United States Environmental Protection Agency guidance on the use of photochemical models for assessing the efficacy of an emissions control strategy for ozone requires that modeling be used in a relative sense. Consequently, testing a modeling system's ability to predict changes in ozone resulting from emission changes is critical. We evaluate model simulations for precursor species (NOx, CO, and volatile organic compounds [VOCs]), radicals (OH and HO2), a secondary pollutant (O3), and the model response of these compounds to weekend/weekday emission changes during California Nexus study in 2010. The modeling system correctly simulated the broad spatial and temporal variation of NOx and O3 in California South Coast. Although the model generally underpredicted the daytime mixing ratios of NO2 at the surface and overpredicted the NO2 column, the simulated weekend to weekday ratios are consistent with each other and match the observed ratios well. The modeling system exhibited reasonable performance in simulating the VOC compounds with fossil fuel origins but has larger bias in simulating certain species associated with noncombustion sources. The modeling system successfully captured the weekend changes of the enhancement ratios for various VOC species to CO and the relative changes of HOx, which are indicators of faster chemical processing on weekends. This work demonstrates satisfactory model performances for O3 and most relevant chemical compounds with more robust performance in simulating weekend versus weekday changes. Improved planetary boundary layer height simulations, a better understanding of OH‐HO2 cycling, continued improvement of emissions, especially urban biogenic emissions and emissions of oxygenated VOCs, are important for future model improvement.


In this paper, we describe O-DEVICE, a memory-based knowledge-based system for reasoning and querying OWL ontologies by implementing RDF/OWL entailments in the form of production rules in order to apply the formal semantics of the language. Our approach is based on a transformation procedure of OWL ontologies into an object-oriented schema and the application of inference production rules over the generated objects in order to implement the various semantics of OWL. In order to enhance the performance of the system, we introduce a dynamic approach of generating production rules for ABOX reasoning and an incremental approach of loading ontologies. O-DEVICE is built over the CLIPS production rule system, using the object-oriented language COOL to model and handle ontology concepts and RDF resources. One of the contributions of our work is that we enable a well-known and efficient production rule system to handle OWL ontologies. We argue that although native OWL rule reasoners may process ontology information faster, they lack some of the key features that rule systems offer, such as the efficient manipulation of the information through complex rule programs. We present a comparison of our system with other OWL reasoners, showing that O-DEVICE can constitute a practical rule environment for ontology manipulation.


This article suggests that property is subject to a fundamental law of entropy, namely that it is affected by a one-directional bias leading towards increasing fragmentation. The application of the laws of entropy to property further indicates that one can avoid this tendency only in the purely abstract world of zero transaction costs. Building upon this consideration, I consider the choice of remedies in property law, focusing on legal rules that are designed to promote (a) functional, (b) legal, and (c) physical unity in property. I provide examples drawn from both common law and civil law systems, supporting the hypothesis that legal rules are instrumental in combating entropy in property.


The late Cenozoic Kongur Shan extensional system lies along the northeastern margin of the Pamir at the western end of the Himalayan-Tibetan orogen, accommodating east-west extension in the Pamir. At the northern end of the extensional system, the Kongur Shan normal fault juxtaposes medium- to high-grade metamorphic rocks in both its hanging wall and footwall, which record several Mesozoic to Cenozoic tectonic events. Schists within the hanging wall preserve a Buchan metamorphic sequence, dated as Late Triassic to Early Jurassic (230–200 Ma) from monazite inclusions in garnet. Metamorphic ages overlap with U-Pb zircon ages from local granite bodies and are interpreted to be the result of regional arc magmatism created by subduction of the Paleo-Tethys ocean. The northern portion of the footwall of the extensional system exposes an upper-amphibolite-facies unit (~650 °C, 8 kbar), which structurally overlies a lowgrade metagraywacke unit. The high-grade unit records late Early Cretaceous crustal thickening at ca. 125–110 Ma, followed by emplacement over the low-grade metagraywacke along a north-northeast–directed thrust prior to ca. 100 Ma. Together these results indicate signifi cant middle Cretaceous crustal thickening and shortening in the northern Pamir prior to the Indo-Asian collision. A third Late Miocene (ca. 9 Ma) amphibolite-facies metamorphic event (~650–700 °C, 8 kbar) is recorded in footwall gneisses of the Kongur Shan massif. North of the Kongur Shan massif, rapid cooling in the footwall beginning at 7–8 Ma is interpreted to date the initiation of exhumation along the Kongur Shan normal fault. A minimum of 34 km of east-west extension is inferred along the Kongur Shan massif based on the magnitude of exhumation since the Late Miocene (~29 km) and the present dip of the Kongur Shan normal fault (~40°). Field observations and interpretation of satellite images along the southernmost segment of the Kongur Shan extensional system indicate that the magnitude of late Cenozoic east-west extension decreases signifi cantly toward the south. This observation is inconsistent with models in which east-west extension in the Pamir is driven by northward propagation of the right-slip Karakoram fault, suggesting instead that extension is driven by vertical extrusion due to topographic collapse, radial thrusting along the Main Pamir Thrust, or oroclinal bending of the entire Pamir region.


The effect of urea applied to apple leaves in autumn on production of ascospores of Venturia inaequalis (black spot) was quantified in four studies. Autumn urea at concentrations from 0-20% reduced ascospore production in spring in proportion to the log of the urea concentration. A single application of 5% urea sprayed onto fallen leaves gave an 88% decrease in ascospore production. Urea applied to apple trees before leaf fall significantly reduced black spot disease on leaves the following spring in cv. Fuji, but not in cv. Royal Gala. Ascospore production was reduced by the fungicide cupric hydroxide, but was not affected by a low concentration of fish fertilizer. Three methods of ascospore assessment were used to detect differences in ascospore production.


Conflicts of interest, bias, and appearance of impropriety continue to plague players in the land use game whose conduct, as public sector officials, must be beyond reproach. This article provides an annual review of reported cases and opinions involving allegations of unethical conduct in land use decision making. Conflicts of interest cases focus on attorneys, and address issues including of counsel relationships, disqualification and fees. Conflicts based upon financial interests for board members are explored, as well as unique relationships that may arise when colleges and universities seek approvals. Criminal aspects of decision maker conduct are also reported. Appearance of improprety issues, including whether absent board members can or should vote on applications, and the filling of vacancies by a "lame duck" board are discussed. Bias and prejudgment issues are discussed in the context of statements made by board members prior to application review, as well as board member conduct and participation in petition efforts, and the use of ethnic slurs at public meetings. The article concludes with an update on opinions related to dual office holding.


Objectives Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly involving cortical and spinal motor neurones. Molecular studies have recently identified different mutations in the ubiquilin-2 (UBQLN2) gene as causative of a familial form of X-linked ALS, 90% penetrant in women. The aim of our study was to analyse the UBQLN2 gene in a large cohort of patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis, with or without frontotemporal dementia (FTD), and in patients with FTD. Methods We analysed the UBQLN2 gene in 819 SALS cases, 226 FALS cases, 53 ALS–FTD patients, and 63 patients with a clinical record of FTD. Molecular analysis of the entire coding sequence was carried out in all FALS and ALS–FTD patients, while SALS and FTD patients were analysed specifically for the genomic region coding for the PXX repeat tract. Healthy controls were 845 anonymous blood donors and were screened for the PXX repeat region only. Results We found five different variants in the UBQLN2 gene in five unrelated ALS patients. Three variants, including two novel ones, involved a proline residue in the PXX repeat region and were found in three FALS cases. The other two were novel variants, identified in one FALS and one SALS patient. None of these variants was present in controls, while one control carried a new heterozygous variant. Conclusions Our data support the role of the UBQLN2 gene in the pathogenesis of FALS, being conversely a rare genetic cause in SALS even when complicated by FTD.


In a 9-month prospective study, sleep and daytime functioning were compared
in a community sample of 86 participants aged 25-50 years: 43 meeting DSM
IV criteria for primary insomnia (26 women & 17 men); and 43 controls (32
women & 11 men).
Assessments were conducted at baseline, 4 and 8 months, and included: the
Pittsburgh Sleep Quality Index; Spielberger StatefTrait Anxiety Inventory;
Eysenck Personality Questionnaire, Beck Depression Inventory; Fatigue
Severity Scale; SF-36; Epworth Sleepiness Scale; Dysfunctional Beliefs About
Sleep Scale; Sleep Hygiene and Practices Scale, Sleep Disturbance
Questionnaire and the Psychomotor Vigilance Task PVT. An instrument to
assess the occupational consequences of insomnia (the Occupational Impact of
Sleep Questionnaire; OISQ) was also developed in the course of the study.
PWI versus control group comparisons were made with repeated measures
multivariate ANOVAs. Differences were consistently and significantly
maintained on measures of state (F = 15.85 P <0.001) and trait anxiety
(F = 23.46; P < 0.001), depression (F = 18.37; P < 0.001), fatigue (F = 22.20;
P < 0.001), and neuroticism (F = 11.09; P < 0.001). Among PWI, mental health
(F = 14.04; P < 0.001), pain (F = 6.92; P < 0.001), role-emotion (F = 10.94;
p < 0.001), general health perceptions (F = 4.77; P < 0.05), social functioning
(F = 6.58; P < 0.01) and energy and vitality (F = 32.08; P < 0.001), on the
SF-36, were consistent with inferior health related QoL. In addition, pre-sleep
arousal (F = 14.76; P < 0.001), sleep hygiene (F = 35.26; P < 0.001) and sleep
disturbance (F = 72.32; P < 0.001) were significantly worse within PWI.
Subjectively reported TIB (F = 9.38; P < 0.01), SOL (F = 11.17; P < 0.01) and
WASO (F = 21.10; P < 0.001), remained greater within PWI, with SE (F = 15.29;
P < 0.001), TST (F = 9.38; P < 0.01) and subjective sleep quality (F = 29.57;
P < 0.001) greater within controls.Data averaged over the duration of data collection (252 days) found PWI
reported an average SOL >30 minutes, an average WASO of> 30 minutes, SE
< 80%. Analysed in terms of night to night sleep quality, both PWI and controls
showed a pattern of 'good' (sleep efficiency >80%) and 'poor' (sleep efficiency
<80%) nights. However, the probability of individual poor nights remained
consistently and significantly higher for PWI across the 9 months of the study.
Actigraphy data failed to confirm between group differences in sleep, and
correlation with diary measures was low in both groups.
PVf performance showed instability. Significant group differences found at
baseline, were no longer present at subsequent data collection points. Data
support the inconsistency surrounding objective performance among PWI within
the literature. However, the inconsistency can be attributed to greater change
within control participant's performance, rather than within PWI.
Data identified the existence of a stable subgroup of PWI reporting symptoms
of daytime sleepiness. Daytime sleepiness was found to be a temporally stable
feature for this sub-group of PWI, who also Showed a distinctive psychological
profile compared to PWI who did not report daytime sleepiness. No difference,
however, was observed in subjectively reported sleep structure, quality or
daytime performance between these subgroups of PWI. Insomnia subgroup
analyses suggest a trait-like difference between sleepy and non sleepy PWI.The OISO showed an acceptable level of internal consistency reliability (alpha
0.93); and successfully discriminated between PWI and controls. The OISO
also showed consistent correlations with measures of global sleep quality and
subjective sleep parameters. Expressed in terms of comparative percentage
decrement, PWI showed a consistent 10% decrement in subjective
occupational performance when compared with controls. The OISO shows that
absenteeism and punctuality may not capture the full impact of insomnia on workplace performance.


