First Direct Measurement of

Type-I x-ray bursts can reveal the properties of an accreting neutron star system when compared with astrophysics model calculations. However, model results are sensitive to a handful of uncertain nuclear reaction rates, such as ^{22}Mg(α,p). We report the first direct measurement of ^{22}Mg(α,p), performed with the Active Target Time Projection Chamber. The corresponding astrophysical reaction rate is orders of magnitude larger than determined from a previous indirect measurement in a broad temperature range. Our new measurement suggests a less-compact neutron star in the source GS1826-24.

Erratum: Direct Observation of Proton Emission in

This corrects the article DOI: 10.1103/PhysRevLett.123.082501.

Direct Observation of Proton Emission in

The elusive ß^{-}p^{+} decay was observed in ^{11}Be by directly measuring the emitted protons and their energy distribution for the first time with the prototype Active Target Time Projection Chamber in an experiment performed at ISAC-TRIUMF. The measured ß^{-}p^{+} branching ratio is orders of magnitude larger than any previous theoretical model predicted. This can be explained by the presence of a narrow resonance in ^{11}B above the proton separation energy.

Topographic approach to the long-term effect of solar exposure on facial skin of Korean automobile commuters.

BACKGROUND: Car drivers are generally exposed to direct sunlight during commuting hours, which may lead to irreversible skin damage; however, topographical analysis for different facial areas has not been reported. METHODS: Facial areas were divided topographically into 11 areas based on esthetic units. We performed a preliminary study to identify the delivery pattern of solar energy on the face in the car during commuting time; subsequently, 15 drivers aged above 50 years were enrolled. Statistical evaluation was performed to investigate topographical differences between the left and right sides of the face and between sexes. RESULTS: The left side of the face was different from the right side for L*, a*, and b* on the infraorbital area and L* and b* on the temporal area. Differences were found for L*, a*, or b* between sexes on the central and right face, but not on the left. The left side had more severe hyperpigmentation and wrinkles than the right on average. CONCLUSION: The left facial area, especially the infraorbital and temporal areas, of Korean automobile commuters was vulnerable to sun damage. Therefore, automobile drivers should care about these areas while driving to prevent long-term effect from chronic solar damage.

First Measurement of the g Factor in the Chiral Band: The Case of the

The g factor of the 56 ns half-life isomeric state in ^{128}Cs has been measured using the time-differential perturbed angular distribution method. This state is the bandhead of the positive-parity chiral rotational band, which emerges when an unpaired proton, an unpaired neutron hole, and an even-even core are coupled such that their angular momentum vectors are aplanar (chiral configuration). g-factor measurements can give important information on the relative orientation of the three angular momentum vectors. The measured g factor g=+0.59(1) shows that there is an important contribution of the core rotation in the total angular momentum of the isomeric state. Moreover, a quantitative theoretical analysis supports the conclusion that the three angular momentum vectors lie almost in one plane, which suggests that the chiral configuration in ^{128}Cs demonstrated in previous works by characteristic patterns of electromagnetic transitions appears only above some value of the total nuclear spin.

Post-stroke restless leg syndrome and periodic limb movements in sleep.

OBJECTIVES: Primary restless leg syndrome (RLS) and periodic limb movements in sleep (PLMS) frequently co-exist, obscuring the boundaries between the two conditions. In such instances, a study of secondary cases with focal lesions such as post-stroke RLS and PLMS (psRLS and psPLMS, respectively) can be helpful in identifying characteristics of the individual conditions. MATERIALS AND METHODS: Patients who had suffered strokes and who subsequently developed psRLS or psPLMS were recruited. To determine the overall features of psRLS/PLMS, historical cases were selected from the literature. All cases with either psRLS or psPLMS alone were further analyzed to elucidate the distinctive pathomechanisms of the two conditions. RESULTS: Six patients with either psRLS or psPLMS were recruited from our hospital; two patients had both conditions contemporaneously. The literature contains details on 30 cases of psRLS or psPLMS. The causative lesion was most frequently located in the pons. We found that psRLS was more often bilateral, and usually detected later in time. Lesions in both the pontine base and tegmentum (together) were associated with unilateral psPLMS, whereas lesions in the corona radiata and adjacent basal ganglia were associated with bilateral RLS. Lesions confined to the corona radiata resulted in either unilateral or bilateral RLS. CONCLUSIONS: The observed differences in the clinical and radiological features of psRLS and psPLMS suggest that the pathophysiologies of the two conditions are distinct. Further research is needed to understand the pathophysiologies of primary RLS and PLMS.

