Pre- and postnatal development of GABA receptors in Macaca monkey visual cortex

GABA is a putative inhibitory neurotransmitter in adult mammalian visual cortex but also has been implicated as playing a crucial role in cortical information processing during development. In order to understand better the role of GABA during primate visual cortex development, we have examined the time course of GABAA and GABAB receptor ontogenesis in 18 Macaca nemestrina monkeys ranging from fetal day 61 (F61d) to adulthood. The GABA and benzodiazepine binding sites of the GABAA receptor were detected by 3H-muscimol (3H-MS) and 3H- flunitrazepam (3H-FZ), respectively. GABAB receptors were detected by 3H-baclofen (3H-BA). All ligands were visualized by in vitro autoradiography. Quantitative analysis of film density was done to compare laminar changes during pre- and postnatal development. Saturation binding experiments were done for MS and FZ binding sites to determine receptor number (Bmax) and affinity (Kd) at selected pre- and postnatal ages. Both MS and FZ binding sites were present at F61d-72d throughout the cortical plate and marginal zone. FZ binding sites were more dense than MS binding sites over the cortical plate at young ages and were especially dense over the marginal zone. FZ binding sites also were present in lesser amounts over the subplate and intermediate zone, but not over the subventricular zone. By F119d-126d, layer 4 could be distinguished by its higher density for both ligands. The basic adult laminar pattern was established for both MS and BZ binding sites by birth (birth = F165d-170d). After birth, MS density increases dramatically in all layers, but layer 4C remains most dense to adulthood. FZ labeling is heavy in both layers 4 and 3 at birth but after 4 weeks after birth (P4 wk) it declines somewhat in the supragranular layers so that layer 4C now predominates. Labeling in layers 5/6 virtually disappears after birth. BA binding sites were present at F126d, at which time layer 4 was slightly lighter than the remainder of striate cortex; this laminar pattern remained basically the same throughout our series to adulthood. Competitive binding of agonist and antagonists for the GABAA receptor showed that MS binding characteristics were similar at F126d and P8.5 years (yr). MS binding site Bmax was about 8% of adult values at F72d, 24% by F126d, and 56% at F152d. Bmax then rose rapidly after birth to peak at P18wk at 169% of adult values, and then declined to P1yr. A second peak of 143% was found around P3.5yr, with adult values reached by P8.5yr.(ABSTRACT TRUNCATED AT 400 WORDS

Radiation- and Phonon-Bottleneck-Induced Tunneling in the Fe8 Single-Molecule Magnet

We measure magnetization changes in a single crystal of the single-molecule magnet Fe8 when exposed to intense, short (<20 $\mu$s) pulses of microwave radiation resonant with the m = 10 to 9 transition. We find that radiation induces a phonon bottleneck in the system with a time scale of ~5 $\mu$s. The phonon bottleneck, in turn, drives the spin dynamics, allowing observation of thermally assisted resonant tunneling between spin states at the 100-ns time scale. Detailed numerical simulations quantitatively reproduce the data and yield a spin-phonon relaxation time of T1 ~ 40 ns.Comment: 6 RevTeX pages, including 4 EPS figures, version accepted for publicatio

Low temperature magnetic hysteresis in Mn12_{12} acetate single crystals

Precise magnetic hysteresis measurements of small single crystals of Mn$_{12}$ acetate of spin 10 have been conducted down to 0.4 K using a high sensitivity Hall magnetometer. At higher temperature (>1.6K) step-like changes in magnetization are observed at regularly spaced magnetic field intervals, as previously reported. However, on lowering the temperature the steps in magnetization shift to higher magnetic fields, initially gradually. These results are consistent with the presence of a second order uniaxial magnetic anisotropy, first observed by EPR spectroscopy, and thermally assisted tunnelling with tunnelling relaxation occurring from levels of progressively lower energy as the temperature is reduced. At lower temperature an abrupt shift in step positions is found. We suggest that this shift may be the first evidence of an abrupt, or first-order, transition between thermally assisted and pure quantum tunnelling, suggested by recent theory.Comment: 8 pages, 4 figures, submitted to Europhys. Let

Quantum tunneling in a three dimensional network of exchange coupled single-molecule magnets

A Mn4 single-molecule magnet (SMM) is used to show that quantum tunneling of magnetization (QTM) is not suppressed by moderate three dimensional exchange coupling between molecules. Instead, it leads to an exchange bias of the quantum resonances which allows precise measurements of the effective exchange coupling that is mainly due to weak intermolecular hydrogen bounds. The magnetization versus applied field was recorded on single crystals of [Mn4]2 using an array of micro-SQUIDs. The step fine structure was studied via minor hysteresis loops.Comment: 4 pages, 4 figure

Stressed backbone and elasticity of random central-force systems

We use a new algorithm to find the stress-carrying backbone of ``generic'' site-diluted triangular lattices of up to 10^6 sites. Generic lattices can be made by randomly displacing the sites of a regular lattice. The percolation threshold is Pc=0.6975 +/- 0.0003, the correlation length exponent \nu =1.16 +/- 0.03 and the fractal dimension of the backbone Db=1.78 +/- 0.02. The number of ``critical bonds'' (if you remove them rigidity is lost) on the backbone scales as L^{x}, with x=0.85 +/- 0.05. The Young's modulus is also calculated.Comment: 5 pages, 5 figures, uses epsfi

