Ultra-Low Leakage, Energy-Efficient Digital Integrated Circuit and System Design

The advances of the complementary metal-oxide-semiconductor (CMOS) technology manufacturing and design over the years have enabled a diverse range of applications across the power consumption, performance, and area (PPA) spectra. Many of the recent and prospective applications rely on the availability of energy-autonomous, miniaturized systems, i.e., ultra-low power (ULP) VLSI systems, which are generally characterized by extreme resource limitations. Some examples of applications are wireless sensing platforms, body-area sensor networks (BASN), biomedical and implantable devices, wearables, hearables, and monitors. Within the context of such applications, the key requirements are long lifetime and miniaturized size (sub-/millimeter-scale). In order to enable both requirements, energy-efficiency is the key metric. It allows for extended battery lifetime and operation with the energy that can be harvested from the environment, and it limits the size (volume) of the energy sources utilized to power these systems. Ultra-low voltage (ULV) operation is a key technique in which the VDD of circuits is reduced from nominal to near or below the threshold voltage of the transistor. It is a powerful knob that has been largely exploited by designers in order to achieve ultra-low power consumption and high energy-efficiency in CMOS. Existing ULP VLSI systems typically operate at a lower supply voltage thereby reducing their energy consumption by one to two orders of magnitude in order to enable the aforementioned applications. While supply voltage scaling is a promising measure for achieving low power and reducing energy consumption, it brings up several challenges. One critical issue is the leakage energy dissipated by the devices, which is magnified in portion to the total energy consumption at ULV. The reason is that, as VDD scales from nominal to near-threshold and sub-threshold, transistors become increasingly slower and they accumulate more leakage (i.e., static) power over longer cycle times. This energy waste accounts for a significant portion of the system's total energy consumption, offsets the gains provided by voltage scaling, defines the minimum energy per operation, and poses a practical limit for the system's energy-efficiency. This thesis presents selected research works on ultra-low leakage, energy-efficient digital integrated circuit design. More specifically, it describes novel and key techniques for minimizing the energy waste of idle/underutilized and always-on hardware. The main goal of such techniques is to push the envelope of energy-efficiency in energy-autonomous, miniaturized VLSI systems. Such techniques are applied to key building blocks of emerging mobile and embedded computing devices resulting in state-of-the-art energy-efficiencies

Antiproliferative Organic Salts Derived from Betulinic Acid: Disclosure of an Ionic Liquid Selective Against Lung and Liver Cancer Cells

In the last few years, we have been witnessing an increasing interest in ionic liquids (ILs) and organic salts, given their potential applications in biological and pharmaceutical sciences. We report the synthesis and in vitro evaluation of novel organic salts combining betulinate, known for its anticancer properties, with antimalarial drugs, primaquine, chloroquine, and mepacrine, and also with the trihexyltetradecylphosphonium ([P6,6,6,14]) cation. The salts were screened for their in vitro activity against tumor lines HepG2 (liver), MG63 (osteosarcoma), T47D (breast), A459 (lung), and RKO (colon), and also on normal human fibroblasts. All betulinates prepared displayed antiproliferative properties, with the trihexyltetradecylphosphonium betulinate standing out for its higher selectivity. This unprecedented disclosure of a betulinic acid (BA)-derived IL with selective antitumor activity constitutes a relevant first step toward development of novel anticancer therapies based on BA-derived IL.info:eu-repo/semantics/publishedVersio

Prospective and randomized study of patients with open fractures of the femoral shaft, treated with plate or open intramedullary locked nail

