Although there have been significant advances in the treatment of visceral leishmaniasis (VL), there remain challenges to ensure that treatments effective in India are also effective in other regions ...of the world and to identify treatment for post kala-azar dermal leishmaniasis as well as the opportunity to develop a safe oral short-course treatment. At the same time, there have been few advances for the treatment of simple or complex forms of cutaneous leishmaniasis (CL), other than topical paromomycin formulations. The main challenge for CL is to ensure that this disease is on the research and development agenda, so that new drugs are evaluated or compounds are screened in appropriate models, and that the standardization of quality of clinical trials is guaranteed. Problems also remain in the treatment of HIV/leishmaniasis co-infected patients. We are some way from having the ideal treatments for VL and CL and drug research and development for these diseases must remain focused.
We report the first detections of the repeating fast radio burst source FRB 121102 above 5.2 GHz. Observations were performed using the 4-8 GHz receiver of the Robert C. Byrd Green Bank Telescope ...with the Breakthrough Listen digital backend. We present the spectral, temporal, and polarization properties of 21 bursts detected within the first 60 minutes of a total of 6 hr of observations. These observations comprise the highest burst density yet reported in the literature, with 18 bursts being detected in the first 30 minutes. A few bursts clearly show temporal sub-structure with distinct spectral properties. These sub-structures superimpose to provide an enhanced peak signal-to-noise ratio at higher trial dispersion measures. Broad features occur in ∼1 GHz wide subbands that typically differ in peak frequency between bursts within the band. Finer-scale structures (∼10-50 MHz) within these bursts are consistent with the structure expected from Galactic diffractive interstellar scintillation. The bursts exhibit nearly 100% linear polarization, and a large average rotation measure of 9.359 0.012 × 104 rad m−2 (in the observer's frame). No circular polarization was found for any burst. We measure an approximately constant polarization position angle in the 13 brightest bursts. The peak flux densities of the reported bursts have average values (0.2 0.1 Jy) similar to those seen at lower frequencies (<3 GHz), while the average burst widths (0.64 0.46 ms) are relatively narrower.
The Galactic Faraday rotation sky 2020 Hutschenreuter, S.; Anderson, C. S.; Betti, S. ...
Astronomy and astrophysics (Berlin),
01/2022, Volume:
657
Journal Article
Peer reviewed
Open access
Aims.
This work provides an update to existing reconstructions of the Galactic Faraday rotation sky by processing almost all Faraday rotation data sets available at the end of the year 2020. ...Observations of extra-Galactic sources in recent years have further illuminated the previously underconstrained southern celestial sky, as well as parts of the inner disc of the Milky Way, along with other regions. This has culminated in an all-sky data set of 55 190 data points, thereby comprising a significant expansion on the 41 330 used in previous works. At the same time, this novelty makes an updated separation of the Galactic component a promising enterprise. The increased source density allows us to present our results in a resolution of about 1.3 × 10
−2
deg
2
(46.8 arcmin
2
), which is a twofold increase compared to previous works.
Methods.
As for previous Faraday rotation sky reconstructions, this work is based on information field theory, namely, a Bayesian inference scheme for field-like quantities that handles noisy and incomplete data.
Results.
In contrast to previous reconstructions, we find a significantly thinner and pronounced Galactic disc with small-scale structures exceeding values of several thousand rad m
−2
. The improvements can mainly be attributed to the new catalog of Faraday data, but are also supported by advances in correlation structure modeling within numerical information field theory. We also provide a detailed discussion on the statistical properties of the Faraday rotation sky and we investigate correlations with other data sets.
Following the results of the first systematic modern low-frequency search for extraterrestrial intelligence using the Murchison Widefield Array (MWA), which was directed toward a Galactic Center ...field, we report a second survey toward a Galactic Anticenter field. Using the MWA in the frequency range 99-122 MHz over a three-hour period, a 625 deg2 field centered on Orion KL (in the general direction of the Galactic Anticenter) was observed with a frequency resolution of 10 kHz. Within this field, 22 exoplanets are known. At the positions of these exoplanets, we searched for narrowband signals consistent with radio transmissions from intelligent civilizations. No such signals were found with a 5 detection threshold. Our sample is significantly different to the 45 exoplanets previously studied with the MWA toward the Galactic Center, since the Galactic Center sample is dominated by exoplanets detected using microlensing, and hence at much larger distances than the exoplanets toward the Anticenter, found via radial velocity and transit detection methods. Our average effective sensitivity to extraterrestrial transmitter power is therefore much improved for the Anticenter sample. Added to this, our data processing techniques have improved, reducing our observational errors, leading to our best detection limit being reduced by approximately a factor of four compared to our previously published results.
Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current "gold standard" for intervertebral disc ...degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body's physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD. Over the past decade, many research groups have invested efforts to find ways to utilize these cells as efficiently and sustainably as possible. This narrative literature review presents a summary of achievements made with the application of MSCs for the regeneration of the IVD in recent years, including their preclinical and clinical applications. Moreover, this review presents state-of-the-art strategies on how the homing capabilities of MSCs can be utilized to repair damaged or degenerated IVDs, as well as their current limitations and future perspectives.