Treatment outcomes among HIV-positive orphaned and non-orphaned children on antiretroviral therapy in Johannesburg, South Africa

Background. Limited research investigating treatment outcomes for HIV-positive orphans compared with non-orphans has shown mixed results, with several studies indicating that HIV-positive orphans are at greater risk of delayed access to HIV care and poor antiretroviral therapy (ART) adherence, while other data suggest that ART outcomes of orphans can be similar to those of non-orphans. Understanding the impact of orphan status on short-term ART outcomes could improve targeted intervention strategies, and subsequent long-term treatment and developmental outcomes, for HIV-positive infants, children and adolescents.Objectives. To evaluate the relationship between orphan status and ART outcomes among HIV-positive infants, children and adolescents initiating ART at two large public sector HIV clinics in Johannesburg, South Africa.Methods. This was a retrospective cohort study of HIV-positive children aged &lt;18 years initiating standard first-line ART between June 2004 and May 2013. Using propensity scores, orphans and non-orphans were matched for age, sex, World Health Organization stage and ART regimen. The effect of orphanhood on attrition from care (all-cause mortality and loss to follow-up) was evaluated using Cox proportional hazards regression analysis, and its effect on having a detectable viral load (≥400 copies/mL) at 12 months on ART using binomial regression analysis with modified Poisson distribution.Results. A total of 251 (29.4%) orphans (maternal, paternal or both) and 603 (70.6%) non-orphans were included at ART initiation. Following multiple imputation for missing data and propensity score matching, 222 orphans and 222 non-orphans were included. Orphans had a median age of 8.0 years (interquartile range (IQR) 4.9 - 10.7) and non-orphans 7.4 years (IQR 4.2 - 10.2). A total of 12 (5.4%) orphans and 33 (14.9%) non-orphans experienced attrition from care during the first 12 months on ART (adjusted hazard ratio 0.32, 95% confidence interval (CI) 0.17 - 0.63). Among those alive and in care, with a viral load at 12 months on ART, 18.0% of orphans (33/183) and 14.8% of non-orphans (24/162) had a detectable viral load (adjusted risk ratio 1.15, 95% CI 1.04 - 1.28).Conclusions. Orphans were less likely than non-orphans to experience attrition, but among those in care at 12 months, orphans were more likely to have detectable viral loads. Lower attrition among orphans may be due to their being in institutional or foster care, ensuring that they make their visits; however, their higher rates of non-suppression may result from lack of psychosocial support or stigma resulting in struggles to adhere. Additional research investigating age-specific outcomes will be important to elucidate these effects further

Relieving frustration: The case of antiferromagnetic Mn-3 molecular triangles

Recently, various triangular [Mn-III](3) molecules have been extensively studied due to the fact that one can modulate the magnitude and the sign of the inter-ion exchange, thereby giving rise to very simple clusters that constitute some of the cleanest and best examples of so-called single-molecule magnets. However, magnetic and electron paramagnetic resonance (EPR) characterizations of low-spin antiferromagnetic [Mn-III](3) complexes have been problematic due to the significant spin frustration that exists for this topology. We show that this frustration is relieved in the highly distorted [NEt4](3)Mn3Zn2(salox)(3)O(N-3)(8)]center dot MeOH molecule: Susceptibility data suggest a well isolated S = 2 ground state; EPR spectroscopy and high-field torquemetry support this conclusion and further indicate the presence of a very significant zero-field-splitting (zfs) separating the lowest-lying m(S) = +/- 2 states from the excited levels within the same S = 2 multiplet. Remarkably, this zfs is sufficient to give rise to magnetic bistability, as evidenced through the observation of low-temperature magnetization hysteresis

Spin-parity dependent tunneling of magnetization in single-molecule magnets

Single-molecule magnets facilitate the study of quantum tunneling of magnetization at the mesoscopic level. The spin-parity effect is among the fundamental predictions that have yet to be clearly observed. It is predicted that quantum tunneling is suppressed at zero transverse field if the total spin of the magnetic system is half-integer (Kramers degeneracy) but is allowed in integer spin systems. The Landau-Zener method is used to measure the tunnel splitting as a function of transverse field. Spin-parity dependent tunneling is established by comparing the transverse field dependence of the tunnel splitting of integer and half-integer spin systems.Comment: 4 pages, 6 figure

Observation of a Distribution of Internal Transverse Magnetic Fields in a Mn12-Based Single Molecule Magnet

A distribution of internal transverse magnetic fields has been observed in single molecule magnet (SMM) Mn12-BrAc in the pure magnetic quantum tunneling (MQT) regime. Magnetic relaxation experiments at 0.4 K are used to produce a hole in the distribution of transverse fields whose angle and depth depend on the orientation and amplitude of an applied transverse ``digging field.'' The presence of such transverse magnetic fields can explain the main features of resonant MQT in this material, including the tunneling rates, the form of the relaxation and the absence of tunneling selection rules. We propose a model in which the transverse fields originate from a distribution of tilts of the molecular magnetic easy axes.Comment: 4 page