A Randomized, Open-label, Phase 3 Study of Acalabrutinib in Combination With Rituximab and Reduced Dose CHOP (R-miniCHOP) in OldEr Adults With Untreated Diffuse Large B-Cell Lymphoma
The goal of this clinical trial is to study the addition of Acalabrutinib to standard R-miniCHOP in older adults with DLBCL. The main question it aims to answer is whether progression free survival kann be prolonged with the addition of Acalabrutinib. Participants will be randomised to receive either R-miniCHOP alone or R-miniCHOP with Acalabrutinib.
Allocation criteria for an initial shortage of a future SARS-CoV-2 vaccine and necessary measures for global immunity
作者: Henn, Wolfram
2020-06-30·Molecular and Cellular Neuroscience
Cyclic regulation of Trpm4 expression in female vomeronasal neurons driven by ovarian sex hormones
作者: Eckstein, Eugenia ; Pyrski, Martina ; Pinto, Silvia ; Freichel, Marc ; Vennekens, Rudi ; Zufall, Frank
The vomeronasal organ (VNO), the sensory organ of the mammalian accessory olfactory system, mediates the activation of sexually dimorphic reproductive behavioral and endocrine responses in males and females. It is unclear how sexually dimorphic and state-dependent responses are generated by vomeronasal sensory neurons (VSNs). Here, we report the expression of the transient receptor potential (TRP) channel Trpm4, a Ca2+-activated monovalent cation channel, as a second TRP channel present in mouse VSNs, in addition to the diacylglycerol-sensitive Trpc2 channel. The expression of Trpm4 in the mouse VNO is sexually dimorphic and, in females, is tightly linked to their reproductive cycle. We show that Trpm4 protein expression is upregulated specifically during proestrus and estrus, when female mice are about to ovulate and become sexually active and receptive. The cyclic regulation of Trpm4 expression in female VSNs depends on ovarian sex hormones and is abolished by surgical removal of the ovaries (OVX). Trpm4 upregulation can be restored in OVX mice by systemic treatment with 17ss-estradiol, requires endogenous activity of aromatase enzyme, and is strongly reduced during late pregnancy. This cyclic regulation of Trpm4 offers a neural mechanism by which female mice could regulate the relative strength of sensory signals in their VSNs, depending on hormonal state. Trpm4 is likely to participate in sex-specific, estrous cycle-dependent and sex hormone-regulated functions of the VNO, and may serve as a previously unknown genetic substrate for dissecting mammalian sexually dimorphic cellular and behavioral responses.
2020-06-20·Science of the Total Environment
Nitrate pollution in springs and headwater streams with agricultural catchments, seasonal climate
作者: Weber, Gero ; Honecker, Ulrich ; Kubiniok, Jochen
The present study examined the dynamics of nitrate pollution in springs and headwater streams in agriculturally used watersheds. The objectives of the study were to record the pollution dynamics throughout the year as a function of different weather patterns and determine the correlation of these dynamics with the degree of agricultural use of the relevant catchments. Moreover, continuous measuring methods should be compared with regular manual sampling procedures. Seven springs with agricultural catchments and their headstreams were studied over 2 years, as well as a reference water body with a forested catchment. At two of the springs, continuous measurements were addnl. performed using ion-selective electrodes. Two agrometeorol. stations were installed to record the relevant weather parameters. Every water body with agriculturally used surroundings exhibited increased nitrate values. A significant correlation was found between the NO-3 concentration and the proportion of arable land in the catchment. The nitrate concentration dynamics exhibited extreme weather-related and seasonal fluctuations. While nitrate maxima in autumn and winter correlated widely with the precipitation curve, heavy rainfall in spring and summer led only to short concentration peaks, followed by lower values, presumably caused by dilution effects. Between the spring and downstream measuring points, the nitrate loads increased by the same extent as the arable land area primarily responsible for their emission. No clear nitrate retention was observed between the springs and headstream measuring points. Grab sampling appeared to be sufficiently accurate to record nitrate concentrations when performed at monthly intervals over a two-year measurement period. However, continuous discharge measurements in parallel seemed necessary to determine the loads. The year of 2015 was characterized by a much drier summer and wetter winter, with universally higher nitrate pollution. If these conditions become more established as climate change progresses, increased nitrate pollution must be expected in future.
