Collisions between Ultracold Molecules and Atoms in a Magnetic Trap.

We prepare mixtures of ultracold CaF molecules and Rb atoms in a magnetic trap and study their inelastic collisions. When the atoms are prepared in the spin-stretched state and the molecules in the spin-stretched component of the first rotationally excited state, they collide inelastically with a rate coefficient k_{2}=(6.6±1.5)×10^{-11} cm^{3}/s at temperatures near 100 µK. We attribute this to rotation-changing collisions. When the molecules are in the ground rotational state we see no inelastic loss and set an upper bound on the spin-relaxation rate coefficient of k_{2}<5.8×10^{-12} cm^{3}/s with 95% confidence. We compare these measurements to the results of a single-channel loss model based on quantum defect theory. The comparison suggests a short-range loss parameter close to unity for rotationally excited molecules, but below 0.04 for molecules in the rotational ground state.

Forest carbon sink neutralized by pervasive growth-lifespan trade-offs.

Land vegetation is currently taking up large amounts of atmospheric CO2, possibly due to tree growth stimulation. Extant models predict that this growth stimulation will continue to cause a net carbon uptake this century. However, there are indications that increased growth rates may shorten trees' lifespan and thus recent increases in forest carbon stocks may be transient due to lagged increases in mortality. Here we show that growth-lifespan trade-offs are indeed near universal, occurring across almost all species and climates. This trade-off is directly linked to faster growth reducing tree lifespan, and not due to covariance with climate or environment. Thus, current tree growth stimulation will, inevitably, result in a lagged increase in canopy tree mortality, as is indeed widely observed, and eventually neutralise carbon gains due to growth stimulation. Results from a strongly data-based forest simulator confirm these expectations. Extant Earth system model projections of global forest carbon sink persistence are likely too optimistic, increasing the need to curb greenhouse gas emissions.

Long Rotational Coherence Times of Molecules in a Magnetic Trap.

Polar molecules in superpositions of rotational states exhibit long-range dipolar interactions, but maintaining their coherence in a trapped sample is a challenge. We present calculations that show many laser-coolable molecules have convenient rotational transitions that are exceptionally insensitive to magnetic fields. We verify this experimentally for CaF where we find a transition with sensitivity below 5 Hz G^{-1} and use it to demonstrate a rotational coherence time of 6.4(8) ms in a magnetic trap. Simulations suggest it is feasible to extend this to more than 1 s using a smaller cloud in a biased magnetic trap.

Enhancing Dipolar Interactions between Molecules Using State-Dependent Optical Tweezer Traps.

We show how state-dependent optical potentials can be used to trap a pair of molecules in different internal states at a separation much smaller than the wavelength of the trapping light. This close spacing greatly enhances the dipole-dipole interaction and we show how it can be used to implement two-qubit gates between molecules that are 100 times faster than existing protocols and than rotational coherence times already demonstrated. We analyze complications due to hyperfine structure, tensor light shifts, photon scattering, and collisional loss, and conclude that none is a barrier to implementing the scheme.

Deep Laser Cooling and Efficient Magnetic Compression of Molecules.

We introduce a scheme for deep laser cooling of molecules based on robust dark states at zero velocity. By simulating this scheme, we show it to be a widely applicable method that can reach the recoil limit or below. We demonstrate and characterize the method experimentally, reaching a temperature of 5.4(7) µK. We solve a general problem of measuring low temperatures for large clouds by rotating the phase-space distribution and then directly imaging the complete velocity distribution. Using the same phase-space rotation method, we rapidly compress the cloud. Applying the cooling method a second time, we compress both the position and velocity distributions.

Magnetic Trapping and Coherent Control of Laser-Cooled Molecules.

We demonstrate coherent microwave control of the rotational, hyperfine, and Zeeman states of ultracold CaF molecules, and the magnetic trapping of these molecules in a single, selectable quantum state. We trap about 5×10^{3} molecules for almost 2 s at a temperature of 70(8) µK and a density of 1.2×10^{5} cm^{-3}. We measure the state-specific loss rate due to collisions with background helium.

