Preparation of Macroscopic Block‐Copolymer‐Based Gyroidal Mesoscale Single Crystals by Solvent Evaporation

Properties arising from ordered periodic mesostructures are often obscured by small, randomly oriented domains and grain boundaries. Bulk macroscopic single crystals with mesoscale periodicity are needed to establish fundamental structure–property correlations for materials ordered at this length scale (10–100 nm). A solvent‐evaporation‐induced crystallization method providing access to large (millimeter to centimeter) single‐crystal mesostructures, specifically bicontinuous gyroids, in thick films (>100 µm) derived from block copolymers is reported. After in‐depth crystallographic characterization of single‐crystal block copolymer–preceramic nanocomposite films, the structures are converted into mesoporous ceramic monoliths, with retention of mesoscale crystallinity. When fractured, these monoliths display single‐crystal‐like cleavage along mesoscale facets. The method can prepare macroscopic bulk single crystals with other block copolymer systems, suggesting that the method is broadly applicable to block copolymer materials assembled by solvent evaporation. It is expected that such bulk single crystals will enable fundamental understanding and control of emergent mesostructure‐based properties in block‐copolymer‐directed metal, semiconductor, and superconductor materials.     

Clinical and genetic analysis of primary bilateral adrenal diseases (micro- and macronodular disease) leading to Cushing syndrome

Primary bilateral adrenocortical diseases are rare entities that have recently been appreciated as potential causes of Cushing syndrome. They include (i) primary pigmented adrenocortical disease (PPNAD), also known as "micronodular adrenal disease", which is a genetic disorder that is often associated with Carney complex, and (ii) massive macronodular adrenocortical disease (MMAD), a rare disorder of unknown etiology that affects older adults. Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects not only the adrenal cortex, but also the pituitary, thyroid, and gonads. It is associated with pigmentation abnormalities as well as myxomas and other mesenchymal and neural crest neoplasms. The inheritance of the complex is autosomal dominant, and genetic mapping has shown that at least two loci are involved in its pathogenesis. MMAD appears to be an isolated finding in most cases, and a genetic defect has not yet been defined. Ectopic expression of hormone receptors has been implicated in several cases of MMAD, but an underlying deficit has not been detected. Bilateral adrenocortical hyperplasia has also been described in McCune-Albright syndrome and MEN type-1, but this finding is not always associated with hypercortisolism. The genetic defects for these diseases are known, but their role in adrenal cortex pathophysiology has not been fully elucidated. Identification of the molecular defects responsible for bilateral adrenocortical disorders is expected to shed light on many aspects of early adrenal gland differentiation and tumorigenesis.     

Correlation analysis of corticotectal interactions in the cat visual system

We have studied the temporal relationship between visual responses in various visual cortical areas [17, 18, postero medial lateral suprasylvian (PMLS), postero lateral lateral suprasylvian (PLLS), 21a]) and the superficial layers of the cat superior colliculus (SC). To this end, simultaneous recordings were performed in one or several visual cortical areas and the SC of anesthetized paralyzed cats, and visually evoked multiunit responses were subjected to correlation analysis. Significant correlations occurred in 117 (24%) of 489 cortex-SC pairs and were found for all cortical areas recorded. About half of the significant correlograms showed an oscillatory modulation. In these cases, oscillation frequencies covered a broad range, the majority being in the alpha- and beta-band. On average, significant center peaks in cross-correlograms had a modulation amplitude of 0.34. Our analysis revealed a considerable intertrial variability of correlation patterns with respect to both correlation strength and oscillation frequency. Furthermore, cortical areas differed in their corticotectal correlation patterns. The percentage of cells involved a corticotectal correlation, as well as the percentage of significantly modulated correlograms in such cases, was low for areas 17 and PMLS but high for areas 18 and PLLS. Analysis of the cortical layers involved in these interactions showed that consistent temporal relationships between cortical and collicular responses were not restricted to layer V. Our data demonstrate a close relationship between corticotectal interactions and intracortical or intracollicular synchronization. Trial-by-trial analysis from these sites revealed a clear covariance of corticotectal correlations with intracortical synchronization. The probability of observing corticotectal interactions increased with enhanced local cortical and collicular synchronization and, in particular, with interareal cortical correlations. Corticotectal correlation patterns resemble in many ways those described among areas of the visual cortex. However, the correlations observed are weaker than those between nearby cortical sites, exhibit usually broader peaks and for some cortical areas show consistent phase-shifts. Corticotectal correlations represent population phenomena that reflect both the local and global temporal organization of activity in the cortical and collicular network and do not arise from purely monosynaptic interactions. Our findings show that both striate and extrastriate inputs affect the superficial SC in a cooperative manner and, thus, do not support the view that responses in the superficial SC depend exclusively on input from the primary visual areas as implied by the concept of "two corticotectal systems." We conclude that the corticotectal projections convey temporal activation patterns with high reliability, thus allowing the SC evaluation of information encoded in the temporal relations between responses of spatially disseminated cortical neurons. As a consequence, information distributed across multiple cortical areas can affect the SC neurons in a coherent way.     

