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High quality-factor (Q) optical resonators are a key component for ultra-narrow linewidth lasers, frequency stabilization, precision spectroscopy and quantum applications. Integration in a photonic waveguide platform is key to reducing cost, size, power and sensitivity to environmental disturbances. However, to date, the Q of all-waveguide resonators has been relegated to below 260 Million. Here, we report a Si3N4 resonator with 422 Million intrinsic and 3.4 Billion absorption-limited Qs. The resonator has 453 kHz intrinsic, 906 kHz loaded, and 57 kHz absorption-limited linewidths and the corresponding 0.060 dB m−1 loss is the lowest reported to date for waveguides with deposited oxide upper cladding. These results are achieved through a careful reduction of scattering and absorption losses that we simulate, quantify and correlate to measurements. This advancement in waveguide resonator technology paves the way to all-waveguide Billion Q cavities for applications including nonlinear optics, atomic clocks, quantum photonics and high-capacity fiber communications.

The generation of ultra-low-noise microwave and mmWave in miniaturized, chip-based platforms can transform communication, radar and sensing systems 1-3 . Optical frequency division that leverages optical references and optical frequency combs has emerged as a powerful technique to generate microwaves with superior spectral purity than any other approaches 4-7 . Here we demonstrate a miniaturized optical frequency division system that can potentially transfer the approach to a complementary metal-oxide-semiconductor-compatible integrated photonic platform. Phase stability is provided by a large mode volume, planar-waveguide-based optical reference coil cavity 8,9 and is divided down from optical to mmWave frequency by using soliton microcombs generated in a waveguide-coupled microresonator 10-12 . Besides achieving record-low phase noise for integrated photonic mmWave oscillators, these devices can be heterogeneously integrated with semiconductor lasers, amplifiers and photodiodes, holding the potential of large-volume, low-cost manufacturing for fundamental and mass-market applications 13 ., (© 2024. The Author(s).)

Photonic integrated lasers with an ultra-low fundamental linewidth and a high output power are important for precision atomic and quantum applications, high-capacity communications, and fiber sensing, yet wafer-scale solutions have remained elusive. Here we report an integrated stimulated Brillouin laser (SBL), based on a photonic molecule coupled resonator design, that achieves a sub-100-mHz fundamental linewidth with greater than 10-mW output power in the C band, fabricated on a 200-mm silicon nitride (Si 3 N 4 ) CMOS-foundry compatible wafer-scale platform. The photonic molecule design is used to suppress the second-order Stokes (S2) emission, allowing the primary lasing mode to increase with the pump power without phase noise feedback from higher Stokes orders. The nested waveguide resonators have a 184 million intrinsic and 92 million loaded Q, over an order of magnitude improvement over prior photonic molecules, enabling precision resonance splitting of 198 MHz at the S2 frequency. We demonstrate S2-suppressed single-mode SBL with a minimum fundamental linewidth of 71±18 mHz, corresponding to a 23±6-mHz 2 /Hz white-frequency-noise floor, over an order of magnitude lower than prior integrated SBLs, with an ∼11-mW output power and 2.3-mW threshold power. The frequency noise reaches the resonator-intrinsic thermo-refractive noise from 2-kHz to 1-MHz offset. The laser phase noise reaches -155 dBc/Hz at 10-MHz offset. The performance of this chip-scale SBL shows promise not only to improve the reliability and reduce size and cost but also to enable new precision experiments that require the high-speed manipulation, control, and interrogation of atoms and qubits. Realization in the silicon nitride ultra-low loss platform is adaptable to a wide range of wavelengths from the visible to infrared and enables integration with other components for systems-on-chip solutions for a wide range of precision scientific and engineering applications including quantum sensing, gravitometers, atom interferometers, precision metrology, optical atomic clocks, and ultra-low noise microwave generation.

Climate change, energy system transitions, and socioeconomic change are compounding influences affecting the growth of electricity demand. While energy efficiency initiatives and distributed resources can address a significant amount of this demand, the United States will likely still need new utility-scale generation resources. The energy sector uses capacity expansion planning models to determine the aggregate need for new generation, but these models are typically at the state or regional scale and are not equipped to address the wide range of location- and technology-specific issues that are increasingly a factor in power plant siting. To help address these challenges, we have developed the Geospatial Raster Input Data for Capacity Expansion Regional Feasibility (GRIDCERF) data package, a high-resolution product to evaluate siting suitability for renewable and non-renewable power plants in the conterminous United States. GRIDCERF offers 264 suitability layers for use with 56 power plant technologies in a harmonized format that can be easily ingested by geospatially-enabled modeling software allowing for customization to robustly address science objectives when evaluating varying future conditions., (© 2023. The Author(s).)