We assessed the complications and treatment outcomes in a prospective and randomized study of two osteosynthesis techniques in open femoral shaft fractures. Between January 2002 and April 2004, 40 patients with open fractures of the femoral shaft were assessed, with 20 being treated with open reamed intramedullary locked nail and 20 with plate. Twenty-six (65%) fractures were classified as Gustilo type -I open fractures; ten (25%) as type II and four (10%), as type IIIA. There were 21 blunt injuries and 19 gunshot injuries. Three patients were excluded from the final assessment. Complications were observed in 12 (32.4%) patients, 4 in the plate group and 8 in the nail group. Reamed intramedullary locked nail resulted in two deep infections (10%), two superficial infections (10%), and one nonunion (5%). With plate techniques, we had one deep infection associated to nonunion (5,8%) and one superficial infection (5.8%). Good and excellent outcomes were found in 28 fractures (75.7%), fair (7.5%) in three cases, and poor (15%) in six, according to Thorensen s criteria. In this study, the stabilization with plate results in lower complications rate when compared to the open intramedullary nail, although with no statistical significance.Trata-se de um estudo prospectivo e randomizado de duas técnicas de osteossíntese no tratamento das fraturas expostas diafisárias do fêmur, realizado entre janeiro de 2002 a abril de 2004. Haste intramedular bloqueada fresada realizada a foco aberto e placa e parafusos foram empregadas no tratamento de 20 pacientes em cada grupo. De acordo com a classificação de Gustilo, 26 (65%) foram tipo I, 10 (25%) tipo II e 4 (10%) tipo IIIA. Quanto ao mecanismo das fraturas, 21 por trauma contuso e 19 por ferimentos de arma de fogo.Três pacientes foram excluídos nas avaliação final. Houve complicação em 12 (32,4%),sendo 4 no grupo de placas e 8 no grupo das hastes. O grupo de haste bloqueada apresentou 2 (10%) infecções profundas, 2 infecções superficiais (10%), 1 falha de consolidação (5%).O grupo de placa e parafusos resultou em 1 infecção profunda associada à falha de consolidação (5,8%), 1 infecção superficial (5,8%). Pela classificação de resultados de Thorensen obteve-se bons e excelentes resultados em 28 (75,7%) fraturas, 3 (7.5%) casos regulares e 6 (15%) casos ruins. A estabilização com placas e parafusos, trouxe menores taxas de complicações, quando comparadas com o uso de hastes fresadas a foco aberto,embora sem significado estatístico.Universidade Federal da Bahia Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Ortopedia e TraumatologiaFaculdade de Medicina Hospital Universitário Professor Edgard Santos Serviço de OrtopediaHUPES Serviço de Ortopedia e TraumatologiaUNIFESP, EPM, Depto. de Ortopedia e TraumatologiaSciEL

Geostatistical simulations with heterotopic hard and soft data without modeling the linear model of coregionalization

Most mining decisions are based on models estimated/simulated given the information obtained from samples. During the exploration stage, samples are commonly taken using diamond drill holes which are accurate and precise. These samples are considered hard data. In the production stage, new samples are added. These last are cheaper and more abundant than the drill hole samples, but imprecise and are here named as soft data. Usually hard and soft data are not sampled at the same locations, they form a heterotopic dataset. This article proposes a framework for geostatistical simulation with completely heterotopic soft data. The simulation proceeds in two steps. First, the variable of interest at the locations where soft data are available is simulated. The local conditional distributions built at these locations consider both hard and soft data and are obtained using simple cokriging with the intrinsic coregionalization model. Second, the variable of interest in the entire simulation grid using the original and previously simulated values at soft data locations is simulated. The results show that the information from soft data improved both the accuracy and precision of the simulated models. The proposed framework is illustrated by a case study with data obtained from an underground copper mine

Lipocalin 2 is present in the EAE brain and is modulated by natalizumab

The authors acknowledge the BiogenIdec, for providing Natalizumab (BiogenIdec, Boston, MA, USA). We are thankful to theCOST(European Cooperation in Science and Technology) Action NEURINFNETBM0603. We also thank Dr. Nadine Santos for critically reviewing this manuscript.Multiple sclerosis (MS) is a demyelinating disease that causes major neurological disability in young adults. A definitive diagnosis at the time of the first episode is still lacking, but since early treatment leads to better prognosis, the search for early biomarkers is needed. Here we characterized the transcriptome of the choroid plexus (CP), which is part of the blood-brain barriers (BBBs) and the major site of cerebrospinal fluid production, in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. In addition, cerebrospinal fluid samples from two cohorts of patients with MS and with optic neuritis (ON) were analyzed to confirm the clinical relevance of the findings. Genes encoding for adhesion molecules, chemokines and cytokines displayed the most altered expression, supporting the role of CP as a site of immune-brain interaction in MS. The gene encoding for lipocalin 2 was the most up-regulated; notably, the cerebrospinal fluid lipocalin 2 levels coincided with the active phases of the disease. Immunostaining revealed that neutrophils infiltrating the CP were the source of the increased lipocalin 2 expression in this structure. However, within the brain, lipocalin 2 was also detected in astrocytes, particularly in regions typically affected in patients with MS. The increase of lipocalin 2 in the cerebrospinal fluid and in astrocytes was reverted by natalizumab treatment. Most importantly, the results obtained in the murine model were translatable into humans since patients from two different cohorts presented increased cerebrospinal fluid lipocalin 2 levels. The findings support lipocalin 2 as a valuable molecule for the diagnostic/monitoring panel of MS.This work was supported by a grant from The Dana Foundation (USA) and by a grant from Fundação para a Ciência e Tecnologia(FCT, Portugal) (PIC/IC/83231/2007). Fernanda Marques and Sandro D. Mesquita are recipients of postdoctoral and doctoral fellow- ships from FCT, Portugal, respectively