Shifting cultivation is often blamed as a principal cause of deforestation in tropical Africa. It is claimed that the practice is unsustainable because shortened fallow lengths result in soils too degraded to support forest vegetation. The decline in fallow lengths is often attributed to increases in population density and greater market participation. The conventional wisdom makes several claims that are as yet unsubstantiated. This paper investigates whether there is evidence to support two of these claims in southern Cameroon. First, using both cross-sectional and panel data, I find that there is indeed a robust negative association between fallow lengths and population density in the study area and weaker evidence for a negative relationship between fallow lengths and market participation. Second, a stochastic frontier production function approach is used to investigate the marginal contribution of fallow to output. Results indicate that fallow lengths are not low enough to be affecting yields and therefore do not appear to be resulting in declines in soil fertility. Thus overall, while some of the assumptions of the conventional wisdom appear to be true, there is little evidence to support its dramatic conclusion that shifting cultivators are causing deforestation in the forested region of Cameroon.


This paper introduces a statistical fitness landscape analysis, based on Weinberger's random walk method and on a time series analysis known as the Box-Jenkins approach, to measure and express the correlation structure of fitness landscapes. The analysis has some additions to and advantages over previous methods for measuring this structure. The analysis is demonstrated on fitness landscapes constructed with Kauffman's NK-model, using two operators (point mutation and a form of crossover) and a combination of the two. Furthermore, the predictive value of the method is shown.


Evaluating the Effects of Strong Teens on High School Student Levels of Internalizing Symptoms and Resilience Austin J. Millet Department of Counseling Psychology and Special Education, BYU Doctor of Philosophy Many adults suffering from mental health problems often report that the onset of these concerns began in adolescence, highlighting the importance of identifying and treating mental health concerns from an early age. In high schools, some students are identified as having externalizing or internalizing disorders. The majority of these students, especially those with internalizing symptoms, go untreated. One potential reason may be that limited school resources are used to correct behavior problems, leaving those with internalizing disorders to silently suffer, which often exacerbates the issues. Recent research suggests many individuals have high levels of resilience which can be taught, and which positively contributes to mental health. Social emotional learning (SEL) is one approach to teaching resilience. In this study we implemented an SEL program called Strong Teens at the high school level. The high school identified students with internalizing symptoms and provided them with this curriculum, intended to reduce those symptoms. We used a time series design to evaluate changes in internalizing symptoms (e.g., depression, anxiety, and withdrawal) and resilience. Results indicated that with the implementation of the Strong Teens curriculum, student levels of internalizing symptoms decreased from pretest to posttest, according to self-report. Teacher reports did not indicate any significant change in internalizing symptoms or resilience. This study supports the findings of the Strong Teens curriculum as a generalizable program which significantly reduces internalizing symptoms.


A space invariant multiple imaging system using an array of tilted mirrors is proposed for optical free-space regular interconnections. The system has the potential for large number and high density of input nodes, high fanout capability, and low power loss. An eighteen-cube interconnection of 512 x 512 nodes could be implemented in this system using a 6 x 6 mirror array. Experimental results for a four-cube interconnection are shown.


This article discusses recent developments in the regulatory and legislative spheres of interest to energy lawyers. The authors reviewed regulatory initiatives, decisions, related case law and legislation from provincial, territorial, and federal authorities. Topics of note include hydraulic fracturing, oil by rail, liquefied natural gas, renewable energy and power, the new Alberta Energy Regulator, oil and gas development, environmental protection, and Aboriginal and other issues. The period covered is May 2013 to April 2014, inclusive.


XML is nowadays the de facto standard for electronic data
interchange on the Web. Available XML data ranges from small Web pages to ever-growing repositories of, e.g., biological and astronomical data, and even to rapidly changing and possibly unbounded streams, as used in Web data integration and publish-subscribe systems.

Animated by the ubiquity of XML data, the basic task of XML querying is becoming of great theoretical and practical importance. The last years witnessed efforts as well from practitioners, as also from theoreticians towards defining an appropriate XML query language. At the core of this common effort has been identified a navigational approach for information localization in XML data, comprised in a
practical and simple query language called XPath.

This work brings together the two aforementioned ``worlds'', i.e., the XPath query evaluation and the XML data streams, and shows as well theoretical as also practical relevance of this fusion. Its relevance can not be subsumed by traditional database management systems, because the latter are not designed for rapid and continuous loading of individual data items, and do not directly support the continuous queries that are typical for stream applications.

The first central contribution of this work consists in the definition and the theoretical investigation of three term rewriting systems to rewrite queries with reverse predicates, like parent or ancestor, into equivalent forward queries, i.e., queries without reverse predicates. Our rewriting approach is vital to the evaluation of queries with reverse predicates against unbounded XML streams, because neither the storage of past fragments of the stream, nor several stream traversals, as required by the evaluation of reverse predicates, are affordable.

Beyond their declared main purpose of providing equivalences between queries with reverse predicates and forward queries, the applications of our rewriting systems shed light on other query language properties, like the expressivity of some of its fragments, the query minimization, or even the
complexity of query evaluation. For example, using these systems, one can rewrite any graph query into an equivalent forward forest query.

The second main contribution consists in a streamed and progressive evaluation strategy of forward queries against XML streams. The evaluation is specified using compositions of so-called stream processing functions, and is implemented using networks of deterministic pushdown transducers. The
complexity of this evaluation strategy is polynomial in both the query and the data sizes for forward forest queries and even for a large fragment of graph queries.

The third central contribution consists in two real monitoring applications that use directly the results of this work: the monitoring of processes running on UNIX computers, and a system for providing graphically real-time traffic and travel information, as broadcasted within ubiquitous radio signals.


This article describes the California 4-H Youth Development Program's (4-H YDP) creation of a Youth Leadership Summit (YLS), as well as information gained from three summits held in the summers of 1999 through 2001. Previous studies (Camino, 2000; Lerner, 2000; Zeldin, 2000) suggested that youth-adult collaborations along with meaningful activities could have a positive impact on youth. Therefore, the summits emphasized the positive youth development model, employed youth-adult collaborations, and encouraged youth to become involved in their communities. In this article, we share the YLS procedures, the roles of youth and adults and the engagement of youth on community issues. The YLS model developed by the California 4-H YDP impacted the individuals and communities involved in important and positive ways and might be a useful model to follow in the establishment of similar youth programs developed by youth professionals.


Thousands of mine workers die every year from mining accidents, and instantaneous coal outbursts in underground coal mines are one of the major killers. Various models for these outbursts have been proposed, but the precise mechanism is still unknown. We hypothesize that the mechanism of coal outbursts is similar to magma fragmentation during explosive volcanic eruptions; i.e., it is caused by high gas pressure inside coal but low ambient pressure on it, breaking coal into pieces and releasing the high-pressure gas in a shock wave. Hence, coal outbursts may be regarded as another type of gas-driven eruption, in addition to explosive volcanic, lake, and possible ocean eruptions. We verify the hypothesis by experiments using a shock-tube apparatus. Knowing the mechanism of coal outbursts is the first step in developing prediction and mitigation measures. The new concept of gas-driven solid eruption is also important to a better understanding of salt-gas outbursts, rock-gas outbursts, and mud volcano eruptions.


Providing robots with accurate and robust visual recognition capabilities in the real-world today is a challenge which prevents the use of autonomous agents for concrete applications. Indeed, the majority of tasks, as manipulation and interaction with other agents, critically depends on the ability to visually recognize the entities involved in a scene. At the same time, computer vision systems based on deep Convolutional Neural Networks (CNNs) are marking a breakthrough in fields as large-scale image classification and retrieval. In this work we investigate how latest results on deep learning can advance the visual recognition capabilities of a robotic platform (the iCub humanoid robot) in a real-world scenario. We benchmark the performance of the resulting system on a new dataset of images depicting 28 objects, named iCubWorld28, that we plan on releasing. As in the spirit of the iCubWorld dataset series, this has been collected in a framework reflecting the typical iCub's daily visual experience. Moreover, in this release we provide four different acquisition sessions, to test incremental learning capabilities over multiple days. Our study addresses the question: how many objects can the iCub recognize today.


