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ABSTRACT
Human cytomegalovirus (HCMV) is a leading cause of birth defects in humans. These birth defects include microcephaly, sensorineural hearing loss, vision loss, and cognitive impairment. The process by which the developing fetus incurs these neurological defects is poorly understood. To elucidate some of these mechanisms, we have utilized HCMV-infected induced pluripotent stem cells (iPSCs) to generate in vitro brain organoids, modeling the first trimester of fetal brain development. Early during culturing, brain organoids generate neural rosettes. These structures are believed to model neural tube formation. Rosette formation was analyzed in HCMV-infected and mock-infected brain organoids at 17, 24, and 31 days postinfection. Histological analysis revealed fewer neural rosettes in HCMV-infected compared to mock-infected organoids. HCMV-infected organoid rosettes incurred multiple structural deficits, including increased lumen area, decreased ventricular zone depth, and decreased cell count. Immunofluorescent (IF) analysis found that nidogen-1 (NID1) protein expression in the basement membrane surrounding neural rosettes was greatly reduced by virus infection. IF analysis also identified a similar downregulation of laminin in basement membranes of HCMV-infected organoid rosettes. Knockdown of NID1 alone in brain organoids impaired their development, leading to the production of rosettes with increased lumen area, decreased structural integrity, and reduced laminin localization in the basement membrane, paralleling observations in HCMV-infected organoids. Our data strongly suggest that HCMV-induced downregulation of NID1 impairs neural rosette formation and integrity, likely contributing to many of HCMV’s most severe birth defects.
IMPORTANCE HCMV infection in pregnant women continues to be the leading cause of virus-induced neurologic birth defects. The mechanism through which congenital HCMV (cCMV) infection induces pathological changes to the dev
Dr Radu Sporea SMIEEE MIET CEng
Eva Bestelink, Ute Zschieschang, Indrachapa Bandara Rajapakshe Mudiyanselage, Hagen Klauk, Radu A. Sporea (2021)The secret ingredient for exceptional contact-controlled transistors, In: Advanced Electronic Materials Wiley
DOI: 10.1002/aelm.202101101
Contact-controlled transistors are rapidly gaining popularity. However, simply using a rectifying source contact often leads to unsatisfactory operation, merely as a thin-film transistor with low drain current and reduced effective mobility. This may cause otherwise promising experiments to be abandoned. Here, we analyse data from literature in conjunction with devices we have recently fabricated in polysilicon, organic and oxide semiconductors, highlighting the main factor in achieving good saturation, namely keeping saturation coefficient γ well below 0.3. We also discuss secondary causes of suboptimal electrical characteristics. Correct design of these alternative device structures will expedite their adoption for high gain, low-frequency applications in emerging sensor circuits.
Raksan Ko, Minseo Kim, Eva Bestelink, Patryk Golec, Jaehyun Hur, Radu A. Sporea, Hocheon Yoo (2024)Operating Principles of Gate Gap on Charge Transport in Split Gate Logic Thin-Film Transistors, In: ACS applied electronic materials6(12)pp. 9134-9141 American Chemical Society
DOI: 10.1021/acsaelm.4c01760
Thin-film transistors with a split gate structure have been continuously studied for integration into future electronic devices. By introduction of a gate gap, a thin-film transistor can perform various logic circuit operations within the single channel region. However, the impact of the gate gap on the electrical characteristics of split gate thin-film transistors has not been well investigated. In this study, we fabricated and characterized split gate thin-film transistors to realize logic OR and AND operations and conducted technology-aided computer design simulations with Silvaco Atlas simulat The history of Póvoa de Varzim, Portugal, and its development as a maritime trade and fishing hub, have been greatly influenced by its location at the entrance to one of Portugal's best natural ports. Permanent settlement in the coastal plain of Póvoa de Varzim dates back to around four to six thousand years ago; around 900 BC, unrest in the region led to the establishment of a fortified city. The ocean has played an important part in its popular culture and economy, through maritime trade and fishing, leading it to establish a fiefdom in the 10th or 11th century, a municipality in 1308 and to become, in the 18th century, the main fishing port in northern Portugal. Póvoa de Varzim and its region had relevant input that allowed the Portuguese discoveries, throw manpower, shipbuilding and seafaring knowledge. Since the 18th century, its beaches have helped it become one of the main tourist areas of the region, which prompted high-culture development since the late 18th century. Its development suffered setbacks due to feudalism, monastic domain, border disputes and, recently, the development of a highly centralized state. However, it gained significant privileges confirmed by successive Portuguese kings such as town limit exception and royal appeal rights. Discoveries of Acheuleanstone tools suggest Póvoa de Varzim has been inhabited since the Lower Palaeolithic, around 200,000 BC. The earliest artifacts, dating to the Paleolithic, were found in Northern Aver-o-Mar, proving the strong attractiveness that the ocean played since very remote eras. The first groups of shepherds settled on the coast where Póvoa de Varzim is now located between the 4th millennium and early 2nd millennium BC. Their dead were deposited in tumuli, which are the oldest monuments found in the municipality. The necropolis, with seven tumuli, dated to end of the Neolithic, early chalcolithic .History of Póvoa de Varzim
Stone Age settlers Prehistory–900 B.C.