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On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

The ability to fabricate 4-level diffractive structures with 1 µm critical dimensions has been demonstrated for the creation of fast (∼f/3.1 at 633 nm) Fresnel zone lenses (FZLs) with >60% diffraction efficiency into the -1 focusing order and nearly complete suppression of 0 and +1 orders. This is done using tooling capable of producing optics with 800 mm apertures. A 4-level grating fabricated in glass at 300 mm aperture is shown to have <15  nm rms holographic phase error. Glass FZLs have also been used as mandrels for casting zero-thermal-expansion, 20 µm thick polymer films created with the 4-level structure as a route to mass replication of efficient diffractive membranes for ultralight segmented space-based telescope applications.

Radiation-driven, low-adiabat, cryogenic DT layered plastic capsule implosions were carried out on the National Ignition Facility (NIF) to study the sensitivity of performance to peak power and drive duration. An implosion with extended drive and at reduced peak power of 350 TW achieved the highest compression with fuel areal density of ~1.3±0.1 g/cm2, representing a significant step from previously measured ~1.0 g/cm2 toward a goal of 1.5 g/cm2. Future experiments will focus on understanding and mitigating hydrodynamic instabilities and mix, and improving symmetry required to reach the threshold for thermonuclear ignition on NIF.

Deuterium-tritium inertial confinement fusion implosion experiments on the National Ignition Facility have demonstrated yields ranging from 0.8 to 7×10(14), and record fuel areal densities of 0.7 to 1.3 g/cm2. These implosions use hohlraums irradiated with shaped laser pulses of 1.5-1.9 MJ energy. The laser peak power and duration at peak power were varied, as were the capsule ablator dopant concentrations and shell thicknesses. We quantify the level of hydrodynamic instability mix of the ablator into the hot spot from the measured elevated absolute x-ray emission of the hot spot. We observe that DT neutron yield and ion temperature decrease abruptly as the hot spot mix mass increases above several hundred ng. The comparison with radiation-hydrodynamic modeling indicates that low mode asymmetries and increased ablator surface perturbations may be responsible for the current performance.

Mixing of plastic ablator material, doped with Cu and Ge dopants, deep into the hot spot of ignition-scale inertial confinement fusion implosions by hydrodynamic instabilities is diagnosed with x-ray spectroscopy on the National Ignition Facility. The amount of hot-spot mix mass is determined from the absolute brightness of the emergent Cu and Ge K-shell emission. The Cu and Ge dopants placed at different radial locations in the plastic ablator show the ablation-front hydrodynamic instability is primarily responsible for hot-spot mix. Low neutron yields and hot-spot mix mass between 34(-13,+50)  ng and 4000(-2970,+17 160)  ng are observed.

Hohlraums are employed at the national ignition facility to convert laser energy into a thermal x-radiation drive, which implodes a fusion capsule, thus compressing the fuel. The x-radiation drive is measured with a low spectral resolution, time-resolved x-ray spectrometer, which views the region around the hohlraum's laser entrance hole. This measurement has no spatial resolution. To convert this to the drive inside the hohlraum, the size of the hohlraum's opening ("clear aperture") and fraction of the measured x-radiation, which comes from this opening, must be known. The size of the clear aperture is measured with the time integrated static x-ray imager (SXI). A soft x-ray imaging channel has been added to the SXI to measure the fraction of x-radiation emitted from inside the clear aperture. A multilayer mirror plus filter selects an x-ray band centered at 870 eV, near the peak of the x-ray spectrum of a 300 eV blackbody. Results from this channel and corrections to the x-radiation drive are discussed.

The National Ignition Facility has been used to compress deuterium-tritium to an average areal density of ~1.0±0.1 g cm(-2), which is 67% of the ignition requirement. These conditions were obtained using 192 laser beams with total energy of 1-1.6 MJ and peak power up to 420 TW to create a hohlraum drive with a shaped power profile, peaking at a soft x-ray radiation temperature of 275-300 eV. This pulse delivered a series of shocks that compressed a capsule containing cryogenic deuterium-tritium to a radius of 25-35 μm. Neutron images of the implosion were used to estimate a fuel density of 500-800 g cm(-3).

We have imaged hard x-ray (>100 keV) bremsstrahlung emission from energetic electrons slowing in a plastic ablator shell during indirectly driven implosions at the National Ignition Facility. We measure 570 J in electrons with E>100 keV impinging on the fusion capsule under ignition drive conditions. This translates into an acceptable increase in the adiabat α, defined as the ratio of total deuterium-tritium fuel pressure to Fermi pressure, of 3.5%. The hard x-ray observables are consistent with detailed radiative-hydrodynamics simulations, including the sourcing and transport of these high energy electrons.

The first soft x-ray radiation flux measurements from hohlraums using both a 96 and a 192 beam configuration at the National Ignition Facility have shown high x-ray conversion efficiencies of ∼85%-90%. These experiments employed gold vacuum hohlraums, 6.4 mm long and 3.55 mm in diameter, heated with laser energies between 150-635 kJ. The hohlraums reached radiation temperatures of up to 340 eV. These hohlraums for the first time reached coronal plasma conditions sufficient for two-electron processes and coronal heat conduction to be important for determining the radiation drive., (© 2011 American Physical Society)

The first 96 and 192 beam vacuum Hohlraum target experiments have been fielded at the National Ignition Facility demonstrating radiation temperatures up to 340 eV and fluxes of 20 TW/sr as viewed by DANTE representing an ∼20 times flux increase over NOVA/Omega scale Hohlraums. The vacuum Hohlraums were irradiated with 2 ns square laser pulses with energies between 150 and 635 kJ. They produced nearly Planckian spectra with about 30±10% more flux than predicted by the preshot radiation hydrodynamic simulations. To validate these results, careful verification of all component calibrations, cable deconvolution, and software analysis routines has been conducted. In addition, a half Hohlraum experiment was conducted using a single 2 ns long axial quad with an irradiance of ∼2×10(15) W/cm(2) for comparison with NIF Early Light experiments completed in 2004. We have also completed a conversion efficiency test using a 128-beam nearly uniformly illuminated gold sphere with intensities kept low (at 1×10(14) W/cm(2) over 5 ns) to avoid sensitivity to modeling uncertainties for nonlocal heat conduction and nonlinear absorption mechanisms, to compare with similar intensity, 3 ns OMEGA sphere results. The 2004 and 2009 NIF half-Hohlraums agreed to 10% in flux, but more importantly, the 2006 OMEGA Au Sphere, the 2009 NIF Au sphere, and the calculated Au conversion efficiency agree to ±5% in flux, which is estimated to be the absolute calibration accuracy of the DANTEs. Hence we conclude that the 30±10% higher than expected radiation fluxes from the 96 and 192 beam vacuum Hohlraums are attributable to differences in physics of the larger Hohlraums.

The static x-ray imager at the National Ignition Facility is a pinhole camera using a CCD detector to obtain images of Hohlraum wall x-ray drive illumination patterns seen through the laser entrance hole (LEH). Carefully chosen filters, combined with the CCD response, allow recording images in the x-ray range of 3-5 keV with 60 μm spatial resolution. The routines used to obtain the apparent size of the backlit LEH and the location and intensity of beam spots are discussed and compared to predictions. A new soft x-ray channel centered at 870 eV (near the x-ray peak of a 300 eV temperature ignition Hohlraum) is discussed.

