We report a study of the CUORE sensitivity to neutrinoless double beta (0νββ) decay. We used a Bayesian analysis based on a toy Monte Carlo (MC) approach to extract the exclusion sensitivity to the ...0νββ decay half-life (T1/20ν) at 90% credibility interval (CI) – i.e. the interval containing the true value of T1/20ν with 90% probability – and the 3σ discovery sensitivity. We consider various background levels and energy resolutions, and describe the influence of the data division in subsets with different background levels. If the background level and the energy resolution meet the expectation, CUORE will reach a 90% CI exclusion sensitivity of 2·1025 year with 3 months, and 9·1025 year with 5 years of live time. Under the same conditions, the discovery sensitivity after 3 months and 5 years will be 7·1024 year and 4·1025 year, respectively.
Reversible covalent chemistry provides access to robust materials with the ability to be degraded and reformed upon exposure to an appropriate stimulus. Photoresponsive units are attractive for this ...purpose, as the spatial and temporal application of light is easily controlled. Coumarin derivatives undergo a 2 + 2 cycloaddition upon exposure to long-wave UV irradiation (365 nm), and this process can be reversed using short-wave UV light (254 nm). Therefore, polymers cross-linked by coumarin groups are excellent candidates as reversible covalent gels. In this work, copolymerization of coumarin-containing monomers with the hydrophilic comonomer N,N-dimethylacrylamide yielded water-soluble, linear polymers that could be cured with long-wave UV light into free-standing hydrogels, even in the absence of a photoinitiator. Importantly, the gels were reverted back to soluble copolymers upon short-wave UV irradiation. This process could be cycled, allowing for recycling and remolding of the hydrogel into additional shapes. Further, this hydrogel can be imprinted with patterns through a mask-based, post-gelation photoetching method. Traditional limitations of this technique, such as the requirement for uniform etching in one direction, have been overcome by combining these materials with a soft-matter additive manufacturing methodology. In a representative application of this approach, we printed solid structures in which the interior coumarin-cross-linked gel is surrounded by a nondegradable gel. Upon exposure to short-wave UV irradiation, the coumarin-cross-linked gel was reverted to soluble prepolymers that were washed away to yield hollow hydrogel objects.
The gene knockdown activity of small interfering RNA (siRNA) has led to their use as target validation tools and as potential therapeutics for a variety of diseases. The delivery of these ...double-stranded RNA macromolecules has proven to be challenging, however, and in many cases, is a barrier to their deployment. Here we report the development of a new diblock copolymer family that was designed to enhance the systemic and intracellular delivery of siRNA. These diblock copolymers were synthesized using the controlled reversible addition fragmentation chain transfer polymerization (RAFT) method and are composed of a positively-charged block of dimethylaminoethyl methacrylate (DMAEMA) to mediate siRNA condensation, and a second endosomal-releasing block composed of DMAEMA and propylacrylic acid (PAA) in roughly equimolar ratios, together with butyl methacylate (BMA). A related series of diblock compositions were characterized, with the cationic block kept constant, and with the ratio of DMAEMA and PAA to BMA varied. These carriers became sharply hemolytic at endosomal pH regimes, with increasing hemolytic activity seen as the percentage of BMA in the second block was systematically increased. The diblock copolymers condensed siRNA into 80–250 nm particles with slightly positive Zeta potentials. SiRNA-mediated knockdown of a model protein, namely glyceraldehyde 3-phosphate dehydrogenase (GAPDH), in HeLa cells generally followed the hemolytic activity trends, with the most hydrophobic second block (highest BMA content) exhibiting the best knockdown. This pH-responsive carrier designed to mediate endosomal release shows significant promise for the intracellular delivery of siRNA.
The blood system is maintained by a small pool of haematopoietic stem cells (HSCs), which are required and sufficient for replenishing all human blood cell lineages at millions of cells per second ...throughout life. Megakaryocytes in the bone marrow are responsible for the continuous production of platelets in the blood, crucial for preventing bleeding--a common and life-threatening side effect of many cancer therapies--and major efforts are focused at identifying the most suitable cellular and molecular targets to enhance platelet production after bone marrow transplantation or chemotherapy. Although it has become clear that distinct HSC subsets exist that are stably biased towards the generation of lymphoid or myeloid blood cells, we are yet to learn whether other types of lineage-biased HSC exist or understand their inter-relationships and how differently lineage-biased HSCs are generated and maintained. The functional relevance of notable phenotypic and molecular similarities between megakaryocytes and bone marrow cells with an HSC cell-surface phenotype remains unclear. Here we identify and prospectively isolate a molecularly and functionally distinct mouse HSC subset primed for platelet-specific gene expression, with enhanced propensity for short- and long-term reconstitution of platelets. Maintenance of platelet-biased HSCs crucially depends on thrombopoietin, the primary extrinsic regulator of platelet development. Platelet-primed HSCs also frequently have a long-term myeloid lineage bias, can self-renew and give rise to lymphoid-biased HSCs. These findings show that HSC subtypes can be organized into a cellular hierarchy, with platelet-primed HSCs at the apex. They also demonstrate that molecular and functional priming for platelet development initiates already in a distinct HSC population. The identification of a platelet-primed HSC population should enable the rational design of therapies enhancing platelet output.
