Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction

Persistent polyclonal B cell lymphocytosis (PPBL) is a rare disorder, diagnosed primarily in adult female smokers and characterized by an expansion of CD19+CD27+IgM+ memory B cells, by the presence of binucleated lymphocytes, and by a moderate elevation of serum IgM. The clinical course is usually benign, but it is not known whether or not PPBL might be part of a process leading to the emergence of a malignant proliferative disorder. In this study we sought to investigate the functional response of B cells from patients with PPBL by use of an optimal memory B cell culture model based on the CD40-CD154 interaction. We found that the proliferation of PPBL B cells was almost as important as that of B cells from normal controls, resulting in high immunoglobulin secretion with in vitro isotypic switching. We conclude that the CD40-CD154 activation pathway is functional in the memory B cell population of PPBL patients, suggesting that the disorder may be due to either a dysfunction of other cells in the microenvironment or a possible defect in another B cell activation pathway

Zero-Emission Regional Aviation in Sweden

Presented at the 33rd ICAS Congress, Sweden (2022).Regional air operations, which can be defined as the transportation of passengers using smaller aircraft over short distances, have been overlooked in recent years by airlines focusing on high volume and profitable routes between large airports. Despite this shift of focus, the airport infrastructure still exists in many smaller communities between which demand for air travel exists. The emergence of new air vehicles designed for shorter routes could stimulate efficient and profitable operations, especially if they leverage currently underutilized and paid-for airports. However, new regional air operations need to be sustainable to be successful in a world striving for a carbon-neutral future, especially since air travel over short distances can be substituted by other means of transportation with a smaller environmental footprint such as cars, trains, or buses. Many different paths are envisioned to reach zero-emission goals. These range from technology advancements to new powertrain configurations, and from new transportation policies to new emission offsetting schemes. It is however not clear how these different paths interact and how solutions could be optimally combined. Analyses are therefore required to estimate future demand for air travel and to assess the feasibility of zero-emission regional aviation with the objective to support decision-making about viable and sustainable paths for new regional air operations. The developed modeling environment is implemented in Sweden and allows for an environmental assessment of various scenarios. Significant untapped demand is uncovered between smaller markets, and given fuel and energy consumption for these operations, it is likely that sustainable advanced regional air mobility will be possible in Sweden provided technology transitions can be made

Nitric Oxide Synthase Inhibition Enhances the Antitumor Effect of Radiation in the Treatment of Squamous Carcinoma Xenografts

This study tests whether the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NNA), combines favorably with ionizing radiation (IR) in controlling squamous carcinoma tumor growth. Animals bearing FaDu and A431 xenografts were treated with L-NNA in the drinking water. IR exposure was 10 Gy for tumor growth and survival studies and 4 Gy for ex vivo clonogenic assays. Cryosections were examined immunohistochemically for markers of apoptosis and hypoxia. Blood flow was assayed by fluorescent microscopy of tissue cryosections after i.v. injection of fluorospheres. Orally administered L-NNA for 24 hrs reduces tumor blood flow by 80% (p<0.01). Within 24 hrs L-NNA treatment stopped tumor growth for at least 10 days before tumor growth again ensued. The growth arrest was in part due to increased cell killing since a combination of L-NNA and a single 4 Gy IR caused 82% tumor cell killing measured by an ex vivo clonogenic assay compared to 49% by L-NNA or 29% by IR alone. A Kaplan-Meyer analysis of animal survival revealed a distinct survival advantage for the combined treatment. Combining L-NNA and IR was also found to be at least as effective as a single i.p. dose of cisplatin plus IR. In contrast to the in vivo studies, exposure of cells to L-NNA in vitro was without effect on clonogenicity with or without IR. Western and immunochemical analysis of expression of a number of proteins involved in NO signaling indicated that L-NNA treatment enhanced arginase-2 expression and that this may represent vasculature remodeling and escape from NOS inhibition. For tumors such as head and neck squamous carcinomas that show only modest responses to inhibitors of specific angiogenic pathways, targeting NO-dependent pro-survival and angiogenic mechanisms in both tumor and supporting stromal cells may present a potential new strategy for tumor control

Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

Constraints on the shallow elastic and anelastic structure of Mars from InSight seismic data

Mars’s seismic activity and noise have been monitored since January 2019 by the seismometer of the InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) lander. At night, Mars is extremely quiet; seismic noise is about 500 times lower than Earth’s microseismic noise at periods between 4 s and 30 s. The recorded seismic noise increases during the day due to ground deformations induced by convective atmospheric vortices and ground-transferred wind-generated lander noise. Here we constrain properties of the crust beneath InSight, using signals from atmospheric vortices and from the hammering of InSight’s Heat Flow and Physical Properties (HP3) instrument, as well as the three largest Marsquakes detected as of September 2019. From receiver function analysis, we infer that the uppermost 8–11 km of the crust is highly altered and/ or fractured. We measure the crustal diffusivity and intrinsic attenuation using multiscattering analysis and find that seismic attenuation is about three times larger than on the Moon, which suggests that the crust contains small amounts of volatiles

SEIS: Insight’s Seismic Experiment for Internal Structure of Mars

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars’ surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking’s Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars’ surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of Mw ∼ 3 at 40◦ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution