Processor Design in 3D Die-Stacking Technologies

Three-dimensional integration is an emerging fabrication technology that vertically stacks multiple integrated chips. The benefits include an increase in device density; much greater flexibility in routing signals, power, and clock; the ability to integrate disparate technologies; and the potential for new 3D circuit and microarchitecture organizations. This article provides a technical introduction to the technology and its impact on processor design. Although our discussions here primarily focus on high-performance processor design, most of the observations and conclusions apply to other microprocessor market segments.     

Postconditioning by Delayed Administration of Ciclosporin A: Implication for Donation after Circulatory Death (DCD)

Heart transplantation is facing a shortage of grafts. Donation after Circulatory Death (DCD) would constitute a new potential of available organs. In the present work, we aimed to evaluate whether Postconditioning (ischemic or with ciclosporin-A (CsA)) could reduce ischemia-reperfusion injury in a cardiac arrest model when applied at the start of reperfusion or after a delay. An isolated rat heart model was used as a model of DCD. Hearts were submitted to a cardiac arrest of 40 min of global warm ischemia (37 °C) followed by 3 h of 4 °C-cold preservation, then 60 min reperfusion. Hearts were randomly allocated into the following groups: control, ischemic postconditioning (POST, consisting of two episodes each of 30 s ischemia and 30 s reperfusion at the onset of reperfusion), and CsA group (CsA was perfused at 250 nM for 10 min at reperfusion). In respective subgroups, POST and CsA were applied after a delay of 3, 10, and 20 min. Necrosis was lower in CsA and POST versus controls (p < 0.01) whereas heart functions were improved (p < 0.01). However, while the POST lost its efficacy if delayed beyond 3 min of reperfusion, CsA treatment surprisingly showed a reduction of necrosis even if applied after a delay of 3 and 10 min of reperfusion (p < 0.01). This cardioprotection by delayed CsA application correlated with better functional recovery and higher mitochondrial respiratory index. Furthermore, calcium overload necessary to induce mitochondrial permeability transition pore (MPTP) opening was similar in all cardioprotection groups, suggesting a crucial role of MPTP in this delayed protection of DCD hearts.     

Overexpression of TcNTPDase-1 Gene Increases Infectivity in Mice Infected with Trypanosoma cruzi

Ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes located on the surface of the T. cruzi plasma membrane, which hydrolyze a wide range of tri-/-diphosphate nucleosides. In this work, we used previously developed genetically modified strains of Trypanosoma cruzi (T. cruzi), hemi-knockout (KO +/−) and overexpressing (OE) the TcNTPDase-1 gene to evaluate the parasite infectivity profile in a mouse model of acute infection (n = 6 mice per group). Our results showed significantly higher parasitemia and mortality, and lower weight in animals infected with parasites OE TcNTPDase-1, as compared to the infection with the wild type (WT) parasites. On the other hand, animals infected with (KO +/−) parasites showed no mortality during the 30-day trial and mouse weight was more similar to the non-infected (NI) animals. In addition, they had low parasitemia (45.7 times lower) when compared with parasites overexpressing TcNTPDase-1 from the hemi-knockout (OE KO +/−) group. The hearts of animals infected with the OE KO +/− and OE parasites showed significantly larger regions of cardiac inflammation than those infected with the WT parasites (p < 0.001). Only animals infected with KO +/− did not show individual electrocardiographic changes during the period of experimentation. Together, our results expand the knowledge on the role of NTPDases in T. cruzi infectivity, reenforcing the potential of this enzyme as a chemotherapy target to treat Chagas disease (CD).     

Approximate and exact hybrid algorithms for private nearest-neighbor queries with database protection

