTH and UCF Sports datasets show that our method achieves better performance than the competing local ST feature-based human action recognition methods.


Thin-film structures composed of nearly nonmagnetostrictive single-layer Co/sub 76/Fe/sub 4/B/sub 20/ or magnetostrictive Fe/sub 80/B/sub 20/ and Co/sub 75/Si/sub 15/B/sub 10/ amorphous layers have been deposited on bowed glass substrates using the RF-sputtering technique. The fabrication procedure induces a postdeposition compressive stress in the thin-film structure when the sample is retrieved from an arching device in the sputtering chamber. This results in an induced magneto-elastic anisotropy that governs the magnetic easy axis of the film, depending on the sign of the magnetostriction constant of each layer. Particular attention is paid here to heterogeneous structures made of bi- or multilayers with magnetic easy axis oriented in a different direction in each layer. Bulk magnetic properties were evaluated from hysteresis loops and thermomagnetization measured by vibrating sample magnetometry (VSM) and quantum interference device (SQUID) magnetometry. Magnetic domain walls and out-of-plane magnetized domains were observed by a Kerr imaging system and magnetic force microscopy. The combination of microstructure and strains induced in the layers determines the orientation of the observed magnetic anisotropies, which vary from high in-plane anisotropies up to out-of-plane orientations for selected films. The results, which provide reassurance that effective anisotropies are induced in each of the layers, are discussed in terms of the interactions between magnetic phases with different induced easy magnetization axes.


Extra Medium is an experiment that seeks to explore the impact of today's rapidly changing media environment. Through the traditional use of interviews, as well as manipulations of the traditional documentary framework, this project seeks to tease out a nuanced angle from a larger cultural environment of media saturation. It seeks to answer this question: what is the cultural impact of the widespread adoption of smartphones and social media in the last ten years? It proposes that the inclination of generation Y and Z towards activities rooted in the physical and tactile – in particular, analog photography – is a manifestation of anxiety surrounding a new and changing media environment.


This article contributes to the academic debate about gender equality change by conceptualizing resistance to gender equality change as characteristic of a system where gendered organizations tend to move back to an equilibrium when confronted with change. It explores the role of change agents and change recipients in challenging this equilibrium using autobiographical reflections on three events of resistance during participatory action research aimed at gender equality in Dutch universities. It argues that resistance can be understood as stakeholders' articulated defence of the organizational identity when research results threaten gendered organizational norms, beliefs and values. Organizational change cognitively and emotionally challenges not only change recipients but also change agents. Reflection on and sharing of personal experiences in groups of researchers may be sources of empowerment, enabling gender equality change agents to continue the conversation with change recipients. This conversation may transform not only change recipients but also change agents.


In recent years, the research of 3D mapping technique in urban environments obtained by mobile robots equipped with multiple sensors for recognizing the robot's surroundings is being studied actively. However, the map generated by simple integration of multiple sensors data only gives spatial information to robots. To get a semantic knowledge to help an autonomous mobile robot from the map, the robot has to convert low-level map representations to higher-level ones containing semantic knowledge of a scene. Given a 3D point cloud of an urban scene, this research proposes a method to recognize the objects effectively using 3D graph model for autonomous mobile robots. The proposed method is decomposed into three steps: sequential range data acquisition, normal vector estimation and incremental graph-based segmentation. This method guarantees the both real-time performance and accuracy of recognizing the objects in real urban environments. Also, it can provide plentiful data for classifying the objects. To evaluate a performance of proposed method, computation time and recognition rate of objects are analyzed. Experimental results show that the proposed method has efficiently in understanding the semantic knowledge of an urban environment.


AbstractVentriculoperitoneal (VP) shunt complications are common, but abdominal complications are rare. The objective of this report is to present 2 cases of intestinal obstruction due to a VP shunt and review the literature for data on this rare occurrence.A 4-month-old boy received surgical resection of a medulloblastoma and a VP shunt was inserted to manage progressive hydrocephalus. Two months later, he was admitted with intermittent vomiting, and plain abdominal radiography showed complete intestinal obstruction. Emergency laparotomy revealed an adhesive intestinal obstruction around the catheter, and approximately 5 cm of necrotic ileum was resected. His recovery was uneventful. In the second case, a 6-year-old boy was diagnosed with a primary nongerminomatous malignant germ cell tumor and a VP shunt was place to treat hydrocephalus. Two weeks after the first course of chemotherapy, he went into a coma; computed tomography demonstrated enlargement of the tumor and gross total resection was performed. Two weeks later, he developed abdominal distention; plain radiography showed intestinal obstruction and laparotomy revealed adhesive intestinal obstruction around the catheter with 15 cm of necrotic ileum. The necrotic bowel was resected. Unfortunately, the patient developed sepsis and despite treatment remained in a vegetative state.Medline, Central, Embase, and Google Scholar databases were searched up to May 9, 2014, using the terms VP shunt, shunting, and/or intestinal obstruction. Only cases involving children or adolescents were included. Eleven reports involving patients with abdominal complications resulting from a VP shunt for hydrocephalus were identified. The dates of the reports spanned from 1971 to 2014. Volvulus was the most common cause of VP shunt-related obstruction, and mechanical obstruction due to twisting of the catheter the second most common. Only 1 case in the literature review was related to intestinal adhesions. Treatment in most cases was laparotomy.Although intestinal obstruction is a rare complication of a VP shunt, it should be considered in the presence of abdominal symptoms and prompt treatment provided to have a good outcome.


The research undertaken concerns the analysis of original Byzantine mortars and the study of new compatible lime-based mixtures, for conservation purposes, which present enhanced resistance to sulphates. The thesis focuses on the effect of barium hydroxide, as an additive, to both the physicochemical properties and the durability of conservation mortars.

Both binary pastes and mortar mixtures, containing varying amounts of barium hydroxide, were prepared and their physicochemical properties and durability determined. Comparisons were made with a reference mixture containing no barium hydroxide.

The laboratory mixtures were synthesised according to the analysis of original mortars, collected from six different Byzantine mosaic pavements.

The durability of the mortar mixtures against sulphate action was studied through the use of accelerated aging tests: crystallisation of soluble salts; electrochemical degradation; sulphate fixation; and resistance to leaching of cementing material. The results of these tests were considered together with the physical properties of the mortars, since these also influence their durability.

From the interpretation of the results it was shown that the setting of lime-based barium mixtures can be described by two mechanisms; the carbonation process of calcium hydroxide and barium hydroxide; and the precipitation of a barium calcium carbonate [BaCa(CO3)2] solid solution.

It has been shown that the presence of barium hydroxide in lime-based mortars has a physical effect on the pore space characteristics of the mortar. It has also been shown that its presence improves the durability of the mortar, playing a protective role against sulphate attack.


A method of growing single‐crystal low‐resistivity (∼103 Ω cm) n‐type AlN is described in which dc ultraviolet electroluminescence is observed for the first time. The emission is in a broad band extending from 215 nm into the blue end of the visible spectrum. AlN grown on tungsten and sapphire substrates is contacted with Al and Nb. Light emission occurs in small spots near the negatively biased contact for currents of a few mA at voltages as low as 17 V, but typically in the range between 30 and 150 V. The external quantum efficiency is 6×10−6, and at constant current the light output is nearly independent of temperature up to several hundred degrees centigrade.


In the paper I propose a definition of higher religions as having their own Holy Scripture. The rating of the higher religions was built on the number of followers, the time of existence and predominance in certain territories. In total, 25 higher religions are identified. Four world religions were chosen as the coordinate basis for building a graphic connection between all 25 higher religions: by rating and by mutual proximity. It turned out that they can be placed in only one specific way. Moreover, all these religions are lined up in the correct absolutely symmetrical matrix—the harmony of the higher religions. This is clear evidence that all higher religions constitute a holistic, mutually reinforcing unity.


Much progress has been made in radiative heat transfer modelling with respect to the treatment of nongrey radiation from both gas-phase species and soot particles, while radiation modelling in turbulent flame simulations is still in its infancy. Aiming at reducing this gap, this paper introduces state-of-the-art models of gas-phase and soot radiation to turbulent flame simulations. The full-spectrum k-distribution method (M.F. Modest, 2003, Journal of Quantitative Spectroscopy & Radiative Transfer, 76, 69–83) is implemented into a three-dimensional unstructured computational fluid dynamics (CFD) code for nongrey radiation modelling. The mixture full-spectrum k-distributions including nongrey absorbing soot particles are constructed from a narrow-band k-distribution database created for individual gas-phase species, and an efficient scheme is employed for their construction in CFD simulations. A detailed reaction mechanism including NO x and soot kinetics is used to predict flame structure, and a detailed soot model using a method of moments is employed to determine soot particle size distributions. A spherical harmonic P1 approximation is invoked to solve the radiative transfer equation. An oxygen-enriched, turbulent, nonpremixed jet flame is simulated, which features large concentrations of gas-phase radiating species and soot particles. Nongrey soot modelling is shown to be of greater importance than nongrey gas modelling in sooty flame simulations, with grey soot models producing large errors. The nongrey treatment of soot strongly influences flame temperatures in the upstream and the flame-tip region and is essential for accurate predictions of NO. The nongrey treatment of gases, however, weakly influences upstream flame temperatures and, therefore, has only a small effect on NO predictions. The effect of nongrey soot radiation on flame temperature is also substantial in downstream regions where the soot concentration is small. Limitations of the P1 approximation are discussed for the jet flame configuration; the P1 approximation yields large errors in the spatial distribution of the computed radiative heat flux for highly anisotropic radiation fields such as those in flames with localized, near-opaque soot regions.