We demonstrate 0.034 dB/m loss waveguides in a 200-mm wafer-scale, silicon nitride (Si 3 N 4 ) CMOS-foundry-compatible integration platform. We fabricate resonators that measure up to a 720 million intrinsic Q resonator at 1615 nm wavelength with a 258 kHz intrinsic linewidth. This resonator is used to realize a Brillouin laser with an energy-efficient 380 µW threshold power. The performance is achieved by reducing scattering losses through a combination of single-mode TM waveguide design and an etched blanket-layer low-pressure chemical vapor deposition (LPCVD) 80 nm Si 3 N 4 waveguide core combined with thermal oxide lower and tetraethoxysilane plasma-enhanced chemical vapor deposition (TEOS-PECVD) upper oxide cladding. This level of performance will enable photon preservation and energy-efficient generation of the spectrally pure light needed for photonic integration of a wide range of future precision scientific applications, including quantum, precision metrology, and optical atomic clocks.

Drinking water supplies of cities are exposed to potential contamination arising from land use and other anthropogenic activities in local and distal source watersheds. Because water quality sampling surveys are often piecemeal, regionally inconsistent, and incomplete with respect to unregulated contaminants, the United States lacks a detailed comparison of potential source water contamination across all of its large cities. Here we combine national-scale geospatial datasets with hydrologic simulations to compute two metrics representing potential contamination of water supplies from point and nonpoint sources for over a hundred U.S. cities. We reveal enormous diversity in anthropogenic activities across watersheds with corresponding disparities in the potential contamination of drinking water supplies to cities. Approximately 5% of large cities rely on water that is composed primarily of runoff from non-pristine lands (e.g., agriculture, residential, industrial), while four-fifths of all large cities that withdraw surface water are exposed to treated wastewater in their supplies., (© 2021. Battelle Memorial Institute.)

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively ( p < 0.00007 ). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its "human teachers" and produced output that was better, on average, than its training data., (© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.)

We used a framework to systematically evaluate which Facebook advertisements promoting safe fish consumption increased traffic to our website. Keeping images and headlines constant, we tested 11 message types in 5 categories between 2 audiences over a 24-hour weekday period. We identified clear preferences in 9 of 10 comparisons and evidence to suggest that more women prefer presentation of question format compared with narratives, marketing compared with patient education copy, and uncertain compared with certain copy. Our test of messages on a social media platform is a quick and inexpensive way to select the most engaging public health messages for broad dissemination.

We describe a gentleman diagnosed with a posterior fossa medulloblastoma in 1998, successfully treated with craniospinal radiation therapy (RT) and posterior fossa RT boost, followed by 12 months of adjuvant chemotherapy. Nineteen years later, at the age of 28, the patient presented with multiple cranial neuropathies and was found to have disseminated high-grade glioma with leptomeningeal dissemination. In addition to the salient features of this case, we provide a brief review of RT-induced malignancies and the need for further research regarding surveillance and prevention strategies.

Objective: Evaluate prevalence and pattern of occipital pneumatization (OP)., Patients: Individuals with imaging evidence of OP on computed tomography (CT)., Intervention(s): High resolution CT scans of the temporal bone., Main Outcome Measure: The prevalence and pattern of OP on 1000 CT scans performed at a large academic healthcare system., Results: OP had a prevalence of 11.8% (n = 118) while occipital condyle pneumatization occurred in only 0.3%. Occipital air cells were right-sided in 27.1% (n = 32), left-sided in 51.7% (n = 61), and bilateral in 21.2% (n = 25), and OP was contiguous with the occipitomastoid suture. In cases of unilateral OP, the contralateral jugular foramen demonstrated relative enlargement (p = 0.006), but a direct association could not be established., Conclusions: The occipital bone is an accessory site of skull base pneumatization in 11.8% of the population undergoing temporal bone CT, while air cell extension into the occipital condyle occurs more rarely. These occipital air cells have a left-sided predilection and are always in direct proximity to the occipitomastoid suture, suggesting developmental egress from the mastoid. OP is a normal variant and lacks features of craniocervical pneumatization, which is a rare disorder.

Objective  The objective of this study was to determine the prevalence of facial nerve vascular contact on magnetic resonance imaging (MRI) in patients without hemifacial spasm (HFS). Study Design  Our radiology database was queried to identify consecutive adult patients without a history of HFS, intracranial tumor, brain radiation therapy, intracranial surgery, traumatic brain injury, or trigeminal nerve vascular compression. One hundred high-resolution MRIs of the posterior fossa were independently reviewed by two neuroradiologists for facial nerve vascular contact (200 sides). Main Outcome Measures  The prevalence of vascular nerve contact in the non-HFS patient, the location of contact along the facial nerve, the culprit vessel, and severity of compression was recorded. Results  The presence of vascular contact in the non-HFS patient may be as high as 53%. It is typically mild to moderate in severity, most commonly involves the cisternal portion, and usually caused by the anterior inferior cerebellar artery. Conclusion  Vascular contact of the facial nerve is frequently identified in asymptomatic individuals but tends to be more peripheral and mild compared with previous descriptions of neurovascular contact in HFS patients. These results should be considered in assessing the candidacy of HFS patients for microvascular decompression.

