Design And Fabrication of Condenser Microphone Using Wafer Transfer And Micro-electroplating Technique

A novel fabrication process, which uses wafer transfer and micro-electroplating technique, has been proposed and tested. In this paper, the effects of the diaphragm thickness and stress, the air-gap thickness, and the area ratio of acoustic holes to backplate on the sensitivity of the condenser microphone have been demonstrated since the performance of the microphone depends on these parameters. The microphone diaphragm has been designed with a diameter and thickness of 1.9 mm and 0.6 $\mu$m, respectively, an air-gap thickness of 10 $\mu$m, and a 24% area ratio of acoustic holes to backplate. To obtain a lower initial stress, the material used for the diaphragm is polyimide. The measured sensitivities of the microphone at the bias voltages of 24 V and 12 V are -45.3 and -50.2 dB/Pa (at 1 kHz), respectively. The fabricated microphone shows a flat frequency response extending to 20 kHz.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Development of the State Optimism Measure

Background Optimism, or positive expectations about the future, is associated with better health. It is commonly assessed as a trait, but it may change over time and circumstance. Accordingly, we developed a measure of state optimism. Methods An initial 29-item pool was generated based on literature reviews and expert consultations. It was administered to three samples: sample 1 was a general healthy population (n = 136), sample 2 was people with cardiac disease (n = 96), and sample 3 was persons recovering from problematic substance use (n = 265). Exploratory factor analysis and item-level descriptive statistics were used to select items to form a unidimensional State Optimism Measure (SOM). Confirmatory factor analysis (CFA) was performed to test fit. Results The selected seven SOM items demonstrated acceptable to high factor loadings on a single dominant factor (loadings: 0.64–0.93). There was high internal reliability across samples (Cronbach\u27s alphas: 0.92–0.96), and strong convergent validity correlations in hypothesized directions. The SOM\u27s correlations with other optimism measures indicate preliminary construct validity. CFA statistics indicated acceptable fit of the SOM model. Conclusions We developed a psychometrically-sound measure of state optimism that can be used in various settings. Predictive and criterion validity will be tested in future studies

Rupture and variable coupling behavior of the Mentawai segment of the Sunda megathrust during the supercycle culmination of 1797 to 1833

We refer to periods of subduction strain accumulation beneath the Mentawai Islands, Sumatra, as “supercycles,” because each culminates in a series of partial ruptures of the megathrust in its final decades. The finale of the previous supercycle comprised two giant earthquakes in 1797 and 1833 and whatever happened in between. This behavior between two great ruptures has implications for how the megathrust will behave between its more recent partial failure, during the M_w 8.4 earthquake of 2007, and subsequent large ruptures. We synthesize previously published coral microatoll records and a large new coral data set to constrain not only these two giant ruptures but also the intervening interseismic megathrust behavior. We present detailed maps of coseismic uplift during the two earthquakes and of interseismic deformation during the periods 1755–1833 and 1950–2000, as well as models of the corresponding slip and coupling on the underlying megathrust. The large magnitudes we derive (M_w 8.6–8.8 for 1797 and M_w 8.8–8.9 for 1833) confirm that the 2007 earthquakes released only a fraction of the moment released during the previous rupture sequence. Whereas megathrust behavior leading up to the 1797 and 2007 earthquakes was similar and comparatively simple, behavior between 1797 and 1833 was markedly different and more complex: several patches of the megathrust became weakly coupled following the 1797 earthquake. We conclude that while major earthquakes generally do not involve rupture of the entire Mentawai segment, they may significantly change the state of coupling on the megathrust for decades to follow, influencing the progression of subsequent ruptures

Clinical practice guidelines for the management of non-specific low back pain in primary care: an updated overview

Objective: The aim of this study was to provide an overview of the recommendations regarding the diagnosis and treatment contained in current clinical practice guidelines for patients with non-specific low back pai

Guidelines of the International Headache Society for Controlled Clinical Trials in Cluster Headache

In 1995, a committee of the International Headache Society developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Cluster Headache. These have not been revised. With the emergence of new medications, neuromodulation devices and trial designs, an updated version of the International Headache Society Guidelines for Controlled Clinical Trials in Cluster Headache is warranted. Given the scarcity of evidence-based data for cluster headache therapies, the update is largely consensus-based, but takes into account lessons learned from recent trials and demands by patients. It is intended to apply to both drug and neuromodulation treatments, with specific proposals for the latter when needed. The primary objective is to propose a template for designing high quality, state-of-the-art, controlled clinical trials of acute and preventive treatments in episodic and chronic cluster headache. The recommendations should not be regarded as dogma and alternative solutions to particular methodological problems should be explored in the future and scientifically validated

Novel 2-benzoyl-6-(2,3- dimethoxybenzylidene)-cyclohexenol confers selectivity toward human MLH1 defective cancer cells through synthetic lethality

DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1 cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1 deficiency

Computerized analysis of coronary artery disease: Performance evaluation of segmentation and tracking of coronary arteries in CT angiograms

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134780/1/mp0294.pd

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.

PRL3-zumab, a first-in-class humanized antibody for cancer therapy

Novel, tumor-specific drugs are urgently needed for a breakthrough in cancer therapy. Herein, we generated a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. We focused on gastric cancer (GC), wherein elevated PRL-3 mRNA levels significantly correlated with shortened overall survival of GC patients. PRL-3 protein was overexpressed in 85% of fresh-frozen clinical gastric tumor samples examined but not in patient-matched normal gastric tissues. Using human GC cell lines, we demonstrated that PRL3-zumab specifically blocked PRL-3(+), but not PRL-3(–), orthotopic gastric tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a monotherapy, rather than simultaneous combination with 5-fluorouracil or 5-fluorouracil alone. PRL3-zumab could also prevent PRL-3(+) tumor recurrence. Mechanistically, we found that intracellular PRL-3 antigens could be externalized to become “extracellular oncotargets” that serve as bait for PRL3-zumab binding to potentially bridge and recruit immunocytes into tumor microenvironments for killing effects on cancer cells. In summary, our results document a comprehensive cancer therapeutic approach to specific antibody-targeted therapy against the PRL-3 oncotarget as a case study for developing antibodies against other intracellular targets in drug discovery

Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

<p>Abstract</p> <p>Background</p> <p>Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking.</p> <p>Methods</p> <p>In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line.</p> <p>Results</p> <p>Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc.</p> <p>Conclusion</p> <p>The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin variant expression in colon cancer cell biology.</p