Thermally stimulated luminescence (TSL) is known as a technique used in radiation dosimetry and dating. However, since the luminescence is very sensitive to the defects in a solid, it can also be ...used in material research. In this review, it is shown how TSL can be used as a research tool to investigate luminescent characteristics and underlying luminescent mechanisms. First, some basic characteristics and a theoretical background of the phenomenon are given. Next, methods and difficulties in extracting trapping parameters are addressed. Then, the instrumentation needed to measure the luminescence, both as a function of temperature and wavelength, is described. Finally, a series of very diverse examples is given to illustrate how TSL has been used in the determination of energy levels of defects, in the research of persistent luminescence phosphors, and in phenomena like band gap engineering, tunnelling, photosynthesis, and thermal quenching. It is concluded that in the field of luminescence spectroscopy, thermally stimulated luminescence has proven to be an experimental technique with unique properties to study defects in solids.
The "super-relaxed state" (SRX) of myosin represents a 'reserve' of motors in the heart. Myosin heads in the SRX are bound to the thick filament and have a very low ATPase rate. Changes in the SRX ...are likely to modulate cardiac contractility. We previously demonstrated that the SRX is significantly reduced in mouse cardiomyocytes lacking cardiac myosin binding protein-C (cMyBP-C). Here, we report the effect of mutations in the cMyBP-C gene (MYBPC3) using samples from human patients with hypertrophic cardiomyopathy (HCM). Left ventricular (LV) samples from 11 HCM patients were obtained following myectomy surgery to relieve LV outflow tract obstruction. HCM samples were genotyped as either MYBPC3 mutation positive (MYBPC3mut) or negative (HCMsmn) and were compared to eight non-failing donor hearts. Compared to donors, only MYBPC3mut samples display a significantly diminished SRX, characterised by a decrease in both the number of myosin heads in the SRX and the lifetime of ATP turnover. These changes were not observed in HCMsmn samples. There was a positive correlation (p < 0.01) between the expression of cMyBP-C and the proportion of myosin heads in the SRX state, suggesting cMyBP-C modulates and maintains the SRX. Phosphorylation of the myosin regulatory light chain in MYBPC3mut samples was significantly decreased compared to the other groups, suggesting a potential mechanism to compensate for the diminished SRX. We conclude that by altering both contractility and sarcomeric energy requirements, a reduced SRX may be an important disease mechanism in patients with MYBPC3 mutations.
Persistent luminescence or afterglow is caused by a gradual release of charge carriers from trapping centers. The energy needed to release these charge carriers is determined by the trap depths. ...Knowledge of these trap depths is therefore crucial in the understanding of the persistent luminescence mechanism. Unfortunately, the trap depths in persistent phosphors are often difficult to evaluate in an accurate and reliable way. The existing analysis methods are mostly based on single experiments, or they ignore the possibility of a continuous distribution of trap depths. We present a procedure to accurately probe the activation energies, even in the presence of a continuous distribution of energy levels. By performing a series of thermoluminescence experiments with varying excitation duration and at varying excitation temperature, and employing the initial rise analysis method, the depth and shape of such a distribution can be estimated. As an example, we investigated the trap system in the violet persistent phosphor CaAl sub(2) O sub(4): Eu, Nd, and show that it consists of a Gaussian-shaped distribution of trap depths. The maximal density of traps lies in the region around 0.9 eV, but the distribution extends to 0.7 eV on the shallow side and 1.2 eV on the deep side. The described procedure can be used to obtain a clear view of the trap system in other persistent phosphors as well. This can lead to a better understanding of the nature of these trapping centers, and the role they play in the persistent luminescent mechanism.
Two different charge carrier trapping processes have been investigated in RE2O2S:Ln3+ (RE = La, Gd, Y, and Lu; Ln = Ce, Pr, and Tb) and RE2O2S:M (M = Ti4+ and Eu3+). Cerium, praseodymium and terbium ...act as recombination centers and hole trapping centers while host intrinsic defects provide the electron trap. The captured electrons released from the intrinsic defects recombine at Ce4+, Pr4+, or Tb4+ via the conduction band. On the other hand, Ti4+ and Eu3+ act as recombination centers and electron trapping centers while host intrinsic defects act as hole trapping centers. For these codopants we find evidence that recombination is by means of hole release instead of electron release. The released holes recombine with the trapped electrons on Ti3+ or Eu2+ and yield broad Ti4+ yellow-red charge transfer (CT) emission or characteristic Eu3+ 4f–4f emission. We will conclude that the afterglow in Y2O2S:Ti4+, Eu3+ is due to hole release instead of more common electron release.
