Architectural-Physical Co-Design of 3D CPUs with Micro-Fluidic Cooling

The performance, energy efficiency and cost improvements due to traditional technology scaling have begun to slow down and present diminishing returns. Underlying reasons for this trend include fundamental physical limits of transistor scaling, the growing significance of quantum effects as transistors shrink, and a growing mismatch between transistors and interconnects regarding size, speed and power. Continued Moore's Law scaling will not come from technology scaling alone, and must involve improvements to design tools and development of new disruptive technologies such as 3D integration. 3D integration presents potential improvements to interconnect power and delay by translating the routing problem into a third dimension, and facilitates transistor density scaling independent of technology node. Furthermore, 3D IC technology opens up a new architectural design space of heterogeneously-integrated high-bandwidth CPUs. Vertical integration promises to provide the CPU architectures of the future by integrating high performance processors with on-chip high-bandwidth memory systems and highly connected network-on-chip structures. Such techniques can overcome the well-known CPU performance bottlenecks referred to as memory and communication wall. However the promising improvements to performance and energy efficiency offered by 3D CPUs does not come without cost, both in the financial investments to develop the technology, and the increased complexity of design. Two main limitations to 3D IC technology have been heat removal and TSV reliability. Transistor stacking creates increases in power density, current density and thermal resistance in air cooled packages. Furthermore the technology introduces vertical through silicon vias (TSVs) that create new points of failure in the chip and require development of new BEOL technologies. Although these issues can be controlled to some extent using thermal-reliability aware physical and architectural 3D design techniques, high performance embedded cooling schemes, such as micro-fluidic (MF) cooling, are fundamentally necessary to unlock the true potential of 3D ICs. A new paradigm is being put forth which integrates the computational, electrical, physical, thermal and reliability views of a system. The unification of these diverse aspects of integrated circuits is called Co-Design. Independent design and optimization of each aspect leads to sub-optimal designs due to a lack of understanding of cross-domain interactions and their impacts on the feasibility region of the architectural design space. Co-Design enables optimization across layers with a multi-domain view and thus unlocks new high-performance and energy efficient configurations. Although the co-design paradigm is becoming increasingly necessary in all fields of IC design, it is even more critical in 3D ICs where, as we show, the inter-layer coupling and higher degree of connectivity between components exacerbates the interdependence between architectural parameters, physical design parameters and the multitude of metrics of interest to the designer (i.e. power, performance, temperature and reliability). In this dissertation we present a framework for multi-domain co-simulation and co-optimization of 3D CPU architectures with both air and MF cooling solutions. Finally we propose an approach for design space exploration and modeling within the new Co-Design paradigm, and discuss the possible avenues for improvement of this work in the future.

A home-based treadmill training reduced epicardial and abdominal fat in postmenopausal women with metabolic syndrome

Introduction: The current study was designed to determine the effect of home-based treadmill training on epicardial and abdominal adipose tissue in postmenopausal women with metabolic syndrome (MS). A secondary objective was to identify significant correlations between imaging and conventional anthropometric parameters. Material and methods: Sixty postmenopausal women with MS volunteered for the current trial. Thirty were randomly assigned to perform a supervised home-based 16-week treadmill training program, 3 sessions/week, consisting of a warm-up, 30-40 min treadmill exercise (increasing 5-minutes each 4-weeks) at a work intensity of 60-75% of peak heart rate (increasing 5% each 4-weeks) and cooling-down. Epicardial fat thickness (EFT) was assessed by echocardiography. Abdominal fat mass in the lumbar regions L1-L4 and L4-L5 was determined by dual X-ray absorptiometry. Results: Epicardial fat thickness and abdominal fat percentages were significantly improved after the completion of the training program. Another striking feature of the current study was the moderate correlation that was found between EFT and waist circumference (WC). Conclusion: Home-based treadmill training reduced epicardial and abdominal fat in postmenopausal women with MS. A secondary finding was that a moderate correlation was found between EFT and WC. While current investigations are promising, future studies are still required to consolidate this approach in clinical application.

Europeanization beyond the EU: The case of Georgia.

320 p.

