Obinutuzumab-Induced B Cell Depletion Reduces Spinal Cord Pathology in a CD20 Double Transgenic Mouse Model of Multiple Sclerosis

B cell-depleting therapies have recently proven to be clinically highly successful in the treatment of multiple sclerosis (MS). This study aimed to determine the effects of the novel type II anti-human CD20 (huCD20) monoclonal antibody (mAb) obinutuzumab (OBZ) on spinal cord degeneration in a B cell-dependent mouse model of MS. Double transgenic huCD20xHIGR3 (CD20dbtg) mice, which express human CD20, were immunised with the myelin fusion protein MP4 to induce experimental autoimmune encephalomyelitis (EAE). Both light and electron microscopy were used to assess myelination and axonal pathology in mice treated with OBZ during chronic EAE. Furthermore, the effects of the already established murine anti-CD20 antibody 18B12 were assessed in C57BL/6 wild-type (wt) mice. In both models (18B12/wt and OBZ/CD20dbtg) anti-CD20 treatment significantly diminished the extent of spinal cord pathology. While 18B12 treatment mainly reduced the extent of axonal pathology, a significant decrease in demyelination and increase in remyelination were additionally observed in OBZ-treated mice. Hence, the data suggest that OBZ could have neuroprotective effects on the CNS, setting the drug apart from the currently available type I anti-CD20 antibodies

Prosthetic Knee for CURE Kenya: Design and Manufacturing

The Prosthetic Knee team is partnered with the CURE International Hospital in Kijabe, Kenya. In the region surrounding our client’s facility, there is a large number of lower-extremity amputations due to various infections and diseases. Often, these patients choose to undergo a more invasive transfemoral amputation to enable them to use a less expensive above-knee prosthesis. The goal of the project is to present the orthopedic workshop at CURE with a manufacturable prosthetic knee design in May of 2023 that provides through-knee amputee patients with a more affordable, aesthetically pleasing, and lightweight prosthetic option, thereby removing the need to undergo an additional amputation above the knee. The poster presents the overarching elements of the prosthetic design in addition to the recently integrated locking and damping components, which aid in the functionality of the knee. Funding for this work provided by The Collaboratory for Strategic Partnerships and Applied Research.https://mosaic.messiah.edu/engr2022/1013/thumbnail.jp

Prosthetic Knee for CURE Kenya

Lower limb amputations are common in sub-Saharan Africa due to the prevalence of disease and infection in communities that lack access to adequate healthcare. Our project, Prosthetic Knee, partners with the CURE International Hospital in Kijabe, Kenya. In the region surrounding our client’s facility, there is a large number of lower-extremity amputations due to various infections and diseases. While many of these amputees only require a through-knee amputation, the lack of an affordable through-knee prosthesis often forces patients to undergo a more invasive transfemoral amputation to enable them to use a cheaper above-knee prosthesis. The goal of our project is to design and manufacture a financially accessible and user-friendly prosthetic knee for knee-disarticulation patients that can be manufactured in Messiah University’s machine shop (and ultimately, at the orthopedic facility in Kijabe). This year, the team’s work has included finalizing the prototype design, conducting finite element analysis in SOLIDWORKS to evaluate the knee’s static and fatigue strength, and beginning the process of physical manufacturing. Additionally, a damping mechanism driven by a spring-loaded system has been developed and integrated into the design after completing motion analysis and SOLIDWORKS modeling. Our future goals include manufacturing a complete metal prototype of the knee, conducting physical strength and fatigue testing on the metal prototype, and continuing iterative prototyping of the damper in preparation for physical implementation.https://mosaic.messiah.edu/engr2021/1014/thumbnail.jp

Photocurrent measurements of supercollision cooling in graphene

The cooling of hot electrons in graphene is the critical process underlying the operation of exciting new graphene-based optoelectronic and plasmonic devices, but the nature of this cooling is controversial. We extract the hot electron cooling rate near the Fermi level by using graphene as novel photothermal thermometer that measures the electron temperature ($T(t)$) as it cools dynamically. We find the photocurrent generated from graphene $p-n$ junctions is well described by the energy dissipation rate $C dT/dt=-A(T^3-T_l^3)$, where the heat capacity is $C=\alpha T$ and $T_l$ is the base lattice temperature. These results are in disagreement with predictions of electron-phonon emission in a disorder-free graphene system, but in excellent quantitative agreement with recent predictions of a disorder-enhanced supercollision (SC) cooling mechanism. We find that the SC model provides a complete and unified picture of energy loss near the Fermi level over the wide range of electronic (15 to $\sim$3000 K) and lattice (10 to 295 K) temperatures investigated.Comment: 7pages, 5 figure

The Lantern Vol. 1, No. 1, May 1933

• Remember: Translation of Rappelle-toi by Alfred de Musset • Lighting the Lantern • Footfalls • To a Lovely Lady • The Sons of Martha • Strategy • Lumine Lunae • Poetry in Retrospect • Nirvana • A Domestic Episode • At Night • Haman and Hitler • This is What He Said • Bookocracy • Four Loves • Cities and Personalitieshttps://digitalcommons.ursinus.edu/lantern/1000/thumbnail.jp

Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice

<p>Abstract</p> <p>Background</p> <p>Exposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. PM can gain access to the gastrointestinal (GI) tract via swallowing of air or secretions from the upper airways or mucociliary clearance of inhaled particles.</p> <p>Methods</p> <p>We measured PM-induced cell death and mitochondrial ROS generation in Caco-2 cells stably expressing oxidant sensitive GFP localized to mitochondria in the absence or presence of an antioxidant. C57BL/6 mice were exposed to a very high dose of urban PM from Washington, DC (200 μg/mouse) or saline via gastric gavage and small bowel and colonic tissue were harvested for histologic evaluation, and RNA isolation up to 48 hours. Permeability to 4kD dextran was measured at 48 hours.</p> <p>Results</p> <p>PM induced mitochondrial ROS generation and cell death in Caco-2 cells. PM also caused oxidant-dependent NF-κB activation, disruption of tight junctions and increased permeability of Caco-2 monolayers. Mice exposed to PM had increased intestinal permeability compared with PBS treated mice. In the small bowel, colocalization of the tight junction protein, ZO-1 was lower in the PM treated animals. In the small bowel and colon, PM exposed mice had higher levels of IL-6 mRNA and reduced levels of ZO-1 mRNA. Increased apoptosis was observed in the colon of PM exposed mice.</p> <p>Conclusions</p> <p>Exposure to high doses of urban PM causes oxidant dependent GI epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut <it>in vitro </it>and <it>in vivo</it>. These PM-induced changes may contribute to exacerbations of inflammatory disorders of the gut.</p

Lifestyle and Horizontal Gene Transfer- Mediated Evolution of \u3ci\u3eMucispirillum schaedleri\u3c/i\u3e, a Core Member of the Murine Gut Microbiota

Mucispirillum schaedleri is an abundant inhabitant of the intestinal mucus layer of rodents and other animals and has been suggested to be a pathobiont, a commensal that plays a role in disease. In order to gain insights into its lifestyle, we analyzed the genome and transcriptome of M. schaedleri ASF 457 and performed physiological experiments to test traits predicted by its genome. Although described as a mucus inhabitant, M. schaedleri has limited capacity for degrading host-derived mucosal glycans and other complex polysaccharides. Additionally, M. schaedleri reduces nitrate and expresses systems for scavenging oxygen and reactive oxygen species in vivo, which may account for its localization close to the mucosal tissue and expansion during inflammation. Also of note, M. schaedleri harbors a type VI secretion system and putative effector proteins and can modify gene expression in mucosal tissue, suggesting intimate interactions with its host and a possible role in inflammation. The M. schaedleri genome has been shaped by extensive horizontal gene transfer, primarily from intestinal Epsilon- and Deltaproteobacteria, indicating that horizontal gene transfer has played a key role in defining its niche in the gut ecosystem

Intrinsic response time of graphene photodetectors

Graphene-based photodetectors are promising new devices for high-speed optoelectronic applications. However, despite recent efforts, it is not clear what determines the ultimate speed limit of these devices. Here, we present measurements of the intrinsic response time of metal-graphene-metal photodetectors with monolayer graphene using an optical correlation technique with ultrashort laser pulses. We obtain a response time of 2.1 ps that is mainly given by the short lifetime of the photogenerated carriers. This time translates into a bandwidth of ~262 GHz. Moreover, we investigate the dependence of the response time on gate voltage and illumination laser power

Lifestyle and Horizontal Gene Transfer- Mediated Evolution of Mucispirillum schaedleri, a Core Member of the Murine Gut Microbiota

Mucispirillum schaedleri is an abundant inhabitant of the intestinal mucus layer of rodents and other animals and has been suggested to be a pathobiont, a commensal that plays a role in disease. In order to gain insights into its lifestyle, we analyzed the genome and transcriptome of M. schaedleri ASF 457 and performed physiological experiments to test traits predicted by its genome. Although described as a mucus inhabitant, M. schaedleri has limited capacity for degrading host-derived mucosal glycans and other complex polysaccharides. Additionally, M. schaedleri reduces nitrate and expresses systems for scavenging oxygen and reactive oxygen species in vivo, which may account for its localization close to the mucosal tissue and expansion during inflammation. Also of note, M. schaedleri harbors a type VI secretion system and putative effector proteins and can modify gene expression in mucosal tissue, suggesting intimate interactions with its host and a possible role in inflammation. The M. schaedleri genome has been shaped by extensive horizontal gene transfer, primarily from intestinal Epsilon- and Deltaproteobacteria, indicating that horizontal gene transfer has played a key role in defining its niche in the gut ecosystem

Microcavity-integrated graphene photodetector

The monolithic integration of novel nanomaterials with mature and established technologies has considerably widened the scope and potential of nanophotonics. For example, the integration of single semiconductor quantum dots into photonic crystals has enabled highly efficient single-photon sources. Recently, there has also been an increasing interest in using graphene - a single atomic layer of carbon - for optoelectronic devices. However, being an inherently weak optical absorber (only 2.3 % absorption), graphene has to be incorporated into a high-performance optical resonator or waveguide to increase the absorption and take full advantage of its unique optical properties. Here, we demonstrate that by monolithically integrating graphene with a Fabry-Perot microcavity, the optical absorption is 26-fold enhanced, reaching values >60 %. We present a graphene-based microcavity photodetector with record responsivity of 21 mA/W. Our approach can be applied to a variety of other graphene devices, such as electro-absorption modulators, variable optical attenuators, or light emitters, and provides a new route to graphene photonics with the potential for applications in communications, security, sensing and spectroscopy.Comment: 19 pages, 4 figure