Scientists are developing intelligent materials that are opening up new avenues in sound reproduction technology: lightweight loudspeakers that use far less energy than their conventional counterparts, novel shapes for sound and signal generators and applications involving noise cancelling textiles. The basis for these smart materials are ultrathin silicone films that can act as artificial muscles with their own built-in sensors.
Professors Stefan Seelecke and Paul Motzki at Saarland University are developing intelligent materials that are opening up new avenues in sound reproduction technology: lightweight loudspeakers that use far less energy than their conventional counterparts, novel shapes for sound and signal generators and applications involving noise cancelling textiles. The basis for these smart materials are ultrathin silicone films that can act as artificial muscles with their own built-in sensors. The research team will be showcasing their new technology at this year's Hannover Messe from 17 to 21 April (Hall 2, Stand B34).
Ultrathin films may well replace the heavy and power-thirsty components found in today's loudspeakers -- making speaker systems lighter and environmentally more sustainable. And that wouldn't just make life easier for the stage technicians and roadies who have to stack speaker towers in stadiums and concert halls, it could also reduce electricity demand in millions of homes. The magnetic speaker drivers that are typically found in public-address systems and stage speaker setups use a lot of electric power. It's not unusual for power levels to reach hundreds of thousands of watts at large-scale events. But power consumption in domestic surround-sound installations (home music or home cinema systems) is also not inconsiderable. Most of us know how quickly a battery-powered (wireless) speaker needs recharging.
But the new technology being developed by Professor Stefan Seelecke and his research team at the Intelligent Material Systems Lab at Saarland University and at ZeMA (Center for Mechatronics and Automation Technology) in Saarbrücken is markedly more energy-efficient. Their technology does not rely on expensive and difficult-to-source materials; all it needs is a silicone film, some carbon black and a smart control unit. These new film-based drive systems offer the possibility of creating loudspeakers with totally new shapes. 'Our smart material systems made from dielectric elastomers are opening up opportunities to rethink much of what we know in the field of acoustics. These systems could help to make loudspeaker technology more sustainable and to develop it in new directions,' said Professor Stefan Seelecke.
The range of possible applications is very broad. For example, the films could be integrated into wall-mounted textiles to actively cancel ambient noise, or if worn on the body, they could emit acoustic signals. The research team from Saarbrücken are showcasing their technology at this year's Hannover Messe, where they will be looking for commercial and industrial partners with whom they can research and develop the technology for new applications.
The technology is based on thin silicone films coated with an electrically conducting layer to create dielectric elastomers that only require very low levels of electrical power to work. By varying the applied electric field, the researcher team can make the elastomer vibrate at high frequency or execute continuously variable flexing motions. If the elastomeric film is rolled up, it can be used as a new type of speaker driver, replacing the heavy, energy-consuming electromagnets or permanent magnets that drive loudspeaker membranes while still delivering rich bass frequencies.
'A highly flexible carbon black-based electrode layer is printed onto both sides of the silicone film,' explained Professor Paul Motzki, who carried out research in this field as a post-doctoral researcher in Seelecke's team. 'If we apply a voltage to the elastomer, the electrodes attract each other, compressing the polymer and causing it to expand out sideways, thus increasing its surface area,' said Motzki, who now holds a cross-institutional professorship in smart material systems for innovative production at Saarland University and at ZeMA, where he heads the research area 'Smart Material Systems'. Because they contract in this way, the polymer films have also been referred to as artificial muscles. And every time they change shape, so too does the electrical capacitance of the film. Each capacitance value corresponds to a specific position of the film. The film essentially becomes its own sensor. By combining the measurement data with intelligent algorithms, the team can program extremely rapid motion sequences and thus precise control the behaviour of the elastomer film. By altering the applied electric field, the researchers can make the film pulse or make it oscillate or flex at some required frequency.
