Cellular systems evolved from a dedicated mobile communication system to an almost omnipresent system with unlimited coverage anywhere and anytime for any device. The growing ubiquity of the network ...stirred expectations to determine the location of the mobile devices themselves. Since the beginning of standardization, each cellular mobile radio generation has been designed for communication services, and satellite navigation systems, such as Global Positioning System (GPS), have provided precise localization as an add-on service to the mobile terminal. Self-contained localization services relying on the mobile network elements have offered only rough position estimates. Moreover, satellite-based technologies suffer a severe degradation of their localization performance in indoors and urban areas. Therefore, only in subsequent cellular standard releases, more accurate cellular-based location methods have been considered to accommodate more challenging localization services. This survey provides an overview of the evolution of the various localization methods that were standardized from the first to the fourth generation of cellular mobile radio, and looks over what can be expected with the new radio and network aspects for the upcoming generation of fifth generation.
Iron copper zeolite (Fe‐Cu‐ZSM‐5) with aqueous hydrogen peroxide is active for the selective oxidation of methane to methanol. Iron is involved in the activation of the carbon–hydrogen bond, while ...copper allows methanol to form as the major product. The catalyst is stable, re‐usable and activates methane giving >90 % methanol selectivity and 10 % conversion in a closed catalytic cycle (see scheme).
Chemical recycling is one of the most promising technologies that could contribute to circular economy targets by providing solutions to plastic waste; however, it is still at an early stage of ...development. In this work, we describe the first light-driven, acid-catalyzed protocol for chemical recycling of polystyrene waste to valuable chemicals under 1 bar of O2. Requiring no photosensitizers and only mild reaction conditions, the protocol is operationally simple and has also been demonstrated in a flow system. Electron paramagnetic resonance (EPR) investigations and density functional theory (DFT) calculations indicate that singlet oxygen is involved as the reactive oxygen species in this degradation process, which abstracts a hydrogen atom from a tertiary C–H bond, leading to hydroperoxidation and subsequent C–C bond cracking events via a radical process. Notably, our study indicates that an adduct of polystyrene and an acid catalyst might be formed in situ, which could act as a photosensitizer to initiate the formation of singlet oxygen. In addition, the oxidized polystyrene polymer may play a role in the production of singlet oxygen under light.
: We studied the subcellular levels of melatonin in cerebral cortex and liver of rats under several conditions. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and ...mitochondrion vary over a 24‐hr cycle, although these variations do not exhibit circadian rhythms. The cell membrane has the highest concentration of melatonin followed by mitochondria, nucleus, and cytosol. Pinealectomy significantly increased the content of melatonin in all subcellular compartments, whereas luzindole treatment had little effect on melatonin levels. Administration of 10 mg/kg bw melatonin to sham‐pinealectomized, pinealectomized, or continuous light‐exposed rats increased the content of melatonin in all subcellular compartments. Melatonin in doses ranging from 40 to 200 mg/kg bw increased in a dose‐dependent manner the accumulation of melatonin on cell membrane and cytosol, although the accumulations were 10 times greater in the former than in the latter. Melatonin levels in the nucleus and mitochondria reached saturation with a dose of 40 mg/kg bw; higher doses of injected melatonin did not further cause additional accumulation of melatonin in these organelles. The results suggest some control of extrapineal accumulation or extrapineal production of melatonin and support the existence of regulatory mechanisms in cellular organelles, which prevent the intracellular equilibration of the indolamine. Seemingly, different concentrations of melatonin can be maintained in different subcellular compartments. The data also seem to support a requirement of high doses of melatonin to obtain therapeutic effects. Together, these results add information that assists in explaining the physiology and pharmacology of melatonin.
