Search for a Dark-Matter-Induced Cosmic Axion Background with ADMX.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

Search for Invisible Axion Dark Matter in the 3.3-4.2 µeV Mass Range.

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 µeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.

Depression and occupational stress in Japanese school principals and vice-principals.

BACKGROUND: Teaching is one of the most stressful occupations. Over the last decade, about 5000 Japanese public school teachers per year have taken sick leave due to a mental illness. School principals and vice principals also face occupational stress, although few studies have examined occupational stress in these groups. AIMS: To clarify the relationship between occupational stress, role problems and depressive symptoms among school principals and vice principals in Japan. METHODS: We conducted a cross-sectional study in 2013 with data from 262 principals and 268 vice principals in Japan. We used the Japanese version of Zung's Self-Rating Depression Scale (SDS) to evaluate depressive symptoms and the Generic Job Stress Questionnaire to evaluate occupational stress and social support. We categorized SDS scores above 49 as indicating depression. We examined the relationship between depressive symptoms and perceived occupational stress using stepwise forward multivariate logistic regression analyses. RESULTS: Thirty-six (14%) principals and 81 (30%) vice-principals were categorized into the depressive group. Quantitative workload (odds ratio, OR = 6.62 [2.63-16.70]) and role ambiguity (OR = 4.94[1.57-15.53]) were associated with higher depressive scores in principals. Social support from supervisors (OR = 4.14 [1.97-8.68]) and role ambiguity (OR = 9.71 [4.08-23.14]) were associated with higher depressive scores in vice-principals. CONCLUSIONS: Clarifying job roles for principals and vice-principals, reducing quantitative workload for principals and increasing supervisory support for vice-principals may be important for mitigating depression for school principals and vice-principals in Japan.

Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: comprehensive immunohistochemical study using a tissue microarray.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is characterised by the loss of cell-to-cell adhesion and gaining of mesenchymal phenotypes. Epithelial-mesenchymal transition is proposed to occur in various developmental processes and cancer progression. 'Cadherin switch', a process in which cells shift to express different isoforms of the cadherin transmembrane protein and usually refers to a switch from the expression of E-cadherin to N-cadherin, is one aspect of EMT and can have a profound effect on tumour invasion/metastasis. The aim of this study was to investigate the clinicopathological significance of EMT-related proteins and cadherin switch in extrahepatic cholangiocarcinoma (EHCC). METHODS: We investigated the association between altered expression of 12 EMT-related proteins and clinical outcomes in patients with EHCC (n=117) using immunohistochemistry on tissue microarrays. RESULTS: Univariate and multivariate analyses revealed that, in addition to N classification (P=0.0420), the expression of E-cadherin (P=0.0208), N-cadherin (P=0.0038) and S100A4 (P=0.0157) was each an independent and a significant prognostic factor. We also demonstrated that cadherin switch was independently associated with poor prognosis (P=0.0143) in patients with EHCC. CONCLUSIONS: These results may provide novel information for selection of patients with EHCC who require adjuvant therapy and strict surveillance.

Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

Involvement of CD56 (NKH-1/Leu-19 antigen) as an adhesion molecule in natural killer-target cell interaction.

The CD56 differentiation antigen, recognized by anti-Leu-19 and NKH-1 mAbs, is a 200-220-kD glycoprotein that is expressed predominantly on human NK cells and a minor subset of T lymphocytes mediating MHC-unrestricted cytotoxicity. The recent finding that CD56 is an isoform of the neural cell adhesion molecule (N-CAM) prompted us to examine the adhesive function of CD56 in the NK-target cell interaction. Synergistic inhibitory effects of anti-CD56 mAbs with anti-LFA-1 and/or anti-LFA-3 mAbs were demonstrated on NK cell-mediated cytotoxicity and on NK cell binding to target cells only when the target cells also express CD56. These findings indicate that CD56 on NK cells can serve as the third pathway of cell adhesion other than those mediated by the CD2/LFA-3 and LFA-1/ICAM-1 interactions, and is involved in NK cell cytotoxicity when interacting with the cells bearing N-CAM.