The state of methamphetamine ('tik') use among youth in the Western Cape, South Africa.

BACKGROUND: Methamphetamine use among youth in the Western Cape Province of South Africa has increased at alarming rates over the past decade. Although current estimates of youth use exist, they range from 2 - 12%. OBJECTIVES: To identify (i) the prevalence of methamphetamine use in Western Cape youth and (ii) the association between use and known risk factors for methamphetamine use. METHODS: Data were obtained from 10 000 Western Cape Province Grade 8 learners in 54 secondary schools (mean age 14.0 years). Prevalence was descriptively reported while risk factors for past-month use were modelled in a hierarchical logistic regression with demographic, socioeconomic status, substance use, sexual activity and relationship predictors. RESULTS: Approximately 5% (n=496) of learners had used methamphetamine within their lifetime. Of these users, 65% (n=322) had used in the past month or week. Compared to never users, past-month users were more likely to be male, less likely to have a present or partially present mother, less likely to live in an apartment/flat/brick house, more likely to have used alcohol and tobacco and more likely to report having a same-sex partner. CONCLUSION: Results replicate previously known methamphetamine risk factors and highlight the need to address methamphetamine use in comprehensive prevention initiatives.

The state of Methamphetamine ('tik') use among Youth in the Western Cape; South Africa

Background. Methamphetamine use among youth in the Western Cape Province of South Africa has increased at alarming rates over the past decade. Although current estimates of youth use exist; they range from 2 - 12%. Objectives. To identify (i) the prevalence of methamphetamine use in Western Cape youth and (ii) the association between use and known risk factors for methamphetamine use. Methods. Data were obtained from 10 000 Western Cape Province Grade 8 learners in 54 secondary schools (mean age 14.0 years). Prevalence was descriptively reported while risk factors for past-month use were modelled in a hierarchical logistic regression with demographic; socioeconomic status; substance use; sexual activity and relationship predictors. Results. Approximately 5% (n=496) of learners had used methamphetamine within their lifetime. Of these users; 65% (n=322) had used in the past month or week. Compared to never users; past-month users were more likely to be male; less likely to have a present or partially present mother; less likely to live in an apartment/flat/brick house; more likely to have used alcohol and tobacco and more likely to report having a same-sex partner. Conclusion. Results replicate previously known methamphetamine risk factors and highlight the need to address methamphetamine use in comprehensive prevention initiatives

The influence of tropical adaptation on plasma concentrations of insulin-like growth factor-I in purebred and crossbred beef cattle.

In an effort to determine whether tropical adaptation influences circulating concentrations of the growth-related hormone IGF-I, 3-breed diallel matings were conducted using temperate Bos taurus (Angus), tropical Bos indicus (Brahman), and tropical Bos taurus (Romosinuano). Purebred Angus, Braham, and Romosinuano and crossbred Angus-Braham, Angus-Romosinuano, and Braham-Romosinuano heifers and steers were evaluated in 2 separate calf crops from 2003 and 2004. Blood samples were obtained from 10 heifers of each breed group (n = 90) for each year at weaning and on d 0 and 84 of postweaning trials. Samples were also taken from 10 steers of each breed group (n = 90) at weaning and on d 0 and 60 of individual finishing phase feeding trials for each year. Concentrations of IGF-I were determined by RIA. Analyses included effects of sire breed, dam breed, year of record, the age of the dam of the calf in years, and interactions. Age of calf in days was investigated as a linear and quadratic covariate. Separate analyses were conducted for steers and heifers. The direct effect of Angus was to reduce (P < 0.03) heifer concentrations of IGF-I at d 84 and in the repeated measures analysis. In the repeated measures analysis, the direct effect of Romosinuano was to increase concentrations of IGF-I (P = 0.01). Relative to the temperate Bos taurus breed, plasma concentrations of IGF-I were numerically greater in male and female tropically adapted breed groups.