Objective: The objective of our study was to review the clinical utility of digital subtraction myelography for the diagnosis of spinal CSF leaks in patients with spontaneous intracranial hypotension (SIH) and those with superficial siderosis., Materials and Methods: Procedure logs from 2007 to 2011 were reviewed to identify cases in which digital subtraction myelography was performed to diagnose spinal CSF leaks. Electronic medical records were reviewed to obtain information regarding diagnosis and outcome. For patients to be included in the study, preprocedural spinal MRI had to show an extradural fluid collection spanning more than one vertebral level and postmyelographic CT had to confirm the presence of an active CSF leak. If digital subtraction myelography successfully showed the site of the CSF leak, the location was documented., Results: Eleven patients (seven men and four women; mean age, 49.0 years) underwent digital subtraction myelography during the study period. Six patients had SIH and five patients had superficial siderosis. The extradural fluid collection on spinal MRI averaged a length of 15.5 vertebral levels. Digital subtraction myelography successfully showed the site of the CSF leak in nine of the 11 patients, and all of the dural tears were located in the thoracic spine between T3 and T11., Conclusion: Digital subtraction myelography is a valuable diagnostic tool for the localization of rapid spinal CSF leaks and should be considered in patients who are clinically suspected to have a dural tear that is accompanied by a longitudinally extensive extradural fluid collection on spinal MRI.

The precise measurement of transition frequencies of trapped atomic samples is susceptible to inaccuracy arising from the inhomogeneous differential shift of the relevant energy levels in the presence of the trapping fields. We demonstrate near-complete cancellation of the differential ac Stark shift ("light shift") of a two-photon magnetic-field-insensitive microwave hyperfine (clock) transition in ^{87}Rb atoms trapped in an optical lattice. Up to 95(2)% of the differential light shift is cancelled while maintaining magnetic-field insensitivity. This technique should have applications in quantum information and frequency metrology.

Background: Conjunctival intraepithelial neoplasia (CIN) is the most common tumor of the ocular surface and is a precursor to invasive squamous cell carcinoma. CIN comprises a spectrum of premalignant epithelial neoplasia that usually begins near the limbus and spreads to the cornea., Methods: This case report reviews the clinical findings and management of CIN, with a discussion of the histopathology and etiology of this tumor., Conclusion: CIN has a variety of clinical presentations, including gelatinous, leukoplakic, or papilliform. Because of their malignant potential, these lesions must be differentiated carefully and treated promptly. Traditional management of CIN is surgical excision with cryotherapy, but other topical treatments are being explored with promising results., (Copyright © 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.)

A 53-year-old woman with superficial siderosis underwent spinal MR imaging, which demonstrated a large cervicothoracic epidural fluid collection compatible with a CSF leak. Conventional and dynamic CT myelography failed to localize the dural tear because of rapid equilibration of myelographic contrast between the thecal sac and the extradural collection. The superior temporal resolution of digital subtraction myelography precisely localized the CSF leak preoperatively and led to the successful surgical correction of the dural tear.

Background: Spontaneous cerebrospinal fluid leak is a well-documented cause of postural headache. We report a medically refractory headache due to multilevel thoracic cerebrospinal fluid leaks., Case Report: A 44-year-old male with an acute onset of postural headache failed to respond to bed rest, hydration, and analgesics. Magnetic resonance imaging demonstrated a large cerebrospinal fluid leak centered at the right T4 and left T11 to 12 levels, with bony pathology evident at the lower thoracic level. Lumbar (L4 to 5) and computed tomography guided T4 to 5 level epidural blood patches provided minimal pain relief. Percutaneous epidural fibrin glue injection at T4 followed by a repeat computed tomography guided epidural blood patch led to significant but incomplete symptom relief. Subsequent imaging demonstrated persistent fluid at the T11 to 12 level. Fibrin glue and epidural blood patches at this level reduced but did not eliminate the leak and residual symptoms. Extensive corrective surgery was offered but declined by the patient., Conclusion: Treatment of multifocal cerebrospinal fluid leaks can be challenging, particularly when at least part of the underlying etiology is fixed structural bony pathology.

We have developed a novel biodegradable, polymeric fiber construct that is coextruded using a wet-spinning process into a core-sheath format with a polysaccharide pre-hydrogel solution as the core fluid and poly(L-lactic acid) (PLLA) as the sheath. The biodegradable, biocompatible fibers were extruded from polymeric emulsions comprised of solutions of various molecular weights of PLLA dissolved in chloroform and containing dispersed, protein-free aqueous phases comprising up to 10% of the emulsion volume. Biologically sensitive agents can be loaded via a dispersed aqueous phase in the polymer, and/or directly into the polysaccharide. We show that this core-sheath fiber format will load a model protein that can be delivered for extended periods in vitro. Bovine serum albumin (BSA) was loaded into the fiber core as a model protein. We have shown that the greater the volume of the protein-free aqueous phase dispersed into the polymeric continuous-phase emulsion, the greater the total release of BSA encapsulated by a core gel comprised of 1% sodium alginate solution. We conclude this fiber format provides a promising vehicle for in vivo delivery of biological molecules. Its biocompatibility and biodegradability also allow for its use as a possible substrate for tissue engineering applications., (Copyright 2006 Wiley Periodicals, Inc.)

