Covid-19, equity, and inclusiveness

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Brain Specificity of Diffuse Optical Imaging: Improvements from Superficial Signal Regression and Tomography

Functional near infrared spectroscopy (fNIRS) is a portable monitor of cerebral hemodynamics with wide clinical potential. However, in fNIRS, the vascular signal from the brain is often obscured by vascular signals present in the scalp and skull. In this paper, we evaluate two methods for improving in vivo data from adult human subjects through the use of high-density diffuse optical tomography (DOT). First, we test whether we can extend superficial regression methods (which utilize the multiple source–detector pair separations) from sparse optode arrays to application with DOT imaging arrays. In order to accomplish this goal, we modify the method to remove physiological artifacts from deeper sampling channels using an average of shallow measurements. Second, DOT provides three-dimensional image reconstructions and should explicitly separate different tissue layers. We test whether DOT's depth-sectioning can completely remove superficial physiological artifacts. Herein, we assess improvements in signal quality and reproducibility due to these methods using a well-characterized visual paradigm and our high-density DOT system. Both approaches remove noise from the data, resulting in cleaner imaging and more consistent hemodynamic responses. Additionally, the two methods act synergistically, with greater improvements when the approaches are used together

Large-scale identification of genetic design strategies using local search

In the past decade, computational methods have been shown to be well suited to unraveling the complex web of metabolic reactions in biological systems. Methods based on flux–balance analysis (FBA) and bi-level optimization have been used to great effect in aiding metabolic engineering. These methods predict the result of genetic manipulations and allow for the best set of manipulations to be found computationally. Bi-level FBA is, however, limited in applicability because the required computational time and resources scale poorly as the size of the metabolic system and the number of genetic manipulations increase. To overcome these limitations, we have developed Genetic Design through Local Search (GDLS), a scalable, heuristic, algorithmic method that employs an approach based on local search with multiple search paths, which results in effective, low-complexity search of the space of genetic manipulations. Thus, GDLS is able to find genetic designs with greater in silico production of desired metabolites than can feasibly be found using a globally optimal search and performs favorably in comparison with heuristic searches based on evolutionary algorithms and simulated annealing.Hertz Foundatio

Spectrally resolved autofluorescence imaging in posterior uveitis.

Clinical discrimination of posterior uveitis entities remains a challenge. This exploratory, cross-sectional study investigated the green (GEFC) and red emission fluorescent components (REFC) of retinal and choroidal lesions in posterior uveitis to facilitate discrimination of the different entities. Eyes were imaged by color fundus photography, spectrally resolved fundus autofluorescence (Color-FAF) and optical coherence tomography. Retinal/choroidal lesions' intensities of GEFC (500-560 nm) and REFC (560-700 nm) were determined, and intensity-normalized Color-FAF images were compared for birdshot chorioretinopathy, ocular sarcoidosis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and punctate inner choroidopathy (PIC). Multivariable regression analyses were performed to reveal possible confounders. 76 eyes of 45 patients were included with a total of 845 lesions. Mean GEFC/REFC ratios were 0.82 ± 0.10, 0.92 ± 0.11, 0.86 ± 0.10, and 1.09 ± 0.19 for birdshot chorioretinopathy, sarcoidosis, APMPPE, and PIC lesions, respectively, and were significantly different in repeated measures ANOVA (p < 0.0001). Non-pigmented retinal/choroidal lesions, macular neovascularizations, and fundus areas of choroidal thinning featured predominantly GEFC, and pigmented retinal lesions predominantly REFC. Color-FAF imaging revealed involvement of both, short- and long-wavelength emission fluorophores in posterior uveitis. The GEFC/REFC ratio of retinal and choroidal lesions was significantly different between distinct subgroups. Hence, this novel imaging biomarker could aid diagnosis and differentiation of posterior uveitis entities

Non-linear electromagnetic response of graphene

It is shown that the massless energy spectrum of electrons and holes in graphene leads to the strongly non-linear electromagnetic response of this system. We predict that the graphene layer, irradiated by electromagnetic waves, emits radiation at higher frequency harmonics and can work as a frequency multiplier. The operating frequency of the graphene frequency multiplier can lie in a broad range from microwaves to the infrared.Comment: 5 pages, 3 figure

Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice

Supraphysiological levels of the osteoblast‐enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase‐1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast‐specific Enpp1 ablation on skeletal structure and metabolic phenotype in mice. Female, but not male, 6‐week‐old mice lacking osteoblast NPP1 expression (osteoblast‐specific knockout [KO]) exhibited increased femoral bone volume or total volume (17.50% vs. 11.67%; p < .01), and reduced trabecular spacing (0.187 vs. 0.157 mm; p < .01) compared with floxed (control) mice. Furthermore, an enhanced ability of isolated osteoblasts from the osteoblast‐specific KO to calcify their matrix in vitro compared to fl/fl osteoblasts was observed (p < .05). Male osteoblast‐specific KO and fl/fl mice showed comparable glucose and insulin tolerance despite increased levels of insulin–sensitizing under‐carboxylated osteocalcin (195% increase; p < .05). However, following high‐fat‐diet challenge, osteoblast‐specific KO mice showed impaired glucose and insulin tolerance compared with fl/fl mice. These data highlight a crucial local role for osteoblast NPP1 in skeletal development and a secondary metabolic impact that predominantly maintains insulin sensitivity

The type III secretion system effector SeoC of salmonella enterica subsp. salamae and S. enterica subsp. arizonae ADP-Ribosylates Src and inhibits opsonophagocytosis

Salmonella species utilize type III secretion systems (T3SSs) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study, we compared a draft genome assembly of Salmonella enterica subsp. salamae strain 3588/07 against the genomes of S. enterica subsp. enterica serovar Typhimurium strain LT2 and Salmonella bongori strain 12419. S. enterica subsp. salamae encodes the Salmonella pathogenicity island 1 (SPI-1), SPI-2, and the locus of enterocyte effacement (LEE) T3SSs. Though several key S Typhimurium effector genes are missing (e.g., avrA, sopB, and sseL), S. enterica subsp. salamae invades HeLa cells and contains homologues of S. bongori sboK and sboC, which we named seoC SboC and SeoC are homologues of EspJ from enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), which inhibit Src kinase-dependent phagocytosis by ADP-ribosylation. By screening 73 clinical and environmental Salmonella isolates, we identified EspJ homologues in S. bongori, S. enterica subsp. salamae, and Salmonella enterica subsp. arizonae The β-lactamase TEM-1 reporter system showed that SeoC is translocated by the SPI-1 T3SS. All the Salmonella SeoC/SboC homologues ADP-ribosylate Src E310 in vitro Ectopic expression of SeoC/SboC inhibited phagocytosis of IgG-opsonized beads into Cos-7 cells stably expressing green fluorescent protein (GFP)-FcγRIIa. Concurrently, S. enterica subsp. salamae infection of J774.A1 macrophages inhibited phagocytosis of beads, in a seoC-dependent manner. These results show that S. bongori, S. enterica subsp. salamae, and S. enterica subsp. arizonae share features of the infection strategy of extracellular pathogens EPEC and EHEC and shed light on the complexities of the T3SS effector repertoires of Enterobacteriaceae

Mean-field driven first-order phase transitions in systems with long-range interactions

We consider a class of spin systems on $\Z^d$ with vector valued spins (\bS_x) that interact via the pair-potentials J_{x,y} \bS_x\cdot\bS_y. The interactions are generally spread-out in the sense that the $J_{x,y}$'s exhibit either exponential or power-law fall-off. Under the technical condition of reflection positivity and for sufficiently spread out interactions, we prove that the model exhibits a first-order phase transition whenever the associated mean-field theory signals such a transition. As a consequence, e.g., in dimensions $d\ge3$, we can finally provide examples of the 3-state Potts model with spread-out, exponentially decaying interactions, which undergoes a first-order phase transition as the temperature varies. Similar transitions are established in dimensions $d=1,2$ for power-law decaying interactions and in high dimensions for next-nearest neighbor couplings. In addition, we also investigate the limit of infinitely spread-out interactions. Specifically, we show that once the mean-field theory is in a unique ``state,'' then in any sequence of translation-invariant Gibbs states various observables converge to their mean-field values and the states themselves converge to a product measure.Comment: 57 pages; uses a (modified) jstatphys class fil

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies