Metastability of diamond ramp-compressed to 2 terapascals.

Carbon is the fourth-most prevalent element in the Universe and essential for all known life. In the elemental form it is found in multiple allotropes, including graphite, diamond and fullerenes, and it has long been predicted that even more structures can exist at pressures greater than those at Earth's core1-3. Several phases have been predicted to exist in the multi-terapascal regime, which is important for accurate modelling of the interiors of carbon-rich exoplanets4,5. By compressing solid carbon to 2 terapascals (20 million atmospheres; more than five times the pressure at Earth's core) using ramp-shaped laser pulses and simultaneously measuring nanosecond-duration time-resolved X-ray diffraction, we found that solid carbon retains the diamond structure far beyond its regime of predicted stability. The results confirm predictions that the strength of the tetrahedral molecular orbital bonds in diamond persists under enormous pressure, resulting in large energy barriers that hinder conversion to more-stable high-pressure allotropes1,2, just as graphite formation from metastable diamond is kinetically hindered at atmospheric pressure. This work nearly doubles the highest pressure at which X-ray diffraction has been recorded on any material.

Concomitant LATE-NC in Alzheimer's disease is not associated with increased tau or amyloid-ß pathological burden.

AIMS: Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is present in approximately 50% of Alzheimer's disease (AD) cases and is associated with accelerated cognitive decline. Studies indicate a potential synergistic relationship between LATE-NC and hyperphosphorylated tau. It is unknown if LATE-NC is an independent driver of cognitive impairment or exerts its influence through synergistic relationships with tau. This cliniconeuropathological study investigated the impact of LATE-NC on quantified measures of AD-associated pathology and its impact on clinical measures. METHODS: A total of 61 AD cases underwent neuropathological assessment for LATE-NC and quantitative assessment [area covered by immunoreactivity (IR)] for early conformational tau (MC-1), late-stage hyperphosphorylated tau (AT8) and amyloid-ß in the amygdala and five neocortical regions. Clinical measures included age of disease onset, final Mini-Mental State Examination (MMSE) score and rate of cognitive decline. RESULTS: LATE-NC was present in 41 AD cases (AD/LATE-NC; 67.2%). No significant differences in MC-1-IR, AT8-IR or 4G8-IR were observed in any region between AD/LATE-NC and AD without LATE-NC, indicating no accelerated aggregation or hyperphosphorylation of tau proteins in the AD/LATE-NC cases. Final MMSE was significantly lower in AD/LATE-NC cases and was significantly associated with LATE-NC score even when controlled for the presence of both MC-1-IR and AT8-IR (P = 0.009). CONCLUSION: The presence of LATE-NC in AD is not associated with an increase in the burden of early or late tau or Aß pathology. LATE-NC is associated with a lower final MMSE score independent of tau pathology.

Heterogeneity in α-synuclein subtypes and their expression in cortical brain tissue lysates from Lewy body diseases and Alzheimer's disease.

AIMS: Lewy body diseases are neuropathologically characterized by the abnormal accumulation of α-synuclein (α-syn) protein within vulnerable neurons. Although studies have evaluated α-syn in post mortem brain tissue, previous findings have been limited by typically employing pan-α-syn antibodies that may not recognize disease-relevant forms of protein. We investigated the presence of α-syn species present in post mortem brain tissues from Lewy body disease and Alzheimer's disease. METHODS: Soluble and insoluble/aggregated α-syn from frontal cortex of post mortem brain tissues form Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and aged control cases were sequentially extracted using buffers with increasing detergent concentrations. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the levels of total-, oligomeric- and phosphorylated-Ser129-α-syn (t-, o- and pS129-α-syn). ELISA data were validated by western blot and compared to histological data from the same region of the contralateral hemisphere. RESULTS: There was no difference in t-α-syn levels between groups in the aqueous-soluble, detergent-soluble or urea-soluble tissue fractions. However, aqueous-soluble non-phosphorylated o-α-syn was increased not only in PD and DLB but also in AD without neocortical Lewy bodies. In PD and AD, pS129-α-syn was increased in the detergent-soluble tissue fragment and, in AD, this was positively correlated with the burden of tau pathology. Increased levels of urea-soluble pS129-α-syn were demonstrated only in DLB tissue lysates but this did not correlate with Lewy body pathological burden. CONCLUSIONS: Taken together, these findings suggest that DLB have elevated levels of insoluble pS129-α-syn, but that increased levels of aqueous-soluble o-α-syn and detergent-soluble pS129-α-syn are also observed in PD and AD, suggesting different changes to α-syn across the spectrum of neurodegenerative proteopathies.

