DNA purification using dynamic solid-phase extraction on a rotationally-driven polyethylene-terephthalate microdevice.

We report the development of a disposable polyester toner centrifugal device for semi-automated, dynamic solid phase DNA extraction (dSPE) from whole blood samples. The integration of a novel adhesive and hydrophobic valving with a simple and low cost microfabrication method allowed for sequential addition of reagents without the need for external equipment for fluid flow control. The spin-dSPE method yielded an average extraction efficiency of ∼45% from 0.6 µL of whole blood. The device performed single sample extractions or accommodate up to four samples for simultaneous DNA extraction, with PCR-readiness DNA confirmed by effective amplification of a ß-globin gene. The purity of the DNA was challenged by a multiplex amplification with 16 targeted amplification sites. Successful multiplexed amplification could routinely be obtained using the purified DNA collected post an on-chip extraction, with the results comparable to those obtained with commercial DNA extraction methods. This proof-of-principle work represents a significant step towards a fully-automated low cost DNA extraction device.

Genetic mapping of brain plasticity across development in Williams syndrome: ERP markers of face and language processing.

In Williams Syndrome (WS), a known genetic deletion results in atypical brain function with strengths in face and language processing. We examined how genetic influences on brain activity change with development. In three studies, event-related potentials (ERPs) from large samples of children, adolescents, and adults with the full genetic deletion for WS were compared to typically developing controls, and two adults with partial deletions for WS. Studies 1 and 2 identified ERP markers of brain plasticity in WS across development. Study 3 suggested that, in adults with partial deletions for WS, specific genes may be differentially implicated in face and language processing.

Itinerant nature of atom-magnetization excitation by tunneling electrons.

We have performed single-atom magnetization curve (SAMC) measurements and inelastic scanning tunneling spectroscopy (ISTS) on individual Fe atoms on a Cu(111) surface. The SAMCs show a broad distribution of magnetic moments with 3.5 µB being the mean value. ISTS reveals a magnetization excitation with a lifetime of 200 fsec which decreases by a factor of 2 upon application of a magnetic field of 12 T. The experimental observations are quantitatively explained by the decay of the magnetization excitation into Stoner modes of the itinerant electron system as shown by newly developed theoretical modeling.

Dynamical magnetic excitations of nanostructures from first principles.

Within time-dependent density functional theory, combined with the Korringa-Kohn-Rostoker Green functions, we devise a real space method to investigate spin dynamics. Our scheme enables one to deduce the Coulomb potential which assures a proper Goldstone mode is present. We illustrate with application to 3d adatoms and dimers on Cu(100).

Viewing the interior of a single molecule: vibronically resolved photon imaging at submolecular resolution.

We report the spatial imaging of the photon transition probability of a single molecule at submolecular resolution. Photon imaging of a ringlike pattern is further resolved as two orthogonal vibronic transitions after incorporating spectral selectivity. A theoretical model and the calculated intensity images reveal that the transition probability is dominated by the symmetry of the positions of the tip and the transition dipole moment. This imaging technique enables the probing of the electronic and optical properties in the interior of a single molecule.

Laser-induced forces in metallic nanosystems: the role of plasmon resonances.

We present calculations of the laser-induced force between metallic nanospheres, similar and dissimilar in character, and that between a metallic nanosphere and a planar surface. When the separation between these objects is in the 0.5-2 nm range, we find very strong resonances in the laser-induced force associated with excitation of plasmon resonances. Measurement of such forces will provide direct access to the plasmon enhancements of laser fields so critical to optical spectroscopy in the nanoenvironment.

The neurobiology of Williams syndrome: cascading influences of visual system impairment?

Williams syndrome (WS) is characterized by a unique pattern of cognitive, behavioral, and neurobiological findings that stem from a microdeletion of genes on chromosome 7. Visuospatial ability is particularly affected in WS and neurobiological studies of WS demonstrate atypical function and structure in posterior parietal, thalamic, and cerebellar regions that are important for performing space-based actions. This review summarizes the neurobiological findings in WS, and, based on these findings, we suggest that people with WS have a primary impairment in neural systems that support the performance of space-based actions. We also examine the question of whether impaired development of visual systems could affect the development of atypical social-emotional and language function in people with WS. Finally, we propose developmental explanations for the visual system impairments in WS. While hemizygosity for the transcription factor II-I gene family probably affects the development of visual systems, we also suggest that Lim-kinase 1 hemizygosity exacerbates the impairments in performing space-based actions.

Ground state of magnetic dimers on metal surfaces.

We present model studies of the ground state for magnetic dimers on metal surfaces. We find it can be neither ferromagnetic nor antiferromagnetic, but is often canted for nearest neighbors. Thus, the system cannot be described using bilinear exchange. We give a criterion which can be used quite generally to interrogate the local stability of ferromagnetically or antiferromagnetically aligned dimers, and which also may be used to infer the canting angle when canted states are stable.

T(3/2) dependence of the interlayer exchange coupling in ferromagnetic multilayers.