Abstract 1484

MDM2, a p53-inducible phosphoprotein, binds to the N-terminus of the p53 and negatively regulates its transcriptional activity. New MDM2 antagonists, such as RO5045337 (Roche) and NSC-66811 (Merck), are now available for Phase I/II clinical development, but their activity is dependent on TP53 mutation status. Therefore, in order to efficiently treat B-progenitor acute lymphoblastic leukemia (ALL) patients with an MDM2 antagonist, we set up a sensitive assay to identify TP53 lesions.

Deletions and uniparental disomy (UPD) involving TP53 were assessed on 146 DNA samples from Philadelphia-positive (Ph+)(n = 126) and Ph-negative (n = 20) ALL patients by Genome-Wide Human SNP 6.0 array (Affymetrix). No 17p UPD events were detected whereas losses were identified in 2% of cases.

Mutations of TP53 were thereafter investigated in 67 samples including 60 Ph+ and 7 Ph-negative cases. Since the majority of the studies in leukemia were focused on genomic alterations and resulted in low rate of TP53 mutations, we aimed to identify RNA mutations and aberrant isoforms due to other mechanisms, such as RNA editing. To this purpose three overlapping shorter amplicons covering the entire coding cDNA sequence (GenBank accession number [NM_000546][1].4) and the untranslated exon 1 [amplicon 1 (491 bp): exons 1–5; amplicon 2 (482 bp): exons 5–8; amplicon 3 (498 bp): exons 8–11)] and a longer amplicon (1,317 bp) starting from exon 1 and ending to exon 11 were sequenced by Sanger method. TP53 mutations were detected in only 6 cases (8.9%), suggesting that these alterations are apparently rare events in B-ALL. They included 4 missense point mutations in the DNA binding domain and in the carboxyl-terminal tetramerization and regulatory domain: C135Y (ex 5), A234T (ex 7), R290C (ex 8) and A347T (ex 10). Interestingly, in two cases we identified aberrant transcripts: 1) a TP53 isoform characterized by retention of introns 5–6–7 and predicted to encode for a truncated protein due a premature stop codon; 2) a TP53 isoform in which the DNA binding domain is lost due to an exon conjunction between the exon 4 and the 3' untraslated region (UTR)(ex4-3'UTR: 7579533–7572842, according to GRCh37/hg19).

Next, in order to investigate if low rate of mutations were detectable, we also analyzed our whole transcriptome data obtained using next generation sequencing technology (Illumina/Solexa Genome Analyzer) on 3 Ph+ ALL patients. Curiously, all patients harbored clones ranging from 45% to 94% with TP53 mutations in the DNA binding and tetramerization domains: C182W (ex 5), T231A (ex 7), L330R (ex 9) in the first patient and Stop394S, D393V/H and G389Y/V (ex 11) in the second one. Moreover, in the first and third patient we detected 10 and 13 base exchanges, respectively, located in intron 6 within 7578166–7578142 region, suggesting a retention of this intron in the primary transcript and the dysfunction of the DNA-binding domain. The mechanism of intron retention (with or without mutations) was particularly intrigued since it could be a new mechanism of functional inactivation of TP53 . To address this hypothesis we performed amplification of TP53 cDNA followed by single cell cloning and subsequent direct sequencing in 4 patients previously resulted wild-type by Sanger sequencing for TP53 . By this approach, all patients showed cDNA alterations. In one case we identified the missense mutation S90P (ex 4) and an aberrant isoform lacking the DNA binding domain and caused by an exon-junction between exons 2 and 7 (ex2-7: 7579866–7577510). In a second patient the P190S (ex 6) and N235S (ex 7) missense mutations were detected. Moreover, an aberrant isoform lacking the DNA binding domain and characterized by an exon-junction between the first part of exon 4 and the last part of exon 7 (ex4-7: 7579581–7577532) was also identified. In the third patient the E285G (ex 8) was found associated with a 3'-UTR base exchange, which was also detected in the remaining fourth patient. In conclusion, we demonstrate for the first time that TP53 alterations at the RNA level, including missense mutations, aberrant exon junctions and internal intron retentions are highly frequent in B-ALL patients and that testing for TP53 mutations with sensitive assay based on RNA analysis is absolutely required. Supported by European LeukemiaNet, AIL, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2009, Ateneo RFO grants, PIO program, Programma di Ricerca Regione – Universita 2007 – 2009.

Disclosures: Soverini: Novartis: Consultancy; ARIAD: Consultancy; Bristol-Myers Squibb: Consultancy. Baccarani: Pfizer Oncology: Consultancy; Novartis: Consultancy; BMS: Consultancy; Ariad: Consultancy; Novartis: Research Funding; Pfizer Oncology: Honoraria; Novartis: Honoraria; BMS: Honoraria; Ariad: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees. Martinelli: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy.

 [1]: /lookup/external-ref?link_type=GEN&access_num=NM_000546&atom=%2Fbloodjournal%2F118%2F21%2F1484.atom


Usage of Dutch regional languages and dialects is very much in decline in favour of usage of standard Dutch. This paper analyses the developments in usage in the period 1995-2003 using data from five measurement points of the national cohort study Primai y Education (PRIMA). A total of 35,000 pupils and their parents were involved in this study. In addition, this paper analyses the relationship between usage of regional languages and dialects on the one hand and a number of family demographical characteristics and the children's Dutch language proficiency on the other. The results show that it is imperative to treat the Netherlands not as a whole but to differentiate between language areas. In contrast to the other regional languages and dialects the future of Limburgish seems less gloomy.


Background Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs. Method A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress–tension. We applied a recently developed twin regression methodology – Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) – to test for evidence consistent with the existence of 'causal' influences between the DASS factors. Results There was evidence consistent with the stress–tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001). Conclusions Our findings suggest a critical role for stress–tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.


The paper examines the repulse of fifteenth century Portuguese slave raids in the Senegambia by the armed forces of the empires of Great Jolof and Imperial Mali, within the context of the ongoing Military Revolution debate and with an emphasis on the military organization and weaponry deployed by both sides. Despite the claims of some historians about early European advantages in naval warfare, any such superiority on the part of the European vessels was not demonstrated in these encounters, with the war-canoes and poisoned arrows of the Jolof and Malian marines proving highly effective against the caravels, cannons, and crossbows of the Portuguese sailors. The African militaries of the Senegambia region were well-organized, well-disciplined, and more than capable of defeating European marauders. If Europeans did develop notable military advantages over West Africans in the sixteenth century, they had not yet begun to do so in the fifteenth.


This article explores the evolving practices of science journalism and public debate in the digital age. The vehicle for this study is the release of digitally stored email correspondence, data and documents from the Climatic Research Unit at the University of East Anglia in the UK in the weeks immediately prior to the United Nations Copenhagen Summit (COP-15) in December 2009. Described using the journalistic shorthand of 'climategate', and initially promoted through socio-technical networks of bloggers, this episode became a global news story and the subject of several formal reviews. 'Climategate' illustrates that media-literate critics of anthropogenic explanations of climate change used digital tools to support their cause, making visible selected, newsworthy aspects of scientific information and the practices of scientists. In conclusion, I argue that 'climategate' may have profound implications for the production and distribution of science news, and how climate science is represented and debated in the digitally mediated public sphere.


Abstract TNF-alpha-targeted therapies during pregnancy is a topic of interest in rheumatology. Etanercept (ETN) is expected to have lower transplacental transfer, however, clinical evidence is lacking on the usefulness and safeness of continuing etanercept throughout pregnancy. We here described the first reported case of relapsing polychondritis where continuous use of ETN throughout pregnancy was required. The patient was a pregnant Japanese woman who presented with bilateral ear cartilage redness, swelling, saddle nose and severe subglottic oedema. Due to severe systemic and life-threatened disease, we decided to continue using ETN throughout pregnancy and resulted in successful vaginal delivery. The treatment with ETN was successful and TNF-alpha levels in umbilical cord blood were not affected. The infant did not have any signs of chondritis although levels of anti-type 2 collagen antibodies in maternal and umbilical cord blood were similar, suggesting that anti-type 2 collagen antibodies crossed the placenta. This case is an important clinical experience that strengthens the safety to continue ETN during the entire pregnancy if necessary.


An mAb directed to the alpha/beta-heterodimer of the rat T cell receptor was used to prevent rejection of cardiac allografts in sensitized (accelerated rejection) recipients. Over a wide dose range, alpha/beta-TCR-directed therapy abrogated accelerated rejection at 24-36 hr and extended cardiac allograft survival in a dose-dependent fashion, both when given after heart transplantation as well as during or before the sensitizing skin transplants (8.9 +/- 1.0 days, 12.7 +/- 0.6 days, or 8.7 +/- 1.5 days, respectively). Pretreatment with R73 completely abrogated host sensitization induced by skin grafting. As a result, post-heart transplant cyclosporine course (15 mg/kg for 7 day) has led to long-term graft acceptance (> 90 days vs. 15.2 +/- 1.6 days with postoperative CsA therapy alone). Administration of R73 mAb produced incomplete depletion (CD5+ cells) and partial modulation (alpha/beta-TCR/CD5 double-positive cells) in the peripheral blood. It suppressed in situ protein expression of many cytokines to background levels, in particular that of IL-2 and IFN-gamma, both when given after as well as before cardiac transplantation. However, only pretransplant mAb application was associated with augmented in situ elaboration of IL-4. alpha/beta-TCR-directed therapy induced strong host anti-idiotypic and, to a lesser degree, anti-isotypic antibody responses. Taken together, these results provide the rationale for a novel immunosuppressive strategy involving induction of hyporesponsiveness by alpha/beta-TCR-directed therapy before the alloantigenic exposure.