Modeling Flood Stage-Duration-Frequency: A Risk Assessment of Critical Infrastructure in the Tidal Potomac

The service of a critical infrastructure, such as a municipal wastewater treatment plant (MWWTP), is taken for granted until a flood or another low frequency, high consequence crisis brings its fragility to attention. The unique aspects of the MWWTP call for a method to quantify the flood stage-duration-frequency relationship. By developing a bivariate joint distribution model of flood stage and duration, this study adds a second dimension, time, into flood risk studies. A new parameter, inter-event time, is developed to further illustrate the effect of event separation on the frequency assessment. The method is tested on riverine, estuary and tidal sites in the Mid-Atlantic region. Equipment damage functions are characterized by linear and step damage models. The Expected Annual Damage (EAD) of the underground equipment is further estimated by the parametric joint distribution model, which is a function of both flood stage and duration, demonstrating the application of the bivariate model in risk assessment. Flood likelihood may alter due to climate change. A sensitivity analysis method is developed to assess future flood risk by estimating flood frequency under conditions of higher sea level and stream flow response to increased precipitation intensity. Scenarios based on steady and unsteady flow analysis are generated for current climate, future climate within this century, and future climate beyond this century, consistent with the WWTP planning horizons. The spatial extent of flood risk is visualized by inundation mapping and GIS-Assisted Risk Register (GARR). This research will help the stakeholders of the critical infrastructure be aware of the flood risk, vulnerability, and the inherent uncertainty.

Producers' Perceptions and Consumers' Behaviour Toward Certified Beans from Integrated Production (IP) in the Brazilian Central Region

Integrated production (IP) is part of the Brazilian government program to promote sustainable agricultural production. IP ensure minimum food quality standards for domestic market, and export. Furthermore, IP is considered a good option to reduce negative environmental impacts of intensive crops in tropical Savannas, including common beans, as a Brazilian staple food. Although its advantages, and the government’s effort to promote IP, few growers are adopting IP. Maybe, the perception about IP usefulness and/or its ease of use is not too clear. Moreover, the production sector is driven by market signs, and there is few information on the consumer's preferences toward IP certified products in Brazil. In this study, we sought to identify some critical factors that can influence the IP adoption in beans' production. Moreover, we sought to verify the consumers’ perceptions and intention of purchasing IP certified beans (hypothetical product). This report comprises four chapters: (1) an introduction illustrating the context in which the research was based; (2) the results on the study of IP adoption based on the Technology Acceptance Model (TAM); (3) the choice experiment results applied to identify consumers preferences and willingness-to-pay (WTP) for IP label; (4) the results on the Theory of Planned Behaviour (TPB) applied to identify consumers’ perception toward IP certified beans. This research contributes with rich information for the beans’ supply chain, providing several insights to growers, retail and other agents, including policy makers. Beans’ production sector seems to be positively intentioned to adopt IP, but further studies should be conducted to test other adoption indicators using TAM model. Surveyed consumers are willing to pay a premium price for IP labelled beans. They showed a positive attitude toward purchasing IP labelled beans. It is an important information to motivate production sector to offer certified beans to the market.

No relationship between most polymorphisms of steroidogenic acute regulatory (StAR) gene with polycystic ovarian syndrome

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine women’s disorders in reproductive age. Hyperandrogenism has a critical role in the etiology of PCOS and it can cause fault in Steroidogenesis process. During steroidogenesis, steroidogenic acute regulatory protein (StAR) seems to increase the delivery of cholesterol through mitochondrial membrane. Therefore, polymorphisms of StAR might effect on this protein and play a role in the etiology of PCOS. Objective: The aim of this study was to investigate the association between StAR SNPs with PCOS. Thus, seven polymorphisms in this gene: rs104894086, rs104894089, rs104894090, rs137852689, rs10489487, rs104894085 were detected. Materials and Methods: In this case control study, 45 PCOS women, 40 male factor/unexplained infertile women, and 40 fertile women as two control groups were participated from 2008-2012. Polymorphisms were detected using restriction fragment length polymorphism (PCR-RFLP) method. Results: Heterozygote genotyping for rs137852689 SNP (amino acid 218 C > T) was only seen in seven PCOS patients, one in normal ovulatory women, and five in male factor/unexplained infertile women (15.5%, 2.5%, 12.5%, respectively) (p= 0.12). While, it has shown no association between other SNPS with PCOs. Conclusion: The RFLP results for seven chosen SNPs, which located in exon 5 and 7 showed normal status in three groups, it means no heterozygous or homozygous forms of selected SNPs were observed. So, it seems evaluation of the active amino acid sites should be investigated and also the study population should be increased.

Understanding ten-eleven translocation-2 in hematological and nervous systems

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. ^ In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. ^ In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.^

Critical behavior in the site-diluted three-dimensional three-state Potts model

We have studied numerically the effect of quenched site dilution on a weak first-order phase transition in three dimensions. We have simulated the site diluted three-states Potts model studying in detail the secondorder region of its phase diagram. We have found that the n exponent is compatible with the one of the three-dimensional diluted Ising model, whereas the h exponent is definitely different.

Acute respiratory distress syndrome: does histology matter?