Activation of peripheral blood T cells via the p75 interleukin 2 receptor.

By using mAb and flow cytometry, a constitutive expression of the p75 IL-2R was revealed in human peripheral blood CD8+ T cells and TCR delta-1+ T cells as well as in CD16+ NK cells. Anti-p75 IL-2R mAb almost completely inhibited the induction of cytolytic activity in these T cells by brief exposure to IL-2, as estimated by anti-TCR/CD3 mAb-targeted cytotoxicity. While anti-p55 IL-2R mAb alone inhibited the response only modestly, maximal inhibition was achieved by combining both anti-p55 and anti-p75 IL-2R mAbs. These results indicate that the p75 IL-2R constitutively expressed on peripheral blood CD8+ T cells and TCR delta-1+ T cells is predominantly responsible for the direct activation of these cells by IL-2.

Predominant expression of T cell receptor V alpha 7 in tumor-infiltrating lymphocytes of uveal melanoma.

Expression of T cell receptor (TCR) V alpha genes in tumor-infiltrating lymphocytes (TILs) within intraocular melanoma was studied. Primers for 18 different human TCR V alpha families were used to analyze TCR V alpha-C alpha gene rearrangements in TIL in these melanomas obtained at surgery. A limited number of TCR V alpha genes were expressed and rearranged in these tumors, and TILs expressing V alpha 7 were found in seven of eight of these uveal melanomas. TCR gene usage is also restricted in experimental autoimmune disease, in T cells within organs like skin and other epithelial tissues, and in the brain of patients with multiple sclerosis (MS). The restricted usage of TCR genes in TIL may indicate that a specific antigen in these melanomas is targeted.

[Ablation devices in arrhythmia surgery].

Creation of a conduction block is the rationale behind arrhythmia surgery. The "cut-and-sew" technique provides complete conduction block and a line of conduction block prevents propagation of abnormal activation and interrupts reentrant circuits. Alternative ablation devices have been developed to replace the "cut-and-sew" lesions in order to simplify the surgical procedure, decrease the risk of bleeding, and shorten the cardiac arrest and operative times during the surgery. However, ablation devices, such as traditional cryoablation, radiofrequency, micro wave, or ultrasound ablations, do not necessarily guarantee transmural and continuous necrosis. If the amount of surviving atrial myocardium in the incomplete ablation is a critical level, atrial activation can pass through the critical isthmus in the non-transmural or non-continuous lesion with slow conduction. Surgeons should know the precise mechanism of each surgical ablation device and have a good command of them to create complete transmural lesion.

Plasma and peritoneal fluid concentrations of ceftriaxone after intravenous and intraperitoneal administration in horses.

Intraperitoneal (IP) use of antimicrobial agents may lead to therapeutic effects with better clinical results than intravenous (IV) administration. The aim of this study was to compare plasma and peritoneal fluid concentrations of ceftriaxone after IP and IV administration in horses, and to evaluate possible adverse effects. One group of five horses received 25mg/kg ceftriaxone diluted in 1L saline solution by IP catheter once daily for 5 days, while a second group of five horses received 25mg/kg ceftriaxone diluted in 250mL saline solution by IV injection once daily for 5days and 1L saline solution by IP catheter once daily for 5 days. Peritoneal fluid and plasma were collected to determine ceftriaxone concentrations after the first and fifth administration. IP administration of ceftriaxone resulted in concentrations above a minimum inhibitory concentration (MIC) of 1µg/mL for 24h in peritoneal fluid and for 12h in plasma, while IV administration of ceftriaxone resulted in lower peritoneal fluid concentrations, which remained above a MIC of 1µg/mL for 12h in peritoneal fluid and 10h in plasma. No adverse effects were observed. Comparisons of ceftriaxone concentrations, time of occurrence of the maximum (Tmax) and minimum (Tmin) concentrations, and the mean residence time (MRT), between the two groups showed that IP administration provided greater availability of cephalosporin in peritoneal fluid. The IP use of ceftriaxone (25mg/kg diluted in 1L saline solution once daily) may be useful for the prophylaxis and/or treatment of peritonitis in horses.