Renal denervation for treatment of uncontrolled hypertension in an Asian population: results from the Global SYMPLICITY Registry in South Korea (GSR Korea).

Reports detailing the response of hypertensive patients to renal denervation (RDN) in Asian patients are limited. We evaluated 6- and 12-month outcomes after RDN in an Asian population and compared outcomes to a primarily Caucasian population. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, worldwide registry that evaluates the safety and effectiveness of RDN and includes the Korean registry substudy (GSR Korea) and a Caucasian subset (GSR Caucasian). Given differences in baseline characteristics among GSR Korea (n=93) as compared with GSR Caucasian (n=169) patients, including lower baseline office systolic blood pressure (SBP), lower body mass index and differences in medications, propensity score adjustment was performed when comparing the change in SBP between subsets. The 6- and 12-month change in SBP in GSR Korea was -19.4±17.2 and -27.2±18.1 mm Hg, respectively (P<0.001 for both vs baseline). GSR Caucasian had a SBP change similar to GSR Korea at 6 months (-20.9±21.4 mm Hg, unadjusted P=0.547, adjusted P=0.998), whereas at 12 months the change was significantly less pronounced (-20.1±23.9 mm Hg, unadjusted P=0.004, adjusted P=0.002). There were no protocol-defined procedure-related adverse events and no chronic adverse events associated with the device in an Asian population. RDN provided a significant reduction in 6- and 12-month office SBP among Asian patients, with a favorable safety profile. The 12-month SBP reduction was larger than that observed in Caucasian patients.

Resection of a physeal bar with complete transverse osteotomy at the metaphysis and Ilizarov external fixation.

The traditional techniques involving an oblique tunnel or triangular wedge resection to approach a central or mixed-type physeal bar are hindered by poor visualisation of the bar. This may be overcome by a complete transverse osteotomy at the metaphysis near the growth plate or a direct vertical approach to the bar. Ilizarov external fixation using small wires allows firm fixation of the short physis-bearing fragment, and can also correct an associated angular deformity and permit limb lengthening. We accurately approached and successfully excised ten central- or mixed-type bars; six in the distal femur, two in the proximal tibia and two in the distal tibia, without damaging the uninvolved physis, and corrected the associated angular deformity and leg-length discrepancy. Callus formation was slightly delayed because of periosteal elevation and stretching during resection of the bar. The resultant resection of the bar was satisfactory in seven patients and fair in three as assessed using a by a modified Williamson-Staheli classification.

Failure to restore sagittal tibiotalar alignment in total ankle arthroplasty: Its relationship to the axis of the tibia and the positioning of the talar component.

The purpose of this study was to evaluate the change in sagittal tibiotalar alignment after total ankle arthroplasty (TAA) for osteoarthritis and to investigate factors affecting the restoration of alignment. This retrospective study included 119 patients (120 ankles) who underwent three component TAA using the Hintegra prosthesis. A total of 63 ankles had anterior displacement of the talus before surgery (group A), 49 had alignment in the normal range (group B), and eight had posterior displacement of the talus (group C). Ankles in group A were further sub-divided into those in whom normal alignment was restored following TAA (41 ankles) and those with persistent displacement (22 ankles). Radiographic and clinical results were assessed. Pre-operatively, the alignment in group A was significantly more varus than that in group B, and the posterior slope of the tibial plafond was greater (p < 0.01 in both cases). The posterior slope of the tibial component was strongly associated with restoration of alignment: ankles in which the alignment was restored had significantly less posterior slope (p < 0.001). An anteriorly translated talus was restored to a normal position after TAA in most patients. We suggest that surgeons performing TAA using the Hintegra prosthesis should aim to insert the tibial component at close to 90° relative to the axis of the tibia, hence reducing posterior soft-tissue tension and allowing restoration of normal tibiotalar alignment following surgery.

Prenatal testosterone excess decreases neurokinin 3 receptor immunoreactivity within the arcuate nucleus KNDy cell population.