Indirect-drive hohlraum experiments at the National Ignition Facility have demonstrated symmetric capsule implosions at unprecedented laser drive energies of 0.7 megajoule. One hundred and ninety-two simultaneously fired laser beams heat ignition-emulate hohlraums to radiation temperatures of 3.3 million kelvin, compressing 1.8-millimeter-diameter capsules by the soft x-rays produced by the hohlraum. Self-generated plasma optics gratings on either end of the hohlraum tune the laser power distribution in the hohlraum, which produces a symmetric x-ray drive as inferred from the shape of the capsule self-emission. These experiments indicate that the conditions are suitable for compressing deuterium-tritium-filled capsules, with the goal of achieving burning fusion plasmas and energy gain in the laboratory.

Studies of mineralization of embryonic spicules and of the sea urchin genome have identified several putative mineralization-related proteins. These predicted proteins have not been isolated or confirmed in mature mineralized tissues. Mature Lytechinus variegatus teeth were demineralized with 0.6 N HCl after prior removal of non-mineralized constituents with 4.0 M guanidinium HCl. The HCl-extracted proteins were fractionated on ceramic hydroxyapatite and separated into bound and unbound pools. Gel electrophoresis compared the protein distributions. The differentially present bands were purified and digested with trypsin, and the tryptic peptides were separated by high pressure liquid chromatography. NH2-terminal sequences were determined by Edman degradation and compared with the genomic sequence bank data. Two of the putative mineralization-related proteins were found. Their complete amino acid sequences were cloned from our L. variegatus cDNA library. Apatite-binding UTMP16 was found to be present in two isoforms; both isoforms had a signal sequence, a Ser-Asp-rich extracellular matrix domain, and a transmembrane and cytosolic insertion sequence. UTMP19, although rich in Glu and Thr did not bind to apatite. It had neither signal peptide nor transmembrane domain but did have typical nuclear localization and nuclear exit signal sequences. Both proteins were phosphorylated and good substrates for phosphatase. Immunolocalization studies with anti-UTMP16 show it to concentrate at the syncytial membranes in contact with the mineral. On the basis of our TOF-SIMS analyses of magnesium ion and Asp mapping of the mineral phase composition, we speculate that UTMP16 may be important in establishing the high magnesium columns that fuse the calcite plates together to enhance the mechanical strength of the mineralized tooth.

The majority of the mineral phase of the Lytechinus variegatus tooth is comprised of magnesium containing calcite crystal elements, collectively arranged so that they appear as a single crystal under polarized light, as well as under X-ray or electron irradiation. However, the crystal elements are small, and in spite of the common alignment of their crystal axes, are not the same size or shape in different parts of the tooth. The toughness of the tooth structure arises from the fact that it is a composite in which the crystals are coated with surface layers of organic matter that probably act to inhibit crack formation and elongation. In the growth region the organic components represent a greater part of the tooth structure. In the most heavily mineralized adoral region the primary plates fuse with inter-plate pillars. Using Scanning Electron Microscopy; TOF-SIMS mapping of the characteristic amino acids of the mineral related proteins; and isolation and characterization of the mineral-protected protein we report that the late-forming inter-plate pillars had more than a three-fold greater Mg content than the primary plates. Furthermore, the aspartic acid content of the mineral-related protein was highest in the high Mg pillars whereas the mineral-protected protein of the primary plates was richer in glutamic acid content.These results suggest that the Asp-rich protein(s) is important for formation of the late developing inter-plate pillars that fuse the primary plates and increase the stiffness of the most mature tooth segment. Supported by NIDCR Grant DE R01-01374 to AV.

A single beamline of the National Ignition Facility (NIF) has been operated at a wavelength of 526.5 nm (2 omega) by frequency converting the fundamental 1053 nm (1 omega) wavelength with an 18.2 mm thick type-I potassium dihydrogen phosphate (KDP) second-harmonic generator (SHG) crystal. Second-harmonic energies of up to 17.9 kJ were measured at the final optics focal plane with a conversion efficiency of 82%. For a similarly configured 192-beam NIF, this scales to a total 2 omega energy of 3.4 MJ full NIF equivalent (FNE).

