Inflammatory cytokines induced by infection or vaccination with adjuvant act directly or indirectly on CD8 T cells to modulate their expansion, contraction, and acquisition of memory characteristics. ...Importantly, the initial exposure of naive T cells to inflammatory cytokines may occur before, during, or after their interaction with stimulating dendritic cells (DC) and it is unknown whether and how the timing of cytokine exposure impacts the CD8 T cell response. In this study, we use an immunization strategy with peptide-coated mature DC that, in the absence of inflammatory cytokines, results in a transient effector phase followed by the accelerated acquisition of memory characteristics by the responding CD8 T cells. Induction of inflammatory cytokines by TLR agonists, at the time of DC immunization or 2-4 days after DC immunization, prevented the early acquisition of memory characteristics by the responding CD8 T cells. Interestingly, although induction of inflammatory cytokines at the time of DC immunization increased the effector response, induction of inflammatory cytokines after DC immunization did not promote further expansion of the responding CD8 T cells but still prevented their early acquisition of memory characteristics. In contrast, induction of inflammatory cytokines 2 days before DC immunization did not prevent the CD8 T cells from early acquisition of memory characteristics. Furthermore, TLR ligand-induced inflammatory cytokines had the most significant impact on the phenotype and function of proliferating CD8 T cells. These data suggest that a default pathway of memory CD8 T cell differentiation is deflected toward sustained effector commitment by encounter with inflammatory cytokines during Ag-driven proliferation.
One-fourths of the patients have medication-resistant seizures and require seizure detection and treatment continuously to cope with sudden seizures. Seizures can be detected by monitoring the brain ...and muscle activities, heart rate, oxygen level, artificial sounds, or visual signatures through EEG, EMG, ECG, motion, or audio/video recording on the human head and body. In this article, we first discuss recent advances in seizure sensing, signal processing, time- or frequency-domain analysis, and classification algorithms to detect and classify seizure stages. Then, we show a strong potential of applying recent advancements in non-invasive brain stimulation technology to treat seizures. In particular, we explain the fundamentals of brain stimulation approaches, including (1) transcranial magnetic stimulation (TMS), (2) transcranial direct current stimulation (tDCS), (3) transcranial focused ultrasound stimulation (tFUS), and how to use them to treat seizures. Through this review, we intend to provide a broad view of both recent seizure diagnoses and treatments. Such knowledge would help fresh and experienced researchers to capture the advancements in sensing, detection, classification, and treatment seizures. Last but not least, we provide potential research directions that would attract seizure researchers/engineers in the field.
Radiotherapy is highly effective for treating squamous cell carcinoma of the head and neck but is often associated with significant toxicities and severe morbidity. Unplanned emergency department ...(ED) visits and hospitalizations are common during treatment and come with a substantial financial and health burden as well as the potential for impaired long-term outcomes due to treatment disruption.
The objective of this study was to identify patient, disease, and treatment characteristics that were associated with ED encounters and admissions.
A cohort of 462 patients with cancer of the head and neck treated with radiotherapy at UT Southwestern between 2010 and 2015 was retrospectively analyzed. The risks of ED visits, admissions, multiple admissions, and extended admissions were determined. Risk factors for an unplanned hospital encounter were analyzed using univariate and multivariate logistic regression.
Overall, 36% of patients had an unplanned hospital encounter during the treatment window. Patients with advanced disease, those with high comorbidity score, and those treated with concurrent chemotherapy were more likely to have unplanned admissions/ED visits. Social factors such as marital status, smoking status, and registration in the public hospital system were also strongly associated with admissions and multiple encounters.
The high rate of admissions and ED visits emphasizes the importance of anticipating and managing toxicities during treatment. Social factors have a strong association with unplanned encounters and may present opportunities for targeted interventions to reduce admissions for patients at highest risk.
•There were no differences in survival between surgery and CRT.•Primary CRT increased gastrostomy dependence but not osteonecrosis or stricture.•Chemotherapy improved survival in the definitive but ...not postoperative RT setting.•Only cisplatin- and taxane-based regimens improved survival.
To determine the comparative effectiveness of primary radiotherapy (RT) and primary surgery (PS) for locally advanced oropharyngeal squamous cell carcinoma (OPSCC).
Eligible individuals were patients in the SEER-Medicare registry diagnosed with locally advanced OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT ± chemotherapy, or PS ± adjuvant RT or chemoradiotherapy (CRT). Overall survival (OS) was analyzed using Cox multivariable analysis (MVA). Risks of gastrostomy dependence (GD), esophageal stricture (ES), and osteoradionecrosis (ORN) were analyzed using logistic regression.
A total of 2754 patients (69% RT, 31% PS) were included in this cohort, with a median age of 72 years. Patients treated with RT, CRT and PS experienced 3-year OS outcomes of 36.1%, 52.8%, and 54.9%, respectively (p < 0.001). Increasing age, unmarried status, increasing comorbidity, lower income, base of tongue (BOT) site, higher stage, no prior PET, and RT alone (but not CRT) were associated with inferior OS. Independent predictors of GD at 6 months included black race, BOT site, advanced stage, and CRT. The risks of ORN and stricture were not associated with treatment modality. Concurrent chemotherapy improved OS with definitive RT but had no impact in adjuvant RT. Only cisplatin- and taxane-containing regimens improved OS, but all concurrent agents, including cetuximab, significantly worsened GD.
