Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and ...prognosis as well as a more efficient TB vaccine. IFN‐γ producing CD4+ T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T‐cell subsets, including classical and nonclassical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights into effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome, is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common comorbidities such as HIV, helminths and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease.
Content List ‐ Read more articles from the symposium: “The 10th International Conference on the Pathogenesis of Mycobacterial Infections”.
The proton is one of the main building blocks of all visible matter in the Universe
. Among its intrinsic properties are its electric charge, mass and spin
. These properties emerge from the complex ...dynamics of its fundamental constituents-quarks and gluons-described by the theory of quantum chromodynamics
. The electric charge and spin of protons, which are shared among the quarks, have been investigated previously using electron scattering
. An example is the highly precise measurement of the electric charge radius of the proton
. By contrast, little is known about the inner mass density of the proton, which is dominated by the energy carried by gluons. Gluons are hard to access using electron scattering because they do not carry an electromagnetic charge. Here we investigated the gravitational density of gluons using a small colour dipole, through the threshold photoproduction of the J/ψ particle. We determined the gluonic gravitational form factors of the proton
from our measurement. We used a variety of models
and determined, in all cases, a mass radius that is notably smaller than the electric charge radius. In some, but not all cases, depending on the model, the determined radius agrees well with first-principle predictions from lattice quantum chromodynamics
. This work paves the way for a deeper understanding of the salient role of gluons in providing gravitational mass to visible matter.
The introduction of agents that inhibit tumor angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling has made a significant impact on the survival of patients with metastasized ...renal cell carcinoma (RCC). Sunitinib, a tyrosine kinase inhibitor of the VEGF receptor, has become the mainstay of treatment for these patients. Although treatment with sunitinib substantially improved patient outcome, the initial success is overshadowed by the occurrence of resistance. The mechanisms of resistance are poorly understood. Insight into the molecular mechanisms of resistance will help to better understand the biology of RCC and can ultimately aid the development of more effective therapies for patients with this infaust disease. In this review we comprehensively discuss molecular mechanisms of resistance to sunitinib and the involved biological processes, summarize potential biomarkers that predict response and resistance to treatment with sunitinib, and elaborate on future perspectives in the treatment of metastasized RCC.
•Sunitinib resistance in renal cell carcinoma appears to be transient and reversible.•Tumor hypoxia plays a crucial role in several resistance mechanisms.•Hypoxia-mediated cMET signaling leads to an increased malignant potential.•Targeting cMET seems to be the most promising pharmacological treatment option.•DNA promoter hypermethylation could represent promising predictive factors.
Next Generation Sequencing (NGS) is expected to lift molecular diagnostics in clinical oncology to the next level. It enables simultaneous identification of mutations in a patient tumor, after which ...targeted therapy may be assigned. This approach could improve patient survival and/or assist in controlling healthcare costs by offering expensive treatment to only those likely to benefit. However, NGS has yet to make its way into the clinic. Health Technology Assessment can support the adoption and implementation of a novel technology, but at this early stage many of the required variables are still unknown.
Scenario drafting and expert elicitation via a questionnaire were used to identify factors that may act as a barrier or facilitate adoption of NGS-based molecular diagnostics. Attention was paid to predominantly elicit quantitative answers, allowing their use in future modelling of cost-effectiveness.
Adequately informing patients and physicians, the latters' opinion on clinical utility and underlying evidence as well as presenting sequencing results within a relevant timeframe may act as pivotal facilitators. Reimbursement for NGS-based testing and accompanying therapies (both general and in case of off-label prescription) was found to be a potential barrier. Competition on the market and demonstrating clinical utility may also be challenging. Importantly, numerous quantitative values for variables related to each of these potential barriers/facilitators, such as such as desired panel characteristics, willingness to pay or the expected number of targets identified per person, were also elicited.
We have identified several factors that may either pose a barrier or facilitate the adoption of NGS in the clinic. We believe acting upon these findings, for instance by organizing educational events, advocating new ways of evidence generation and steering towards the most cost-effective solution, will accelerate the route from bench-to-bedside. Moreover, due to the methodology of expert elicitation, this study provides parameters that can be incorporated in future cost-effectiveness modeling to steer the development of NGS gene panels towards the most optimal direction.
A
bstract
A comprehensive set of azimuthal single-spin and double-spin asymmetries in semi-inclusive leptoproduction of pions, charged kaons, protons, and antiprotons from transversely polarized ...protons is presented. These asymmetries include the previously published HERMES results on Collins and Sivers asymmetries, the analysis of which has been extended to include protons and antiprotons and also to an extraction in a three-dimensional kinematic binning and enlarged phase space. They are complemented by corresponding results for the remaining four single-spin and four double-spin asymmetries allowed in the one-photon-exchange approximation of the semi-inclusive deep-inelastic scattering process for target-polarization orientation perpendicular to the direction of the incoming lepton beam. Among those results, significant non-vanishing cos (
ϕ−ϕ
S
) modulations provide evidence for a sizable worm-gear (II) distribution,
g
1
T
q
x
p
T
2
. Most of the other modulations are found to be consistent with zero with the notable exception of large sin (
ϕ
S
) modulations for charged pions and
K
+
.
Healthcare workers treating SARS-CoV-2 patients are at risk of infection by respiratory exposure to patient-emitted, virus-laden aerosols. Source control devices such as ventilated patient isolation ...hoods have been shown to limit the dissemination of non-infectious airborne particles in laboratory tests, but data on their performance in mitigating the airborne transmission risk of infectious viruses are lacking.
We used an infectious airborne virus to quantify the ability of a ventilated hood to reduce infectious virus exposure in indoor environments.
We nebulized 109 plaque forming units (pfu) of bacteriophage PhiX174 virus into a ∼30-m3 room when the hood was active or inactive. The airborne concentration of infectious virus was measured by BioSpot-VIVAS and settle plates using plaque assay quantification on the bacterial host Escherichia coli C. The airborne particle number concentration (PNC) was also monitored continuously using an optical particle sizer.
The median airborne viral concentration in the room reached 1.41 × 105 pfu/m3 with the hood inactive. When active, the hood reduced infectious virus concentration in air samples by 374-fold. The deposition of infectious virus on the surface of settle plates was reduced by 87-fold. This was associated with a 109-fold reduction in total airborne particle number escape rate.
A personal ventilation hood significantly reduced airborne particle escape, considerably lowering infectious virus contamination in an indoor environment. Our findings support the further development of source control devices to mitigate nosocomial infection risk among healthcare workers exposed to airborne viruses in clinical settings.
The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics ...and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities
that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities
map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades
. Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.
The CLAS12 Geant4 simulation Ungaro, M.; Angelini, G.; Battaglieri, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2020, Letnik:
959, Številka:
C
Journal Article
Recenzirano
Odprti dostop
The Geant4 Monte-Carlo (GEMC) package is used to simulate the passage of particles through the various CLAS12 detectors. The geometry is implemented through a database of Geant4 volumes created ...either through the GEMC native API, by the CLAS12 geometry service, or imported from the CAD engineering model. The truth information is digitized with a plugin mechanism by routines specific to each detector and includes the use of the CLAS12 calibration database constants to produce both ADC and TDC response functions. Theoretical models that produce the generated events interface with GEMC through the LUND data format. The merging of simulated data with real random trigger data provides a mechanism to include both beam and electronic background into the simulation of generated events to accurately model beam data from the CLAS12 detector. The performance of simulation is demonstrated by comparison with the experimental data.
Enhanced UV light detection using a p-terphenyl wavelength shifter Joosten, S.; Kaczanowicz, E.; Ungaro, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2017, Letnik:
870, Številka:
C
Journal Article
Recenzirano
Odprti dostop
UV-glass photomultiplier tubes (PMTs) have poor photon detection efficiency for wavelengths below 300 nm due to the opaqueness of the window material. Costly quartz PMTs could be used to enhance the ...efficiency below 300 nm. A less expensive solution that dramatically improves this efficiency is the application of a thin film of a p-terphenyl (PT) wavelength shifter on UV-glass PMTs. This improvement was quantified for Photonis XP4500B PMTs for wavelengths between 200 nm and 400 nm. The gain factor ranges up to 5.4±0.5 at a wavelength of 215 nm, with a material load of 110±10μg∕cm2 (894 nm). The wavelength shifter was found to be fully transparent for wavelengths greater than 300 nm. The resulting gain in detection efficiency, when used in a typical C̆erenkov counter, was estimated to be of the order of 40%. Consistent coating quality was assured by a rapid gain testing procedure using narrow-band UV LEDs. Based on these results, 200 Photonis XP4500B PMTs were treated with PT for the upgraded low-threshold C̆erenkov counter (LTCC) to be used in the CEBAF Large Acceptance Spectrometer upgraded detector (CLAS12) at the Thomas Jefferson National Accelerator Facility.
PDF
