Fabrication of Nano-Scale Gaps in Integrated Circuits

Nano-size objects like metal clusters present an ideal system for the study of quantum phenomena and for constructing practical quantum devices. Integrating these small objects in a macroscopic circuit is, however, a difficult task. So far the nanoparticles have been contacted and addressed by highly sophisticated techniques which are not suitable for large scale integration in macroscopic circuits. We present an optical lithography method that allows for the fabrication of a network of electrodes which are separated by gaps of controlled nanometer size. The main idea is to control the gap size with subnanometer precision using a structure grown by molecular beam epitaxy.Comment: 4 pages, 3 figure

AUG sequences are required to sustain nonsense-codon-mediated suppression of splicing

More than 90% of human genes are rich in intronic latent 5′ splice sites whose utilization in pre-mRNA splicing would introduce in-frame stop codons into the resultant mRNAs. We have therefore hypothesized that suppression of splicing (SOS) at latent 5′ splice sites regulates alternative 5′ splice site selection in a way that prevents the production of toxic nonsense mRNAs and verified this idea by showing that the removal of such in-frame stop codons is sufficient to activate latent splicing. Splicing control by SOS requires recognition of the mRNA reading frame, presumably recognizing the start codon sequence. Here we show that AUG sequences are indeed essential for SOS. Although protein translation does not seem to be required for SOS, the first AUG is shown here to be necessary but not sufficient. We further show that latent splicing can be elicited upon treatment with pactamycin—a drug known to block translation by its ability to recognize an RNA fold—but not by treatment with other drugs that inhibit translation through other mechanisms. The effect of pactamycin on SOS is dependent neither on steady-state translation nor on the pioneer round of translation. This effect is found for both transfected and endogenous genes, indicating that SOS is a natural mechanism

Presurgical thalamic hubness predicts surgical outcome in temporal lobe epilepsy.

OBJECTIVE: To characterize the presurgical brain functional architecture presented in patients with temporal lobe epilepsy (TLE) using graph theoretical measures of resting-state fMRI data and to test its association with surgical outcome. METHODS: Fifty-six unilateral patients with TLE, who subsequently underwent anterior temporal lobectomy and were classified as obtaining a seizure-free (Engel class I, n = 35) vs not seizure-free (Engel classes II-IV, n = 21) outcome at 1 year after surgery, and 28 matched healthy controls were enrolled. On the basis of their presurgical resting-state functional connectivity, network properties, including nodal hubness (importance of a node to the network; degree, betweenness, and eigenvector centralities) and integration (global efficiency), were estimated and compared across our experimental groups. Cross-validations with support vector machine (SVM) were used to examine whether selective nodal hubness exceeded standard clinical characteristics in outcome prediction. RESULTS: Compared to the seizure-free patients and healthy controls, the not seizure-free patients displayed a specific increase in nodal hubness (degree and eigenvector centralities) involving both the ipsilateral and contralateral thalami, contributed by an increase in the number of connections to regions distributed mostly in the contralateral hemisphere. Simulating removal of thalamus reduced network integration more dramatically in not seizure-free patients. Lastly, SVM models built on these thalamic hubness measures produced 76% prediction accuracy, while models built with standard clinical variables yielded only 58% accuracy (both were cross-validated). CONCLUSIONS: A thalamic network associated with seizure recurrence may already be established presurgically. Thalamic hubness can serve as a potential biomarker of surgical outcome, outperforming the clinical characteristics commonly used in epilepsy surgery centers

Increased microstructural white matter correlations in left, but not right, temporal lobe epilepsy.

Microstructural white matter tract correlations have been shown to reflect known patterns of phylogenetic development and functional specialization in healthy subjects. The aim of this study was to establish intertract correlations in a group of controls and to examine potential deviations from normality in temporal lobe epilepsy (TLE). We investigated intertract correlations in 28 healthy controls, 21 left TLE (LTLE) and 23 right TLE (RTLE). Nine tracts were investigated, comprising the parahippocampal fasciculi, the uncinate fasciculi, the arcuate fasciculi, the frontoparietal tracts, and the fornix. An abnormal increase in tract correlations was observed in LTLE, while RTLE showed intertract correlations similar to controls. In the control group, tract correlations increased with increasing fractional anisotropy (FA), while in the TLE groups tract correlations increased with decreasing FA. Cluster analyses revealed agglomeration of bilateral pairs of homologous tracts in healthy subjects, with such pairs separated in our LTLE and RTLE groups. Discriminant analyses aimed at distinguishing LTLE from RTLE, revealing that tract correlations produce higher rates of accurate group classification than FA values. Our results confirm and extend previous work by showing that LTLE compared to RTLE patients display not only more extensive losses in microstructural orientation but also more aberrant intertract correlations. Aberrant correlations may be related to pathologic processes (i.e., seizure spread) or to adaptive processes aimed at preserving key cognitive functions. Our data suggest that tract correlations may have predictive value in distinguishing LTLE from RTLE, potentially moving diffusion imaging to a place of greater prominence in clinical practice

Gray Matter Abnormalities in Temporal Lobe Epilepsy: Relationships with Resting-State Functional Connectivity and Episodic Memory Performance.