Background: Intracranial dural-based lesions can be due to benign or malignant processes. Imaging characteristics cannot always discern between different pathologic conditions. A thorough clinical evaluation may reveal likely diagnostic possibilities. However, in certain cases, the etiology of the underlying lesion may require biopsy or resection to appropriately treat the patient., Review Summary: We report the case of a large dural-based adenocarcinoma of the prostate clinically and radiographically mimicking a meningioma. We review the history and physical evaluation of the patient and subsequent treatment and response. We discuss the implications of dural-based intracranial lesions in patients with prostate cancer and review the literature of dural metastases, including the pathogenesis, tumor types, and clinical presentations., Conclusion: The differential diagnosis of dural-based lesions in the brain varies from incidental and benign to symptomatic and malignant. Careful vigilance in patients with a history of cancer and presenting with new symptoms or imaging evidence of dural-based lesions is critically important to provide timely intervention.

Successful peripheral nerve regeneration is still limited in artificial conduits, especially for long lesion gaps. In this study, porous poly(L-lactide-co-DL-lactide, 75:25) (PLA) conduits were manufactured with 16 poly(L-lactide) (PLLA) microfilaments aligned inside the lumen. Fourteen and 18 mm lesion gaps were created in a rat sciatic nerve lesion model. To evaluate the combined effect of permeable PLA conduits and microfilament bundles on axon growth, four types of implants were tested for each lesion gap: PLA conduits with 16 filaments; PLA conduits without filaments; silicone conduits with 16 filaments; and silicone conduits without filaments. Ten weeks following implantation, regeneration within the distal nerve was compared between corresponding groups. Antibodies against the markers S100, calcitonin gene related peptide (CGRP), RMDO95, and P0 were used to identify Schwann cells, unmyelinated axons, myelinated axons, and myelin, respectively. Results demonstrated that the filament scaffold enhanced tissue cable formation and Schwann cell migration in all groups. The filament scaffold enhanced axonal regeneration toward the distal stump, especially across long lesion gaps, but significance was only achieved with PLA conduits. When compared to corresponding silicone conduits, permeable PLA conduits enhanced myelinated axon regeneration across both lesion gaps and achieved significance only in combination with filament scaffolds. Myelin staining indicated PLA conduits supported axon myelination with better myelin quantity and quality when compared to silicone conduits.

Bioresorbable polymeric support devices (stents) are being developed in order to improve the biocompatibility and drug reservoir capacity of metal stents, as well as to offer a temporary alternative to permanent metallic stents. These temporary devices may be utilized for coronary, urethral, tracheal, and other applications. The present study focuses on the mechanical properties of bioresorbable fibers as well as stents developed from these fibers. Fibers made of poly(L-lactide) (PLLA), polydioxanone (PDS), and poly(glycolide-co-epsilon-caprolactone) (PGACL) were studied in vitro. These fibers combine a relatively high initial strength and modulus together with sufficient ductility and flexibility, and were therefore chosen for use in stents. The effect of degradation on the tensile mechanical properties and morphology of these fibers was examined. The expandable stents developed from these fibers demonstrated excellent initial radial compression strength. The PLLA stents exhibited excellent in vitro degradation resistance and can therefore support body conduits such as blood vessels for prolonged periods of time. PDS and PGACL stents can afford good support for 5 and 2 weeks, respectively, and can therefore be utilized for short-term applications. The degradation resistance of the stents correlates with the profile of mechanical property deterioration of the corresponding bioresorbable fibers., (Copyright 2005 Wiley Periodicals, Inc.)

Biodegradable fibers of poly(L-lactic acid) (PLLA) and poly(D,L-lactide-co-glycolide) (PLGA) that encapsulated a water-soluble drug were created by a patented technique consisting of wet-spinning a water-in-oil emulsion. These fibers are 2.4% by mass drug, which is slowly released, making these fibers potential candidates for implantation as drug delivery devices and/or tissue-engineering substrates. Drug release kinetics and changes in molecular weight were investigated over time. This study demonstrated that drug release rates and molecular weight degradation are a function of the amount of aqueous phase added as an emulsion during fabrication. The type of polymer used (PLLA or PLGA) determines the molecular weight degradation rates, but has little effect on drug release kinetics.

We report the first observation of a charm-strange meson D(+)(sJ)(2632) at a mass of 2632.5+/-1.7 MeV/c(2) in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, D(+)(s)eta and D0K+. In the D(+)(s)eta decay mode we observe a peak with 101 events over a combinatoric background of 54.9 events at a mass of 2635.4+/-3.3 MeV/c(2). There is a corresponding peak of 21 events over a background of 6.9 at 2631.5+/-2.0 MeV/c(2) in the decay mode D0K+. The decay width of this state is <17 MeV/c(2) at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(D(+)(s)eta) is 0.14+/-0.06. The mechanism that keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the D(+)(s)eta decay mode.

Phase-sensitive measurements were made on Sr2RuO4 to establish unambiguously the odd-parity pairing in this material. The critical current of Au(0.5)In(0.5)-Sr2RuO4 superconducting quantum interference devices prepared on Sr2RuO4 single crystals was found to be a maximum for devices with junctions on the same side of the crystal and a minimum for devices with junctions on opposite sides, in the limit of zero magnetic flux; these findings indicate that the phase of the superconducting order parameter in Sr2RuO4 changes by pi under inversion. This result verifies the odd-parity pairing symmetry and the formation of spin-triplet Cooper pairs in Sr2RuO4.

