A novel and simple synthesis route for the production of ZnS:Cu,Al sub-micron phosphor powder is reported. Both the host and activator cations were co-precipitated from an ethanol medium by mixing ...with a diluted ammonium sulfide solution. The co-precipitated ZnS:Cu,Al was in cubic zinc blende structure after an intermediate-temperature furnace annealing. Strong photoluminescent and cathodoluminescent (CL) emission were observed, which was attributed to the 3d
10-3d
94s
1 radiative transition at those copper sites. At an accelerating voltage of 1
kV, the CL intensity of the co-precipitated ZnS:Cu,Al sample was recorded 94% of the commercial reference phosphor with the same composition made by high temperature solid-state-reaction method. The particle size of the co-precipitated phosphor powders was found to be controllable simply through adjusting the reactant concentrations. The particle size of the annealed samples was measured by dynamic light scattering, which showed a mean particle diameter between 200 and 700
nm depending on the co-precipitation conditions.
Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig‐to‐nonhuman primate (NHP) model has not been ...demonstrated. Here, we report that pig islet grafts survived and maintained normoglycemia for >6 months in four of five consecutive immunosuppressed NHPs. Pig islets were isolated from designated pathogen‐free (DPF) miniature pigs and infused intraportally into streptozotocin‐induced diabetic rhesus monkeys under pretreatment with cobra venom factor (CVF), anti‐thymocyte globulin (ATG) induction and maintenance with anti‐CD154 monoclonal antibody and low‐dose sirolimus. Ex vivo expanded autologous regulatory T cells were adoptively transferred in three recipients. Blood glucose levels were promptly normalized in all five monkeys and normoglycemia (90–110 mg/dL) was maintained for >6 months in four cases, the longest currently up to 603 days. Intravenous glucose tolerance tests during the follow‐up period showed excellent glucose disposal capacity and porcine C‐peptide responses. Adoptive transfer of autologous regulatory T cells was likely to be associated with more stable and durable normoglycemia. Importantly, the recipients showed no serious adverse effects. Taken together, our results confirm the clinical feasibility of pig islet transplantation to treat T1D patients without the need for excessive immunosuppressive therapy.
The authors report control of diabetes for longer than six months in four consecutive nonhuman primates by the transplantation of adult pig islets using a modest immunosuppressive regimen with an acceptable adverse effect profile.
Multicellular organs are composed of distinct cell types with unique assemblages of translated mRNAs. Here, ribosome-associated mRNAs were immunopurified from specific cell populations of intact ...seedlings using Arabidopsis thaliana lines expressing a FLAG-epitope tagged ribosomal protein L18 (FLAG-RPL18) via developmentally regulated promoters. The profiling of mRNAs in ribosome complexes, referred to as the translatome, identified differentially expressed mRNAs in 21 cell populations defined by cell-specific expression of FLAG-RPL18. Phloem companion cells of the root and shoot had the most distinctive translatomes. When seedlings were exposed to a brief period of hypoxia, a pronounced reprioritization of mRNA enrichment in the cell-specific translatomes occurred, including a ubiquitous rise in 49 mRNAs encoding transcription factors, signaling proteins, anaerobic metabolism enzymes, and uncharacterized proteins. Translatome profiling also exposed an intricate molecular signature of transcription factor (TF) family member mRNAs that was markedly reconfigured by hypoxia at global and cell-specific levels. In addition to the demonstration of the complexity and plasticity of cell-specific populations of ribosome-associated mRNAs, this study provides an in silico dataset for recognition of differentially expressed genes at the cell-, region-, and organ-specific levels.
The JSNS\(^{2}\) (J-PARC Sterile Neutrino Search at J-PARC Spallation Neutron Source) experiment aims to search for neutrino oscillations over a 24 m short baseline at J-PARC. The JSNS\(^{2}\) inner ...detector is filled with 17 tons of gadolinium(Gd)-loaded liquid scintillator (LS) with an additional 31 tons of unloaded LS in the intermediate \(\gamma\)-catcher and an optically separated outer veto volumes. A total of 120 10-inch photomultiplier tubes observe the scintillating optical photons and each analog waveform is stored with the flash analog-to-digital converters. We present details of the data acquisition, processing, and data quality monitoring system. We also present two different trigger logics which are developed for the beam and self-trigger.
The first measurements of differential branching fractions of inclusive semileptonic B→X_{u}ℓ^{+}ν_{ℓ} decays are performed using the full Belle data set of 711 fb^{-1} of integrated luminosity at ...the ϒ(4S) resonance and for ℓ=e, μ. With the availability of these measurements, new avenues for future shape-function model-independent determinations of the Cabibbo-Kobayashi-Maskawa matrix element |V_{ub}| can be pursued to gain new insights in the existing tension with respect to exclusive determinations. The differential branching fractions are reported as a function of the lepton energy, the four-momentum-transfer squared, light-cone momenta, the hadronic mass, and the hadronic mass squared. They are obtained by subtracting the backgrounds from semileptonic B→X_{c}ℓ^{+}ν_{ℓ} decays and other processes, and corrected for resolution and acceptance effects.
