There is a great current interest in developing target-specific radiopharmaceuticals for early detection of diseases and radiotherapy of cancers. This critical review will focus on the role of coordination chemistry in the development of target-specific radiopharmaceuticals. It will also discuss the recent development in technetium, copper, gallium, indium, yttrium and lanthanide chemistry, as well as analytical tools for quality control and characterization of radiolabeled small biomolecules (159 references).
Current treatments for chronic xerostomia, or “dry mouth”, do not offer long-term therapeutic benefits for head and neck cancer survivors previously treated with curative radiation. Towards the goal of creating tissue-engineered constructs for the restoration of salivary gland functions, we developed new hyaluronic acid (HA)-based hydrogels using thiolated HA (HA-SH) and acrylated HA (HA-AES) with a significant molecular weight mismatch. Four hydrogel formulations with varying HA concentration, (1–2.4 wt%) and thiol/acrylate ratios (2/1 to 36/1) and elastic moduli (G’: 35 to 1897 Pa, 2 h post-mixing) were investigated. In our system, thiol/acrylate reaction was initiated rapidly upon mixing of HA-SH/HA-AES to establish thioether crosslinks with neighboring ester groups, and spontaneous sulfhydryl oxidation occurred slowly over several days to install a secondary network. The concurrent reactions cooperatively create a cell-permissive network to allow for cell expansion and aggregation. Multicellular spheroids formed readily from a robust ductal epithelial cell line (Madin-Darby Canine Kidney, MDCK cells) in all hydrogel formulations investigated. Primary salivary human stem/progenitor cells (hS/PCs), on the other hand, are sensitive to the synthetic extracellular environment, and organized acini-like structures with an average diameter of 50 µm were obtained only in gels with G’ ≤ 216 Pa and a thiol/acrylate ratio ≥18. The spheroid size and size distribution were dependent on the HA content in the hydrogel. Cells in hS/PC spheroids formed tight junctions (occludin), remained viable and proliferative, secreted structural proteins (collagen IV and laminin) found in the basement membrane and maintained key stem/progenitor markers. We conclude that incorporation of time-dependent, dynamic features into a covalently crosslinked HA network produces an adaptable hydrogel framework that promotes hS/PC assembly and supports early aspects of salivary morphogenesis, key to reconstitution of a fully functional implantable salivary gland.
Epidemiological studies have suggested inconclusive associations between 25-hydroxyvitamin D and total cancer incidence and mortality. The aim of this study was to quantitatively assess these associations by combining results from prospective cohort studies. A systematic literature search was implemented in PubMed and Scopus databases in April 2019. Comparing the highest with the lowest categories, the multivariate-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled using a random-effects model. A trend estimation was performed using a two-stage, dose-response, meta-analysis method. Twenty-three independent prospective studies were included for data synthesis. Eight studies investigated the association between 25-hydroxyvitamin D and the risk of cancer incidence (7511 events and 70,018 participants), and the summary estimate showed that 25-hydroxyvitamin D is marginally associated with cancer risk (Summary RR = 0.86; 95% CI: 0.73, 1.02; I2 = 70.8%; p = 0.001). Sixteen studies investigated the association between 25-hydroxyvitamin D and the risk of cancer mortality (8729 events and 101,794 participants), and a higher 25-hydroxyvitamin D concentration was inversely associated with the risk of cancer mortality (Summary RR = 0.81; 95% CI: 0.71, 0.93; I2 = 48.8%, p = 0.012). Dose-response analysis indicated that the risk of cancer incidence was reduced by 7% (RRs = 0.93; 95% CI: 0.91, 0.96), and the risk of cancer mortality was reduced by 2% (RRs = 0.98; 95% CI: 0.97, 0.99), with each 20 nmol/L increment of 25-hydroxyvitamin D concentration. This meta-analysis provides evidence that a higher 25-hydroxyvitamin D concentration is associated with a lower cancer incidence and cancer mortality.