Functional recovery after large excision of dorsal roots is absent because of both the limited regeneration capacity of the transected root, and the inability of regenerating sensory fibers to traverse the dorsal root entry zone. In this study, bioresorbable guidance conduits were used to repair 6-mm dorsal root lesion gaps in rats, while neurotrophin-encoding adenoviruses were used to elicit regeneration into the spinal cord. Polyester conduits with or without microfilament bundles were implanted between the transected ends of lumbar dorsal roots. Four weeks later, adenoviruses encoding NGF or GFP were injected into the spinal cord along the entry zone of the damaged dorsal roots. Eight weeks after injury, nerve regeneration was observed through both types of implants, but those containing microfilaments supported more robust regeneration of calcitonin gene-related peptide (CGRP)-positive nociceptive axons. NGF overexpression induced extensive regeneration of CGRP(+) fibers into the spinal cord from implants showing nerve repair. Animals that received conduits containing microfilaments combined with spinal NGF virus injections showed the greatest recovery in nociceptive function, approaching a normal level by 7-8 weeks. This recovery was reversed by recutting the dorsal root through the centre of the conduit, demonstrating that regeneration through the implant, and not sprouting of intact spinal fibers, restored sensory function. This study demonstrates that a combination of PNS guidance conduits and CNS neurotrophin therapy can promote regeneration and restoration of sensory function after severe dorsal root injury.

Tissue engineering represents a potential method for repairing damaged skeletal muscle tissue. Extracellular matrix (ECM) proteins were evaluated for their ability to aid in cell attachment, whereas a poly(L-lactic acid) (PLLA) fiber scaffold was tested as a substrate for the differentiation of human skeletal muscle cells. In comparison to uncoated or gelatin-coated PLLA films, cell attachment increased significantly (p < 0.001) on PLLA films coated with ECM gel, fibronectin, or laminin. Myoblasts differentiated into multinucleated myofibers on ECM gel-coated PLLA fibers, and expressed muscle markers such as myosin and alpha-actinin. Oligonucleotide microarray analysis showed similar gene expression profiles for human skeletal muscle cells on ECM gel-coated PLLA fibers as to that observed for myofibers on tissue culture plates. Therefore, PLLA fibers coated with ECM proteins provide a scaffold for the development of skeletal muscle tissue for tissue engineering and cell transplantation applications., (Copyright 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 373-381, 2004)

The success of entubulation for peripheral nerve regeneration is still limited, especially with long lesion gaps. In this study, we examined if regeneration could be enhanced by constructing implants to both align axonal growth and promote Schwann cell proliferation and migration. Silicone implants were used to bridge a 1.4-cm gap in the rat sciatic nerve. Adult female Sprague-Dawley rats were divided into four groups of tubes containing either 1) Matrigel; 2) Matrigel and heregulin; 3) Matrigel and poly(L-lactic acid) (PLLA) microfilaments; or 4) Matrigel, PLLA microfilaments, and heregulin. Ten weeks postimplantation, the number of axons and Schwann cells were measured at the distal end of implants. Implants with microfilaments displayed better tissue cable formation, increased Schwann cell migration, and regeneration of anti-calcitonin gene-related peptide-positive axons, but not RMDO95-positive axons compared with nonfilament-containing groups. Heregulin treatment caused an increase in Schwann cell number, but it demonstrated no significant improvement in either tissue cable formation or axon number. Extensive regeneration was observed through implants containing Matrigel, microfilaments, and heregulin, which induced significant improvements in the number and longitudinal organization of both Schwann cells and axons. These results indicate that physical guidance of microfilaments and the Schwann cell growth factor, heregulin, act synergistically to improve nerve regeneration across long lesion gaps., (Copyright 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 247-258, 2004)

A comprehensive axisymmetric diffusion model of drug release from a fiber is developed to account for both the initial burst (IB) phenomenon as well as the later diffusion-dominated release. This model is an enhancement over previous models in that a set of four IB parameters are calculated, which both describe the initial burst phenomenon as well as improve the fit for the diffusion-dominated release phase. This model is also an enhancement over previous models in allowing: finite dissolution volumes, finite stirring levels of the medium, and user-specified initial drug dispersion within the device. Five different drug release data sets are used to verify the model and to derive values for the IB parameters. Two of the data sets are from experiments conducted in this study, and the other three sets are from previously published data. These data sets were selected to cover a wide range of possibilities, i.e., from nearly 0% to nearly 100% of the total drug release during IB, yet the model handles all cases equally well.

