A cryogenic beam of refractory, chemically reactive molecules with expansion cooling

Cryogenically cooled buffer gas beam sources of the molecule thorium monoxide (ThO) are optimized and characterized. Both helium and neon buffer gas sources are shown to produce ThO beams with high flux, low divergence, low forward velocity, and cold internal temperature for a variety of stagnation densities and nozzle diameters. The beam operates with a buffer gas stagnation density of ~10^15-10^16 cm^-3 (Reynolds number ~1-100), resulting in expansion cooling of the internal temperature of the ThO to as low as 2 K. For the neon (helium) based source, this represents cooling by a factor of about 10 (2) from the initial nozzle temperature of about 20 K (4 K). These sources deliver ~10^11 ThO molecules in a single quantum state within a 1-3 ms long pulse at 10 Hz repetition rate. Under conditions optimized for a future precision spectroscopy application [A C Vutha et al 2010 J. Phys. B: At. Mol. Opt. Phys. 43 074007], the neon-based beam has the following characteristics: forward velocity of 170 m/s, internal temperature of 3.4 K, and brightness of 3x10^11 ground state molecules per steradian per pulse. Compared to typical supersonic sources, the relatively low stagnation density of this source, and the fact that the cooling mechanism relies only on collisions with an inert buffer gas, make it widely applicable to many atomic and molecular species, including those which are chemically reactive, such as ThO

Advanced cold molecule electron EDM

Measurement of a non-zero electric dipole moment (EDM) of the electron within a few orders of magnitude of the current best limit of |d_e| < 1.05 × 10^(−27) e⋅cm [1] would be an indication of physics beyond the Standard Model. The ACME Collaboration is searching for an electron EDM by performing a precision measurement of electron spin precession in the metastable H^3Δ_1 state of thorium monoxide (ThO) using a slow, cryogenic beam. We discuss the current status of the experiment. Based on a data set acquired from 14 hours of running time over a period of 2 days, we have achieved a 1-sigma statistical uncertainty of δd_e = 1 × 10^(−28) e⋅cm/√T, where T is the running time in days

Advanced cold molecule electron EDM

Measurement of a non-zero electric dipole moment (EDM) of the electron within a few orders of magnitude of the current best limit of |de| < 1.05×10−27 e · cm would be an indication of physics beyond the Standard Model. The ACME Collaboration is searching for an electron EDM by performing a precision measurement of electron spin precession in the metastable H 3Delta_1 state of thorium monoxide (ThO) using a slow, cryogenic beam. We discuss the current status of the experiment. Based on a data set acquired from 14 hours of running time over a period of 2 days, we have achieved a 1-sigma statistical uncertainty of d(de) = 1×10^−28 e · cm/√T ,where T is the running time in days.Physic

Stimulated Raman Adiabatic Passage Preparation of a Coherent Superposition of ThO H3Δ1 States for an Improved Electron Electric-Dipole-Moment Measurement

Experimental searches for the electron electric-dipole moment (EDM) probe new physics beyond the standard model. The current best EDM limit was set by the ACME Collaboration [Science 343, 269 (2014), 10.1126/science.1248213], constraining time-reversal symmetry (T ) violating physics at the TeV energy scale. ACME used optical pumping to prepare a coherent superposition of ThO H3Δ1 states that have aligned electron spins. Spin precession due to the molecule's internal electric field was measured to extract the EDM. We report here on an improved method for preparing this spin-aligned state of the electron by using stimulated Raman adiabatic passage (STIRAP). We demonstrate a transfer efficiency of 75 %±5 % , representing a significant gain in signal for a next-generation EDM experiment. We discuss the particularities of implementing STIRAP in systems such as ours, where molecular ensembles with large phase-space distributions are transferred via weak molecular transitions with limited laser power and limited optical access.Physic

Cytokinin functions as an asymmetric and anti-gravitropic signal in lateral roots

