The Little Ice Age in Scientiac Perspective: Cold Spells and Caveats In "The Waning of the Little Ice Age: Climate Change in Early Modern Europe," Kelly and Ó Gráda argue that European temperature estimates extending back into late medieval times contain no major breaks, cycles, or trends, that could be associated with a Little Ice Age (lia). They use a selection of frost fairs and contracting glaciers, as well as disappearing British vineyards and Arctic colonies, to imply the irrelevance of climate forcing and sequential cooling. The arst sentence of their abstract in this issue's table of contents, aptly, if skeptically, posits the existence of a cool lia period and its putative consequences for economic, political, and cultural history, far beyond the realm of climatology: "The supposed ramiacations of the Little Ice Age, a period of cooling temperatures straddling several centuries in northwestern Europe, reach far beyond meteorology into economic, political, and cultural history." Clearly, the issues surrounding the lia are complex.1 This comment on their article points to several factors that challenge the hypothesis of a missing palaeoclimatic signal for the


During the last fifteen years a fundamental change has occurred in the settlement patterns associated with resource projects in remote regions of Australia and Canada. The earlier practice of establishing new mine townships has virtually ceased. Most new projects rely on a "rotational" workforce which is regularly transported between the work site and scheduled pick-up points. These are typically major population centers, where the workers' families continue to reside. This shift to Long Distance Commuting (LDC) has profound implications for native peoples, but as yet these implications are poorly understood. The information which is available indicates that while LDC allows some native people to reconcile their need to earn cash incomes with their desire to maintain elements of a traditional lifestyle, it can also have negative effects both on individuals and on native societies. A number of areas are identified where additional research is needed if native peoples are to be in a position to make informe...


Background Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow limitation, is a highly prevalent lung disease worldwide and imposes increasing disease burdens globally. Emphysema is one of the primary pathological features contributing to the irreversible decline of pulmonary function in COPD patients, but the pathogenetic mechanisms remain unclear. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein localized in the secretory pathway of living cells. Rcn3 in type II alveolar epithelial cell (AECIIs) has been reported to play a critical role in regulating perinatal lung development and bleomycin-induced lung injury-repair processes. We hypothesized that Rcn3 deficiency is associated with the development of emphysema during COPD, which is associated with the dysfunction of injury-repair modulated by alveolar epithelial cells. Materials and Methods We examined Rcn3 expression in lung specimens from COPD patients and non-COPD control patients undergoing lung lobectomy or pneumonectomy. Two mouse models of emphysema were established by cigarette smoke (CS) exposure and intratracheal instillation of porcine pancreatic elastase (PPE). Rcn3 expression was detected in the lung tissues from these mice. Furthermore, conditional knockout (CKO) mice with Rcn3 deletion specific to AECIIs were used to explore the role of Rcn3 in PPE-induced emphysema progression. Rcn3 protein expression in lung tissues was evaluated by Western blot and immunohistochemistry. Rcn3 mRNA expression in lung tissues was detected by qPCR. Results Rcn3 expression was significantly increased in the lung specimens from COPD patients versus non-COPD patients and the level of Rcn3 increase was associated with the degree of emphysema. Rcn3 expression were also significantly up-regulated in both CS-induced and PPE-induced emphysematous mouse lungs. Moreover, the selective ablation of Rcn3 in AECIIs significantly alleviated severity of the mouse emphysema in response to intratracheal installation of PPE. Conclusion Our data, for the first time, indicated that suppression of Rcn3 expression in AECIIs has a beneficial effect on PPE-induced emphysema.


Poly(aniline-co-o-anthranilic acid (PAA) copolymers which are soluble in aqueous alkaline solutions and in some organic solvents were obtained from the chemical polymerization of aniline and o-anthranilic acid. The copolymers have MWs ranging from 84K to 126K depending on the composition. The copolymers are recovered in the oxidized state and have a strong EPR signal. The FTIR and UV-visible spectra indicated that the anthranilic acid groups restrict the n-conjugation along the polymer chain. The electrical conductivity of the PAA copolymers decreases dramatically along the series from the polyaniline value of 5.2 S/cm to the poly(o-anthranilic acid) value of 10 -8 S/cm. Films of the PAA copolymers on a platinum foil can be oxidized and reduced at potentials between 0.0 and 1.0 V vs the Ag/AgCl reference electrode when immersed in 1.2 M HCl. The waves in the voltammogram for the stepwise oxidation of the polymer which are normally observed with polyaniline become merged into a single broad wave with the incorporation of the anthranilic acid. The films exhibited multiple color changes from clear yellow to green to dark brown during the redox process. Poly(o-anthranilic acid) itself is fairly inactive, revealing little or no electrical conductivity and electroactivity


Background: Chronic obstructive pulmonary disease (COPD) is a preventable disease with some significant extra pulmonary effects that may contribute to the severity in individual patients.. The systemic manifestations  of  COPD  include  a number of endocrine disorders , such  as  those  involving the pituitary, the thyroid , the gonads, the adrenals  and  the pancreas.  The  mechanisms  by which COPD  alters  endocrine function are incompletely understood  but likely involve  hypoxemia , hypercapnia , systemic inflammation and  glucocorticoid  administration.
Objective:  To evaluate the relationship between pulmonary function tests and thyroid gland function in patient with chronic obstructive pulmonary disease (COPD).
Subjects and Methods:  Cross  sectional  study   was  done  in  Baghdad teaching hospital  from  April 2012  to October  2012  in  respiratory  outpatient. Thirty eight  patients  were  included  in  the study (36 male  and  2 females) who  had  stable  COPD ,  thyroid function tests and FEV1%  were  done  to all of  them.  Patients  were  classified  into four  groups  according  to GOLD criteria: mild  COPD ( > 80) FEV1% , moderate  (80 – 50)%,  severe ( 50 – 30)% and  very severe < 30%.
Results: one  patient   has  decreased  level   of  TSH , one patient has decreased T3 hormone and one patient has increased free T3 hormone level, all other  patient  had  normal  thyroid  hormones  levels. The results of study showed no significant changes in thyroid hormones concentrations with COPD and its severity.
Conclusion:  We found no significant changes in thyroid hormones in patients with COPD, and any changes that occur in TFT in these patients are may be due to other causes than COPD.


Author(s): Chang, Young Hwan | Advisor(s): Tomlin, Claire | Abstract: Breast cancer signaling pathways and neural systems are composed of networks of mutually dependent and thus interconnected genes or neurons. Systems biology is an emerging interdisciplinary field of study that focuses on understanding these complex interactions using a systematic approach. The main goal is transforming biology into a fully quantitative, theory-rich science to understand complex behavior and produce effective predictions. However, since often only incomplete abstracted hypotheses exist to explain observed complex behavior and functions, new techniques for identifying breast cancer signaling pathways and neural systems need to be able to incorporate different types of experimental data and varying levels of prior knowledge.This dissertation describes several efforts aimed towards an understanding of these systems by developing system identification tools and computational analysis techniques to facilitate these studies. In systems biology, models may focus on different features, different aspects and different objectives, so there can exist several model classes. The first class of tools that we present includes the hybrid Boolean framework and optimization-based inference, and is developed in conjunction with existing mathematical tools. For example, the former is a combination of ordinary differential equations (ODEs) and Boolean networks (BNs), and the latter is that of graph models and linear time-varying systems. These tools take advantage of existing mathematical models and compensate for their limitations or disadvantages. The second class of tools that we present includes data-driven graph reconstruction using compressive sensing, discrete mode identification via sparse subspace clustering, and low-rank representation of neural activity. These adopt a data-driven approach using little prior knowledge which has its origin in the computer vision literature. Case studies of Human Epidermal growth factor Receptor 2 overexpressed breast cancer and neural systems for a Brain Machine Interface are given. Since the challenge in systems biology has become to show that the identified networks and corresponding mathematical models are enough to represent the underlying system, these tools are developed both for identifying models and also suggesting experimental directions to better understand the systems. The ultimate goal of the work presented is to create a framework to broaden the spectrum of different modeling approaches since each model can be described through a different perspective and may highlight different aspects of the system.


Viral hepatitis B (HBV) and hepatitis C (HCV) pose a major health problem globally and if untreated, both viruses lead to severe liver damage resulting in liver cirrhosis and cancer. While HBV has a vaccine, HCV has none at the moment. The risk of drug resistance, combined with the high cost of current therapies, makes it a necessity for cost-effective therapeutics to be discovered and developed. The recent surge in interest in Medical Cannabis has led to interest in evaluating and validating the therapeutic potentials of Cannabis and its metabolites against various diseases including viruses. Preliminary screening of cannabidiol (CBD) revealed that CBD is active against HCV but not against HBV in vitro. CBD inhibited HCV replication by 86.4% at a single concentration of 10 μM with EC50of 3.163 μM in a dose-response assay. These findings suggest that CBD could be further developed and used therapeutically against HCV.


Foliar ozone (O3) injury is common on watermelon grown in eastern North Carolina. During the 2000 and 2001 growing seasons, 93 cultivars and breeding lines (i.e., cultigens) were evaluated for foliar injury caused by ambient levels of O3. One tetraploid, 42 diploid, and 50 triploid cultigens were evaluated. Injury developed on all cultigens in both years, but severity of injury varied among cultigens and between years. Visible foliar injury (percent surface area necrotic or chlorotic) was rated 1 week after the first harvest in both years. Mean injury for all cultigens was 39% in 2000 (range = 16 to 66%) and 20% in 2001 (range = 2.5 to 60%). This corresponded to greater mean seasonal O3 levels (12-h [0900 to 2100 h EST] mean daily O3 concentration between early May and mid-June) in 2000 (58 ppb) than in 2001 (52 ppb). Triploid cultigens were less sensitive to injury than diploid cultigens. Mean injury for all triploids was 31% in 2000 and 16% in 2001, whereas injury for diploids was 47% in 2000 and 25% in 2001. Injury level was consistently negatively correlated with average number of days between transplanting and harvest. Correlations between injury level and yield, fruit size, fruit shape, and fruit sweetness were inconsistent between years and/or insignificant. O3 tolerance in watermelon cultivars should receive increased attention in watermelon breeding programs and in cultivar selection in areas of high O3 pollution.


