High Speed Test Interface Module Using MEMS Technology

With the transient frequency of available CMOS technologies exceeding hundreds of gigahertz and the increasing complexity of Integrated Circuit (IC) designs, it is now apparent that the architecture of current testers needs to be greatly improved to keep up with the formidable challenges ahead. Test requirements for modern integrated circuits are becoming more stringent, complex and costly. These requirements include an increasing number of test channels, higher test-speeds and enhanced measurement accuracy and resolution. In a conventional test configuration, the signal path from Automatic Test Equipment (ATE) to the Device-Under-Test (DUT) includes long traces of wires. At frequencies above a few gigahertz, testing integrated circuits becomes a challenging task. The effects on transmission lines become critical requiring impedance matching to minimize signal reflection. AC resistance due to the skin effect and electromagnetic coupling caused by radiation can also become important factors affecting the test results. In the design of a Device Interface Board (DIB), the greater the physical separation of the DUT and the ATE pin electronics, the greater the distortion and signal degradation. In this work, a new Test Interface Module (TIM) based on MEMS technology is proposed to reduce the distance between the tester and device-under-test by orders of magnitude. The proposed solution increases the bandwidth of test channels and reduces the undesired effects of transmission lines on the test results. The MEMS test interface includes a fixed socket and a removable socket. The removable socket incorporates MEMS contact springs to provide temporary with the DUT pads and the fixed socket contains a bed of micro-pins to establish electrical connections with the ATE pin electronics. The MEMS based contact springs have been modified to implement a high-density wafer level test probes for Through Silicon Vias (TSVs) in three dimensional integrated circuits (3D-IC). Prototypes have been fabricated using Silicon On Insulator SOI wafer. Experimental results indicate that the proposed architectures can operate up to 50 GHz without much loss or distortion. The MEMS probes can also maintain a good elastic performance without any damage or deformation in the test phase

The era of bioengineering: how will this affect the next generation of cancer immunotherapy?

Immunotherapy consists of activating the patient's immune system to fight cancer and has the great potential of preventing future relapses thanks to immunological memory. A great variety of strategies have emerged to harness the immune system against tumors, from the administration of immunomodulatory agents that activate immune cells, to therapeutic vaccines or infusion of previously activated cancer-specific T cells. However, despite great recent progress many difficulties still remain, which prevent the widespread use of immunotherapy. Some of these limitations include: systemic toxicity, weak immune cellular responses or persistence over time and most ultimately costly and time-consuming procedures. Synthetic and natural biomaterials hold great potential to address these hurdles providing biocompatible systems capable of targeted local delivery, co-delivery, and controlled and/or sustained release. In this review we discuss some of the bioengineered solutions and approaches developed so far and how biomaterials can be further implemented to help and shape the future of cancer immunotherapy. The bioengineering strategies here presented constitute a powerful toolkit to develop safe and successful novel cancer immunotherapies

Doe Study of Polyurethane Processing Parameters Affects on Microphase Separation and Material Properties

In this study, a design of experiments (DOE) has been setup to better understand the effects of percentage of hard segment (%HS), mixing index, temperature, and environmental humidity on the microstructure development, tensile properties, and thermal properties of an MDI based poly(ester urethane) with 1,4 butane diol chain extender. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC) were utilized to better investigate the amount of microphase separation. Tensile testing was conducted to measure the elongation, tensile strength at break, and the resistance to tear. Finally, scanning electron microscopy (SEM) was used to examine any microstructure or superstructure development or phase separation. A DOE statistical regression analysis was completed to insure adequate sample sizes, low factor aliasing, and high statistical confidence and signal-to-noise (low p-value and high T-stat). Regression models are presented. Results indicate that the amount of hard segment had a large influence on hydrogen bonded carbonyl groups. However, these formations remained in amorphous state and did not form well structured, phase separated blocks. Results also show that the mixing temperature has a large effect on both tensile and tear strengths. Moreover, DSC results indicate a significant impact of mixing temperature on the crystallinity of the sample. A large second order interaction between relative humidity and the samples glass transition temperature has been observed. However, humidity effects were not detectable in FTIR spectrums.Materials Science and Engineerin

Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human.