Function of the corpus luteum in beef heifers is affected by acute submaintenance feeding but is not correlated with residual feed intake.

Seventy-four Angus and Angus × Hereford heifers were used in 2 successive years (yr 1, n = 43; yr 2, n = 31) to determine if luteal function of heifers during acute submaintenance feeding is related to variation in utilization of feed as determined by residual feed intake (RFI). Residual feed intake was determined for heifers beginning at 12.3 ± 0.1 mo of age in yr 1 and at 9.1 ± 0.1 mo of age in yr 2. Heifers were assigned to dry-lot pens (n = 6 to 9 heifers/pen) with electronic gates to measure individual feed intake of a total mixed ration for 70 and 72 d in yr 1 and 2, respectively. Residual feed intake was calculated as the difference between actual DMI and expected DMI from linear regression of DMI on mid-test BW(0.75) and ADG. At 14.4 ± 0.1 mo of age, all heifers were provided a restricted amount of feed to supply 40% of their maintenance energy requirements for 21 d. Estrous cycles of heifers were synchronized with PGF(2α) on d -10, 0, and 11 relative to start of restriction. Concentrations of progesterone in plasma on d 14 to 21 of restriction were used to determine if heifers ovulated. Overall ADG and ADFI were 0.83 ± 0.02 and 7.37 ± 0.67 kg/d, respectively, for yr 1; and 0.50 ± 0.02 and 5.66 ± 0.09 kg/d, respectively, for yr 2. There was no correlation between RFI and BW, ADG, ADFI, or ultrasound measure of backfat, nor was RFI related to concentrations of IGF-I in plasma. All heifers lost BW and had reduced backfat (P < 0.001) at the end of restricted feeding. All heifers had reproductive cycles before dietary restriction started. During acute nutritional restriction, 4 heifers became anovulatory. Sixteen heifers had concentrations of progesterone in plasma during restricted feeding that were atypical of normal luteal function. There was no relationship between luteal function during nutrient restriction and RFI of heifers. Circulating IGF-1 was greater at weaning and after restricted feeding in heifers with a smaller RFI (>0.5 SD below the mean) than heifers with a greater RFI (>0.5 SD above the mean). It is concluded that RFI is not related to luteal function during acute submaintenance feeding, but that short-term restriction of nutrient intake can alter luteal function that may compromise fertility, even in heifers that exhibit estrus and ovulate.

Mtbp haploinsufficiency in mice increases tumor metastasis.

Mdm2 inhibits the function of the p53 tumor suppressor. Mdm2 is overexpressed in many tumors with wild-type p53 suggesting an alternate mechanism of loss of p53 activity in tumors. An Mdm2-binding protein (MTBP) was identified using a yeast two-hybrid screen. In tissue culture, MTBP inhibits Mdm2 self-ubiquitination, leading to stabilization of Mdm2 and increased degradation of p53. To address the role of MTBP in the regulation of the p53 pathway in vivo, we deleted the Mtbp gene in mice. Homozygous disruption of Mtbp resulted in early embryonic lethality, which was not rescued by loss of p53. Mtbp+/- mice were not tumor prone. When mice were sensitized for tumor development by p53 heterozygosity, we found that the Mtbp+/-p53+/- mice developed significantly more metastatic tumors (18.2%) as compared to p53+/- mice (2.6%). Results of in vitro migration and invasion assays support the in vivo findings. Downmodulation of Mtbp in osteosarcoma cells derived from p53+/- mice resulted in increased invasiveness, and overexpression of Mtbp in Mtbp+/-p53+/- osteosarcoma cells inhibited invasiveness. These results suggest that MTBP is a metastasis suppressor. These results advance our understanding of the cellular roles of MTBP and raise the possibility that MTBP is a novel therapeutic target for metastasis.

Healthwise South Africa: cultural adaptation of a school-based risk prevention programme.