Echinoderm teeth are continuously growing calcite-mineralized tissues of complex structure. Two features are of special interest: (1) cell division takes place in a restricted aboral domain, the plumula, and the cells immediately merge into multinucleated syncytial layers; (2) the major part of the heavily mineralized tooth elongates and moves towards the adoral incisal tip continuously as the syncytial cells actively expand the syncytium and intermembrane mineral phase. As the first step to understanding the nature of the mineralization processes, we have isolated the proteins of the plumula and of the mature mineralized portions of the tooth, and begun their characterization. Peptide sequences were used to screen a plumula cDNA library by polymerase chain reaction. One primer set yielded a prominent amplified product which was cloned, and sequenced. Comparison with the nucleotide and protein data banks revealed the protein to be Mortalin, a member of the hsp-70 family, with >75% of its sequences identical to that of human mortalin. Immunocytochemical localization of mortalin within the plumula, using Anti-human Grp75, showed staining of the odontoblast cytosol and matrix at the point where syncytial formation was occurring. The cytosol of the syncytial layers was weakly stained. The nuclei within the syncytia were stained at their periphery. In the mature part of the tooth, the perinuclear staining of the nuclei was more prominent. We conclude that mortalin is involved in syncytium formation and maintenance. The urchin mortalin has a distinctive aspartic acid and serine-rich C-terminal domain that may link it to the mineralization process.

The National Ignition Facility (NIF) is the world's largest laser system. It contains a 192 beam neodymium glass laser that is designed to deliver 1.8 MJ at 500 TW at 351 nm in order to achieve energy gain (ignition) in a deuterium-tritium nuclear fusion target. To meet this goal, laser design criteria include the ability to generate pulses of up to 1.8 MJ total energy, with peak power of 500 TW and temporal pulse shapes spanning 2 orders of magnitude at the third harmonic (351 nm or 3omega) of the laser wavelength. The focal-spot fluence distribution of these pulses is carefully controlled, through a combination of special optics in the 1omega (1053 nm) portion of the laser (continuous phase plates), smoothing by spectral dispersion, and the overlapping of multiple beams with orthogonal polarization (polarization smoothing). We report performance qualification tests of the first eight beams of the NIF laser. Measurements are reported at both 1omega and 3omega, both with and without focal-spot conditioning. When scaled to full 192 beam operation, these results demonstrate, to the best of our knowledge for the first time, that the NIF will meet its laser performance design criteria, and that the NIF can simultaneously meet the temporal pulse shaping, focal-spot conditioning, and peak power requirements for two candidate indirect drive ignition designs.

The first hohlraum experiments on the National Ignition Facility (NIF) using the initial four laser beams tested radiation temperature limits imposed by plasma filling. For a variety of hohlraum sizes and pulse lengths, the measured x-ray flux shows signatures of filling that coincide with hard x-ray emission from plasma streaming out of the hohlraum. These observations agree with hydrodynamic simulations and with an analytical model that includes hydrodynamic and coronal radiative losses. The modeling predicts radiation temperature limits with full NIF (1.8 MJ), greater, and of longer duration than required for ignition hohlraums.

The first hydrodynamic experiments were performed on the National Ignition Facility. A supersonic jet was formed via the interaction of a laser driven shock ( approximately 40 Mbar) with 2D and 3D density perturbations. The temporal evolution of the jet's spatial scales and ejected mass were measured with point-projection x-ray radiography. Measurements of the large-scale features and mass are in good agreement with 2D and 3D numerical simulations. These experiments provide quantitative data on the evolution of 3D supersonic jets and provide insight into their 3D behavior.

A birefringent wedge in a collimated 351-nm beam provides polarization smoothing at the Omega laser facility and provided it for the Nova laser. At the National Ignition Facility, the best place to put such an optic is after the final focus lens. In a converging beam, a flat birefringent plate can closely mimic the polarization-smoothing action of a wedge. In this new design the flat plate is nearly a Z-cut crystal; for the wedges, the optical axis of the crystal lies far from the plate normal.

