Large-scale integrated quantum photonic technologies will require on-chip integration of identical photon sources with reconfigurable waveguide circuits. Relatively complex quantum circuits have been ...demonstrated already, but few studies acknowledge the pressing need to integrate photon sources and waveguide circuits together on-chip. A key step towards such large-scale quantum technologies is the integration of just two individual photon sources within a waveguide circuit, and the demonstration of high-visibility quantum interference between them. Here, we report a silicon-on-insulator device that combines two four-wave mixing sources in an interferometer with a reconfigurable phase shifter. We configured the device to create and manipulate two-colour (non-degenerate) or same-colour (degenerate) path-entangled or path-unentangled photon pairs. We observed up to 100.0 ± 0.4% visibility quantum interference on-chip, and up to 95 ± 4% off-chip. Our device removes the need for external photon sources, provides a path to increasing the complexity of quantum photonic circuits and is a first step towards fully integrated quantum technologies.
Integrated quantum photonic waveguide circuits are a promising approach to realizing future photonic quantum technologies. Here, we present an integrated photonic quantum technology platform ...utilizing the silicon-on-insulator material system, where quantum interference and the manipulation of quantum states of light are demonstrated in components orders of magnitude smaller than previous implementations. Two-photon quantum interference is presented in a multi-mode interference coupler, and the manipulation of entanglement is demonstrated in a Mach-Zehnder interferometer, opening the way to an all-silicon photonic quantum technology platform.
The specific accumulation of a hydrophobic protein, subunit c of ATP synthase, in lysosomes from the cells of patients with the late infantile form of NCL (LINCL) is caused by a defect in the CLN2 ...gene product, tripeptidyl peptidase I (TPP-I). The data here show that TPP-I is involved in the initial degradation of subunit c in lysosomes and suggest that its absence leads directly to the lysosomal accumulation of subunit c. The inclusion of a specific inhibitor of TPP-I Ala-Ala-Phe-chloromethylketone (AAF-CMK) in the culture medium of normal fibroblasts induced the lysosomal accumulation of subunit c. In an in vitro incubation experiment the addition of AAF-CMK to mitochondrial-lysosomal fractions from normal cells inhibited the proteolysis of subunit c, but not the β-subunit of ATP synthase. The use of two antibodies that recognize the aminoterminal and the middle portion of subunit c revealed that the subunit underwent aminoterminal proteolysis, when TPP-I, purified from rat spleen, was added to the mitochondrial fractions. The addition of both purified Tpp-I and the soluble lysosomal fractions, which contain various proteinases, to the mitochondrial fractions resulted in rapid degradation of the entire molecule of subunit c, whereas the degradation of subunit c was markedly delayed through the specific inhibition of TPP-I in lysosomal extracts by AAF-CMK. The stable subunit c in the mitochondrial-lysosomal fractions from cells of a patient with LINCL was degraded on incubation with purified TPP-I The presence of TPP-I led to the sequential cleavage of tripeptides from the N-terminus of the peptide corresponding to the amino terminal sequence of subunit c.
CTLA-4 is expressed on the surface of activated T cells and negatively regulates T cell activation. Because a low-level expression of CTLA-4 on the cell surface is sufficient to induce negative ...signals in T cells, the surface expression of CTLA-4 is strictly regulated. We previously demonstrated that the association of CTLA-4 with the clathrin-associated adaptor complex AP-2 induces internalization of CTLA-4 and keeps the surface expression low. However, the mechanism to induce high expression on the cell surface upon stimulation has not yet been clarified. To address this, we investigated the intracellular dynamics of CTLA-4 by analyzing its localization and trafficking in wild-type and mutant CTLA-4-transfected Th1 clones. CTLA-4 is accumulated in intracellular granules, which we identified as lysosomes. CTLA-4 is degraded in lysosomes in a short period, and the degradation process may serve as one of the mechanisms to regulate CTLA-4 expression. Upon TCR stimulation, CTLA-4-containing lysosomes are secreted as proven by the secretion of cathepsin D and beta-hexosaminidase in parallel with the increase of surface expression of CTLA-4 and lysosomal glycoprotein 85, a lysosomal marker. These results suggest that the cell surface expression of CTLA-4 is up-regulated upon stimulation by utilizing a mechanism of secretory lysosomes in CD4(+)T cells.
There are good options to maximize upper limb function for the child with arthrogryposis. Preservation of available elbow and wrist motion is essential. A comprehensive plan for upper limb treatment ...includes operative and nonoperative care.
Because determination of neurologic integrity after severe limb trauma is crucial in patient care, the authors assessed magnetic resonance (MR) imaging as a tool to map denervated motor units of ...skeletal muscle in patients with traumatic peripheral neuropathy. Denervation was confirmed in 22 patients with use of electromyography, surgery, or both. MR imaging was performed with moderately T1- and T2-weighted spin-echo and short-tau inversion-recovery (STIR) sequences. MR imaging was unreliable in depicting acute denervation. Muscles of patients with subacute denervation had prolonged T1 and T2, which contributed to conspicuous hyperintensity on STIR images. Chronically denervated muscles showed marked atrophy, variable changes on STIR images, and conspicuous fatty infiltration on T1-weighted images. Normal variants in motor unit anatomy were seen in denervated muscle volumes outside the expected distribution of the injured nerve. MR imaging is promising for the noninvasive mapping and monitoring of denervated muscle in subacute and chronic phases of peripheral neuropathy.
Glenoid dysplasia and posterior shoulder subluxation with resultant shoulder stiffness is a well-recognized complication in infants with neonatal brachial plexus palsy. It is generally considered to ...be the result of a slowly progressive glenohumeral deformation secondary to muscle imbalance, physeal trauma, or both. Recent publications about infantile posterior shoulder dislocation have suggested that the onset of dysplasia occurs at an earlier age than has been previously recognized. The prevalence of early dislocation in infants with this disorder has not been previously reported, to our knowledge.