This paper focuses on the analysis and synthesis of hypo and hyperarticulated speech in the framework of HMM-based speech synthesis. First of all, a new French database matching our needs was created, which contains three identical sets, pronounced with three different degrees of articulation: neutral, hypo and hyperarticulated speech. On that basis, acoustic and phonetic analyses were performed. It is shown that the degrees of articulation significantly influence, on one hand, both vocal tract and glottal characteristics, and on the other hand, speech rate, phone durations, phone variations and the presence of glottal stops. Finally, neutral, hypo and hyperarticulated speech are synthesized using HMM-based speech synthesis and both objective and subjective tests aiming at assessing the generated speech quality are performed. These tests show that synthesized hypoarticulated speech seems to be less naturally rendered than neutral and hyperarticulated speech.


We investigate the current transfer in strongly-coupled oriented superconductors of the MgB2 type and related system by Monte Carlo simulation. Taking into account the grain boundary effects on the critical current density JcG in a separate grain (L. V. Belevtsov, Europhys. Lett. 59 (2002) 768) we extend our study to the bulk characteristics of transport. The motivation for this work was to investigate the dependence of bulk Jc on magnetic field, grain-coupling strength, normalized grain size and mass anisotropy. We have found the strong correlation between the grain and massive transport properties.


We report the preparation of a new type of anion exchange membrane (AEM) from a random terpolymer of poly n-butyl acrylate (PnBA), polyacrylonitrile (PAN) and poly(2-dimethyl aminoethyl)methacrylate (PDMA) through quaternization and cross-linking. Moderate amounts of hydrophobic and soft PnBA (ca. 18 wt%) in the terpolymer considerably influenced the electrochemical properties and desalination performance of the membrane. Standardization experiments revealed that a membrane (AEM-2) prepared from a terpolymer containing 18 wt% PnBA, 50 wt% PAN and 32 wt% PDMA exhibited low power consumption (W) (0.66–0.95 kW h kg−1) and high current efficiency (CE) (94–96%) at an applied potential of 1.5–2 volts per cell pair during the desalination of water (containing 2000 mg L−1 NaCl) via electrodialysis (ED). On the other hand, membranes prepared from the bi-component PAN-co-PDMA with a similar PDMA content (28–34 wt%) exhibited a relatively higher W (0.94–1.32 kW h kg−1) and lower CE (68–80%) under similar experimental conditions compared to AEM-2. The remarkable effect of hydrophobic PnBA on AEM-2 performance is attributed to the nanophase separation of quaternized PAN-co-PDMA domains, low degree of water uptake (12%) along with the absence of freezing bound water in the membrane. Rapid desalination (low W) with high CE by five pairs of alternative AEM-2 and standard cation exchange membrane in the ED unit (13 × 5 cm2) shows promise for the development of en energy efficient ED unit.


In this paper, the latent stochastic frontier model is used to estimate the technical efficiency of UK airports. These airports are ranked according to their technical efficiency for the period 2000--06 and the airports are disentangled and segmented by the cost frontier model, which leads us to advise the implementation of policies by segments. Economic implications arising from the study are also considered.


Humans, like their close primate relatives, live in social networks based primarily on family group membership. They are therefore born into a world which is rich in potential teachers and learning experiences. Research has shown that even in infancy we are adept at interpreting subtle social signals that we observe in the interactions that occur around us. Social referencing studies provide evidence that infants utilise emotional expressions as a source of feedback and knowledge regarding stimuli in their environment (e.g. Feinman & Lewis, 1983; Sorce, Emde, Campos & Klinnert, 1985; Hornik & Gunnar, 1988), and looking-time studies have indicated infants' can not only to encode preference information from emotional expressions to predict agents' object-targeted actions (e.g. Kuhlmeier, Wynn & Bloom, 2003), but also form expectations regarding social affiliations on the basis of interactions they observe. However, no research has investigated infants' ability to utilise emotional expressions in the social domain to encode information about third-party social affiliations. The present thesis aimed to address this shortfall in current understanding and provides evidence that by 14 months infants successfully predict the outcome of social interactions on the basis of the valence of emotional displays of one actress toward another, thereby extending upon results in the object domain (Gergely, Egyed & Kiralyi, 2007). Mediating factors influencing infants' processing of attitude information are identified, including the presence or absence of ostensive cues, the availability of alternative preference information and the relative frequency of information presentation. Findings are discussed in terms of their implications for our understanding of not only infants' emerging social processing skills but also for theories on learning, specifically Csibra and Gergely's proposed Pedagogical System (2006), and future research directions regarding the processes underlying infants' differential information processing in ostensive and non-ostensive learning episodes are outlined.


A novel approach to the treatment of bone tumors using tissue-engineered implants is reported in this study. The number of mesenchymal stem cells (MSCs) obtained from each patient's bone marrow cells was first increased, and the MSCs were forced to differentiate into osteoblasts followed by bone matrix formation on hydroxyapatite (HA) ceramics. The strong osteogenic ability of the implants, as evidenced by high osteoblastic activity, was confirmed. Consequently, the HA surface was covered with the patient's derived cultured osteoblast/bone matrix. The tissue-engineered HA was used to fill the patient's bone cavity after tumor curettage. Immediate healing potential was found by serial plain radiographs and computed tomograhy images, and no adverse reactions were noted in these patients. The results indicate that tissue-engineered osteogenic ceramics might be an alternative to autologous bone grafts.


In celebrating Sustainable Food Systems, World Food Day is recognising the need for systemic change to end hunger and malnutrition. Systemic change is urgent because even though for decades the world has produced one and half times enough food for every man, woman and child on the planet, nearly 840 million people go hungry while almost 870 million are chronically undernourished. Unsustainable models of development and uncontrolled population growth are degrading the natural environment, threatening ecosystems and biodiversity that will be needed for our future food supply.


A permanent field station, Sermilikstationen, was opened by the University of Kobenhavn in 1970 at Mitdluagkat Gletscher on Angmagssalik 0, west Greenland. It is some 30 km from the town of Angmagssalik and has reasonably easy connections with the airfields at Kulusuk and Stondre Stromfjord. The building consists of a Norwegian "Langmoen" mountain hut built of prefabricated insulated components and measuring 16-2 x 66 m. It contains three bedrooms, each equipped for two persons, together with a wash room, kitchen, and living area. There is also a store-room built some distance away in case of fire. Training of students and field-work in physico-geographical studies will be based at the hut.


Objective: The study aimed to investigate the acute effect of a single dose of green tea on the quality and quantity of tears in normal eye subjects. Methods: Forty normal eye subjects (22 men and 18 women) aged 19–39 years were enrolled in the study. Also, an age matching control group (20 males and 20 females) was enrolled for comparison. McMonnies dry eye symptoms questionnaire and slit lamp were used for the exclusion criteria determination. Phenol red thread (PRT) test was performed on both eyes of each subject. A tear sample was collected from the lower tear meniscus of the right eye of each subject for the tear ferning (TF) test, which was performed before (30 minutes) and after (60 minutes) drinking green tea. Results: The median PRT measurement after green tea consumption was lower (median [IQR] = 23.50 [8.00] mm) compared to that before consumption (median [IQR] = 27.00 [8.75] mm). In contrast, the median TF grade was significantly higher following green tea consumption than that before consumption (median [IQR] = 2.65 [1.23] vs 1.50 [0.88] mm, respectively). The results show that TF grades increased in 97.5%, and the red phenol thread scores decreased in 80% of the subjects after green tea consumption compared to those before consumption. The PRT readings and TF grades were significantly different ( P , 0.05) before and after green tea consumption. Conclusion: Drinking green tea could have a significant effect on the eye tear film quality. Tear quality appeared to decrease after green tea consumption. 10,11 and antiviral activities. 12 In addition, green tea has beneficial effects against degenerative diseases, 13 oxidative stress, 14 and chronic diseases, 15 and decreases the body fat, 4 lipid profile, 16 and body weight.


This retrospective study conducted within a large paediatric clinical practice identified eleven patients who were operated on during the period of 1996-2011, using the Anderson-Kestenbaum procedure. These patients, aged 4 to 17 years, were operated on by the same surgeon. Visual acuity was measured using age-appropriate linear or single optotypes and results were compared pre- and post-operatively. Observations of head posture by ophthalmologist, orthoptist and parent were recorded pre- and post-operatively. Results showed the Anderson-Kestenbaum procedure reduced the compensatory head posture and improved visual acuity in 75% of patients, with a mean improvement in visual acuity of 3.75 letters. Patients showed minimal residual head posture. This study is limited by its retrospective nature and small subject numbers.


The term 'bone strength' is often used to explain why some children's bones fracture while others do not. Bone strength describes the general integrity of bone; a complex organ with multiple structural levels and an array of biomechanical properties. Key biomechanical properties of bone include stiffness, toughness, ductility and mechanical strength. When measured in bone tissue, these properties are known as the intrinsic biomechanical properties of bone, while the extrinsic biomechanical properties reflect the structural behaviour of a whole bone. The fine balance between various and often opposing intrinsic and extrinsic biomechanical properties of bone is crucial for fracture resistance. When clinically evaluating a child with a fracture, an understanding of basic bone biomechanics helps determine the likely mechanism of injury and whether underlying reduced fracture resistance exists.


