Experimental Line Parameters of the b^(1)Σ^(+)_g ← X^(3)Σ^(-)_g Band of Oxygen Isotopologues at 760 nm Using Frequency-Stabilized Cavity Ring-Down Spectroscopy

Positions, intensities, self-broadened widths, and collisional narrowing coefficients of the oxygen isotopologues ^(16)O^(18)O, ^(16)O^(17)O, ^(17)O^(18)O, and ^(18)O^(18)O have been measured for the b^(1)Σg + ← X^(3)Σg − (0,0) band using frequency-stabilized cavity ring-down spectroscopy. Line positions of 156 P-branch transitions were referenced against the hyperfine components of the ^(39)K D_1 (4s ^(2)S_(1/2) → 4p ^(2)P_(1/2)) and D_2 (4s ^(2)S_(1/2) → 4p ^(2)P_(3/2)) transitions, yielding precisions of ~0.00005 cm^(−1) and absolute accuracies of 0.00030 cm^(−1) or better. New excited b^(1)Σg + state molecular constants are reported for all four isotopologues. The measured line intensities of the ^(16)O^(18)O isotopologue are within 2% of the values currently assumed in molecular databases. However, the line intensities of the ^(16)O^(17)O isotopologue show a systematic, J-dependent offset between our results and the databases. Self-broadening half-widths for the various isotopologues are internally consistent to within 2%. This is the first comprehensive study of the line intensities and shapes for the ^(17)O^(18)O or ^(18)O_2 isotopologues of the b^(1)Σg + ← X^(3)Σg − (0,0) band of O_2. The ^(16)O_2, ^(16)O^(18)O, and ^(16)O^(17)O line parameters for the oxygen A-band have been extensively revised in the HITRAN 2008 database using results from the present study

NAFTA Students'Whistle-blowing Perceptions: A Case of Sexual Harassment (La percepción advertidora de Ios alumnos en TLC: un caso de acoso sexual

Abstract, Whistle-blowing mechanisms in the U.S. have gained more prominence as an element of legal compliance and antifraud programs. Sexual harassment is asignificant business risk in terms of financial costs and the loss of reputation. lt is important for corporations to develop sexual harassment policies and to provide mechanisms for employees toreport sexual harassment behaviors to upper level management. This paper reports on business students' responses to a possible Sexual Harassment scenario from Arthur Andersen's Business Ethics Program and the actions that the characters in the video should take in terms of whistle-blowing. l fall 2004,78 students from two U.S. universities and one Mexican and one Canadian university participated in the project as part of the NAFIA Challenges of Accounting and Busrness Sysfems Granf funded by the United States Department of Education Fund for the lmprovement of PostSecondary Education (FIPSE), Human Resources Development Canada (HRDC), and Mexico's Secretaría de Educación Pública (SEP). Students from the three NAFTA countries were shown the vignette and asked to respond to a pre-questionnaire concerning the characters' behaviors and possible actions. The students were then asked to discuss the situation and write a report from the ooints of view of the three characters in the vignette and also to find a copy of an organizations' sexual harassment policy from the Internet. At the end of the project the students responded to a postquestionnaire. The students were asked to consider whether the characters should report the possible harasser iotheir supervisor, end thus engage in whistle-blowing behavior. Hypoiheses are formulated for the three NAFTA countries based on Hofstede's cultural dimensions and comparisons are made based on overall responses to the pre-and posfquestionnaire. There were significant differences, but in some cases not in the direction expected. Gender differences are also explored, but there were few significant differences. The authors are working under the NAFTA Challenges of Accounting and Busrness Sysfems Grant from the United States Depaftment of Education Fund for the lmprovement of PosfSecondary Education (FIPSE), Human Resources Development Canada (HRDC), and Mexico's Secretaría de Educación Pública (SEP). Resúmen. Los llamados "mecanismos de silbato de alerta" en los Estados Unidos han ganado más prominencia como elemento de la conformidad legal y de los programas antifraude. El hostigamiento sexual es un riesgo significativo del negocio en términos de costos financieros y la pérdida de reputación. Esimportante que las corporaciones desarrollen políticas para prevenir y sancionar el hostigamiento sexual en los centros de trabajo y proporcionen los mecanismos para los empleados sobre los comportamientos de hostigamiento sexual y ofrezcan información al respecto a la gerencia. Esta investigaciónnternacional por medio de sus resultadosfrece las respuestas de los estudiantes de las escuelas de negocios de México, Canadá y Estados Unidos sobre un panorama de posible hostigamiento sexual, y forma parte del programa del ética de negocio de promover en las Universidades la firma internacional de consultoría Arturo Andersen y de las acciones que se observaron elos caracteresn un vídeo realizado para este propósito, y que acciones deben tomar en términos de la utilización del "silbato de altera". En otoño del 2004, 78 estudiantes de dos universidades EEUU, una universidad mexicana y una canadiense participaron en el proyecto como parte de los Retos de NAFTA de los sistemas Grant de contabilidad y negocios financiados por el departamento de Educación delos Estados Unidos Secretaría Poste-Secundario de Educación Pública (SEPT) de la educación (FIPSE), del desarrollo de recursos humanos en Canadá (HRDC), y de México. Mediante uso de video y escenificación que fue enviado y posteriormente fueron recibidas las respuestas de los estudiantes delos tres países de NAFTA además de responder a un cuestionario referente a los comportamientos y a las acciones posibles de los caracteres del video. Posteriormente y mediante el uso de Internet, los estudiantes pudieron discutir lasituación y escribir un informe de los puntos de la vista de los tres caracteres en el video y elaborar una propuesta de una política sobre hostigamiento sexual de las organizaciones. Al final del proyecto los estudiantes respondieron a un cuestionario. Pidieron considerar si los caracteres deben divulgar el hostigamiento posible a su supervisor, y como los estudiantes se comprometían a utilizar el mecanismo de silbato de alerta. Las hipótesis se formulan para los tres países del NAFTA basados en las dimensiones culturales de Hofstede y se hacen las comparaciones baado en respuestas totales a los cuestionarios. Se encontraron diferencias significativas, pero en algunos casos no en la dirección esperada. Las diferencias del género también se exploran, pero había pocas diferencias significativas. Los autor autores están trabajando bajo desafíos de NAFTA de los sistemas Grant de la contabilidad y del negocio del departamento de Estados Unidos del fondo de la educación para la mejora de Secretaría Poste-Secundario de Educación Pública (SEPT) de lp educación (FIPSE), del desarrollo de recursos humanos Canadá (HRDC), y de México

