Cenozoic global ice volume and temperature simulations over the past 40 million years

Variations in global ice volume and temperature over the Cenozoic era have been investigated with a set of one-dimensional (1-D) ice-sheet models. Simulations include three ice sheets representing glaciation in the Northern Hemisphere, i.e. in Eurasia, North America and Greenland, and two separate ice sheets for Antarctic glaciation. The continental mean Northern Hemisphere surface-air temperature has been derived through an inverse procedure from observed benthic d18O records. These data have yielded a mutually consistent and continuous record of temperature, global ice volume and benthic d18O over the past 35 Ma. The simple 1-D model shows good agreement with a comprehensive 3-D ice-sheet model for the past 3 Ma. On average, differences are only 1.0°C for temperature and 6.2 m for sea level. Most notably, over the 35 Ma period, the reconstructed ice volume-temperature sensitivity shows a transition from a climate controlled by Southern Hemisphere ice sheets to one controlled by Northern Hemisphere ice sheets. Although the transient behaviour is important, equilibrium experiments show that the relationship between temperature and sea level is linear and symmetric, providing limited evidence for hysteresis. Furthermore, the results show a good comparison with other simulations of Antarctic ice volume and observed sea level.

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques.

Mining Police-Recorded Offence and Incident Data to Inform a Definition of Repeat Domestic Abuse Victimization for Statistical Reporting

Following inspections in 2013 of all police forces, Her Majesty’s Inspectorate of Constabulary found that one-third of forces could not provide data on repeat victims of domestic abuse (DA) and concluded that in general there were ambiguities around the term ‘repeat victim’ and that there was a need for consistent and comparable statistics on DA. Using an analysis of police-recorded DA data from two forces, an argument is made for including both offences and non-crime incidents when identifying repeat victims of DA. Furthermore, for statistical purposes the counting period for repeat victimizations should be taken as a rolling 12 months from first recorded victimization. Examples are given of summary statistics that can be derived from these data down to Community Safety Partnership level. To reinforce the need to include both offences and incidents in analyses, repeat victim chronologies from policerecorded data are also used to briefly examine cases of escalation to homicide as an example of how they can offer new insights and greater scope for evaluating risk and effectiveness of interventions.

Wave and turbulence measurements at a tidal energy site

This work presents the analysis of wave and turbulence measurements collected at a tidal energy site. A new method is introduced to produce more consistent and rigorous estimations of the velocity fluctuations power spectral densities. An analytical function is further proposed to fit the observed spectra and could be input to the numerical models predicting power production and structural loading on tidal turbines. Another new approach is developed to correct for the effect of the Doppler noise on the high frequencies power spectral densities. The analysis of velocity time series combining wave and turbulent contributions demonstrates that the turbulent motions are coherent throughout the water column, rendering the wave coherence-based methods not applicable to our dataset. To avoid this problem, an alternative approach relying on the pressure data collected by the ADCP is introduced and shows appreciable improvement in the wave-turbulence separation.

The regulation of cancer cell invasive behaviour by Chloride Interacellular Channel 3 (CLIC3) and Transglutaminasae 2

A study into the role of secreted CLIC3 in tumour cell invasion. The initiation and progression of cancers is thought to be linked to their relationship with a population of activated fibroblasts, which are associated with tumours. I have used an organotypic approach, in which plugs of collagen I are preconditioned with fibroblastic cells, to characterise the mechanisms through which carcinoma-associated fibroblasts (CAFs) influence the invasive behaviour of tumour cells. I have found that immortalised cancer-associated fibroblasts (iCAFs) support increased invasiveness of cancer cells, and that this is associated with the ability of CAFs to increase the fibrillar collagen content of the extracellular matrix (ECM). To gain mechanistic insight into this phenomenon, an in-depth SILAC-based mass proteomic analysis was conducted, which allowed quantitative comparison of the proteomes of iCAFs and immortalised normal fibroblast (iNFs) controls. Chloride Intracellular Channel Protein 3 (CLIC3) was one of the most significantly upregulated components of the iCAF proteome. Knockdown of CLIC3 in iCAFs reduced the ability of these cells to remodel the ECM and to support tumour cell invasion through organotypic plugs. A series of experiments, including proteomic analysis of cell culture medium that had been preconditioned by iCAFs, indicated that CLIC3 itself was a component of the iCAF secretome that was responsible for the ability of iCAFs to drive tumour cell invasiveness. Moreover, addition of soluble recombinant CLIC3 (rCLIC3) was sufficient to drive the extension of invasive pseudopods in cancer cell lines, and to promote disruption of the basement membrane in a 3D in vitro model of the ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition. My investigation into the mechanism through which extracellular CLIC3 drives tumour cell invasiveness led me to focus on the relationship between CLIC3 and the ECM modifying enzyme, transglutaminase-2 (TG2). Through this, I have found that TG2 physically associates with CLIC3 and that TG2 is necessary for CLIC3 to drive tumour cell invasiveness. These data identifying CLIC3 as a key pro-invasive factor, which is secreted by CAFs, provides an unprecedented mechanism through which the stroma may drive cancer progression.

Seizure and Profound Hypokalemia: Unusual Presentation of Primary Hyperparathyroidism

A 68-year-old man was admitted because of tonic–clonic convulsion. He had been receiving 200 mg itraconazole for 10 days. He had hypokalaemia (2.2 mEq/l), hypercalcaemia (Cacorr 11.0 mg/dl) and elevated serum parathyroid hormone (PTH, 95 pg/ml). Ultrasound examination of the neck revealed a low echoic tumour. Cessation of itraconazole and fluid supplementation eradicated clinical symptoms and profound hypokalaemia, but serum potassium remained low normal (3.4 mEq/l) and the mild hypercalcaemia and elevated PTH were unchanged. To conclude, a small amount of itraconazole (200 mg) precipitated profound hypokalaemia and seizure in a patient with mild hyperparathyroidism and low normal serum potassium.

An alternative benchmarking approach for electricity utility regulation using maximum entropy

The main purpose of this study is to present an alternative benchmarking approach that can be used by national regulators of utilities. It is widely known that the lack of sizeable data sets limits the choice of the benchmarking method and the specification of the model to set price controls within incentive-based regulation. Ill-posed frontier models are the problem that some national regulators have been facing. Maximum entropy estimators are useful in the estimation of such ill-posed models, in particular in models exhibiting small sample sizes, collinearity and non-normal errors, as well as in models where the number of parameters to be estimated exceeds the number of observations available. The empirical study involves a sample data used by the Portuguese regulator of the electricity sector to set the parameters for the electricity distribution companies in the regulatory period of 2012-2014. DEA and maximum entropy methods are applied and the efficiency results are compared.

DopSCAT: A mission concept for simultaneous measurements of marine winds and surface currents

A radar scatterometer operates by transmitting a pulse of microwave energy toward the ocean's surface and measuring the normalized (per-unit-surface) radar backscatter coefficient (σ°). The primary application of scatterometry is the measurement of near-surface ocean winds. By combining σ° measurements from different azimuth angles, the 10 m vector wind can be determined through a Geophysical Model Function (GMF), which relates wind and backscatter. This paper proposes a mission concept for the measurement of both oceanic winds and surface currents, which makes full use of earlier C-band radar remote sensing experience. For the determination of ocean currents, in particular, the novel idea of using two chirps of opposite slope is introduced. The fundamental processing steps required to retrieve surface currents are given together with their associated accuracies. A detailed description of the mission proposal and comparisons between real and retrieved surface currents are presented. The proposed ocean Doppler scatterometer can be used to generate global surface ocean current maps with accuracies better than 0.2 m/s at a spatial resolution better than 25 km (i.e., 12.5 km spatial sampling) on a daily basis. These maps will allow gaining some insights on the upper ocean mesoscale dynamics. The work lies at a frontier, given that the present inability to measure ocean currents from space in a consistent and synoptic manner represents one of the greatest weaknesses in ocean remote sensing.

