Collimated, single-pass atom source from a pulsed alkali metal dispenser for laser-cooling experiments

We have developed an improved scheme for loading atoms into a magneto-optical trap (MOT) from a directed alkali metal dispenser in < 10^-10 torr ultra-high vacuum conditions. A current-driven dispenser was surrounded with a cold absorbing "shroud" held at < 0 C, pumping rubidium atoms not directed into the MOT. This nearly eliminates background alkali atoms and reduces the detrimental rise in pressure normally associated with these devices. The system can be well-described as a current-controlled, rapidly-switched, two-temperature thermal beam, and was used to load a MOT with 3 x 10^8 atoms.Comment: 5 pages, 4 figure

Congenital adrenal hyperplasia: a qualitative study on disease and treatment, doubts, anguishes and relationships (part I)

OBJECTIVE: To understand the meanings/thoughts of a group of parents, patients and physicians regarding congenital adrenal hyperplasia (CAH), and to evaluate their anguishes, doubts and anxieties. METHODS: We selected 21 subjects: 7 pediatric endocrinologists from five Brazilian Public Health System institutions, 9 parents and 6 patients with CAH, according to the qualitative research model. Three of the studied categories are presented: disease and treatment, doubts and anguishes and relationships. RESULTS: Parents' main anguishes relate to the situation of an unnamed sex at birth. A sense of loneliness when dealing with the disease is the major anguish among patients, whereas physicians show hopelessness with the passivity parents and patients. CONCLUSIONS: The apparent submissiveness of patients/parents during consultations must be evaluated cautiously. University Hospitals outpatient clinic dynamics have a direct effect on this behavior: physicians do not talk openly with parents who in turn do not talk with their children, whereas patients chose to protect their parents from additional suffering. Thus, some miscommunication is noticeable among these subjects. These observations suggest that a special mindful measure should be built for these patients.OBJETIVO: Compreender significados e pensamentos de um grupo de pais, pacientes e médicos sobre a hiperplasia adrenal congênita (HAC) e analisar angústias, dúvidas e ansiedades. MÉTODOS: Foram selecionados 21 sujeitos: 7 especialistas de cinco instituições do Sistema Único de Saúde (SUS), 9 familiares e 6 pacientes com HAC, seguindo padrões da pesquisa qualitativa. Neste artigo, apresentaram-se três categorias: doença e tratamento, dúvidas e angústias e relacionamentos. RESULTADOS: As principais angústias dos pais relacionam-se à indefinição sexual ao nascimento. Para pacientes, a angústia maior relaciona-se ao sentimento de solidão ao lidar com a doença e seu tratamento, enquanto médicos mostram-se inconformados com a passividade dos pais/pacientes. CONCLUSÕES: A passividade de pacientes/familiares nas consultas deve ser avaliada com cautela, pois a dinâmica do ambulatório dos hospitais-escola tem efeito neste comportamento: os médicos não conversam abertamente com os pais, enquanto estes não conversam com seus filhos, que, por sua vez, poupam os pais de mais sofrimento. Constatou-se dificuldade de comunicação entre esses vários sujeitos. Essas observações permitem sugerir que uma medida especial de atenção a esses pacientes deva ser construída.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaHospital Infantil Darcy VargasUNIFESP Departamento de PediatriaHospital e Maternidade São LuizUNIFESP, Depto. de MedicinaUNIFESP, Depto. de PediatriaSciEL

Glutamine/Glutamate Metabolism Studied with Magnetic Resonance Spectroscopic Imaging for the Characterization of Adrenal Nodules and Masses