For decades antimonials were the drugs of choice for the treatment of visceral leishmaniasis (VL), but the recent emergence of resistance has made them redundant as first-line therapy in the endemic ...VL region in the Indian subcontinent. The application of other drugs has been limited due to adverse effects, perceived high cost, need for parenteral administration and increasing rate of treatment failures. Liposomal amphotericin B (AmB) and miltefosine (MIL) have been positioned as the effective first-line treatments; however, the number of monotherapy MIL-failures has increased after a decade of use. Since no validated molecular resistance markers are yet available, monitoring and surveillance of changes in drug sensitivity and resistance still depends on standard phenotypic in vitro promastigote or amastigote susceptibility assays. Clinical isolates displaying defined MIL- or AmB-resistance are still fairly scarce and fundamental and applied research on resistance mechanisms and dynamics remains largely dependent on laboratory-generated drug resistant strains. This review addresses the various challenges associated with drug susceptibility and -resistance monitoring in VL, with particular emphasis on the choice of strains, susceptibility model selection and standardization of procedures with specific read-out parameters and well-defined threshold criteria. The latter are essential to support surveillance systems and safeguard the limited number of currently available antileishmanial drugs.
The intervertebral disc (IVD) is a complex tissue, and its degeneration remains a problem for patients, without significant improvement in treatment strategies. This mostly age-related disease ...predominantly affects the nucleus pulposus (NP), the central region of the IVD. The NP tissue, and especially its microenvironment, exhibit changes that may be involved at the outset or affect the progression of IVD pathology. The NP tissue microenvironment is unique and can be defined by a variety of specific factors and components characteristic of its physiology and function. NP progenitor cell interactions with their surrounding microenvironment may be a key factor for the regulation of cellular metabolism, phenotype, and stemness. Recently, celltransplantation approaches have been investigated for the treatment of degenerative disc disease, highlighting the need to better understand if and how transplanted cells can give rise to healthy NP tissue. Hence, understanding all the components of the NP microenvironment seems to be critical to better gauge the success and outcomes of approaches for tissue engineering and future clinical applications. Knowledge about the components of the NP microenvironment, how NP progenitor cells interact with them, and how changes in their surroundings can alter their function is summarised. Recent discoveries in NP tissue engineering linked to the microenvironment are also reviewed, meaning how crosstalk within the microenvironment can be adjusted to promote NP regeneration. Associated clinical problems are also considered, connecting bench-to-bedside in the context of IVD degeneration.
For years, researchers have searched for a suitable biomaterial to regenerate the intervertebral disc (IVD). A promising candidate is silk, as there have been several approaches in the past where ...silk fibroin was used to repair the IVD's nucleus pulposus (NP) and annulus fibrosus (AF). However, to date, nobody has attempted to recreate IVD tissue with dimensions and cell densities comparable to a human IVD using silk and human mesenchymal stromal cells (MSC). Therefore, silk scaffolds were produced from Bombyx mori yarn. To mimic the AF, the yarn was embroidered into a ring-like structure or patch. To mimic the NP, fibre-additive manufacturing was applied to create highly porous constructs. Half of the NP scaffolds were functionalized with the growth differentiation factor 5 (GDF5). The scaffolds were seeded with MSCs from five human donors in a density of one-third of the density found in the human IVD and cultured for 7, 14 or 21 days in transforming growth factor β1 (TGF-β1)-enriched medium. All scaffolds were biocompatible as cell numbers increased by a factor 4-5. Furthermore, the scaffolds generally showed an anabolic phenotype, which was positively influenced by GDF5, and tissue-like characteristics were promoted based on the scaffolds' morphology. In conclusion, the here proposed silk scaffolds showed IVD-like characteristics with a size and cell density comparable to human IVD tissue.
New formulations, therapeutic switching of the established drugs amphotericin B and paromomycin, and the serendipitous discovery of miltefosine have markedly improved leishmaniasis chemotherapy in ...the past 21 years. The situation for the two trypanosomiases has been less encouraging. Apart from the introduction of eflornithine for the treatment of late-stage human African trypanosomiasis, with its serious limitations in terms of cost and difficulty of administration, no new drugs have been incorporated into the chemotherapeutic arsenal in the past 25 years, despite important advances in knowledge of the biology of the etiological agents and the pathophysiology of these diseases. In the case of Chagas disease, several classes of compound that target the validated biochemical pathways of the parasite (e.g. inhibitors of sterol biosynthesis and cysteine proteases) are in the pipeline. With the availability of complete genome sequences for all three pathogens, and methods for rapid validation of targets, it is hoped that much-needed amelioration will occur soon. Financial constraints continue to represent a major hurdle to drug development. However, the appearance of not-for-profit product-development partnerships offers a new paradigm for bringing new drugs to patients.
The retina processes visual images to compute features such as the direction of image motion. Starburst amacrine cells (SACs), axonless feed-forward interneurons, are essential components of the ...retinal direction-selective circuitry. Recent work has highlighted that SAC-mediated dendro-dendritic inhibition controls the action potential output of direction-selective ganglion cells (DSGCs) by vetoing dendritic spike initiation. However, SACs co-release GABA and the excitatory neurotransmitter acetylcholine at dendritic sites. Here we use direct dendritic recordings to show that preferred direction light stimuli evoke SAC-mediated acetylcholine release, which powerfully controls the stimulus sensitivity, receptive field size and action potential output of ON-DSGCs by acting as an excitatory drive for the initiation of dendritic spikes. Consistent with this, paired recordings reveal that the activation of single ON-SACs drove dendritic spike generation, because of predominate cholinergic excitation received on the preferred side of ON-DSGCs. Thus, dendro-dendritic release of neurotransmitters from SACs bi-directionally gate dendritic spike initiation to control the directionally selective action potential output of retinal ganglion cells.
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