Prevalence of major depressive disorder in self-referred patients in a late onset hypogonadism clinic.

The goal was to clarify the rate of major depressive disorder (MDD) in self-referred patients who visited our late onset hypogonadism (LOH) clinic and the importance of screening of MDD in LOH clinic. Two hundred consecutive self-referred patients who visited our LOH clinic were evaluated. MDD was diagnosed using, the Mini International Neuropsychiatric Interview (MINI) questionnaire. Scores of the Aging Males Symptom (AMS) scale were compared between the MDD and non-MDD groups with and without low testosterone values. Forty-two percent of all patients were categorized into the MDD group. Only 4% of the patients were considered to be LOH. The MDD group had significantly higher scores on the AMS scale than the LOH and non-MDD with normal testosterone groups. In conclusion, significant numbers of undiagnosed MDD patients visited the LOH clinic. Screening for MDD is an essential step in the LOH outpatient clinic.

[Left ventriculoplasty for ischemic cardiomyopathy with a left ventricular aneurysm].

We report 3 cases of left ventriculoplasty (LVP). They were chosen according to classification of the preoperative left venticle (LV) shape; an apex type and anteroseptal type. We think that an apex type has an indication for a Dor operation and the treatment of an anteroseptal type should be chosen between the following 2 methods. One is an overlapping method. It has the advantage of having to use no intracardiac patch which would remain akinetic area. It is therefore suitable for relatively small LV aneurysms without involvement of the proximal diagonal branches. However, it has the disadvantage of having to cut some distal diagonal branches in order to perform the volume reduction. The other method is a septal anterior ventricular exclusion (SAVE) operation. It is suitable for larger LV aneurysms which involve the proximal diagonal branches due to its advantage of being able to perform the LVP without cutting the diagonal branches. However, it has the disadvantage of leaving an akinetic area that corresponds to the intracardiac patch. We believe that choice of the LVP method according to the preoperative LV shape will bring about a better postoperative LV function and shape.

T-cell receptor V beta gene expression differs in tumor-infiltrating lymphocytes within primary and metastatic melanoma.

Expression of T-cell receptor (TCR) gene rearrangements in tumor-infiltrating lymphocytes (TILs) within primary and metastatic melanoma specimens was studied. In order to analyze TCR gene transcription in TILs within these tissues, we analyzed reverse transcribed complementary DNA from mRNA directly from tissues using the polymerase chain reaction. The polymerase chain reaction-amplified products were confirmed by dot or Southern blot hybridization with C alpha or C beta oligoprobes. First, we investigated the diversity of TCR V alpha and V beta gene usage in human malignant melanoma patients with multiple metastasis. We found in one patient, bearing multiple skin lesions, that the patterns of TCR V alpha and V beta repertoires in different sites of the skin (leg and chest wall) were almost the same. However, in another patient with skin and brain melanomas, different TCR repertoires were presented. Next, we examined the usage of murine TCR V beta genes in TILs within the primary and metastatic sites (liver, lung, and brain) of C57BL/6 mice bearing B16-F10 murine melanoma. The population of TILs in each primary and metastatic site expressed from one to four TCR V beta genes. In each metastatic site, the profile of TCR V beta gene expression was different. A different TCR V beta usage in TILs distributed within metastases of various organs may reflect differences in tumor antigenicity at these sites or may be due to differential homing patterns to these tumors.

Phase I study of irinotecan and cisplatin with granulocyte colony-stimulating factor support for advanced non-small-cell lung cancer.

PURPOSE: Since leukopenia was one of the dose-limiting toxicities of the combination of irinotecan (CPT-11) and cisplatin in a previous trial, we conducted a phase I trial to investigate whether support with recombinant human granulocyte colony-stimulating factor (rhG-CSF) would permit further intensification of the CPT-11 dose in combination with a fixed cisplatin dose. PATIENTS AND METHODS: Twenty previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) were treated with CPT-11 on days 1, 8, and 15 in combination with cisplatin 80 mg/m2 intravenously on day 1. In addition, rhG-CSF (2 micrograms/kg/d) was administered on days 4 to 21, except on the days of CPT-11 treatment. The starting dose of CPT-11 was 70 mg/m2, and the CPT-11 dose was escalated in 10-mg/m2 increments until the maximum-tolerated dose was reached. RESULTS: Diarrhea was the dose-limiting toxicity at 90 mg/m2. Two of six patients experienced either grade 3 or 4 diarrhea or grade 3 leukopenia during the first course of therapy at this dose level. Modest escalation of the CPT-11 dose from 80 to 90 mg/m2 resulted in a marked increase in the plasma concentration of 7-ethyl-10-hydroxycamptothecin (SN-38). Occurrence of diarrhea was well correlated with the peak plasma concentration (Cmax) of SN-38 (P = .035). There were 10 partial responses (50%) among 20 patients. CONCLUSION: The recommended dose for phase II studies is 80 mg/m2 of CPT-11, and 80 mg/m2 of cisplatin plus rhG-CSF. With the use of rhG-CSF, the CPT-11 dose can be increased 33% above that in the original regimen (60 mg/m2 of CPT-11 and 80 mg/m2 of cisplatin).

Phospholipase A2 activity of Fc gamma 2b receptors of thioglycollate-elicited murine peritoneal macrophages.

The detergent lysate of plastic adherent cell population of thioglycollate-elicited peritoneal exudate cells from 100 individual Swiss mice was subjected to affinity chromatography on two different media, Sepharose coupled to heat-aggregated human IgG (IgG-Sepharose) and Sepharose coupled to the phosphatidylcholine analog, rac-1-(9-carboxyl)nonyl-2-hexadecylglycero-3 -phosphorylcholine (PC-Sepharose). Both IgG- and PC-binding proteins were further purified by Sephadex G-100 gel filtration and isoelectric focusing in the presence of 6M urea. Both IgG- and PC-binding proteins thus purified appear to be homogeneous in size as well as charge properties. The IgG-binding proteins of a molecular weight of 25,000 had an isoelectric point of 4.8, whereas the PC-binding proteins of a molecular weight of 42,000 were more basic and had an isoelectric point of 6.0. Both materials retained their IgG-binding capabilities as judged by their inhibitory capacity of murine EA gamma rosetting systems. The subclass specificities of the IgG- and the PC-binding proteins were for IgG2a and IgG2b, respectively. The PC-binding proteins possessed a typical phospholipase A2 activity, which was maximal at pH 9.5, depended on Ca++, and was specific for cleavage of fatty acid from the sn-2 position of phosphatidylcholine. The binding of aggregated IgG2b to the PC-binding proteins caused the ninefold increase in noted enzymatic activity in the presence of, but not in the absence of, Ca++ (5mM). The IgG-binding proteins on the other hand, lacked any detectable phospholipase A2 activity. Thus, the biochemical and biological properties of the PC- and IgG-binding proteins isolated from murine peritoneal macrophages are essentially identical to those homologous proteins previously isolated from P388D1 cells [20].