Wet-etch figuring utilizes free surface flows driven by surface tension gradients (the Marangoni effect) to confine and stabilize the size and shape of an etchant droplet attached to the underside of a glass surface. This droplet, or wetted zone, is translated on the surface, etching where it contacts and leaving behind no residue, to facilitate an etching-based small-tool figuring process that is free of mechanical and thermal stresses. The optic needs no backing plate, and its back side is free for inspection by optical means. When transmissive optics is figured, the optical thickness between the front and the rear surfaces of the optic is measured interferometrically and used in real time to control the local dwell time of the etchant zone. This truly closed-loop figuring process is robust, environmentally insensitive, and fully automated. It is particularly suited for figuring patterns such as phase plates, corrective elements, and optical flats on very thin (<< 1-mm) substrates that are difficult to figure with traditional abrasive polishing methods.

Our objective was to investigate whether clopidogrel added to low-dose aspirin reduced vascular events in male patients at our VA hospital who had "failed" aspirin therapy because of a mild-to-moderate stroke or a transient ischemic attack. Of 179 consecutive patients who both reported daily aspirin usage at the time of their newest ischemic event as well as were then operationally defined as aspirin "failures," 134 (group A) were treated with combined aspirin-clopidogrel, 15 (group B) underwent an early arterial procedure, 25 (group C) were anticoagulated, and 5 were not entered or continued because of either non-compliance or a refusal to participate. Study therapies were modified because of a vascular event in 4.5% of group A (one non-fatal ischemic stroke, one non-fatal myocardial infarction, and four transient ischemic attacks) and 33% of group B (one non-fatal ischemic stroke, one non-fatal myocardial infarction, and three transient ischemic attacks). No major or fatal bleeding events occurred in any of those on combined aspirin-clopidogrel therapy, with minor bleeding in 10 of 134 (7.5%) and 2 of 15 (13.3%) of group A and B patients, respectively. Patients were followed for 18 +/- 9.7 months. Combined aspirin-clopidogrel therapy appears both safe as well as effective in this single-center, observational study.

Background: Early treatment with intra-arterial thrombolysis has been shown to be effective in the treatment of acute ischemic stroke because of occlusion of the middle cerebral artery. It is unclear how to use this therapy, however, when there is also occlusion of the parent internal carotid artery., Case Report: A 43-year-old woman presented within 15 minutes of symptom onset caused by a large right anterior circulation ischemic stroke. Computed tomography scan showed a hyperdense right middle cerebral artery sign. Carotid angiography showed occlusion of the right internal carotid artery just distal to its origin. After balloon angioplasty of the internal carotid artery, the occluded right middle cerebral artery was successfully recanalized using intra-arterial tissue plasminogen activator. The patient had dramatic clinical improvement after the procedure, with almost complete resolution of her deficits., Conclusion: Acute middle cerebral artery thrombosis is occasionally associated with acute thrombotic occlusion of the parent internal carotid artery. In this situation, carotid occlusion may be treated first with percutaneous transluminal balloon angioplasty. Intra-arterial thrombolysis may then be applied directly to the site of middle cerebral artery thrombosis, improving chances for overall recanalization and excellent clinical response.

We describe the advantages of using diffractive (Fresnel) lenses on thin membranes over conventional optics for, among others, future space telescope projects. Fabrication methods are presented for lenses on two types of freestanding membrane up to 50 cm in size. The first is a Fresnel lens etched into a thin (380-microm) glass sheet, and the second is an approximately 50-microm-thick polymer membrane containing a Fresnel lens made by replication process from a specially made fused-silica master. We show optical performance analysis of all the lenses that are fabricated, including a diffraction-limited Airy spot from a 20-m- focal-length membrane lens in a diffractive telescope system.