Traumatic spinal cord injury causes an inflammatory reaction involving blood-derived macrophages and central nervous system (CNS)-resident microglia. Intra-vital two-photon microscopy enables the study of macrophages and microglia in the spinal cord lesion in the living animal. This can be performed in adult animals with a traumatic injury to the dorsal column. Here, we describe methods for distinguishing macrophages from microglia in the CNS using an irradiation bone marrow chimera to obtain animals in which only macrophages or microglia are labeled with a genetically encoded green fluorescent protein. We also describe a injury model that crushes the dorsal column of the spinal cord, thereby producing a simple, easily accessible, rectangular lesion that is easily visualized in an animal through a laminectomy. Furthermore, we will outline procedures to sequentially image the animals at the anatomical site of injury for the study of cellular interactions during the first few days to weeks after injury.


INTRODUCTION
Trophozoites of Giardia lamblia present in the upper gastro-intestinal tract may cause inflammation of the duodenal mucosa, impair secretory activity of goblet cells, damage the enterocytes, and in case of intestinal villi atrophy, they may induce the malabsorption syndrome. The increase in number of endothelial lymphocytes in the epithelium of the duodenal mucosa indicates the involvement of local immune processes. THE AIM of the study was to assess the concentrations of chosen cytokines in the gastric mucosa in children infested with Giardia lamblia, before and after treatment, with simultaneous morphological evaluation of the duodenal mucosa before treatment.

MATERIAL AND METHODS
The study included 12 children infested with Giardia lamblia and 15 children constituting controls. Giardiasis was diagnosed basing on the presence of trophozoites in the mucus taken from the duodenum during endoscopy (brush swab). In all patients, samples from the prepyloric section of the gastric and duodenal mucosa were examined histologically. In bioptates, concentrations of chosen cytokines were determined by ELISA method.

RESULTS
Histopathological examination of the gastric mucosa showed chronic antral gastritis in 8.3% and duodenal mucosa inflammation in 58.3%. Mean concentrations of cytokines determined in the antral mucosa before treatment equaled: IL-2 - 53.1; IL-4 -27.7; IL-5 -39.4; IL-8 - 41.4; IL-10 - 33.0; IFN-gamma - 60.3; TNF-alpha - 27.7 pq/mg of protein. Concentrations of mucosal cytokines, apart from IL-10 (82.7 pq/mg of protein), decreased due to targeted treatment with the simultaneous improvement of histopathological changes reported before treatment.

CONCLUSION
In children infested with Giardia lamblia, an increased local production of proinflammatory and proallergic cytokines was observed in the gastric mucosa.


The History of Medicine Division of the National Library of Medicine has prepared a bibliography of imprints published in the United States before 1821. Robert B. Austin, who has recently retired after 30 years of service to the Library, was largely responsible for the volume. Approximately 70 libraries or societies are the repositories for the items listed, including the Royal College of Surgeons of England. There are several imprints that seem to me especially worthy of note. Undoubtedly, others would compile quite a different list of interests. The activities of county and state medical societies and county and city health departments are well documented in this period. Nine editions of William Cullen's First Lines of the Practice of Physic were published between 1781 and 1816 and 3 editions of his Synopsis of Methodical Nosology between 1783 and 1793. Daniel DeFoe's story of the 1665 epidemic of the plague in London


We present novel exact expressions and accurate closed-form approximations for the level crossing rate (LCR) and the average fade duration (AFD) of the double Nakagami-m random process. These results are used to study the second order statistics of multiple input multiple output (MIMO) keyhole fading channels with space-time block coding. Numerical and computer simulation examples validate the accuracy of the presented mathematical analysis and show the tightness of the proposed approximations.


Gonadotrophin treatment was given to 81 patients with functional sterility. Individualised dosage proved possible, depending on close therapeutic monitoring. General input can be rationalised along with growing experience.--WHO Group I included 7.4 per cent of the patients reviewed. The pregnancy rate of this Group was 83 per cent. WHO Group II included 90.4 per cent. Their pregnancy rate was 37 per cent. Clomiphene failure was recorded from 79 per cent of the patients. The overall pregnancy rate amounted to 39.5 per cent, even with additional presence of tubal and andrological sterility factors. Overstimulation was recordable from 18.5 per cent of the probands. Multiple pregnancy occurred to 9.4 per cent. Rates of abortion could be kept as low as 9.4 per cent by early sick leave and progesterone substitution.--Young age of patient, short time of desire of children, and hypogonadotrophic normoprolactinaemic amenorrhoea proved to be the most favourable set of indications for gonadotrophin therapy.


The amino-terminal-copper-and-nickel-binding (ATCUN) motif, a tripeptide sequence ending with a histidine, confers important functions to proteins and peptides. Few high-resolution studies have been performed on the ATCUN motifs of membrane-associated proteins and peptides, limiting our understanding of how they stabilize Cu2+/Ni2+ in membranes. Here, we leverage solid-state NMR to investigate metal-binding to piscidin-1 (P1), a host-defense peptide featuring F1F2H3 as its ATCUN motif. Bound to redox ions, P1 chemically and physically damages pathogenic cell membranes. We design 13C/15N correlation experiments to detect and assign the deprotonated nitrogens produced and/or shifted by Ni2+-binding. Occupying multiple chemical states in P1-apo, H3 and the neighboring H4 respond to metalation by populating only the τ-tautomer. H3, as a proximal histidine, directly coordinates the metal, compared to the distal H4. Density functional theory calculations reflect this noncanonical arrangement and point toward cation-π interactions between the F1/F2/H4 aromatic rings and metal. These structural findings, which are relevant to other ATCUN-containing membrane peptides, could help design new therapeutics and materials for use in the areas of drug-resistant bacteria, neurological disorders, and biomedical imaging.


Molecular mechanisms governing the development of mammalian cochlea, the hearing organ, remain largely unknown. Through genome sequencing in three subjects from two families with non-syndromic cochlear aplasia, we identified homozygous 221 KB and 338 KB deletions in a non-coding region on chromosome 8 with an ~200 KB overlapping section. Genomic location of the overlapping deleted region was starting from ~350 KB downstream of GDF6. Otic lineage cells differentiated from induced pluripotent stem cells derived from an affected individual show reduced expression of GDF6 compared to control cells. A mouse knock-out of Gdf6 reveals cochlear aplasia closely resembling the human phenotype. We conclude that GDF6 plays a necessary role in early cochlear development controlled by cis-regulatory elements located within ~500 KB region of the genome in humans and that its disruption leads to deafness due to cochlear aplasia.


Abstract: This article aims to study the effects of shock-disturbed cracks on the cutting features of cone bits. By utilizing the Walsh's model, a crack model was established for the damaged rock surrounding the induced hole, the intrusive coefficient of the cone bit was derived, and the drilling rate equation around the induced hole was formulated. The effects of crack density and disturbance frequency on elastic modulus, intrusive coefficient, and cutting force were studied. With an increase in crack density, both the effective elastic modulus and the intrusive coefficient decreased. Under a certain range of internal friction angle, with an increase in crack density, the drilling rate increased. Under a certain axial load, as the disturbance frequency increased, the cutting force of one-cone bits decreased.


(1) Secretory epithelia and the active transport of ions; (2) Electrical and chemical excitation. The scientific programme will also include symposia organised by the Union's Special and Affiliated Commissions on (3) The role of proteins in membranes; (4) Ionic channels; ionophores, and noise in membranes; (5) The dynamics of macromolecules; (6) Spectroscopic methods and biological structure; (7) Cell injury and repair processes; (8) Fundamental studies with light and other types of radiation; (9) The assembly and structure of membranes; (10) Bioenergetics; (11) Contractile systems; (12) Structural characteristics and rheology of biological membranes. On two evenings there will be symposia in memory of Aharon Katchalsky. Contributed communications will be presented at 'Poster sessions'. Those wishing to attend the Congress should apply for pre-registration forms to:


Background: Host response to M. tuberculosis (M.tb) infection leads to tissue destruction and impairs the ability of drugs to reach the bacteria. New anti-inflammatory adjuvant therapies could enhance bacterial clearance. Curcumin (diferuloylmethane) is a lipophilic phytochemical present in turmeric (Curcuma longa). Encapsulation of curcumin with polymers (NanoCurcuminTM) increased absorption and bioavailability of curcumin and is being investigated as host-directed therapies for the treatment various diseases. Methods and Results: We investigated the effect of free and encapsulated NanocurcuminTM on M.tb induced host inflammatory responses in M.tb infected J774 macrophages. Bacterial burden and cytokine levels were enumerated by standard microbiological and immunological methods. We utilized physiologically achievable levels of NanocurcuminTM (based on prior in vivo studies) and found a dose dependent decrease in the levels of TNF-α in M.tb infected J774 macrophages. Conclusions: NanoCurcumin™ can modulate TNF-α and could be utilized as a host-directed therapy to enhanced bacterial clearance and potentially shorten TB drug regimen.


AIM
To specify a 24-h profile of arterial pressure (AP) in hypertensive patients working in duty regime in the Far North (Tyumen Region).

MATERIAL AND METHODS
AP parameters were studied in 155 males aged 25-59 with hypertension of stage I, II who were employed for duty work in the Far North areas and 38 control patients with hypertension stage I, II living in a moderate climatic zone (Tyumen). The groups were comparable by gender, age, duration of hypertension, office systolic and diastolic AP (SAP and DAP). All the patients have undergone 24-h monitoring of AP with assessment of basic mean parameters.

RESULTS
The study group patients had scare symptoms and lower mean 24-h SAP, but high AP variability, high DAD as reflection of more significant structural changes of vessels and special functioning of the autonomic nervous system in the North. Mean 24-h AP showed more unfavourable changes in hypertensive subjects who had flight from Yamburg-Moscow-Yamburg.

CONCLUSION
The data of the study dictate the necessity to develop a differentiated risk strategy for health promotion, prevention and treatment of hypertension in those who work in the North of Tyumen Region in duty regime.


