The wavelength down conversion approach to solid‐state lighting (SSL) uses down conversion materials to produce visible light when excited by near‐UV or blue emission from InGaN LEDs. This review ...discusses two classes of down conversion materials: phosphors and semiconductor quantum dots (QDs). Strong absorption of the excitation wavelength; high luminous efficacy of radiation, which enables white light with a high color rendering index and a low correlated color temperature; high quantum efficiency; and thermal and chemical stability are some of the criteria for down converters used in SSL. This review addresses the challenges in the development of down converters that satisfy all these criteria. We will discuss the advantages and disadvantages of several phosphor compositions for blue and near‐UV LEDs. The use of core/shell architectures to improve the photoluminescence and moisture resistance of phosphors is presented. QDs are another class of down conversion materials for near‐UV and blue LEDs. Strategies to improve the photostability and reduce the thermal quenching of QDs include strain‐graded core/shell interfaces and alloying. We discuss Cd‐containing II–VI QDs, and Cd‐free III–V and I–III–VI QDs and their potential for SSL applications. Finally, a description of different methods to integrate the phosphors and QDs with the LED is given.
Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape. Although ...many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells. Using class I prediction algorithms, we identify mutant spectrin-β2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-β2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting.
Recent synthetic advances have made available very monodisperse zincblende CdSe/CdS quantum dots having near-unity photoluminescence quantum yields. Because of the absence of nonradiative decay ...pathways, accurate values of the radiative lifetimes can be obtained from time-resolved PL measurements. Radiative lifetimes can also be obtained from the Einstein relations, using the static absorption spectra and the relative thermal populations in the angular momentum sublevels. One of the inputs into these calculations is the shell thickness, and it is useful to be able to determine shell thickness from spectroscopic measurements. We use an empirically corrected effective mass model to produce a “map” of exciton wavelength as a function of core size and shell thickness. These calculations use an elastic continuum model and the known lattice and elastic constants to include the effect of lattice strain on the band gap energy. The map is in agreement with the known CdSe sizing curve and with the shell thicknesses of zincblende core/shell particles obtained from TEM images. If selenium–sulfur diffusion is included and lattice strain is omitted from the calculation then the resulting map is appropriate for wurtzite CdSe/CdS quantum dots synthesized at high temperatures, and this map is very similar to one previously reported ( J. Am. Chem. Soc. 2009, 131, 14299 ). Radiative lifetimes determined from time-resolved measurements are compared to values obtained from the Einstein relations, and found to be in excellent agreement. For a specific core size (2.64 nm diameter, in the present case), radiative lifetimes are found to decrease with increasing shell thickness. This is similar to the size dependence of one-component CdSe quantum dots and in contrast to the size dependence in type-II quantum dots.
Infantile globoid cell leukodystrophy (GLD, Krabbe disease) is a demyelinating disease caused by the deficiency of the lysosomal enzyme galactosylceramidase (GALC) and the progressive accumulation of ...the toxic metabolite psychosine. We showed previously that central nervous system (CNS)-directed, adeno-associated virus (AAV)2/5-mediated gene therapy synergized with bone marrow transplantation and substrate reduction therapy (SRT) to greatly increase therapeutic efficacy in the murine model of Krabbe disease (Twitcher). However, motor deficits remained largely refractory to treatment. In the current study, we replaced AAV2/5 with an AAV2/9 vector. This single change significantly improved several endpoints primarily associated with motor function. However, nearly all (14/16) of the combination-treated Twitcher mice and all (19/19) of the combination-treated wild-type mice developed hepatocellular carcinoma (HCC). 10 out of 10 tumors analyzed had AAV integrations within the Rian locus. Several animals had additional integrations within or near genes that regulate cell growth or death, are known or potential tumor suppressors, or are associated with poor prognosis in human HCC. Finally, the substrate reduction drug L-cycloserine significantly decreased the level of the pro-apoptotic ceramide 18:0. These data demonstrate the value of AAV-based combination therapy for Krabbe disease. However, they also suggest that other therapies or co-morbidities must be taken into account before AAV-mediated gene therapy is considered for human therapeutic trials.
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Brain-directed, adeno-associated-virus-mediated gene therapy synergizes with bone-marrow transplantation and substrate reduction therapy to dramatically increase treatment efficacy in mice with Krabbe disease. However, nearly 95% of the treated mice developed liver cancer. DNA sequence analysis revealed AAV integrations within or near the Rian locus, tumor suppressors, and proto-oncogenes.
Cutaneous squamous cell carcinoma (cSCC) has among the highest mutation burdens of all cancers, reflecting its pathogenic association with the mutagenic effects of UV light exposure. Although ...mutations in cancer-relevant genes such as TP53 and NOTCH1 are common in cSCC, they are also tolerated in normal skin and suggest that other events are required for transformation; it is not yet clear whether epigenetic regulators cooperate in the pathogenesis of cSCC. KDM6A encodes a histone H3K27me2/me3 demethylase that is frequently mutated in cSCC and other cancers. Previous sequencing studies indicate that roughly 7% of cSCC samples harbor KDM6A mutations, including frequent truncating mutations, suggesting a role for this gene as a tumor suppressor in cSCC. Mice with epidermal deficiency of both Kdm6a and Trp53 exhibited 100% penetrant, spontaneous cSCC development within a year, and exome sequencing of resulting tumors reveals recurrent mutations in Ncstn and Vcan. Four of 16 tumors exhibited deletions in large portions of chromosome 1 involving Ncstn, whereas another 25% of tumors harbored deletions in chromosome 19 involving Pten, implicating the loss of other tumor suppressors as cooperating events for combined KDM6A- and TRP53-dependent tumorigenesis. This study suggests that KDM6A acts as an important tumor suppressor for cSCC pathogenesis.