More than money:developing an integrative multi-factorial measure of entrepreneurial success

This article conceptualises and operationalizes ‘subjective entrepreneurial success’ in a manner which reflects the criteria employed by entrepreneurs, rather than those imposed by researchers. Using two studies, a first qualitative enquiry investigated success definitions using interviews with 185 German entrepreneurs; five factors emerged from their reports: firm performance, workplace relationships, personal fulfilment, community impact, and personal financial rewards. The second study developed a questionnaire, the Subjective Entrepreneurial Success–Importance Scale (SES-IS), to measure these five factors using a sample of 184 entrepreneurs. We provide evidence for the validity of the SES-IS, including establishing systematic relationships of SES-IS with objective indicators of firm success, annual income and entrepreneur satisfaction with life and financial situation. We also provide evidence for the cross-cultural invariance of SES-IS using a sample of Polish entrepreneurs. The quintessence of our studies being that subjective entrepreneurial success is a multi-factorial construct, i.e. entrepreneurs value various indicators of success with money as only one possible option

The major brain cholesterol metabolite 24(s)-hydroxycholesterol is a potent allosteric modulator of N-methyl-d-aspartate receptors

N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. NMDARs govern experience-dependent synaptic plasticity and have been implicated in the pathophysiology of various neuropsychiatric disorders including the cognitive deficits of schizophrenia and certain forms of autism. Certain neurosteroids modulate NMDARs experimentally but their low potency, poor selectivity, and very low brain concentrations make them poor candidates as endogenous ligands or therapeutic agents. Here we show that the major brain-derived cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC) is a very potent, direct, and selective positive allosteric modulator of NMDARs with a mechanism that does not overlap that of other allosteric modulators. At submicromolar concentrations 24(S)-HC potentiates NMDAR-mediated EPSCs in rat hippocampal neurons but fails to affect AMPAR or GABA(A) receptors (GABA(A)Rs)-mediated responses. Cholesterol itself and other naturally occurring oxysterols present in brain do not modulate NMDARs at concentrations ≤10 μm. In hippocampal slices, 24(S)-HC enhances the ability of subthreshold stimuli to induce long-term potentiation (LTP). 24(S)-HC also reverses hippocampal LTP deficits induced by the NMDAR channel blocker ketamine. Finally, we show that synthetic drug-like derivatives of 24(S)-HC, which potently enhance NMDAR-mediated EPSCs and LTP, restore behavioral and cognitive deficits in rodents treated with NMDAR channel blockers. Thus, 24(S)-HC may function as an endogenous modulator of NMDARs acting at a novel oxysterol modulatory site that also represents a target for therapeutic drug development

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Spatial quantitation of drugs in tissues using liquid extraction surface analysis mass spectrometry imaging

Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported

Targeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy

Despite progress in the treatment of acute lymphoblastic leukemia (ALL), T-cell ALL (T-ALL) has limited treatment options, particularly in the setting of relapsed/refractory disease. Using an unbiased genome-scale CRISPR-Cas9 screen we sought to identify pathway dependencies for T-ALL which could be harnessed for therapy development. Disruption of the one-carbon folate, purine and pyrimidine pathways scored as the top metabolic pathways required for T-ALL proliferation. We used a recently developed inhibitor of SHMT1 and SHMT2, RZ-2994, to characterize the effect of inhibiting these enzymes of the one-carbon folate pathway in T-ALL and found that T-ALL cell lines were differentially sensitive to RZ-2994, with the drug inducing a S/G2 cell cycle arrest. The effects of SHMT1/2 inhibition were rescued by formate supplementation. Loss of both SHMT1 and SHMT2 was necessary for impaired growth and cell cycle arrest, with suppression of both SHMT1 and SHMT2 inhibiting leukemia progression in vivo. RZ-2994 also decreased leukemia burden in vivo and remained effective in the setting of methotrexate resistance in vitro. This study highlights the significance of the one-carbon folate pathway in T-ALL and supports further development of SHMT inhibitors for treatment of T-ALL and other cancers

Measurement of B(Ds+ -->ell+ nu) and the Decay Constant fDs From 600/pb of e+e- Annihilation Data Near 4170 MeV

We examine e+e- --> Ds^-D_s^{*+} and Ds^{*-}Ds^{+} interactions at 4170 MeV using the CLEO-c detector in order to measure the decay constant fDs with good precision. Previously our measurements were substantially higher than the most precise lattice based QCD calculation of (241 +/- 3) MeV. Here we use the D_s^+ --> ell^+ nu channel, where the ell^+ designates either a mu^+ or a tau^+, when the tau^+ --> pi^+ anti-nu. Analyzing both modes independently, we determine B(D_s^+ --> mu^+ nu)= 0.565 +/- 0.045 +/- 0.017)%, and B(D_s^+ --> mu^+ nu)= (6.42 +/- 0.81 +/- 0.18)%. We also analyze them simultaneously to find an effective value of B^{eff}(D_s^+ --> mu^+ nu)= (0.591 +/- 0.037 +/- 0.018)% and fDs=(263.3 +/- 8.2 +/- 3.9) MeV. Combining with the CLEO-c value determined independently using D_s^+ --> tau^+ nu, tau^+ --> e^+ nu anti-nu decays, we extract fDs=(259.5 +/- 6.6 +/- 3.1) MeV. Combining with our previous determination of B(D^+ --> mu^+ nu), we extract the ratio fDs/fD+=1.26 +/- 0.06 +/- 0.02. No evidence is found for a CP asymmetry between Gamma(D_s^+ --> mu^+\nu) and \Gamma(D_s^- --> mu^- nu); specifically the fractional difference in rates is measured to be (4.8 +/- 6.1)%. Finally, we find B(D_s^+ --> e^+ nu) < 1.2x10^{-4} at 90% confidence level.Comment: 26 pages, 16 figure

Search for D0 to p e- and D0 to pbar e+

Using data recorded by CLEO-c detector at CESR, we search for simultaneous baryon and lepton number violating decays of the D^0 meson, specifically, D^0 --> p-bar e^+, D^0-bar --> p-bar e^+, D^0 --> p e^- and D^0-bar --> p e^-. We set the following branching fraction upper limits: D^0 --> p-bar e^+ (D^0-bar --> p-bar e^+) p e^- (D^0-bar --> p e^-) < 1.2 * 10^{-5}, both at 90% confidence level.Comment: 10 pages, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PRD. Comments: changed abstract, added reference for section 1, vertical axis in Fig.5 changed (starts from 1.5 rather than 2.0), fixed typo

Dalitz Plot Analysis of Ds to K+K-pi+

We perform a Dalitz plot analysis of the decay Ds to K+K-pi+ with the CLEO-c data set of 586/pb of e+e- collisions accumulated at sqrt(s) = 4.17 GeV. This corresponds to about 0.57 million D_s+D_s(*)- pairs from which we select 14400 candidates with a background of roughly 15%. In contrast to previous measurements we find good agreement with our data only by including an additional f_0(1370)pi+ contribution. We measure the magnitude, phase, and fit fraction of K*(892) K+, phi(1020)pi+, K0*(1430)K+, f_0(980)pi+, f_0(1710)pi+, and f_0(1370)pi+ contributions and limit the possible contributions of other KK and Kpi resonances that could appear in this decay.Comment: 21 Pages,available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR