gebhart/patrepeval huggingface dataset:
New Generation Oxyntomodulin Peptides with Improved Pharmacokinetic Profiles Exhibit Weight Reducing and Anti-Steatotic Properties in Mice (2020)

Oxyntomodulin (OXM) is an intestinal peptide hormone that activates both glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors. The natural peptide reduces body weight in obese subjects and exhibits direct acute glucoregulatory effects in patients with type II diabetes. However, the clinical utility of OXM is limited due to its lower <i>in vitro</i> potency and short <i>in vivo</i> half-life. To overcome these issues, we developed stapled, long-acting, and highly potent OXM analogs with balanced activities at both GLP-1 and GCG receptors. The lead molecule <b>O14</b> exhibits potent and long-lasting effects on glucose control, body weight loss, and reduction of hepatic fat reduction in DIO mice. Importantly, <b>O14</b> significantly reversed hepatic steatosis; reduced liver weight, total cholesterol, and hepatic triglycerides; and improved markers of liver function in a nonalcoholic steatohepatitis (NASH) mouse model. A symmetrical version of the peptide was also shown to be more efficacious and long-lasting in controlling glucose than semaglutide and the clinical candidate cotadutide in wild-type mice, highlighting the utility of our designs of the dual agonist as a potential new therapy for diabetes and liver diseases.
EPDR1 is a noncanonical effector of insulin-mediated angiogenesis regulated by an endothelial-specific TGF-β receptor complex (2022)

Insulin signaling in blood vessels primarily functions to stimulate angiogenesis and maintain vascular homeostasis through the canonical PI3K and MAPK signaling pathways. However, angiogenesis is a complex process coordinated by multiple other signaling events. Here, we report a distinct crosstalk between the insulin receptor and endoglin/activin receptor-like kinase 1 (ALK1), an endothelial cell-specific TGF-β receptor complex essential for angiogenesis. While the endoglin-ALK1 complex normally binds to TGF-β or bone morphogenetic protein 9 (BMP9) to promote gene regulation via transcription factors Smad1/5, we show that insulin drives insulin receptor oligomerization with endoglin-ALK1 at the cell surface to trigger rapid Smad1/5 activation. Through quantitative proteomic analysis, we identify ependymin-related protein 1 (EPDR1) as a major Smad1/5 gene target induced by insulin but not by TGF-β or BMP9. We found endothelial EPDR1 expression is minimal at the basal state but is markedly enhanced upon prolonged insulin treatment to promote cell migration and formation of capillary tubules. Conversely, we demonstrate EPDR1 depletion strongly abrogates these angiogenic effects, indicating that EPDR1 is a crucial mediator of insulin-induced angiogenesis. Taken together, these results suggest important therapeutic implications for EPDR1 and the TGF-β pathways in pathologic angiogenesis during hyperinsulinemia and insulin resistance.
Lektion 2: Grundlagen der Rheologie (2017)

No AccessTechnologie der ExtrusionDec 2017Lektion 2: Grundlagen der RheologieHelmut Greif, Andreas Limper, Gordon FattmannHelmut Greif, Andreas Limper, Gordon Fattmannhttps://doi.org/10.3139/9783446436947.002SectionsAboutPDF ToolsAdd to FavoritesDownload CitationTrack CitationsCopy LTI LinkPDF key 'share (en)' returned an object instead of string.FacebookTwitterEmailLinkedIn previous chapternext chapter FiguresReferencesRelatedDetails 2017Pages: 19-27Print ISBN: 978-3-446-43693-0eISBN: 978-3-446-43694-7 Copyright & Permissions© 2017 Carl Hanser Verlag GmbH & Co. KGPDF downloadLoading ...
Experimental characterization of adhesion between micro-size polymer particles and silicon substrates (2008)

Understanding the adhesion between a micro/nano-size particle and a substrate is of both scientific and technological interest. Recently we developed a rolling resistance moment based particle adhesion characterization technique. The particle-substrate adhesion was deduced from the response of the adhered particle to a lateral pushing force. With a custom-made nanomanipulator, lateral pushing tests on microsize polymer spheres were performed in the vacuum chamber of a scanning electron microscope and also in the ambient environment. An increasing lateral force was applied to the micro-particle, and the displacement of the particle in response to the lateral force was recorded. From the force-displacement relationship, the work of adhesion between the particle and the substrate was obtained. Experimental results were compared with the available data, and good agreement between the theoretical predictions and the experimental values was found.
Polarity dependent implanted p-type dopant activation in GaN (2019)