Kao et al. have reported in Critical Care the histological findings of 101 patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy. Diffuse alveolar damage (DAD), the histological hallmark of ARDS, was present in only 56.4 % of cases. The presence of DAD was associated with higher mortality. Evidence from this and other studies indicates that the clinical criteria for the diagnosis of ARDS identify DAD in only about half of the cases. On the contrary, there is evidence that the clinical course and outcome of ARDS differs in patients with DAD and in patients without DAD. The discovery of biomarkers for the physiological (increased alveolocapillary permeability) or histological (DAD) hallmarks of ARDS is thus of paramount importance.

Climate change adaptation solutions for the green sectors of selected zones in the MENA region

In this paper, we propose climate adaptation solutions for the green sectors in three different zones of MENA: Egypt’s Delta (irrigated), Karak, in the highlands of Jordan (rainfed), and Lebanon’s Orontes basin (mixed: rainfed-irrigated). We analysed land use and crop intensification, and calculated the economic productivity of water – a critical scarce resource in MENA. By integrating the results with evidence from literature on the potential impacts of climate change and socio-economic factors, we could identify vulnerability levels of the three regions and propose adaptation measures relying of the concept of the “food-water-energy nexus.” While the vulnerability levels are found to be high in the Delta (Egypt) and Karak (Jordan), mainly due to water scarcity and poor adaptive capacity, the vulnerability level is moderate in the Orontes zone (Lebanon) due to a diversified agricultural sector and good market development, coupled with moderate water scarcity. Proposed adaptation solutions range from measures to improve technical efficiency, to measures that encourage economically efficient allocation by use of market forces. For both cases, the development of market opportunities is emphasized to make the proposed measures attractive to farmers.

Metabolic syndrome and associated factors in a population-based sample of schoolchildren in Colombia: The FUPRECOL Study

In contrast to the definition of metabolic syndrome (MetS) in adults, there is no standard definition of MetS in pediatric populations. We aimed to assess the differences in the prevalence of MetS in children and adolescents aged 9–17 years in the city of Bogota (Colombia) using four different operational definitions for these age groups and to examine the associated variables. A total of 673 children and 1,247 adolescents attending public schools in Bogota (54.4% girls; age range 9–17.9 years) were included. The prevalence of MetS was determined by the definitions provided by the International Diabetes Federation (IDF) and three published studies by Cook et al., de Ferranti et al., and Ford et al. The prevalence of MetS was 0.3%, 6.3%, 7.8%, and 11.0% according to the IDF, Cook et al., Ford et al., and de Ferranti et al. definitions, respectively. The most prevalent components were low high-density lipoprotein cholesterol and high triglyceride levels, whereas the least prevalent components were abdominal obesity and hyperglycemia. Overall, the prevalence of MetS was higher in obese than in non-obese schoolchildren. In conclusion, MetS diagnoses in schoolchildren strongly depend on the definition chosen. These findings may be relevant to health promotion efforts for Colombian youth to develop prospective studies and to define which cut-offs are the best indicators of future morbidity.

Modelo de gestión para la atención integral de pacientes con enfermedades huérfanas o raras en Colombia

Las enfermedades raras o huérfanas corresponden a aquellas con baja prevalencia en la población, y en varios países tienen una definición distinta de acuerdo con el número de pacientes que afectan en la población. La Organización Mundial de la Salud (OMS), las define como un trastorno que afecta de 650 a 1.000 personas por millón de habitantes, de las que se han identificado alrededor de 7.000. En Colombia su prevalencia es menor de 1 por cada 5.000 personas y comprenden: las enfermedades raras, las ultra-huérfanas y las olvidadas. Los pacientes con este tipo de enfermedades imponen retos a los sistemas sanitarios, pues si bien afectan a un bajo porcentaje de la población, su atención implica una alta carga económica por los costos que involucra su atención, la complejidad en su diagnóstico, tratamiento, seguimiento y rehabilitación. El abordaje de las enfermedades raras requiere un manejo interdisciplinar e intersectorial, lo que implica la organización de cada actor del sistema sanitario para su manejo a través de un modelo que abraque las dinámicas posibles entre ellos y las competencias de cada uno. Por lo anterior, y teniendo en cuenta la necesidad de formular políticas sanitarias específicas para la gestión de estas enfermedades, el presente trabajo presenta una aproximación a la formulación de un modelo de gestión para la atención integral de pacientes con enfermedades raras en Colombia. Esta investigación describe los distintos elementos y características de los modelos de gestión clínica y de las enfermedades raras a través de una revisión de literatura, en la que se incluye la descripción de los distintos actores del Sistema de Salud Colombiano, relacionados con la atención integral de estos pacientes para la documentación de un modelo de gestión integral.