Sexual self-awareness and body Image

broadly describes the internal representations of the body structure and the physical appearance of the individual in regards him/herself and others. Sexual self-awareness (ACS) can be understood as the evaluation that each of us makes of his/her feelings and actions related to his/her sexuality and sexual behaviour, describing what each of us thinks about sex and what we feel about behaviours. Objective: Identify dimensions of sexual self-awareness and body image in sexual satisfaction of the young. Methods Correlational descriptive study, a convenience sample of 84 students of a health school (29.8 % male, 20.2 % female), with ages between 19 and 34 years. As data collection instrument a poll through questionnaire, incorporating a Body Image Satisfaction and a Multidimensional Sexual Self-awareness scale, was used. Results The majority of the sample subjects indicate having a partner (59.5 %), perceive themselves as having the ideal weight (75.0 %), the ideal height (65.5 %) and a normal appearance (76.2 %). Globally a high and statistically significant ACS was observed (t-Student = 12.520; GL = 83; p-value < 0.001) and significant statistical differences exist between having/not having a partner and the ACS (Student t = 2,965; GL = 82; p-value = 0.004) showing that those who mention having a partner have a higher average ACS (average = 3.812; SD = 0.412) compared to those without (average = 3.496; SD = 0.563). No statistically significant correlations were observed between ACS and Body Image.

Diagnostic value of diffusion weighted MRI and ADC in differential diagnosis of cavernous hemangioma of the liver.

Aims: To investigate the use of diffusion weighted magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) values in the diagnosis of hemangioma. Materials and methods: The study population consisted of 72 patients with liver masses larger than 1 cm (72 focal lesions). DWI examination with a b value of 600 s/mm2 was carried out for all patients. After DWI examination, an ADC map was created and ADC values were measured for 72 liver masses and normal liver tissue (control group). The average ADC values of normal liver tissue and focal liver lesions, the “cut-off” ADC values, and the diagnostic sensitivity and specificity of the ADC map in diagnosing hemangioma, benign and malignant lesions were researched. Results: Of the 72 liver masses, 51 were benign and 21 were malignant. Benign lesions comprised 38 hemangiomas and 13 simple cysts. Malignant lesions comprised 9 hepatocellular carcinomas, and 12 metastases. The highest ADC values were measured for cysts (3.782±0.53×10-3 mm2/s) and hemangiomas (2.705±0.63×10-3 mm2/s). The average ADC value of hemangiomas was significantly higher than malignant lesions and the normal control group (p<0.001). The average ADC value of cysts were significantly higher when compared to hemangiomas and normal control group (p<0.001). To distinguish hemangiomas from malignant liver lesions, the “cut-off” ADC value of 1.800×10-3 mm2/s had a sensitivity of 97.4% and a specificity of 90.9%. To distinguish hemangioma from normal liver parenchyma the “cut-off” value of 1.858×10-3 mm2/s had a sensitivity of 97.4% and a specificity of 95.7%. To distinguish benign liver lesions from malignant liver lesions the “cut-off” value of 1.800×10-3 mm2/s had a sensitivity of 96.1% and a specificity of 90.0%. Conclusion: DWI and quantitative measurement of ADC values can be used in differential diagnosis of benign and malignant liver lesions and also in the diagnosis and differentiation of hemangiomas. When dynamic examination cannot distinguish cases with vascular metastasis and lesions from hemangioma, DWI and ADC values can be useful in the primary diagnosis and differential diagnosis. The technique does not require contrast material, so it can safely be used in patients with renal failure. Keywords:

Error estimation and adaptive mesh refinement for aerodynamic flows

This lecture course covers the theory of so-called duality-based a posteriori error estimation of DG finite element methods. In particular, we formulate consistent and adjoint consistent DG methods for the numerical approximation of both the compressible Euler and Navier-Stokes equations; in the latter case, the viscous terms are discretized based on employing an interior penalty method. By exploiting a duality argument, adjoint-based a posteriori error indicators will be established. Moreover, application of these computable bounds within automatic adaptive finite element algorithms will be developed. Here, a variety of isotropic and anisotropic adaptive strategies, as well as $hp$-mesh refinement will be investigated.