Objective: To describe the spectral and color Doppler imaging findings in 2 cases of internal carotid artery occlusion with vasa vasorum collateral flow, which we term the "pseudostring sign.", Methods: Spectral and color Doppler imaging findings in both cases were reviewed. Magnetic resonance angiography in 2 cases and conventional angiography in 1 case were also reviewed., Results: Both patients had color Doppler images showing that the internal carotid artery was a narrow, stringlike vessel with arterial flow that had normal spectral Doppler features (velocity < 125 cm/s with a normal waveform). Magnetic resonance angiography in 1 patient showed total occlusion of the proximal internal carotid artery with patent vasa vasorum collaterals reconstituting the lumen distally. In the second patient, magnetic resonance angiography showed total occlusion of the proximal internal carotid artery, and conventional angiography showed proximal occlusion with collateral flow through the vasa vasorum., Conclusion: Proximal internal carotid artery occlusion with vasa vasorum collateral flow should be considered when color Doppler imaging shows a seemingly narrow internal carotid artery with tortuosity and normal spectral Doppler features. Patients with these features should not undergo carotid endarterectomy directly on the basis of only the Doppler findings.

A bioresorbable, expandable poly(L-lactic acid) stent has been designed, based on a linear, continuous coil array principle, by which multiple furled lobes convert to a single lobe upon balloon expansion, without heating. Stent strength and compliance are sufficient to permit deployment by a conventional balloon angioplasty catheter. Several multiple lobe configurations were investigated, with expansion ratios ranging from 1.4 to 1.9 and expanded diameters ranging from 2.3 to 4.7 mm. Compression resistance of the expanded stent is dependent on fiber coil density and fiber ply. A range sufficient for endovascular service was obtained, with less than 4% elastic recoil in six day saline incubation studies. Surface plasma treatment with di(ethylene glycol) vinyl ether significantly reduced platelet adhesion in a 1 h porcine arteriovenous shunt model. Patency was maintained in one week implant studies in the porcine common femoral artery. However, a strong inflammatory response, and significant reduction of the vascular lumen were observed following two weeks implantation. The design principles and fabrication techniques for this bioresorbable stent are sufficiently versatile that a broad range of applications can be addressed. Much work remains to be done, including long-term evaluation of the inflammatory response, and of polymer degradation. The results of this study demonstrate the feasibility of expandable biodegradable stent design and deployment by conventional means.

We report the first systematic study of the electrical transport and magnetic properties of BaRu6O12, which has a quasi-one-dimensional (quasi-1D) hollandite structure. We show that BaRu6O12 is quasi-1D electronically as well. Its physical properties were found to be extremely sensitive to disorder. Furthermore, a transition from being metallic with a resistance drop around 2 K to being weakly insulating as the applied magnetic field was increased was also found. We propose that these two features are related to the possible presence of a quantum phase transition in this material system.

After injury, axonal regeneration occurs across short gaps in the peripheral nervous system, but regeneration across larger gaps remains a challenge. To improve regeneration across extended nerve defects, we have fabricated novel microfilaments with the capability for drug release to support cellular migration and guide axonal growth across a lesion. In this study, we examine the nerve repair parameters of non-loaded filaments. To examine the influence of packing density on nerve repair, wet-spun poly(L-Lactide) (PLLA) microfilaments were bundled at densities of 3.75, 7.5, 15, and 30% to bridge a 1.0-cm gap lesion in the rat sciatic nerve. After 10 weeks, nerve cable formation increased significantly in the filament bundled groups when compared to empty-tube controls. At lower packing densities, the number of myelinated axons was more than twice that of controls or the highest packing density. In a consecutive experiment, PLLA bundles with lower filament-packing density were examined for nerve repair across 1.4- and 1.8-cm gaps. After 10 weeks, the number of successful regenerated nerves receiving filaments was more than twice that of controls. In addition, nerve cable areas for control groups were significantly less than those observed for filament groups. Axonal growth across 1.4- and 1.8-cm gaps was more consistent for the filament groups than for controls. These initial results demonstrate that PLLA microfilaments enhance nerve repair and regeneration across large nerve defects, even in the absence of drug release. Ongoing studies are examining nerve regeneration using microfilaments designed to release neurotrophins or cyclic AMP., (Copyright 2003 Wiley-Liss, Inc.)

Metal stents and, more recently, polymer-coated metal stents are used to stabilize dissections, eliminate vessel recoil, and guide remodeling after balloon angioplasty and other treatments for arterial disease. Bioresorbable polymeric stents are being developed to improve the biocompatibility and the drug reservoir capacity of metal stents, and to offer a transient alternative to the permanent metallic stent implant. Following a brief review of metal stent technology, the emerging class of expandable, bioresorbable polymeric stents is described, with emphasis on developments in the authors' laboratory.

We observe a signal for the doubly charmed baryon Xi(+)(cc) in the charged decay mode Xi(+)(cc)-->Lambda(+)(c)K-pi(+) in data from SELEX, the charm hadroproduction experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.1+/-0.5 events, a statistical significance of 6.3sigma. The observed mass of this state is 3519+/-1 MeV/c(2). The Gaussian mass width of this state is 3 MeV/c(2), consistent with resolution; its lifetime is less than 33 fs at 90% confidence.

The tunneling spectrum of the superconducting phase with Tc approximately 3.0 K has been measured in the Ru-embedded region of Sr2RuO4 using cleaved junctions. A sharp zero-bias conductance peak (ZBCP) has been observed below 3 K. All characteristics of this ZBCP suggest that it originates from Andreev surface bound states, indicating that the pairing in the 3-K phase is also non- s-wave. Below the bulk Tc of Sr2RuO4 (approximately 1.5 K), a crossover from sharp to bell-shaped ZBCP was found. This supports the theory that there is a phase transition in the 3-K phase region near the bulk Tc.

