InAs quantum dashes (Qdash) engineered to emit near 2 μm are envisioned to be promising quantum emitters for next-generation technologies in sensing and communications. In this study, we explore the ...effect of punctuated growth (PG) on the structure and optical properties of InP-based InAs Qdashes emitting near the 2-μm wavelength. Morphological analysis revealed that PG led to an improvement in in-plane size uniformity and increases in average height and height distribution. A 2 × boost in photoluminescence intensity was observed, which we attribute to improved lateral dimensions and structural stabilization. PG encouraged formation of taller Qdashes while photoluminescence measurements revealed a blue-shift in the peak wavelength. We proposed that the blue-shift originates from the thinner quantum well cap and decreased distance between the Qdash and InAlGaAs barrier. This study on the punctuated growth of large InAs Qdashes is a step toward realizing bright, tunable, and broadband sources for 2-μm communications, spectroscopy, and sensing.
The autocrine and paracrine activation of the renin–angiotensin system (RAS) within cells of the kidney plays a role in the overall pathophysiology of the renal disease due to diabetes. In this ...study, we focus on components of the RAS in the podocyte as these cells are important in the pathogenesis of glomerulosclerosis and proteinuria. Immortalized mouse podocytes were exposed to media containing normal glucose (NG) or high glucose (HG) for in vitro studies. In vivo studies utilized kidney tissue obtained from rats treated for 3 months with streptozotocin to induce diabetes. Angiotensinogen (AGT) and the angiotensin II (AII) type 1 receptor mRNA and protein were significantly increased in the podocytes cultured under the high glucose conditions. Both angiotensins I and II levels were significantly higher in cell lysates and the conditioned media of cells grown in high glucose. There were no differences in renin activity, angiotensin-converting enzyme level, or AII type 2 receptor level. Glomerular AGT and AII type 1 receptor assessed by means of immunohistochemistry were increased in diabetic rats compared with the control rats. Other measured components of the RAS within the glomeruli were not different. We suggest that increased AGT, an attendant increase in AII and increased AII type 1 receptor in podocytes experiencing diabetic conditions play an important role in the pathogenesis of diabetic nephropathy.
Summary
Background Allergic contact dermatitis (ACD) is a delayed type of T cell‐mediated cutaneous inflammatory response, in which multiple cell types are involved. Dasatinib and LCB 03‐0110 are ...small molecule multityrosine kinase inhibitors, and they share remarkably similar target kinases such as the c‐Src family, Btk and Syk, which play key roles in the cell signalling of T cells and other inflammatory cells.
Objectives To test the anti‐ACD activity of dasatinib and LCB 03‐0110 and compare it with that of tacrolimus (FK506) and triamcinolone acetonide (a glucocorticoid), which are widely used for topical treatment of ACD, and to examine the two compounds for their capacity to induce skin atrophy, a side‐effect.
Methods ACD was induced on the ears of mice by repeated topical application of oxazolone. Each test compound was then topically applied on the ear. Ear swelling, epidermal thickness and levels of inflammatory cytokines were measured. The skin atrophy induced by the compounds was tested during prolonged application on the dorsal skin of hairless mice, followed by haematoxylin and eosin staining.
Results Dasatinib and LCB 03‐0110 suppressed the symptoms of ACD such as ear swelling, increase in epidermal thickness and synthesis of inflammatory cytokines (i.e. interleukin‐1β, tumour necrosis factor‐α and interferon‐γ) in a dose‐dependent manner. The two compounds showed near‐equal potency to tacrolimus; however, their potency was lower than that of triamcinolone acetonide. Prolonged treatment with the two compounds did not induce any skin atrophy, whereas use of steroidal agents induced severe atrophy.
Conclusions Dasatinib and LCB 03‐0110 could be used as effective agents for the treatment of ACD without the adverse side‐effect of skin atrophy.