Neuroendocrine tumors comprise a range of neoplasms with varying spectra of origin, biological activity, clinical features, and histological appearance. In this case report, we present a pregnant ...33-year-old female who was brought to the emergency department (ED) complaining of acute right iliac fossa pain accompanied by diarrhea and vomiting. Initial management showed no improvement. Lab results, clinical history, and physical exam were suggestive of appendicitis, so an exploratory minimally invasive laparoscopic exam was performed. The histopathological analysis of the excised appendix confirmed the diagnosis of acute appendicitis and periappendicitis. Incidentally, a 0.6 cm neuroendocrine tumor (carcinoid tumor) was identified on the wall of the appendiceal tip. The tumor extended at multiple points into the subserosal fat, and the serous surface and the resection margin were negative for the tumor. After seven days of the initial procedure, the patient presented with abdominal pain and a fever. An abdominal ultrasound was performed, revealing the presence of free fluid. A second exploratory laparoscopy revealed adhesions between the fallopian tubes and cecum, as well as a collection of purulent fluid. The management consisted of adhesiolysis, cavity lavage, and drainage, along with antibiotic therapy, pain management, and close monitoring of the mother's and fetus's status. The patient had a successful recovery and was discharged home a week after surgery. She gave birth to a full-term, healthy baby and remains free of tumor relapse. This case highlights the importance of obtaining histopathological interpretation of any extracted tissue during surgery. Guidelines regarding the management of carcinoids during pregnancy are not available, and when considering surgical intervention, an open or laparoscopic approach must be carefully evaluated.
The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling intracellular levels of cyclic adenosine 3',5'-monophosphate in the immune and central nervous system. We have ...previously shown that inhibitors of this enzyme are potent neuroprotective and anti-inflammatory agents. In addition, we also demonstrated that PDE7 inhibition induces endogenous neuroregenerative processes toward a dopaminergic phenotype. Here, we show that PDE7 inhibition controls stem cell expansion in the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the subventricular zone (SVZ) in the adult rat brain. Neurospheres cultures obtained from SGZ and SVZ of adult rats treated with PDE7 inhibitors presented an increased proliferation and neuronal differentiation compared to control cultures. PDE7 inhibitors treatment of neurospheres cultures also resulted in an increase of the levels of phosphorylated cAMP response element binding protein, suggesting that their effects were indeed mediated through the activation of the cAMP/PKA signaling pathway. In addition, adult rats orally treated with S14, a specific inhibitor of PDE7, presented elevated numbers of proliferating progenitor cells, and migrating precursors in the SGZ and the SVZ. Moreover, long-term treatment with this PDE7 inhibitor shows a significant increase in newly generated neurons in the olfactory bulb and the hippocampus. Also a better performance in memory tests was observed in S14 treated rats, suggesting a functional relevance for the S14-induced increase in SGZ neurogenesis. Taken together, our results indicate for the first time that inhibition of PDE7 directly regulates proliferation, migration and differentiation of neural stem cells, improving spatial learning and memory tasks. Stem Cells 2017;35:458-472.
Tumour mutational burden (TMB) has been retrospectively correlated with response to immune checkpoint blockade. We prospectively explored the association of high tissue TMB (tTMB-high) with outcomes ...in ten tumour-type-specific cohorts from the phase 2 KEYNOTE-158 study, which assessed the anti-PD-1 monoclonal antibody pembrolizumab in patients with selected, previously treated, advanced solid tumours.
In the multi-cohort, open-label, non-randomised, phase 2 KEYNOTE-158 study, patients were enrolled from 81 academic facilities and community-based institutions across 21 countries in Africa, the Americas, Asia, and Europe. Eligible patients were aged 18 years or older, had a histologically or cytologically confirmed advanced (ie, unresectable or metastatic, or both) incurable solid tumour (eligible tumour types were anal, biliary, cervical, endometrial, mesothelioma, neuroendocrine, salivary, small-cell lung, thyroid, and vulvar), progression on or intolerance to one or more lines of standard therapy, had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) assessed by independent central radiological review, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, adequate organ function, and a tumour sample for biomarker analysis. Participants were given pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles. Tissue TMB (tTMB) was assessed in formalin-fixed paraffin-embedded tumour samples using the FoundationOne CDx assay (Foundation Medicine, Cambridge, MA, USA). The prespecified definition of tTMB-high status was at least 10 mutations per megabase. The primary endpoint was the proportion of patients with an objective response (complete or partial response) as per Response Evaluation Criteria in Solid Tumours (version 1.1) by independent central review. This prespecified analysis assessed the association between antitumour activity and tTMB in treated patients with evaluable tTMB data. Efficacy was assessed in all participants who received at least one dose of pembrolizumab, had evaluable tTMB data, and were enrolled at least 26 weeks before data cutoff (June 27, 2019), and safety was assessed in all participants who received at least one dose of pembrolizumab and had tTMB-high status. KEYNOTE-158 is registered at ClinicalTrials.gov, NCT02628067, and is ongoing.