The film can also be made to generate individual acoustic tones or even multiple tones if several vibrational frequencies are superimposed on one another -- turning the elastomeric film into its own loudspeaker. 'Depending on the application, we can use the film as both a drive system and a sound generator at the same time. We can develop technical solutions with novel shapes and designs that are also incredibly compact, just a few millimetres thick,' explained Sophie Nalbach, who worked on smart films as part of her doctoral dissertation work in Professor Seelecke's group and is now a group leader in the 'Smart Material Systems' research area at ZeMA. While the films do not displace enough air to match the performance of today's conventional loudspeakers, they could certainly be incorporated into textiles that would then be able to emit acoustic warning signals.
The technology discussed here has been studied and developed in several doctoral research projects. The results have been published as papers in a variety of scientific journals. The research work has also received support from numerous sources. For example, the Saarland state government provided financial support through the BEAT project, a collaborative project with the Saarland-based company Stamer GmbH, and through the ERDF (European Regional Development Fund) project iSMAT. EU funding was provided through a Marie Curie research fellowship.
Professor Seelecke's team is currently working on a number of different research projects aimed at developing these film-based drive systems for a range of different applications, including ways to interconnect them so that they can communicate and cooperate collectively. To do this the researchers will need to impart new capabilities to surfaces and interfaces, which in turn requires further miniaturization of the technology.
The company 'mateligent GmbH' was spun off from Professor Seelecke's department to facilitate the transfer of the results of their applications-driven research to commercial and industrial applications.
Researchers have discovered a strong immunological effect of the molecule LecB -- and a way to prevent it.
Bacteria of the species Pseudomonas aeruginosa are antibiotic-resistant hospital germs that can enter blood, lungs and other tissues through wounds and cause life-threatening infections. In a joint project, researchers from the Universities of Freiburg and Strasbourg in France have discovered a mechanism that likely contributes to the severity of P. aeruginosa infections. At the same time, it could be a target for future treatments. The results were recently appeared in the journal EMBO Reports.
Many bacterial species use sugar-binding molecules called lectins to attach to and invade host cells. Lectins can also influence the immune response to bacterial infections. However, these functions have hardly been researched so far. A research consortium led by Prof. Dr. Winfried Römer from the Cluster of Excellence CIBSS -- Centre for Integrative Biological Signalling Studies at the University of Freiburg and Prof. Dr. Christopher G. Mueller from the IBMC -- Institute of Molecular and Cell Biology at the CNRS/University of Strasbourg has investigated the effect of the lectin LecB from P. aeruginosa on the immune system. It found that isolated LecB can render immune cells ineffective: The cells are then no longer able to migrate through the body and trigger an immune response. The administration of a substance directed against LecB prevented this effect and led to the immune cells being able to move unhindered again.
LecB barricades the path for immune cells
As soon as they perceive an infection, cells of the innate immune system migrate to a nearby lymph node, where they activate T and B cells and trigger a targeted immune response. LecB, according to the current study, prevents this migration. "We assume that LecB not only acts on the immune cells themselves in this process, but also has an unexpected effect on the cells lining the inside of the blood and lymph vessels," Römer explains. "When LecB binds to these cells, it triggers extensive changes in them." Indeed, the researchers observed that important structural molecules were relocated to the interior of the cells and degraded. At the same time, the cell skeleton became more rigid. "The cell layer thus becomes an impenetrable barrier for the immune cells," Römer said.
An effective agent against LecB
Can this effect be prevented? To find out, the researchers tested a specific LecB inhibitor that resembles the sugar building blocks to which LecB otherwise binds. "The inhibitor prevented the changes in the cells, and T-cell activation was possible again," Mueller said, summarizing the promising results of the current study. The inhibitor was developed by Prof. Dr. Alexander Titz, who conducts research at the Helmholtz Institute for Pharmaceutical Research Saarland and Saarland University.
Further studies are needed to determine how clinically relevant the inhibition of the immune system by LecB is to the spread of P. aeruginosa infection and whether the LecB inhibitor has potential for therapeutic application. "The current results provide further evidence that lectins are a useful target for the development of new therapies, especially for antibiotic-resistant pathogens such as P. aeruginosa," the authors conclude.
