System and Method for Analog-to-Digital Signal Conversion

Example embodiments relate to systems and methods for analog-to-digital signal conversion. One embodiment includes a system for analog-to-digital signal conversion. The system includes an analog input signal. The system also includes a digital-to-analog converter configured to generate a reference signal. Further, the system includes an amplifier configured to amplify an error signal that includes a difference between the analog input signal and the reference signal. Additionally, the system includes a level-crossing based sampling circuit that includes a first comparator configured to compare the error signal with respect to a first reference level, and a second comparator configured to compare the error signal with respect to a second reference level, thereby generating event-based reset signals corresponding to a plurality of sampling instances in order to reset the digital-to-analog converter. Yet further, the system includes a trigger circuit configured to generate reset signals asynchronous to the event-based reset signals

Thermo-mechanical analysis of flexible and stretchable systems

This paper presents a summary of the modeling and technology developed for flexible and stretchable electronics. The integration of ultra thin dies at package level, with thickness in the range of 20 to 30 μ m, into flexible and/or stretchable materials are demonstrated as well as the design and reliability test of stretchable metal interconnections at board level are analyzed by both experiments and finite element modeling. These technologies can achieve mechanically bendable and stretchable subsystems. The base substrate used for the fabrication of flexible circuits is a uniform polyimide layer, while silicones materials are preferred for the stretchable circuits. The method developed for chip embedding and interconnections is named Ultra Thin Chip Package (UTCP). Extensions of this technology can be achieved by stacking and embedding thin dies in polyimide, providing large benefits in electrical performance and still allowing some mechanical flexibility. These flexible circuits can be converted into stretchable circuits by replacing the relatively rigid polyimide by a soft and elastic silicone material. We have shown through finite element modeling and experimental validation that an appropriate thermo mechanical design is necessary to achieve mechanically reliable circuits and thermally optimized packages

Dose-Response Relationships Following Oral Administration of DuP 753 to Normal Humans

We assessed the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy volunteers. In a single dose study, doses of 2.5, 5, 10, 20, and 40 mg of DuP 753 or placebo were tested serially at one week intervals. In the multiple dose study, the administration of placebo or DuP 753 (5, 10, 20, or 40 mg, per os once daily) for eight consecutive days was evaluated. The blood pressure response to angiotensin I and II was inhibited in a dose-dependent fashion with a blocking effect still present 24 h post drug. DuP 753 also induced a dose-dependent compensatory rise in plasma renin. This new compound was well tolerated by these normal volunteers. Thus, DuP 753 appears to be a well tolerated, orally active, potent and long-lasting antagonist of angiotensin II in humans. Am J Hypertens 1991;4:350S-354

Nonpeptide angiotensin II receptor antagonists.

ABSTRACT ABBREVIATIONS: All, angiotensin II; DuP 753,

Aberrant APOBEC3B Expression in Breast Cancer Is Linked to Proliferation and Cell Cycle Phase

APOBEC3B (A3B) is aberrantly overexpressed in a subset of breast cancers, where it associates with advanced disease, poor prognosis, and treatment resistance, yet the causes of A3B dysregulation in breast cancer remain unclear. Here, A3B mRNA and protein expression levels were quantified in different cell lines and breast tumors and related to cell cycle markers using RT-qPCR and multiplex immunofluorescence imaging. The inducibility of A3B expression during the cell cycle was additionally addressed after cell cycle synchronization with multiple methods. First, we found that A3B protein levels within cell lines and tumors are heterogeneous and associate strongly with the proliferation marker Cyclin B1 characteristic of the G2/M phase of the cell cycle. Second, in multiple breast cancer cell lines with high A3B, expression levels were observed to oscillate throughout the cell cycle and again associate with Cyclin B1. Third, induction of A3B expression is potently repressed throughout G0/early G1, likely by RB/E2F pathway effector proteins. Fourth, in cells with low A3B, induction of A3B through the PKC/ncNF-κB pathway occurs predominantly in actively proliferating cells and is largely absent in cells arrested in G0. Altogether, these results support a model in which dysregulated A3B overexpression in breast cancer is the cumulative result of proliferation-associated relief from repression with concomitant pathway activation during the G2/M phase of the cell cycle.</p

Transcriptomic properties of her2+ ductal carcinoma in situ of the breast associate with absence of immune cells

SIMPLE SUMMARY: Tumor-infiltrating lymphocytes (TILs) are likely to play a role in the biological behavior of HER2+ ductal carcinoma in situ (DCIS). To prevent invasiveness, the potential of targeted immune-modulating treatment of HER2+ DCIS has been explored. We identified a 29-gene expression profile that was associated with the density of TILs. These genes included CCND3, DUSP10 and RAP1GAP, which may guide towards more rationalized choices with respect to immune-mediated therapy in HER2+ DCIS, such as targeted vaccine therapy. ABSTRACT: The identification of transcriptomic alterations of HER2+ ductal carcinoma in situ (DCIS) that are associated with the density of tumor-infiltrating lymphocytes (TILs) could contribute to optimizing choices regarding the potential benefit of immune therapy. We compared the gene expression profile of TIL-poor HER2+ DCIS to that of TIL-rich HER2+ DCIS. Tumor cells from 11 TIL-rich and 12 TIL-poor DCIS cases were micro-dissected for RNA isolation. The Ion AmpliSeq Transcriptome Human Gene Expression Kit was used for RNA sequencing. After normalization, a Mann–Whitney rank sum test was used to analyze differentially expressed genes between TIL-poor and TIL-rich HER2+ DCIS. Whole tissue sections were immunostained for validation of protein expression. We identified a 29-gene expression profile that differentiated TIL-rich from TIL-poor HER2+ DCIS. These genes included CCND3, DUSP10 and RAP1GAP, which were previously described in breast cancer and cancer immunity and were more highly expressed in TIL-rich DCIS. Using immunohistochemistry, we found lower protein expression in TIL-rich DCIS. This suggests regulation of protein expression at the posttranslational level. We identified a gene expression profile of HER2+ DCIS cells that was associated with the density of TILs. This classifier may guide towards more rationalized choices regarding immune-mediated therapy in HER2+ DCIS, such as targeted vaccine therapy

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA):long-term outcomes of a multicentre, double-blind, randomised controlled trial

Background: Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. Methods: In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan–Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Findings: Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4–64.8), 24.7% (95% CI: 12.7–38.8), 29.8% (95% CI: 17.9–42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248–0.614, p &lt; 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309–0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Interpretation: Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. Funding: B. Braun.</p

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA):long-term outcomes of a multicentre, double-blind, randomised controlled trial

Background: Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. Methods: In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan–Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Findings: Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4–64.8), 24.7% (95% CI: 12.7–38.8), 29.8% (95% CI: 17.9–42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248–0.614, p &lt; 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309–0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Interpretation: Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. Funding: B. Braun.</p