The aim of this paper is to establish rigorous results on the
large time behavior of nonlocal models for aggregation, including
the possible presence of nonlinear diffusion terms modeling local
repulsions. We show that, as expected from the practical
motivation as well as from numerical simulations, one obtains
concentrated densities (Dirac $\delta$ distributions) as
stationary solutions and large time limits in the absence of
diffusion. In addition, we provide a comparison for aggregation
kernels with infinite respectively finite support. In the first
case, there is a unique stationary solution corresponding to
concentration at the center of mass, and all solutions of the
evolution problem converge to the stationary solution for large
time. The speed of convergence in this case is just determined by
the behavior of the aggregation kernels at zero, yielding either
algebraic or exponential decay or even finite time extinction. For
kernels with finite support, we show that an infinite number of
stationary solutions exist, and solutions of the evolution problem
converge only in a measure-valued sense to the set of stationary
solutions, which we characterize in detail.

Moreover, we also consider the behavior in the presence of nonlinear diffusion terms,
the most interesting case being the one of small diffusion coefficients. Via the implicit function theorem we give a
quite general proof of a rather natural assertion for such models, namely that there exist stationary solutions
that have the form of a local peak around the center of mass. Our approach even yields the order of the size of
the support in terms of the diffusion coefficients.

All these results are obtained via a reformulation of the
equations considered using the Wasserstein metric for probability
measures, and are carried out in the case of a single spatial
dimension.


: In this paper we show that the sensitivity of absorption imaging of ultracold atoms can be significantly improved by imaging in a standing-wave configuration. We present simulations of single-atom absorption imaging both for a travelling-wave and a standing-wave imaging setup, based on a scattering approach to calculate the optical density of a single atom. We find that the optical density of a single atom is determined only by the numerical aperture of the imaging system. We determine optimum imaging parameters, taking all relevant sources of noise into account. For reflective imaging we find an improvement of 1.7 in the maximum signal-to-noise ratio can be achieved. This is particularly useful for imaging in the vicinity of an atom chip, where a reflective surface is naturally present.


Objective: Ovarian cancer is a leading cause of death from gynecological cancers. Late diagnosis and resistance to therapy results in mortality and effective screening is required for early diagnosis and better treatments. Expression of the Fanconi Anemia complementation group D2 protein (FANCD2) is reduced in ovarian surface epithelial cells (OSE) in patients with ovarian cancer. FANCD2 has been studied for its role in DNA repair; however multiple studies have suggested that FANCD2 has a role outside the nucleus. We sought to determine whether subcellular localization of FANCD2 correlates with patient outcome in ovarian cancer. Methods: We examined the subcellular localization of FANCD2 in primary OSE cells from consenting patients with ovarian cancer or a normal ovary. Ovarian tissue microarray was stained with anti-FANCD2 antibody by immunohistochemistry and the correlation of FANCD2 localization with patient outcomes was assessed. FANCD2 binding partners were identified by immunoprecipitation of cytoplasmic FANCD2. Results: Nuclear and cytoplasmic localization of FANCD2 was observed in OSEs from both normal and ovarian cancer patients. Patients with cytoplasmic localization of FANCD2 (cFANCD2) experienced significantly longer median survival time (50 months), versus patients without cytoplasmic localization of FANCD2 (38 months; p < 0.05). Cytoplasmic FANCD2 was found to bind proteins involved in the innate immune system, cellular response to heat stress, amyloid fiber formation and estrogen mediated signaling. Conclusions: Our results suggest that the presence of cytoplasmic FANCD2 modulates FANCD2 activity resulting in better survival outcome in ovarian cancer patients.


This study investigated the effects of a mindfulness-based intervention (MBI) called mindfulness-based peak performance (MBPP) on athletic performance and cognitive functions in archers, as well as the role of psychological status and the dose-response relationship of MBPP in archery performance. Twenty-three archers completed a simulated archery competition and the Stroop task prior to and after MBPP training, which consisted of eight sessions over four weeks, while the mindfulness and rumination levels of the archers were assessed at three time points, namely, before, at the mid-point of, and after the MBPP program. The results revealed that the MBPP program significantly improved the shooting performance (p = 0.002, d = 0.27), multiple cognitive functions (ps < 0.001, d = 0.51~0.71), and mindfulness levels of the archers on the post-test, compared to the pre-test (p = 0.032, ηp2 = 0.15 for general; p = 0.004, ηp2 = 0.22 for athletic). Additionally, negative ruminations level was decreased from the pre-test to the middle-test and post-test (ps < 0.001, ηp2 = 0.43). These findings provide preliminary evidence to support the view that MBPP could serve as a promising form of training for fine motor sport performance, cognitive functions, and specific psychological status, such that it warrants further study.


Yeonwoo Mudae is an exemplary theatre company of Korean theatre of the 1980s. It focused on newly created pieces (changjak-geuk) to provide a critical and historical understanding of contemporary Korean politics and culture. Using Brechean epic theatre, elements of madang-geuk (outdoor, episodic performances colored by traditional Korean theatre aesthetics), and local literature or history as its source, the company transitioned from a student workshop with no space of its own to a group with a permanent little theatre-style space in first the Shinchon area and then the Daehakro theatre district. Its exemplary productions both reflected and spurred the movement toward democratization and freedom of speech in the fraught political environment of a country repressed by the military-led government of President Chun Doo-Hwan.


This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH) in spontaneously hypertensive rats (SHR). Defatted hemp seed meal was hydrolyzed consecutively with pepsin and pancreatin to yield HMH, which was incorporated into rat feed as a source of antioxidant peptides. Young (8-week old) SHRs were divided into three groups (8 rats/group) and fed diets that contained 0.0%, 0.5% or 1.0% (w/w) HMH for eight weeks; half of the rats were sacrificed for blood collection. After a 4-week washout period, the remaining 20-week old SHRs were fed for an additional four weeks and sacrificed for blood collection. Plasma total antioxidant capacity (TAC) and superoxide dismutase (SOD), catalase (CAT) and total peroxides (TPx) levels were determined. Results showed that plasma TAC, CAT and SOD levels decreased in the older 20-week old SHRs when compared to the young SHRs. The presence of HMH in the diets led to significant (p < 0.05) increases in plasma SOD and CAT levels in both young and adult SHR groups; these increases were accompanied by decreases in TPx levels. The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.


The momentum measurement capability of the ATLAS muon spectrometer relies fundamentally on the intrinsic single-hit spatial resolution of the monitored drift tube precision tracking chambers. Optimal resolution is achieved with a dedicated calibration program that addresses the specific operating conditions of the 354 000 high-pressure drift tubes in the spectrometer. The calibrations consist of a set of timing offsets and drift time to drift distance transfer relations, and result in chamber resolution functions. This paper describes novel algorithms to obtain precision calibrations from data collected by ATLAS in LHC Run 2 and from a gas monitoring chamber, deployed in a dedicated gas facility. The algorithm output consists of a pair of correction constants per chamber which are applied to baseline calibrations, and determined to be valid for the entire ATLAS Run 2. The final single-hit spatial resolution, averaged over 1172 monitored drift tube chambers, is 81.7 ± 2.2 μm.


I am privileged to still be seeing patients in our primary care practice within the Division of Internal Medicine at Sidney Kimmel Medical College (formerly Jefferson Medical College). Parenthetically, I am also the oldest physician in the group. Like many primary care physicians, I have recently seen an increase in the number of patients who bring results of proprietary genetic testing to the office. These results, often from companies such as 23andMe, a DNA analysis service, represent a sea change in at least one aspect of the doctor–patient relationship. In what some have called the "democratization" of information (see Eric Topol's wonderful book, The Creative Destruction of Medicine),1 genetic typing is potentially the first step toward our realization of personalized medicine.

As of now, however, I do not believe we are quite there yet. In other words, I am unable to thoroughly interpret the results of testing from companies such as 23andMe, and the opportunities to modify a medication regimen, make solid evidentiary-based recommendations for changes in behavior, or for future clinical testing for patients are limited.

Let us first examine the public's view of personalized medicine, and then review some examples of where we currently are, and where we may be in the future.

According to a March 2014 survey of public opinion conducted on behalf of the Personalized Medicine Coalition by KRC Research, a reputable public opinion research consultancy based in Washington, DC, a large majority (62%) of the 1024 American adults polled on the topic had not heard of personalized medicine, but they reacted positively when it was described to them.2 Among the surveyed adults who had heard the term (38%), only 2 in 10 believed they were very informed about personalized medicine. Furthermore, only 11% said that their doctor had discussed or had recommended any aspect of personalized medicine to them.2

First, let us define our terms. The investigators at KRC Research used the following description of personalized medicine when conducting the survey: "Personalized medicine is an emerging field that uses diagnostic tools to identify specific biologic markers, often genetic, to help determine which medical treatments and procedures will be best for each patient. By combining this information with an individual's medical records and circumstances, personalized medicine allows doctors and patients to develop targeted prevention and treatment plans. The goal is to provide the right treatment in the right dose to the right patient at the right time."2

The KRC Research investigators further noted that the majority of the survey participants were "excited about the potential benefits of personalized medicine, including choosing a treatment that is most likely to work for them and the potential to prevent illness."2 A large majority of those surveyed "also recognize the value of these technologies and that they should be covered by insurance."2 Finally, "the idea that personalized medicine can provide useful prevention and treatment information, help avoid or reduce side effects, avoid trial-and-error medicine, and give more control to prevent or treat illness are very compelling benefits."2

One could quibble slightly with KRC Research's definition of personalized medicine, but my hunch is that the results truly reflect the positions of the survey responders. Who could argue with treatment that avoids trial and error, is more focused on the individual, and that has long-term benefits when done correctly? So, yes, parts of these results are dependent on how we ask the question; however, although the public is not currently well informed, this situation will very likely change in the very near term.