We studied 134 consecutive infants with neonatal brachial plexus palsy who were seen at our institution over a period of two years. All infants were examined at monthly intervals to assess neurological recovery and the status of the upper extremity until recovery occurred or a treatment plan was established. The type of brachial plexus involvement was classified. Specific clinical signs associated with subluxation and dislocation were recorded. These included asymmetry of skin folds of the axilla or the proximal aspect of the arm, apparent shortening of the humeral segment, a palpable asymmetric fullness in the posterior region of the shoulder, or a palpable click during shoulder manipulation. The infants who were identified as having these clinical signs were evaluated with ultrasonographic imaging studies.
Eleven (8%) of the 134 infants had a posterior shoulder dislocation. The mean age at the time of diagnosis was six months (range, three to ten months). There was no correlation between the occurrence of dislocation and the type of initial neurological deficit. A rapid loss of passive external rotation between monthly examinations indicated a posterior shoulder dislocation.
Posterior shoulder dislocation can occur earlier (before the age of one year) and more rapidly in infants with neonatal brachial plexus palsy than has been appreciated previously. As with developmental dysplasia of the hip, a high index of suspicion, recognition of clinical signs, and the use of ultrasonography will allow the diagnosis to be established. Following early diagnosis, attention should be focused on improving the stability and congruency of the shoulder joint.
Oxidative modification of LDL plays an important role in early atherogenesis but the mechanisms, nonenzymatic and/or enzymatic, by which LDL is oxidized in vivo remain to be established. Several ...lines of evidence suggest that cellular 15-lipoxygenase (arachidonate 15-oxidoreductase, EC.1.13.11.13) (15-LO) may contribute to oxidative modification of LDL, including recent studies demonstrating that murine fibroblasts overexpressing 15-LO have an enhanced capacity to oxidize LDL in the medium. The present studies were undertaken to better understand the mechanisms by which cells expressing 15-LO bring about oxidative modification of LDL. LDL incubated 1-2 h with the 15-LO-enriched cells showed a much higher lipoperoxide (LOOH) content than did LDL incubated with control cells. By far the largest absolute increase occurred in cholesteryl ester hydroperoxide (CE-OOH), a much lesser increase in free fatty acid hydroperoxides (FFA-OOH), and only a very small increase in phospholipid hydroperoxides (PL-OOH). Addition of EDTA to the medium abolished these increases in LDL lipid hydroperoxides. Enrichment of LDL with probucol or vitamin E also prevented CE-OOH accumulation. Incubation of LDL with linoleic acid hydroperoxide in the absence of cells also caused a significant increase in CE-OOH and this was markedly inhibited by EDTA. These findings provide further evidence for the potential of 15-LO to participate in LDL oxidation by way of a mechanism involving introduction of LOOH into the LDL particle followed by metal-catalyzed propagation.
An important prognostic factor in neonatal brachial plexus palsy is the time interval to biceps muscle recovery. Although the natural history is not clear, biceps muscle recovery after more than ...three months of age has been used to predict poor long-term shoulder function. The absence of biceps muscle function at three months of age has been adopted as an indication for early brachial plexus microsurgery, in an attempt to improve recovery. To provide a benchmark for outcome comparison, the long-term outcome of patients with absent biceps muscle function at three months of age was studied.
Between 1980 and 1992, 170 patients with neonatal brachial plexus palsy were entered into a prospective study in which details of the birth and serial clinical examinations were recorded. Patients were grouped according to the level of injury and the time interval to biceps muscle recovery. Twenty-nine patients were observed to have absent biceps muscle function at three months of age. Twenty-eight of those patients were available for long-term followup at a mean age of eleven years and one month. At the time of follow-up, patients answered a questionnaire and underwent manual muscle strength testing, sensory evaluation, and grading of their shoulder function according to Gilbert's modification of the Mallet score, in which the function was graded as II, III, or IV with class I (no function) and V (normal) eliminated. The level of injury and the time that biceps muscle function returned were compared with the final outcomes.
The level of injury was C5-C6 in thirteen (46%) of our twenty-eight patients with absent biceps muscle function at three months of age, C5-C7 in five (18%), and pan-plexus (C5-T1) in ten (36%). Biceps contraction was observed by six months of age in twenty patients (71%), including all thirteen patients with a C5-C6 level of injury. Twenty-two patients did not have surgery on the brachial plexus, but nine of those patients had subsequent orthopaedic procedures. At the time of follow-up, twenty-seven of the twenty-eight patients had at least antigravity biceps muscle function. Patients who regained biceps muscle function between three and six months of age had better scores for abduction (p = 0.04) and for hand-to-neck (p = 0.05) and hand-to-back (p < 0.001) function than did patients who regained biceps muscle function after six months of age. Patients with a C5-C6 lesion had better scores for external rotation (p = 0.04) and for hand-to-neck (p = 0.05), hand-to-mouth (p < 0.01), and hand-to-back (p < 0.001) function than did patients with a pan-plexus lesion. Twelve (55%) of the twenty-two patients who did not have brachial plexus surgery had a class-IV shoulder (good function) according to the modified Mallet score. Of the twelve patients with a C5-C6 level of injury who did not have brachial plexus surgery, eight had a class-IV shoulder.
This study indicated associations between prolonged neurological recovery and a more extensive level of injury and worse long-term shoulder function. Patients with a C5-C6 injury and absent biceps muscle function at three months of age often have good long-term shoulder function without brachial plexus surgery.
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