This case report follows a 10-year-old castrated male Miniature Schnauzer dog presented with a history of incomplete surgical resection of an oral malignant melanoma (amelanotic type) on the right ...mandible. Melanoma vaccine therapy was administered due to incomplete surgical resection, however, new masses were detected on the contralateral mandible and suspected pulmonary metastasis occurred at 2 weeks and 7 months, respectively, following the first melanoma vaccination. At the time of detecting the pulmonary metastasis, targeted chemotherapy was initiated with the owner's consent using imatinib (10 mg/kg/day, p.o.), a tyrosine kinase inhibitor (TKI). The patient did not show any significant adverse events related to both anticancer treatments. Three months following the first dose of imatinib, the absence of the suspected pulmonary metastatic nodules on radiography indicated complete remission. In conclusion, this report describes the achievement of clinical remission of suspected pulmonary metastatic oral malignant melanoma and an extension of survival time in a dog given a combination treatment of immunotherapy and tyrosine kinase inhibitor.
Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to ...be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance.
We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab.
Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting.
Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer.
Rectal carcinoid tumors are often found incidentally during screening colonoscopy and can be resected using various endoscopic techniques. This study aimed to compare the safety and efficacy of ...endoscopic submucosal dissection (ESD) with endoscopic mucosal resection (EMR) for rectal carcinoid tumors.
Between January 2003 and June 2009, 74 patients (74 lesions) underwent either EMR (n = 28) or ESD (n = 46) for rectal carcinoid tumors. The rate of endoscopic complete resection, pathological complete resection, procedure complications, and tumor recurrence were analyzed retrospectively.
The endoscopic complete resection rate was significantly higher in the ESD group (46 lesions, 100 %) compared with the EMR group (25 lesions, 89.3 %) ( P = 0.049). The pathological complete resection rate was higher in the ESD group (38 lesions, 82.6 %) compared with the EMR group (18 lesions, 64.3 %); however, this difference was borderline significant ( P = 0.067). Overall complication rate was not significantly different between the EMR group (3.6 %) and the ESD group (6.3 %). There was one case of remnant lesion in the EMR group, which was managed by ESD, and no recurrence has been detected in either the EMR or ESD groups.
This study suggests that ESD might be a feasible treatment technique for small rectal carcinoid tumors. It showed superior efficacy and comparable safety to EMR.
Ausforming of medium carbon steel Seo, S.-W.; Jung, G.-S.; Lee, J. S. ...
Materials science and technology,
20/3/1/, Volume:
31, Issue:
4
Journal Article
Peer reviewed
The prospect of enhancing the hardness of low alloy steel for the manufacture of fasteners is examined using ausforming, in which the austenite is deformed rapidly at a low temperature to increase ...its dislocation density before quenching in order to obtain the harder martensite. Surprisingly, small deformations accomplish large gains in hardness and the dislocation density of martensite, with diminishing returns at larger deformations. The main contribution to the hardness has been identified as the extra dislocations inherited by the martensite from the deformed austenite, rather than the refinement of microstructure by the ausforming process. Clear evidence is reported for the mechanical stabilisation of the austenite due to ausforming. Tempering heat treatments tend to diminish the advantages of ausforming.
The epigenetic information present in mammalian gametes and whether it is transmitted to the progeny are relatively unknown. We find that many promoters in mouse sperm are occupied by RNA polymerase ...II (Pol II) and Mediator. The same promoters are accessible in GV and MII oocytes and preimplantation embryos. Sperm distal ATAC-seq sites containing motifs for various transcription factors are conserved in monkeys and humans. ChIP-seq analyses confirm that Foxa1, ERα, and AR occupy distal enhancers in sperm. Accessible sperm enhancers containing H3.3 and H2A.Z are also accessible in oocytes and preimplantation embryos. Furthermore, their interactions with promoters in the gametes persist during early development. Sperm- or oocyte-specific interactions mediated by CTCF and cohesin are only present in the paternal or maternal chromosomes, respectively, in the zygote and 2-cell stages. These interactions converge in both chromosomes by the 8-cell stage. Thus, mammalian gametes contain complex patterns of 3D interactions that can be transmitted to the zygote after fertilization.