Abstract Here we present a direct comparison between the activation of implanted Mg ions in N–polar and Ga–polar substrates to produce p-type GaN via symmetric multicycle rapid thermal annealing (SMRTA). Physical dopant activation was achieved by annealing in moderate nitrogen pressures (3.3 MPa) in conjunction with a bi-layer cap. Photoluminescence shows activation was more readily achieved for N–polar films with measured UV luminescence up to ∼15× as intense as yellow/green luminescence compared to ∼2.4× for Ga–polar films. The greater activation of N–polar material was primarily due to a higher thermal stability compared to Ga–polar films. This demonstration of implanted Mg activation by SMRTA enables a facile route toward next generation vertical devices.
Supplementary Figure S5 from Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity (2023)

&lt;p&gt;Inhibition of NFkB activities in APN-conditioned mDCs is dependent on STAT3 and SOCS3 pathway.&lt;/p&gt;
Screening for microorganisms producing D-malate from maleate (1992)

More than 300 microorganisms were screened for their ability to convert maleate into D-malate as a result of the action of maleate hydratase. Accumulation of fumarate during incubation of permeabilized cells with maleate was shown to be indicative of one of the two enzymes known to transform maleate. The ratio in which fumarate and malate accumulated could be used to estimate the enantiomeric composition of the malate formed. Many strains (n = 128) were found to be capable of converting maleate to D-malate with an enantiomeric purity of more than 97%. Pseudomonas pseudoalcaligenes NCIMB 9867 was selected for more detailed studies. Although this strain was not able to grow on maleate, permeabilized cells were able to degrade maleate to undetectable levels, with a concomitant formation of D-malate. The D-malate was formed with an enantiomeric purity of more than 99.97%.
Correlating optical damage threshold with intrinsic defect populations in fused silica as a function of heat treatment temperature (2013)

Here, chemical vapor deposition (CVD) is used for the production of fused silica optics in high-power laser applications. However, relatively little is known about the ultraviolet laser damage threshold of CVD films and how they relate to intrinsic defects produced during deposition. We present here a study relating structural and electronic defects in CVD films to 355 nm pulsed-laser damage threshold as a function of post-deposition annealing temperature (T<sub>HT</sub>). Plasma-enhanced CVD based on SiH<sub>4</sub>/N<sub>2</sub>O under oxygen-rich conditions was used to deposit 1.5, 3.1 and 6.4 µm thick films on etched SiO2 substrates. Rapid annealing was performed using a scanned CO2 laser beam up to T<sub>HT</sub> ~ 2100 K. The films were then characterized using x-ray photoemission spectroscopy, Fourier transform infrared spectroscopy (FTIR) and photoluminescence spectroscopy. A gradual transition in the damage threshold of annealed films was observed for T<sub>HT</sub> values up to 1600 K, correlating with a decrease in non-bridging silanol and oxygen deficient centres. An additional sharp transition in damage threshold also occurs at ~1850 K indicating substrate annealing. Based on our results, a mechanism for damage-related defect annealing is proposed, and the potential of using high-T<sub>HT</sub> CVD SiO<sub>2</sub> to mitigate optical damage is also discussed.
Abstract 23075: Machine Learning Outperformed ACC/AHA Pooled Cohort Equations Risk Calculator for Detection of High-Risk Asymptomatic Individuals and Recommending Treatment for Prevention of Cardiovascular Events in the Multi-Ethnic Study of Atherosclerosis (MESA) (2017)