Capital Asset Pricing model (CAPM) is widely researched, tested, and paradoxically both generally accepted and rejected model of asset pricing. From its beginning (1964) it has occupied the pride of place among the financial economist's research, and still part of the text books on finance in the leading business schools all over the world. The study covered monthly data of Indian companies' from the 'National Stock Exchange' (NSE) for the period 2005 to 2009. In our first model, betas are estimated where the risk free rate is the intercept term. The results show that for the State Bank of India (SBIN), HDFC bank, and Tata Motors, the betas are more than one and significant, and for the Reliance, it is near one, and for Infosystch, it is less than one and statistically significant. The second model of 'Jen's alphas' results show that for only SBIN, and Reliance group, 'Jensen's alpha' is positive, and for other three companies, it is negative. For positive values of 'Jensen's alpha', the conclusion is that those companies earned return more than the companies of similar betas, and for negative values, those companies earned less than the companies of similar betas. Over the sample period, for SBIN, HDFC, and Reliance companies, the actual return is are greater than the required returns, and for Tata Motors, and Infosystch, the actual return is less than the required returns. There is an equity risk premium for many of the Indian securities during the sample period. On the whole, the CAPM model could satisfactorily explain the risk-return relationship in the Indian Stock market.


P2X7 receptor is a crucial receptor related to neuronal activation, neurosensitization, and pain transmission, and increasing evidences indicated that glial cells is thought to be a major contributor to the chronic neuropathic pain after nerve injury. In present study, we designed to investigate whether the P2X7R in glial plays a role in chronic neuropathic pain. We divided adult male Sprague Dawley rats were respectively into four groups:(1) vehicle group (Veh), (2) CCI (C group), (3) P2X7 inhibitor group (P group), (4) CCI+ P2X7R inhibition (CP group). Behavior test, real-time polymerase chain reaction, western blot, immunofluorescence staining, and transmission electron microscope were used to analyze the scientific hypothesis. The results of the experiment is that(i) P2X7R of microglia was downregulated by A-70003 after CCI. (ii) Downregulation of P2X7R on microglia is coincident with remission of NP after CCI. (iii) P2X7R of microglia participates in NP via regulating autophagy and apoptosis. In summary, our results support P2X7R inhibition can counteract the CCI-induced NP due to microglia activation via a modulation of autophagy and apoptosis in mPFC and spinal cord. This may provide an importantly neuroprotective mechanism for the improved NP and also help devising new therapeutic to improve chronic pain in patients.


Recent work of M. Yoshinaga shows that in some instances certain higher homotopy groups of arrangements map onto non-resonant homology. This is in contrast to the usual Hurewicz map to untwisted homology, which is always the zero homomorphism in degree greater than one. In this work we examine this dichotomy, generalizing both results.


The article exposes a smart device designed for mitigating the coronavirus disease (COVID-19) risk using the internet of things. A portable smart alerting device is designed for ensuring safety in public places which can alert people when the guidelines given by the government were not followed and alert health authorities when any abnormalities found. By doing so, the spread of this fatal disease can be stopped. The modules of the proposed system include the face mask detection module, social distance alerting module, crowd detection and analysis module, health screening module and health assessment module. The proposed system can be placed in any public entrances to monitor people without human intervention. Firstly, the human face images are captured for face mask check, then the crowd analysis of the particular entrance where the person is entering is performed, thereafter health screening of the person is done and the values were imported to the health assessment module to check for any abnormalities. Finally, after all the conditions were met the door is opened automatically. The smart device can be installed and effectively used in many scenarios such as malls, stores, crowded places and campuses to avoid the risk of spread of the coronavirus.


Visible light irradiation of 18 microM bilirubin ditaurate (BR-DT) at pH 7.0 for 30 min showed a 10% decrease in absorbance at 445 nm. When the reaction was carried out in the presence of a trace amount of uroporphyrin (UP), the spectrum of BR-DT disappeared without a concomitant formation of biliverdin. Photooxidation products were confirmed to be dipyrrole-containing compounds. Photo-bleaching of BR-DT was accelerated by the increasing concentration of UP and was inhibited, when UP was replaced by Cu2+UP. Formation of 2,2,6,6-tetramethylpiperidine N-oxyl through the irradiation of UP was diminished by sodium azide, a potent scavenger of singlet oxygen. The efficiency of singlet oxygen formation through visible light irradiation was in the order UP, coproporphyrin > Cu2+UP. Both bilirubin and BR-DT bound to human serum albumin (HSA) were photooxidized effectively in the presence of UP. The results indicate that irradiation of UP produces singlet oxygen with high efficiency which then rapidly oxidizes free and conjugated bilirubin.


The purpose of this article is to answer the following questions: In Mexico, what has been the development of the teaching career in primary education between 1930 and 2017? What are the changes that have impacted this career in relation to the historical-political context? And what have been the elements and criteria that have oriented such regulation of the teaching profession? In an analysis of laws, regulations and norms, the authors found that Mexico has focused on three career approaches. The first is the credentialist, as a consequence of the development of the nascent education system and the political pacts between the teacher's unions and the State. The second is the transitory approach, which incorporated elements of meritocracy into a credentialist legal structure. The third is the meritocratic, which stands out for the use of performance evaluations for teacher regulation, for which new regulatory instances were created in order to displace the union from regulatory processes. The authors also observed that the particularities of the educational system, as well as the historical-political context, mark specific paths of Mexican teaching regulation.


Many applications utilizing Unmanned Aerial Vehicles (UAVs) require the use of computer vision algorithms to analyze the information captured from their on-board camera. Recent advances in deep learning have made it possible to use single-shot Convolutional Neural Network (CNN) detection algorithms that process the input image to detect various objects of interest. To keep the computational demands low these neural networks typically operate on small image sizes which, however, makes it difficult to detect small objects. This is further emphasized when considering UAVs equipped with cameras where due to the viewing range, objects tend to appear relatively small. This paper therefore, explores the trade-offs involved when maintaining the resolution of the objects of interest by extracting smaller patches (tiles) from the larger input image and processing them using a neural network. Specifically, we introduce an attention mechanism to focus on detecting objects only in some of the tiles and a memory mechanism to keep track of information for tiles that are not processed. Through the analysis of different methods and experiments we show that by carefully selecting which tiles to process we can considerably improve the detection accuracy while maintaining comparable performance to CNNs that resize and process a single image which makes the proposed approach suitable for UAV applications.


Background Although well-designed instruments to assess communication during medical interviews and complex encounters exist, assessment tools that differentiate between communication, empathy, decision-making, and moral judgment are needed to assess different aspects of communication during situations defined by ethical conflict. To address this need, we developed an assessment tool that differentiates competencies associated with practice in ethically challenging situations. The competencies are grouped into three distinct categories: communication skills, civility and respectful behavior, clinical and ethical judgment and decision-making. Objective The overall objective of this project is to develop an assessment tool for ethically sensitive scenarios that measures the degree of respect for the attitudes and beliefs of patients and family members, the demands of clinical decision-making, and the success in dealing with ethical conflicts in the clinical context. In this article, we describe the research method we will use during the pilot-test study using the neonatal context to provide validity evidence to support the features of the Assessment Communication Tool for Ethics (ACT4Ethics) instrument. Methods This study is part of a multiphase project designed according to modern validity principles including content, response process, internal structure, relation to other variables, and social consequences. The design considers threats to validity such as construct underrepresentation and factors exerting nonrandom influence on scores. This study consists of two primary steps: (1) train the raters in the use of the new tool and (2) pilot-test a simulation using an Objective Structured Clinical Examination. We aim to obtain a total of 90 independent assessments based on the performance of 30 trainees rated by 15 trained raters for analysis. A comparison of raters' responses will allow us to compute a measure of interrater reliability. We will additionally compare the results of ACT4Ethics with another existing instrument. Results This study will take approximately 18 months to complete and the results should be available by September 2019. Conclusions ACT4Ethics should allow clinician-teachers to assess and monitor the development of competency of trainees' judgments and communication skills when facing ethically sensitive clinical situations. The instrument will also guide the provision of meaningful feedback to ensure that trainees develop specific communication, empathy, decision-making, and ethical competencies. International Registered Report Identifier (IRRID) PRR1-10.2196/12039


Object-oriented concepts offer the potential for significant improvement to the software development process, and many organisations are investigating ways to gain experience in using object-oriented techniques. However, issues such as which proposed techniques are appropriate at different development phases, and how to ensure consistency and traceability between phases are not entirely clear. Faced with these concerns, a development group at The MITRE Corporation performed a short-term development exercise to prototype the object-oriented development process itself. In this paper we describe the exercise and its results.