As the majority of ovarian cancer (OC) patients are diagnosed with metastatic disease, less than 40% will survive past 5 years after diagnosis. OC is characterized by a succession of remissions and recurrences. The most promising time point for immunotherapeutic interventions in OC is following debulking surgery. Accumulating evidence shows that T cells are important in OC; thus, cancer vaccines capable of eliciting antitumor T cells will be effective in OC treatment. In this review, we discuss different cancer vaccines and propose strategies for their incorporation into the OC standard-of-care regimens. Using the murine ID8 ovarian tumor model, we provide evidence that a cancer vaccine can be effectively combined with OC standard-of-care to achieve greater overall efficacy. We demonstrate several important similarities between the ID8 model and OC patients, in terms of response to immunotherapies, and the ID8 model can be an important tool for evaluating combinatorial regimens and clinical trial designs in OC. Other emerging models, including patient-derived xenograft and genetically engineered mouse models, are continuing to improve and can be useful for evaluating cancer vaccination therapies in the near future. Here, we provide a comprehensive review of the completed and current clinical trials evaluating cancer vaccines in OC

Validation of the Diabetes Attitude Scale on a sample of Quebec health-care professionals

The following study aimed to: (1) compose a French version ofAnderson et al.'s (1989) original Diabetes Attitude Scale (DAS) by sampling 5 groups of Quebec health care professionals; (2) increase the reliability and validity ofthe DAS (Anderson et al., 1989) through the creation ofa revised version ofthis instrument. This scale, entitled the revised Diabetes Attitude Scale (DAS-R), was developed through the efforts of a panel of 6 diabetes educators from Notre Dame Hospital, Montreal, Quebec. Thirty-eight items, thirty-one of these with Cronbach alphas greater than 0.37, were selected from the original DAS (1989) and combined with 27 items that had been created by members of the panel to form a 65-item scale. The items were revised by the panel and those deemed to be redundant or to increase scale variability were dropped. A total of fifteen items were dropped, and the final version of the scale contained 50 questions. The 50 -item scale was then mailed to 478 health care professionals, nurses, dietitians, physicians, pharmacists, and psychologists (specialists and nonspecialists in diabetes care) in all regions of Quebec. Four-hundred additional surveys were distributed to health care professionals through Quebec Diabetes Association conferences. The surveys were returned by 62 nurses, 49 dietitians, 149 physicians, 55 pharmacists, and 5 psychologists, totaling 320 returns (a return rate of 36%). The returned surveys were analyzed, and a 37-item DAS-R composed of 8 subscales resulted. Evidence for the reliability and validity ofthe 37-item DAS-R are included in this study. The Diabetes Behaviour Scale (DBS) was created to provide evidence for the validity of the DAS-R. This 13-item scale was developed specifically to accompany the DAS-R and is a measure ofdiabetes management-related behaviours applicable to physicians. The development ofthe DBS was based on information obtained from specialized texts in diabetes care and opinions from a specialist in diabetes care and education (Notre Dame Hospital, Montreal). The scale is comprised of questions based on various behavioural issues appropriate to diabetes care (i.e. are patients referred to cardiologists, ophthalmologists when required? Does the physician attend diabetes workshops, seminars? Are patients referred to outpatient education clinics?). An item analysis ofthe scale revealed that 7 items had poor item-total correlations. These were dropped from further analyses. The resulting 6-item scale had a satisfactory Cronbach alpha value (alpha= .48). Analyses of the results showed that there were significant correlations between two ofthe DAS-R subscales and the DBS. This is the first time in diabetes care research that an attempt at discovering a correlation between attitudes and behaviours has been accomplished using scales derived specifically for their measurement. The relationship between attitudes and behaviours found in this study supports Ajzen and Fishbein's theory of reasoned action

Cryoablation and Immunotherapy: An Enthralling Synergy to Confront the Tumors.