Between Jan 15, 2016, and June 25, 2019, 1073 patients were enrolled. 1066 participants were treated as of data cutoff (June 27, 2019), of whom 805 (76%) were evaluable for TMB, and 105 (13%) of 805 had tTMB-high status and were assessed for safety. 1050 (98%) of 1066 patients enrolled by at least 26 weeks before data cutoff, of whom 790 (75%) were evaluable for TMB and included in efficacy analyses. 102 (13%) of these 790 patients had tTMB-high status (≥10 mutations per megabase), and 688 (87%) patients had non-tTMB-high status (<10 mutations per megabase). Median study follow-up was 37·1 months (IQR 35·0–38·3). Objective responses were observed in 30 (29%; 95% CI 21–39) of 102 patients in the tTMB-high group and 43 (6%; 5–8) of 688 in the non-tTMB-high group. 11 (10%) of 105 patients had treatment-related serious adverse events. 16 (15%) participants had a grade 3–5 treatment-related adverse event, of which colitis was the only such adverse event that occurred in more than one patient (n=2). One patient had fatal pneumonia that was assessed by the investigator to be treatment related.
tTMB-high status identifies a subgroup of patients who could have a robust tumour response to pembrolizumab monotherapy. tTMB could be a novel and useful predictive biomarker for response to pembrolizumab monotherapy in patients with previously treated recurrent or metastatic advanced solid tumours.
Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
Single‐ and few‐layer transition metal dichalcogenides have recently emerged as a new family of layered crystals with great interest , not only from the fundamental point of view, but also because of ...their potential application in ultrathin devices. Here the electronic properties of semiconducting MX2, where M =Mo or W and X = S or Se, are reviewed. Based on of density functional theory calculations, which include the effect of spin‐orbit interaction, the band structure of single‐layer, bilayer and bulk compounds is discussed. The band structure of these compounds is highly sensitive to elastic deformations, and it is reviewed how strain engineering can be used to manipulate and tune the electronic and optical properties of those materials. Further, the effect of disorder and imperfections in the lattice structure and their effect on the optical and transport properties of MX2 is discussed. The superconducting transition in these compounds, which has been observed experimentally, is analyzed, as well as the different mechanisms proposed so far to explain the pairing. Finally, a discussion on the excitonic effects which are present in these systems is included.
The recent isolation of atomically thin films of semiconducting transition metal dichalcogenides MX2(M = Mo, W and X = S, Se) has opened new opportunities for the application of two‐dimensional crystals in digital electronics, spintronics and optoelectronics devices. This family of semiconductors presents a number of remarkable features such as spin‐valley coupling, superconductivity, excitonic effects etc., which dramatically depend on their thickness (number of layers) and which are briefly reviewed in this article.
We explore the impact of negative policy rates on banks using data on 5200 banks from 27 advanced European and Asian countries, 2010–2017. Our cross-country panel specification allows us to condition ...on global shocks and bank-specific fixed effects. Banks offset interest income losses under negative rates with lower deposit expenses and gains in non-interest income, including fees and capital gains. Small and low deposit-ratio banks drive most results. Banks respond to negative rates by increasing lending activity and raising their share of deposit funding. Overall, our results indicate benign implications of negative rates to date for bank profitability.
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