This study investigated the use of alendronate in the formation of new dentin in vitro. Extracted human premolar and molar teeth with immature apices were grown in tissue culture medium for 60 days. Six control specimens were grown without alendronate in the medium, and 22 experimental specimens were grown with alendronate at [10(-9) M] in the medium. Newly formed dentin was stained with tetracycline and procion brilliant red at days 1 to 3, 30 to 33, and 60. Specimens were decalcified and 5-micron sections were prepared for examination using fluorescent microscopy. New dentin formation was measured in microns at the most apical region, at 125-micron from the apical measurement and at 250-micron from the apical measurement. The alendronate group had 57.15% more growth than the control group at the most apical region, and this difference was significant (p = 0.0001). The results indicate that alendronate at [10(-9) M] is effective in accelerating dentin formation in vitro.

A diffractive Alvarez lens is demonstrated that consists of two separate phase plates, each having complementary 16-level surface-relief profiles that contain cubic phase delays. Translation of these two components in the plane of the phase plates is shown to produce a variable astigmatic focus. Both spherical and cylindrical phase profiles are demonstrated with good accuracy, and the discrete surface-relief features are shown to cause less than lambda/10 wave-front aberration in the transmitted wave front over a 40 mm x 80 mm region.

Background: Selegiline hydrochloride, a selective MAO-B inhibitor is known to improve motor functions in Parkinson's disease (PD). The present study was undertaken to study the effect of selegiline on memory and intelligence of PD patients., Material and Method: Thirty two patients of PD were divided in two groups: selegiline group (n = 17) received 10 mg selegiline per day and control group (n = 15) did not receive selegiline. Patients receiving trihexyphenidyl and selegiline were excluded. All other treatment remained unchanged. All patients were examined at baseline and after three months for change in UPDRS score, WAIS score, memory test and P300., Results: Patients in selegiline group had less severe disease (UPDRS score 24.11 +/- 14.07) as compared to controls (UPDRS score 40.53 +/- 18.52). There was significant improvement in UPDRS score (p < 0.05), WAIS (p < 0.001) and memory (p < 0.001) in selegiline group. In the control group there was a significant prolongation of P300 latency (p < 0.05)., Conclusion: The study suggests that selegiline improves memory functions and intelligence in PD patients in addition to motor functions. It also prevents prolongation of P300 latency which is a marker of cognitive function.

Continuous or intermittent deviation of head seen in spasmodic torticollis (ST) may result in abnormalities of blink reflex or brain stem auditory evoked potentials (BAEP). The present study was undertaken on 10 patients of ST and an equal number ofage and sex matched healthy controls. BAEP showed no difference in the two groups. R1 and contralateral R2 of blink reflex were similar in the patients and the controls. R2 contralateral to torticollis was also similar to controls but R2 ipsilateral to torticollis was prolonged in ST patients (32.28??1.91 msec) as compared to controls (30.96??1.53 msec) (p<0.05). Our findings suggest brainstem dysfunction in some patients with spasmodic torticollis.

We studied the admission rate, risk factors, neurological complications and sequelae of heat stroke (HS) during the 1995 heat wave in Madison, Wisconsin. HS was epidemic in 1995 (2.3 cases/1000 admissions), compared to the ten-fold lower endemic rate in 1994 (0.2/ 1000). There were 11 cases of HS, 9 males and 2 females. Contributing factors were athletic events (2), working outdoors (3) and indoor activity with malfunctioning air-conditioning (6). Medical conditions contributing to poor temperature regulation included schizophrenia with neuroleptic treatment (2), amyotrophic lateral sclerosis receiving nortriptiline (1), multiple sclerosis (1), attention deficit disorder (1), cystic fibrosis (1) and alcoholism (1). Acute neurological complications occurred in all patients on presentation including coma (8/11.73%), stupor (2/ 11.18%) and seizures (1/11.9%). Two patients (1856) had persistent neurological sequelae in the form of a pan-cerebellar syndrome while the remaining 9 recovered fully. Importantly, avoidable factors contributed to all of the patients with underlying diseases. These patients are particularly at risk and should take adequate precautions during summer months.

