T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1

T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when overexpressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in pre-implantation embryos, where it plays an important role in blastomere proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We have also observed that Tcl1-/-adult mice exhibit alopecia and deep ulcerations. This finding has led us to investigate the role of TCL1 in mouse skin and hair follicles. We have found that TCL1 is expressed in the proliferative structure (i.e.The secondary hair germ) and in the stem cell niche (i.e.The bulge) of the hair follicle during regeneration phase and it is constitutively expressed in the basal layer of epidermis where it is required for the correct proliferative-differentiation program of the keratinocytes (KCs). Taking advantage of the murine models we have generated, including the Tcl1-/-and the K14-TCL1 transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the molecular pathways involved. We provide evidence that in the epidermal compartment TCL1 has a role in the regulation of KC proliferation, differentiation, and apoptosis. In particular, the colony-forming efficiency (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/-mice when compared to WT. Moreover, the expression of differentiation markers such as cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are necessary for the correct proliferation and differentiation of the interfollicular KC

Ice Shapes on a Tail Rotor

Testing of a thermally-protected helicopter rotor in the Icing Research Tunnel (IRT) was completed. Data included inter-cycle and cold blade ice shapes. Accreted ice shapes were thoroughly documented, including tracing, scanning and photographing. This was the first time this scanning capability was used outside of NASA. This type of data has never been obtained for a rotorcraft before. This data will now be used to validate the latest generation of icing analysis tools

Narrow Spectral Feature In Resonance Fluorescence With A Single Monochromatic Laser Field

We describe the resonance fluorescence spectrum of an atomic three-level system where two of the states are coupled by a single monochromatic laser field. The influence of the third energy level, which interacts with the two laser-coupled states only via radiative decays, is studied in detail. For a suitable choice of parameters, this system gives rise to a very narrow structure at the laser frequency in the fluorescence spectrum which is not present in the spectrum of a two-level atom. We find those parameter ranges by a numerical analysis and use the results to derive analytical expressions for the additional narrow peak. We also derive an exact expression for the peak intensity under the assumption that a random telegraph model is applicable to the system. This model and a simple spring model are then used to describe the physical origins of the additional peak. Using these results, we explain the connection between our system, a three-level system in V-configuration where both transitions are laser driven, and a related experiment which was recently reported.Comment: 14 pages, 15 figures, extension of the spring mode

Investigation of Anti-Relaxation Coatings for Alkali-Metal Vapor Cells Using Surface Science Techniques

Many technologies based on cells containing alkali-metal atomic vapor benefit from the use of anti-relaxation surface coatings in order to preserve atomic spin polarization. In particular, paraffin has been used for this purpose for several decades and has been demonstrated to allow an atom to experience up to 10,000 collisions with the walls of its container without depolarizing, but the details of its operation remain poorly understood. We apply modern surface and bulk techniques to the study of paraffin coatings, in order to characterize the properties that enable the effective preservation of alkali spin polarization. These methods include Fourier transform infrared spectroscopy, differential scanning calorimetry, atomic force microscopy, near-edge X-ray absorption fine structure spectroscopy, and X-ray photoelectron spectroscopy. We also compare the light-induced atomic desorption yields of several different paraffin materials. Experimental results include the determination that crystallinity of the coating material is unnecessary, and the detection of C=C double bonds present within a particular class of effective paraffin coatings. Further study should lead to the development of more robust paraffin anti-relaxation coatings, as well as the design and synthesis of new classes of coating materials.Comment: 12 pages, 12 figures. Copyright 2010 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in the Journal of Chemical Physics and may be found at http://link.aip.org/link/?JCP/133/14470

Breakthrough pain in oncology: a longitudinal study.

Abstract CONTEXT: Existing studies on breakthrough pain (BP) have reported different prevalence rates because of different settings, populations, and assessment methods. These studies have used cross-sectional designs, and the relationship of BP with analgesic treatment has not been evaluated. OBJECTIVES: The aim of this study was to longitudinally assess BP in cancer patients admitted to oncology units. METHODS: A consecutive sample of patients admitted to oncology centers was selected. At admission (T0), three months after admission (T3), and six months after admission (T6), data on background pain and BP were recorded. BP was assessed in terms of its intensity, duration, number of episodes, onset with movement, spontaneous relief after stopping activity, limitation of physical activity, and effectiveness of analgesics. RESULTS: Three hundred two patients completed the study. At T0, T3, and T6, 39%, 38%, and 33% patients, respectively, had continuous pain (P=0.294). Pain intensity significantly decreased (P=0.004 and 0.027 at T3 and T6, respectively). Most patients had BP at T0 (87.1%), T3 (80.9%), and T6 (73.2%), and there was a significant decrease in the prevalence of BP over time (P=0.016). Of 149 patients with BP, pain on movement was recorded in 43.6%, 43.4%, and 32.4% at T0, T3, and T6, respectively (P=0.228). Pain spontaneously decreased or ceased when stopping physical activity in 66%, 56%, and 62% at T0, T3, and T6, respectively (P=0.537). Pain on movement strongly limited physical activity in most patients. CONCLUSION: These data expand current information about BP and underline the need for a longitudinal assessment of a phenomenon that is invariably dependent on stage of disease, patient, and therapeutic factors