"Black holes" and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli

Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in approximately 90% of E. coli strains but is uniformly absent in Shigella strains. When the gene for LDC, cadA, was introduced into Shigella flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited greatly. The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC. Comparison of the S. flexneri 2a and laboratory E. coli K-12 genomes in the region of cadA revealed a large deletion in Shigella. Representative strains of Shigella spp. and enteroinvasive E. coli displayed similar deletions of cadA. Our results suggest that, as Shigella spp. evolved from E. coli to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions. The formation of these "black holes," deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence. Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy. Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases.     

Stereotactic pallidotomy and thalamotomy using individual variations of anatomic landmarks for localization

OBJECTIVE: The optimal choice of imaging and localization for stereotactic surgery for movement disorders remains uncertain, with controversy surrounding the use of microelectrode recording and the role of distortion of magnetic resonance imaging (MRI) scans in reducing the accuracy of lesion placement. We review our experience with 67 pallidotomies and 35 thalamotomies performed without microelectrode recording, using instead individual variations in anatomic landmarks. METHODS: Computed tomography is used as the primary modality, with comparison with carefully angled MRI scans and the use of neural structures, such as the mamillary bodies and the vascular anatomy. Pallidal target sites are chosen immediately lateral and superior to the optic tract on a line bisecting the axis of the peduncle, with macrostimulation guiding the final adjustment of target position. Forty-seven patients undergoing unilateral pallidotomies were studied in the "off" state and the "on" state using a modified Unified Rating Scale for Parkinson's disease (URSP) score and a dyskinesia scale, preoperatively and postoperatively at 2 weeks, 2 months, 6 months, and 12 months. In the 31 patients undergoing thalamotomy, tremor was rated preoperatively and postoperatively as near-complete resolution, partial resolution, and failure. RESULTS: The "off" state Unified Rating Scale for Parkinson's disease motor score declined from 42.0 to 32.2 at 2 weeks after surgery (P < 0.0001, n = 42). The Unified Rating Scale for Parkinson's disease motor score was 34.2 at 2 months (P < 0.0001, n = 35), 29.4 at 6 months (P < 0.0001, n = 27), and 24.9 at 12 months (P = 0.005, n = 12), representing an overall improvement in "off" state motor function of approximately 25 to 40%. The "on" state dyskinesia score fell from 5.5 to 2.0 at 2 weeks (P < 0.0001) and persisted in the later visits. The dyskinesia score for the contralateral side fell from 2.5 preoperatively to 0.26 at 2 weeks, 0.28 at 2 months, 0.22 at 6 months, and 0.0 at 12 months. Of the patients undergoing thalamotomies, 65% experienced near-complete or complete tremor resolution, 23% experienced partial tremor relief, and 13% were considered treatment failures. CONCLUSION: Stereotactic procedures for movement disorders requiring high precision can be safely and successfully performed without the use of microelectrode recording techniques. Meticulous alignment of MRI and computed tomographic scans based on visualized anatomy allows precise lesion placement and avoids the distortion inherent in MRI scans.     

High-frequency audibility: benefits for hearing-impaired listeners

The present study was a systematic investigation of the benefit of providing hearing-impaired listeners with audible high-frequency speech information. Five normal-hearing and nine high-frequency hearing-impaired listeners identified nonsense syllables that were low-pass filtered at a number of cutoff frequencies. As a means of quantifying audibility for each condition, Articulation Index (AI) was calculated for each condition for each listener. Most hearing-impaired listeners demonstrated an improvement in speech recognition as additional audible high-frequency information was provided. In some cases for more severely impaired listeners, increasing the audibility of high-frequency speech information resulted in no further improvement in speech recognition, or even decreases in speech recognition. A new measure of how well hearing-impaired listeners used information within specific frequency bands called "efficiency" was devised. This measure compared the benefit of providing a given increase in speech audibility to a hearing-impaired listener to the benefit observed in normal-hearing listeners for the same increase in speech audibility. Efficiencies were calculated using the old AI method and the new AI method (which takes into account the effects of high speech presentation levels). There was a clear pattern in the results suggesting that as the degree of hearing loss at a given frequency increased beyond 55 dB HL, the efficacy of providing additional audibility to that frequency region was diminished, especially when this degree of hearing loss was present at frequencies of 4000 Hz and above. A comparison of analyses from the "old" and "new" AI procedures suggests that some, but not all, of the deficiencies of speech recognition in these listeners was due to high presentation levels.     