Background: Studies have shown that the status quo for atherosclerotic cardiovascular disease (ASCVD) prediction in the U.S. - using ACC/AHA Pooled Cohort Equations Risk Calculator - is inaccurate and results in overtreatment of low-risk and undertreatment of high-risk individuals. Machine Learning (ML) is poised to revolutionize healthcare. We used ML to develop a new ASCVD risk calculator and tackled the problem. Methods: We developed a ML Risk Calculator using the latest 13-year follow up dataset from MESA (Multi-Ethnic Study of Atherosclerosis) of 6,814 participants who were free of clinical CVD at baseline. We gave identical input to both calculators and compared their accuracy for recommending statin to 5,415 subjects (age 60.6 ± 9.7 years; 47.3% males) who were not on lipid lowering treatment at baseline. Results: Over 13 years, 775 (14.3%) “All CVD” and 381 (7.0%) “Hard CVD” events occurred. According to ACC/AHA Risk Calculator and a 7.5% 10-year risk threshold for treatment, 42.9% would be recommended to take statin. Despite the high proportion recommended for statin treatment, 25.7% of “Hard CVD” and 26.3% of “All CVD” events occurred in those not recommended statin, resulting in sensitivity (Sn) 0.74, specificity (Sp) 0.60, and AUC 0.72 for “Hard CVD” and Sn 0.73, Sp 0.62, and AUC 0.73 for “All CVD”. In sharp contrast, the ML Risk Calculator recommended only 10.6% to take statin, and only 15.0% of “Hard CVD” and 4.9% of “All CVD” events occurred in those not recommended statin, resulting in Sn 0.84, Sp 0.95, and AUC 0.92 for “Hard CVD” and Sn 0.95, Sp 0.88, and AUC 0.95 for “All CVD”. Conclusions: ML clearly outperformed the ACC/AHA Risk Calculator by recommending less drug therapy and missing fewer events. Further studies are underway to validate these findings in other cohorts. As we introduce our ML model to more data particularly to cases in which events occurred weeks or months following data collection instead of years, short-term risk prediction may be possible.
Adaptive-weighted packet scheduling for premium service (2002)

This paper presents a new scheduling scheme to support a premium service in the differentiated service (DiffServ) architecture. It is based on weighted packet scheduling policies such as weighted round robin or fair queueing. The key feature of the new scheduling scheme is to change the scheduling weights of behavior aggregates adaptively. By adaptively adjusting the weights according to the dynamics of the average queue size of the premium service, the proposed scheme can achieve low loss rate, low delay and delay jitter for the premium service. Moreover, it requires neither rigid admission control nor accurate traffic conditioning to support the premium service in the DiffServ architecture. This adaptive packet scheduling is shown to absorb the transient burstiness of the expedited forwarding (EF) aggregate-which is caused by the traffic distortion inside the network-without incurring packet loss or increasing the queueing delay.
Elucidating the Functional Roles of Helper and Cytotoxic T Cells in the Cell-Mediated Immune Responses of Olive Flounder (Paralichthys olivaceus) (2021)

In higher vertebrates, helper and cytotoxic T cells, referred to as CD4 and CD8 T lymphocytes, respectively, are mainly associated with adaptive immunity. The adaptive immune system in teleosts involves T cells equivalent to those found in mammals. We previously generated monoclonal antibodies (mAbs) against olive flounder (<i>Paralichthys olivaceus</i>) CD4 T cells, CD4-1 and CD4-2, and used these to describe the olive flounder's CD4 Tcell response during a viral infection. In the present study, we successfully produced mAbs against CD8 T lymphocytes and their specificities were confirmed using immuno-blotting, immunofluorescence staining, flow cytometry analysis andreverse transcription polymerase chain reaction (RT-PCR). The results showed that these mAbs are specific for CD8 T lymphocytes. We also investigated variations in CD4 and CD8 T cells populations, and analyzed the expression of immune-related genes expressed by these cells in fish infected with nervous necrosis virus or immunized with thymus dependent and independent antigens. We found that both CD4 and CD8 T lymphocyte populations significantly increased in these fish and Th1-related genes were up-regulated compared to the control group. Collectively, these findings suggest that the CD4 and CD8 T lymphocytes in olive flounder are similar to the helper and cytotoxic T cells found in mammals, and Th1 and cytotoxic immune responses are primarily involved in the early adaptive immune response against extracellular antigens.
Unravelling Robustness of Deep Learning Based Face Recognition Against Adversarial Attacks (2018)