TOKYO, Jan. 23, 2023 /PRNewswire/ -- ThinkCyte, a biotechnology company pioneering a novel artificial intelligence (AI)-based cell analysis, characterization, and isolation platform, announced today the appointments of Dr. Diether Recktenwald Ph.D. and Dr. Bo E. H. Saxberg M.D., Ph.D. to its senior Scientific Advisory Board (SAB). The appointments complement the strengths of ThinkCyte's existing advisory team and bring deep experiential insights into emerging flow cytometry markets, strategic product development, and clinical applications to ThinkCyte's SAB.
Dr. Recktenwald has an expansive career in the development of flow cytometry instruments. He spent over three decades at Becton Dickinson (BD) Biosciences, culminating as Vice President of Advanced Technology where he guided the late-stage development of several novel flow cytometry technologies and product lines. Prior to that, he served as Director of Industrial and Environmental Bioscience at BD, where he was responsible for assessing and developing novel flow cytometric detection methods for emerging markets. Earlier in his career as VP R&D for BD Biosciences Immunocytometry Systems, he led the completion of several new flow cytometry systems, consumables, and accessory lines. He holds B.S and M.S. degrees in Chemistry from Saarland University, earned a Ph.D. in Biology from the Ruhr-University Bochum in Germany, and performed postdoctoral research in cell biology and biophysics at Stanford University.
"I was honored to join ThinkCyte's Advisory Board to contribute to their excellent team's approach and vision," said Dr. Recktenwald. "By combining the fluorescence detection capabilities of traditional flow cytometry with a new way of getting morphological detail and data about single cells and applying AI, it unlocks new applications in life science research and beyond. I look forward to working with the extremely accomplished team as a member of the Advisory Board to help bring this vision to reality."
Dr. Saxberg has a distinguished career spanning the pharmaceutical, academic, and government research sectors, helping to drive innovations in pharmaceutical and diagnostic therapeutics and related development technologies, including serving as a Founding Investor and subsequently Board Chairman for IntelliCyt, a pioneer in the field of high-throughput flow cytometry. Prior to this he served as Vice President, Corporate Staff, Advanced Communications at Johnson & Johnson and Vice President, New Business Development and Advanced Communications for eJNJ, LLC, a Johnson & Johnson subsidiary founded in 2000 to focus on opportunities in digital eHealth. Earlier, he was at Eli Lilly as Director of Information Sciences leading projects at the interface of new technologies and pharmaceutical industry innovation. Dr. Saxberg graduated summa cum laude from the University of Washington, where he received an Honors B.S. degree in Mathematics and an Honors B.S. degree in Chemistry. Dr. Saxberg also earned an Honours B.A./M.A. Cantab. in Physics from Cambridge University in England, an M.D. from Harvard University, and a Ph.D. in Physics from the Massachusetts Institute of Technology.
"ThinkCyte's unique morphology-based approach to single cell analysis and sorting is a fundamental advancement in the field and one of the main reasons I am so excited to be joining the Advisory Board," said Dr. Saxberg. "By combining a truly novel means of looking at cells with the power of AI to discover hidden patterns in data, ThinkCyte is enabling an entirely new way to view the relationship between cellular phenotypes and disease."
"We are thrilled to have Drs. Recktenwald and Saxberg join our SAB alongside a team of renowned interdisciplinary experts in technology and science," said Janette Phi, Chief Business Officer at ThinkCyte. "Their experience in identifying where novel cytometry technologies can bring value to biomedical research and healthcare markets complements the strengths of our current Advisory Board and will position us well to advance ThinkCyte's vision of bringing a new dimension in cellular analysis to the world."
About ThinkCyte Inc.
ThinkCyte, founded in 2016 with offices in Tokyo, Japan and San Carlos, California is a biotechnology company that develops innovative scientific instruments based on integrated, multidisciplinary technologies to enable life science research, diagnostics, and therapeutic development. The company pioneered Ghost Cytometry, a proprietary AI-based, label-free cell sorting technology and partners with major global biopharmaceutical companies and leading academic research institutes to further drive pioneering research. For more information, please visit thinkcyte.com.
To learn more about research collaborations or other partnering opportunities with ThinkCyte, email [email protected].
Willem Westra, Ph.D.
SOURCE ThinkCyte Inc.