Two different trapping and detrapping processes of charge carriers have been investigated in GdAlO3:Ce3+,Ln3+ (Ln = Pr, Er, Nd, Ho, Dy, Tm, Eu, and Yb) and GdAlO3:Ln3+,RE3+ (Ln = Sm, Eu, and Yb; RE = ...Ce, Pr, and Tb). Cerium is the recombination center and lanthanide codopants act as electron-trapping centers in GdAlO3:Ce3+,Ln3+. Different lanthanide codopants generate different trap depths. The captured electrons released from the lanthanide recombine at cerium via the conduction band, eventually producing the broad 5d–4f emission centered at ∼360 nm from Ce3+. On the other hand, Sm3+, Eu3+, and Yb3+ act as recombination centers, while Ce3+, Pr3+, and Tb3+ act as hole-trapping centers in GdAlO3: Ln3+,RE3+. In this situation, we find evidence that recombination is by means of hole release instead of the more commonly reported electron release. The trapped holes are released from Pr4+ or Tb4+ and recombine with the trapped electrons on Sm2+, Eu2+, or Yb2+ and yield characteristic trivalent emission from Sm3+, Eu3+, or Yb3+ at ∼600, ∼617, or ∼980 nm, respectively. Lanthanum was introduced to engineer the valence band energy and change the trap depth in Gd1–x La x AlO3:Eu3+,Pr3+ and Gd1–x La x AlO3:Eu3+,Tb3+. The results show that the valence band moves upward and the trap depth related to Pr3+ or Tb3+ decreases.
ZnGa2O4:Cr3+ presents near-infrared long-lasting phosphorescence (LLP) suitable for in vivo bioimaging. It is a bright LLP material showing a main thermally stimulated luminescence (TSL) peak around ...318 K. The TSL peak can be excited virtually by all visible wavelengths from 1.8 eV (680 nm) via d–d excitation of Cr3+ to above ZnGa2O4 band gap (4.5 eV–275 nm). The mechanism of LLP induced by visible light excitation is entirely localized around CrN2 ion that is a Cr3+ ion with an antisite defect as first cationic neighbor. The charging process involves trapping of an electron–hole pair at antisite defects of opposite charges, one of them being first cationic neighbor to CrN2. We propose that the driving force for charge separation in the excited states of chromium is the local electric field created by the neighboring pair of antisite defects. The cluster of defects formed by CrN2 ion and the complementary antisite defects is therefore able to store visible light. This unique property enables repeated excitation of LLP through living tissues in ZnGa2O4:Cr3+ biomarkers used for in vivo imaging. Upon excitation of ZnGa2O4:Cr3+ above 3.1 eV, LLP efficiency is amplified by band-assistance because of the position of Cr3+4T1 (4F) state inside ZnGa2O4 conduction band. Additional TSL peaks emitted by all types of Cr3+ including defect-free CrR then appear at low temperature, showing that shallower trapping at defects located far away from Cr3+ occurs through band excitation.
Abstract Objectives To determine the phenotype and outcome of patients with QTc of at least 500 ms and to create a pro-QTc risk score for mortality. Patients and Methods An institution-wide ...computer-based QT alert system was developed and implemented at Mayo Clinic in Rochester, Minnesota. This system screens all electrocardiograms (ECGs) performed and alerts the physician if the QTc is 500 ms or greater. Between November 10, 2010, and June 30, 2011, 86,107 ECGs were performed in 52,579 patients. Clinical diagnoses, laboratory abnormalities, and medications known to influence the QT interval were collected from the medical records and summarized in a new pro-QTc score. Survival was compared with that of the 51,434 Mayo Clinic patients with a QTc less than 500 ms during the same period. Results QT alerts were sent for 1145 patients (2%); of these, 470 (41%) had no other identifiable ECG reason for QT prolongation (eg, pacing). All-cause mortality during a mean ± SD of 224±174 days of follow-up was 19% in those with QTc of 500 ms or greater compared with 5% in patients with QTc less than 500 ms (log-rank P <.001). The pro-QTc score was an age-independent predictor of mortality (pro-QTc score: hazard ratio, 1.18; 95% CI, 1.05-1.32; P =.006; age: hazard ratio, 1.02; 95% CI, 1.01-1.03; P =.004.). QT-prolonging medications accounted for 37% of the pro-QTc score. Conclusion This novel institution-wide QT alert system identified patients with a high risk of mortality. The pro-QTc score, reflecting patients’ multimorbidity and multipharmacy, was an independent predictor of mortality. The QT alert system may increase a physician’s awareness of a high-risk patient. Potentially lifesaving interventions can be facilitated by reducing the modifiable factors of the pro-QTc score.
Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells ...for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.
Recent studies have revealed that, in critically ill patients, lung microbiota are altered and correlate with alveolar inflammation. The clinical significance of altered lung bacteria in critical ...illness is unknown.
To determine if clinical outcomes of critically ill patients are predicted by features of the lung microbiome at the time of admission.
We performed a prospective, observational cohort study in an ICU at a university hospital. Lung microbiota were quantified and characterized using droplet digital PCR and bacterial 16S ribosomal RNA gene quantification and sequencing. Primary predictors were the bacterial burden, community diversity, and community composition of lung microbiota. The primary outcome was ventilator-free days, determined at 28 days after admission.
Lungs of 91 critically ill patients were sampled using miniature BAL within 24 hours of ICU admission. Patients with increased lung bacterial burden had fewer ventilator-free days (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88), which remained significant when the analysis was controlled for pneumonia and severity of illness. The community composition of lung bacteria predicted ventilator-free days (
= 0.003), driven by the presence of gut-associated bacteria (e.g., species of the Lachnospiraceae and Enterobacteriaceae families). Detection of gut-associated bacteria was also associated with the presence of acute respiratory distress syndrome.
Key features of the lung microbiome (bacterial burden and enrichment with gut-associated bacteria) predict outcomes in critically ill patients. The lung microbiome is an understudied source of clinical variation in critical illness and represents a novel therapeutic target for the prevention and treatment of acute respiratory failure.
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