The JSNS\(^{2}\) (J-PARC Sterile Neutrino Search at J-PARC Spallation Neutron Source) experiment aims to search for neutrino oscillations over a 24\,m short baseline at J-PARC. The JSNS\(^{2}\) inner ...detector is filled with 17 tons of gadolinium-loaded liquid scintillator (LS) and both the intermediate \(\gamma\)-catcher and the optically separated outer veto are filled with un-loaded LS. Optical photons from scintillation are observed by 120 Photomultiplier Tubes (PMTs). A total of 130 PMTs for the JSNS2 experiment were both donated by other experiments and purchased from Hamamatsu. Donated PMTs were purchased around 10 years ago, therefore JSNS\(^{2}\) did pre-calibration of the PMTs including the purchased PMTs. 123 PMTs demonstrated acceptable performance for the JSNS\(^{2}\) experiment, and 120 PMTs were installed in the detector.
Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened ...long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in older surgical patients would reduce PND risk or severity.
MARBLE is a randomized, blinded, placebo-controlled phase II sequential dose escalation trial designed to evaluate perioperative administration of an apoE mimetic peptide drug, CN-105, in older adults (age≥60 years). The primary aim is evaluating the safety of CN-105 administration, as measured by adverse event rates in CN-105 versus placebo-treated patients. Secondary aims include assessing perioperative CN-105 administration feasibility and its efficacy for reducing postoperative neuroinflammation and PND severity.
201 patients undergoing non-cardiac, non-neurological surgery will be randomized to control or CN-105 treatment groups and receive placebo or drug before and every six hours after surgery, for up to three days after surgery. Chart reviews, pre- and postoperative cognitive testing, delirium screening, and blood and CSF analyses will be performed to examine effects of CN-105 on perioperative adverse event rates, cognition, and neuroinflammation. Trial results will be disseminated by presentations at conferences and peer-reviewed publications.
MARBLE is a transdisciplinary study designed to measure CN-105 safety and efficacy for preventing PND in older adults and to provide insight into the pathogenesis of these geriatric syndromes.
Targeting repeated injection users with education interventions aimed at highlighting the extent of their current use and increasing awareness of the oral preparation options may reduce unnecessary ...injection use. The aim of this retrospective observational study was to investigate the patient factors related to repeated use of injection formulation analgesics in patients with musculoskeletal disorders who were frequent users of ambulatory healthcare services. Population-based national health insurance claims data for the time period July 2011 - December 2011 were analyzed. Patients aged 18 - 80 years with a musculoskeletal disorder, attended ambulatory healthcare settings > 25 times, and were prescribed pain relievers such as non-steroidal anti-inflammatory drugs and narcotic analgesics in an oral formulation for ≥ 14 days or in an injection formulation ≥ 3 times during the study period were included in the study. There were 742,675 repeated systemic analgesic users, and 64.1% (n = 476,021) of these patients were injection users. The average use of injections per patient during the 6-month period was 8.3. Tramadol was the most frequently prescribed medication for injection, followed by diclofenac, piroxicam, and ketorolac. Statistical analyses showed significant correlations between prevalent injection formulation use and patient factors such as gender, age, area of residence, days of healthcare utilization, number of healthcare centers visited, type of healthcare center visited, total medical expenditure, and total out-of-pocket expenditure. These factors could possibly be used to determine the target population for educational interventions aimed at changing behavior relating to the preference for injectable formulations.
In studies on human platelets, nitroprusside (NP) alone at 1–10 µmol/l increased platelet cyclic AMP (cAMP) by 40–70%, whereas increases in cyclic GMP (cGMP) were much larger in percentage though not ...in concentration terms. Collagen enhanced these increases in cAMP up to fourfold, without affecting cGMP. This effect was partly prevented by indomethacin or aspirin, indicating that platelet cyclo‐oxygenase products acted synergistically with NP to increase cAMP. ADP released from the platelets by collagen tended to restrict this cAMP accumulation. Addition of 2′,5′‐dideoxyadenosine (DDA), an inhibitor of adenylyl cyclase, decreased both the inhibition of collagen‐induced platelet aggregation by NP and the associated accumulation of cAMP without affecting cGMP, indicating that cAMP mediates part of the inhibitory effect of NP. Unlike DDA, 1H‐1,2,4oxadiazolo4,3‐aquinoxalin‐1‐one (ODQ), an inhibitor of guanylyl cyclase, blocked all increases in both cGMP and cAMP caused by NP, as well as the inhibition of platelet aggregation, suggesting that cAMP accumulation was secondary to that of cGMP. Human platelet cGMP‐dependent protein kinase (PKG) coelectrophoresed with the purified bovine type Iβ isoenzyme. An inhibitor of this enzyme (Rp)‐β‐phenyl‐1,N2‐etheno‐8‐bromoguanosine 3′,5′‐cyclic‐monophosphorothioate, diminished the inhibition of collagen‐induced platelet aggregation by NP, but had little additional effect when DDA was present. This showed that both PKG and cAMP participate in the inhibition of collagen‐induced platelet aggregation by NP. Moreover, selective activators of PKG and cAMP‐dependent protein kinases had supra‐additive inhibitory effects, suggesting that an optimal inhibitory effect of NP requires simultaneous activation of both enzymes.
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