Prenatal exposure of the female ovine foetus to excess testosterone leads to neuroendocrine disruptions in adulthood, as demonstrated by defects in responsiveness with respect to the ability of gonadal steroids to regulate gonadotrophin-releasing hormone (GnRH) secretion. In the ewe, neurones of the arcuate nucleus (ARC), which co-expresses kisspeptin, neurokinin B (NKB) and dynorphin (termed KNDy cells), play a key role in steroid feedback control of GnRH and show altered peptide expression after prenatal testosterone treatment. KNDy cells also co-localise NKB receptors (NK3R), and it has been proposed that NKB may act as an autoregulatory transmitter in KNDy cells where it participates in the mechanisms underlying steroid negative-feedback. In addition, recent evidence suggests that NKB/NK3R signalling may be involved in the positive-feedback actions of oestradiol leading to the GnRH/luteinising hormone (LH) surge in the ewe. Thus, we hypothesise that decreased expression of NK3R in KNDy cells may be present in the brains of prenatal testosterone-treated animals, potentially contributing to reproductive defects. Using single- and dual-label immunohistochemistry we found NK3R-positive cells in diverse areas of the hypothalamus; however, after prenatal testosterone treatment, decreased numbers of NK3R immunoreactive (-IR) cells were seen only in the ARC. Moreover, dual-label confocal analyses revealed a significant decrease in the percentage of KNDy cells (using kisspeptin as a marker) that co-localised NK3R. To investigate how NKB ultimately affects GnRH secretion in the ewe, we examined GnRH neurones in the preoptic area (POA) and mediobasal hypothalamus (MBH) for the presence of NK3R. Although, consistent with earlier findings, we found no instances of NK3R co-localisation in GnRH neurones in either the POA or MBH; in addition, > 70% GnRH neurones in both areas were contacted by NK3R-IR presynaptic terminals suggesting that, in addition to its role at KNDy cell bodies, NKB may regulate GnRH neurones by presynaptic actions. In summary, the finding of decreased NK3R within KNDy cells in prenatal testosterone-treated sheep complements previous observations of decreased NKB and dynorphin in the same population, and may contribute to deficits in the feedback control of GnRH/LH secretion in this animal model.

Synthetic lethal screening reveals FGFR as one of the combinatorial targets to overcome resistance to Met-targeted therapy.

Met is a receptor tyrosine kinase that promotes cancer progression. In addition, Met has been implicated in resistance of tumors to various targeted therapies such as epidermal growth factor receptor inhibitors in lung cancers, and has been prioritized as a key molecular target for cancer therapy. However, the underlying mechanism of resistance to Met-targeting drugs is poorly understood. Here, we describe screening of 1310 genes to search for key regulators related to drug resistance to an anti-Met therapeutic antibody (SAIT301) by using a small interfering RNA-based synthetic lethal screening method. We found that knockdown of 69 genes in Met-amplified MKN45 cells sensitized the antitumor activity of SAIT301. Pathway analysis of these 69 genes implicated fibroblast growth factor receptor (FGFR) as a key regulator for antiproliferative effects of Met-targeting drugs. Inhibition of FGFR3 increased target cell apoptosis through the suppression of Bcl-xL expression, followed by reduced cancer cell growth in the presence of Met-targeting drugs. Treatment of cells with the FGFR inhibitors substantially restored the efficacy of SAIT301 in SAIT301-resistant cells and enhanced the efficacy in SAIT301-sensitive cells. In addition to FGFR3, integrin ß3 is another potential target for combination treatment with SAIT301. Suppression of integrin ß3 decreased AKT phosphorylation in SAIT301-resistant cells and restored SAIT301 responsiveness in HCC1954 cells, which are resistant to SAIT301. Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin ß3 are resistant to crizotinib treatment, suggesting that FGFR and integrin ß3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs.

[Analysis of bacterial communities of two Lake Baikal endemic sponge species].

Bacterial diversity of two Lake Baikal endemic sponges characterized by different life forms, branching Lubomirskia baicalensis and cortical Baikalospongia sp., was studied using the method of 454 pyrosequencing of the 16S rRNA gene fragments. In the communities associated with L. baicalensis and Baikalospongia sp., 426 and 428 OTUs, respectively, were identified. In microbial associations of these spong- es, 24 bacterial phyla were identified, with predominance of Bacteroidetes, Proteobacteria, and Actinobacteria. Analysis of the taxonomic composition of bacterial communities of the sponges was carried out by search of the dominant phylotypes within the phylum level cluster. Comparison of bacterial associations of the sponges with Lake Baikal bacterioplankton revealed both the shared OTUs and the unique ones characteristic of the studied species.

Assessing sources of inconsistencies in genotypes and their effects on genome-wide association studies with HapMap samples.