Purpose. To assess glutamine/glutamate (Glx) and lactate (Lac) metabolism using proton magnetic resonance spectroscopic imaging (1H-MRS) in order to differentiate between adrenal gland nodules and masses (adenomas, pheochromocytomas, carcinomas, and metastases). Materials and Methods. Institutional review board approval and informed consent were obtained. A total of 130 patients (47 men) with 132 adrenal nodules/masses were prospectively assessed (54 +/- 14.8 years). A multivoxel system was used with a two-dimensional point-resolved spectroscopy/chemical-shift imaging sequence. Spectroscopic data were interpreted by visual inspection and peak amplitudes of lipids (Lip), choline (Cho), creatine (Cr), Lac, and Glx. Lac/Cr and Glx/Cr were calculated. Glx/Cr was assessed in relation to lesion size. Results. Statistically significant differences were observed in Glx/Cr results between adenomas and pheochromocytomas (P < 0.05), however, with a low positive predictive value (PPV). Glx levels were directly proportional to lesion size in carcinomas. A cutoff point of 1.44 was established for the differentiation between carcinomas larger versus smaller than 4 cm, with 75% sensitivity, 100% specificity, 100% PPV, and 80% accuracy. Lac/Cr results showed no differences across lesions. A cutoff point of -6.5 for Lac/Cr was established for carcinoma diagnosis. Conclusion. Glx levels are directly proportional to lesion size in carcinomas. A cutoff point of -6.5 Lac/Cr differentiates carcinomas from noncarcinomas.Universidade Federal de São Paulo, Dept Diagnost Imaging, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Endocrinol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Urol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imaging, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Endocrinol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Urol, BR-04024002 São Paulo, BrazilWeb of Scienc

REM34 and REM35 control female and male gametophyte development in Arabidopsis thaliana

The REproductive Meristem (REM) gene family encodes for transcription factors belonging to the B3 DNA binding domain superfamily. In Arabidopsis thaliana the REM gene family is composed of 45 members, preferentially expressed during flower, ovule and seed development. Only a few members of this family have been functionally characterized: VERNALIZATION1 (VRN1) and most recently TARGET OF FLC AND SVP1 (TFS1) regulate flowering time and VERDANDI (VDD), together with VALKYRIE (VAL) control the death of the receptive synergid cell in the female gametophyte. We investigated the role of REM34, REM35 and REM36, three closely related and linked genes similarly expressed in both female and male gametophytes. Simultaneous silencing by RNA interference (RNAi) caused about 50% of the ovules to remain unfertilized. Careful evaluation of both ovule and pollen development showed that this partial sterility of the transgenic RNAi lines was due to a post meiotic block in both female and male gametophytes. Furthermore, protein interaction assays revealed that REM34 and REM35 interact, which suggests that they work together during the first stages of gametogenesis

The simulation of the activity dependent neural network growth

It is currently accepted that cortical maps are dynamic constructions that are altered in response to external input. Experience-dependent structural changes in cortical microcurcuts lead to changes of activity, i.e. to changes in information encoded. Specific patterns of external stimulation can lead to creation of new synaptic connections between neurons. The calcium influxes controlled by neuronal activity regulate the processes of neurotrophic factors released by neurons, growth cones movement and synapse differentiation in developing neural systems. We propose a model for description and investigation of the activity dependent development of neural networks. The dynamics of the network parameters (activity, diffusion of axon guidance chemicals, growth cone position) is described by a closed set of differential equations. The model presented here describes the development of neural networks under the assumption of activity dependent axon guidance molecules. Numerical simulation shows that morpholess neurons compromise the development of cortical connectivity.Comment: 10 pages, 2 figure

Fabrication and heating rate study of microscopic surface electrode ion traps

We report heating rate measurements in a microfabricated gold-on-sapphire surface electrode ion trap with trapping height of approximately 240 micron. Using the Doppler recooling method, we characterize the trap heating rates over an extended region of the trap. The noise spectral density of the trap falls in the range of noise spectra reported in ion traps at room temperature. We find that during the first months of operation the heating rates increase by approximately one order of magnitude. The increase in heating rates is largest in the ion loading region of the trap, providing a strong hint that surface contamination plays a major role for excessive heating rates. We discuss data found in the literature and possible relation of anomalous heating to sources of noise and dissipation in other systems, namely impurity atoms adsorbed on metal surfaces and amorphous dielectrics.Comment: 17 pages, 5 figure