Objective. Transcranial temporally interfering stimulation (tTIS) is a noninvasive neuromodulation method, which has been reported to be able to affect the activity of small neuronal populations. To pinpoint smaller regions of the brain, a multi-channel tTIS strategy is proposed with larger numbers of electrodes and multiple sets of interfering fields. Approach. First, a computational model is adopted to prove the concept of multi-channel tTIS theoretically. Besides, animal experiments are implemented to activate motor cortex neurons in living mice and different frequencies are attempted. Finally, to better understand the envelope modulation properties of the two applied fields, tissue phantom measurement is conducted. Main results. The focality of six-channel (six electrode pairs) tTIS is increased by 46.7% and 70.2% respectively, compared with that of single-channel tTIS when maximal amplitude value drops by 3 dB and 6 dB in a numerical computation experiment. Furthermore, the focality of multi-channel tTIS is less sensitive to the electrode position. Confirmed with the myoelectricity signal, the movement frequencies of the contralateral forepaw are consistent with the corresponding difference frequencies. What is more, compared to single-channel (one electrode pair) tTIS with multi-channel (three electrode pairs) tTIS, the intensity of multi-channel tTIS stimulation is decreased by 28.5% on average in animal experiments. The c-fos-positive neurons of the target region are significantly higher than that of the non-target region. Results of the modulated envelope distribute around the whole region and its amplitude reaches a maximum at the interfering region. Significance. Both computational modeling and animal experiment validate the feasibility of the proposed multi-channel tTIS strategy and confirm that it can enhance focality and reduce scalp sensation.
This paper presents a new approach to determine the senses of words in queries by using WordNet. In our approach, noun phrases in a query are determined first. For each word in the query, information associated with it, including its synonyms, hyponyms, hypernyms, definitions of its synonyms and hyponyms, and its domains, can be used for word sense disambiguation. By comparing these pieces of information associated with the words which form a phrase, it may be possible to assign senses to these words. If the above disambiguation fails, then other query words, if exist, are used, by going through exactly the same process. If the sense of a query word cannot be determined in this manner, then a guess of the sense of the word is made, if the guess has at least 50% chance of being correct. If no sense of the word has 50% or higher chance of being used, then we apply a Web search to assist in the word sense disambiguation process. Experimental results show that our approach has 100% applicability and 90% accuracy on the most recent robust track of TREC collection of 250 queries. We combine this disambiguation algorithm to our retrieval system to examine the effect of word sense disambiguation in text retrieval. Experimental results show that the disambiguation algorithm together with other components of our retrieval system yield a result which is 13.7% above that produced by the same system but without the disambiguation, and 9.2% above that produced by using Lesk's algorithm. Our retrieval effectiveness is 7% better than the best reported result in the literature.
We study the translational and rotational dynamics of neutrally buoyant finite-size spheroids in hydrodynamic turbulence by means of fully resolved numerical simulations. We examine axisymmetric shapes, from oblate to prolate, and the particle volume dependences. We show that the accelerations and rotations experienced by non-spherical inertial-scale particles result from volume filtered fluid forces and torques, similar to spherical particles. However, the particle orientations carry signatures of preferential alignments with the surrounding flow structures, which are reflected in distinct axial and lateral fluctuations for accelerations and rotation rates. The randomization of orientations does not occur even for particles with volume-equivalent diameter size in the inertial range, here up to $60$ dissipative units ( $\eta$ ) at Taylor-scale Reynolds number ${Re_{\lambda }=120}$ . Additionally, we demonstrate that the role of fluid boundary layers around the particles cannot be neglected in reaching a quantitative understanding of particle statistical dynamics, as they affect the intensities of the angular velocities and the relative importance of tumbling with respect to spinning rotations. This study brings to the fore the importance of inertial-scale flow structures in homogeneous and isotropic turbulence and their impacts on the transport of neutrally buoyant bodies with sizes in the inertial range.
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