The discordance in results of independent genome-wide association studies (GWAS) indicates the potential for Type I and Type II errors. We assessed the repeatibility of current Affymetrix technologies that support GWAS. Reasonable reproducibility was observed for both raw intensity and the genotypes/copy number variants. We also assessed consistencies between different SNP arrays and between genotype calling algorithms. We observed that the inconsistency in genotypes was generally small at the specimen level. To further examine whether the differences from genotyping and genotype calling are possible sources of variation in GWAS results, an association analysis was applied to compare the associated SNPs. We observed that the inconsistency in genotypes not only propagated to the association analysis, but was amplified in the associated SNPs. Our studies show that inconsistencies between SNP arrays and between genotype calling algorithms are potential sources for the lack of reproducibility in GWAS results.

BAX inhibitor-1 enhances cancer metastasis by altering glucose metabolism and activating the sodium-hydrogen exchanger: the alteration of mitochondrial function.

The anti-apoptotic protein, BAX inhibitor-1 (BI-1), has a role in cancer/tumor progression. BI-1-overexpressing HT1080 and B16F10 cells produced higher lung weights and tumor volumes after injection into the tail veins of mice. Transfection of BI-1 siRNA into cells before injection blocked lung metastasis. in vitro, the overexpression of BI-1 increased cell mobility and invasiveness, with highly increased glucose consumption and cytosolic accumulation of lactate and pyruvate, but decreased mitochondrial O(2) consumption and ATP production. Glucose metabolism-associated extracellular pH also decreased as cells excreted more H(+), and sodium hydrogen exchanger (NHE) activity increased, probably as a homeostatic mechanism for intracellular pH. These alterations activated MMP 2/9 and cell mobility and invasiveness, which were reversed by the NHE inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting a role for NHE in cancer metastasis. In both in vitro and in vivo experiments, C-terminal deleted (CDeltaBI-1) cells showed similar results to control cells, suggesting that the C-terminal motif is required for BI-1-associated alterations of glucose metabolism, NHE activation and cancer metastasis. These findings strongly suggest that BI-1 reduces extracellular pH and regulates metastasis by altering glucose metabolism and activating NHE, with the C-terminal tail having a pivotal role in these processes.

Comparison of inflammatory markers and angiographic outcomes after implantation of sirolimus and paclitaxel-eluting stents.

OBJECTIVE: We compared the degree of systemic inflammation and its relation to the angiographic outcomes after drug-eluting stent (DES) implantations. METHODS: We implanted a single DES in 79 stable angina patients (50 men; 60.4 (9.5) years of age; sirolimus-eluting stent (SES), n = 38; paclitaxel-eluting stent (PES), n = 41). The high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) levels were determined before and at 24 hours, 72 hours, and 4 weeks after the percutaneous coronary intervention (PCI). An angiography and intravascular ultrasound (IVUS) were performed. RESULTS: The hs-CRP and IL-6 levels at baseline did not differ between the two groups. The hs-CRP increased significantly from baseline at 24 hours and 72 hours after the PCI in both groups and there was a significant increase in the IL-6 level at 24 hours after the PCI in both groups. However, there was no significant difference between the two groups in any of the hs-CRP or IL-6 measurements. At follow-up, the late lumen loss was significantly higher in the PES group than in the SES group (0.57 (0.56) mm vs 0.28 (0.58) mm, respectively, p = 0.020). The neointimal hyperplasia (NIH) volume in the PES group was significantly higher than that in the SES group (23.1 (22.7) vs 3.8 (7.1) mm(3), respectively, p = 0.000). The percentage luminal volume reduction was higher in the PES group than in the SES group (18.9 vs 3.9%, p = 0.002). The absolute values or change in the inflammatory markers did not correlate with the NIH or stent volume reduction. CONCLUSIONS: Our study showed that the benefits obtained from the SES, which reduce neointimal proliferation, are not probably mediated by the attenuation of the systemic inflammatory markers hs-CRP or IL-6.

Developmental toxic potential of 1,3-dichloro-2-propanol in Sprague-Dawley rats.

This study investigated the potential adverse effects of 1,3-dichloro-2-propanol (1,3-DCP) on pregnant dams and the embryo-fetal development after maternal exposure on gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 10, 30, and 90mg/kg per day (n=10 for each group). All dams underwent Caesarean sections on GD 20, and their fetuses were examined for morphological abnormalities. Maternal toxicity was noted at 90mg/kg/day. Manifestations of toxicity included clinical signs of illness, lower body weight gain, decreased food intake, and increases in the weight of the adrenal glands and the liver. Developmental toxic effects including decreases in fetal body weight and increases in visceral and skeletal variations also occurred at the highest dose. At 30mg/kg, only a minimal maternal toxicity, including a decrease in maternal food intake and an increase in the liver weight, was observed. No adverse maternal or developmental effects were observed at 10mg/kg/day. These results revealed that a 14-day repeated oral dose of 1,3-DCP was minimally embryotoxic but not teratogenic at a maternal toxic dose (90mg/kg/day), and was not embryotoxic at a minimally maternal toxic dose (30mg/kg/day) in rats. Because the developmental toxicity of 1,3-DCP was observed only in the presence of maternal toxicity, it is concluded that the developmental findings observed in the present study are secondary effects to maternal toxicity. Under these experimental conditions, the no-observed-adverse-effect level of 1,3-DCP is considered to be 10mg/kg/day for dams and 30mg/kg/day for embryo-fetal development.

Low coherent hybrid detection technique for differential mode delay in a multimode optical fiber.

We present a low coherent hybrid detection technique for the differential model delay (DMD) measurement of a conventional optical multimode fiber with a modified Mach-Zehnder interferometer. A low coherent hybrid detection technique enhances mode coupling between guided modes and the reference mode to easily resolve the modal distribution. An optical spectrum analyzer and a broadband source were used to obtain time-resolved optical beat signals. The measured interference signal was Fourier transformed to obtain time-delay information. A scanning offset launching method was used to excite every available mode in a multimode fiber (MMF). Measurements of a conventional 8-m-long MMF demonstrated the validity of our proposed method. The experimental results of our proposed method agree well with results obtained using a conventional time domain measurement method. Our proposed method can be used to measure the DMD in a short length of optical MMF with a temporal resolution better than 0.72 ps when using an 8-m-long single-mode fiber as a reference.

Evaluation of embryo-fetal development in rats housed in concrete or hwangto cages during pregnancy.

BACKGROUND: Recently, it was reported that the 4-week exposure of rats to a concrete building environment under cool temperatures (11.7-12.1 degrees C) had adverse effects on the general health parameters. This study examined the potential effects of concrete and hwangto building environments on pregnant dams and embryo-fetal development in Sprague-Dawley rats. METHODS: Groups of 10 mated females were exposed to polycarbonate (control), concrete, or hwangto cages from gestational days (GD) 0 to 20 under cool temperatures (11.9-12.5 degrees C). All the females underwent a caesarean section on GD 20, and their fetuses were examined for any morphological abnormalities. RESULTS: The temperatures in the cages were similar in all groups but the relative humidity in the concrete and hwangto groups were higher than in the control group. The concentration of volatile organic compounds in the hwangto group during the study period was lower than in the control group. In the concrete group, maternal effects manifested as an increase in the incidence of clinical signs, a lower body weight, and a decrease in the thymus and ovary weights. Developmental effects included increased post-implantation loss and decreased litter size. In contrast, in the hwangto group, there were no exposure-related adverse effects on the maternal and developmental parameters. CONCLUSIONS: Overall, the exposure of pregnant rats to a concrete building environment under cool temperatures has adverse effects on the clinical signs, body weight, organ weight, and embryo-fetal development. On the other hand, exposure to a hwangto building environment does not have any adverse effects on pregnant dams or on embryo-fetal development in rats.

alpha-Synuclein gene duplication is present in sporadic Parkinson disease.

OBJECTIVE: alpha-Synuclein gene (SNCA) multiplication was found in familial Parkinson disease (PD). We examined SNCA multiplication in patients with familial and sporadic PD and multiple system atrophy (MSA). METHODS: We screened 1,106 patients with parkinsonism (PD = 906, MSA = 200) for SNCA multiplication by multiplex PCR. Fluorescent in situ hybridization was done to confirm the multiplication. [(123)I]N-omega-Fluoropropyl-2 beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]FP-CIT) SPECT was done in the patients with SNCA multiplication and their family members. RESULTS: Three patients were identified as having SNCA duplication. One patient had a positive family history, and two patients were sporadic. Each patient had asymptomatic carriers in their families. The familial case had early onset parkinsonism with rapidly progressive course, cognitive impairment, and dysautonomia. Sporadic cases were more typical of PD. [(123)I]FP-CIT SPECT was abnormal in the patients and normal in the asymptomatic carriers. CONCLUSION: SNCA multiplication is present in sporadic Parkinson disease (PD) and needs to be screened. Low penetrance, clinical heterogeneity, and normal dopamine transporter imaging in asymptomatic carriers may suggest the presence of other genetic modifiers or environmental triggers that play a role in the pathogenesis of PD due to SNCA duplication.