Recent advances in the large-scale production of antibody fragments using lower eukaryotic microorganisms

BACKGROUND AND OBJECTIVES: Magnetic resonance microscopy (MRM) is a technique that is worthwhile for anesthesiologists because it allows spinal cord and plexus anatomy to be visualized three dimensionally and followed over time in the same animal. For example, the long-term effect of indwelling intrathecal or plexus catheters can be studied in situ, and convective and diffusive forces within intrathecal, epidural, or nerve sheath spaces can be investigated. Further, diffusion-weighted MRM, which measures an "apparent diffusion coefficient" (ADC), can be used to track the presence of ischemia, hypoperfusion, or cytotoxic edema. This study investigates problems associated with the use of in vivo MRM for spinal cord and peripheral nerve studies in the rat. METHODS: Twenty-one anesthetized female Fisher CDF rats were used. Group 1 (n=7) was used for anatomic three-dimensional studies. Groups 2 (n=4), 3 (n=4), and 4 (n=6) were used for measurements of the ADC. Group 2 served as controls, group 3 received lumbar intrathecal catheters, and group 4 received cervical intrathecal catheters. RESULTS: Cervical spine, lumbar spine, and spinal nerves and ganglia were accurately visualized with MRM. As a rule, spinal cord gray and white matter were better demonstrated using diffusion-weighted proton stains. By contrast, T2-weighted proton staining superiorly demonstrated structures surrounding the spinal cord. In groups 3 and 4, indwelling intrathecal catheters did not affect the spinal cord ADC, indicating normal blood flow and no cytotoxic edema. Contrast studies revealed nonhomogeneous distribution of contrast predominately in the lateral and ventral intrathecal space. CONCLUSION: Three-dimensional diffusion-weighted MRM displays cervical and lumbar spine anatomy accurately in vivo. Apparent diffusion coefficients measurements are feasible in rat cervical spinal cord with intrathecal catheters. Spinal cord ADCs are unaffected by intrathecal catheters, indicating normal spinal cord perfusion.     

于锁集合算法的增强型数据竞争检测方法

针对锁集合算法误报率高的缺点,采用增强型数据竞争检测方法对锁集合算法及算法实现两方面进行改进.增强型锁集合算法提出了更强必要条件的检测算法.该算法通过分析线程结束情况和理解变量的线程信息,精化数据竞争检测条件.算法实现采用系统体系结构扩展的方法,通过扩展锁表部件,将集合操作精确映射到位图操作,进一步提高检测精度和减少误报.实现了无干扰免插桩检测技术,避免了二进制代码插桩带来的干扰性和不确定性问题.与同类系统的对比实验结果表明,该方法能够有效地将误报率减小到0.67,并且具有很高的检测效率.     

Bench-scale testing of a magnetic ion exchange resin for removal of disinfection by-product precursors

The objective of this research was to compare enhanced coagulation with anion exchange for removal of disinfection by-product (DBP) precursors (i.e. natural organic matter (NOM) and bromide). Treatment with a magnetic ion exchange resin (MIEX((R))) was the primary focus of this study. Raw waters from four utilities in California were evaluated. The waters had low turbidity, low to moderate organic carbon concentrations, a wide range of alkalinities, and moderate to high bromide ion concentrations. The treated waters were compared based on removal of ultraviolet (UV) absorbance, dissolved organic carbon (DOC), trihalomethane formation potential (THMFP), and haloacetic acid formation potential (HAAFP). The results indicated that treatment with MIEX is more effective than coagulation at removing UV-absorbing substances and DOC. Treatment with MIEX and treatment with MIEX followed by coagulation yielded similar results, suggesting that coagulation of MIEX-treated water does not provide additional removal of organic carbon. MIEX treatment reduced the THMFP and HAAFP in all waters, and did so to a greater extent than coagulation. Treatment with MIEX was most effective in raw waters having a high specific UV absorbance and a low anionic strength. Following MIEX treatment, subsequent chlorination resulted in a shift to the more brominated THM and HAA species as compared to chlorination of the raw water. MIEX also removed bromide to varying degrees, depending on the raw water alkalinity and initial bromide ion concentration.