The effect of chaperone compounds on glucocerebrosidase stability and activity in fibroblasts from Gaucher Disease patients with different genotypes

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014

Apoptotic properties of Citrus sudachi Hort, ex Shirai (Rutaceae) extract on humanA549 and HepG2 cancer cells

Purpose: To investigate whether Citrus sudachi harvested at two stages of maturity can induce toxicity in a cell-specific manner and to determine the possible mechanisms of Citrus sudachi-induced cytotoxic responses in two types of cancer cells (human lung adenocarcinoma A549 and hepatocellular carcinoma HepG2 cells) and two normal cell lines (lung 16HBE140- and liver CHANG cells). Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodidle assay were used to test the antiproliferative activity and apoptosis of methanol extract of Citrus sudachi, respectively. Griess reaction and reverse transcriptase-polymerase chain reaction (RT-PCR) were carried out to evaluate nitric oxide (NO•) production and the mRNA levels of inhibitors of apoptosis (IAP). Results: Citrus sudachi exerted cytotoxicity in a time-dependent manner in cancer cells which increased with increase in maturity but did not affect normal cells. Citrus sudachi was found to induce accumulation of cells in the sub-G1 cell cycle phase, fragmentation of DNA and cell death with characteristics of apoptosis, in both types of cancer cells. Moreover, Citrus sudachi upregulated cellular NO• produced by activation of nitric oxide synthase (NOS), while it suppressed the levels of IAP mRNA in both types of cancer cells. Conclusion: The results obtained suggest that Citrus sudachi induces apoptosis in A549 and HepG2 cells, which may be mediated by NO•. There is need for further studies on the role of Citrus sudachi in cancer treatment.

Genome-Wiide estimates of coancestry, in breeding and effective population size in the Spanish Holstein population

Estimates of effective population size in the Holstein cattle breed have usually been low despite the large number of animals that constitute this breed. Effective population size is inversely related to the rates at which coancestry and inbreeding increase and these rates have been high as a consequence of intense and accurate selection. Traditionally, coancestry and inbreeding coefficients have been calculated from pedigree data. However, the development of genome-wide single nucleotide polymorphisms has increased the interest of calculating these coefficients from molecular data in order to improve their accuracy. In this study, genomic estimates of coancestry, inbreeding and effective population size were obtained in the Spanish Holstein population and then compared with pedigree-based estimates. A total of 11,135 animals genotyped with the Illumina BovineSNP50 BeadChip were available for the study. After applying filtering criteria, the final genomic dataset included 36,693 autosomal SNPs and 10,569 animals. Pedigree data from those genotyped animals included 31,203 animals. These individuals represented only the last five generations in order to homogenise the amount of pedigree information across animals. Genomic estimates of coancestry and inbreeding were obtained from identity by descent segments (coancestry) or runs of homozygosity (inbreeding). The results indicate that the percentage of variance of pedigree-based coancestry estimates explained by genomic coancestry estimates was higher than that for inbreeding. Estimates of effective population size obtained from genome-wide and pedigree information were consistent and ranged from about 66 to 79. These low values emphasize the need of controlling the rate of increase of coancestry and inbreeding in Holstein selection programmes.

Intervalo de confiança para o parâmetro estimado pelo estimador de Horvitz-Thompson

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Exatas, Departamento de Estatística, 2016.