We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground ...Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.
Optically variable devices (OVDs) are in tremendous demand as optical indicators against the increasing threat of counterfeiting. Conventional OVDs are exposed to the danger of fraudulent replication ...with advances in printing technology and widespread copying methods of security features. Metasurfaces, two-dimensional arrays of subwavelength structures known as meta-atoms, have been nominated as a candidate for a new generation of OVDs as they exhibit exceptional behaviors that can provide a more robust solution for optical anti-counterfeiting. Unlike conventional OVDs, metasurface-driven OVDs (mOVDs) can contain multiple optical responses in a single device, making them difficult to reverse engineered. Well-known examples of mOVDs include ultrahigh-resolution structural color printing, various types of holography, and polarization encoding. In this review, we discuss the new generation of mOVDs. The fundamentals of plasmonic and dielectric metasurfaces are presented to explain how the optical responses of metasurfaces can be manipulated. Then, examples of monofunctional, tunable, and multifunctional mOVDs are discussed. We follow up with a discussion of the fabrication methods needed to realize these mOVDs, classified into prototyping and manufacturing techniques. Finally, we provide an outlook and classification of mOVDs with respect to their capacity and security level. We believe this newly proposed concept of OVDs may bring about a new era of optical anticounterfeit technology leveraging the novel concepts of nano-optics and nanotechnology.
We report the identification of metastable isomeric states of
228
Ac at 6.28 keV, 6.67 keV and 20.19 keV, with lifetimes of an order of 100 ns. These states are produced by the
β
-decay of
228
Ra, a ...component of the
232
Th decay chain, with
β
Q-values of 39.52 keV, 39.13 keV and 25.61 keV, respectively. Due to the low Q-value of
228
Ra as well as the relative abundance of
232
Th and their progeny in low background experiments, these observations potentially impact the low-energy background modeling of dark matter search experiments.
Context:
Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition that arises from mutations in CYP21A2 gene, which encodes for the steroidogenic enzyme 21-hydroxylase. To prevent ...genital ambiguity in affected female fetuses, prenatal treatment with dexamethasone must begin on or before gestational week 9. Currently used chorionic villus sampling and amniocentesis provide genetic results at approximately 14 weeks of gestation at the earliest. This means that mothers who want to undergo prenatal dexamethasone treatment will be unnecessarily treating seven of eight fetuses (males and three of four unaffected females), emphasizing the desirability of earlier genetic diagnosis in utero.
Objective:
The objective of the study was to develop a noninvasive method for early prenatal diagnosis of fetuses at risk for CAH.
Patients:
Fourteen families, each with a proband affected by phenotypically classical CAH, were recruited.
Design:
Cell-free fetal DNA was obtained from 3.6 mL of maternal plasma. Using hybridization probes designed to capture a 6-Mb region flanking CYP21A2, targeted massively parallel sequencing (MPS) was performed to analyze genomic DNA samples from parents and proband to determine parental haplotypes. Plasma DNA from pregnant mothers also underwent targeted MPS to deduce fetal inheritance of parental haplotypes.
Results:
In all 14 families, the fetal CAH status was correctly deduced by targeted MPS of DNA in maternal plasma, as early as 5 weeks 6 days of gestation.
Conclusions:
MPS on 3.6 mL plasma from pregnant mothers could potentially provide the diagnosis of CAH, noninvasively, before the ninth week of gestation. Only affected female fetuses will thus be treated. Our strategy represents a generic approach for noninvasive prenatal testing for an array of autosomal recessive disorders.