Where are we now regarding the implementation of personalized medicine? Clearly, this is a complex issue. I have written about this complexity elsewhere,3 but it is fair to say that personalized medicine has not yet delivered on its "hype." I certainly expected that by late 2014 we would be doing a buccal smear on our primary care patients, assessing their genotype quickly in the office, and making very specific, evidence-based recommendations for their future health and well-being. We have not yet realized this dream.

For example, findings from a recent meta-analysis by Stergiopoulos and Brown show that a "genotype-guided dosing strategy [for warfarin] did not result in a greater percentage of time that the INR [international normalized ratio] was within the therapeutic range, fewer patients with an INR greater than 4, or a reduction in major bleeding or thromboembolic events compared with clinical dosing algorithms."4 In other words, despite the availability of pharmacogenomic testing to determine who may benefit from therapy with warfarin and appropriate dosing, this meta-analysis of randomized clinical trials revealed no difference between our current standard of care and care complemented by genetic testing. In an editorial accompanying the meta-analysis, Kazi and Hlatky state that the "routine use of genetic testing to guide warfarin management cannot be recommended."5

Warfarin is just one example. There are now a score of drugs that have been assessed in the literature based on genetic testing, and the take-home message is very mixed. Kazi and Hlatky conclude that "evidence of improved clinical outcomes, not biological causability or hype, should drive the adoption of genetic tests into practice."5

Although the example of warfarin is not compelling, evidence in psychiatric care (and other clinical areas, such as cancer care) may present a different story. In an article on pharmacogenomic testing, Winner states that "given that the current strengths of pharmacogenomics testing align directly with the common pharmacologic challenges in the elderly and the need for better outcomes with lower costs, the aging population may be the first large group of individuals to benefit from a paradigm shift in treatment with integrated pharmacogenomic testing."6 Winner further suggests that within the burgeoning arena of geriatric psychiatry, pharmacogenomic testing will identify individual genetic differences as they relate to response to therapy, and that this can be used to personalize medication treatment for the large number of elderly patients with depression.

What about the future? In August, I had the opportunity to participate in a leadership panel program sponsored by Pennsylvania Bio (www.pabio.org), a large membership organization headquartered in suburban Philadelphia that represents more than 600 companies in the life sciences. At this leadership program entitled "From Personalized Medicine to Precision Prevention—What Will It Mean for You?," the group of participating experts were very enthusiastic about the future of personalized medicine. Despite the regulatory and scientific challenges, these experts from across the state were very upbeat in their assessment of the future of personalized medicine. They also cited an increase in Wall Street's interest in companies working in this arena.

With that in mind, I am personally intrigued by the work of companies such as Genelex Corporation and their YouScript system, a personalized prescribing system that uses genetic screening to reduce adverse drug events.7 For example, a description of YouScript's services notes that "more than 75% of patients have detectable variations in their DNA that may increase their risk of unwanted side effects and adverse drug events."8 YouScript brochures suggest that its testing is recommended for patients who take multiple medications, complain that their medications are not working or who are wary of standard dosing based on negative experiences, and are using complex drug treatment plans. This description applies to the vast majority of my own patients. So perhaps companies and services such as YouScript, 23andMe, and others are going to enjoy a very successful future.

We are certainly on the right road, but we're not there yet. Although common therapeutic regimens involving drugs such as warfarin and tricyclic antidepressants are reporting variable outcomes within the personalized medicine arena, I am confident that with new technology, we will overcome any current limitations, and my dream of practicing personalized medicine will be realized in my own practice lifetime. Let us get past the hype and improve the science so we can make real advances in this field. For me, time is of the essence.

As always, I am interested in your views, and you can reach me at email@example.com.


It's a pleasure to be able to comment on these two papers. They both engage the analysis of asylum in rich and provocative ways. My remarks will focus especially on the culture question-on the ways in which culture and asylum get tangled up with, and indeed co-produce, one another in asylum contexts. In so doing, I will draw not only on these two papers but also on work I have done on political (or "cultural") asylum cases involving female genital mutilation (FGM), especially the 1996 landmark Kasinga asylum case,1 for which I served as a (minor) expert witness. Ranji Khanna's paper locates the figure of asylum, and the contemporary asylum seeker, within a nexus of broader theoretical categories (sovereignty, states of exception, biopolitical disciplinary regimes) and within a field of sites (the mental asylum, places of religious sanctuary) that bear family resemblance to the site of refuge for the asylum seeker today-the nation itself. She suggests that we think of political asylum less as refuge or sanctuary and more as reinscription of state power and sovereign authority, thus urging us to read the offer of hospitality (that is inherent to the granting of asylum) as an act of exclusion and violence-and a reassertion of state power. Asylum, Khanna argues, represents the right of institutions over bodies rather than of individuals over institutions or states. But more, she also asks us to consider thinking of asylum in its dystopic, biopolitical form as symptomatic of our times, as norm rather than exception, as universal condition. We are all refugees living in an "age of asylum." Khanna also suggests that gendering the asylum seeker as paradigmatically female and theorizing the category asylum through a Marxist-feminist optic might cause us not only to acknowledge or bring into recognition that which often remains unrecognized-for the Marxist-feminist, "affective" or "immaterial" labor as well as the exclusions and violences of family and community, for the asylum seeker, the work she is performing for the sovereign and the violence to which she is subjected by the state-but also to explore the site of asylum as a doubled space of excess, desire and Utopian hope. I find the analysis immensely suggestive, and simply want to extend its reach by raising some questions about some of its main points. First, I would like to hear more about how we get from the iron cage (or "melancholia") of the first half of the essay to the Utopian space of desire of the second? If, as Khanna suggests, asylum is saturated with state surveillance and control, how does one ever escape such disciplinary regimes to inhabit a more emancipatory space? Second, Agamben seems to haunt this text but is never mentioned.2 Are not the disciplinary regimes of Agamben's concentration camp precisely those of the insane asylum, and is not the principle of the "state of exception become norm" that Agamben invokes so powerfully around the figure of the camp not also the point Khanna is trying to make for political asylum? Moreover, what about that other contemporary sovereignty theorist, Achille Mbembe? He suggests in his work on "necropolitics"3 that we need today to supplement the biopolitical with the necropolitical, that sovereignty in today's world is inextricably linked with death-dealing and, thus, with the taking (as much as the granting) of life. Since domestic regimes of surveillance and incarceration and those of global war are so intimately connected in this post-9/11 world, and since the figure of the asylum seeker-clutched from the jaws of death by the offer of life and hospitality-is so implicated in such a world (as a transgressor of its boundaries), it would seem that thinking asylum through its relationship to the necropolitical might also be necessary. Indeed, does not the asylum seeker escape one form of necropolitics only to submit herself to another? Third, I wonder about Khanna's periodizing moves, especially her characterization of the contemporary era. …


EU law provides explicitly that intermediaries may not be obliged to monitor their service in a general manner in order to detect and prevent the illegal activity of their users. However, a misunderstanding of the difference between monitoring specific content and monitoring FOR specific content is a recurrent theme in the debate on intermediary liability and a central driver of the controversy surrounding it. Rightly understood, a prohibited general monitoring obligation arises whenever content – no matter how specifically it is defined – must be identified among the totality of the content on a platform. The moment platform content must be screened in its entirety, the monitoring obligation acquires an excessive, general nature. Against this background, a content moderation duty can only be deemed permissible if it is specific in respect of both the protected subject matter and potential infringers.

This requirement of 'double specificity' is of particular importance because it prevents encroachments upon fundamental rights. The jurisprudence of the Court of Justice of the European Union has shed light on the anchorage of the general monitoring ban in primary EU law, in particular the right to the protection of personal data, the freedom of expression and information, the freedom to conduct a business, and the free movement of goods and services in the internal market. Due to their higher rank in the norm hierarchy, these legal guarantees constitute common ground for the application of the general monitoring prohibition in secondary EU legislation, namely Article 15(1) of the E-Commerce Directive ('ECD') and Article 17(8) of the Directive on Copyright in the Digital Single Market ('CDSMD').

With regard to the Digital Services Act ('DSA'), this result of the analysis implies that any further manifestation of the general monitoring ban in the DSA would have to be construed and applied – in the light of applicable CJEU case law – as a safeguard against encroachments upon the aforementioned fundamental rights and freedoms. If the final text of the DSA does not contain a reiteration of the prohibition of general monitoring obligations known from Article 15(1) ECD and Article 17(8) CDSMD, the regulation of internet service provider liability, duties of care and injunctions would still have to avoid inroads into the aforementioned fundamental rights and freedoms and observe the principle of proportionality. The double specificity requirement plays a central role in this respect.


Synovial cysts are infrequent findings in the spine and mostly located in the lumbar area. Even rarer is the occurrence of a synovial cyst in the cervical spine. The pathology arises from the facet joint and may cause pain, radiculopathy, or myelopathy. Few cases of symptomatic subaxial synovial cysts have been reported in the literature. Surgery is indicated in the presence of severe pain and neurologic compromise and involves the decompression of the cyst and the associated neural elements. Hemilaminectomy is the surgical treatment most commonly reported in the literature. However, other procedures such as complete laminectomy, CT-guided aspiration, and anterior corpectomy have been described. On the background of available literature till date, we report an unconventional and novel therapeutic technique of anterior indirect decompression in an uncommon case of a C6-C7 synovial cyst. A 67-year-old female patient had left upper limb radicular pain along the forearm and lateral fingers for 2 months. She had severe neck pain in extension and weak triceps (4/5) with the Neck Disability Index (NDI) score of 51.11% and visual analog scale (VAS) score of 8/10. Plain x-rays were suggestive of spondylosis. T2WI of MRI scan demonstrated cystic lesion on ventral aspect of C6-C7 (L) facet suggestive of synovial cyst. Anterior cervical discectomy and fusion was done, and indirect posterior decompression of the cyst was achieved. There was a complete resolution of radiculopathy immediate postoperative period with magnetic resonance imaging (MRI) showing the evidence. Motor weakness resolved by 3 months with NDI score of 8.88% and VAS of 2/10. She was asymptomatic with no evidence of disease recurrence on MRI at 24 months.