An iterative algorithm for constructing fully continuous phase screens for tailoring far-field intensity profiles is presented. The algorithm is robust, stable, and, if run properly, maintains the continuous nature of the phase throughout the iterative process. The iterative procedure is applied to generate continuous phase screens to produce a 12th-power super-Gaussian far-field intensity profile.

Gabapentin (GBP) has been shown to be effective an add-on drug for the treatment of refractory partial epilepsy. We undertook an open clinical trial to test its efficacy for the first time in India. Twenty-six patients with refractory partial seizures (> 4 per month) were given GBP in a titrated dose and the seizure frequency was noted for 3 months. The mean reduction in seizures was significant: 15.87 (SD = 4.5) vs 5.80 (SD = 10.25). The mean percentage change (PCH) from the baseline was -36. Twenty-one of 26 (80%) patients had a reduction in the number of seizures, and 13/26 (50%) were identified as responders (> 50% reduction in seizures). The responders were significantly younger than the nonresponders. Adverse events were mild and noted in 46% patients. Although the trial has its limitations, this is probably the first trial of GBP in a developing country.

Hsp47, an endoplasmic reticulum-resident heat shock protein in fibroblasts, has gelatin-binding properties. It had been hypothesized that it functions as a chaperone regulating procollagen chain folding and/or assembly, but the mechanism of the hsp47-procollagen I interaction was not clear. Hsp47 could bind to both denatured and native procollagen I. A series of competition studies were carried out in which various collagens and collagen domain peptides were incubated with 35[S]-methionine-labeled murine 3T6 cell lysates prior to mixing with gelatin-Sepharose 4B beads. The gelatin-bound proteins were collected and analyzed by gel electrophoresis and autoradiography. Collagenase digested procollagen I had the same effect as denatured intact procollagen, indicating that the propeptides were the major interaction sites. The addition of intact pro alpha 1(I)-N-propeptide at 25 micrograms/ml completely inhibited hsp47 binding to the gelatin-Sepharose. Even the pentapeptide VPTDE, residues 86-90 of the pro alpha 1(I)-N-propeptide, inhibits hsp47-gelatin binding. These data implicating the pro alpha 1(I)-N-propeptide domain were confirmed by examination of polysome-associated pro alpha chains. The nascent pro alpha 1(I)-chains with intact N-propeptide regions could be precipitated by monoclonal hsp47 antibody 11D10, but could not be precipitated by monoclonal anti-pro alpha 1 (I)-N-propeptide antibody SP1.D8 unless dissociated from the hsp47. GST-fusion protein constructs of residues 23-108 (NP1), 23-151 (NP2), and 23-178 (NP3) within the pro alpha 1 (I)- N-propeptide were coupled to Sepharose 4B and used as affinity beads for collection of hsp47 from 3T6 cell lysates. NP1 and NP2 both showed strong specific binding for lysate hsp47. Finally, the interaction was studied in membrane-free in vitro cotranslation systems in which the complete pro alpha 1(I)- and pro alpha 2(I)-chain RNAs were translated alone and in mixtures with each other and with hsp47 RNA. There was no interaction evident between pro alpha 2(I)-chains and hsp47, whereas there was strong interaction between pro alpha 1(I)-chains and nascent hsp47. SP1.D8 could not precipitate pro alpha 1(I)-chains from the translation mix if nascent hsp47 was present. These data all suggest that if hsp47 has a "chaperone" role during procollagen chain processing and folding it performs this specific role via its preferential interaction with the pro alpha 1 (I) chain, and the pro alpha 1(I) amino-propeptide region in particular.

A versatile, rapidly convergent, iterative algorithm is presented for the construction of kinoform phase plates for tailoring the far-field intensity distribution of laser beams. The method consists of repeated Fourier transforming between the near-field and the far-field planes with constraints imposed in each plane. For application to inertial confinement fusion, the converged far-field pattern contains more than 95% of the incident energy inside a desired region and is relatively insensitive to beam aberrations.