Quantum jumps induced by the center-of-mass motion of a trapped atom

We theoretically study the occurrence of quantum jumps in the resonance fluorescence of a trapped atom. Here, the atom is laser cooled in a configuration of level such that the occurrence of a quantum jump is associated to a change of the vibrational center-of-mass motion by one phonon. The statistics of the occurrence of the dark fluorescence period is studied as a function of the physical parameters and the corresponding features in the spectrum of resonance fluorescence are identified. We discuss the information which can be extracted on the atomic motion from the observation of a quantum jump in the considered setup

Single-mode instability in optical bistability

This paper gives a detailed description of the plane-wave Gaussian models of optical bistability and of the experimental investigations of the single-mode instability induced on a beam of sodium atoms in a cavity by an external driving field. Our goal is to provide a careful comparison of the theoretical and experimental results. We focus on the shape of the instability domain, the nature and behavior of the spontaneous output oscillations produced by the instability, and their frequency dependence on the control parameters. We carry out this comparison using both the plane-wave and Gaussian models. Our analysis shows that the latter is in good quantitative agreement with the experimental results. We investigate in detail the main assumption of the Gaussian model, namely, that the internal cavity field retains the same radial profile as the input field

Systematic vs. on-demand early palliative care in gastric cancer patients: a randomized clinical trial assessing patient and healthcare service outcomes

Purpose: Early palliative care (EPC) has shown a positive impact on quality of life (QoL), quality of care, and healthcare costs. We evaluated such effects in patients with advanced gastric cancer. Methods: In this prospective, multicenter study, 186 advanced gastric cancer patients were randomized 1:1 to receive standard cancer care (SCC) plus on-demand EPC (standard arm) or SCC plus systematic EPC (interventional arm). Primary outcome was a change in QoL between randomization (T0) and T1 (12 weeks after T0) in the Trial Outcome Index (TOI) scores evaluated through the Functional Assessment of Cancer Therapy-Gastric questionnaire. Secondary outcomes were patient mood, overall survival, and family satisfaction with healthcare and care aggressiveness. Results: The mean change in TOI scores from T0 to T1 was − 1.30 (standard deviation (SD) 20.01) for standard arm patients and 1.65 (SD 22.38) for the interventional group, with a difference of 2.95 (95% CI − 4.43 to 10.32) (p = 0.430). The change in mean Gastric Cancer Subscale values for the standard arm was 0.91 (SD 14.14) and 3.19 (SD 15.25) for the interventional group, with a difference of 2.29 (95% CI − 2.80 to 7.38) (p = 0.375). Forty-three percent of patients in the standard arm received EPC. Conclusions: Our results indicated a slight, albeit not significant, benefit from EPC. Findings on EPC studies may be underestimated in the event of suboptimally managed issues: type of intervention, shared decision-making process between oncologists and PC physicians, risk of standard arm contamination, study duration, timeliness of assessment of primary outcomes, timeliness of cohort inception, and recruitment of patients with a significant symptom burden. Clinical trial registration: ClinicalTrials.gov (NCT01996540)

MicroRNA profiling reveals that miR-21, miR486 and miR-214 are upregulated and involved in cell survival in Sézary syndrome

Sézary syndrome (SS) is an incurable leukemic variant of cutaneous T-cell lymphoma and its pathogenesis is still unknown. Diagnosis/prognosis may strongly ameliorate the management of SS individuals. Here, we profiled the expression of 470 microRNAs (miRNAs) in a cohort of 22 SS patients, and we identified 45 miRNAs differentially expressed between SS and controls. Using predictive analysis, a list of 19 miRNAs, including miR-21, miR-214, miR-486, miR-18a, miR-342, miR-31 and let-7 members were also found. Moreover, we defined a signature of 14 miRNAs including again miR-21, potentially able to discriminate patients with unfavorable and favorable outcome. We validated our data for miR-21, miR-214 and miR-486 by qRT-PCR, including an additional set of array-independent SS cases. In addition, we also provide an in vitro evidence for a contribution of miR-214, miR-486 and miR-21 to apoptotic resistance of CTCL cell line