Treatment of solid tumors by ablation techniques has gained momentum in the recent years due to their technical simplicity and reduced morbidity as juxtaposed to surgery. Cryoablation is one of such techniques, known for its uniqueness to destroy the tumors by freezing to lethal temperatures. Freezing the tumor locally and allowing it to remain in situ unleashes an array of tumor antigens to be exposed to the immune system, paving the way for the generation of anti-tumor immune responses. However, the immune responses triggered in most cases are insufficient to eradicate the tumors with systemic spread. Therefore, combination of cryoablation and immunotherapy is a new treatment strategy currently being evaluated for its efficacy, notably in patients with metastatic disease. This article examines the mechanistic fabric of cryoablation for the generation of an effective immune response against the tumors, and various possibilities of its combination with different immunotherapies that are capable of inducing exceptional therapeutic responses. The combinatorial treatment avenues discussed in this article if explored in sufficient profundity, could reach the pinnacle of future cancer medicine

A cancer vaccine with dendritic cells differentiated with GM-CSF and IFNα and pulsed with a squaric acid treated cell lysate improves T cell priming and tumor growth control in a mouse model.

<i> <b>Introduction:</b> </i> Ovarian cancer is one of the most lethal gynecologic cancers. Relapses after remission are common, hence novel strategies are urgently needed. Our group has previously developed a vaccination approach based on dendritic cells pulsed with HOCl-oxidized tumor lysates. Here we investigate the improvement of this vaccine strategy using squaric acid treatment of cancer cells during tumor lysate preparation and by differentiating dendritic cells in the presence of GM-CSF and IFNα. <i> <b>Methods:</b> </i> Induction of cell death by squaric acid treatment was assessed with propidium iodide (PI) and Annexin V in ID8 tumor cells. High mobility group box 1 (HMGB1) immunogenic status was analyzed using a western blot-based method, as previously described. For immunological tests, ID8 cells expressing ovalbumin (ova-ID8) were treated with squaric acid before cell lysis. DCs prepared with the canonical GM-CSF and IL-4 differentiation cocktail or IFNα and GM-CSF were pulsed with tumor cell lysates and further matured in the presence of IFNγ and LPS (4-DCs and α-DCs respectively). DCs were then used in co-culture assays with ova-specific T cells and IFNγ and IL-4 secretion measured by ELISA. DC phenotypes were characterized by FACS. Finally, DCs were tested in an ovarian cancer mouse model measuring body weight and animal survival. <i> <b>Results:</b> </i> Squaric acid treatment of mouse ovarian cancer cells induced tumor cell death as well as preserve HMGB1, a crucial Damage-associated molecular pattern (DAMP) signal, in its active reduced form. Squaric acid treatment of ID8-ova cells increased IFNγ and decreased IL-4 production from ova-specific T cells in co-culture experiments, promoting a more immunogenic cytokine secretion pattern. DCs differentiated in the presence of IFNα induced a considerable decrease in IL-4 production compared to canonical 4-DCs, without affecting IFNγ release. DC phenotyping demonstrated a more mature and immunogenic phenotype for IFNα-differentiated DCs. Vaccination in tumor-bearing mice showed that IFNα-differentiated DCs pulsed with squaric acid-treated lysates were the most potent at delaying tumor growth, improving animal survival. <i> <b>Conclusion:</b> </i> We identified squaric acid as a novel immunogenic treatment of tumor cells for cancer vaccines particularly efficient in prolonging animal survival when used in combination with IFNα-differentiated DCs. These promising results support future efforts for the clinical translation of this approach

Whole Tumor Antigen Vaccines: Where Are We?

With its vast amount of uncharacterized and characterized T cell epitopes available for activating CD4? T helper and CD8? cytotoxic lymphocytes simultaneously, whole tumor antigen represents an attractive alternative source of antigens as compared to tumor-derived peptides and full-length recombinant tumor proteins for dendritic cell (DC)-based immunotherapy. Unlike defined tumor-derived peptides and proteins, whole tumor lysate therapy is applicable to all patients regardless of their HLA type. DCs are essentially the master regulators of immune response, and are the most potent antigen-presenting cell population for priming and activating naïve T cells to target tumors. Because of these unique properties, numerous DC-based immunotherapies have been initiated in the clinics. In this review, we describe the different types of whole tumor antigens that we could use to pulse DCs ex vivo and in vivo. We also discuss the different routes of delivering whole tumor antigens to DCs in vivo and activating them with toll-like receptor agonists