The Photon Underproduction Crisis

We examine the statistics of the low-redshift Lyman-alpha forest from smoothed particle hydrodynamic simulations in light of recent improvements in the estimated evolution of the cosmic ultraviolet background (UVB) and recent observations from the Cosmic Origins Spectrograph (COS). We find that the value of the metagalactic photoionization rate required by our simulations to match the observed properties of the low-redshift Lyman-alpha forest is a factor of 5 larger than the value predicted by state-of-the art models for the evolution of this quantity. This mismatch results in the mean flux decrement of the Lyman-alpha forest being underpredicted by at least a factor of 2 (a 10-sigma discrepancy with observations) and a column density distribution of Lyman-alpha forest absorbers systematically and significantly elevated compared to observations over nearly two decades in column density. We examine potential resolutions to this mismatch and find that either conventional sources of ionizing photons (galaxies and quasars) must be significantly elevated relative to current observational estimates or our theoretical understanding of the low-redshift universe is in need of substantial revision.Comment: Submitted to ApJ Letters; 6 pages including 3 figure

A Pilot Sexual Device Adaptation Project for Occupational Therapy Students: A Skills-Based Approach to Teaching Sexual Activity as an ADL Through Assistive Technology

Despite being categorized as an activity of daily living since the first edition of the Occupational Therapy Practice Framework, no Accreditation Council for Occupational Therapy Education (ACOTE) standards exist to provide guidance on teaching occupational therapy students about sexual activity as an activity of daily living (ADL). When discussed, sexual activity is usually taught via didactic lecture, but is a subject that would benefit from a skills-based approach to teaching. This pilot pedagogical exercise in a two-credit assistive technology class taught occupational therapy students to address the ADL of sexual activity with clients by having students adapt a sexual toy using basic soldering techniques and adaptive switches for a mock client. By providing a hands-on adaptive project for students, students practiced applying occupational analysis to the adaptation of assistive technology, which can generalize to other assistive technologies (such as those for adaptive gaming) and occupations, while also providing students with experience discussing sexual activity as an ADL in practice. This project is an option for occupational therapy programs looking to integrate more education on sexual activity into their current curricula, while also satisfying the requirements of assistive technology ACOTE standards

Sesame eliciting and safe doses in a large sesame allergic population

Background: Sesame is a significant food allergen causing severe and even fatal reactions. Given its increasing prevalence in western diet, sesame is listed as an allergenic food requiring labeling in the United States and EU. However, data on the population reaction doses to sesame are limited. Methods: All sesame oral food challenges (OFCs), performed either for diagnosis or for threshold identification before the beginning of sesame oral immunotherapy (OIT) between November 2011 and July 2021 in Shamir medical center were analyzed for reaction threshold distribution. Safe-dose challenges with 90–120 min intervals were also analyzed. Results: Two hundred and fifty patients underwent 338 positive OFCs, and additional 158 safe-dose OFCs were performed. The discrete and cumulative protein amounts estimated to elicit an objective reaction in 1% (ED01) of the entire cohort (n = 250) were 0.8 mg (range 0.3–6.3) and 0.7 mg (range 0.1–7.1), respectively, and those for 5% of the population (ED05) were 3.4 mg (range 1.2–20.6) and 4.5 mg (range 1.2–28.8), respectively. Safe-dose OFCs showed similar values of ED01 (0.8, 0.4–7.5 mg) and ED05 (3.4, 1.2–22.9 mg). While doses of ≤1 mg sesame protein elicited oral pruritus in 11.6% of the patients, no objective reaction was documented to this amount in any of the challenges, including safe-dose OFCs. Conclusions: This study provides data on sesame reaction threshold distribution in the largest population of allergic patients studied, with no right or left censored data, and with validation using a safe-dose OFC. It further supports the current methods for ED determination as appropriate for establishing safety precautions for the food industry

A genetically encoded reporter of synaptic activity in vivo

To image synaptic activity within neural circuits, we tethered the genetically encoded calcium indicator (GECI) GCaMP2 to synaptic vesicles by fusion to synaptophysin. The resulting reporter, SyGCaMP2, detected the electrical activity of neurons with two advantages over existing cytoplasmic GECIs: it identified the locations of synapses and had a linear response over a wider range of spike frequencies. Simulations and experimental measurements indicated that linearity arises because SyGCaMP2 samples the brief calcium transient passing through the presynaptic compartment close to voltage-sensitive calcium channels rather than changes in bulk calcium concentration. In vivo imaging in zebrafish demonstrated that SyGCaMP2 can assess electrical activity in conventional synapses of spiking neurons in the optic tectum and graded voltage signals transmitted by ribbon synapses of retinal bipolar cells. Localizing a GECI to synaptic terminals provides a strategy for monitoring activity across large groups of neurons at the level of individual synapses

CowN Sustains Nitrogenase Turnover in the Presence of the Inhibitor Carbon Monoxide

Nitrogenase is the only enzyme capable of catalyzing nitrogen fixation, the reduction of dinitrogen gas (N2) to ammonia (NH3). Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Nitrogen-fixing bacteria rely on the protein CowN to grow in the presence of CO. However, the mechanism by which CowN operates is unknown. Here, we present the biochemical characterization of CowN and examine how CowN protects nitrogenase from CO. We determine that CowN interacts directly with nitrogenase and that CowN protection observes hyperbolic kinetics with respect to CowN concentration. At a CO concentration of 0.001 atm, CowN restores nearly full nitrogenase activity. Our results further indicate that CowN’s protection mechanism involves decreasing the binding affinity of CO to nitrogenase’s active site approximately tenfold without interrupting substrate turnover. Taken together, our work suggests CowN is an important auxiliary protein in nitrogen fixation that engenders CO tolerance to nitrogenase

Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study.

BackgroundVB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM).MethodsPatients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).ResultsVB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease.ConclusionsPatients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study

Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE)

Focusing of light in the diffusive regime inside scattering media has long been considered impossible. Recently, this limitation has been overcome with time reversal of ultrasound-encoded light (TRUE), but the resolution of this approach is fundamentally limited by the large number of optical modes within the ultrasound focus. Here, we introduce a new approach, time reversal of variance-encoded light (TROVE), which demixes these spatial modes by variance encoding to break the resolution barrier imposed by the ultrasound. By encoding individual spatial modes inside the scattering sample with unique variances, we effectively uncouple the system resolution from the size of the ultrasound focus. This enables us to demonstrate optical focusing and imaging with diffuse light at an unprecedented, speckle-scale lateral resolution of ~5 µm

Translation correlations in anisotropically scattering media

Controlling light propagation across scattering media by wavefront shaping holds great promise for a wide range of communications and imaging applications. However, finding the right wavefront to shape is a challenge when the mapping between input and output scattered wavefronts (i.e. the transmission matrix) is not known. Correlations in transmission matrices, especially the so-called memory-effect, have been exploited to address this limitation. However, the traditional memory-effect applies to thin scattering layers at a distance from the target, which precludes its use within thick scattering media, such as fog and biological tissue. Here, we theoretically predict and experimentally verify new transmission matrix correlations within thick anisotropically scattering media, with important implications for biomedical imaging and adaptive optics.Comment: main article (18 pages) and appendices (6 pages