Purpose
The aim of the study is to evaluate the level of sensible impairment after mastectomy or implant-based breast reconstruction (IBBR). In addition, factors influencing breast sensibility were ...evaluated.
Methods
A cross-sectional study was performed in Maastricht University Medical Center between July 2016 and August 2018. Women with unilateral mastectomy with or without IBBR were included. Objective sensory measurements were performed using Semmes–Weinstein monofilaments. Their healthy breast served as control, using a paired
t
test. Differences between mastectomy with and without IBBR were evaluated using the independent
t
test. Linear regression was performed to evaluate the association between patient characteristics on breast sensibility. The paired
t
test was used to evaluate in which part of the breast the sensibility is best preserved.
Results
Fifty-one patients were eligible for inclusion. Sixteen patients underwent IBBR after mastectomy. Twenty-three patients received radiotherapy and 35 patients received chemotherapy. Monofilament values were significantly higher in the operated group compared to the reference group (
p
< 0.001). Linear regression showed a statistically significant association between IBBR and objectively measured impaired sensation (
p
= 0.008). After mastectomy, the cutaneous protective sensation is only diminished. After IBBR, it is lost in the majority of the breast. The medial part of the breast was significantly more sensitive than the lateral part in all operated breasts (
p
< 0.001).
Conclusion
IBBR has a significantly negative impact on the breast sensibility compared to mastectomy alone. This study shows that the protective sensation of the skin in the breast is lost after IBBR. To our knowledge, this is the first study to evaluate the level of sensible impairment after mastectomy or IBBR. More research is necessary to confirm these results.
In the last few years, additive manufacturing (AM) has been gaining great interest in the fabrication of complex structures for soft-to-hard tissues regeneration, with tailored porosity, and boosted ...structural, mechanical, and biological properties. 3D printing is one of the most known AM techniques in the field of biofabrication of tissues and organs. This technique opened up opportunities over the conventional ones, with the capability of creating replicable, customized, and functional structures that can ultimately promote effectively different tissues regeneration. The uppermost component of 3D printing is the bioink, i.e. a mixture of biomaterials that can also been laden with different cell types, and bioactive molecules. Important factors of the fabrication process include printing fidelity, stability, time, shear-thinning properties, mechanical strength and elasticity, as well as cell encapsulation and cell-compatible conditions. Collagen-based materials have been recognized as a promising choice to accomplish an ideal mimetic bioink for regeneration of several tissues with high cell-activating properties. This review presents the state-of-art of the current achievements on 3D printing using collagen-based materials for hard tissue engineering, particularly on the development of scaffolds for bone and cartilage repair/regeneration. The ultimate aim is to shed light on the requirements to successfully print collagen-based inks and the most relevant properties exhibited by the so fabricated scaffolds. In this regard, the adequate bioprinting parameters are addressed, as well as the main materials properties, namely physicochemical and mechanical properties, cell compatibility and commercial availability, covering hydrogels, microcarriers and decellularized matrix components. Furthermore, the fabrication of these bioinks with and without cells used in inkjet printing, laser-assisted printing, and direct in writing technologies are also overviewed. Finally, some future perspectives of novel bioinks are given.
Highlights•Validation of automated delineation of organs at risk in head and neck cancer. •Automated delineation is more time efficient. •Automated delineation reduces interobserver variability.
A series of excellent poly(vinyl alcohol) (PVA)/polymers blend hydrogel were reviewed using different crosslinking types to obtain proper polymeric dressing materials, which have satisfied ...biocompatibility and sufficient mechanical properties. The importance of biodegradable–biocompatible synthetic polymers such as PVA, natural polymers such as alginate, starch, and chitosan or their derivatives has grown significantly over the last two decades due to their renewable and desirable biological properties. The properties of these polymers for pharmaceutical and biomedical application needs have attracted much attention. Thus, a considered proportion of the population need those polymeric medical applications for drug delivery, wound dressing, artificial cartilage materials, and other medical purposes, where the pressure on alternative polymeric devices in all countries became substantial. The review explores different polymers which have been blended previously in the literature with PVA as wound dressing blended with other polymeric materials, showing the feasibility, property change, and purpose which are behind the blending process with PVA.
Abstract Radioresistance is one of the main determinants of treatment outcome in oral cancer, but the prediction of radioresistance is difficult. The authors aimed to establish radioresistant oral ...squamous cell carcinoma (OSCC) cell lines to identify genes with altered expression in response to radioresistance. To induce radioresistant cell lines, the authors treated OSCC cell lines with an accumulated dosage of 60 Gy over 30 cycles of radiotherapy. They compared the results from cDNA arrays and proteomics between non-radiated and radioresistant cell lines in order to identify changes in gene expression. Western blot analysis was used to validate the results. The cDNA array revealed 265 commonly up-regulated genes and 268 commonly down-regulated genes in radioresistant cell lines, 30 of which were cancer-related genes. Proteomics identified 51 proteins with commonly altered expression in radioresistant cell lines, 18 of which were cancer-related proteins. Both the cDNA array and proteomics indicated that NM23-H1 and PA2G4 were over-expressed. Western blot analysis showed increased expression of NM23-H1, but not PA2G4, in radioresistant cell lines. The authors concluded that NM23-H1 may be a radioresistance-related gene and over-expression of NM23-H1 could serve as a biomarker to predict radioresistance in OSCC.
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