Time series data compression is emerging as an important problem with the growth in IoT devices and sensors. Due to the presence of noise in these datasets, lossy compression can often provide significant compression gains without impacting the performance of downstream applications. In this work, we propose an error-bounded lossy compressor, LFZip, for multivariate floating-point time series data that provides guaranteed reconstruction up to user-specified maximum absolute error. The compressor is based on the prediction-quantization-entropy coder framework and benefits from improved prediction using linear models and neural networks. We evaluate the compressor on several time series datasets where it outperforms the existing state-of-the-art error-bounded lossy compressors. The code and data are available at https://github.com/shubhamchandak94/LFZip.


Most Chinese pre-trained models take character as the basic unit and learn representation according to character's external contexts, ignoring the semantics expressed in the word, which is the smallest meaningful utterance in Chinese. Hence, we propose a novel word-aligned attention to exploit explicit word information, which is complementary to various character-based Chinese pre-trained language models. Specifically, we devise a pooling mechanism to align the character-level attention to the word level and propose to alleviate the potential issue of segmentation error propagation by multi-source information fusion. As a result, word and character information are explicitly integrated at the fine-tuning procedure. Experimental results on five Chinese NLP benchmark tasks demonstrate that our method achieves significant improvements against BERT, ERNIE and BERT-wwm.


This publication provides a comprehensive overview of topics related to the assessment, analysis, and management of various types of risks in the field of Islamic banking. It is an attempt to provide a high-level framework (aimed at non-specialist executives) attuned to the current realities of changing economies and Islamic financial markets. The Islamic financial system is not limited to banking; it also covers capital formation, capital markets, and all types of financial intermediation and risk transfer. Islamic finance was practiced predominantly in the Muslim world throughout the middle ages, fostering trade and business activities with the development of credit. The growth of Islamic finance coincided with the current account surpluses of oil-exporting Islamic countries. The Middle East saw a mushrooming of small commercial banks competing for surplus funds. The Islamic Republics of Iran, Pakistan, and Sudan announced their intention to make their financial systems compliant with Shariah.


Describes the first-phase of an investigation into techniques for automatic cloud masking in remote sensing data. BCM Projection Pursuit networks are explored as a method of unsupervised feature extraction from AVIRIS images. Search vectors in this method discover directions in the data in which the projected data is skew or multimodal, by minimizing a projection index which depends on higher moments of the projected data distribution. Ensemble methods are used to fuse information from extracted BCM features and to smooth the mapping of these features to classification of image pixels. Ensemble hierarchies contain multiple levels of networks, combining BCM at the lowest levels with backward propagation (BP) algorithms, based on cross-entropy minimization, at higher levels in the ensembles. Predicted cloud masks are compared against cloud masks derived from human interpretation; ensembles achieve better overall classification accuracy than single BP networks.<<ETX>>


Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high-fat diet (HF). At day 18.5 (term=19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.


Evaluation of a neuropathological series of 160 HIV infected patients, almost all in the terminal AIDS stage of the infection, allowed recognition of novel syndromes which can be regarded as HIV specific neuropathology because: 1) they are not observed in non HIV tissues; 2) HIV is, in our hands consistently by immunocytochemistry, demonstrable in large amounts within these lesions; 3) other pathogens are not detectable within these lesions; and 4) these lesions may occur in isolated fashion within CNS tissues (40% of HIV‐specific neuropathology in this series), without any other CNS pathology. HIV specific neuropathology was found in 34% in this series and comprised two prototypes within a spectrum of frequently overlapping changes: multifocal microgranulomatous lesions of HIV encephalitis, and diffuse white matter damage of HIV leukoencephalopathy. In almost all cases, multinucleated giant cells signal the local presence of HIV in routine stains. In contrast to HIV‐specific neuropathology, various unspecific nervous tissue syndromes do not consistently exhibit the local presence of HIV and thus are designated HIV associated or possibly HIV induced lesions: lymphocytic meningitis, vacuolar myelopathy, multifocal vacuolar leukoencephalopathy, and diffuse poliodystrophy. Although these unspecific syndromes may also contribute to clinical manifestations, their pathogenetic relation with HIV remains to be established.


Steeply tilted late Oligocene caldera systems in the Stillwater caldera complex record a number of unusual features including extreme thickness of caldera-related deposits (>4–5.5 km), lack of conclusive evidence for structural doming of the calderas despite intrusion of cogenetic plutonic rocks, and preservation of vertical compositional zoning in the plutonic rocks. The Stillwater caldera complex comprises three partly overlapping ash-flow calderas and subjacent plutonic rocks that were steeply tilted during early Miocene extension. The calderas and cogenetic plutonic rocks are exposed in cross section over an unusually large depth range of ∼10 km.

The Job Canyon caldera, the oldest (ca. 29–28 Ma) caldera, consists of two structural blocks. The north block consists of 0–1500 m of precollapse intermediate composition lava flows and breccias overlain by 2000 m of intracaldera rhyolite ash-flow tuff locally interbedded with thick sequences of caldera-collapse breccia, overlain in turn by 2500 m of intermediate lava flows and minor lacustrine and fluvial sedimentary rocks. The south block consists of thinner sequences (total thickness ≤2500 m) of intermediate lava flows and ash-flow tuff with local interbedded collapse breccia. The north part of the caldera is intruded by the cogenetic IXL pluton, which is vertically zoned downward from granodiorite to quartz monzodiorite.

The 25 to 23 Ma Poco Canyon and Elevenmile Canyon calderas and underlying Freeman Creek pluton overlap in time and space with each other. Caldera-related deposits in the Poco Canyon caldera comprise two cooling units of crystal-rich rhyolite and high-silica rhyolite tuff (tuff of Poco Canyon) separated by a unit of crystal-poor high-silica rhyolite tuff and caldera-collapse breccia (megabreccia of Government Trail Canyon) and by a thick unit of crystal-rich rhyolite and trachydacite ash-flow tuff related to the Elevenmile Canyon caldera (tuff of Elevenmile Canyon). Total thickness of caldera-related deposits is locally >4500 m in the Poco Canyon caldera. The Elevenmile Canyon caldera is filled by >3000 m of ash-flow tuff (tuff of Elevenmile Canyon), locally overlain by a unit of water-laid rhyolite tuff and sedimentary rocks and by a locally thick unit of rhyolite ash-flow tuff (tuff of Lee Canyon). Total thickness of caldera-related deposits in the Elevenmile Canyon caldera is >4000 m. The composite Freeman Creek pluton intrudes the central and north parts of these calderas and consists of an older granodiorite porphyry phase probably related to the Elevenmile Canyon caldera and a younger granite phase probably related to the Poco Canyon caldera. A 7-km-long, texturally zoned rhyolite-porphyry to granite-porphyry dike intruded the north edges of these calderas and is probably a ring-fracture dike related to the Poco Canyon caldera.

Caldera collapse occurred mostly along subvertical ring-fracture faults that penetrated to depths of >5 km and were repeatedly active during eruption of ash-flow tuffs. Subsidiary growth faults with relatively minor displacement are present in caldera-related deposits in the interior of the Job Canyon caldera. A fault separating the two structural blocks of the Job Canyon caldera later served as the north walls of both the Poco Canyon and the Elevenmile Canyon calderas. A second, long-active fault formed the south margin of the Job Canyon caldera, separated the Poco Canyon and Elevenmile Canyon calderas into blocks with greatly different amounts of caldera-related deposits, and later was reactivated during early Miocene extension. The calderas collapsed as large piston-like blocks, and there is no evidence for chaotic collapse. Preserved parts of caldera floors are relatively flat surfaces several kilometers across.


GNSS-based Road User Charging (RUC) systems have recently attracted special attention because of their flexibility and reduced roadside infrastructure. For instance, German and Slovak motorways already perform truck toll collection by means of GPS receivers installed on the vehicles. Road toll belongs to the so-called liability critical applications, which are characterized by the fact that they must use trustful positioning data in order to control the navigation errors and their negative legal or economical consequences. Consequently, integrity monitoring of GNSS signals plays a key role in such systems. Nevertheless, the design of GNSS integrity algorithms like RAIM requires a deep knowledge of the characteristics of the application, the received signals and the environment effects on them. This paper analyzes and provides the required parameters to develop RAIM algorithms for road tolling applications in urban and rural environnements.