Given that Enlightenment rationality developed in Europe as European nations aggressively claimed other parts of the world for their own enrichment, scholars have made rationality the subject of postcolonial critique, questioning its universality and objectivity. In On Reason , the late philosopher Emmanuel Chukwudi Eze demonstrates that rationality, and by extension philosophy, need not be renounced as manifestations or tools of Western imperialism. Examining reason in connection to the politics of difference—the cluster of issues known variously as cultural diversity, political correctness, the culture wars, and identity politics—Eze expounds a rigorous argument that reason is produced through and because of difference. In so doing, he preserves reason as a human property while at the same time showing that it cannot be thought outside the realities of cultural diversity. Advocating rationality in a multicultural world, he proposes new ways of affirming both identity and difference.

Eze draws on an extraordinary command of Western philosophical thought and a deep knowledge of African philosophy and cultural traditions. He explores models of rationality in the thought of philosophers from Aristotle, Rene Descartes, Francis Bacon, and Thomas Hobbes to Noam Chomsky, Richard Rorty, Hilary Putnam, and Jacques Derrida, and he considers portrayals of reason in the work of the African thinkers and novelists Chinua Achebe, Ngugi wa Thiong'o, and Wole Soyinka. Eze reflects on contemporary thought about genetics, race, and postcolonial historiography as well as on the interplay between reason and unreason in the hearings of South Africa's Truth and Reconciliation Commission. He contends that while rationality may have a foundational formality, any understanding of its foundation and form is dynamic, always based in historical and cultural circumstances.


Seven NHS trusts made up more than half of all inappropriate out of area placements (OAPs) for acute mental health inpatient care between December 2018 and February 2019, according to data from NHS Digital.1

OAPs occur when a person requiring adult mental health acute inpatient care is placed in a unit outside of their local services, normally away from their family and care coordinator.

The government pledged to eliminate inappropriate mental health OAPs in mental health by 2020-21 as part of the Five Year Forward View.

The latest figures showed, however, that the number of inappropriate OAP …


In nature, bacteria are exposed to multiple stress conditions posing threat to their life. However, bacteria evolve constantly and employ myriad of genetic and phenotypic strategies for successful survival. One such adaptive process is phase variation - a random, frequent and reversible ON/OFF switching of contingency genes generating phenotypical variations within the bacterial population. Pathogenic and commensal bacteria make use of this heritable process as a tool for adaptation, generating intra-strain diversity and immune evasion. Unveiling molecular basis of this aspect of bacterial pathogenesis is vital in yielding significant implications to understand health and diseases. The current review was planned to overview this hot topic of research, its molecular basis and biological significance.


This article con siders the current theoretical and practical problem of methodology of building and practical realization of dispatcher's decision making support system of SCADA-subsystem. Objectives and problems of dispatcher control are reviewed on a gas production and main transfer example. Some problems occurred with operator inclusion in control loop are described. Dispatcher's decision making support system structure and methods necessary for its creation are offered in this article. Dispatcher's decision making support system realization based on these methods is also described.


Objectives The aims of this study were to assess malnutrition risk in Chinese geriatric inpatients using Nutritional Risk Screening 2002 (NRS2002) and Mini-Nutritional Assessment (MNA), and to identify the most appropriate nutritional screening tool for these patients. Design Cross-sectional study. Setting Eight medical centres in Hubei Province, China. Participants A total of 425 inpatients aged ≥70 years were consecutively recruited between December 2014 and May 2016. Primary and secondary outcome measures Nutritional risk was assessed using NRS2002, MNA, anthropometric measurements and biochemical parameters within 24 hours of admission. Comorbidities and length of hospitalisation were recorded. Nutritional parameters, body mass index (BMI) and length of hospital stay (LOS) were employed to compare MNA and NRS2002. Kappa analysis was used to evaluate the consistency of the two tools. Results The average age was 81.2±5.9 years (range, 70–98). The prevalence of undernutrition classified by NRS2002 and MNA was 40.9% and 58.6%, respectively. Patients undergoing malnutrition had lower BMI, haemoglobin, albumin and prealbumin (p<0.05), and longer LOS (p<0.05). The NRS2002 showed moderate agreement (κ=0.521, p<0.001) with MNA. Both tools presented significant correlation with age, BMI and laboratory parameters (p<0.001). In addition, a significant association between both tools and LOS was found (p<0.05). In addition, the NRS2002 was not different from MNA in predicting nutritional risk in terms of the area under the receiver operating characteristic curve (p>0.05). Conclusions The results show a relatively high prevalence of malnutrition risk in our sample cohort. We found that NRS2002 and MNA were both suitable in screening malnutrition risk among Chinese geriatric inpatients.


In dynamic computed tomography (CT) reconstruction, the data acquisition speed limits the spatio-temporal resolution. Recently, compressed sensing theory has been instrumental in improving CT reconstruction from far few-view projections. In this paper, we present an adaptive method to train a tensor-based spatio-temporal dictionary for sparse representation of an image sequence during the reconstruction process. The correlations among atoms and across phases are considered to capture the characteristics of an object. The reconstruction problem is solved by the alternating direction method of multipliers. To recover fine or sharp structures such as edges, the nonlocal total variation is incorporated into the algorithmic framework. Preclinical examples including a sheep lung perfusion study and a dynamic mouse cardiac imaging demonstrate that the proposed approach outperforms the vectorized dictionary-based CT reconstruction in the case of few-view reconstruction.


With the world's incidence of non-communicable diseases (NCDs) increasing, colon and rectal cancers now form the 3rd most common form of cancer globally, the need to find new solutions to colorectal cancer (CRC) is paramount, as current treatment is limited and comes with many unfavourable side effects. Studies on probiotic bacteria and prebiotic compounds spanning the last ten years reveal promising results describing their ability to act against colorectal cancer development. After screening papers with a specific inclusion criterion, 23 papers were selected for this review. The primary endpoints, biomarkers, and other data were analysed. The results show that overall, the prebiotics and probiotic bacteria included in this study (predominantly the genera Lactobacillus and Bifidobacterium) have promising anti-neoplastic effects against colorectal cancer, although in varying amounts. Other prebiotics such as fructooligosaccharides, branched fructans, and other plant extracts, were shown to have equally positive effects. The concept of using probiotics/prebiotics in addition to established cancer treatment seems more feasible with the various benefits highlighted in this review. At the very least, probiotics/prebiotics may be useful adjuvants, to be used alongside pre-existing colorectal cancer treatment. Probiotics/prebiotics may help alleviate some undesirable side effects of pre-existing treatment (i.e., fluorouracil) such as dysbiosis. Thus, this review aims to build upon the foundations established in microbiome research and encourage the course of future prebiotic and probiotic testing, to further our understanding related to the effect of probiotics/prebiotics on gut health and help treat the growing burden of colorectal cancer.


With the use of high performance capillary electrophoretic system, the authors developed a micellar electrokinetic chromatographic method with direct sample injection to separate and assay serum or bile fluid bilirubin subspecies. The four bilirubins, alpha, beta, gamma and delta subspecies, in serum or in bile fluid were successfully separated within 20 min. Under the concentration of combined bilirubin (bilirubin ditaurite), there was a good relationship between the concentration and the peak area. The detection limit reached 1.5 mumol/L. Being compared with the results of the first run with a concentration of 255 mumol/L and migration time of 16 min, the results of the 50th run were 238 mumol/L and 16.7 min respectively.


A total of 79 infants born at less than 32 weeks' gestation were studied with serial renal ultrasound scans to assess the incidence of nephrocalcinosis. Twenty one infants developed renal calcification giving an overall incidence of 26.6% in the study group. Affected infants were significantly smaller (mean (SD) birth weight 940 (323) g) and significantly less mature (mean (SD) gestation 26.9 (1.9) weeks). In 17 patients the calcification was represented by hyperechogenic renal pyramids alone, and in four patients renal calculi were demonstrated. Factors associated with renal calcification included hypophosphataemia, hypercalcaemia, hypercreatininaemia, and prolonged oxygen requirement during the first month of life. Multivariate analysis showed that the strongest clinical indicator of calcification was duration of oxygen treatment. Infants who still required oxygen treatment at 28 days had a 62% chance of developing renal calcification.


Trypanosomes are principally responsible for two human diseases: human African trypanosomiasis (HAT) or sleeping sickness (caused by Trypanosoma brucei gambiense and T. b. rhodesiense), and Chagas disease, also called South American trypanosomiasis (T. cruzi). However, some trypanosomes that are natural parasites only of animals can sometimes infect humans and cause the so-called "atypical human trypanosomiases" (aHT). T. evansi, the agent causing surra in camels, horses, dogs, and bovines, and T. lewisi, a cosmopolite rat parasite, are the most frequently involved. These atypical infections involve no or only minor symptoms, but major symptoms are sometimes present. Parasite elimination is generally spontaneous, but can require treatment. Molecular tools, such as polymerase chain reaction, have improved the accuracy of parasite identification. Immunological techniques, mainly immunoenzymatic assays, can detect asymptomatic subjects. Several causes, most often concomitant, have been hypothesized, including immune immaturity, immunodeficiency, and close contact with infected animals. Innate immunity to animal trypanosomes depends on a trypanolytic factor called apolipoprotein L-I, present in human serum. A deficit in both apolipoprotein L-I alleles has been reported in an Indian patient infected by T. evansi. The prevalence of aHT is probably underestimated. Moreover, these trypanosomes might become potential emerging zoonotic pathogens, due to their ability to invade new hosts. An international network has been set up to survey these aHT (NAHIAT: Network on Atypical Human Infections by Animal Trypanosomes).