Directional organ growth allows the plant root system to strategically cover its surroundings. Intercellular auxin transport is aligned with the gravity vector in the primary root tips, facilitating downward organ bending at the lower rootflank. Here we show that cytokinin signaling functions as a lateral root specific anti-gravitropic component, promoting the radial distribution of the root system. We performed a genome-wide association study and reveal that signal peptide processing of Cytokinin Oxidase 2 (CKX2) affects its enzymatic activity and, thereby, determines the degradation of cytokinins in naturalArabidopsis thaliana accessions. Cytokinin signaling interferes with growth at the upper lateral rootflank and thereby prevents downward bending. Our interdisciplinary approach proposes that two phytohormonal cues at opposite organflanks counterbalance each other’s negative impact on growth, suppressing organ growth towards gravity and allow for radial expansion of the root system

STING-dependent type I IFN production inhibits cell-mediated immunity to Listeria monocytogenes.

Infection with Listeria monocytogenes strains that enter the host cell cytosol leads to a robust cytotoxic T cell response resulting in long-lived cell-mediated immunity (CMI). Upon entry into the cytosol, L. monocytogenes secretes cyclic diadenosine monophosphate (c-di-AMP) which activates the innate immune sensor STING leading to the expression of IFN-β and co-regulated genes. In this study, we examined the role of STING in the development of protective CMI to L. monocytogenes. Mice deficient for STING or its downstream effector IRF3 restricted a secondary lethal challenge with L. monocytogenes and exhibited enhanced immunity that was MyD88-independent. Conversely, enhancing STING activation during immunization by co-administration of c-di-AMP or by infection with a L. monocytogenes mutant that secretes elevated levels of c-di-AMP resulted in decreased protective immunity that was largely dependent on the type I interferon receptor. These data suggest that L. monocytogenes activation of STING downregulates CMI by induction of type I interferon

Student Interviews: 1967

A series of fifteen- to thirty-minute interviews was conducted with eight members of the first graduating class of the University of California, Santa Cruz, and with four sophomores who were members of the first four-year class to graduate from the Santa Cruz campus. The students spoke quite candidly about the strengths and weaknesses of the University, administration, faculty, classes, and general campus life, and commented on the changes that they thought should or would occur as the campus grows larger

Student Interviews: 1967

A series of fifteen- to thirty-minute interviews was conducted with eight members of the first graduating class of the University of California, Santa Cruz, and with four sophomores who were members of the first four-year class to graduate from the Santa Cruz campus. The students spoke quite candidly about the strengths and weaknesses of the University, administration, faculty, classes, and general campus life, and commented on the changes that they thought should or would occur as the campus grows larger

Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation.

PurposeGranulocyte-macrophage colony-stimulating factor (GM-CSF) -secreting tumor vaccines have demonstrated bioactivity but may be limited by disease burdens and immune tolerance. We tested the hypothesis that cyclophosphamide (CY) and doxorubicin (DOX) can enhance vaccine-induced immunity in patients with breast cancer.Patients and methodsWe conducted a 3 x 3 factorial (response surface) dose-ranging study of CY, DOX, and an HER2-positive, allogeneic, GM-CSF-secreting tumor vaccine in 28 patients with metastatic breast cancer. Patients received three monthly immunizations, with a boost 6 to 8 months from study entry. Primary objectives included safety and determination of the chemotherapy doses that maximize HER2-specific immunity.ResultsTwenty-eight patients received at least one immunization, and 16 patients received four immunizations. No dose-limiting toxicities were observed. HER2-specific delayed-type hypersensitivity developed in most patients who received vaccine alone or with 200 mg/m(2) CY. HER2-specific antibody responses were enhanced by 200 mg/m(2) CY and 35 mg/m(2) DOX, but higher CY doses suppressed immunity. Analyses revealed that CY at 200 mg/m(2) and DOX at 35 mg/m(2) is the combination that produced the highest antibody responses.ConclusionFirst, immunotherapy with an allogeneic, HER2-positive, GM-CSF-secreting breast tumor vaccine alone or with CY and DOX is safe and induces HER2-specific immunity in patients with metastatic breast cancer. Second, the immunomodulatory activity of low-dose CY has a narrow therapeutic window, with an optimal dose not exceeding 200 mg/m(2). Third, factorial designs provide an opportunity to identify the most active combination of interacting drugs in patients. Further investigation of the impact of chemotherapy on vaccine-induced immunity is warranted