Mobile devices with global positioning capabilities allow users to retrieve points of interest (POI) in their proximity. To protect user privacy, it is important not to disclose exact user coordinates to un-trusted entities that provide location-based services. Currently, there are two main approaches to protect the location privacy of users: (i) hiding locations inside cloaking regions (CRs) and (ii) encrypting location data using private information retrieval (PIR) protocols. Previous work focused on finding good trade-offs between privacy and performance of user protection techniques, but disregarded the important issue of protecting the POI dataset D. For instance, location cloaking requires large-sized CRs, leading to excessive disclosure of POIs (O(|D|) in the worst case). PIR, on the other hand, reduces this bound to \(O(\sqrt{|D|})\), but at the expense of high processing and communication overhead. We propose hybrid, two-step approaches for private location-based queries which provide protection for both the users and the database. In the first step, user locations are generalized to coarse-grained CRs which provide strong privacy. Next, a PIR protocol is applied with respect to the obtained query CR. To protect against excessive disclosure of POI locations, we devise two cryptographic protocols that privately evaluate whether a point is enclosed inside a rectangular region or a convex polygon. We also introduce algorithms to efficiently support PIR on dynamic POI sub-sets. We provide solutions for both approximate and exact NN queries. In the approximate case, our method discloses O(1) POI, orders of magnitude fewer than CR- or PIR-based techniques. For the exact case, we obtain optimal disclosure of a single POI, although with slightly higher computational overhead. Experimental results show that the hybrid approaches are scalable in practice, and outperform the pure-PIR approach in terms of computational and communication overhead.     

Improving Scalability of Application-Level Checkpoint-Recovery by Reducing Checkpoint Sizes

The execution times of large-scale parallel applications on nowadays multi/many-core systems are usually longer than the mean time between failures. Therefore, parallel applications must tolerate hardware failures to ensure that not all computation done is lost on machine failures. Checkpointing and rollback recovery is one of the most popular techniques to implement fault-tolerant applications. However, checkpointing parallel applications is expensive in terms of computing time, network utilization and storage resources. Thus, current checkpoint-recovery techniques should minimize these costs in order to be useful for large scale systems. In this paper three different and complementary techniques to reduce the size of the checkpoints generated by application-level checkpointing are proposed and implemented. Detailed experimental results obtained on a multicore cluster show the effectiveness of the proposed methods to reduce checkpointing cost.     

Differential Plasma Metabolites between High- and Low-Grade Meningioma Cases

Meningiomas (MGMs) are currently classified into grades I, II, and III. High-grade tumors are correlated with decreased survival rates and increased recurrence rates. The current grading classification is based on histological criteria and determined only after surgical tumor sampling. This study aimed to identify plasma metabolic alterations in meningiomas of different grades, which would aid surgeons in predefining the ideal surgical strategy. Plasma samples were collected from 51 patients with meningioma and classified into low-grade (LG) (grade I; n = 43), and high-grade (HG) samples (grade II, n = 5; grade III, n = 3). An untargeted metabolomic approach was used to analyze plasma metabolites. Statistical analyses were performed to select differential biomarkers among HG and LG groups. Metabolites were identified using tandem mass spectrometry along with database verification. Five and four differential biomarkers were identified for HG and LG meningiomas, respectively. To evaluate the potential of HG MGM metabolites to differentiate between HG and LG tumors, a receiving operating characteristic curve was constructed, which revealed an area under the curve of 95.7%. This indicates that the five HG MGM metabolites represent metabolic alterations that can differentiate between LG and HG meningiomas. These metabolites may indicate tumor grade even before the appearance of histological features.     

Dipotassium Glycyrrhizinate on Melanoma Cell Line: Inhibition of Cerebral Metastases Formation by Targeting NF-kB Genes-Mediating MicroRNA-4443 and MicroRNA-3620—Dipotassium Glycyrrhizinate Effect on Melanoma