Glycoconjugate vaccine is composed of polysaccharides (PSs) covalently linked with carrier protein. Glycosylation site selection, as a significant factor leading to heterogeneities of glycoconjugate structure, draws more and more attentions for its impact on the immunogenicity of glycoconjugate vaccine. To elucidate the relationship between glycosylation connectivity and immunogenicity of glycoconjugate vaccine, in this study, anti-E. coli O157:H7 glycoconjugate O-PS-MBP with defined connectivity, and three selected peptide segments GS1, GS2, GS3 derived from O-PS-MBP was synthesized. Immunogenicity results showed that only peptides adjacent to the glycosylation sites (GS1 and GS2) promoted the generation of PS-specific IgG antibodies and contributed to PS-specific IgG subclass distribution. Furthermore, GS1 and GS2 had significant priming effect for eliciting PS-specific IgG antibodies. These results indicated that different locations of glycosylation sites could lead to diverse presentation of peptides and glycopeptides to APCs and influence the immunogenicity of glycoconjugate vaccine, which extend the current understanding of mechanism for adaptive immune system activation by glycoconjugate vaccine, and have implications for rational glycoconjugate vaccine design.


The study of communication designs in the context of the Raid system, a robust and adaptable distributed database system for transaction processing, is discussed. Related research work on local interprocess communication, remote interprocess communication, and communication protocols for both local area and wide area networks is briefly summarized. A series of experiments on the performance of the facilities available for building the Raid communication software is described. Raid's communication software, called Raidcomm, has evolved as a result of the knowledge gained both from other systems and from the authors' experiments. Several communication services and mechanisms that can be used to make Raid efficient are identified.<<ETX>>


This study aimed to determine the effect of the extrusion process on the nutritional and bioactive profiles of brewer's spent grain (BSG), contributing to nutrition security by applying a circular economy concept. Response surface methodology was used to optimize the effect extrusion parameters (moisture content, screw speed, and barrel temperature ) had on BSG's soluble dietary fiber, free glucose, and overall antioxidant capacity. Proximate composition analyses, amino acid profile, extractable polyphenolic content, and antioxidant capacity of BSG and brewer's spent grain extruded under optimal conditions (BSGE) were carried out. Food safety was analyzed by their microbiological quality, gluten, and acrylamide content. Optimal extrusion conditions were 15.8% of moisture content, 164.3 revolutions per min and 122.5 °C. BSGE presented 61% more soluble dietary fiber than BSG, lower digestible starch, 0.546% of free glucose, and protein quality parameters mostly like those reported for egg, soy, and milk. Despite this, BSG's overall antioxidant capacity was not improved after thermomechanical processing; BSGE had significantly higher extractable polyphenolic content in its alkali extracts, which were determined qualitatively by high-performance liquid chromatography quadrupole time-of-flight assay in its hydro-alcoholic acid extracts. Furthermore, although it is not gluten free, BSGE is a safe food ingredient with acceptable microbiological quality and no acrylamide.


Time-dependent Hartree-Fock theory has been used to study the electronic optical response of a series of linear polyene cations (+1 and +2) in strong laser fields. The interaction of ethylene, butadiene, and hexatriene, with pulsed and CW fields corresponding to 8.75 x 10(13) W/cm(2) and 760 nm, have been calculated using the 6-31G(d,p) basis set. Nonadiabatic processes including nonlinear response of the dipole moment to the field and non-resonant energy deposition into excited states were more pronounced for the monocations in comparison with dications. For a given charge state and geometry, the nonadiabatic effects in the charge distribution and instantaneous dipole increased with the length of the polyene. For pulsed fields, the instantaneous dipole continued to oscillate after the field returned to zero and corresponded to a non-resonant electronic excitation involving primarily the lowest electronic transition. For a given molecule and fixed charge state, the degree of nonadiabatic coupling and excitation was greater for geometries with lower excitation energies.


SAR images are different from optical images in many ways. Therefore, the traditional compression methods, which have been used for compression, are not so efficient for the compression of the SAR images. Generally, 2-dimensional Fourier transform (2D-FT) is used for representing a complex SAR image. But the energy of the coefficients of 2D-FT on the complex SAR image distributes in the whole frequency domain also. Typically the frequency signals are divided into two parts, i.e., real and imaginary parts. A Wavelet transform gives very strong de-correlation ability and can be used for local analysis in time and frequency with different scales. Wavelet transform have also been applied to complex SAR image compression, as it is suitable for nonstationary signal processing. We have embodied the wavelet transform with SPIHT for compression of SAR images. Also FFT is used for converting the complex SAR image into a real image before applying it to DWT. In particular, we have used Le Gall 5/3 biorthogonal wavelet for calculating the wavelet transform.


Introduction YBX2 protein binds to Y-box promotors and to mRNAs in the cytoplasm of pachytene spermatocytes and round spermatids in rodents. Knock-out of YBX2 leads to maturation arrest in animal models. YBX2 binds PRM1 and 2 mRNA, which is transcribed early and sequestrated for translation during late spermatogenesis. Objective This study aimed to determine if the loss of YBX2 is associated with MA arrest due to the loss of sequestration of protamines in the human testis. As a second aim, we examined the expression of YBX2, and its transcription factors in maturation arrest (MA)(early and late) and normal controls in men. Methods RNAseq was performed using RNA extracted from human testis samples from 44 men with non-obstructive azoospermia and ten from healthy controls. Differential expression was performed using JMPgenomics, FDR<0.001. FANTOM5 was used to predict enhancers and inhibitors of YBX2 expression. Immunofluorescence (IF) was used to stain testis tissue sections with antibodies against YBX2, SYCP3, and PRM2 in normal and MA samples. Flow cytometry was utilized to characterize YBX2 positive cells. Results Expression of YBX2 mRNA was significantly downregulated in early and late MA compared to controls. Surprisingly, PRM1&2 mRNAs were also depleted in men with MA. Multifactorial regression analysis demonstrated a decrease in YBX2 expression in MA is due to decrease in COMP levels (p<0.0001). IF localized YBX2 protein in spermatocytes and round spermatids among fertile men, with rare YBX2 positive spermatocytes stained in LMA. PRM1&2 proteins were absent or abnormally sequestrated within spermatocytes. Conclusions Decrease in YBX2 protein expression in men with LMA leads to loss of translational suppression and lack of PRM1 and PRM2 necessary to complete spermatogenesis.


Adaptive resistance of myeloma cells to proteasome inhibition is poorly understood. It is suggested to base on point mutations in PSMB5 and/or downmodulation of the activation state of the unfolded protein response (UPR) via reduced activity of its major regulatory axis IRE-1/XBP-1. We have generated subclones of the AMO-1 myeloma cell line resistant to bortezomib > 1000 nM (AMO-BTZ), or carfilzomib > 1000 nM (AMO-CFZ), that do or do not carry the PSMB5 A310G mutation in the β5 substrate pocket. We combine this model with a global quantitative proteomics approach, the analysis of the activation status of the IRE-1/XBP-1 pathway, and with an advanced set of proteasome activity-specific fluorescent affinity probes that allow direct, selective, simultaneous visualization of the activity of all six active β-subunits of the constitutive and the immunoproteasome. Our results demonstrate that the A310G mutation has a modest impact on β5c proteasome inhibition by bortezomib (increasing the IC50 from 25nM to 80 nM), and likewise by carfilzomib (IC50 increase from 10 nM to 50 nM). Strikingly, when AMO-CFZ or AMO-BTZ were exposed to the same functional level of proteasome inhibition (> 90% inhibition of β5c/5i, 20% inhibition of β1/1i, β2/2i) that resulted in 70-90% cytotoxicity in AMO-1 cells, no cytotoxicity was observed in AMO-BTZ and AMO-CFZ cells. Likewise, AMO-BTZ and AMO-CFZ cells were resistant to the next generation proteasome inhibitors ixazomib, oprozomib and dalanzomib, irrespective of the presence or absence of the PSMB5 mutation. Analysis of the UPR and its major regulators on protein and mRNA levels revealed that all clones of AMO-BTZ and AMO-CFZ showed significantly lower expression of IRE-1 and its product, spliced XBP-1, compared to AMO-1 cells, in contrast to all other major regulators of the UPR (ATF6, PERK, elF2a). Proteasome inhibitor treatment induced phosphorylation of IRE-1 and the induction of sXBP1 similarly in AMO-1, AMO-BTZ and AMO-CFZ cells, however, the induction of downstream proteins of the UPR (ATF4, PDI) was exclusively found in AMO-1 cells. Mass spectrometry-based quantitative global proteomic analysis was performed to compare AMO-1 cells with AMO-BTZ and AMO-CFZ with a cut off of at least a 50% change in abundance of differentially expressed proteins in at least 2 out of triplicate experiments. This yielded > 3500 identified individual proteins in proteasome inhibitor adapted cells, of which > 600 were differentially expressed and subsequently subjected to a protein-protein interaction (PPI) search and a Gene Ontology (GO) analysis, resulting in an average of 30 GO terms for the overexpressed proteins and 10 for downregulated species in AMO-BTZ and AMO-CFZ. Manual grouping of GO into functionally related clusters resulted in 5-6 groups that were largely concordant between AMO-BTZ and AMO-CFZ. The clusters found overexpressed in AMO-BTZ and AMO-CFZ were proteins involved in protein catabolism, redox control and protein folding. Uniform downregulation was observed for protein clusters involved in transcription/translation, differentiation, apoptosis and structural/cytoskeletal functions. The quantitatively largest group of proteins with significantly altered expression levels in AMO-BTZ/AMO-CFZ vs. AMO-1 control cells consisted of proteins involved in metabolic regulation. This big cluster comprised close to 50 % of all polypeptides with significant quantitative changes, suggesting a key role for metabolic homeostasis. The quantitatively most significantly upregulated protein in both AMO-CFZ and AMO-BTZ was NADPH dehydrogenase, the most important reducing enzyme in eukaryotic cells (4-6 x upregulated). The top individual upregulated protein in AMO-CFZ was the p-glycoprotein 1 (Pgp, 12 x upregulated), while the transcription factor IKZF3 was among the top downregulated proteins in AMO-BTZ cells (0.2 x). Our data indicate that proteasome gene mutations are not required for proteasome inhibitor resistance of myeloma cells, that proteasome inhibitor adapted myeloma cells can compensate subtotal proteasome inhibition irrespective of the type of inhibitor used, and that they have undergone complex adaptive changes in particular in proteins that regulate metabolic functions. Thus we suggest that the metabolic machinery rather than the proteasome should be explored for drug targets in myeloma cells with acquired proteasome inhibitor resistance. Disclosures No relevant conflicts of interest to declare.