Patients with AML that develops after cytotoxic therapy (tAML) have overall inferior outcomes relative to de novo AML due to both patient-related factors and the intrinsic biology of the disease. ...Treatment of patients with tAML is challenging. The key initial clinical decision is whether a patient is a candidate for or likely to benefit from intensive induction chemotherapy, a determination which we argue should not be predicated on chronologic age alone. For those determined likely to tolerate intensive induction chemotherapy, CPX-351 is likely superior to conventional induction with cytarabine and daunorubicin. For those deemed inappropriate for intensive induction, hypomethylating agents have the strongest evidence base in elderly adults with AML, and are an attractive option in tAML. This is particularly true in patients with TP53 mutations who are less likely to respond to conventional induction chemotherapy. Exciting options on the therapeutic horizon for tAML include combination therapies incorporating BCL2 inhibitors, Hedgehog pathway inhibitors, and isocitrate dehydrogenase inhibitors.
Globoid cell leukodystrophy (GLD, Krabbe disease) is a lysosomal storage disease (LSD) caused by a deficiency in galactocerebrosidase (GALC) activity. In the absence of GALC activity, the cytotoxic ...lipid, galactosylsphingosine (psychosine), accumulates in the CNS and peripheral nervous system. Oligodendrocytes and Schwann cells are particularly sensitive to psychosine, thus leading to a demyelinating phenotype. Although hematopoietic stem-cell transplantation provides modest benefit in both presymptomatic children and the murine model (Twitcher), there is no cure for GLD. In addition, GLD has been relatively refractory to virtually every experimental therapy attempted. Here, Twitcher mice were simultaneously treated with CNS-directed gene therapy, substrate reduction therapy, and bone marrow transplantation to target the primary pathogenic mechanism (GALC deficiency) and two secondary consequences of GALC deficiency (psychosine accumulation and neuroinflammation). Simultaneously treating multiple pathogenic targets resulted in an unprecedented increase in life span with improved motor function, persistent GALC expression, nearly normal psychosine levels, and decreased neuroinflammation. Treating the primary pathogenic mechanism and secondary targets will likely improve therapeutic efficacy for other LSDs with complex pathological and clinical presentations.
Science Plus ELA Shea, Lauren M.; Shanahan, Therese
Science and children,
07/2020, Letnik:
57, Številka:
9
Journal Article
Recenzirano
Science often takes a back burner to English Language Arts (ELA) and Math. With ELA and Math being tested from early years and school funding relying on each, many teachers are pushed by ...administrators to spend as much time as possible on those two subjects. During the authors' years as classroom teachers and professional development providers, they have attempted to find creative ways to make sure that students experience the joy, wonder, and excitement of science "through" other content areas--for their sense of responsibility to their students and per their administrators' requests. Learners have to talk "about something," listen "about something," read "about something," and write "about something." The authors' thinking and practice centers around making "that something" be science. In this article, the authors share their process of cross-curricular design via a lesson about forces. They have implemented this lesson with their K-2 and 3-5 students and teacher-learners. The content is relatable and comprehensible to teachers across grade levels. This lesson serves as an example of the process the authors follow for all their science and ELA lessons.
Rare earth tantalate materials are of considerable interest in energy and environmentally related applications including photocatalytic H2 generation or contaminant decomposition, ion conductivity ...for batteries and fuel cells, and phosphors for light-emitting diodes (LEDs). These Eu-doped rare earth tantalate pyrochlore nanoparticles, K1−2x LnTa2O7−x :Eu3+ (Ln = Lu, Y, Gd; x = 1/3 for Gd, x = 0 for Lu and Y), have quantum yields up to 78% when excited with blue light (464 nm), which is remarkable for nanoparticle forms that can suffer efficiency loss by surface effects or poor crystallinity, and are furthermore quite suitable for LED applications. The Gd analogue with its framework distortions has particularly high quantum yields. The blue excitation peak matches the emission of the GaN LED. The combination of the high quantum yield under blue excitation, low thermal quenching, and chemical stability renders these new materials promising red phosphors for blue-excitation white LEDs for solid-state lighting. In addition, the pyrochlore lattice is very accommodating to dopants and vacancies and will incorporate virtually any metal and coordination environment ranging from four-coordinate to eight-coordinate. Thus, there are virtually unlimited possibilities for tailoring and optimizing photoluminescent properties, as demonstrated by these scoping studies.
Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require ...immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of POD24 and the assessment of cumulative incidence of histologic transformation (HT) in POD24 versus non-POD24 groups. The study included 524 patients with 143 (27%) in POD24 and 381 (73%) in non-POD24 groups. Patients with POD24 had inferior OS compared to those without POD24, regardless of the type of systemic therapy received (rituximab monotherapy or immunochemotherapy) at diagnosis. After adjusting for factors associated with inferior OS in the univariate Cox model, POD24 remained associated with significantly inferior OS (HR = 2.50, 95% CI = 1.53-4.09, p = 0.0003) in multivariable analysis. The presence of monoclonal protein at diagnosis and those who received first-line rituximab monotherapy had higher odds of POD24 on logistic regression analysis. Patients with POD24 had a significantly higher risk for HT compared to those without POD24. POD24 in MZL might be associated with adverse biology and could be used as an additional information point in clinical trials and investigated as a marker for worse prognosis.
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