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is necessary to produce reductions in episodic memory recall. The latter, in particular, demonstrates the complex structure/function interactions at work when trying to understand cognition in TLE, suggesting that subtle network effects can emerge bearing specific relationships to hemisphere and the type of pathology

A test of the role of the medial temporal lobe in single-word decoding.

The degree to which the MTL system contributes to effective language skills is not well delineated. We sought to determine if the MTL plays a role in single-word decoding in healthy, normal skilled readers. The experiment follows from the implications of the dual-process model of single-word decoding, which provides distinct predictions about the nature of MTL involvement. The paradigm utilized word (regular and irregularly spelled words) and pseudoword (phonetically regular) stimuli that differed in their demand for non-lexical as opposed lexical decoding. The data clearly showed that the MTL system was not involved in single word decoding in skilled, native English readers. Neither the hippocampus nor the MTL system as a whole showed significant activation during lexical or non-lexical based decoding. The results provide evidence that lexical and non-lexical decoding are implemented by distinct but overlapping neuroanatomical networks. Non-lexical decoding appeared most uniquely associated with cuneus and fusiform gyrus activation biased toward the left hemisphere. In contrast, lexical decoding appeared associated with right middle frontal and supramarginal, and bilateral cerebellar activation. Both these decoding operations appeared in the context of a shared widespread network of activations including bilateral occipital cortex and superior frontal regions. These activations suggest that the absence of MTL involvement in either lexical or non-lexical decoding appears likely a function of the skilled reading ability of our sample such that whole-word recognition and retrieval processes do not utilize the declarative memory system, in the case of lexical decoding, and require only minimal analysis and recombination of the phonetic elements of a word, in the case of non-lexical decoding

Extratemporal functional connectivity impairments at rest are related to memory performance in mesial temporal epilepsy.

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of focal epilepsy. At rest, there is evidence that brain abnormalities in MTLE are not limited to the epileptogenic region, but extend throughout the whole brain. It is also well established that MTLE patients suffer from episodic memory deficits. Thus, we investigated the relation between the functional connectivity seen at rest in fMRI and episodic memory impairments in MTLE. We focused on resting state BOLD activity and evaluated whether functional connectivity (FC) differences emerge from MTL seeds in left and right MTLE groups, compared with healthy controls. Results revealed significant FC reductions in both patient groups, localized in angular gyri, thalami, posterior cingulum and medial frontal cortex. We found that the FC between the left non-pathologic MTL and the medial frontal cortex was positively correlated with the delayed recall score of a non-verbal memory test in right MTLE patients, suggesting potential adaptive changes to preserve this memory function. In contrast, we observed a negative correlation between a verbal memory test and the FC between the left pathologic MTL and posterior cingulum in left MTLE patients, suggesting potential functional maladaptative changes in the pathologic hemisphere. Overall, the present study provides some indication that left MTLE may be more impairing than right MTLE patients to normative functional connectivity. Our data also indicates that the pattern of extra-temporal FC may vary as a function of episodic memory material and each hemisphere\u27s capacity for cognitive reorganization

Hippocampal functional connectivity patterns during spatial working memory differ in right versus left temporal lobe epilepsy.

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM task. Results revealed that both TLE groups displayed a negative relation between WM performance and FC between the left hippocampus and ipsilateral parahippocampal gyrus. We also found a positive relationship between performance and FC between the left hippocampus seed and the precuneus, in the right TLE group. Lastly, the left TLE specifically demonstrated a negative relationship between performance and FC between both hippocampi and ipsilateral cerebellar clusters. Our findings indicate that right and left TLE groups may develop different patterns of FC to implement visuospatial WM. Indeed, the present result suggests that FC provides a unique means of identifying abnormalities in brain networks, which cannot be discerned at the level of behavioral output through neuropsychological testing. More broadly, our findings demonstrate that FC methods applied to task-based fMRI provide the opportunity to define specific task-related networks