There is a need for effective prevention programmes aimed at reducing risk behaviour among South African adolescents. HealthWise South Africa is a school-based programme designed to reduce sexual and substance use risk behaviour, and promote positive use of leisure time among high-school learners (students). Based on successful programmes in the United States of America, HealthWise was developed for use in South Africa and pilot tested in four South African high schools. We carried out a process evaluation to establish the fidelity of implementation and make sure HealthWise was culturally relevant. Data sources comprised focus groups with educators and learners, lesson evaluations and observations, and interviews with school principals. Qualitative analysis of data highlighted pertinent cultural and contextual factors and identified areas for modifying HealthWise in order to promote better programme-consumer fit. These areas centred on time, language, and leisure. We noted a dynamic tension between the educators' desire to adhere to plan, and to make adaptations in accordance with learners' needs and the context. Ultimately, researchers need to find a balance between fidelity of implementation and programme adaptation to obtain effective programmes that are culturally acceptable to local consumers.

CREB-binding protein regulates apoptosis and growth of HMECs grown in reconstituted ECM via laminin-5.

Interactions between normal mammary epithelial cells and extracellular matrix (ECM) are important for mammary gland homeostasis. Loss of interactions between ECM and normal mammary epithelial cells are thought to be an early event in mammary carcinogenesis. CREB-binding protein (CBP) is an important regulator of proliferation and apoptosis but the role of CBP in ECM signaling is poorly characterized. CBP was suppressed in basal-cytokeratin-positive HMECs (CK5/6+, CK14+, CK8-, CK18-, CK19-). Suppression of CBP resulted in loss of reconstituted ECM-mediated growth control and apoptosis and loss of laminin-5 alpha3-chain expression. Suppression of CBP in normal human mammary epithelial cells (HMECs) resulted in loss of CBP occupancy of the LAMA3A promoter and decreased LAMA3A promoter activity and laminin-5 alpha-3 chain expression. Exogenous expression of CBP in CBP-negative HMECs that have lost reconstituted ECM-mediated growth regulation and apoptosis resulted in (1) CBP occupancy of the LAMA3A promoter, (2) increased LAMA3A activity and laminin-5 alpha3-chain expression, and (3) enhancement of reconstituted ECM-mediated growth regulation and apoptosis. Similarly, suppression of laminin-5 alpha3-chain expression in HMECs resulted in loss of reconstituted ECM-mediated growth control and apoptosis. These observations suggest that loss of CBP in basal-cytokeratin-positive HMECs results in loss of reconstituted ECM-mediated growth control and apoptosis through loss of LAMA3A activity and laminin-5 alpha3-chain expression. Results in these studies may provide insight into early events in basal-type mammary carcinogenesis.

Retinoids and retinoic acid receptors regulate growth arrest and apoptosis in human mammary epithelial cells and modulate expression of CBP/p300.

Retinoids and retinoic acid receptors (RARs) are important mediators of normal epithelial cell homeostasis. To assess the role of retinoids and RARs in regulating growth arrest and apoptosis in benign and malignant mammary epithelial cells, two model systems were developed: 1) RAR function was suppressed in retinoid-sensitive normal human mammary epithelial cells (HMECs) by the dominant-negative retinoic acid receptor, RARalpha403 (DNRAR), and 2) retinoid-resistant MCF-7 breast cancer cells were transduced with a functional RARbeta2. Inhibition of RAR function by the DNRAR in HMECs resulted in retinoid-resistance, increased proliferation, and dysregulated growth when cells were cultured in reconstituted extracellular matrix (rECM). Expression of RARbeta2 in MCF-7 cells resulted in sensitivity to retinoid-induced growth arrest and apoptosis. The CREB-binding protein (CBP) and the homologous protein p300 are tightly regulated, rate-limiting integrators of diverse signaling pathways and are recruited during retinoid-mediated transcriptional activation. The relationship between retinoid receptor expression, growth regulation, and transcriptional regulation of CBP/p300 is poorly understood. Inhibition of RAR function in HMECs by DNRAR suppressed expression of CBP/p300 and expression of RARbeta2 in MCF-7 cells promoted induction of CBP/p300 when cells were treated with 1.0 microM all-trans-retinoic acid (ATRA). These results suggest that ATRA and RARs regulate growth arrest of HMECs and modulate CBP/p300 protein expression. Since CBP and p300 are normally present in limiting amounts, their regulation by ATRA and RARs may be an important element in the control of transcriptional activation of genes regulating growth arrest and apoptosis.