Efeito da suplementação com óleo de avocado (Persea americana Mill) na temperatura superficial corpórea de equinos antes e após exercício em esteira / [Effect of supplementation with avocado oil (Persea americana Mill) on body surface temperature of horses before and after exercise on treadmill]

Oito equinos foram distribuídos em delineamento randomizado cruzado, sendo um grupo sem suplementação (GC) e outro grupo suplementado com óleo de avocado (GOAv) por um período de sete semanas. Ao fim da sexta semana, os animais foram submetidos a teste padrão de exercício progressivo (TPEP) e, após sete dias, a teste de baixa intensidade e longa duração (BILD). Após o primeiro ciclo, houve período de descanso "washout" de 30 dias para troca de grupos para o segundo ciclo, que seguiu o protocolo do primeiro. A termorregulação foi avaliada com base na temperatura retal e na temperatura superficial corpórea, obtidas por termografia, de 15 regiões de interesse. A temperatura retal e as imagens termográficas foram obtidas antes, um minuto e 15 minutos após o exercício. Não houve diferença entre os grupos GC e GOAv em nenhum momento. Os resultados obtidos neste estudo revelaram que a suplementação de 5% da matéria seca (MS) com óleo de avocado por seis e sete semanas não influenciou na termorregulação com base na temperatura superficial corpórea dos equinos submetidos ao teste padrão de exercício progressivo (TPEP) e ao exercício de baixa intensidade e longa duração (BILD), respectivamente.(AU)

Eight equines were distributed in a randomized crossover design, one control group (CG) without supplementation and another group supplemented (SG) with avocado oil for a period of six weeks. At the end of the sixth week, the animals were submitted to standard exercise test (SET) and after seven days to the low intensity test (LIT). After the first cycle, there was a 30-day washout rest period to exchange groups for the second cycle, which followed the protocol of the first one. Thermoregulation was evaluated based on rectal temperature and body surface temperature of 15 regions of interest obtained by thermography. Rectal temperature and thermographic images were obtained before, one minute and 15 minutes after exercise. There was no difference between the CG and SG at any time. The results obtained in this study revealed that the supplementation of 5% of dry matter with avocado oil for six and seven weeks did not influence the thermoregulation based on the body surface temperature of the horses submitted to SET and LIT, respectively.(AU)

RpoS-dependent regulation of genes expressed at late stationary phase in Escherichia coli.

We have identified 6 Escherichia coli genomic genes, including 4 new genes, responsive to the stationary phase. One of them was regulated positively by RpoS at the stationary phase, and the remaining 5 negatively at a late stationary phase, all of them responding to multiple environmental stresses. Nucleotide sequences as well as such multiple responses revealed that those genes may have more than one overlapping-promoter recognized by different sigma-factors which regulate gene expressions during their cell growth.

High-temperature, nonradioactive primer extension assay for determination of a transcription-initiation site.

We have developed a simple and safe method for the determination of a transcription-initiation site. In this method, reverse transcriptase of the avian myeloblastosis virus or rTth DNA polymerase from Thermus thermopilus was used with a fluorescein isothiocyanate (FITC)-labeled primer. The primer-extension reaction can be performed at a high temperature, which reduces the hindering effect of the secondary structure in RNA, and can omit the annealing step between RNA and the primer. Almost all steps can be done in one tube. This procedure can provide reliable and reproducible data when compared with the conventional procedure at low temperature. Moreover, the sequencing ladder that is required for determining the position of extended products can be obtained with the same FITC-labeled primer.

Interleukin-2 activated T cells (T-LAK) express CD16 antigen and are triggered to target cell lysis by bispecific antibody.

Human PBMCs from healthy donors were cultured with 100 U/ml rIL-2 for up to 5 weeks and tested at short and long activation times for the ability to mediate CD3 and CD16 targeted cytotoxicity using chemically cross-linked bispecific antibodies. At each period, LAK activity was augmented with the use of bispecific antibodies (BA), whereas interestingly enough, at later periods (4-5 weeks) when CD16 positive lymphocytes are not present by flow cytometry, CD16 targeted cytotoxicity was induced. We suspected the possibility of CD16 expression on activated T cells and have purified the T cell subpopulations to see the targeted cytotoxicity. Populations enriched for T cells by Percoll density centrifugation, treatment with anti-CD16 plus complement or sorting for CD5+ cells, were all able to mediate CD16 targeted cytotoxicity following activation with rIL-2. These data suggest that IL-2 activated T cells express CD16 in addition to CD3.