Light-field-driven electronics in the mid-infrared regime: Schottky rectification

The speed of an active electronic semiconductor device is limited by RC timescale, i.e., the time required for its charging and discharging. To circumvent this ubiquitous limitation of conventional electronics, we investigate diodes under intense mid-infrared light-field pulses. We choose epitaxial graphene on silicon carbide as a metal/semiconductor pair, acting as an ultrarobust and almost-transparent Schottky diode. The usually dominant forward direction is suppressed, but a characteristic signal occurs in reverse bias. For its theoretical description, we consider tunneling through the light-field–modulated Schottky barrier, complemented by a dynamical accumulation correction. On the basis only of the DC parametrization of the diode, the model provides a consistent and accurate description of the experimentally observed infrared phenomena. This allows the conclusion that cycle-by-cycle dynamics determines rectification. As the chosen materials have proven capabilities for transistors, circuits, and even a full logic, we see a way to establish light-field-driven electronics with rapidly increasing functionality

Impact of prototyping resource environments and timing of awareness of constraints on idea generation in product design

Research and development laboratories in universities and firms around the world try to maximize innovation with a limited set of resources. However, questions remain about the influence of resource constraints on idea generation in early-stage product design. Multiple embedded case studies were conducted with engineering students and faculty at two university campuses in Mexico. Students developed sketches for products that would satisfy an open-ended design problem in a constrained-resource setting, where the variables were the timing of when information about these constraints was revealed, and the regular prototyping environment of the student. The evidence suggests that the timing of awareness of constraints can have an impact on design outcomes, but that this effect varies depending on the designer's regular prototyping resource environment.MIT International Science and Technology InitiativeLegatum Center for Development & Entrepreneurship (Massachusetts Institute of Technology)National Science Foundation (U.S.) (Award CMMI-1130791

HPV16 Oncoproteins Induce MMPs/RECK-TIMP-2 Imbalance in Primary Keratinocytes: Possible Implications in Cervical Carcinogenesis

Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome

Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

<p>Abstract</p> <p>Background</p> <p>Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability.</p> <p>Methods</p> <p>We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for <it>HLA-DQA1</it>, <it>DRB1 </it>and <it>DQB1 </it>genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis.</p> <p>Results</p> <p>European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between <it>DQB1*05 </it>(adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions of <it>HLA DRB1*1302 </it>carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with <it>DRB1*15 </it>was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association between <it>DRB1*04 </it>and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the <it>E6 </it>gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association between <it>DQB1*05 </it>and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89).</p> <p>Conclusion</p> <p>Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.</p

Dynamics of biofilm formation and the interaction between Candida albicans and methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA)

Polymicrobial biofilms are an understudied and a clinically relevant problem. This study evaluates the interaction between C. albicans, and methicillin- susceptible (MSSA) and resistant (MRSA) S. aureus growing in single- and dual-species biofilms. Single and dual species adhesion (90 min) and biofilms (12, 24, and 48 h) were evaluated by complementary methods: counting colony-forming units (CFU mL-1), XTT-reduction, and crystal violet staining (CV). The secretion of hydrolytic enzymes by the 48 h biofilms was also evaluated using fluorimetric kits. Scanning electron microscopy (SEM) was used to assess biofilm structure. The results from quantification assays were compared using two-way ANOVAs with Tukey post-hoc tests, while data from enzymatic activities were analyzed by one-way Welch-ANOVA followed by Games-Howell post hoc test ( = 0.05). C. albicans, MSSA and MRSA were able to adhere and to form biofilm in both single or mixed cultures. In general, all microorganisms in both growth conditions showed a gradual increase in the number of cells and metabolic activity over time, reaching peak values between 12 h and 48 h (<0.05). C. albicans single- and dual-biofilms had significantly higher total biomass values (<0.05) than single biofilms of bacteria. Except for single MRSA biofilms, all microorganisms in both growth conditions secreted proteinase and phospholipase-C. SEM images revealed extensive adherence of bacteria to hyphal elements of C. albicans. C. albicans, MSSA, and MRSA can co-exist in biofilms without antagonism and in an apparent synergistic effect, with bacteria cells preferentially associated to C. albicans hyphal forms.CNPq (Council for Technical and Scientific Development) (Grant 400658/2012-7)Fundação para a Ciência e Tecnologia (FCT), Portugal (SFRH/BPD/71076/2010)CAPES(Coordination for the Improvement of Higher Level Personnel

Predicting haplogroups using a versatile machine learning program (PredYMaLe) on a new mutationally balanced 32 Y-STR multiplex (CombYplex): Unlocking the full potential of the human STR mutation rate spectrum to estimate forensic parameters

We developed a new mutationally well-balanced 32 Y-STR multiplex (CombYplex) together with a machine learning (ML) program PredYMaLe to assess the impact of STR mutability on haplogourp prediction, while respecting forensic community criteria (high DC/HD). We designed CombYplex around two sub-panels M1 and M2 characterized by average and high-mutation STR panels. Using these two sub-panels, we tested how our program PredYmale reacts to mutability when considering basal branches and, moving down, terminal branches. We tested first the discrimination capacity of CombYplex on 996 human samples using various forensic and statistical parameters and showed that its resolution is sufficient to separate haplogroup classes. In parallel, PredYMaLe was designed and used to test whether a ML approach can predict haplogroup classes from Y-STR profiles. Applied to our kit, SVM and Random Forest classifiers perform very well (average 97 %), better than Neural Network (average 91 %) and Bayesian methods (< 90 %)

Legitimacy intermediation in the multilevel European polity and its collapse in the euro crisis

This essay re-examines the dual – republican and liberal – foundations of democratic legitimacy in the Western traditions of normative political theory. Considered in isolation, the European Union conforms to liberal standards but cannot satisfy republican criteria. Given these conflicting standards, debates on the alleged European democratic deficit have remained inconclusive. Moreover, they have failed to pay sufficient attention to the multilevel character of the European polity and to the normative potential of legitimacy intermediation in its two-step compliance and legitimating relationships. I argue, however, that the capacity of democratic member states to legitimate the exercise of European governing functions is being destroyed in the present euro crisis, and I briefly discuss the implications of this new constellation.In der westlichen Tradition der normativen politischen Theorie beruht demokratische Legitimität auf der doppelten Grundlage republikanischer und liberaler Prinzipien. Für sich betrachtet entspricht die Europäische Union zwar liberalen Kriterien, aber eben nicht den republikanischen Anforderungen. Angesichts so unterschiedlicher Kriterien konnte es auch im Streit über das angebliche europäische Demokratiedefizit keine Einigung geben. Überdies ignorierte diese Diskussion den Mehrebenen-Charakter der europäischen Politik und das normative Potenzial der Legitimationsvermittlung zwischen Union und Bürgern durch die demokratisch verfassten Mitgliedstaaten. Die gegenwärtige Eurokrise allerdings zerstört die Fähigkeit demokratischer Mitgliedstaaten, die Ausübung europäischer Herrschaftsfunktionen zu legitimieren. Der Aufsatz erörtert die Implikationen dieser neuen Konstellation.1 Introduction 2 Legitimacy discourses The republican discourse The liberal discourse Differences 3 Constitutional democracies – and the European Union? 4 Legitimacy intermediation in the multilevel European polity 5 The end of legitimacy intermediation in the euro crisis Monetary Union and the failure of output legitimacy Rescuing the euro through supranational intervention 6 Legitimate supranational government? Input-oriented European legitimacy? 7 Reducing the burden on European legitimacy Reference