The temperature dependence of the interlayer exchange coupling in ferromagnetic films coupled across nonmagnetic spacers is determined via in situ ferromagnetic resonance experiments for various systems. Clear evidence for a T(3/2) law is found over a wide temperature regime.

III. Electrophysiological studies of face processing in Williams syndrome.

Williams Syndrome (WMS) is a genetically based disorder characterized by pronounced variability in performance across different domains of cognitive functioning. This study examined brain activity linked to face-processing abilities, which are typically spared in individuals with WMS. Subjects watched photographic pairs of upright or inverted faces and indicated if the second face matched or did not match the first face. Results from a previous study with normal adults showed dramatic differences in the timing and distribution of ERP effects linked to recognition of upright and inverted faces. In normal adults, upright faces elicited ERP differences to matched vs. mismatched faces at approximately 320 msec (N320) after the onset of the second stimulus. This "N320" effect was largest over anterior regions of the right hemisphere. In contrast, the mismatch/match effect for inverted faces consisted of a large positive component between 400 and 1000 msec (P500) that was largest over parietal regions and was symmetrical. In contrast to normal adults, WMS subjects showed an N320-mismatch effect for both upright and inverted faces. Additionally, the WMS subjects did not display the N320 right-hemisphere asymmetry observed in the normal adults. WMS subjects also displayed an abnormally small negativity at 100 msec (N100) and an abnormally large negativity at 200 msec (N200) to both upright and inverted faces. This ERP pattern was observed in all subjects with WMS but was not observed in the normal controls. These results may be linked to increased attention to faces in subjects with WMS and might be specific to the disorder. These results were consistent with our ERP studies of language processing in WMS, which suggested abnormal cerebral specialization for spared cognitive functions in individuals with WMS.

Electrophysiological studies of language and language impairment.

The organization of language-relevant brain systems was examined in normally developing and language-impaired children. Atypical patterns of brain activity were observed in subsets of children with specific language impairment (SLI) for both sensory (auditory and visual) and language processing. However, it was not the same groups of children who displayed abnormalities across the different tasks. The results supported a multiple-factors and multiple-subtypes framework for interpreting the neurobiology of SLI. The roots of SLI were also considered in normal infants and late talkers in studies of primary language acquisition. These studies suggest that the organization of neural systems important in language acquisition display dramatic changes during this time. Some of these are linked to the attainment of language milestones and appear to be independent of chronological age. Moreover, abnormalities in the lateral organization of electrophysiological activity may help predict which late talkers will catch up and who will later display SLI. More generally, the event-related potential technique is a powerful tool in studying the neurobiology of language and language impairment.

Language acquisition and cerebral specialization in 20-month-old infants.

Abstract The purpose of the present study was to examine patterns of neural activity relevant to language processing in 20-month-old infants, and to determine whether or not changes in cerebral organization occur as a function of specific changes in language development. Event-related potentials (ERPs) were recorded as children listened to a series of words whose meaning was understood by the child, words whose meaning the child did not understand, and backward words. The results showed that specific and different ERP components discriminated comprehended words from unknown and from backward words. Distinct lateral and anterior-posterior specializations were apparent in EW responsiveness to the different types of words. Moreover, the results suggested that increasing language abilities were associated with increasing cerebral specialization for language processing over the temporal and parietal regions of the left hemisphere.

Fractionating language: different neural subsystems with different sensitive periods.

Theoretical considerations and psycholinguistic studies have alternatively provided criticism and support for the proposal that semantic and grammatical functions are distinct subprocesses within the language domain. Neurobiological evidence concerning this hypothesis was sought by (1) comparing, in normal adults, event-related brain potentials (ERPs) elicited by words that provide primarily semantic information (open class) and grammatical information (closed class) and (2) comparing the effects of the altered early language experience of congenitally deaf subjects on ERPs to open and closed class words. In normal-hearing adults, the different word types elicited qualitatively different ERPs that were compatible with the hypothesized different roles of the word classes in language processing. In addition, whereas ERP indices of semantic processing were virtually identical in deaf and hearing subjects, those linked to grammatical processes were markedly different in deaf and hearing subjects. The results suggest that nonidentical neural systems with different developmental vulnerabilities mediate these different aspects of language. More generally, these results provide neurobiological support for the distinction between semantic and grammatical functions.

Analysis of breast cancer screening in women younger than 50 years.

The five-year screening experience for 10,128 asymptomatic women whose conditions were evaluated at the Louisville Breast Cancer Detection Demonstration Project disclosed 163 breast carcinomas in women aged 35 to 74 years. Thirty-four percent of patients with proved carcinoma were younger than 50 years; 31% with infiltrating carcinoma had axillary metastases at the time of diagnosis. In younger patients, carcinomas disclosed at intervals between scheduled screenings were more commonly metatastic. Minimal breast cancer was more prevalent in the screened population (29%) than the unscreened population (less than 5%), and appeared with similar frequency in screenees of each age category. Screening women younger than 50 years allow earlier diagnosis and treatment of breast cancer in a favorable stage that is comparable with that noted in the older screenees.