37 research outputs found
Charakterisierung von Hepatozyten in einem miniaturisierten 3D-Durchflussbioreaktor
Medikamentenentwicklung ist ein ressourcen- und zeitintensiver Prozess mit einem hohen Risiko, zu scheitern10. Um möglichst schnell und kostengünstig82 festzustellen, ob ein Medikament zulassungsfähig ist oder nicht, ist es notwendig, über möglichst gute präklinische Systeme zur Medikamententestung zu verfügen, insbesondere für pHH, da die Leber für den Großteil des Scheiterns von Medikamenten verantwortlich ist14. Da dies mit dem momentanen Goldstandard, der 2D-Kultur, aufgrund der raschen Dedifferenzierung der pHH15,16,19,20 nur eingeschränkt möglich ist, gilt es, Systeme zu entwickeln, die der 3D in vivo Situation, wie z.B. der Leber, möglichst nahe zu kommen. So sollen rasch ungeeignete Medikamente identifiziert und von der weiteren Entwicklung ausgeschlossen werden können.
Im Rahmen der Dissertation wurde das System des r3D-KITChip Bioreaktors beschrieben, wobei Huh7 und pHH kultiviert wurden. Dabei konnte gezeigt werden, dass die in 3D kultivierten Huh7 eine gegenüber den in 2D kultivierten Huh7 in gesteigertem Maß Glucose und Urea freisetzen und über eine gesteigerte MDR1-Aktivität verfügen. Im Gegensatz dazu zeigten die in 3D kultivierten pHH eine geringere oder ähnliche Freisetzung von Glucose, Urea, Albumin, APAP-Metaboliten und Diclofenac-Metaboliten sowie eine geringere MDR1-Aktivität.
Zusammenfassend konnten die in der Literatur beschriebenen Vorteile einer 3D-Kultivierung für pHH15,16,19,20 mit dem hier verwendeten System nicht reproduziert werden. Mögliche problematische Aspekte, wie das Gehäuse, die Perfusion und die Handhabung des Bioreaktors wurden beschrieben und können als mögliche Ansatzpunkte für eine Verbesserung des Systems dienen
Interleukin-1 beta - a friend or foe in malignancies?
Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development
QUBE – Quantum Key Distribution with CubeSat
QUBE (Quantum Key Distribution with CubeSat) is one out of three pilot projects in the frame of the national
German initiative QUTEGA to promote quantum technologies. The project is funded by the German Federal Ministry
of Education and Research (BMBF) with co-funding of industry as preparation for the European flagship on Quantum
Technology. With the current development pace in quantum computation, it has been predicted that in less than two
decades quantum computers will be able to break encryption codes deployed today, which are currently based on
mathematical problems difficult to solve with classical computation. This shows the urgent need for quantum-safe
encryption that is resistant to attacks of both, quantum and classical, computers. A long term solution for quantumsafe encryption is the use of a completely random, so-called One-Time-Pad generated with true Random Number
Generation (RNG) and distributed via Quantum Key Distribution (QKD). The QKD in fiber networks is limited to
approx. 100 km due to damping within the carrier medium. For longer distances so far only satellite based techniques
are able to transmit the keys. As a pathfinder, QUBE plans perform an in-orbit demonstration of the core technologies
on a CubeSat platform
individual participant data meta-analysis of randomised trials study protocol
Introduction Parenteral anticoagulants may improve outcomes in patients with
cancer by reducing risk of venous thromboembolic disease and through a direct
antitumour effect. Study-level systematic reviews indicate a reduction in
venous thromboembolism and provide moderate confidence that a small survival
benefit exists. It remains unclear if any patient subgroups experience
potential benefits. Methods and analysis First, we will perform a
comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library,
hand search scientific conference abstracts and check clinical trials
registries for randomised control trials of participants with solid cancers
who are administered parenteral anticoagulants. We anticipate identifying at
least 15 trials, exceeding 9000 participants. Second, we will perform an
individual participant data meta-analysis to explore the magnitude of survival
benefit and address whether subgroups of patients are more likely to benefit
from parenteral anticoagulants. All analyses will follow the intention-to-
treat principle. For our primary outcome, mortality, we will use multivariable
hierarchical models with patient-level variables as fixed effects and a
categorical trial variable as a random effect. We will adjust analysis for
important prognostic characteristics. To investigate whether intervention
effects vary by predefined subgroups of patients, we will test interaction
terms in the statistical model. Furthermore, we will develop a risk-prediction
model for venous thromboembolism, with a focus on control patients of
randomised trials. Ethics and dissemination Aside from maintaining participant
anonymity, there are no major ethical concerns. This will be the first
individual participant data meta-analysis addressing heparin use among
patients with cancer and will directly influence recommendations in clinical
practice guidelines. Major cancer guideline development organisations will use
eventual results to inform their guideline recommendations. Several knowledge
users will disseminate results through presentations at clinical rounds as
well as national and international conferences. We will prepare an evidence
brief and facilitate dialogue to engage policymakers and stakeholders in
acting on findings. Trial registration number PROSPERO CRD4201300352
Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens
Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association
Influence of Stimulant Medication and Response Speed on Lateralization of Movement-Related Potentials in Attention-Deficit/Hyperactivity Disorder
Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes.A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology
Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies
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Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks
无线传感器网络,作为全球未来十大技术之一,集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术,可实时感知、采集、处理、传输网络分布区域内的各种信息数据,在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议,并针对大规模的无线传感器网络设计了一种树状路由协议,它根据节点地址信息来形成路由,从而简化了复杂繁冗的路由表查找和维护,节省了不必要的开销,提高了路由效率,实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR(AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位:工学硕士院系专业:信息科学与技术学院通信工程系_通信与信息系统学号:2332007115216
Interleukin-1 Beta—A Friend or Foe in Malignancies?
Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development