Shock Compression of Liquid Deuterium up to 1 TPa.

We present laser-driven shock compression experiments on cryogenic liquid deuterium to 550 GPa along the principal Hugoniot and reflected-shock data up to 1 TPa. High-precision interferometric Doppler velocimetry and impedance-matching analysis were used to determine the compression accurately enough to reveal a significant difference as compared to state-of-the-art ab initio calculations and thus, no single equation of state model fully matches the principal Hugoniot of deuterium over the observed pressure range. In the molecular-to-atomic transition pressure range, models based on density functional theory calculations predict the maximum compression accurately. However, beyond 250 GPa along the principal Hugoniot, first-principles models exhibit a stiffer response than the experimental data. Similarly, above 500 GPa the reflected shock data show 5%-7% higher compression than predicted by all current models.

The design of a line velocity interferometer for any reflector for inertial confinement experiments on the Z-machine.

A line VISAR (Velocity Interferometer System for Any Reflector) has been designed and commissioned at the Sandia National Laboratory's Z-machine. The instrument consists of an F/2 collection system, beam transport, and an interferometer table that contains two Mach-Zehnder type interferometers and an eight channel Gated Optical Imaging (GOI) system. The VISAR probe laser operates at the 532 nm wavelength, and the GOI bandpass is 540-600 nm. The output of each interferometer is passed to an optical streak camera with four selectable sweep speeds. The system is designed with three interchangeable optics modules to select a full field of view of 1 mm, 2 mm, or 4 mm. The optical beam transport system connects the target image plane to the interferometers and the gated optical imagers. The target is integrated into a sacrificial final optics assembly that is integral to the transport beamline.

Theoretical and experimental investigation of the equation of state of boron plasmas.

We report a theoretical equation of state (EOS) table for boron across a wide range of temperatures (5.1×10^{4}-5.2×10^{8} K) and densities (0.25-49 g/cm^{3}) and experimental shock Hugoniot data at unprecedented high pressures (5608±118 GPa). The calculations are performed with first-principles methods combining path-integral Monte Carlo (PIMC) at high temperatures and density-functional-theory molecular-dynamics (DFT-MD) methods at lower temperatures. PIMC and DFT-MD cross-validate each other by providing coherent EOS (difference <1.5 Hartree/boron in energy and <5% in pressure) at 5.1×10^{5} K. The Hugoniot measurement is conducted at the National Ignition Facility using a planar shock platform. The pressure-density relation found in our shock experiment is on top of the shock Hugoniot profile predicted with our first-principles EOS and a semiempirical EOS table (LEOS 50). We investigate the self-diffusivity and the effect of thermal and pressure-driven ionization on the EOS and shock compression behavior in high-pressure and -temperature conditions. We also study the sensitivity of a polar direct-drive exploding pusher platform to pressure variations based on applying pressure multipliers to LEOS 50 and by utilizing a new EOS model based on our ab initio simulations via one-dimensional radiation-hydrodynamic calculations. The results are valuable for future theoretical and experimental studies and engineering design in high-energy density research.

Stereological approaches to dementia research using human brain tissue.

The relationship between the clinical features of dementia disorders and the resultant changes in underlying neuropathological mechanisms has long been of interest to researchers working in the field of neurodegenerative disorders. The majority of neuropathological research in dementia has utilized semi-quantitative analysis of protein inclusions, which have defined the hallmark histological features of the conditions. However, the advent of three-dimensional stereological techniques has enabled unbiased and fully quantitative assessment of brain tissue. The present review focuses on studies that have used these techniques to elucidate important relationships between neuropathological changes and clinical features and, in doing so, revealed important mechanistic insights into the pathophysiology of dementia disorders.

Treatment with corticosteroids--a risk factor for the development of clinical cytomegalovirus disease in AIDS.