Like every other kind of historical research, the subject matter of this study cannot be considered exhausted. Both for the limitations to historical research and writing in general, and more so for the period involved (pre-colonial), it could not have been possible for everything pertaining to Luyana history at this time to be fully unearthed and documented here. This is not to say that the work is inadequate.For, it contains a fair amount of new data, as well as fresh interpretations to Luyana history in particular and that of Buloai (Western Province) in general. In the main, the following issues have been discussed: First, the identity of the people in question. Existing Bulozi history uses the term Luyana to denote the iniling group in Bulozi prior to the coming of the Kololo. The word is used interchangeably with the word Luyi which refers to the same people. Consequently, the Luyana of Kalabo are precluded from this definition, and are referred to only by their individual names: Makoma, Nyengo, Mwenyi, Imilangu and Liuwa. In contrast to this view, my study makes a distinction between the names Luyi and Luyana. (See Appendix B, 1). It then reserves use of the former name to the ruling group, while applying the latter to the above mentioned peoples, as well as the other Luyi offshoots such as the Kwangwa and Kwandi.Second, this study discusses the question of the origins of the Luyana peoples, including the manner of their migration into the Luyana region. Here again, there is a marked contrast between the prevailing views and ray findings.Whereas existing literature considers the Luyana as being non-Luyi, and to have come to Bulozi earlier than them, my thesis is that most Luyana broke from the Luyi and the recognized Luyi offshoots viz: the Kwangwa, Kwandi and Mbowe.Their coming to Luyanaland is shown as a gradual process, in which different clansmen came to the area either as hunters or as refugees. And for historical reasons, these clans eventually merged into the major peoples now existing.Third, we have a discussion on the economy and government of the Luyana peoples. Both are discussed under various periods.An early period, when Luyana affairs were administered by their clan heads (makulututu), a period when there were independent chieftaincies in Nyengo and Makoma prior to the incorporation of these areas into the Central Luyi Administration, and the period of Luyi rule in the region. A number of interesting factors emerge from these discussions. The scientific mind of the early Luyana as exemplified by their preparation of crystalline salt, and Luyana inclusion into the Luyi'Administration through the lifunga system, are notable
examples.Interesting too is the issue of Luyana militarism. Whereas existing literature says practically nothing regarding Luyana warfare, apart from stating their being conquered by the Luyi, my study shows that some Luyana played significant roles in some wars that were fought in Bulozi. Ngombala's conquest of the independent chieftaincies in Luyanaland for example, was achieved through the corroboration of some Luyana men.
Finally, this study deals with the crucial issue of the advent of colonialism. The Luyana were under the Luyi then, and Lewanika's treaties with the British resulted in Luyana 'country' falling under the British sphere of influence. Unfortunately for the people, some of their kinsmen came under the Portuguese, who had been advancing from their trading posts in present day Angola.An Administrative station (Lukona) was established in 1906, to effect British rule in Luyanaland. The date marks the terminal point for this study.It is sincerely hoped that what the work contains will interest scholars, to the extent that some of them may conduct further research in the region.


Parallel fiber-optic links promise to be a key enabling technology for distributed computing, substantially increasing transmission distance and bandwidth. The drive to include more and more processors and I/O devices in parallel-processor complexes has created a need for box-to-box interconnection links capable of delivering bandwidth comparable to system backplanes. Point-to-point links overcome the speed and cost constraints of shared buses. However, copper-based point-to-point links can reliably carry high-speed data only a limited distance. Parallel fiber-optic links substantially increase transmission distance and surpass copper's bandwidth capability. Our research addresses the integration of parallel fiber-optic data links into system designs that require a high-bandwidth link over moderate distances. To demonstrate the feasibility of using parallel fiber-optic technology as a fundamental building block in large-scale commercial and parallel machines, we constructed a link testbed.


ABSTRACT This study investigated the relationship between engaging in free choice STEM activities (hobbies) and career selection with the goal of understanding the factors that influence the development of science interests and science identity for those who chose a STEM career and those that did not. The 2864 participants in the study were adult hobbyists that included birders, astronomers, gardeners, model builders, insect collectors, rock/fossil collectors, home brewers, beekeepers, inventors, and environmental monitors. Participants completed a survey about their educational background, levels of hobby participation, motivation to participate in the hobby, perceived benefits of participating in the hobby, influences to continue to continue to engage in the hobby, reported influences on career choice influences, and perceived science identity. Results showed hobbyists with STEM careers were significantly more likely than those without STEM careers to rate elementary, middle, and high school experiences as well as college, museums and science centers, and clubs as influential on the development of the hobby. Those hobbyists with STEM careers were significantly more likely than those without a STEM career to report more ability in science, mathematics, and technology and to report that their choice of a career was influenced by factors such as enjoyment, encouragement from family, and hobby involvement. Conclusions suggest that engagement in a science hobby can provide support for youth to continue on to a STEM career as an adult.


Abstract This paper examines the phenomenon of lability in Estonian. We describe the types of lability found in our database and the distribution of verbs according to formal (derivational) and semantic verb classes, and we propose an explanation for the spread of lability in the Estonian verbal lexicon. Estonian displays a wealth of labile verbs, compared with Finnish, for instance, a closely related language which uses similar (derivational and morphosyntactic) valency changing devices. We argue that Estonian lability has been co-conditioned by the following factors: a) intensive contact with German, a language rich in labile verbs, b) fluctuations in the productivity and regularity of the valency-decreasing derivation in the recent history of Estonian, c) the phonetic merger of different derivational suffixes leading to misinterpretation of the valency patterns of their derivatives, and d) form-driven analogy. In relation to the last factor we introduce the notion of "clustered lability," which designates the expansion of the labile pattern over verbs sharing the same root.


Finite element simulations are increasingly used in structural analysis and design, especially in cases where complex structural and loading conditions are involved. Due to considerable progresses in computer technology as well as nonlinear finite-element analysis techniques in past years, it has become possible to pursue an accurate analysis of the complex blast-induced structural effects by means of numerical simulations. This paper aims to develop a better understanding of the behavior of steel-concrete composite beams (SCCB) under localized blast loading through a numerical parametric study. A finite element model is set up to simulate the blast-resistant features of SCCB using the transient dynamic analysis software LS-DYNA. It is demonstrated that there are three dominant failure modes for SCCB subjected to localized blast loading. The effect of loading position on the behavior of SCCB is also investigated. Finally, a simplified model is proposed for assessing the overall response of SCCB subjected to localized blast loading.


Lipid metabolism of intestine, liver and kidney was examined in daunomycin-induced nephrotic rats. 1) Phospholipids, triglycerides and cholesterol contents in chylomicrons were increased in daunomycin-induced nephrotic rats. 2) Cholesterol absorption in intestine (in vivo and situ) was similar in daunomycin-induced nephrotic rats and control rats. 3) Total bile acids levels in bile and portal vein were similar in two groups. 4) There was no difference in incorporation of 14C-mevalonate into cholesterol by liver and kidney slices in two groups. The oxidation of 14CO2 from 14C-mevalonate in kidney slices was decreased in daunomycin-induced nephrotic rats. These results show that the hypercholesterolemia in daunomycin-induced nephrotic rats are not caused by increased absorption of cholesterol in intestine. The increased cholesterol esters in liver are not derived from decreased bile acids catabolism. The increased cholesterogenesis in the liver of daunomycin-induced nephrotic rats may be due to an increased rate at the step prior to mevalonate. The oxidation of 14CO2 from mevalonate by shunt pathway may be decreased in the kidney of daunomycin-induced nephrotic rats.


This paper investigates the nano-macro transition in magnetic shape memory alloy(MSMA) thin films using a recently developed sharp phase front-based three-dimensional (3D) constitutive model outlined by Stoilov (JSMS 2005), and originally proposed in the 1D context by Stoilov and Bhattacharyya (Acta Mat 2002). The key ingredient in the model is the recognition of martensitic variants as separate phases in a MSMA domain. Evolution of the interface between these phases is taken as an indicator of the process of reorientation in progress. A formulation of the Helmholtz free energy potential based on Ising model has been derived. The implications of the external magnetic field on the initiation of phase transformation are studied for various mechanical loading modes.


A series of thirty consecutive epithelial ovarian cancer patients were reviewed after long-term follow-up (more than 5 y) since their second-look operation (SLO). All patients had advanced tumors (stages IIb-IV). Primary chemotherapy consisted of a cisplatin-associated regimen. For all patients adjuvant treatment had been planned after completion of the SLO. Mean follow-up after SLO was 68 months (47-103 months). Tumor status at SLO divided the patients in 2 subgroups: Group A = 13 patients (43%), with no evidence of histologically proved disease at time of operation (NED); Group B = 17 patients (57%), with macroscopic persistence of tumor. Survival was significantly better in the first group than in the second (77% at 5 yr vs less than 25%). Recurrence rate in the NED group was 7.7% (1 recurrence at 32 months). Eight of 17 patients with gross tumor at SLO underwent satisfactory resection. However, recurrence rate was high (75%) and survival rate was low (25% at 5 yrs). This result was not significantly better than that of patients with no optimal resection at SLO (9 patients, survival 22%). Second effort resection at SLO does not seem to be beneficial in these patients after partial failure of initial chemotherapy with cisplatin. The usefulness of systematic second look operations is discussed. Controlled randomized trials should be made to determine the exact role of SLO in ovarian cancer treatment.


A taxonomic account of the Elaphoglossum species occurring on the Tristan de Cunha, Gough Island and Marion Island groups in the South Atlantic and Southern Ocean are provided. Two new species, Elaphoglossum lasiolepium J. P. Roux from Gough Island and E. gracilifolium J.P. Rotix from Inaccessible Island, are described. A key and descriptions are given where they previously were not available or were incomplete. Notes on habitats, distribution and relationships are provided. The spores are illustrated by means electron micrographs.


Fisher's Linear Discriminant Analysis (FLD) is a well-known technique for linear classification, feature extraction and dimension reduction. The empirical FLD relies on two key estimations from the data -- the mean vector for each class and the (inverse) covariance matrix. To improve the accuracy of FLD under the High Dimension Low Sample Size (HDLSS) settings, Covariance-Regularized FLD (CRLD) has been proposed to use shrunken covariance estimators, such as Graphical Lasso, to strike a balance between biases and variances. Though CRLD could obtain better classification accuracy, it usually incurs bias and converges to the optimal result with a slower asymptotic rate. Inspired by the recent progress in de-biased Lasso, we propose a novel FLD classifier, DBLD, which improves classification accuracy of CRLD through de-biasing. Theoretical analysis shows that DBLD possesses better asymptotic properties than CRLD. We conduct experiments on both synthetic datasets and real application datasets to confirm the correctness of our theoretical analysis and demonstrate the superiority of DBLD over classical FLD, CRLD and other downstream competitors under HDLSS settings.


The mean shift algorithm is a statistical iterative algorithm based on kernel density estimation which has been widely used in many fields. This paper improves the mean shift algorithm by adopting the following approaches. Firstly, we present a novel approach named Random Sampling with Contexts (RSC) to speed up the mean shift algorithm. Secondly, we introduce Dempster-Shafer (D-S) theory for the fusion of features to improve the segmenting quality. Moreover, experimental results show that the new algorithm is superior to the typical mean shift algorithm.