Deep neural network (DNN) architecture based models have high expressive power and learning capacity. However, they are essentially a black box method since it is not easy to mathematically formulate the functions that are learned within its many layers of representation. Realizing this, many researchers have started to design methods to exploit the drawbacks of deep learning based algorithms questioning their robustness and exposing their singularities. In this paper, we attempt to unravel three aspects related to the robustness of DNNs for face recognition: (i) assessing the impact of deep architectures for face recognition in terms of vulnerabilities to attacks inspired by commonly observed distortions in the real world that are well handled by shallow learning methods along with learning based adversaries; (ii) detecting the singularities by characterizing abnormal filter response behavior in the hidden layers of deep networks; and (iii) making corrections to the processing pipeline to alleviate the problem. Our experimental evaluation using multiple open-source DNN-based face recognition networks, including OpenFace and VGG-Face, and two publicly available databases (MEDS and PaSC) demonstrates that the performance of deep learning based face recognition algorithms can suffer greatly in the presence of such distortions. The proposed method is also compared with existing detection algorithms and the results show that it is able to detect the attacks with very high accuracy by suitably designing a classifier using the response of the hidden layers in the network. Finally, we present several effective countermeasures to mitigate the impact of adversarial attacks and improve the overall robustness of DNN-based face recognition.
Advanced Bioresponsive Multitasking Hydrogels in the New Era of Biomedicine (2021)

Abstract Advanced forms of hydrogels have many inherently desirable properties and can be designed with different structures and functions. In particular, bioresponsive multifunctional hydrogels can carry out sophisticated biological functions. These include in situ single‐cell approaches, capturing, analysis, and release of living cells, biomimetics of cell, tissue, and tumor‐specific niches. They can allow in vivo cell manipulation and act as novel drug delivery systems, allowing diagnostic, therapeutic, vaccination, and immunotherapy methods. In the present review of multitasking hydrogels, new approaches and devices classified into point‐of‐care testing (POCT), microarrays, single‐cell/rare cell approaches, artificial membranes, biomimetic modeling systems, nanodoctors, and microneedle patches are summarized. The potentials and application of each format are critically discussed, and some limitations are highlighted. Finally, how hydrogels can enable an “all‐in‐one platform” to play a key role in cancer therapy, regenerative medicine, and the treatment of inflammatory, degenerative, genetic, and metabolic diseases is being looked forward to.
In-vivo X-ray dark-field computed tomography for the detection of radiation-induced lung damage in mice (2021)

The applicability of X-ray dark-field computed tomography for the detection of radiation-induced lung damage was demonstrated in a pre-clinical mouse model. The presented results illustrate the differences between dark-field and absorption contrast and show that dark-field tomography could be advantageous in future clinical settings.
Direct chirp measurement of electro absorption modulator using optical homodyne quadrature demodulation technique (2014)

We propose a novel method to measure chirp of an electro-absorption modulator at any frequency using optical homodyne quadrature demodulation technique. Chirp parameters are directly obtained in the small-signal vector space, enabling practical chirp assessment for advanced modulation optical transmission.
Vertically scaled 80‐nm‐gate InP‐based HEMTs with a cutoff frequency of 450 GHz (2008)

Abstract We have successfully fabricated vertically scaled 80‐nm‐gate InP‐based HEMTs with fully SiN passivated gate‐recess regions and achieved high cutoff frequency of 450 GHz. By reducing gate‐recess length to 50 nm, high performance was realized even with a rather long gate length of 80 nm. We also employed a fully passivated gate‐recess structure, which is essential for obtaining thermally stable devices. Au interconnections with benzocyclobutene as an interlayer dielectric film were formed on this device and no change in DC characteristics was observed. These results indicate that the device reported in this paper is promising for integrated circuits used in millimeter‐wave applications. (© 2008 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Mechanisims of asthma and allergic disease – 1066. Ceruloplasmin oxidase activity in allergic asthma and allergic rhinitis (2013)