Tamoxifen, an estrogen receptor (ER) antagonist, is the mainstay treatment of breast cancer and the development of resistance represents a major obstacle for a cure. Although long non-coding RNAs ...such as HOTAIR have been implicated in breast tumorigenesis, their roles in chemotherapy resistance remain largely unknown. In this study, we report that HOTAIR (HOX antisense intergenic RNA) is upregulated in tamoxifen-resistant breast cancer tissues compared to their primary counterparts. Mechanistically, HOTAIR is a direct target of ER-mediated transcriptional repression and is thus restored upon the blockade of ER signaling, either by hormone deprivation or by tamoxifen treatment. Interestingly, this elevated HOTAIR increases ER protein level and thus enhances ER occupancy on the chromatin and potentiates its downstream gene regulation. HOTAIR overexpression is sufficient to activate the ER transcriptional program even under hormone-deprived conditions. Functionally, we found that HOTAIR overexpression increases breast cancer cell proliferation, whereas its depletion significantly impairs cell survival and abolishes tamoxifen-resistant cell growth. In conclusion, the long non-coding RNA HOTAIR is directly repressed by ER and its upregulation promotes ligand-independent ER activities and contributes to tamoxifen resistance.
Background: We conducted a prospective randomized controlled trial comparing surgery alone (S) with concurrent chemoradiotherapy followed by surgery (CRT-S) for resectable esophageal squamous cell ...carcinoma (SCC) based on our previous report. Patients and methods: One hundred and one patients with stage II/III esophageal SCC were randomized to receive either S (50 patients) or CRT-S (51 patients). The chemoradiotherapy (CRT) consisted of cisplatin 60 mg/m2 intravenously (i.v.) on day 1, 5-fluorouracil (5-FU) 1000 mg/m2 i.v. on days 2–5, cisplatin 60 mg/m2 i.v. on day 22 combined with radiation therapy (45.6 Gy, 1.2 Gy b.i.d. on days 1–28). Surgery was performed 3–4 weeks after radiotherapy was completed. For patients with disease that was stable or responsive to CRT, three additional cycles of chemotherapy (cisplatin 60 mg/m2 i.v. on day 1, 5-FU 1000 mg/m2 on days 2–5 every 4 weeks) were given after surgical resection. Results: The median age was 62 years. The toxicity of CRT was acceptable and did not affect the post-operative morbidity and the duration of hospital stay. Clinical response was 86% including 21% of complete response (CR) rate. Pathological CR was achieved in 43% 95% confidence interval (CI) 27–59 of the patients who underwent surgery after CRT. At a median follow-up of 25 months, median overall survival (OS) was 27.3 months in S and 28.2 months in CRT-S (P = 0.69). Event-free survival (EFS) at 2 years was 51% in S and 49% in CRT-S (P = 0.93). This trial, which was statistically powered to detect a relatively large difference in 2-year survival rate from 30% to 50% with 80% power, was discontinued at interim analysis because of the unexpectedly high drop-out rate for esophagectomy (31%) and resultant excessive locoregional failure rate in CRT-S arm (22% versus 12%, P = 0.31), though it was not statistically significant. Conclusion: Although preoperative CRT induced high clinical and pathological response, there was no statistically significant benefit in OS and EFS.
p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in ...various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer.
Progressive muscular atrophy (PMA) is clinically characterized by signs of lower motor neuron dysfunction and may evolve into amyotrophic lateral sclerosis (ALS). Whether PMA is actually a form of ...ALS has important consequences clinically and for therapeutic trials. We compared the survival of patients with PMA or ALS to analyze the clinical features that influence survival in PMA.
We reviewed the medical records of patients with PMA (n = 91) or ALS (n = 871) from our ALS Center and verified survival by telephoning the families or using the National Death Index.
In PMA, patients were more likely to be male (p < 0.001), older (p = 0.007), and lived longer (p = 0.01) than in ALS. Cox model analysis suggested that the risk of death increased with age at onset in both patient groups (p < 0.005). Upper motor neuron (UMN) signs developed in 22% of patients with PMA within 61 months after diagnosis. Demographic and other clinical variables did not differ at diagnosis between those who did or did not develop UMN signs. In PMA, the factors present at diagnosis that predicted shorter survival were greater number of body regions affected, lower forced vital capacity, and lower ALS Functional Rating Scale-Revised score. Noninvasive ventilation and gastrostomy were used frequently in PMA.