Multiple Desmoid Tumors In A Patient With Gardner's Syndrome - Report Of A Case.

Desmoid tumor (DT) is a common manifestation of Gardner's Syndrome (GS), although it is a rare condition in the general population. DT in patients with GS is usually located in the abdominal wall and/or intra-abdominal cavity. We report a case of a 32 years-old female patient with familial adenomatous polyposis (FAP), who was already submitted to total colectomy and developed multiple DT, located in the abdominal wall and in the left breast. The patient underwent several surgical procedures, with a multidisciplinary team of surgeons. Wide surgical resections of the left breast and the abdominal wall tumors were performed in separate steps. Polypropylene mesh reconstruction and muscle flaps were needed to cover the defects of the thoracic and abdominal walls. After partial necrosis of the adipose-cutaneous flap in the abdomen that required a new skin graft, she had a satisfactory outcome with complete healing of the surgical incisions. DT is frequent in GS, however, breast localization is very rare, with few cases reported in the literature. Recurrence of DT is not negligible, even after a wide surgical resection. GS patients must be followed up closely, and clinical examination, associated with imaging studies, should be performed to detect any signs of tumor. DT represents one of the most significant causes of the morbidity and mortality that affects FAP patients following colectomy. In general, the surgical procedures to excise DT are highly complex, requiring a multidisciplinary team.

[climacteric Syndrome In A Northeastern Brazilian City: A Household Survey].

To assess the prevalence of Climacteric Syndrome (CS) in women from a municipality of Northeastern Brazil which is less developed socioeconomically. A prospective household survey was performed in São Luís, Maranhão, Brazil with 1,210 climacteric women aged 45 to 60 years. Interviews were applied using previously tested standard questionnaires from April to July 2008. The severity of climacteric symptoms was analyzed by circulatory and psychological indexes and the latter were associated with menopausal status. Multiple correspondence analysis was used to assess the relation among climacteric symptoms. Most patients were 55 to 60 years old (35.3%), mulatto (37.9%), with 9-11 years of schooling (39.8%), with a partner (56%), Catholic (73.9%) and belonged to the socioeconomic class C (51.1%). The prevalence of CS was 85.9%, and hot flashes (56.4%) and sweating (50.4%) were the most prevalent symptoms. The most frequent psychological symptoms were nervousness (45%) and emotional liability (44.8%). The severity of vasomotor and psychological symptoms was significantly higher during the peri and postmenopausal period (p<0.05). Vaginal dryness (62.7%) was the most prevalent urogenital complaint. The prevalence of CS was high among women from São Luís, Maranhão, Brazil.

Genetic Predictors Of Long-term Response To Growth Hormone (gh) Therapy In Children With Gh Deficiency And Turner Syndrome: The Influence Of A Socs2 Polymorphism.

There is great interindividual variability in the response to GH therapy. Ascertaining genetic factors can improve the accuracy of growth response predictions. Suppressor of cytokine signaling (SOCS)-2 is an intracellular negative regulator of GH receptor (GHR) signaling. The objective of the study was to assess the influence of a SOCS2 polymorphism (rs3782415) and its interactive effect with GHR exon 3 and -202 A/C IGFBP3 (rs2854744) polymorphisms on adult height of patients treated with recombinant human GH (rhGH). Genotypes were correlated with adult height data of 65 Turner syndrome (TS) and 47 GH deficiency (GHD) patients treated with rhGH, by multiple linear regressions. Generalized multifactor dimensionality reduction was used to evaluate gene-gene interactions. Baseline clinical data were indistinguishable among patients with different genotypes. Adult height SD scores of patients with at least one SOCS2 single-nucleotide polymorphism rs3782415-C were 0.7 higher than those homozygous for the T allele (P < .001). SOCS2 (P = .003), GHR-exon 3 (P= .016) and -202 A/C IGFBP3 (P = .013) polymorphisms, together with clinical factors accounted for 58% of the variability in adult height and 82% of the total height SD score gain. Patients harboring any two negative genotypes in these three different loci (homozygosity for SOCS2 T allele; the GHR exon 3 full-length allele and/or the -202C-IGFBP3 allele) were more likely to achieve an adult height at the lower quartile (odds ratio of 13.3; 95% confidence interval of 3.2-54.2, P = .0001). The SOCS2 polymorphism (rs3782415) has an influence on the adult height of children with TS and GHD after long-term rhGH therapy. Polymorphisms located in GHR, IGFBP3, and SOCS2 loci have an influence on the growth outcomes of TS and GHD patients treated with rhGH. The use of these genetic markers could identify among rhGH-treated patients those who are genetically predisposed to have less favorable outcomes.