Urinary tract infections are often associated with urinary anomalies. An appropriate pharmacologic treatment may prevent, or may at least limit, any kidney damage due to pyelonephritis. The antibiotic prophylaxis plays a role as significant as early surgical therapy, taking into consideration also the present limitative trend for a softer therapeutic regimen. In the past few years a greater bacterial resistance has emerged against some commonly administered antibiotics. Cefixime (3rd generation cephalosporin) has been used on a wide series of patients suffering from urinary infections associated with urinary tract anomalies. A few significative results emerge from the present study. In conclusion, cefixime's effectiveness long-term prophylaxis of urinary infections associated with anomalies.


Background Uncomplicated dacryocystorhinostomy after dacryocystitis with lacrimal sac obstruction has a successrate of 85%. However therapy of restenosis poses a problem. Vast destruction of lacrimal and nasal mucosa renders the drainage system susceptible for further stenosis. This article presents a new surgical procedure for the treatment of restenosis of the nasolacrimal apparatus. The major difference from other techniques is the endonasal implantation of a silicon foil. This counters the development of synechiae and promotes the epitheliasation of wound surfaces. As a result the nasal mucosa can easier gain access to lacrimal mucosa. A complete mucosal coating of the reconstructed lacrimal drainage system is an important condition for the sufficient drainage of the tearfilm. Patients and Methods In 30 patients with restenosis after one or multiple dacryocystorhinostomies a silicon foil was implanted endonasally as part of their surgical revision. After skin incision and removal of scar tissue the bony ostium was enlarged. The canaliculi were intubated with silastic tubing. Afterwards the endonasal synechiae were split and a 0.2-0.4 mm silicon foil was implanted endonasally und fixed. The silastic tubing was brought through a hole in the silicon foil and knoted inside the nose. Then the wound was closed. Postoperative evaluation of the surgical success ranged from 3 to 36 months (mean 16 months). Results The postoperative result was good in 24 patients. Sixteen patients were without symptoms. 8 had epiphora only on stress. The latter felt their situation to be greatly improved. The long-term results were directly proportional to the amount of reconstructable mucosa and inversely proportional to the severity of canaliculus damage. Adverse reaction to the silicon foil were not noted. Conclusion Endonasal implantation of a silicon foil is a new, easy and successful technique for the treatment of endonasal synechiae and restenosis of the nasolacrimal apparatus


Unknown to many readers in the United States, New Zealand enjoys a rich tradition of short fiction dating back well into the nineteenth-century. Now there is a book that brings together a wide range of these marvelous tales in one handsome, compact volume. The Oxford Book of New Zealand Short Stories brings together the new and the old, the traditional and the experimental. Nineteenth-century writing is represented by authors as Henry Lawson, Lady Barker, Clara Cheeseman and G.B. Lancaster, some of whose stories are collected here for the first time. In more recent times the genre has attracted the talents of Katherine Mansfield, Frank Sargeson, Dan Davin, Maurice Gee, Janet Frame, and Greville Texidor, all of whom are included here. A unique feature of this splendid anthology is the inclusion of works by such leading Maori writers as Patricia Grace and Witi Ihimaera (there is a helpful glossary of Maori and Samoan words in an appendix), and a whole new generation of writers, including Peter Wells and Keri Hulme. For anyone who appreciates great literature, The Oxford Book of New Zealand Short Stories will offer some fascinating surprises along with hours of good reading.


Highly active antiretroviral therapy (HAART) suppresses viral replication and improves immune function. However the inflammatory component of immune restoration can have clinically deleterious effects on previously asymptomatic infections. We report the development of acute respiratory failure in a patient after the institution of HAART, following 2 months of appropriate therapy for pulmonary tuberculosis. Necrotizing granulomas with acid-fast bacilli were found on lung biopsy, but cultures were negative for Mycobacterium tuberculosis and no other pathogens were isolated. Polymerase chain reaction of lung biopsy tissue for all mycobacterial species was positive only for M. tuberculosis. Rapid clinical improvement followed corticosteroid therapy. After initiating HAART, clinicians should be aware of the possibility of an inflammatory response to a previously quiescent tuberculous infection, even while on antituberculosis therapy.


INTRODUCTION
Midwifery in the United States suffers from a lack of diversity. More than 91% of midwives are white, and more than 98% are women. Little research has explored the experiences of midwives who are men or transgender.

METHODS
Invitation to an Internet survey was sent to the membership of the American College of Nurse-Midwives. Thirty-one participants who identified as men or transgender completed the survey, which included quantitative and open-ended questions about the impact of gender on education and practice. Data analysis of qualitative responses used qualitative description methodology to identify common themes.

RESULTS
Four themes described participating men's experiences of education and practice of midwifery. Challenges included feeling singled out as different and being excluded. Supportive factors came from the social support of family, friends, colleagues, and patients, as well as from taking pride in one's work as a midwife. Midwives who identify as transgender described the challenges of others' confusion about their gender, having to hide their true gender identity, and struggling with the resulting loneliness.

DISCUSSION
This survey highlights the challenges faced by midwives who are men or transgender in education and practice. Midwifery values of respect and acceptance for all women and families need to be applied internally to all members of the profession. This will support increased diversity and openness in midwifery.


OBJECTIVE
User-centered design can improve engagement with and the potential efficacy of behavioral interventions, but is underutilized in health care. This work demonstrates how design methodologies can inform the design of a mobile behavioral intervention for binge eating and obesity.

METHOD
A needs assessment was conducted with end-users (N = 22 adults with obesity and recurrent binge eating [≥12 episodes in 3 months] who were interested in losing weight and addressing binge eating), which included assessing participants' past/current and future willingness to engage with 20 treatment targets for managing binge eating and weight. Targets focused on improving dietary intake, increasing physical activity, and reducing overvaluation of weight and/or shape, unhealthy weight control practices, and negative affect.

RESULTS
Participants' past and current use of targets varied. For all targets except those addressing unhealthy weight control practices, on average, participants had increasing levels of willingness to try targets. Among participants not currently using a target, at least some were willing to use every target again.

DISCUSSION
Findings inform ways to personalize how users begin treatment. Furthermore, this study exemplifies how user-centered design can inform ways to ensure that digital interventions are designed to meet end-users' needs to improve engagement and clinical impact.


To investigate the association between depression and vision, 100 cataract operation patients (25 were men and 75 women) aged 71 to 76 years were studied. One day before the operation and 3 mo. after, the patients' depression was tested with the short form of the Beck Depression Inventory and their personalities with Mini-Mult MMPI. The cataract operation restored visual acuity sufficient for reading (minimum E-test value 0.40) to 79% of the subjects. The analysis indicated that their depression was significantly correlated with vision only after the cataract operation. Depression increased with weakened visual acuity and diminished with improved visual acuity. Part of the postoperation depression was, however, associated with glaucoma and serious somatic diseases (asthma, cerebrovascular disorders, and heart diseases).


One of the biggest problems associated with the antibiotic therapy is resistance. Recently published studies have revealed that enterobacteriaceae, like E. coli and Klebsiella, isolated from several Indian centers are resistant to many antibiotics including some highly potent antibiotics like carbapenems. It has been proposed that this resistance is because of a carbapenemase enzyme called NDM- 1 (New Delhi Metallo-betalactamase-1). This carbapenemase is class B carbapenemase also called metallolactamases as they require zinc at their active site. This enzyme is coded by a gene called bla - NDM -1 or gene NDM -1. NDM -1 containing enterobacteriaceae can be screened in laboratory by few techniques. Metallolactamase production can be detected by disk approximation test or Modified Hodge test and NDM -1 gene can be detected by polymerase chain reaction by the use of specific primer targeting the gene. Infections caused by such bacteria are associated with high morbidity and mortality. Two classes of antibiotics i.e., polymyxins (colistin) and glycylcyclines (tigecyclines), have shown in vitro activity against NDM -1 harboring enterobacteriaceae. The safety profile of both of these antibiotics is questionable. There is a need for active screening of microorganisms for NDM -1 and research should be directed towards the development of safe antibiotics for the treatment of these kinds of infections.