In adult newts, basal epidermal cells adjacent to a fresh wound move toward the damaged area by migrating over the epidermal basement membrane. In an attempt to determine which basement membrane components mediate this migration, small pieces of glass coated with various natural matrices, purified proteins, or fragments of proteins were implanted into skin wounds such that epidermal cells attempting to form a wound epithelium would encounter the implants. Laminin derived from a cell line (M1536-B3) that produces no type IV collagen was inactive as a migration substrate. Migration on recombinant entactin was somewhat better than on laminin but was still only approximately 14% of that on type I collagen. M15 matrix, a laminin and entactin-containing product of M1536-B3 cells, was no better than entactin alone. Type IV collagen was an excellent substrate, producing slightly more migration than corresponding concentrations of type I collagen at nearly all concentrations tested. Migration on type IV lacking the NC1 domain was at least as good as on intact type IV. All the activity in type IV was present in a 95 kD fragment (alpha 1(IV)95) from the carboxy terminal two-thirds of the alpha 1 chain. Approximately 60% of the activity on alpha 1(IV)95 was obtained on implants coated with a 110 amino acid fragment of the alpha 1 chain derived from the carboxy terminal half of alpha 1(IV)95. Adding the synthetic peptide, arg-gly-asp-ser (RGDS) to the medium, blocked migration on fibronectin-coated implants but had no effect on implants coated with type IV, suggesting that migration on type IV involves different cell surface receptors than those mediating migration over fibronectin. Matrigel, a commercial product containing most basement membrane components, was a poor migration substrate. Thus if type IV mediates basal cell migration toward a wound in vivo, there may have to be some alterations in basement membrane structure to allow epidermal receptors to access type IV active site(s).

We discuss the design and fabrication of 80-cm-diameter random phase plates for target-plane beam smoothing on the Nova laser. Random phase plates have been used in a variety of inertial confinement fusion target experiments, such as studying direct-drive hydrodynamic stability and producing spatially smooth x-ray backlighting sources. These phase plates were produced by using a novel sol-gel dip-coating technique developed by us. The sol-gel phase plates have a high optical damage threshold at the second- and third-harmonic wavelengths of the Nd:glass laser and have excellent optical performance.

Although elastin depletion is thought to be an etiologic factor in abdominal aortic aneurysm, little is known about its transcription and posttranslational modification in normal and diseased human aorta. Our objectives were to quantify total elastin and elastin cross-links (desmosine/isodesmosine [DID]) and to determine if elastin mRNA was detectable in the disease-prone infrarenal aorta from patients with abdominal aortic aneurysm and a comparative group with no aneurysmal diseases. After preliminary extraction and thermolysin digestion, content of DID and the elastin tetrapeptide, valine-alanine-proline-glycine (VAPG), were determined by high-performance liquid chromatography. Tissue mRNA was studied by Northern blot analysis. Mean values (+/- SE) were compared by Student's t test. The proportion of insoluble elastin was markedly decreased in abdominal aortic aneurysm tissue (1.3% +/- 0.04% vs 12% +/- -2.8%; p less than 0.001). There was no difference in the small percentage of elastin solubilized during extraction in abdominal aortic aneurysm (5.3% +/- 1%) and no aneurysmal disease (6.0% +/- 1.2%; p = 0.71) tissues. The DID concentration of insoluble elastin was not different for abdominal aortic aneurysm and no aneurysmal disease tissue (0.18% +/- 0.07 vs 0.18 +/- 0.05 nm DID/nm VAPG; p = 0.97). On the basis of VAPG content, only 26% +/- 4% of the sodium hydroxide insoluble residue from abdominal aortic aneurysm was elastin; the predominate protein(s) was high in polar amino acids. Elastin mRNA was detectable in all tissues.(ABSTRACT TRUNCATED AT 250 WORDS)