Germline Pol I RNA polymerase I (Pol I)–directed ribosomal RNA (rRNA) transcription has been extensively studied in mammalian cell lines and yeast. However, the functional significance of cell-specific regulation of Pol I transcription within developmental contexts in vivo remains unclear. Zhang et al. (p. 298) characterized a Drosophila Pol I regulatory complex and found that germline stem cells (GSCs) of the ovary exhibited increased levels of rRNA transcription relative to their immediate daughter cells. High levels of rRNA expression promoted GSC proliferation, with attenuation of Pol I activity showing effects during early germ cell differentiation. The RNA polymerase I regulatory complex promotes dynamic regulation of ribosomal RNA synthesis within the Drosophila germline. Ribosome biogenesis drives cell growth and proliferation, but mechanisms that modulate this process within specific lineages remain poorly understood. Here, we identify a Drosophila RNA polymerase I (Pol I) regulatory complex composed of Under-developed (Udd), TAF1B, and a TAF1C-like factor. Disruption of udd or TAF1B results in reduced ovarian germline stem cell (GSC) proliferation. Female GSCs display high levels of ribosomal RNA (rRNA) transcription, and Udd becomes enriched in GSCs relative to their differentiating daughters. Increasing Pol I transcription delays differentiation, whereas reducing rRNA production induces both morphological changes that accompany multicellular cyst formation and specific decreased expression of the bone morphogenetic protein (BMP) pathway component Mad. These findings demonstrate that modulating rRNA synthesis fosters changes in the cell fate, growth, and proliferation of female Drosophila GSCs and their daughters.


We developed a process-based model to predict the probability of arsenic exceeding 5 microg/L in drinking water wells in New England bedrock aquifers. The model is being used for exposure assessment in an epidemiologic study of bladder cancer. One important study hypothesis that may explain increased bladder cancer risk is elevated concentrations of inorganic arsenic in drinking water. In eastern New England, 20-30% of private wells exceed the arsenic drinking water standard of 10 micrograms per liter. Our predictive model significantly improves the understanding of factors associated with arsenic contamination in New England. Specific rock types, high arsenic concentrations in stream sediments, geochemical factors related to areas of Pleistocene marine inundation and proximity to intrusive granitic plutons, and hydrologic and landscape variables relating to groundwater residence time increase the probability of arsenic occurrence in groundwater. Previous studies suggest that arsenic in bedrock groundwater may be partly from past arsenical pesticide use. Variables representing historic agricultural inputs do not improve the model, indicating that this source does not significantly contribute to current arsenic concentrations. Due to the complexity of the fractured bedrock aquifers in the region, well depth and related variables also are not significant predictors.


Real-world, social phenomena produce various types of data, like explicit networks or user-emitted text. When different sets of data describe the same entities, the data is termed multi-view or multi-modal. A distinct advantage of multi-view data is that different views may better capture different aspects of the latent structure of the data. However, there are difficulties in combining that data to produce something like a clustering of the data. Multi-view clustering techniques, primarily developed for image or biological use cases or network only use cases, have typically not been used for clustering social-based use cases. I investigate the use of multi-view clustering on various social-based, multi-view data sets, and propose new techniques for multi-view clustering of social-based data. In the first part of this thesis I discuss the use of multi-view clustering for socialbased data, and propose a new paradigm and new techniques for multi-view clustering. In chapter two I propose a new hybrid paradigm of multi-view clustering, which combines elements of late paradigm and intermediate paradigm integration. I test the various intermediate, late, and hybrid paradigm algorithms on a wide range of benchmark data sets from social-based data scenarios. The results of the empirical testing demonstrate a wide variance in the performance of multi-view clustering techniques. This is in part because social-based data often have high interand intraview variances that are not present in other data scenarios, which presents difficulties for existing techniques. Only two techniques proposed in the chapter have good performance across all of the data sets and are robust to interand intra-view differences. From the results in chapter two, I devise a new algorithm based in network modularity and graph learning to cluster multi-view social data in chapter three. I present the results of a series of empirical tests of the new technique, as well as possible variations on the technique. The results demonstrate that the presented technique often performs well across a wide range of social-scenarios that give rise to multi-view data, is scalable to large data sets, and is robust to interand intra-view variance. In the second part of this thesis I use the new techniques to do clustering analyses of real-world data. In chapter four I use multi-view clustering on Twitter data collected during the initial stages of the COVID-19 pandemic. This analysis is the first ever use of multi-view clustering to cluster hashtags from large, social-media data sets. The results display that hashtags form topical clusters and that these topical clusters have changed over the course of the pandemic. In chapter five I use multi-view clustering to cluster malware samples. The results demonstrate that a multi-view clustering of malware samples provides insight into communities of malware use, and confirm the techniques developed can be applied to a wide range of social-based data scenarios. In sum, I demonstrate the suitability of, and create techniques for, multi-view clustering of complex, multi-view, social-based data. This thesis advances practical clustering analyses of large-scale, noisy, social-based data and contributes to the field of multi-view clustering in general.


With the wealth of data provided by modern imaging and redshift surveys, it has become essential to obtain measurements of galaxy properties in an automated fashion, and analyse them in a statistical manner.
In this thesis we focus on two fundamental characteristics of the galaxy populations, their distributions in luminosity and their spatial clustering signal.
We examine galaxies from the SDSS-II galaxy redshift survey, quantifying their distribution in luminosity as a function of rest-frame colour and visual morphology taken from the Galaxy Zoo project. In forming samples of the galaxies selected by colour, morphology and luminosity we observe that there are significant populations of both red spiral galaxies and blue early-type galaxies at redshifts of 0.01 < z < 0.2.
To aid us in the description and analysis of these distributions we fit them with a parametric model, the well known Schechter function, in which we include parameterisations for the redshift evolution of absolute magnitude and number density. In comparing the results of fitting our various samples with the function we find that blue galaxies exhibit significantly different behaviour to spiral galaxies and that red galaxies exhibit significantly different behaviour to early-type galaxies.
We then go on to measure the 2-point clustering statistics of the galaxies in order to explore the dependence of galaxy clustering bias on luminosity and colour. We fit our measurements of scale dependent galaxy clustering with several phenomenological models of galaxy bias. This allows us to describe how the large-scale bias and the transition to non-linear clustering behaviour depend on luminosity and colour. Our key result from this investigation is that red and blue galaxies exhibit significantly different clustering behaviour in both the amplitude of their large scale bias and their non-linear bias contributions at smaller scales.
In conclusion we find that in order to extract the maximum amount of cosmological information from future surveys they must be planned and analysed with the understanding that galaxy clustering depends strongly on both luminosity and colour, and that galaxy morphology contains considerable information about a galaxies formation history, independent
of its colour.


Background: Suicide rose dramatically among young adults in Scotland between 1980–1982 and 1999–2001, especially among those living in deprived areas. Objective: To determine whether there are statistically significant geographical clusters of suicide and undetermined deaths among those aged 15 to 44 years in Scotland, and whether these persist through time. Methods: Deaths from suicide and undetermined causes by young adults in Scotland for three periods—1980 to 1982, 1990 to 1992, and 1999 to 2001—were aggregated into 10 058 small areas for Scotland. Tests for significant (p<0.05) geographical clustering of suicide were carried out for each period separately. Methods of suicide inside the identified clusters were compared with those in the rest of Scotland. Results: A significant geographical cluster of suicide among young adults was identified in east Glasgow in all three time periods (involving 92, 159, and 245 cases). Compared with the rest of Scotland, significantly more deaths in these clusters were caused by poisoning from liquids or solids over the entire period, but this was not the case in the most recent period (1999 to 2001). All three clusters could be explained by the concentration of socioeconomic deprivation in this part of Scotland. Conclusions: One interpretation of this large, persistent, and statistically significant cluster of suicides among young adults in east Glasgow is that suicide is geographically contagious, but the present results suggest that it is explained by the concentration of deprivation in this area. Suicide prevention strategies targeting at-risk populations living in east Glasgow are necessary to reduce the suicide burden in Scotland.


This research examined the following questions: (1) how do drug dealers acquire their inventories of prescription medications? and (2) which types of prescription medications do dealers most commonly sell? Data are drawn from a National Institute on Drug Abuse-funded research study that examined prescription drug diversion and abuse in South Florida. In-depth semi-structured interviews (n = 50) were conducted with an ethnically diverse sample of prescription drug dealers from a variety of milieus to assess patterns of diversion. Audiotapes of the interviews were transcribed, coded, and thematically analysed using the NVivo 8 software program. Dealers relied on a wide array of diversion methods including visiting multiple pain clinics, working with pharmacy employees to steal medications from pharmacies, and purchasing medications from indigent patients. The type of medication most commonly sold by dealers was prescription opioid analgesics, and to a lesser extent benzodiazepines such as alprazolam. These findings inform public health policy makers, criminal justice officials, the pharmaceutical industry and government regulatory agencies in their efforts to reduce the availability of diverted prescription drugs in the illicit market. Specifically, these data support the need for statewide prescription drug monitoring programs and increased training for healthcare workers who have access to controlled medications.


A 14-year-old girl presented to an outpatient clinic for evaluation of dizziness and fainting. She had been diagnosed with congenital hypertrophic cardiomyopathy (HCMP) after birth. Her father was 45 years old and had asymptomatic HCMP (septal wall thickness, 3.0 cm). Her younger sister also had septal hypertrophy (septal wall thickness, 3.5 cm). Her mother had no history of gestational diabetes or corticosteroid exposure. There was no history of sudden cardiac death in their family, including in their siblings. No infiltrative cardiomyopathies such as storage diseases or chromosomal abnormalities were detected. She had been lost to follow-up since the age of 7 years. One year before the herein-described presentation, she visited an outpatient clinic for exertional dyspnea. Echocardiography and cardiac magnetic resonance image (MRI) revealed 6- to 7-cm extreme septal wall hypertrophy with left mid-ventricular outflow obstruction, but without left ventricular outflow tract obstruction (Fig. 1A, parasternal long-axis echocardiography; Fig. 1B, cardiac MRI). Holter monitoring and a treadmill test revealed no abnormal findings. β-Blockers and calcium channel blockers were administered. At the present admission, an electrocardiogram (ECG) showed sustained ventricular tachycardia that was converted to sinus rhythm after 50-J direct-current cardioversion (Fig. 2A, baseline ECG; Fig. 2B, ECG on second hospitalization). She planned to undergo placement of an implantable cardioverter defibrillator that she had previously refused.

Figure 1.

Extreme septal hypertrophy (*) with mid-ventricular outflow obstruction. (A) Parasternal long-axis echocardiography. (B) Cardiac magnetic resonance image in systole.

Figure 2.

Electrocardiogram at (A) baseline and (B) second hospitalization. (A) Marked high voltage and tall T wave represent severe left ventricular hypertrophy. (B) Wide QRS tachycardia represent sustained ventricular tachycardia.

Congenital HCMP is a very rare condition that is caused by a genetic abnormality, maternal diabetes, hyperinsulinism, corticosteroid exposure, and metabolic disorders. A poor prognosis has been reported in symptomatic patients. Although clear evidence has not been provided, septal myomectomy and/or heart transplantation might be considered in refractory cases.

In summary, we have reported a patient with congenital HCMP and extreme septal hypertrophy who survived to adolescence despite symptoms of heart failure without management. We suggest a multidisciplinary approach to this rare condition for careful diagnosis and management.


We develop a uni ed equilibrium model of competitive insurance markets that incorporates the demand and supply of insurance as well as insurers' asset and liability risks. Insurers' assets may be exposed to both idiosyncratic and systemic shocks. We obtain new insights into the relationship between insurance premia and insurers' internal capital that potentially reconcile the con icting predictions of previous theories that investigate the relation using partial equilibrium frameworks. Equilibrium e ects lead to a non-monotonic U-shaped relation between insurance price and internal capital. We study the e ects of systemic risk on the optimal asset and liquidity management by insurers as well as risk-sharing between insurers and insurees. In the rst-best benchmark scenario, we show that, when systemic risk is low, both insurees and insurers hold no liquidity reserves, insurees are fully insured, and insurers bear all the systemic risk. When systemic risk takes intermediate values, both insurees and insurers still hold no liquidity reserves, but insurees partially share systemic risk with insurers. When systemic risk is high, however, both insurees and insurers hold some liquidity reserves, and insurees partially share systemic risk with insurers. The rst best asset and liquidity management policies as well as the systemic risk allocation can be implemented through a regulatory intervention policy that combines a minimum liquidity requirement, ex post taxation contingent on the aggregate state, comprehensive insurance policies, and reinsurance. We also provide implications for the solvency regulation of insurers facing systemic risk.


To investigate the association between the ambient air pollution levels during the prenatal and postnatal stages and early childhood neurobehavioral development, our study recruited 533 mother-infant pairs from 11 towns in Taiwan. All study subjects were asked to complete childhood neurobehavioral development scales and questionnaires at 6 and 18 months. Air pollution, including particulate matter ≤10 μm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and hydrocarbons, was measured at air quality monitoring stations in the towns where the subjects lived. Multilevel analyses were applied to assess the association between air pollution and childhood neurobehavioral development during pregnancy and when the children were 0 to 6 months, 7 to 12 months, and 13 to 18 months old. At 18 months, poor subclinical neurodevelopment in early childhood is associated with the average SO2 exposure of prenatal, during all trimesters of pregnancy and at postnatal ages up to 12 months (first trimester β = −0.083, se = 0.030; second and third trimester β = −0.114, se = 0.045; from birth to 12 months of age β = −0.091, se = 0.034). Furthermore, adverse gross motor below average scores at six months of age were associated with increased average non-methane hydrocarbon, (NMHC) levels during the second and third trimesters (β = −8.742, se = 3.512). Low-level SO2 exposure prenatally and up to twelve months postnatal could cause adverse neurobehavioral effects at 18 months of age. Maternal NMHC exposure during the 2nd and 3rd trimesters of pregnancy would be also associated with poor gross motor development in their children at 6 months of age.


Three-dimensional printing is a revolutionary technique that uses computer aided design software and programming to create three dimensional objects by placing material on a substrate. 3D printing is an additive layer manufacturing techniques, where consecutive layers of material are deposited or solidified to form a 3D structure. Medicinal substances is configured in three dimensional with computer assisted design module and transformed to a machine legible form which suggests the exterior emerge of the 3D dose form, then it sliced this surface into number of different printable coats and convey these layers to the machine. The different 3D printing techniques has been developing and developed to fabricate novel solid dosage forms, which are among the most well-known and discrete products today. The 3D printing process desires to be espoused by pharmaceutical sector and capable of exploring the marvels fetched by the approach. 3D printing can include a very new possibilities to optimized medicine. The current review is an effort of briefing various methods (Thermal Ink jet printing, Ink jet printing, Fused deposition modeling, Extrusion 3D Printing, Zip dose, Hot melt extrusion, 3D printer, Stereolithography, Selective laser sintering, Laser-Based Writing System, Continuous Layer Interface Production, Powder Based 3D Printing), advantages, limitations, applications of 3D printing in pharmaceutical technology.


This paper describes a scalable method for parallelizing sampling-based motion planning algorithms. It subdivides configuration space (C-space) into (possibly overlapping) regions and independently, in parallel, uses standard (sequential) sampling-based planners to construct roadmaps in each region. Next, in parallel, regional roadmaps in adjacent regions are connected to form a global roadmap. By subdividing the space and restricting the locality of connection attempts, we reduce the work and inter-processor communication associated with nearest neighbor calculation, a critical bottleneck for scalability in existing parallel motion planning methods. We show that our method is general enough to handle a variety of planning schemes, including the widely used Probabilistic Roadmap (PRM) and Rapidly-exploring Random Trees (RRT) algorithms. We compare our approach to two other existing parallel algorithms and demonstrate that our approach achieves better and more scalable performance. Our approach achieves almost linear scalability on a 2400 core LINUX cluster and on a 153,216 core Cray XE6 petascale machine.


This article is a cross-cultural study of the work of the first North American single woman missionary educator Isabella Thoburn who was sent overseas by the Woman's Foreign Missionary Society of the Methodist Episcopal Church. The objective of this article is to examine the motives of Isabella, her career in India, and the impact of her work on women's education. It also highlights the facts that Isabella was an extraordinary woman and carved spaces for herself as professional, administrator, mentor, and matriarchs, first in her parent society and then in cross-cultural contexts, for which there was no precedent. The early growth of the institution founded by Isabella enables one to remap the problematic issue of gender and culture. Isabella Thoburn College, one of the liberal Arts women's colleges in Asia, grew out of Isabella's class that began with six girls in 1870, and this institution still exists in India.


In this paper, we propose Proteus, a generic query model for the discovery of operations offered by heterogeneous services. We demonstrate the need for such a model, and show how it unifies the task of service discovery through abstractions, which allow for the technology-independent formulation of service advertisements, queries, and query responses. On top of these generic elements, we build an intuitive, fuzzy-based query evaluation mechanism that supports the service matchmaking process by employing and appropriately combining existing similarity metrics. Thanks to the generality of Proteus, it is possible to seamlessly accommodate the discovery of operations provided by various types of services without the need of changing the existing service infrastructure. Thus, our approach is applicable to a variety of settings ranging from traditional web services to service-oriented grids, peer-to-peer networks, geospatial information systems, and so on. Overall, compared to the existing query models supported by standard service discovery technologies, our approach is marked by openness, flexibility, and improved performance in terms of precision and recall. The feasibility and efficiency of Proteus are verified by a series of experiments.


Simultaneous co-channel transmission and reception, denoted as in-band full duplex (FD) communication, has been promoted as an attractive solution to improve the spectral efficiency of cellular networks. However, in addition to the selfinterference problem, cross-mode interference (i.e., between uplink and downlink) imposes a major obstacle for the deployment of FD communication in cellular networks. More specifically, the downlink to uplink interference represents the performance bottleneck for FD operation due to the uplink limited transmission power and venerable operation when compared to the downlink counterpart. While the positive impact of FD communication to the downlink performance has been proved in the literature, its effect on the uplink transmission has been neglected. This paper focuses on the effect of downlink interference on the uplink transmission in FD cellular networks in order to see whether FD communication is beneficial for the uplink transmission or not, and if yes for which type of network. To quantify the expected performance gains, we derive a closed form expression of the maximum achievable uplink capacity in FD cellular networks. In contrast to the downlink capacity which always improves with FD communication, our results show that the uplink performance may improves or degrades depending on the associated network parameters. Particularly, we show that the intensity of base stations (BSs) has a more prominent effect on the uplink performance than their transmission power.