The ultraviolet radiation (UVR) doses received by staff who are occupationally exposed to artificial sources of UVR found in dermatology departments have been measured using personal UV monitors. The results show that staff may receive actinic (UVB and UVC) doses which are in excess of recommended maximum permissible limits for occupational exposure, but that the UVA doses are well within these limits.


ICCTs have been established on a belying enforcement paradox between their significant mandate and their inherent lack of enforcement powers due to absence of systemic law enforcement. This article is premised on the idea that ICCTs fail to procure substantial results due to their delusive persistence in rejecting the factoring of politics in their operation. Thus, I suggest a perspective for arrest warrant enforcement that not only recognizes the relevance of politics but also capitalizes on it. Accordingly, I argue that by fully comprehending its enforcement tools and making use of its political role, the ICC may increase its rates in the apprehension of suspects, and therefore secure higher levels of judicial enforcement. Based on different compliance theories, I argue that the Office of The Prosecutor of the ICC (OTP) can improve compliance with ICC arrest warrants by making use of third states and non-state actors. In Part I, I address the way states and international actors may assist the OTP towards unwilling to arrest states through inducements, reputational sanctions, and support for enforcement agencies. I propose that external pressure in the form of positive inducements (membership, development aid) or negative inducements (travel bans, asset freezes) as well as condemnation and reputational damage towards non-compliant states, are likely to increase compliance with arrest warrants. In Part II, I examine a strategy for the OTP towards states that are willing to arrest but are unable to do so. In these cases, the OTP would benefit from improving its institutional capacity to identify and use overlapping interests with activist states in the field of human rights and international justice through the establishment of a diplomatic arm within its Jurisdiction, Complementarity and Cooperation Division (JCCD). I unpack the question of what this engagement may look like by examining such a potential relationship between the US and the ICC. Finally, in Part III, I focus on the instances, where civil society has the ability to influence third states or situation states to assist in the execution of arrest warrants. I argue that the OTP ought to include more actively different actors within the global civil society, such as NGOs, transnational networks, and individuals, during its bargaining efforts.


OBJECTIVE
To study the effect of parathyroid hormone-related protein (PTHrP) on nonalcoholic fatty liver disease (NAFLD) induced by methionine choline-deficient diet (MCD) in mice.

METHODS
Twelve male C57BL/6J mice were randomized into blank control group, vehicle group and PTHrP group (n=4). The mice in vehicle group and PTHrP group received injections of a control adeno-associated virus (AAV) vector and an AVV vector carrying PTHrP (AAV-PTHrP) gene, respectively, followed one week later by MCD feeding for 3 weeks; the mice in the blank control were fed a normal diet for 4 weeks. Body weight changes of the mice were monitored during the experiment. At the end of the experiment, liver tissues were harvested from the mice for histological analysis using HE staining, oil red O staining, and Sirius red staining. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride, and free fatty acids (FFAs) in the liver and serum were detected to assess hepatic impairment and lipid metabolism of the mice. Cell models of NAFLD were established in mouse and human normal liver cells by treatment with 250 μmol/L FFAs for 24 h, and the effect of AAV-PTHrP on lipid deposition and viability of the cells were tested using Oil Red O and Nile red staining and CCK8 assay.

RESULTS
Treatment with AAV-PTHrP, as compared with the control AVV vector, caused more rapid reduction of body weight in mice with MCD feeding and significantly increased the levels of AST (P < 0.05), ALT (P < 0.05), triglyceride (P < 0.01) and FFA (P < 0.05) in the liver and the scores of NAS (P < 0.01) and SAF (P < 0.05). HE and Oil red O staining of the liver tissue revealed obvious lipid deposition after MCD feeding, which was more serious in PTHrP group. In the cell experiment, FFAs induced steatosis in both mouse and human hepatocytes, and treatment with PTHrP increased the accumulation of lipid droplets and lowered the viability of the cell model of NAFLD (P < 0.01 or 0.05).

CONCLUSION
PTHrP may aggravate MCD-induced NAFLD in mice by promoting the deposition of lipid droplets in the hepatocytes.


The oil sands of western Canada represent the third largest hydrocarbon deposit in the world. Bitumen, a very heavy petroleum, is recovered from mined oil sands using warm water extraction followed by separation treatments to isolate the bitumen product. The high energy, water use, as well as tailings remediation challenges associated with the warm water extraction process raise major environmental concerns. Non-aqueous extraction using organic solvents at room temperature has been investigated extensively as an alternative to the warm water extraction process. The main challenge to the large-scale implementation of non-aqueous extraction is the retention of solvent in the tailings. The objective of this work was to present and validate a computational model for the interaction of solvents used in non-aqueous extraction with minerals, such as the abundant and adsorbent clay mineral kaolinite. The model system contained a periodically extended kaolinite platelet immersed in a solvent and all were treated at the atomic level using the 3D Reference Interaction Site Model with the Kovalenko-Hirata closure approximation (3D-RISM-KH) molecular theory of solvation. The solvent solvation free energy of interaction with kaolinite as well as site-specific adsorption energies and kinetic barriers for desorption were computed based on the solvent site density distribution functions. Moreover, the lateral and integrated density distributions were computed to analyze the organization of solvent at kaolinite surfaces. The integrated density distribution profiles were correlated with experimental adsorption isotherms. The results showed very strong adsorption of ethanol and weak adsorption of hydrocarbon solvents on kaolinite, which were in qualitative agreement with experimental solvent extraction reports. The model and these findings are valuable in understanding the mechanism of solvent retention in tailings after non-aqueous extraction and highlight the action of hydroxylated cosolvent additives to enhance extraction using nonpolar solvents.


In summer 2021, severe drought and heatwaves hit the Western United States, Canada, and many other areas around the world. At the same time, record-breaking floods devastated Western Europe (WE) and Central China. Drought and flooding are a water imbalance problem, and heatwaves are always coupled with drought or originate from hot, arid areas. Global average evaporation and precipitation are balanced and steady. When some areas receive less precipitation, other areas receive more, often as heavy downpours. This study analyses one particular freshwater imbalance area – the Mediterranean Basin (MB), from a historical view and of recent trends. The net water vapor output from MB is equivalent to about 20 times the Nile River discharge. The north-south seesaw precipitation trends across Europe clearly indicate a water vapor transfer from MB to Western and Northern Europe. An upper low-pressure system and abundant water vapor supply from MB are an ideal combination for lingering heavy downpours and floods over WE, such as the case in July 2021. The root cause of MB freshwater imbalance is identified as the Sahara expansion. The breach of the green Sahara about 5700 years ago was the desiccation of the Atlas Basin. Based on water cycle stability a solution is suggested to restore the Sahara back to green.


Nickel contact dermatitis appears to be almost exclusively a disease of females despite the increasing exposure of males to nickel. Successful murine models of nickel allergic contact dermatitis have been described. The purpose of this study is to investigate the kinetics and specificity of the response in this model and to examine if any differences exist between male and female. Mice were sensitised epicutaneously with nickel sulphate in aqueous solution of varying concentration, volume and duration of application. Following intradermal challenge, dose dependent response kinetics which approximated linearity were demonstrated upto the point of toxicity. Sensitised mice were challenged with Cobaltous chloride, Chromic chloride and Cupric sulphate and demonstrated no evidence of cross sensitivity to cobalt or chrome. Copper produced an irritant response making interpretation difficult. Earlier and stronger responses were observed in female mice, however these differences fell short of statistical significance. The results of the present study therefore establishes a reliable model for nickel hypersensitivity, that demonstrates both specificity and dose dependent kinetics without significant sex differences.


It is estimated that in 2017 there were about 1.5 million people living with Human immunodeficiency virus (HIV) in Kenya, of which 105,000 (7%) were adolescents. Adolescents have poorer antiretroviral therapy (ART) outcomes compared to adults. This study aimed to determine the treatment outcomes of adolescents on ART in Machakos County, Kenya. Adolescents on ART for at least two years from nine facilities were randomly selected in this retrospective cohort study. Data on their clinical and laboratory information at baseline and follow-up were abstracted from patient files. Descriptive analyses were used for central tendency while univariate and multivariate analysis was performed using SPSS version 16.0. A total of 182 adolescents consisting of 102 (56%) females and 80 (44%) males participated in the study. There were 54 (29.7%) young adolescents aged 12-15 years and 128 (70.3%) older adolescents (over 15 years). A total of 119 (65.4%) adolescents were retained after a mean follow-up period of 34.5 months. Almost all [180 (98.9%)] the adolescent had their weight and height documented, 143 (78.6%) had at least one viral load test, 140 (76.9%) at least one CD4 test and 164 (90.1%) had TB screening at the last visit. At first viral load test, 73% of adolescents were virally suppressed while 4.9% died in the course of follow-up. Additionally, 16.5% of adolescents were lost-to follow-up; 10.4% were transferred out, 20.3% had a treatment interruption and 6.6% were switched to second line treatment. Older adolescents had worse treatment outcomes compared to younger adolescents. They had lower retention rates; 60.2% compared to 77.8%; lower viral suppression: 70.4% compared to 75.6% and higher mortality: 6.3% compared to 1.9%. Suboptimal treatment outcomes were found despite good clinical follow-up, which were worse in the older adolescents. There is an opportunity to improve adolescent HIV treatment to meet national and global goals.

 Key words: Treatment outcomes, antiretroviral therapy, adolescents, human immunodeficiency virus (HIV), Machakos, viral suppression, Kenya.