Display omitted
•ATAC-seq accessibility at sperm and oocyte promoters is maintained in the embryo•Sperm enhancers containing transcription factors are conserved in mammals•Accessible sperm enhancers are also open in oocytes and preimplantation embryos•Interactions mediated by FoxA1 and CTCF and cohesin persist from gametes to embryos
Jung et al. show that sperm and oocyte promoters and enhancers contain ATAC-seq accessible sites suggesting the presence of Pol II, Foxa1, ERα, and AR. Accessibility in gametes persists in early embryos. Interactions mediated by CTCF in gametes are inherited from each parent and become the same in 8-cell embryos.
Background
Conventional anorectal manometric parameters based on linear waves cannot properly predict balloon expulsion (BE) time. We aimed to determine the correlation between integrated pressurized ...volume (IPV) parameters during simulated evacuation (SE) and BE time in healthy individuals and constipated patients and to assess the correlation between each parameter and symptoms.
Methods
A total of 230 male participants (including 26 healthy volunteers and 204 chronically constipated patients) underwent high‐resolution anorectal manometry (HRAM) and BE tests. The IPV was calculated by multiplying the amplitude, distance, and time from the HRAM profile. Receiver operating characteristic curve (ROC) analysis and partial least square regression (PLSR) were performed.
Key Results
ROC analysis indicated that the IPV ratio between the upper 1 cm and lower 4 cm of the anal canal was more effective for predicting BE time (area under the curve AUC: 0.74, 95% confidence interval CI: 0.67‐0.80, P < .01) than the conventional anorectal parameters, including defecation index and rectoanal gradient (AUC: 0.60, 95% CI: 0.52‐0.67, P = .01). PLSR analysis of a linear combination of IPV parameters yielded an AUC of 0.79. Moreover, the IPV ratio showed a greater clinical correlation with patient symptoms than conventional parameters.
Conclusions and Inferences
The IPV parameters and the combination of IPV parameters via PLSR were more significantly correlated with BE time than the conventional parameters. Thus, this study presents a useful diagnostic tool for the evaluation of pathophysiologic abnormalities in dyssynergic defecation using IPV and BE time.
The novel integrated pressurized volume (IPV) parameters and the combination of IPV parameters via partial least square regression were more significantly correlated with balloon expulsion (BE) time than the conventional parameters. IPV parameters can be useful diagnostic tools for the evaluation of pathophysiologic abnormalities in dyssynergic defecation using high‐resolution anorectal manometry and BE tests.
We report the intracranial efficacy of selpercatinib, a highly potent and selective RET inhibitor, approved in the United States for
fusion-positive non-small cell lung cancers (NSCLC).
In the global ...phase 1/2 LIBRETTO-001 trial (NCT03157128) in advanced
-altered solid tumors, selpercatinib was dosed orally (160 mg twice every day) in 28-day cycles. Patients with baseline intracranial metastases had MRI/CT scans every 8 weeks for 1 year (12 weeks thereafter). In this pre-planned analysis of patients with
fusion-positive NSCLC with baseline intracranial metastases, the primary endpoint was independently assessed intracranial objective response rate (ORR) per RECIST 1.1. Secondary endpoints included intracranial disease control rate, intracranial duration of response, and intracranial progression-free survival (PFS) independently reviewed.
Eighty patients with NSCLC had brain metastases at baseline. Patients were heavily pretreated (median = 2 systemic therapies, range = 0-10); 56% of patients received ≥1 course of intracranial radiation (14% whole brain radiotherapy, 45% stereotactic radiosurgery). Among 22 patients with measurable intracranial disease at baseline, intracranial ORR was 82% 95% confidence interval (CI), 60-95, including 23% with complete responses. Among all intracranial responders (measurable and nonmeasurable,
= 38), median duration of intracranial response was not reached (95% CI, 9.3-NE) at a median duration of follow-up of 9.5 months (IQR = 5.7, 12.0). At 12 months, 55% of intracranial responses were ongoing. In all 80 patients, median intracranial PFS was 13.7 months (95% CI, 10.9-NE) at a median duration of follow-up of 11.0 months (IQR = 7.4, 16.5). No new safety signals were revealed in patients with brain metastases compared with the full NSCLC trial population.
Selpercatinib has robust and durable intracranial efficacy in patients with
fusion-positive NSCLC.
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