Because the Fortune Teller Told Me / music by Howard and Emmerson; words by Howard and Emmerson and Maurice J. Steinberg

Cover: drawing of an African American male listening to a fortune teller with outlayed cards; photo inset of John E. Brennan and Florence Sinnott; Publisher: T. B. Harms and Co. (New York)https://egrove.olemiss.edu/sharris_b/1007/thumbnail.jp

Porous Media Matric Potential and Water Content Measurements During Parabolic Flight

Control of water and air in the root zone of plants remains a challenge in the microgravity environment of space. Due to limited flight opportunities, research aimed at resolving microgravity porous media fluid dynamics must often be conducted on Earth. The NASA KC-135 reduced gravity flight program offers an opportunity for Earth-based researchers to study physical processes in a variable gravity environment. The objectives of this study were to obtain measurements of water content and matric potential during the parabolic profile flown by the KC-135 aircraft. The flight profile provided 20–25 s of microgravity at the top of the parabola, while pulling 1.8 g at the bottom. The soil moisture sensors (Temperature and Moisture Acquisition System: Orbital Technologies, Madison, WI) used a heat-pulse method to indirectly estimate water content from heat dissipation. Tensiometers were constructed using a stainless steel porous cup with a pressure transducer and were used to measure the matric potential of the medium. The two types of sensors were placed at different depths in a substrate compartment filled with 1–2 mm Turface (calcined clay). The ability of the heat-pulse sensors to monitor overall changes in water content in the substrate compartment decreased with water content. Differences in measured water content data recorded at 0, 1, and 1.8 g were not significant. Tensiometer readings tracked pressure differences due to the hydrostatic force changes with variable gravity. The readings may have been affected by changes in cabin air pressure that occurred during each parabola. Tensiometer porous membrane conductivity (function of pore size) and fluid volume both influence response time. Porous media sample height and water content influence time-to-equilibrium, where shorter samples and higher water content achieve faster equilibrium. Further testing is needed to develop these sensors for space flight applications

Experimental nonlocal and surreal Bohmian trajectories

Weak measurement allows one to empirically determine a set of average trajectories for an ensemble of quantum particles. However, when two particles are entangled, the trajectories of the first particle can depend nonlocally on the position of the second particle. Moreover, the theory describing these trajectories, called Bohmian mechanics, predicts trajectories that were at first deemed “surreal” when the second particle is used to probe the position of the first particle. We entangle two photons and determine a set of Bohmian trajectories for one of them using weak measurements and postselection. We show that the trajectories seem surreal only if one ignores their manifest nonlocality.Full Tex

Diurnal secretion of growth hormone, cortisol, and dehydroepiandrosterone in pre- and perimenopausal women with active rheumatoid arthritis: a pilot case-control study

Rheumatoid arthritis (RA) is associated with neuroendocrine and immunologic dysfunction leading to rheumatoid cachexia. Although excess proinflammatory cytokines can decrease somatotropic axis activity, little is known about the effects of RA on growth hormone/insulin-like growth factor-1 (GH/IGF-I) axis function. We tested the hypothesis that patients with active RA exhibit decreased GH/IGF-I axis activity. To do so, we conducted a pilot case-control study at a clinical research center in 7 pre- and perimenopausal women with active RA and 10 age- and body mass index-matched healthy women. Participants underwent blood sampling every 20 minutes for 24 hours (8 a.m. to 8 a.m.), and sera were assayed for GH, cortisol, and dehydroepiandrosterone (DHEA). Sera obtained after overnight fasting were assayed for IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, C-reactive protein (CRP), interleukin-6 (IL-6), glucose, insulin, and lipids. Body composition and bone mineral density were evaluated by DEXA (dual emission x-ray absorptiometry) scans. In patients with RA, mean disease duration was 7.6 ± 6.8 years, and erythrocyte sedimentation rate, CRP, and IL-6 were elevated. GH half-life was shorter than in control subjects (p = 0.0037), with no other significant group differences in GH deconvolution parameters or approximate entropy scores. IGF-I (p = 0.05) and IGFBP-3 (p = 0.058) were lower, whereas IGFBP-1 tended to be higher (p = 0.066), in patients with RA, with nonsignificantly increased 24-hour total GH production rates. There were no significant group differences in cortisol or DHEA secretion. Lean body mass was lower in patients with RA (p = 0.019), particularly in the legs (p = 0.01). Women with active RA exhibit a trend toward GH insensitivity and relatively diminished diurnal cortisol and DHEA secretion for their state of inflammation. Whether these changes contribute to rheumatoid cachexia remains to be determined

Reward, learning and games

The link between reward and learning has chiefly been studied scientifically in the context of reinforcement learning. This type of learning, which relies upon midbrain dopaminergic response, differs greatly from the learning valued by educators, which typically involves declarative memory formation. However, with recent insights regarding the modulation of hippocampal function by midbrain dopamine, scientific understanding of the midbrain response to reward may be becoming more relevant to education. Here, we consider the potential for our current understanding of reward to inform educational learning, and consider its implications for game-like interventions in the classroom

A single dose polyanhydride-based nanovaccine against paratuberculosis infection

Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) causes Johne’s disease in ruminants and is characterized by chronic gastroenteritis leading to heavy economic losses to the dairy industry worldwide. The currently available vaccine (inactivated bacterin in oil base) is not effective in preventing pathogen shedding and is rarely used to control Johne’s disease in dairy herds. To develop a better vaccine that can prevent the spread of Johne’s disease, we utilized polyanhydride nanoparticles (PAN) to encapsulate mycobacterial antigens composed of whole cell lysate (PAN-Lysate) and culture filtrate (PAN-Cf) of M. paratuberculosis. These nanoparticle-based vaccines (i.e., nanovaccines) were well tolerated in mice causing no inflammatory lesions at the site of injection. Immunological assays demonstrated a substantial increase in the levels of antigen-specific T cell responses post-vaccination in the PAN-Cf vaccinated group as indicated by high percentages of triple cytokine (IFN-γ, IL-2, TNF-α) producing CD8+ T cells. Following challenge, animals vaccinated with PAN-Cf continued to produce significant levels of double (IFN-γ, TNF-α) and single cytokine (IFN-γ) secreting CD8+ T cells compared with animals vaccinated with an inactivated vaccine. A significant reduction in bacterial load was observed in multiple organs of animals vaccinated with PAN-Cf, which is a clear indication of protection. Overall, the use of polyanhydride nanovaccines resulted in development of protective and sustained immunity against Johne’s disease, an approach that could be applied to counter other intracellular pathogens

Mechanistic Basis of Branch-Site Selection in Filamentous Bacteria

Many filamentous organisms, such as fungi, grow by tip-extension and by forming new branches behind the tips. A similar growth mode occurs in filamentous bacteria, including the genus Streptomyces, although here our mechanistic understanding has been very limited. The Streptomyces protein DivIVA is a critical determinant of hyphal growth and localizes in foci at hyphal tips and sites of future branch development. However, how such foci form was previously unknown. Here, we show experimentally that DivIVA focus-formation involves a novel mechanism in which new DivIVA foci break off from existing tip-foci, bypassing the need for initial nucleation or de novo branch-site selection. We develop a mathematical model for DivIVA-dependent growth and branching, involving DivIVA focus-formation by tip-focus splitting, focus growth, and the initiation of new branches at a critical focus size. We quantitatively fit our model to the experimentally-measured tip-to-branch and branch-to-branch length distributions. The model predicts a particular bimodal tip-to-branch distribution results from tip-focus splitting, a prediction we confirm experimentally. Our work provides mechanistic understanding of a novel mode of hyphal growth regulation that may be widely employed

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

A multiscale hybrid model for pro-angiogenic calcium signals in a vascular endothelial cell

Cytosolic calcium machinery is one of the principal signaling mechanisms by which endothelial cells (ECs) respond to external stimuli during several biological processes, including vascular progression in both physiological and pathological conditions. Low concentrations of angiogenic factors (such as VEGF) activate in fact complex pathways involving, among others, second messengers arachidonic acid (AA) and nitric oxide (NO), which in turn control the activity of plasma membrane calcium channels. The subsequent increase in the intracellular level of the ion regulates fundamental biophysical properties of ECs (such as elasticity, intrinsic motility, and chemical strength), enhancing their migratory capacity. Previously, a number of continuous models have represented cytosolic calcium dynamics, while EC migration in angiogenesis has been separately approached with discrete, lattice-based techniques. These two components are here integrated and interfaced to provide a multiscale and hybrid Cellular Potts Model (CPM), where the phenomenology of a motile EC is realistically mediated by its calcium-dependent subcellular events. The model, based on a realistic 3-D cell morphology with a nuclear and a cytosolic region, is set with known biochemical and electrophysiological data. In particular, the resulting simulations are able to reproduce and describe the polarization process, typical of stimulated vascular cells, in various experimental conditions.Moreover, by analyzing the mutual interactions between multilevel biochemical and biomechanical aspects, our study investigates ways to inhibit cell migration: such strategies have in fact the potential to result in pharmacological interventions useful to disrupt malignant vascular progressio

Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study

Purpose: Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade. Methods: A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day. The primary outcome was objective response rate. Correlative studies included mandatory collection of pretreatment and during-treatment biopsy specimens, which were assessed to define SCLC immunephenotypes: desert (CD8-positive T-cell prevalence low), excluded (CD8-positive T cells in stroma immediately adjacent/within tumor), and inflamed (CD8-positive T cells in direct contact with tumor). Results: A total of 20 patients were enrolled. Their median age was 64 years, and most patients (60%) had platinum-resistant/refractory disease. Of 19 evaluable patients, two were observed to have partial or complete responses (10.5%), including a patient with EGFR-transformed SCLC. Clinical benefit was observed in four patients (21.1% [95% confidence interval: 6.1%–45.6%]) with confirmed responses or prolonged stable disease (≥8 months). The most common treatment-related adverse events were anemia (80%), lymphopenia (60%), and leukopenia (50%). Nine of 14 tumors (64%) exhibited an excluded phenotype; 21% and 14% of tumors exhibited the inflamed and desert phenotypes, respectively. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Of the five tumors without an inflamed phenotype at baseline, no during-treatment increase in T-cell infiltration or programmed death ligand 1 expression on tumor-infiltrating immune cells was observed. Conclusions: The study combination did not meet the preset bar for efficacy. Pretreatment and during-treatment biopsy specimens suggested that tumor immune phenotypes may be relevant for SCLC responses to immune checkpoint blockade combinations. The predictive value of preexisting CD8-positive T-cell infiltrates observed in this study needs to be confirmed in larger cohorts