Daratumumab monotherapy in refractory warm autoimmune hemolytic anemia and cold agglutinin disease

Autoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment. Daratumumab, a monoclonal antibody targeting CD38, could be beneficial by suppression of CD38+ plasma cells and thus autoantibody secretion. In addition, because CD38 is also expressed by activated T cells, daratumumab may also act via immunomodulatory effects. We evaluated the efficacy and safety of daratumumab monotherapy in an international retrospective study including 19 adult patients with heavily pretreated refractory AIHA. In warm AIHA (wAIHA, n = 12), overall response was 50% with a median response duration of 5.5 months (range, 2-12), including ongoing response in 2 patients after 6 and 12 months. Of 6 nonresponders, 4 had Evans syndrome. In cold AIHA (cAIHA, n = 7) overall hemoglobin (Hb) response was 57%, with ongoing response in 3 of 7 patients. One additional patient with nonanemic cAIHA was treated for severe acrocyanosis and reached a clinical acrocyanosis response as well as a Hb increase. Of 6 patients with cAIHA with acrocyanosis, 4 had improved symptoms after daratumumab treatment. In 2 patients with wAIHA treated with daratumumab, in whom we prospectively collected blood samples, we found complete CD38+ T-cell depletion after daratumumab, as well as altered T-cell subset differentiation and a severely diminished capacity for cell activation and proliferation. Reappearance of CD38+ T cells coincided with disease relapse in 1 patient. In conclusion, our data show that daratumumab therapy may be a treatment option for refractory AIHA. The observed immunomodulatory effects that may contribute to the clinical response deserve further exploration.</p

EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL

gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies

Psychiatry during the Nazi era: ethical lessons for the modern professional

For the first time in history, psychiatrists during the Nazi era sought to systematically exterminate their patients. However, little has been published from this dark period analyzing what may be learned for clinical and research psychiatry. At each stage in the murderous process lay a series of unethical and heinous practices, with many psychiatrists demonstrating a profound commitment to the atrocities, playing central, pivotal roles critical to the success of Nazi policy. Several misconceptions led to this misconduct, including allowing philosophical constructs to define clinical practice, focusing exclusively on preventative medicine, allowing political pressures to influence practice, blurring the roles of clinicians and researchers, and falsely believing that good science and good ethics always co-exist. Psychiatry during this period provides a most horrifying example of how science may be perverted by external forces. It thus becomes crucial to include the Nazi era psychiatry experience in ethics training as an example of proper practice gone awry

Functional diversification of AGAMOUS lineage genes in regulating tomato flower and fruit development

AGAMOUS clade genes encode MADS box transcription factors that have been shown to play critical roles in many aspects of flower and fruit development in angiosperms. Tomato possesses two representatives of this lineage, TOMATO AGAMOUS (TAG1) and TOMATO AGAMOUS-LIKE1 (TAGL1), allowing for an analysis of diversification of function after gene duplication. Using RNAi (RNA interference) silencing, transgenic tomato lines that specifically down-regulate either TAGL1 or TAG1 transcript accumulation have been produced. TAGL1 RNAi lines show no defects in stamen or carpel identity, but show defects in fruit ripening. In contrast TAG1 RNAi lines show defects in stamen and carpel development. In addition TAG1 RNAi lines produce red ripe fruit, although they are defective in determinacy and produce ectopic internal fruit structures. e2814, an EMS- (ethyl methane sulphonate) induced mutation that is temperature sensitive and produces fruit phenotypes similar to that of TAG1 RNAi lines, was also characterized. Neither TAG1 nor TAGL1 expression is disrupted in the e2814 mutant, suggesting that the gene corresponding to the e2814 mutant represents a distinct locus that is likely to be functionally downstream of TAG1 and TAGL1. Based on these analyses, possible modes by which these gene duplicates have diversified in terms of their functions and regulatory roles are discussed