Wafer-level packaged RF-MEMS switches fabricated in a CMOS fab

Reports on wafer-level packaged RF-MEMS switches fabricated in a commercial CMOS fab. Switch fabrication is based on a metal surface micromachining process. A novel wafer-level packaging scheme is developed, whereby the switches are housed in on-chip sealed cavities using benzocyclobutene (BCB) as the bonding and sealing material. Measurements show that the influence of the wafer-level package on the RF performance can be made very small.\ud \u

Blunted neural response to anticipation, effort and consummation of reward and aversion in adolescents with depression symptomatology

Neural reward function has been proposed as a possible biomarker for depression. However how the neural response to reward and aversion might differ in young adolescents with current symptoms of depression is as yet unclear. 33 adolescents were recruited. 17 scoring low on the Mood and Feelings Questionnaire (MFQ) (Low Risk: LR) and 16 scoring high on the MFQ (High Risk: HR). Our fMRI task measured; anticipation (pleasant/unpleasant cue), effort (achieve a pleasant taste or avoid an unpleasant taste) and consummation (pleasant/unpleasant tastes) in Regions of Interest; ventral medial prefrontal cortex (vmPFC), pregenual cingulate cortex (pgACC), the insula and ventral striatum. We also examined whole brain group differences. In the ROI analysis we found reduced activity in the HR group in the pgACC during anticipation and reduced pgACC and vmPFC during effort and consummation. In the whole brain analysis we also found reduced activity in the HR group in the prefrontal cortex and the precuneus during anticipation. We found reduced activity in the hippocampus during the effort phase and in the anterior cingulate/frontal pole during consummation in the HR group. Increased anhedonia measures correlated with decreased pgACC activity during consummation in the HR group only. Our results are the first to show that adolescents with depression symptoms have blunted neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This study suggests that interventions in young people at risk of depression, that can reverse blunted responses, might be beneficial as preventative strategies

The effect of induced sadness and moderate depression on attention networks

This study investigates how sadness and minor/moderate depression influences the three functions of attention: alerting, orienting, and executive control using the attention network test. The aim of the study is to investigate whether minor to moderate depression is more similar to sadness or clinical depression with regards to attentional processing. It was predicted that both induced sadness and minor to moderate depression will influence executive control by narrowing spatial attention and in turn this will lead to less interference from the flanker items (i.e., less effects of congruency) due to a focused attentional state. No differences were predicted for alerting or orienting functions. The results from the two experiments, the first inducing sadness (Experiment 1) and the second measuring subclinical depression (Experiment 2), show that, as expected, participants who are sad or minor to moderately depressed showed less flanker interference compared to participants who were neither sad nor depressed. This study provides strong evidence, that irrespective of its aetiology, sadness and minor/moderate depression have similar effects on spatial attention

Diagnostic value of MRI-based PSA density in predicting transperineal sector-guided prostate biopsy outcomes

PURPOSE: Prostate-specific antigen (PSA) density (PSAD) has potential to increase the diagnostic utility of PSA, yet has had poor uptake in clinical practice. We aimed to determine the diagnostic value of magnetic resonance imaging-derived PSAD (MR-PSAD) in predicting transperineal sector-guided prostate biopsy (TPSB) outcomes. MATERIALS AND METHODS: Men presenting for primary TPSB from 2007 to 2014 were considered. Histological outcomes were assessed and defined as: presence of any cancer or significant cancer defined as presence of Gleason 4 and/or maximum tumour core length (MCCL) ≥ 4 mm (G4); or Gleason 4 and/or MCCL ≥ 6 mm (G6). Sensitivity, specificity and positive and negative predictive values were calculated, and receiver operating characteristics (ROC) curves were generated to compare MR-PSAD and PSA. RESULTS: Six hundred fifty-nine men were evaluated with mean age 62.5 ± 9 years, median PSA 6.7 ng/ml (range 0.5-40.0), prostate volume 40 cc (range 7-187) and MR-PSAD 0.15 ng/ml/cc (range 0.019-1.3). ROC area under the curve (95% CI) was significantly better for MR-PSAD than PSA for all cancer definitions (p < 0.001): 0.73 (0.70-0.76) versus 0.61 (0.57-0.64) for any cancer; 0.75 (0.71-0.78) versus 0.66 (0.62-0.69) for G4; and 0.77 (0.74-0.80) versus 0.68 (0.64-0.71) for G6. Sensitivities for MR-PSAD < 0.1 ng/ml/cc were 85.0, 89.9 and 91.9% for any, G4 and G6 cancer, respectively. CONCLUSION: MR-PSAD may be better than total PSA in determining risk of positive biopsy outcome. Its use may improve risk stratification and reduce unnecessary biopsies

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

Toll-Like Receptors 2 and 4 Regulate the Frequency of IFNγ-Producing CD4+ T-Cells during Pulmonary Infection with Chlamydia pneumoniae

TLR2 and TLR4 are crucial for recognition of Chlamydia pneumoniae in vivo, since infected TLR2/4 double-deficient mice are unable to control the infection as evidenced by severe loss of body weight and progressive lethal pneumonia. Unexpectedly, these mice display higher pulmonary levels of the protective cytokine IFNγ than wild type mice. We show here, that antigen-specific CD4+ T-cells are responsible for the observed IFNγ-secretion in vivo and their frequency is higher in TLR2/4 double-deficient than in wild type mice. The capacity of TLR2/4 double-deficient dendritic cells to re-stimulate CD4+ T-cells did not differ from wild type dendritic cells. However, the frequency of CD4+CD25+Foxp3+ T-cells was considerably higher in wild type compared to TLR2/4 double-deficient mice and was inversely related to the number of IFNγ-secreting CD4+ effector T-cells. Despite increased IFNγ-levels, at least one IFNγ-mediated response, protective NO-secretion, could not be induced in the absence of TLR2 and 4. In summary, CD4+CD25+Foxp3+ regulatory T-cells fail to expand in the absence of TLR2 and TLR4 during pulmonary infection with C. pneumoniae, which in turn enhances the frequency of CD4+IFNγ+ effector T-cells. Failure of IFNγ to induce NO in TLR2/4 double-deficient cells represents one possible mechanism why TLR2/4 double-deficient mice are unable to control pneumonia caused by C. pneumoniae and succumb to the infection

On the Dialectics of Global Governance in the Twenty-first Century : A Polanyian Double Movement?

Following decades of economic globalisation and market-oriented reforms across the world, Karl Polanyi’s double movement has been invoked not only to explain what is happening but also to give reasons for being hopeful about a different future. Some have suggested a pendulum model of history: a swing from markets to society leading, in the next phase, to a swing from society to markets, and so on. The double movement can also be understood dialectically as a description of an irreversible historical development following its own inner laws or schemes of development. Going beyond a thesis – antithesis – synthesis pattern, I maintain that conceptions and schemes drawn from dialectics, and especially dialectical critical realism, can provide better geo-historical hypotheses for explaining past changes and for building scenarios about possible future changes. I analyse political economy contradictions and tendencies, and focus on normative rationality, to assess substantial claims about rational tendential directionality of world history. I argue that democratic global Keynesianism would enable processes of decommodification and new syntheses concerning the market/social nexus. A learning process towards qualitatively higher levels of reflexivity can help develop global transformative agency. Existing contradictions can be resolved by means of rational collective actions and building more adequate common institutions. These collective actions are likely to involve new forms of political agency such as world political parties.Peer reviewe

The Nature Drawings of Peter Karklins

https://via.library.depaul.edu/museum-publications/1010/thumbnail.jp

The PARP inhibitor AZD2461 provides insights into the role of PARP3 inhibition for both synthetic lethality and tolerability with chemotherapy in preclinical models

The PARP inhibitor AZD2461 was developed as a next-generation agent following olaparib, the first PARP inhibitor approved for cancer therapy. In BRCA1-deficient mouse models, olaparib resistance predominantly involves overexpression of P-glycoprotein,so AZD2461 was developed as a poor substrate for drug transporters. Here we demonstrate the efficacy of this compound against olaparib-resistant tumors that overexpress P-glycoprotein. In addition, AZD2461 was better tolerated in combination with chemotherapy than olaparib in mice, which suggests that AZD2461 could have significant advantages over olaparib in the clinic. However, this superior toxicity profile did not extend to rats. Investigations of this difference revealed a differential PARP3 inhibitory activity for each compound and a higher level of PARP3 expression in bone marrow cells from mice as compared with rats and humans. Our findings have implications for the use of mouse models to assess bone marrow toxicity for DNA-damaging agents and inhibitors of the DNA damage response. Finally, structural modeling of the PARP3-active site with different PARP inhibitors also highlights the potential to develop compounds with different PARP family member specificity profiles for optimal antitumor activity and tolerability