Suppression of p53 function in normal human mammary epithelial cells increases sensitivity to extracellular matrix-induced apoptosis.

Little is known about the fate of normal human mammary epithelial cells (HMECs) that lose p53 function in the context of extracellular matrix (ECM)-derived growth and polarity signals. Retrovirally mediated expression of human papillomavirus type 16 (HPV-16) E6 and antisense oligodeoxynucleotides (ODNs) were used to suppress p53 function in HMECs as a model of early breast cancer. p53+ HMEC vector controls grew exponentially in reconstituted ECM (rECM) until day 6 and then underwent growth arrest on day 7. Ultrastructural examination of day 7 vector controls revealed acinus-like structures characteristic of normal mammary epithelium. In contrast, early passage p53- HMEC cells proliferated in rECM until day 6 but then underwent apoptosis on day 7. p53- HMEC-E6 passaged in non-rECM culture rapidly (8-10 passages), lost sensitivity to both rECM-induced growth arrest and polarity, and also developed resistance to rECM-induced apoptosis. Resistance was associated with altered expression of alpha3-integrin. Treatment of early passage p53- HMEC-E6 cells with either alpha3- or beta1-integrin function-blocking antibodies inhibited rECM-mediated growth arrest and induction of apoptosis. Our results indicate that suppression of p53 expression in HMECs by HPV-16 E6 and ODNs may sensitize cells to rECM-induced apoptosis and suggest a role for the alpha3/beta1-heterodimer in mediating apoptosis in HMECs grown in contact with rECM.

Human papillomavirus type 16 E6 inactivation of p53 in normal human mammary epithelial cells promotes tamoxifen-mediated apoptosis.

Aberrant p53 expression is frequently observed in mammary epithelial cells obtained from women at high risk for developing breast cancer and is a predictor for the subsequent development of malignancy. Tamoxifen has recently been shown to reduce the incidence of noninvasive breast cancer in high-risk women, but the molecular mechanism of tamoxifen chemoprevention in mammary epithelial tissue that does not overexpress the estrogen receptor is poorly understood. We suppressed p53 expression by retroviral-mediated expression of human papillomavirus type-16 E6 protein (HPV-16 E6) in human mammary epithelial cells (HMECs) to develop an in vitro model of tamoxifen chemoprevention in the context of p53 loss. Early passage p53(-) HMEC-E6-transduced cells treated with 1.0 microM tamoxifen rapidly underwent apoptosis. In contrast, early passage p53(+) HMEC-LXSN vector controls treated with 1.0 microM tamoxifen underwent G1-G0-phase arrest but did not undergo apoptosis. p53(-) HMEC-E6 cells rapidly acquired resistance to tamoxifen-mediated apoptosis after 10 passages in culture (in the absence of tamoxifen). Both p53(+) and p53(-) HMECs exhibited a low level of estrogen receptor staining and minimal estrogen binding, characteristic of proliferating normal luminal mammary epithelial cells. Tamoxifen-mediated apoptosis in p53(-) HMEC-E6 cells was not blocked by inhibitors of transcription and protein synthesis. These data suggest that the acute loss of p53 function in HMECs by expression of HPV-16 E6 results in marked sensitivity to tamoxifen-mediated apoptosis but that resistance to apoptosis rapidly develops within 10 passages in vitro. Observations in our model system predict a critical role for the early institution of tamoxifen chemoprevention.

Tamoxifen but not 4-hydroxytamoxifen initiates apoptosis in p53(-) normal human mammary epithelial cells by inducing mitochondrial depolarization.