Effect of Graphite Nanosheets on Properties of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)

The influence of different contents, 0.25, 0.50, and 1.00 wt%, of graphite nanosheets (GNS) on the properties of poly(3-hydroxybutyrate- co-3-hydroxyvalerate) (PHBV) nanocomposites obtained by solution casting method has been studied. GNS were prepared by three steps: intercalation (chemical exfoliation), expansion (thermal treatment), and the GNS obtainment (physical treatment by ultrasonic exfoliation). X-ray diffraction (XRD), Raman spectroscopy, and field emission gun-scanning electron microscopy (FE-SEM) showed that the physical, chemical, and thermal treatments preserved the graphite sheets structure. XRD and Raman results also showed that GNS were dispersed in the PHBV matrix. The degree of crystallinity (Xc) of the nanocomposites did not change when the graphite nanosheets were added. However, the GNS acted as nucleation agent for crystallizationthat is, in the second heating the samples containing GNS showed two melting peaks. The addition the GNS did not change the thermal stability of the PHBV.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fed Univ Sao Paulo UNIFESP, Grp Polymers & Macromol, Inst Sci & Technol, Sao Jose Dos Campos, SP, BrazilNatl Inst Space Res INPE, Associated Lab Sensors & Mat LAS, Sao Jose Dos Campos, SP, BrazilInstitute of Science and Technology, Universidade Federal de São Paulo (UNIFESP), Group of Polymers and Macromolecules, São José dos Campos, SP, BrazilCNPq: 303287/2013-6CNPq: 158961/2014-5Web of Scienc

Neudesin is involved in anxiety behavior: structural and neurochemical correlates

Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.This work is supported by a grant from FCT (PTDC/SAU-OSM/104475/2008) under POCTI-COMPETE funds. Ashley Novais, Ana Catarina Ferreira, Ana David-Pereira and Filipa L. Campos are recipients of doctoral fellowships and Fernanda Marques is a recipient of postdoctoral fellowship from Fundacao para a Ciencia e Tecnologia (FCT), Portugal. We acknowledge Merck Serono for providing the neudesin-null mouse strain. We are thankful to Despina Papasava and Vasileios Kafetzopoulos for the assistance given in the HPLC analysis of neurotransmitters

3D printing as a tool in anatomy teaching: An integrative review

Anatomy is essentially a three-dimensional content and learning its structures, through 3D impressions, for example, is of notable importance. In this context, traditional teaching methods, despite being highly effective, still have some limitations. Therefore, 3D printing has been introduced in the teaching of Anatomy, bringing several advantages, such as accuracy, personalized study and easy handling. Based on these premises, the objective of this work was to carry out an integrative review on the use of 3D printing in the teaching of human anatomy. A study was carried out in science direct, PUBMED, Scielo databases between 2010 and 2021 using the following descriptors 3D printing and teaching of anatomy. It was found that among the benefits of using 3D parts, there are: accuracy, durability, ease of production, good cost-benefit ratio and reduction of security risks linked to the fixation of cadaver and plastinated specimens. It was observed that in some studies most students preferred the use of 3D printing to traditional methods. Other studies have shown the importance of the use of 3D printing as a complementary tool to traditional methods of teaching anatomy. It was found that the use of 3D printing as a teaching tool may reduce the demand for bodies and overcome some of the governmental legal and ethical problems in the cadaver study, further studies should be carried out to assess the long-term impact of using 3D printing

Análise da sensibilidade do modelo geológico no sequenciamento de lavra

00