Although patients with progressive muscular atrophy (PMA) tended to live longer than those with amyotrophic lateral sclerosis (ALS), shorter survival in PMA is associated with the same risk factors that predict poor survival in ALS. Additionally, PMA is relentlessly progressive, and UMN involvement can occur, as also reported in imaging and postmortem studies. For these reasons, PMA should be considered a form of ALS.
Background and purpose
The occurrence of stroke in cancer patients is caused by conventional vascular risk factors and cancer‐specific mechanisms. However, cryptogenic stroke in patients with cancer ...was considered to be more related to cancer‐specific hypercoagulability. In this study, we investigated the potential of the D‐dimer level to serve as a predictor of early neurologic deterioration (END) in cryptogenic stroke patients with active cancer.
Methods
We recruited 109 cryptogenic stroke patients with active cancer within 72 h of symptom onset. We defined END as an increase of ≥1 point in the motor National Institutes of Health Stroke Scale (NIHSS) score or ≥2 points in the total NIHSS score within 72 h of admission. After adjusting for potential confounding factors in the multivariate analysis, we calculated the odds ratios (ORs) and confidence intervals (CIs) of D‐dimer in the prediction of END.
Results
Among 109 patients, END events were identified in 34 (31%) patients within 72 h. END was significantly associated with systemic metastasis, multiple vascular territory lesions on the initial magnetic resonance imaging (MRI), initial NIHSS score and D‐dimer levels. In the multivariate analysis, the D‐dimer level (adjusted OR, 1.11; 95% CI, 1.04–1.17; P < 0.01) and initial NIHSS score (adjusted OR, 1.08; 95% CI, 1.01–1.15; P = 0.03) predicted END after adjusting for potential confounding factors. In the subgroup analysis of 72 follow‐up MRIs, D‐dimer level was also correlated with new territory lesions on the follow‐up MRI in a dose‐dependent manner.
Conclusion
Ischemic stroke patients with active cancer and elevated D‐dimer levels appear to be at increased risk for END recurrent thromboembolic stroke.
An experiment was conducted to investigate the supplementation of direct-fed microbials (DFM) as an alternative to antibiotics on growth performance, immune response, cecal microbial population, and ...ileal morphology of broiler chickens. A total of 800 one-day-old male broiler chicks (Ross × Ross) were randomly allotted to 4 dietary treatments with 4 replicate pens per treatment (50 birds/replicate pen). The 4 dietary treatments fed for 35 d were a corn-soybean meal basal diet (control); control plus 0.1% virginiamycin, as an antibiotic growth promoter (AGP); control plus 0.1% direct-fed microbials that contained Lactobacillus reuteri (DFM 1); and control plus 0.1% direct-fed microbials that contained a mixture of L. reuteri, Bacillus subtilis, and Saccharomyces cerevisiae (DFM 2). Results showed that dietary AGP and DFM supplementation significantly increased (P < 0.05) the BW gain of broilers during 0 to 21 d. The feed intake was reduced, whereas the feed conversion was improved significantly when birds were fed DFM 2 at 0 to 7 d of age. The white blood cell and monocyte levels were significantly higher in the DFM 2 group compared with the control. In addition, feeding DFM significantly (P < 0.05) increased the plasma immunoglobulin levels where a higher level was observed in DFM 2 compared with those of the other treatments. Neither DFM nor AGP treatments affected the cecal Lactobacillus and Salmonella content; however, cecal Escherichia coli content significantly decreased in broiler chickens fed DFM and AGP. The ileal villus height, and width and total thickness of muscularis externa were significantly increased when birds were fed DFM compared with AGP and control. These results indicate that the dietary supplementation of DFM increases the growth performance of birds at an early age, stimulates the immune response, decreases the number of E. coli, and improves the ileal morphology of broiler chickens. Thus, DFM that contained a mixture of several beneficial microorganisms could be a viable alternative to antibiotics in the broiler diets.
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