Despite the widespread clinical use of tamoxifen as a breast cancer prevention agent, the molecular mechanism of tamoxifen chemoprevention is poorly understood. Abnormal expression of p53 is felt to be an early event in mammary carcinogenesis. We developed an in vitro model of early breast cancer prevention to investigate how tamoxifen and 4-hydroxytamoxifen may act in normal human mammary epithelial cells (HMECs) that have acutely lost p53 function. p53 function was suppressed by retrovirally mediated expression of the human papillomavirus type 16 E6 protein. Tamoxifen, but not 4-hydroxytamoxifen, rapidly induced apoptosis in p53(-) HMEC-E6 cells as evidenced by characteristic morphologic changes, annexin V binding, and DNA fragmentation. We observed that a decrease in mitochondrial membrane potential, mitochondrial condensation, and caspase activation preceded the morphologic appearance of apoptosis in tamoxifen-treated early passage p53(-) HMEC-E6 cells. p53(-) HMEC-E6 cells rapidly developed resistance to tamoxifen-mediated apoptosis within 10 passages in vitro. Resistance to tamoxifen in late passage p53(-) HMEC-E6 cells correlated with an increase in mitochondrial mass and a lack of mitochondrial depolarization and caspase activation following tamoxifen treatment. We hypothesize that an early event in the induction of apoptosis by tamoxifen involves mitochondrial depolarization and caspase activation, and this may be important for effective chemoprevention.

High-spectral-resolution lidar with iodine-vapor filters: measurement of atmospheric-state and aerosol profiles.

A high-spectral-resolution lidar can measure vertical profiles of atmospheric temperature, pressure, the aerosol backscatter ratio, and the aerosol extinction coefficient simultaneously. We describe a system with these characteristics. The transmitter is a narrow-band (FWHM of the order of 74 MHz), injection-seeded, pulsed, double YAG laser at 532 nm. Iodine-vapor filters in the detection system spectrally separate the molecular and aerosol scattering and greatly reduce the latter (-41 dB). Operating at a selected frequency to take advantage of two neighboring lines in vapor filters, one can obtain a sensitivity of the measured signal-to-air temperature ratio equal to 0.42%/K. Using a relatively modest size transmitter and receiver system (laser power times telescope aperture equals 0.19 Wm(2)), our measured temperature profiles (0.5-15 km) over 11 nights are in agreement with balloon soundings to within 2.0 K over an altitude range of 2-5 km. There is good agreement in the lapse rates, tropopause altitudes, and inversions. In principle, to invert the signal requires a known density at one altitude, but in practice it is convenient to also use a known temperature at that altitude. This is a scalable system for high spatial resolution of vertical temperature profiles in the troposphere and lower stratosphere, even in the presence of aerosols.

Combination Interferon alfa-2b/ribavirin therapy for the treatment of hepatitis C: nursing implications.

An effective new therapeutic option consisting of Intron A (Interferon alfa-2b, recombinant; Schering Corporation, Kenilworth, NJ) Injection and Rebetol (Ribavirin, USP) Capsules is now available for the initial therapy of patients with hepatitis C and for patients who had previously responded to alpha interferon but subsequently relapsed. The combination of recombinant interferon alfa-2b/ribavirin therapy increases hepatitis C viral clearance 10-fold in hepatitis C relapse patients and almost threefold in previously untreated patients compared with alpha interferon monotherapy. There is no synergistic toxicity apparent with the two-drug combination. Ribavirin does not significantly worsen the side effects associated with interferon alfa-2b, which are predictable, manageable, and reversible. The major side effects of combination therapy include flulike symptoms, neutropenia, psychiatric disorders, and anemia; however, these side effects are well known and can be managed with dose modifications and nursing intervention. The assistance of nurses in patient education, in side effect management, in hematologic parameter monitoring, and in medication dosing and administration is crucial to maximizing patient compliance and therapy outcome.