This paper deals with the use of bicycle messengers, also called bike couriers, in the modern 2010 supply chain. In the era where almost everybody, from policy makers to senior managers, is thinking about the environment, new innovative concepts are being developed worldwide. The paper shows how sustainability of business activities, environmental friendly methods, energy efficiency gains and related policies are hot topics. Targets to lower emissions are set, policies are implemented. On the other hand, solutions improving efficiency and overall sustainability of the supply chain and overall business activities are already available in the market. Reinventing the wheel all over again might not be necessary. An abundance of new concepts and more efficient process designs exists. One of the techniques, used for a very long time in the biggest cities of the United States, is the transport of freight by bike. This can be transport of post, parcels or freight with a low volume of weight. Bike messengers are proven to be fast and reliable. A specific market seems to exist for transport by bike in an urban context. The research question of this paper concerning bicycle messengers is if these companies can be a viable alternative for fossil fuel powered transport. The paper draws conclusions about the market structure for these services and the weaknesses and opportunities encountered. First, the market structure will be discussed. What is the (niche) market the bike messengers work in? Is the special context of large importance? Can characteristics for the freight transported be identified? How is the price- and cost structure of these companies and what is their average scale? What is the balance of power between big (logistics) companies and the bike messenger services? This will be looked at from an international perspective, with a translation towards the Belgian market. After identifying the market structure in the first part, the link is made towards other logistics companies. Is an integration of the services with bigger companies possible? Other issues encountered during the research will be highlighted in the last part. Is legislation influencing bike transport? And to what extend are bike messengers able to integrate in the worldwide transport network.


In this article considered the violence against of women, which is a global problem. Exactly, we will investigate the social conditions and factors of commit and preventing of domestic violence in modern Kazakhstan.


This article presents a set of control enhancements for standard vector current control (VCC) that improves its stability and dynamic performance in an extended range of SCRs. Increasingly, the local SCR as seen by the converter fluctuates, making it difficult to tune the control algorithms. Usually, stability is prioritised over performance and converters become less responsive. The modifications proposed in this article allow VCC to maintain high dynamic performance and stability, optimised to the real-time grid conditions. These modifications do not alter the standard operation of the outer loops, the current controller or the phase-locked loop. Instead, a Pre-emptive Voltage Decoupler (PVD) is introduced to compensate reactive current for changes in active current, thus decoupling the local voltage from active power. The PVD is optimised to the grid conditions by an impedance estimator. Further, an instability detector is proposed, anticipating instability and triggering preventive action, improving the resiliency of the converter. Supervisory control is employed to coordinate instability detection, prevention, impedance estimation and PVD optimisation. As a result, VCC is more responsive and adaptable to variable grid conditions. It is also more resilient to grid events, such as the loss of a transmission line.


ABSTRACT A series of parameters are proposed to describe the grain size frequency distribution of sandy-gravels. They are shown to be selective in distinguishing variations in the proportions of the two modes, especially at 25% sand, an important point in the packing of bimodal materials. A number of samples from the Solent, a channel between Hampshire, England, and the Isle of Wight, are considered as examples of the sedimentary significance of the use of the parameters in a tidal environment.


A steady-state two-dimensional groundwater flow and transport model of a fractured carbonate aquifer in central Wurttemberg (southwest Germany) was used to study the feasibility of applying stable isotopes in model calibration and to define the capture zone of the mineral springs in Stuttgart-Bad Cannstatt. Differences in the stable isotope composition of 18 O and 2 H in the groundwater caused by variations in altitude, were determined to be approximately 0.4‰ δ 18 O per 100 m within the study area. They allow the verification of the underlying numerical flow model. The area of the capture zone is independent of transmissivities and recharge rates as long as both are coupled to each other by calibration on the basis of measured heads. Within the possible bandwidths of transmissivities and recharge rates, linear variations of these parameters will still yield the same head distribution but different discharge rates for the springs (the discharge rate is not exactly known). The distribution of the isotopic composition and the capture zone remain unchanged.


We report that an electro-osmotic instability of concentration enrichment in curved geometries for an aqueous electrolyte, as opposed to the well-known one, is initiated exclusively at the enriched interface (anode), rather than at the depleted one (cathode). For this instability, the limitation of unrealistically high material Peclet number in planar geometry is eliminated by the strong electric field arising from the line charge singularity. In a model setup of concentric circular electrodes, we show by stability analysis, numerical simulation, and experimental visualization that instability occurs at the inner anode, below a critical radius of curvature. The stability criterion is also formulated in terms of a critical electric field and extended to arbitrary (2d) geometries by conformal mapping. This discovery suggests that transport may be enhanced in processes limited by salt enrichment, such as reverse osmosis, by triggering this instability with needle-like electrodes.


In this paper, we show that downstream mergers increase the incentives of an up-stream firm to invest in cost-reducing R&D. The upstream firm revenues increase with industry profits, which in turn increase with concentration downstream and this explains the positive link between concentration and investment. This effect is so important that it outweights the negative effect on prices due to lower competition. Therefore, in our context, horizontal mergers are pro-competitive.


This is the first volume of a treatise on "Materia Medica and Therapeutics." It includes a consideration of the historical development of materia medica and pharmacology, the general principles of pharmacology, the forms of administration of drugs, the routes of administration, the technique of prescription writing, and a table of drug preparations and doses. Following this preliminary material there is the first section of systematic therapeutics which will be continued presumably in subsequent volumes. This section deals with parasites, both external and internal, and their remedies. The book is written in Spanish and reflects the viewpoint of the Argentine authors. If the volumes completing the set follow the example of the first volume, it would appear to be a useful reference as to therapeutics (more so than as to pharmacology) for the Spanish-speaking physician.


Optimal hearing is one goal of otologic surgery. This study examines the long-term functional success rate of cartilage as graft material for ossicular chain reconstruction in type III tympanoplasty. A retrospective review of seventy-nine patients having undergone type III tympanoplasty (53 with closed techniques and 26 with open techniques) was made. Lateral graft ("onlay") techniques were used in almost all cases. All operations were performed by one of the authors, a well-established otologic surgeon. Seventy-four percent of the reconstructions were performed in an one-stage procedure. The mean period of follow-up was 54 months (range 1-17 years). The results of air-bone gap closure and complications of the surgery are presented. Our results show that a significant percentage of patients gain a long-term substantial improvement in their hearing with minimal risk. However, this hearing improvement tends to decline eventually in a progressive manner. A post-operative air-bone closure equal or < 30 dB was achieved in 92.2% of the all cases (n = 79) with a mean gain of 9.72 dB. Functional outcomes in closed techniques were slightly better than in open techniques. There were few complications. Perforation and retraction of the tympanic graft were the most common observed complications. In conclusion, cartilage is an available, costless, reliable and technically easy to use graft material for functional reconstructions of the ossicular chain. It is a well-tolerated element in middle ear space as well as by the tympanic membrane, it has a very low risk of extrusion and a good long-term functional viability. Therefore, update cartilage is an interesting option in functional restoration of the ossicular chain as graft placed on the stapes capitulum.


Most ageism research has focused on prejudice against older people without considering their multiple intersecting identities. We investigated perceptions of ageist acts that targeted older individuals with intersecting racial (Black/White) and gender identities (men/women). Both young (18–29) and older (65+) adult Americans evaluated the acceptability of a variety of instances of hostile and benevolent ageism. Replicating prior work, benevolent ageism was seen as more acceptable compared to hostile ageism, and young adults rated ageist acts as more acceptable than older adults. Small intersectional identity effects were observed such that young adult participants perceived older White men to be the most acceptable targets of hostile ageism. Our research suggests that ageism is viewed differently depending on the age of the perceiver and the type of behavior exhibited. These findings also suggest intersectional memberships should be considered, but further research is needed given the relatively small effect sizes.


In the framework of the Satellite Application Facility for Climate Monitoring (CM-SAF) an upgraded formulation of the HELIOSAT surface global irradiance retrieval scheme is proposed, which is suitable for real-time application to METEOSAT Second Generation (MSG) satellite data. The new scheme includes image georeferencing, pixel-wise snow-cover detection, special treatment of clouds above snow and correction of terrain effects over the Alpine region. Results show that the mean bias difference between the revised irradiance estimates from satellite and from ground measurements can be substantially reduced by correctly distinguishing between clouds and snow, and by applying the new cloud-index scheme for clouds blue above snow. The increase of the root mean square difference with increasing altitude can be mainly attributed to the increase of the variability of the natural irradiance field. We strongly recommend the use of MSG-based irradiance estimates for locations at more than 4 km distance to the next measurement site.