Glycyrrhizic acid (GA), a natural compound isolated from licorice (Glycyrrhiza glabra), has exhibited anti-inflammatory and anti-tumor effects in vitro. Dipotassium glycyrrhizinate (DPG), a dipotassium salt of GA, also has shown an anti-tumor effect on glioblastoma cell lines, U87MG and T98G. The study investigated the DPG effects in the melanoma cell line (SK-MEL-28). MTT assay demonstrated that the viability of the cells was significantly decreased in a time- and dose-dependent manner after DPG (IC₅₀ = 36 mM; 24 h). DNA fragmentation suggested that DPG (IC₅₀) induced cellular apoptosis, which was confirmed by a significant number of TUNEL-positive cells (p-value = 0.048) and by PARP-1 [0.55 vs. 1.02 arbitrary units (AUs), p-value = 0.001], BAX (1.91 vs. 1.05 AUs, p-value = 0.09), and BCL-2 (0.51 vs. 1.07 AUs, p-value = 0.0018) mRNA compared to control cells. The proliferation and wound-healing assays showed an anti-proliferative effect on DPG-IC₅₀-treated cells, also indicating an inhibitory effect on cell migration (p-values < 0.001). Moreover, it was observed that DPG promoted a 100% reduction in melanospheres formation (p-value = 0.008). Our previous microRNAs (miRs) global analysis has revealed that DPG might increase miR-4443 and miR-3620 expression levels. Thus, qPCR showed that after DPG treatment, SK-MEL-28 cells presented significantly high miR-4443 (1.77 vs. 1.04 AUs, p-value = 0.02) and miR-3620 (2.30 vs. 1.00 AUs, p-value = 0.01) expression compared to control cells, which are predicted to target the NF-kB, CD209 and TNC genes, respectively. Both genes are responsible for cell attachment and migration, and qPCR revealed significantly decreased CD209 (1.01 vs. 0.54 AUs, p-value = 0.018) and TNC (1.00 vs. 0.31 AUs, p-value = 2.38 × 10⁻⁶) mRNA expression levels after DPG compared to untreated cells. Furthermore, the migration of SK-MEL-28 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) was attenuated by adding DPG by wound-healing assay (48 h: p-value = 0.004; 72 h: p-value = 7.0 × 10⁻⁴). In addition, the MMP-9 expression level was inhibited by DPG in melanoma cells stimulated by TPA and compared to TPA-treated cells (3.56 vs. 0.99 AUs, p-value = 0.0016) after 24 h of treatment. Our results suggested that DPG has an apoptotic, anti-proliferative, and anti-migratory effect on SK-MEL-28 cells. DPG was also able to inhibit cancer stem-like cells that may cause cerebral tumor formation.     

Anti-inflammatory effect of aqueous extracts of roasted and green Coffea arabica L.

Green coffee contains a large quantity and variety of polyphenols and flavonoids. The roasting affects the composition of the polyphenols in coffee, due to the formation of compounds generated by Maillard reaction, which can have anti-inflammatory or antioxidant potential. The anti-inflammatory and antioxidant effects of aqueous extracts of green (AGCa) and roasted (ARCa) coffee beans were investigated in animal models and using a DPPH radical scavenging test. In the formalin test the extracts reduced licking activity only in the late phase. The inhibitory values of oedema at 3 h post-carrageenan were 53% and 74% for 100 and 300 mg/kg of the AGCa extract and 36% for ARCa (300 mg/kg). Leukocyte recruitment into the peritoneal cavity was inhibited by the extracts. The antioxidant activities of the extracts were higher than the reference antioxidants, ascorbic acid and butylated hydroxytoluene. These results indicate that coffee extracts exhibit anti-inflammatory and antioxidant properties.     

Inactivation of Vibrio parahaemolyticus in Hard Clams (Mercanaria mercanaria) by High Hydrostatic Pressure (HHP) and the Effect of HHP on the Physical Characteristics of Hard Clam Meat

Shellfish may internalize dangerous pathogens during filter feeding. Traditional methods of depuration have been found ineffective against certain pathogens. The objective was to explore high hydrostatic pressure (HHP) as an alternative to the traditional depuration process. The effect of HHP on the survival of Vibrio parahaemolyticus in live clams (Mercanaria mercanaria) and the impact of HHP on physical characteristics of clam meat were investigated. Clams were inoculated with up to 7 log CFU/g of a cocktail of V. parahaemolyticus strains via filter feeding. Clams were processed at pressures ranging from 250 to 552 MPa for hold times ranging between 2 and 6 min. Processing conditions of 450 MPa for 4 min and 350 MPa for 6 min reduced the initial concentration of V. parahaemolyticus to a nondetectable level (<10¹ CFU/g), achieving >5 log reductions. The volume of clam meat (processed in shell) increased with negligible change in mass after exposure to pressure at 552 MPa for 3 min, while the drip loss was reduced. Clams processed at 552 MPa were softer compared to those processed at 276 MPa. However, all HHP processed clams were found to be harder compared to unprocessed. The lightness (L*) of the meat increased although the redness (a*) decreased with increasing pressure. Although high pressure‐processed clams may pose a significantly lower risk from V. parahaemolyticus, the effect of the accompanied physical changes on the consumer's decision to purchase HHP clams remains to be determined. Practical Application : Shellfish may contain dangerous foodborne pathogens. Traditional methods of removing those pathogen have been found ineffective against certain pathogens. The objective of this research was to determine the effect of high hydrostatic pressure on V. parahaemolyticus in clams. Processing conditions of 450 MPa for 4 min and 350 MPa for 6 min reduced the initial concentration of V. parahaemolyticus to a nondetectable level, achieving >5 log reductions.