This thesis deals with the subject of terrain aided underwater navigation for underwater vehicles. The term "navigation" is throughout the thesis understood as the task of estimating the position and attitude of a vehicle, together with the corresponding uncertainties. The main focus is on autonomous underwater vehicles (AUVs), but the methods discussed can also be readily used by other underwater vehicles. Terrain aided navigation is an attractive concept for obtaining submerged position fixes for the main navigation system, in most cases an inertial navigation system, for which the deterioration of the position accuracy necessitates external aiding methods. Terrain navigation has been used for decades in land and air applications, e.g. in aircraft and cruise missiles. In recent years, the technique has been applied also in underwater vehicles. The thesis concentrates on what is known as "bathymetric terrain navigation", in which bathymetric measurements are matched directly with a map, as opposed to the related area of "feature-based navigation", in which features extracted from the bottom measurements are used for position updates. Throughout the thesis, the terrain navigation system is treated as an external module, providing measurement updates for the main navigation system in a loosely coupled manner. This approach makes the terrain navigation module more portable and the overall system more robust to errors in the terrain navigation updates, although it is more difficult to exploit the internal states of the main navigation system in the terrain navigation algorithm. The thesis starts with a recapitulation of existing methods for terrain navigation (Chapter 2), with focus on Bayesian estimation methods. The problem is formulated as a recursive state-space estimation problem, which is highly nonlinear, due to the nonlinear nature of the terrain measurement function. As a consequence, nonlinear estimation methods like point mass filters (PMFs), particle filters (PFs) and sigma point Kalman filters (SPKFs) must be used. Special emphasis is put on the fact that, due to the computational complexity of the estimation methods, one must often use lowdimensional state-space models, leading to discrepancies between the true system and the filter model. Such discrepancies sometimes lead to inaccuracies and overconfidence in the estimators. Chapter 3 continues with a discussion on the special difficulties that arise when using terrain navigation techniques underwater, e.g. different sensor characteristics, the effect of tide compensation etc. It is also shown how unknown depth biases can be handled, either through estimation of the bias in the filter, or by using relative depth information only. A novel formulation of the filter process model is also developed, in an attempt to model the drift in the main navigation system more accurately. Chapter 4 gives an overview of map databases, which are essential to the success of terrain navigation. The main contributions of the thesis are related to the computational results presented in Chapter 5. The behavior in different terrain types of the TERCOM (Terrain Contour Matching) algorithm, the PMF algorithm, various particle filters and the SPKF are compared, using sea data from an AUV equipped with a multibeam echosounder. All the tested methods are able to estimate the position of the AUV with an accuracy within the horizontal resolution of the terrain map, with the PMF as the most accurate and robust, though also the most computationally demanding, method. A clear positive effect on accuracy and robustness from the inclusion of the depth bias is observed. The main problem with the methods discussed in the thesis is their tendency of overconfidence, i.e. the estimated uncertainty is too low compared to the true uncertainty. This can be partially solved by sub-sampling the terrain measurements, minimizing the effect of unmodeled correlations. Results from computations using the novel process model derived in Chapter 3 show that this approach does not solve the inconsistency problem, though the accuracy and stability are slightly improved on the tested data. Chapter 5 closes with some simulations using a map database based on real MBE data from an area with pockmarks, i.e. small craters on the sea floor. The sea floor in the area is otherwise flat. The simulations indicate that the pockmarks contain enough terrain information to facilitate the use of terrain navigation in areas previously thought of as unsuited


The outer hair cells of the cochlea occur in three distinct and geometrically precise rows and, unusually, display both sensing and motor properties. As well as sensing sound, outer hair cells (OHCs) undergo cycle-by-cycle length changes in response to stimulation. OHCs are central to the way in which the cochlea processes and amplifies sounds, but how they do so is presently unknown. In explanation, this paper proposes that outer hair cells act like a single-port surface acoustic wave (SAW) resonator in which the interdigital electrodes—the three distinctive rows—exhibit the required electromechanical and mechanoelectrical properties. Thus, frequency analysis in the cochlea might occur through sympathetic resonance of a bank of interacting cells whose microscopic separation largely determines the resonance frequency. In this way, the cochlea could be tuned from 20 Hz at the apex, where the spacing is largest, to 20 kHz at the base, where it is smallest. A suitable candidate for a wave that could mediate such a short-wavelength interaction—a 'squirting wave' known in ultrasonics—has recently been described. Such a SAW resonator could thereby underlie the 'cochlear amplifier'—the device whose action is evident to auditory science but whose identity has not yet been established.


Voluntary commitments are playing an ever-greater role in environmental governance at all scales. In the years preceding the signing of the Paris Agreement in 2015, a flurry of non-state and state actors signed on to various declarations and commitments to reduce deforestation as one globally significant climate mitigation solution. This paper focuses on the Rio Branco Declaration (RBD) and the 30 first-order subnational jurisdictions located in Brazil, Indonesia, Mexico, and Peru that signed it between 2014 and 2018, committing to reduce deforestation 80% by 2020, conditional upon adequate support from the international community. We assess each study jurisdiction's progress toward that commitment in terms of reducing deforestation, and examine a subset of the potential factors supporting or slowing progress, including the existence of commensurate targets within jurisdictions' legal frameworks and the international financial support pledged to jurisdictions. We found that progress toward achieving the target was slow and likely unattainable in most jurisdictions outside of Brazil. Among the four jurisdictions likely to achieve the target under current deforestation trajectories, only Mato Grosso State has a target within its legal framework that is more ambitious than the RBD target. We found that the international response to the RBD was sluggish and likely inadequate – with only one financial pledge made in direct response to the declaration and the majority of funding to support jurisdictional efforts coming from one source. We did not find a clear relationship between international finance pledged and progress toward the RBD deforestation target; however, more often, jurisdictions that received pledges earlier have made more progress. We explore what may explain individual jurisdictions' performance with respect to the target, including specific jurisdictional circumstances, national context, and international support. We estimate that, if current deforestation trajectories continue, the RBD signatories in our study could contribute approximately 3.7% (0.65 GtCO2e) of the greenhouse gas emissions reduction needed to keep global warming at 1.5°C, compared with a potential 5.7% (0.98 GtCO2e) if they were to all meet the RBD target.


The article adapts and develops the network-based analysis of the transport connections to the Hungarian road network. Based on the mutual road distance of 48 Hungarian cities from each other, the author calculates the average distance of each city from the others, the average bee-line distances, the relative share of the two for each cities, and also repeats the calculation with road distances after a ten-year period.


The flow past a cylindrical obstacle in an enclosed channel is examined when the entire configuration is rotating rapidly about an axis which is aligned with that of the obstacle. When viewed from a frame of reference which is rotating with the channel, Coriolis forces dominate and act to constrain the motion to be two-dimensional. The channel is considered to have depth varying linearly across its width, producing effects equivalent to the so-called β-plane approximation and permitting waves to travel away from the obstacle, both upstream and downstream. For the eastward flow considered in this paper, this leads to the formation of a lee-wavetrain downstream of the obstacle and, under some conditions, a region of retarded, or 'blocked', flow upstream of the obstacle. The flow regime studied is essentially inviscid, although one form of frictional effect on the flow, introduced through the Ekman layers, is included. The properties of this system are examined numerically and compared with the theoretical predictions from other studies, which are applicable in asymptotic limits of the parameters. In particular, the relevance of 'Long's model' solutions is considered.


The current study investigated the influence of rewards on very young children's helping behavior. After 20-month-old infants received a material reward during a treatment phase, they subsequently were less likely to engage in further helping during a test phase as compared with infants who had previously received social praise or no reward at all. This so-called overjustification effect suggests that even the earliest helping behaviors of young children are intrinsically motivated and that socialization practices involving extrinsic rewards can undermine this tendency.


Women of low income and education have lower levels of peripartum depression (PPD) literacy, limiting their ability to recognize symptoms and make informed healthcare decisions. Existing digital solutions and underlying development frameworks for PPD lack an integrative approach addressing health literacy and related disparities. Therefore, we develop an integrative framework for digital content engineering in PPD self-management consisting of (a) user needs analysis, (b) inclusion of eHealth literacy principles (science and health literacy), and (c) mapping user needs to the Behavioral Intervention Technology model. Results revealed that perinatal women seeking mental health care prefer information in multisensory formats, and knowledge needs were identified in areas such as medication management and coping with abnormal results. Results were mapped to eHealth literacy features of whiteboard videos covering essential PPD knowledge, and social media features where patients can articulate information needs. Initial evaluation of proposed features against existing PPD self-management solutions are discussed.


Increasing numbers of workers in an ever-widening range of disciplines have been discovering that a theory of information provides new insights into their field. Hans Christian von Baeyer, for example, argued in his 2003 book that information is the new language of science. Wolfgang Hofkirchner argues that our understanding of information is
undergoing a paradigm shift with far-reaching consequences, and the philosopher of Information Luciano Floridi has put forward the thesis that information underpins a fourth revolution (following the three due to Copernicus, Darwin and Freud) which repositions our sense of identity.
Albert Borgmann identified three roles for information: information about reality; information for reality and information as reality. This paper explores information about, for and as religion.
Information about religion concerns the use of information-thinking to describe and understand religion. Information for religion concerns information as a tool of religion. Information as religion, is information replacing religion or delivering a religion itself.
The potential scope of an exploration of the value of information ideas to religion is very large. This presentation suggests a framework for thinking about the field and points to a few specific examples.


CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses selumetinib (Koselugo), 10 mg and 25 mg oral capsules.
Indication: For the treatment of pediatric patients aged 2 years and above, with neurofibromatosis type1 who have symptomatic, inoperable plexiform neurofibromas.