Multiple approaches are needed to achieve robustness in speech recognition in an automobile due to various noise sources, relatively enclosed cabin acoustics, and the manner of speech of the driver under stress. A HMM‐based word recognizer was developed for automobile applications, by integrating cepstral normalization into the front end and by training model parameters in multiple conditions according to a few driving scenarios mainly in city traffic. Speaker‐dependent models were built and evaluated for a male and a female speaker using samples recorded in an automobile, and conducted a road test in city traffic. It was found that the system works well with several percentage points degradation in recognition accuracy compared with the laboratory experiments. The difference was attributed to the errors in word boundary detection.


Abstract First, we analyze how regular days off from competition and a time-dependent price pattern affect firm performance. Second, we examine the effects on firms' profitability from consumers' changing search- and timing behavior. We use microdata from gasoline retailing in Norway. From 2004 to 2017, firms practiced an industry-wide day off from competition, starting on Mondays at noon, by increasing prices to a common level given by the recommended prices (decided and published in advance). In turn, a foreseeable low-price window is open before every restoration. During the data period, we observe an additional weekly restoration on Thursdays at noon. The additional day off from competition increases firm performance. As expected, a conventional price search of where to buy reduces firms' profitability. In contrast, consumers who are aware of the cycle and spend effort on when to buy have a positive impact on firms' profitability. If consumers spend effort on when to buy, they attempt to tank during low price windows. By its very nature, this shrink consumers' ability to compare prices at several outlets. Consequently, more attention to when to buy may soften price competition.


These guidelines are designed to address the developing area of practice known as parenting coordination. In response to the recognition by family courts and substantial evidence in the empirical and clinical literature that divorce does not end patterns of high parental conflict for some families (Garrity & Baris, 1994; Hetherington, 1999; Johnston, 1994; Maccoby & Mnookin, 1992; Wallerstein & Kelly, 1980), parenting coordination interventions began to be developed more than two decades ago. In the past decade, parenting coordination work has expanded across states and jurisdictions (Kirkland, 2008; Kirkland & Sullivan, 2008). The course of the divorce process is commonly one of heightened anger and conflict, anxiety, diminished communication, and sadness or depression for one or both partners. These negative emotions are often accelerated by the separation and the adversarial nature of the divorce process. Although the majority of parents significantly diminish their anger and conflict in the first two to three years following divorce, between 8% and 15% continue to engage in conflict in the years following divorce, with little reduction in intensity of their feelings (Deutsch & Pruett, 2009; Hetherington, 1999; Hetherington & Kelly, 2002; Johnston, Roseby, & Kuehnle, 2009; Kelly, 2000, 2003; Maccoby & Mnookin, 1992; Wallerstein & Kelly, 1980). Generally, this relatively small group of parents is not able to settle their child-related disputes in custody mediation, through lawyer-assisted negotiations, or on their own. They turn to litigation in the years following separation and divorce to settle these disputes and utilize disproportionate resources and time of the courts. They are more likely to have significant psychological problems, which may interfere with their parenting, and they more often expose their children to intense conflict and intimate partner violence, also commonly referred to as domestic violence (Johnston et al., 2009). As the negative impacts of continued high conflict on children became well established in the empirical and clinical literature (Clarke-Stewart & Brentano, 2006; Deutsch & Pruett, 2009; Emery, 1999; Grych, 2005; Hetherington, 1999; Johnston et al., 2009), family court judges, divorce intervention researchers, and psychologists practicing in the divorce and family area explored alternative interventions that would diminish the use of the adversarial process to resolve child-related disputes and deal effectively with these parents to reduce the conflict to which children were exposed (e.g., Cookston, Braver, Griffin, deLusé, & Miles, 2007; Cowan, Cowan, Pruett, & Pruett, 2007; Emery, Kitzman, & Waldron, 1999; Henry, Fieldstone, & Bohac, 2009; Johnston, 2000; Kelly, 2002, 2004; Pruett & Barker, 2009; Pruett & Johnston, 2004; Sandler, Miles, Cookston, & Braver, 2008; Wolchik, Sandler, Winslow, & Smith-Daniels, 2005). Parenting coordination began gaining recognition in the 1990s as a result of presentations and trainings first offered at conferences, such as those of the Association of Family and Conciliation Courts (AFCC), and by experienced parenting coordinators (PCs). Initially, there were variations in role, source and degree of authority, and practice in different jurisdictions, and different titles were used to describe this innovative intervention model, including special masters, coparenting facilitators, or mediator/arbitrators. In 2003, AFCC appointed an interdisciplinary task force to develop guidelines for parenting coordination to guide mental health professionals, mediators, and lawyers with respect to training, practice, and ethics (AFCC Task Force on Parenting Coordination, 2006). The complex and hybrid parenting coordination model continues to be refined in professional deliberations about the role, emerging statutes and case law, and court and local rules and regulations governing parenting coordination practice at the local jurisdictional level. These American Psychological Association (APA) "Guidelines for the Practice of Parenting Coordination" are intended to provide a specific framework and direction for psychologists for professional conduct and decision making in the practice of parenting coordination. Although designed for psychologists, many aspects of these guidelines may be relevant to other professionals as well. The literature reviewed in drafting these guidelines was selected by the members of the APA Task Force for the Development of Parenting Coordination Guidelines


We present the analysis of parametric and Raman effects in the framework of a single approach. We discuss the transformation of gain spectra for Stokes and anti-Stokes waves under pump wavelength tuning from the region of positive group-velocity dispersion to the region of negative group-velocity dispersion for different types of phase-matching mechanism in a birefringent fiber.


I. INTRODUCTION The unique nature of violence between intimates presents unique challenges to prosecutors of domestic violence. In many instances, victims of domestic violence are unable or unwilling to testify. (1) As a result, much of the important evidence available against the accused is hearsay, often statements made by the victim at the time of the incident, raising issues of confrontation under the Sixth Amendment of the United States Constitution. (2) While the recent United States Supreme Court decision, Davis v. Washington, handed down in June of 2006, raised some cause for concern about the continued success of domestic violence prosecution, it also provided guidance for prosecutors facing critical issues of confrontation. (3) For purposes of battling domestic violence through prosecution, the Davis decision will force prosecutors to re-focus efforts and re-shape strategies. This Note examines the progression of Confrontation Clause jurisprudence from Ohio v. Roberts (4) to Crawford v. Washington, (5) to the recent Supreme Court decision in Davis. In particular, this Note will focus on the effect of Davis and its predecessors on the prosecution of domestic violence. Part I discusses the problems involved in the prosecution of domestic violence prior to the Crawford decision, namely the impact of the Confrontation Clause and the emergence of evidence-based prosecution. Part II details the Crawford decision and its influence on the prosecution of domestic violence. Part III carefully examines Davis, its newly articulated standard, and the factual contexts of the dual-decision. Part IV compares the application of the Davis standard in domestic violence cases around the country. Finally, Part V discusses the effect of Davis on the future of domestic violence prosecution and outlines potential solutions for the continued success of such prosecution. II. PROBLEMS IN PROSECUTION Victims of domestic violence are more likely than victims of other violent crime "to recant or refuse to cooperate" in prosecutorial efforts. (6) Some attribute these recants and refusals to the unique aspects of domestic violence. "Domestic violence is a pattern of coercive behavior that includes the physical, sexual, economic, emotional, and psychological abuse of one person by another." (7) Violence between intimates has been identified as a cyclical display of this abusive behavior. (8) Generally, abusive relationships cycle through three stages. (9) First, the "tension-building" stage, where the batterer is controlling of, and verbally abusive toward the victim, exerting power over all aspects of the victim's daily life and demeaning her independent existence and her self esteem. (10) Second, the "violent" stage, where the batterer engages in physically abusive behavior with varying levels of severity. (11) Finally, the "honeymoon" stage, where the batterer "engages in loving contrition" apologizing to the victim for his violent behavior and assuring his continued love and affection. (12) It is the cyclical nature of the abuse that creates the power dynamic between the batterer and the victim, resulting in an endless cycle of domination and control of batterer over victim. (13) Because a victim becomes the expert in reading the signs of her batterer's violence, subtle cues which would not signal a threat to the everyday observer are critical warning signs to a victim that violence is fast approaching. (15) For a victim of domestic violence, there is often no end and no escape, and the emergency is ongoing and unavoidable. (15) Commentators have identified various reasons for the recants and refusals of victims in the prosecution of domestic violence, including fear of reprisal or retaliation by the batterer, intimidation and threat by the batterer, financial dependence of the victim on the batterer, continued emotional attachment to and reuniting with the batterer, issues of custody and child support, fear that the victim or batterer will be deported, distrust of the legal system, and even "genuine belief' by the victim that no wrong was committed. …


Using data collected from two provinces in China through an online survey, the current study aimed to investigate left‐behind children's emotional and academic adjustment during the COVID‐19 pandemic in China. The participants included 1780 left‐behind (960 boys) and 1500 non‐left‐behind (811 boys) children in elementary and junior high school with a mean age of 11.23. Self‐reported questionnaires concerning children's depression, loneliness, anxiety, and academic adjustment, and parents' coping with children's negative emotions were completed. The results suggested that compared with non‐left‐behind children, left‐behind children's depression and anxiety symptoms were more severe and their academic adjustment was poorer. However, left‐behind children had lower levels of loneliness than non‐left‐behind children. Additionally, supportive coping types, especially emotion‐focused and problem‐focused reactions, were significantly negatively correlated with children's depression and anxiety. Unsupportive coping types, especially distress and punitive reactions, were significantly positively correlated with children's depression and anxiety symptoms. Moreover, the relationships between punitive reactions and depression, ignoring and loneliness and problem‐focused reactions and academic adjustment were significantly stronger in left‐behind children. Hence, during the pandemic, left‐behind children were still at a disadvantage even with their parents' company. However, parents' coping style towards left‐behind children's negative emotions played a significant role in their adjustment.