OBJECTIVE: To assess the frequency with which HIV-seropositive patients treated with corticosteroids develop cytomegalovirus (CMV) disease. DESIGN: Retrospective case-controlled study. METHODS: All 130 patients receiving systemic corticosteroids over a 20-month period at the HIV Unit, Westminster Hospital, London, UK were reviewed for the development of clinical CMV disease within 28 days. The incidence of CMV disease in this group was compared with that in a cohort admitted during the same period, which was matched for admission diagnosis, HIV risk group, antiretroviral therapy and CD4 lymphocyte subset count (+/- 20%) at admission. RESULTS: Eleven of the 130 patients given corticosteroids developed CMV disease within 28 days, compared with two patients in the case-controlled cohort. All patients who developed CMV disease had a CD4 count < 50 x 10(6)/l on admission. CONCLUSION: The use of corticosteroids in patients with advanced immunosuppression due to HIV infection should be reviewed carefully in view of the possible increased incidence of CMV disease.

Comparison of nebuliser efficiency for aerosolizing pentamidine.

Inhaled pentamidine has become an important method of treatment and prophylaxis for Pneumocystis carinii pneumonia and we have compared nebuliser efficiency in terms of drug output and droplet sizes in four brands of jet nebuliser (Acorn-22, Inspiron, Cirrus, Respirgard II) and one brand of ultrasonic nebuliser (Fisoneb), at 2 pentamidine concentrations and 3 flow rates, using a laser particle sizer. Droplet size (which varied from 1.2 to 4.7 microns mass median diameter) was dependent in all cases, except with the Respirgard II system, on the flow rate of the gas driving the equipment and the concentration of pentamidine used. Drug output varied significantly between nebuliser brands and for a 300 mg dose of pentamidine was: 61% for the Acorn-22, 62% for the Inspiron, 49% for the Fisoneb and 43% for the Respirgard II. Both droplet size and drug output are important in determining nebuliser efficiency.

A high-resolution two-dimensional imaging velocimeter.

Velocity interferometers are typically used to measure velocities of surfaces at a single point or along an imaged line as a function of time. We describe an optical arrangement that enables high-resolution measurements of the two-dimensional velocity field across a shock front or shocked interface. The technique is employed to measure microscopic fluctuations in shock fronts that have passed through materials being considered as ablators for indirect-drive inertial confinement fusion. With picosecond time resolution the instrument captures velocity modes with wavelengths as short as 2.5 microm at a resolution of approximately 10 m/s rms on velocity fields averaging many km/s over an 800 microm field of view.

Transposon mutagenesis in Proteus mirabilis.

A technique of transposon mutagenesis involving the use of Tn5 on a suicide plasmid was developed for Proteus mirabilis. Analysis of the resulting exconjugants indicated that Tn5 transposed in P. mirabilis at a frequency of ca. 4.5 x 10(-6) per recipient cell. The resulting mutants were stable and retained the transposon-encoded antibiotic resistance when incubated for several generations under nonselective conditions. The frequency of auxotrophic mutants in the population, as well as DNA-DNA hybridizaiton to transposon sequences, confirmed that the insertion of the transposon was random and the Proteus chromosome did not contain significant insertional hot spots of transposition. Approximately 35% of the mutants analyzed possessed plasmid-acquired ampicillin resistance, although no extrachromosomal plasmid DNA was found. In these mutants, insertion of the Tn5 element and a part or all of the plasmid had occurred. Application of this technique to the study of swarmer cell differentiation in P. mirabilis is discussed.

Proteus mirabilis mutants defective in swarmer cell differentiation and multicellular behavior.

Proteus mirabilis is a dimorphic bacterium which exists in liquid cultures as a 1.5- to 2.0-microns motile swimmer cell possessing 6 to 10 peritrichous flagella. When swimmer cells are placed on a surface, they differentiate by a combination of events that ultimately produce a swarmer cell. Unlike the swimmer cell, the polyploid swarmer cell is 60 to 80 microns long and possesses hundreds to thousands of surface-induced flagella. These features, combined with multicellular behavior, allow the swarmer cells to move over a surface in a process called swarming. Transposon Tn5 was used to produce P. mirabilis mutants defective in wild-type swarming motility. Two general classes of mutants were found to be defective in swarming. The first class was composed of null mutants that were completely devoid of swarming motility. The majority of nonswarming mutations were the result of defects in the synthesis of flagella or in the ability to rotate the flagella. The remaining nonswarming mutants produced flagella but were defective in surface-induced elongation. Strains in the second general class of mutants, which made up more than 65% of all defects in swarming were motile but were defective in the control and coordination of multicellular swarming. Analysis of consolidation zones produced by such crippled mutants suggested that this pleiotropic phenotype was caused by a defect in the regulation of multicellular behavior. A possible mechanism controlling the cyclic process of differentiation and dediferentiation involved in the swarming behavior of P. mirabilis is discussed.