ABSTRACT Escherichia coli strains of phylogenetic group B2 are often associated with urinary tract infections (UTIs) and several other diseases. Recent genomic and transcriptomic analyses have not suggested or identified specific genes required for virulence, but have instead suggested multiple virulence strategies and complex host-pathogen interactions. Previous analyses have not compared core gene expression between phylogenetic groups or between pathogens and nonpathogens within phylogenetic groups. We compared the core gene expression of 35 strains from three phylogenetic groups that included both pathogens and nonpathogens after growth in a medium that allowed comparable growth of both types of strains. K-means clustering suggested a B2 cluster with 17 group B2 strains and two group A strains; an AD cluster with six group A strains, five group D strains and one B2 strain; and four outliers which included the highly studied model uropathogenic E. coli strains UTI89 and CFT073. Half of the core genes were differentially expressed between B2 and AD cluster strains, including transcripts of genes for all aspects of macromolecular synthesis—replication, transcription, translation, and peptidoglycan synthesis—energy metabolism, and environmental-sensing transcriptional regulators. Notably, core gene expression between nonpathogenic and uropathogenic transcriptomes within phylogenetic groups did not differ. If differences between pathogens and nonpathogens exist, then the differences do not require transcriptional reprogramming. In summary, B2 cluster strains have a distinct transcription pattern that involves hundreds of genes. We propose that this transcription pattern is one factor that contributes to virulence. IMPORTANCE Escherichia coli is a diverse species and an opportunistic pathogen that is associated with various diseases, such as urinary tract infections. When examined, phylogenetic group B2 strains are more often associated with these diseases, but the specific properties that contribute to their virulence are not known. From a comparative transcriptomic analysis, we found that group B2 strains grown in a nutrient-rich medium had a distinct transcription pattern, which is the first evidence that core gene expression differs between phylogenetic groups. Understanding the consequences of group B2 transcription pattern will provide important information on basic E. coli biology, the basis for E. coli virulence, and possibly for developing therapies for a majority of urinary tract infections and other group B2-associated diseases. Escherichia coli is a diverse species and an opportunistic pathogen that is associated with various diseases, such as urinary tract infections. When examined, phylogenetic group B2 strains are more often associated with these diseases, but the specific properties that contribute to their virulence are not known. From a comparative transcriptomic analysis, we found that group B2 strains grown in a nutrient-rich medium had a distinct transcription pattern, which is the first evidence that core gene expression differs between phylogenetic groups. Understanding the consequences of group B2 transcription pattern will provide important information on basic E. coli biology, the basis for E. coli virulence, and possibly for developing therapies for a majority of urinary tract infections and other group B2-associated diseases.


A mathematical model for the impact of slip velocity on peristaltic transport of blood flow has been investigated by utilizing the Herschel-Bulkley model in a flexible tube.
The closed-form solutions are obtained for velocity, plug flow velocity, and volume flux. It is noticed that the impact of yield stress, amplitude ratio, Darcy number,
velocity slip parameter, elastic parameters and fluid behavior index plays a vital role in controlling the flux in an elastic tube. The outcomes acquired from the flow
quantities reveal that, the volume flux in a flexible tube decreases with an increase in the porous parameter and it increases with an increase in the slip parameter. Further,
the results of Newtonian, Bingham plastic and Power-law models have been presented graphically and analysed


A series of evidences suggests that enhanced susceptibility to programmed cell death (PCD) is a major pathogenetic factor in Alzheimer's disease (AD). We investigated this issue, analyzing amyloid beta-protein (A beta) production in a model of neuronal PCD, induced by staurosporine in a murine neuroblastoma cell line. When PCD was induced, a 280-290% secreted A beta occurred, in spite of a 20% metabolism and an unchanged A betaPP expression. The increased intracellular A beta reactivity largely colocalized with a marker of ER. Inhibition of caspases blocked the cleavage at the C-terminus of beta PP, but only partially rescued A beta overproduction caused by staurosporine treatment. Our findings suggest that PCD fosters the physiological pathways of A beta production characteristic of neuronal cells, and they confirm the theory that unbalance of PCD is a central event in AD pathogenesis. Moreover, our data indicate that still unidentified cellular mechanisms, other than caspases activation, are responsible of the specific alteration of A betaPP processing during PCD.


ABSTRACT We evaluate the effects of a carbon tax in the Brazilian economy using an input–output framework. First, we consider the impacts of a carbon tax of US$ 10 and US$ 50/metric ton of CO2 equivalent. As usual, the adoption of the carbon tax generates adverse effects on GDP, wages and jobs in the short term, but reduces emissions and generates new government revenues, especially in the case of the greater tax. Second, we consider a broader tax system reform. In this reform, we replace distortionary taxes by a tax on value added. To compensate for the loss of government revenue, we assume a carbon tax with equivalent revenue. We find that the net effect is a GDP increase of 0.47%, the creation of 533 thousand jobs and reduction of 1.6 million tons of CO2 emissions. Both scenarios exempt exports and levy imports to correct adverse effects on the country's competitiveness.


Introduction: The receptor tyrosine kinase c-MET displays aberrant activation in the malignant phenotype of various tumors, and thus, has drawn considerable attention as drug target for cancer therapy. Many c-MET inhibitors are now under clinical investment, and one of them – Cabozantinib – has been approved by US FDA in 2012 for the treatment of medullary thyroid cancer, which further proved the feasibility of c-MET inhibition method in cancer therapy. Areas covered: This article briefly outlines the role of c-MET in oncogenesis and provides a broad overview of the assays used to characterize new inhibitors. Then, a series of representative small-molecule inhibitors of c-MET, especially from the published patent literature from 2011 to 2013, are recorded. Herein, the challenges in the kinase inhibitor design, such as the inhibitor selectivity and resistance mutations, are also discussed. Expert opinion: Up to now, at least 17 inhibitors of c-MET are under clinical evaluation, and several agents exhibit encouraging results. Thus, inhibiting c-MET signaling has major therapeutic value in cancer therapy. Focus on the selectivity of both types of inhibitors, with potent selectivity or multi-targets, have demonstrated antitumor efficacy. The network pharmacology and clinical trials integrated would provide powerful tools to further evaluate the superiority of both inhibitors in continued efficacy and toxicity.


SUMMARY The effect of level of N fertilizer on the composition, yield and quality of 21 crops was studied in experiments on adjacent sites of the same field to aid in the development of fertilizer recommendations. Yield of each of the crops first increased and then either remained the same or declined with further increases of N fertilizer. Interpretation by means of a simple model enabled response curves to be characterized by two parameters; one representing the beneficial component of the response and the other the detrimental component. Both varied greatly from crop to crop. The magnitude of the beneficial component of the response of most non-leguminous crops was largely determined by the potential demand of the crop for nitrogen; the exceptions were some root crops which responded less than would be expected on this basis. The adverse component was serious with root crops and those crops that are in the soil for only a short period. High levels of N increased the ratio of foliage to storage root dry weights even when total dry matter was unaffected. The changes were associated with a considerable increase in the % N in the dry matter of the roots. When crops were grown with their optimum levels of N fertilizer a simple linear. relationship between the mean %N in the dry matter and the total weight of dry matter per unit area covered all crops. Simple relationships also existed between total dry matter of non-leguminous crops and (a) the amount of N taken up by the crop from unfertilized soil, (b) the recovery of added fertilizer by the crop and (c) the beneficial component of the response of crops harvested before October. Percentage N in the dry matter at harvest was not a sensitive indicator of the extent to which plant growth was restricted by lack of nitrogen; a difference of 0·1% N in the plant material was associated with a 10% increase in yield. N fertilizer levels influenced the % dry matter and the incidence of crop disorders such as rotten roots and tissue discoloration, but the effects were seldom appreciable with practicable levels of fertilizer application.


Background: Endothelin-1 is considered to be a central pathogenic factor in connective tissue diseases (CTDs) such as systemic sclerosis (SSc), leading to vasoconstriction, fibrosis, hypertrophy and inflammation. A frequent complication of CTD is pulmonary arterial hypertension (PAH), which has a major effect on functioning and quality of life, and is associated with a particularly poor prognosis. Objective: To present a subgroup analysis that summarises experiences from the pivotal studies and their open-label extensions with the oral dual endothelin-1 receptor antagonist bosentan in patients with PAH and CTD, mostly SSc and lupus erythematosus. Methods: 66 patients with PAH secondary to CTD, in World Health Organization functional class III or IV, were randomised to two double-blind, placebo-controlled studies and followed up for 12 and 16 weeks, respectively. The primary end point was change in exercise capacity, assessed using the 6-min walk test. In both studies and their extensions, survival was assessed from start of treatment to death or data cut-off and analysed as Kaplan–Meier estimates. Results: 44 patients with PAH secondary to CTD who were treated with bosentan were stable in 6-min walk distance at the end of the study (+19.5 m, 95% confidence interval (CI) −3.2 to 42.2), whereas patients treated with placebo deteriorated (−2.6 m, 95% CI −54.0 to 48.7). 64 patients subsequently received bosentan in an open-label long-term extension study. Mean (standard deviation (SD)) exposure to bosentan was 1.6 (0.9) years, and duration of observation was 1.8 (0.8) years. 8 (16%) patients received epoprostenol as add-on treatment and 7 (14%) after discontinuation of bosentan. Survival in those receiving bosentan was 85.9% after 1 year and 73.4% after 2 years. Conclusion: Short-term bosentan treatment in a subgroup of patients with PAH secondary to CTD seems to have a favourable effect compared with placebo. The long-term follow-up of these patients suggests that first-line bosentan, with the subsequent addition of other PAH treatments if required, is safe for long-term treatment and may have a positive effect on outcome.


This paper describes the Arabic broadcast transcription system fielded by IBM in the GALE Phase 3.5 machine translation evaluation. Key advances compared to our Phase 2.5 system include improved discriminative training, the use of Subspace Gaussian Mixture Models (SGMM), neural network acoustic features, variable frame rate decoding, training data partitioning experiments, unpruned n-gram language models and neural network language models. These advances were instrumental in achieving a word error rate of 8.9% on the evaluation test set.