Trace textile fiber evidence is found at numerous crime scenes and plays an important role in linking a suspect to the respective scene. In this work, investigations into the fluorescence of fiber dyes and fibers themselves, as well as a methodology for discriminating between fibers using room temperature fluorescence (RTF) are reported. Initial systematic analysis was conducted on dye standards and extracts taken from fibers colored with the respective dyes of interest. Absorbance, excitation and fluorescence spectra were compared between standards and extracts to determine the optimal area of the fiber to investigate dyes, fluorescent impurities or the whole fiber. High performance liquid chromatography investigations were performed to obtain detailed information on the number of dye and fluorescent components present in extracts. Three-way Excitation Emission Matrix (EEM) data were found to give the greatest amount of spectral information and provide the highest level of discrimination. Successful discrimination between non-similar and similar fibers was achieved with the aid of second order MCR-ALS chemometric analysis. The level of discrimination obtained via RTF-EEM spectroscopy was sufficient to differentiate among two types of visually indistinguishable fibers and among fibers obtained from two separate cloths of the same material and colored with the same dye reagent.


WIPO's World Intellectual Property Indicators provides a wide range of indicators covering various areas of intellectual property: patents, utility models, trademarks, industrial designs, microorganisms and plant varieties. It draws on data from national and regional IP offices, WIPO, the World Bank and UNESCO.


Is talc the elusive "next big thing" long sought by the plaintiffs' bar? Recent verdicts against cosmetic talc defendants, including Johnson & Johnson ("J & J"), suggest that talc litigation, at a minimum, is a material threat to talc defendants and the insurance industry. In 2016, J & J and other defendants suffered three large verdicts for exposure to its baby powder in St. Louis, Mo.: $72M, $70M and $55M. All three verdicts, in a jurisdiction considered favorable to asbestos plaintiffs, included substantial punitive damages. The plaintiffs in each of these cases alleged that exposure to talc contained in J&J's baby powder caused them to contract ovarian cancer. Also in 2016, a Los Angeles jury awarded $18M to a plaintiff who sued a cosmetic talc defendant alleging exposure to cosmetic talc cause the plaintiff to contract mesothelioma. Assuming talc litigation is not going away any time soon, several questions are raised. Are all talc claims the same? What is the relationship between talc and asbestos, if any? What defendants are at risk in the talc litigation? What are the insurance implications of talc claims, and are they alike or different from asbestos and other long-tail coverage claims?


Penny Pether often focused her considerable energy and talents on marginalised, invisibilised and absent bodies and subjects. Her work also sometimes focussed on texts of national imaginaries, what she called, drawing on Robert Cover, Constitutional Epics, narratives that provide the necessary supplement to the rules of law (Cover 1983: 4-5; Pether 2009: 110-111). One of her current, unfinished, projects was a book titled 'Perverts', 'Terrorists', and Business as Usual: Comparative Indefinite Detention before and after 9/11,1 which brings together both of these concerns. Her book proposal and first chapter maps a genealogy of indefinite detention through colonial India and Ireland, US chattel slavery and Jim Crow era convict leasing, twentieth century Australian detention camps for Aboriginal people, sexually violent predator laws targeted at homosexual men post WWII that provided for the indefinite detention of 'sex psychopaths', the current mass incarceration of black men under life sentences without parole in the US, detention at Guantanamo Bay and immigration and asylum seeker detention. Her focus was on governmental imperatives, the shapes and boundaries of the nation, and constitutional epics of the indefinite detention of marginal subjects. Pether's interdisciplinary expertise across constitutional and criminal law, law and literature, critical legal studies, analyses of race and gender, colonial and postcolonial studies, and political economy, among other areas, a range matched by few scholars, is evident in even this brief sketch of her proposed book. This journal article is available in Law Text Culture: http://ro.uow.edu.au/ltc/vol19/iss1/3 39 Law Text Culture Vol 19 2015 00 Sexual Minorities and the Proliferation of Regulation in Australia's Asylum Seeker Detention Camps


BACKGROUND AND OBJECTIVE:Parental refusal and delay of childhood vaccines has increased in recent years and is believed to cluster in some communities. Such clusters could pose public health risks and barriers to achieving immunization quality benchmarks. Our aims were to (1) describe geographic clusters of underimmunization and vaccine refusal, (2) compare clusters of underimmunization with different vaccines, and (3) evaluate whether vaccine refusal clusters may pose barriers to achieving high immunization rates. METHODS: We analyzed electronic health records among children born between 2000 and 2011 with membership in Kaiser Permanente Northern California. The study population included 154 424 children in 13 counties with continuous membership from birth to 36 months of age. We used spatial scan statistics to identify clusters of underimmunization (having missed 1 or more vaccines by 36 months of age) and vaccine refusal (based on International Classification of Diseases, Ninth Revision, Clinical Modification codes). RESULTS: We identified 5 statistically significant clusters of underimmunization among children who turned 36 months old during 2010-2012. The underimmunization rate within clusters ranged from 18% to 23%, and the rate outside them was 11%. Children in the most statistically significant cluster had 1.58 (P , .001) times the rate of underimmunization as others. Underimmunization with measles, mumps, rubella vaccine and varicella vaccines clustered in similar geographic areas. Vaccine refusal also clustered, with rates of 5.5% to 13.5% within clusters, compared with 2.6% outside them. CONCLUSIONS: Underimmunization and vaccine refusal cluster geographically. Spatial scan statistics may be a useful tool to identify locations with challenges to achieving high immunization rates, which deserve focused intervention.


If there's one thing that's consistent in today's business world, it's rapid change. So how do you not only stay steady but actually grow'and quickly enough to stay safely ahead of your competitors? Built for Growth delivers specific solutions to create a brand and presence that generates true customer passion, as you lay a solid foundation for long-term success. Author Arthur Rubinfeld was a major driver in Starbucks' unprecedented retail expansion from 100 stores to more than 4000-- and its transformation into one of the world's most recognized brands. Here he draws on his singular expertise to present a proven, holistic approach to conceiving, designing, and executing your business plan: creating exciting concepts, growing them to fruition in local markets, expanding rapidly, and keeping your brand fresh and relevant as it matures. His revolutionary approach to business strategy embodies strong personal values, promotes exceptional creativity, leverages scientific methodology in finance and market analysis, and brings it all together with 'old-time' customer service.


Most sociological theories consider murder an outcome of the differential distribution of individual, neighborhood, or social characteristics. And while such studies explain variation in aggregate homicide rates, they do not explain the social order of murder, that is, who kills whom, when, where, and for what reason. This article argues that gang murder is best understood not by searching for its individual determinants but by examining the social networks of action and reaction that create it. In short, the social structure of gang murder is defined by the manner in which social networks are constructed and by people's placement in them. The author uses a network approach and incident-level homicide records to recreate and analyze the structure of gang murders in Chicago. Findings demonstrate that individual murders between gangs create an institutionalized network of group conflict, net of any individual's participation or motive. Within this network, murders spread through an epidemic-like process of social contagion as gangs evaluate the highly visible actions of others in their local networks and negotiate dominance considerations that arise during violent incidents.


Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTKs), which includes EGFR (HER1), c-erbB2 (HER2), c-erbB3 (HER3), and c-erbB4 (HER4) (1). These four receptors share an extracellular domain in N-terminal position corresponding to the ligand binding site, a transmembrane domain, and an intracellular domain in C-terminal position having tyrosine kinase (TK) activity, except for HER3, whose kinase domain is inactive. Apart for HER2, for which no ligand has been identified, for other members of the HER family, ligands bind to the receptor leading to homo- or hetero-dimerisation, and self-activation of tyrosine residues in the C terminal domain, and transduction of signal via the Ras/Raf/MEK/ERK and the PI3K/AKT/mTOR pathways (2-3) involved in cell survival, migration, apoptosis and proliferation.


ABSTRACT Extracellular signal-regulated kinase 3 (ERK3) is an unstable mitogen-activated protein kinase homologue that is constitutively degraded by the ubiquitin-proteasome pathway in proliferating cells. Here we show that a lysineless mutant of ERK3 is still ubiquitinated in vivo and requires a functional ubiquitin conjugation pathway for its degradation. Addition of N-terminal sequence tags of increasing size stabilizes ERK3 by preventing its ubiquitination. Importantly, we identified a fusion peptide between the N-terminal methionine of ERK3 and the C-terminal glycine of ubiquitin in vivo by tandem mass spectrometry analysis. These findings demonstrate that ERK3 is conjugated to ubiquitin via its free NH2 terminus. We found that large N-terminal tags also stabilize the expression of the cell cycle inhibitor p21 but not that of substrates ubiquitinated on internal lysine residues. Consistent with this observation, lysineless p21 is ubiquitinated and degraded in a ubiquitin-dependent manner in intact cells. Our results suggests that N-terminal ubiquitination is a more prevalent modification than originally recognized.


Alignment nanofibers of PAni.CSA/PEO blends with different concentration of polyethylene oxide (PEO) have been prepared using the electrospinning technique. The details of the preparation method are well described. The method is relatively simple and is easily controlled. A systematic investigation on the effect of annealing temperature on the structure of PAni.CSA/PEO nanofibers was studied. Morphology and diameters of the as-spun and annealing nanofibers were studied byAtomic ForceMicroscope and found the annealing increases the nanofiber diameter and had clear effect on the morphology and orientation of nanofibers. The X-ray diffraction analysis shows the effect of annealing on the nanofibers PAni.CSA/PEO crystallization is unsystematic and depended on the concentration of PEO in the blend.