This article was originally published online on 23 April 2013 The known functions of ceruloplasmin oxidase activity (COA) include copper transportation, iron metabolism, antioxidant defense and involvement in angiogenesis and coagulation. The role of ceruloplasmin oxidase involving the interaction of oxidant and anti-oxidant balance in allergic diseases is still unknown. It was previously reported that synthesis of ceruloplasmin was situmulated by interleukin-1 in normal and copper-deficient rat models concluding that ceruloplasmin is dependent for oxidase activity. Moreover, the copper ions had been suggested as an explanation for the sensitivity of asthmatic individuals by their biologic effects of inhaled particulate air pollution. In vivo experiments on finding the cytokines involved in acute-phase protein response showed that there are three major cytokines; interleukin 1-beta, 6 and TNF-alpha. Our study was designed to examine the changes in COAs in severe persistent asthma-allergic rhinitis, new diagnosed allergic asthma-allergic rhinitis and allergic rhinitis patients. The study included 20 age- and sex-matched healthy individuals as control group (group I); group II was including 15 newly diagnosed allergic asthma - allergic rhinitis; group III was including 15 patients with severe persistent asthma - allergic rhinitis and in the fourth group there were 20 patients with allergic rhinitis. Group III was divided in two groups, severe persistent asthma-allergic rhinitis who were pre- (III-A) and post-treated (III-B) with omalizumab. Group IV was divided to two groups, pre- (IV-A) and post-treatment (IV-B) with specific subcutaneous immunotherapy modalities. All the post-treatment measurements were 12 months after the therapy. All the patients were assessed by the skin prick test, high sensitive C-reactive protein (hs-CRP) and COA. hs-CRP and COA levels were measured in all groups. There were significant differences between group I and groups III-A, III-B, IV-A and IV-B; group II and groups III-A, III-B, IV-A and IV-B; group III-A and groups III-B, IV-A and IV-B; group III-A and groups IV-A and IV-B; and group IV-A and IV-B. Interestingly, there was a correlation between the hs-CRP and COA levels in Group III-A. Our data suggest that hs-CRP and COA levels might be an indicator of an inflammation and important in revelation of patients with allergy related diseases, especially of asthma patients.
Lessons Learned About Autonomous AI: Finding a Safe, Efficacious, and Ethical Path Through the Development Process (2020)

Artificial intelligence (AI) describes systems capable of making decisions of high cognitive complexity; autonomous AI systems in healthcare are AI systems that make clinical decisions without human oversight. Such rigorously validated medical diagnostic AI systems hold great promise for improving access to care, increasing accuracy, and lowering cost, while enabling specialist physicians to provide the greatest value by managing and treating patients whose outcomes can be improved. Ensuring that autonomous AI provides these benefits requires evaluation of the autonomous AI's effect on patient outcome, design, validation, data usage, and accountability, from a bioethics and accountability perspective. We performed a literature review of bioethical principles for AI, and derived evaluation rules for autonomous AI, grounded in bioethical principles. The rules include patient outcome, validation, reference standard, design, data usage, and accountability for medical liability. Application of the rules explains successful US Food and Drug Administration (FDA) de novo authorization of an example, the first autonomous point-of-care diabetic retinopathy examination de novo authorized by the FDA, after a preregistered clinical trial. Physicians need to become competent in understanding the potential risks and benefits of autonomous AI, and understand its design, safety, efficacy and equity, validation, and liability, as well as how its data were obtained. The autonomous AI evaluation rules introduced here can help physicians understand limitations and risks as well as the potential benefits of autonomous AI for their patients.
The importance of monitoring adverse drug reactions in elderly patients: the results of a long-term pharmacovigilance programme (2015)

The ViGer project demonstrated that active pos-marketing pharmacovigilance programmes are a valid strategy to increase awareness on geriatrics pharmacology, reduce underreporting and provide important information on previous unknown ADRs and DDIs, resulting in a therapy optimisation in clinical practice in the geriatric setting.
Sequential knowledge-driven scene recognition model (2005)

Eye movements are an important aspect of human visual behavior. The temporal and space-variant nature of sampling a visual scene requires frequent attentional gaze shifts, saccades, to fixate onto different parts of an image. Experimental evidence suggests that fixations are often directed towards the most informative regions in the visual scene. We develop a model and its simulation that can select such regions based on prior knowledge of similar scenes. Having representations of scene categories as a probabilistic combination of hypothetical objects, i.e., prototypical regions with certain properties, it is possible to assess the likely contribution of each image region to the successive recognition process. Using conditional probabilities for each region given the scene category, the model can then predict its informative value and initiate a sequential spatial information-gathering algorithm, analogous to an eye movement saccade to a new fixation. This algorithm establishes the most likely scene category for a given image.
Technology-enabled practice: A vision statement by the ASHP Section of Pharmacy Informatics and Technology (2009)

Journal Article Technology-enabled practice: A vision statement by the ASHP Section of Pharmacy Informatics and Technology Get access American Journal of Health-System Pharmacy, Volume 66, Issue 17, 1 September 2009, Pages 1573–1577, https://doi.org/10.2146/ajhp090073 Published: 01 September 2009