Local therapy decisions for locally advanced OPSCC must be individualized, with CRT increasing acute and chronic GD. The differential survival impact of concurrent chemotherapy in the definitive and adjuvant setting may be a consideration in decision-making.
Density functional theory (DFT) calculations were carried out to explore the geometric, spectroscopic, and electronic properties of three magic silver clusters Ag
(n = 8, 18, and 20) in detail. The ...computed results show that the global minima of these clusters are compact, near-spherical structures, while other low-lying isomers exhibit oblate or prolate shapes. Vertical ionization energies for the low-lying isomers were also computed and assigned with respect to available experimental values. Although several isomers were predicted to have similar energies, their electronic and vibrational signatures were quite distinctive, meaning that they could be used as fingerprint signals to distinguish between isomers. In addition, the electronic structures of these systems were explored using the phenomenological shell model. Calculations for the coinage metal clusters M
(M = Cu, Ag, Au) indicated that the structures and properties of the Ag cluster are similar to those of the Cu cluster in that both Cu
and Ag
prefer a compact structure whereas Au
prefers to adopt a tetrahedral form. Graphical abstract Shell Orbitals of Ag
Cluster.
Density functional theory (DFT) calculations are employed to examine the adsorption behaviors of cysteine on the gold surface using Au
6
and Au
8
species as model reactants. Computed results show ...that cysteine molecules prefer to bind with gold clusters via the S-atom of the thiol group in vacuum and thiolate group in water. The gas-phase adsorption energies are around 20.2 kcal/mol for Au
6
and 24.4 kcal/mol for Au
8
. In water environment, such values are slightly reduced for Au
6
(19.6 kcal/mol), but increased a little more for Au
8
(25.6 kcal/mol). As a result, if a visible light with a frequency of ν ≈ 6 × 10
14
Hz (500 nm) is applied, the time for the recovery of Au
6
and Au
8
from the most stable complexes will be about 0.38 and 9.3 × 10
3
s, respectively, at 298 K in water. The Au
6
is in addition found to benefit from a larger change of energy gap that could be converted to an electrical signal for detection of cysteine.
Although environmental training program has become a vital solution to minimize environmental challenges, the existing literature has paid little attention to (1) the connection between environmental ...training and employee in-role green performance (EIGP), (2) the mediating role of employee environmental commitment in this environmental training-EIGP connection, and (3) the cultural perspective (Western and Local) influences on interrelationships between environmental training, EIGP, and employee environmental commitment. Drawing on the social exchange theory and cultural perspective, a quantitative study based on survey data collected from 301 respondents at hotels in Vietnam was employed to fill these research gaps. Findings reveal that environmental training program is as an important tool to drive EIGP directly, and this environmental training-EIGP relationship is significantly mediated by employee environmental commitment. Interestingly, the study indicates support for our prediction that the mediating role of employee environmental commitment on the environmental training-EIGP link is stronger at hotels managed by Western hospitality companies. However, unexpectedly, cultural influence does not moderate the effect of environmental training on EIGP. Other than theoretical contributions, our study carries important practical implications that can help organizations reduce their carbon footprint. Limitations and further research directions have also been discussed.
•Environmental training influences employee in-role green performance (EIGP).•Employee environmental commitment mediates the environmental training-EIGP link.•The mediating effect is stronger at hotels managed by Western corporations.•Cultural influence (Western & Local) does not moderate the environmental training-EIGP link.•Our research is the first paper to examine these relationships in the hospitality sector.
Endogenous tags have become invaluable tools to visualize and study native proteins in live cells. However, generating human cell lines carrying endogenous tags is difficult due to the low efficiency ...of homology-directed repair. Recently, an engineered split mNeonGreen protein was used to generate a large-scale endogenous tag library in HEK293 cells. Using split mNeonGreen for large-scale endogenous tagging in human iPSCs would open the door to studying protein function in healthy cells and across differentiated cell types. We engineered an iPS cell line to express the large fragment of the split mNeonGreen protein (mNG2
) and showed that it enables fast and efficient endogenous tagging of proteins with the short fragment (mNG2
). We also demonstrate that neural network-based image restoration enables live imaging studies of highly dynamic cellular processes such as cytokinesis in iPSCs. This work represents the first step towards a genome-wide endogenous tag library in human stem cells.
Since the concept of Cognitive Radio (CR) was first introduced, it has been considered as a key technology of future wireless devices to better utilize radio spectrum. A number of CR-MAC protocols ...have been studied for Cognitive Radio Networks (CRNs), but most state-of-the-art frequencyhopping based protocols focus mainly on channel mobility and spectrum resource allocation. They lack integration of other essential features such as time synchronization and cooperative spectrum sensing, which are practically crucial, into a full-blown CR-MAC protocol. In this paper, we propose MSHCS-MAC: a mac protocol for Multi-hop CRNs based on Slow Hopping and Cooperative Sensing approach which is the cutting edge frequency hopping scheme. The contributions of MSHCS-MAC are threefold: (1) Support of multi-hop communication without dedicated control channel and multiple transceivers, (2) Integration of essential CR-MAC features such as bootstrapping, multi-channel operation, cooperative spectrum sensing and time synchronization, (3) Practical implementation and evaluation on commercial devices. The evaluation results show that MSHCS-MAC provides reasonable performance in the experimental testbed with supporting multihop communication and essential CR-MAC features.