The minimal supersymmetric standard model, when extended to embed the seesaw mechanism, obtains two dimensionful parameters in its superpotential: the µ parameter and the right-handed neutrino mass MN. These mass parameters, belonging to the supersymmetric sector of the theory, pose serious naturalness problems as their scales are left completely undetermined. In fact, for correct phenomenology, µ must be stabilized at the electroweak scale while MN lies at an intermediate scale. In this work we construct an explicit model of the hidden sector of N = 1 supergravity for inducing both µ and MN at their right scales. The model we build utilizes lepton number conservation and continuous R invariance as two fundamental global symmetries to forbid bare µ and MN appearing in the superpotential, and induces them at phenomenologically desired scales via spontaneous breakdown of the global symmetries and the supergravity. We discuss briefly various phenomenological implications of the model.


Weak images, which pass through two kinds of suspension media with sizes of randomly-moving suspension particles about 0.05-0.1 cm and 0.01-0.001 cm respectively, are deteriorated by light scattering of particles, but restored and amplified effectively by two-wave mixing in photorefractive crystals with different time constants.


A lymphographic and phleobographic study of the lymph and blood outflow in 61 patients with postmastectomy upper limb edema showed that a complete block of the lymphatic vessels was observed in 86.5% and a partial block in 13.5% of the patients. Combined injuries of the lymphatic vessels and major veins aggravated the degree of limb edema. The presence of upper limb lymphostasis in the compensated venous outflow is an indication to the use of the microvenous shunting or dermatoplastic operations.


Second language learning has become very important because of globalization and as a result, many online language learning platforms have gained popularity. Despite their popularity and convenience, they still lack the human factor and meaningful interaction. Robot-assisted language learning (RALL) is a concept where social robots are employed to assist in language learning, adding meaningful and human-like interactions to the process. In the case of online learning platforms, a similar approach can be taken using virtual robots. Virtual robots are similar to social robots as they can have a visual appearance, communication capabilities as well as human-like features. This research aims to understand the potential users', i.e., university students' perceptions, and expectations of a virtual robot as a language learning companion. We are focusing on three major aspects of its design: appearance, interaction and rewarding behavior. This is a qualitative and explorative study, which employs a human-centered design (HCD) approach by conducting a co-design workshop with five groups of university-level language students (n = 25) and a theme interview with seven design students. This article presents the first phase of the HCD process. The participants were asked questions about the appearance, behavior, movements, motivational factors, sound and rewarding features of the potential virtual language companion robot. The findings show that the idea of having an interactive virtual robot to assist online language learning was accepted and appreciated by all the participants but their expectations about the robot's design varied. The potential users preferred a robot-like appearance rather than a human-like one for the virtual language learning companion, however, different robot-like appearances were mentioned in terms of their body parts, hands, head, shapes etc. Human-like gestures and movements were appreciated by the participants. Finally, seven design implications were formulated to support the further design of a virtual robot that can act as a virtual language learning companion as part of an online learning platform for university students.


Uncontrolled urban population growth in metropolitan areas of developing countries in recent years has made solid waste management an important issue. Generally, collection and hauling efforts cover a substantial amount of total expenditures on the solid waste management by city authorities. Success of an integrated solid waste management system is directly proportional to the success of solid waste collection and transport systems since all depends on an even and a timely manner collection process. The more populated cities bring increasing difficulties on the reach and utilise services. In order to reduce cost and time on these services, it is very crucial for authorities to search for optimisation possibilities. In this manner, for local authorities, one of the most important issues on solid waste management practices is an optimised solid waste collection function. An optimised collection function has become more important in metropolitan areas having improved and sophisticated road systems. In this study, in order to minimise the route and collection cost by employing GIS and using numerical road data, a solid waste collection route optimisation study was carried in Fatih District of Istanbul, Turkey.


Betel nuts in Taiwan might contribute to strong angiogenesis & invasion with resistance to traditional therapies. In our research, betel-nuts exposed HNSCC cell line, TW2.6, had high PDL1, defective p53 mutation, p16 loss, and BCL2 overexpression. PI3K/AKT/mTOR inhibitors, anti-angiogenesis therapies, CDK4/6 inhibitors, DDR interventions, and immunotherapy-containing regimens will be future backbones and reverse treatment refractoriness(AACR-AHNS2017). The genomic signature of TW2.6 has been figured out(AACR2020) mainly with PIK3CA H1047R mutation, high TMB(8.42 muts /Mb)/MSS, p53/MYC/HRAS/DDR2/ PDGFRbeta/ EPHB1/ATM mutations, FAT1 loss, amplification of VEGF-A/TERT/ FGF10/CCND3/SOX9/IL-7R/SDHA/RICTOR/FLCN, CDK12 loss of function, and deletions of STK11/ARID1B/MITF/TNFAIP3. CDK4/6 inhibitor was effective in HPV-negative and pRB-positive HNSCC and had strong immuno-modulation(suppress Treg, increase CTLs, enhance MHC I/II upregulation and antigen presentation). Palbociclib was effective on TW2.6 and could resensitize TW2.6 to docetaxel, afatinib, & radiation & enhance further response to BYL719& foretinib(VEGFR2/c-MET/Axl triple inhibitor). Western blotting showed (1) Slug, Snail, N-cadherin, Twist, Vimentin, Claudin-1, Axl, p-Akt and p70S6K decrease; (2) BMI-1, pRB, and PDL1 drop(ASCO218).SCC4, SCC9, SCC15, SCC25, FaDu, KB, Cal27, SAS, and TW2.6 for (1)in vitro sensitivity to palbociclib, ribociclib, abemaciclib; (2)synergistic effects with other therapies by MTT assay, colony formation assay, and western blotting. NGS studies were used to study molecular biomarkers of CDK4/6 inhibitors efficacy.Palbociclib had greatest efficacy over SCC15(classical HPV-negative type with EGFR overexpression) followed by SCC25, SAS, TW2.6(HPV-negative EMT type), & CAL27; but little efficacy over KB. In HPV-positive cell lines, palbociclib had (1) promising response on SCC25(classical HPV+ type); (2) little response on FaDu(HPV+ mesenchymal type) & KB(basal type in TCGA). In other HNSCC cell lines with basal types, however, SAS & CAL27 responded well to palbocilclib. Palbociclib response seemed to correlate to CCND1 gain and CDKN2A deletion; but FaDu had not so good palbociclib response with these two changes and TW2.6 had good response even without these two. TW2.6 was most sensitive to palbociclib, moderately sensitive to ribociclib, and mildly sensitive to abemaciclib.TW2.6 is responsive to CDK4/6 inhibitor(palbociclib>ribociclib>abemaciclib). FAT1 loss, CCND1/3 overt amplification, PI3K/AKT/mTOR derangements, and FGFR amplification might confer CDK4/6 inhibitor resistance in our genomic study. Based on immuno-modulatory effects of CDK4/6 inhibitor, we have initiated a study using ribociclib with spartalizumab in R/M HNSCC(RISE-HN: NCT04213404). We might develop a ctDNA-driven(intact PTEN & FAT1, CDKN2A deletion, high CDK4/6 copy numbers, no CCND1/3 overt amplification or FGFR amplification or other PI3K/AKT/mTOR derangements) clinical trial with palbocilcib and avelumab in betel-nuts related R/M HNSCC in Taiwan. Abemaciclib may have better immune-modulation.


Developing collaborative mobile applications is a tedious and error-prone task, as collaboration functionality often has do be developed from scratch. To ease this process, we propose WatchMyPhone, a developer toolkit being focused on the creation of collaborative applications on mobile devices, especially sharing user interface components like text views in a multi-user setting. We provide an implementation of the toolkit as well as a demo application for shared text editing based on Android. WatchMyPhone is integrated in the Mobilis open source framework thus adding another facet to enable fast and efficient development of mobile social apps.


Preface. 1. The Challenge of Human-Environment Interactions Research. The Evolution of Social Ecological Systems. Characterization of Contemporary Global Environmental Changes. History of the Development of the Human Dimensions Agenda. Characteristics of the Research on the Human Dimensions. The Way Forward: Integrative Science. 2. Theories and Concepts from the Social Sciences. Population, Technology and Central Place Theories . Population and Environment Theories. Agency and History. Decision-theoretic Approaches. Political Economy and Political Ecology. Cultural Ecology. 3. Theories and Concepts from the Biological Sciences. Evolution by Natural Selection. Species respond individualistically, not as communities, to environmental change. Interactions with other species help determine if a particular species will persist in a particular place (Niche and Neutral Theories). Top-down vs. bottom-up control in ecosystems. Succession. Island Biogeography. Equilibrium/non-equilibrium theories of competition, coexistence, community composition Biodiversity and ecosystem processes/services. The Ecosystem Concept in Biology and the Social Sciences. 4. Spatially-Explicit Approaches. Remote Sensing and GIS. A Case Study using GIS/ Remote Sensing to study Amazonian Deforestation. Urban-rural spatial dynamics. Modeling and GIS. 5. Multi-Scale and Multi-temporal Analysis. An approach to multi-disciplinary, multi-scale research. Scale. Local level of analysis. Regional Level of Analysis. Global Level of Analysis. Future Directions. 6. Bio-complexity in Ecological Systems. Spatially-explicit Processes in Ecological and Social Systems. Agent-Based Modeling of Complex Systems. Hierarchical Modeling. Conclusions. 7. Environmental Decision-Making. Institutional Analysis. Individual Behavior and Environmental Decisions. Decisions and Social Context. Conclusions. 8. Towards Sustainability Science. Sustainability Science Research Priorities. Scales of Sustainability. Cities and Sustainability Science. Climate Change and Sustainability. Conclusions. Bibliography.