Understanding the complexities of electronic and magnetic ground states in solids is one of the main goals of solid-state physics. Transition-metal oxides have proved to be particularly fruitful in this regard, especially for those materials with the perovskite structure, where the special characteristics of transition-metal-oxygen orbital hybridization determine their properties. Ruthenates have recently emerged as an important family of perovskites because of the unexpected evolution from high-temperature ferromagnetism in SrRuO3 to low-temperature superconductivity in Sr2RuO4 (refs 1, 2). Here we show that a ruthenate in a different structural family, La4Ru6O19, displays a number of highly unusual properties, most notably non-Fermi-liquid behaviour. The properties of La4Ru6O19 have no analogy among the thousands of previously characterized transition-metal oxides. Instead, they resemble those of CeCu6-xAux-a widely studied f-electron-based heavy fermion intermetallic compound that is often considered as providing the best example of non-Fermi-liquid behaviour. In the ruthenate, non-Fermi-liquid behaviour appears to arise from just the right balance between the interactions of localized electronic states derived from Ru-Ru bonding and delocalized states derived from Ru-O hybridization.

We report new precision measurements of the lifetimes of the Lambda(+)(c) and D0 from SELEX, the charm hadroproduction experiment at Fermilab. Based upon 1630 Lambda(+)(c) and 10 210 D0 decays we observe lifetimes of tau[Lambda(+)(c)] = 198.1+/-7.0+/-5.6 fs and tau[D0] = 407.9+/-6.0+/-4.3 fs.

Cellular channels during development and after peripheral nerve injury are thought to provide guidance cues to growing axons. In tissue culture where these cues are absent, neurites from dorsal root ganglion neurons grow with a radial distribution. To induce directional axonal growth and to enhance the rate of axonal growth after injury, we have designed microfilaments of poly(L-lactide). We demonstrate that dorsal root ganglia grown on these filaments in vitro extend longitudinally oriented neurites in a manner similar to native peripheral nerves. The extent of neurite growth was significantly higher on laminin-coated filaments compared with uncoated and poly-L-lysine-coated filaments. As high as 5.8 +/- 0.2 mm growth was observed on laminin-coated filaments compared with 2.0 +/- 0.2 mm on uncoated and 2.2 +/- 0.3 mm on poly-L-lysine-coated filaments within 8 days. Schwann cells were found to grow on all types of filaments. They were, however, absent in the leading edges of growth on laminin-coated filaments. Photolysis of Schwann cells caused a significant reduction in the neurite length on all types of filaments. Laminin-coated filaments, however, induced significantly longer neurites compared with uncoated and/or poly-L-lysine-coated filaments even in the absence of Schwann cells. Our results suggest that laminin-coated poly(L-lactide) filaments are suitable for inducing directional and enhanced axonal growth. Implants designed by arranging these microfilaments into bundles should aid regenerating axons by providing guidance cues and channels to organize matrix deposition, cell migration, axon growth, and improve functional recovery.

To enhance the drug uptake and release capacity of silicone rubber (SR), N-isopropylacrylamide (NIPA) hydrogel particles have been incorporated into a SR membrane. The NIPA particles were thoroughly blended with uncured SR with a certain ratio at room temperature. The mixture was then cast in a Petri dish to 1 mm thickness and cured 10 hours at 90 degrees C. The SR/NIPA composite gel can absorb water approximately equal to its dry weight. Brilliant blue, used as a mock drug, was loaded into the composite gel. Drug release increased exponentially to a final value that is temperature dependent: low at T> =34 degrees C, and high at T< 34 degrees C. This finding is because the hydrophobicity of NIPA changes with temperature. Pulsed release in response to temperature switching between 20 and 39 degrees C has been achieved. Drug uptake and release capability strongly depends upon the structure of the composite gel. The optimal range of NIPA composition is between 75 and 87% by volume. In the cited range, the NIPA particles form an interconnected network that provides a channel for diffusion of drug solution. The SR/NIPA composite gel has promising attributes as a wound dressing and other uses.

Purpose: To determine whether sustained elevation of vascular endothelial growth factor (VEGF) in the vitreous cavity causes retinal hyperpermeability [blood-retinal barrier (BRB) breakdown] before the development of retinal neovascularization (NV) and to document the kinetics of the integrity of BRB breakdown versus time., Methods: Poly(L-lactide-co-glycolide)based devices loaded with VEGF were implanted intravitreally in rabbit eyes. Contrast-enhanced magnetic resonance imaging (MRI) methods were used to identify and quantitate the retinal permeability at various time points after implantation. This was done with the newly developed MR tracer AngioMARK (Epix Medical, Boston, MA). After the MRI measurements, fundus photography and fluorescein angiography (FA) also were performed on the same set of animals., Results: At 3 days after implantation, the MR images showed a significant retinal leakage into the vitreous cavity (BRB breakdown) of the VEGF-implanted eyes. To quantitate this leakage, the permeability surface area product (PS) was measured. At 3 days, the mean PS product was 1.25 +/-0.25 x 10(-5) cm3/min. Based on the VEGF in vitro release study, this 3-day BRB breakdown corresponded to a total sustained release of 7.42 +/- 0.54 microg/ml of VEGF. The fundus and FA photographs of these VEGF-implanted eyes taken at 4 days after implantation also showed a considerable level of retinal vascular dilation and tortuosity. By 12 days after implantation, the mean PS product decreased to 5.83 +/- 1.38 x 10(-6) cm3/min. However, the retinal NV was observed only after the second week after implantation. By this time, a total of 10.70 +/- 0.92 microg/ml of VEGF was released in a sustained fashion. Also, after the retinal NV development, retinal detachment also was observed. The control eyes, however, which were implanted with blank devices, remained unchanged and normal during the entire course of this study (PS = 5.57 +/- 0.66 x 10(-7) cm3/min). CONCLUSIONS. The findings indicate that sustained delivery of elevated amounts of VEGF in the vitreous cavity induces a BRB breakdown even earlier than 3 days after implantation. This was achieved after a total sustained release of 7.42 +/- 0.54 microg/ml of VEGF. This retinal leakage regressed by more than half by the time the retinal NV developed. Furthermore, a retinal detachment occurred after this retinal NV. These results are similar to proliferative diabetic retinopathy (PDR). The sustained elevation of VEGF in the vitreous cavity of rabbit eyes is potentially a good model to test VEGF antagonists to treat or prevent PDR in humans. The quantifiable change of BRB breakdown by the contrast-enhanced MRI method is ideal to assess the therapeutic intervention in vivo without killing the animal and may prove to be clinically useful in humans.

We report the first observation of the Cabibbo-suppressed charm baryon decay Ξ&#95;{c}^{+}→pK^{-}π^{+}. We observe 150±22±5 events for the signal. The data were accumulated using the SELEX spectrometer during the 1996-1997 fixed target run at Fermilab, chiefly from a 600 GeV/c Σ^{-} beam. The branching fractions of the decay relative to the Cabibbo-favored Ξ&#95;{c}^{+}→Σ^{+}K^{-}π^{+} and Ξ&#95;{c}^{+}→Ξ^{-}π^{+}π^{+} are measured to be B(Ξ&#95;{c}^{+}→pK^{-}π^{+})/B(Ξ&#95;{c}^{+}→Σ^{+}K^{-}π^{+})=0.22±0.06±0.03 and B(Ξ&#95;{c}^{+}→pK^{-}π^{+})/B(Ξ&#95;{c}^{+}→Ξ^{-}π^{+}π^{+})=0.20±0.04±0.02, respectively.

Decreased hepatocyte adhesion to polymeric constructs limits the function of tissue engineered hepatic assist devices. We grafted adhesion peptides (RGD and YIGSR) to polycaprolactone (PCL) and poly-L-lactic acid (PLLA) in order to mimic the in vivo extracellular matrix and thus enhance hepatocyte adhesion. Peptide grafting was done by a novel technique in which polyethylene glycol (PEG)-adhesion peptide was linked to allyl-amine coated on the surface of PCL and PLLA by pulsed plasma deposition (PPD). Peptide grafting density, quantified by radio-iodinated tyrosine in YIGSR, was 158 fmol/cm(2) on PLLA and 425 fmol/cm(2) on PCL surfaces. The adhesion of hepatocytes was determined by plating 250,000 hepatocytes/well (test substrates were coated on 12 well plates) and quantifying the percentage of adhered cells after 6 h by MTT assay. Adhesion on PCL surfaces was significantly enhanced (p < 0.05) by both YIGSR (percentage of adhered cells = 53 +/- 7%) and RGD (53 +/- 12%) when compared to control surfaces (31 +/- 8%). Hepatocyte adhesion on PLLA was significantly (p < 0.05) enhanced on PLLA-PEG-RGD surfaces (76 +/- 14%) compared to control surfaces (42 +/- 19%) and more (68 +/- 25%) but not statistically significant (p = 0.15) on PLLA-PEG-YIGSR surfaces compared to control surfaces. These results indicate that hepatocyte adhesion to PCL and PLLA based polymeric surfaces can be enhanced by a novel adhesion peptide grafting technique using pulsed plasma deposition and PEG cross-linking.

Polymer surface-peptide binding interactions have been shown previously to lead to reductions in peptide matrix assisted laser desorption/ionization (MALDI) ion signals. In previous studies, increases in surface-peptide binding were characterized by the increases in both the initially adsorbed and retained quantities of 125I-radiolabeled peptides. The present studies establish a specific correlation between the peptide retention properties of the polymer surface and the reduction in the peptide MALDI ion signal. This correlation is demonstrated by obtaining MALDI mass spectra of angiotensin I applied to various polymer surfaces having a range of peptide adsorption and retention properties. In addition, the use of a MALDI based method of standard additions is shown to allow the quantitation of the polymer surface-peptide retention affinity for angiotensin I and porcine insulin. The MALDI standard additions method for measurement of surface-peptide retention affinities offers a number of significant advantages over conventional radiolabeled peptide binding methods and promises to be a valuable tool for the determination of this important biomaterial characteristic.