ABSTRACT
Photonic cluster states are a resource for quantum computation based solely on single-photon measurements. We use semiconductor quantum dots to deterministically generate long strings of polarization-entangled photons in a cluster state by periodic timed excitation of a precessing matter qubit. In each period, an entangled photon is added to the cluster state formed by the matter qubit and the previously emitted photons. In our prototype device, the qubit is the confined dark exciton, and it produces strings of hundreds of photons in which the entanglement persists over five sequential photons. The measured process map characterizing the device has a fidelity of 0.81 with that of an ideal device. Further feasible improvements of this device may reduce the resources needed for optical quantum information processing.
ABSTRACT
Seizures affect each patient differently, so personalization is a vital part of developing a reliable nonEEG based seizure detection system. This personalization must be done while the patient is undergoing video EEG monitoring in an epilepsy monitoring unit (EMU) because seizure detection by EEG is considered to be the ground truth. We propose the use of confidence interval analysis for determining how many seizures must be captured from a patient before we can reliably personalize such a seizure detection system for him/her. Our analysis indicates that 6 to 8 seizures are required. In addition, we create seizure likelihood tables for future use by said system by comparing the number of times a prespecified biosignal activity level is induced by seizure to the total number of occurrences of that level of activity. We focus on complex partial seizures in this paper because they are more difficult to detect than are generalized seizures.
Subject(s)
Epilepsies, Partial/diagnosis , Precision Medicine/methods , Electroencephalography , Humans , Probability , Video RecordingABSTRACT
Single signal seizure detection algorithms suffer from high false positive rates. We have found a set of signals which can be easily monitored by a wristworn device and which produce a distinctive pattern during seizure for patients in an epilepsy monitoring unit (EMU). This pattern is much less likely to be reproduced by nonseizure events in the patient's daily life than are changes in heart rate alone. We collected 108 hours of data from three EMU patients who suffered a combined total of seven seizures, then developed a time series analysis/pattern recognition based algorithm which distinguishes the seizures from nonseizure events with 100% accuracy.
Subject(s)
Algorithms , Biosensing Techniques/methods , Epilepsy/diagnosis , Heart Rate , Monitoring, Physiologic/methods , Epilepsy/physiopathology , Humans , Monitoring, Physiologic/instrumentationABSTRACT
EEG based monitoring for the purpose of assessing a patient's neurological status is conspicuous and uncomfortable at best. We are analyzing a set of physiological signals that may be monitored comfortably by a wrist worn device. We have found that these signals and machine based classification allows us to accurately discriminate among four stress states of individuals. Further, we have found a clear change in these signals during the 70 minutes preceding a single convulsive epileptic seizure. Our classification accuracy on all data has been greater than 90% to date.
Subject(s)
Epilepsy/physiopathology , Electroencephalography , Epilepsy/diagnosis , Epilepsy/psychology , Humans , Monitoring, Physiologic , Sensitivity and Specificity , Stress, Physiological , Stress, Psychological/diagnosis , Stress, Psychological/physiopathology , WristABSTRACT
A computer-aided drug design strategy leads to the identification of a new class of p38 inhibitors based on the 2-tolyl-(1,2,3-triazol-1-yl-4-carboxamide) scaffold. The tolyl triazole amides provided a potent platform amenable to optimization. Further exploration leads to compounds with greater than 100-fold improvement in binding affinity to p38. Derivatives prepared to alter the physicochemical properties produced inhibitors with IC(50)'s in human whole blood as low as 83 nM.
Subject(s)
Drug Design , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Triazoles/chemical synthesis , Triazoles/pharmacology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Binding Sites , Computer-Aided Design , Enzyme Inhibitors/blood , Enzyme Inhibitors/chemistry , Humans , Inhibitory Concentration 50 , Molecular Structure , Structure-Activity Relationship , Triazoles/blood , Triazoles/chemistryABSTRACT
Optimization of pyrazinoindolone inhibitors of MAPKAP-K2 (MK2) provides a reasonable balance of cellular potency and physicochemical properties. Mechanistic studies support the inhibition of MK2 which is responsible for the sub-micromolar cellular efficacy.
Subject(s)
Combinatorial Chemistry Techniques , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Indoles/chemical synthesis , Indoles/pharmacology , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Protein Serine-Threonine Kinases/antagonists & inhibitors , Pyrazoles/chemical synthesis , Pyrazoles/pharmacology , Enzyme Inhibitors/chemistry , Indoles/chemistry , Inhibitory Concentration 50 , Molecular Structure , Pyrazoles/chemistry , Structure-Activity RelationshipABSTRACT
Total resection of a massive osteochondroma situated in the posteromedial part of proximal humeral shaft was achieved via an extended deltopectoral approach. We discuss the surgical approach to the posteromedial part of the proximal humeral diaphysis by type of lesion to operate.
Subject(s)
Bone Neoplasms/surgery , Dissection/methods , Humerus , Osteochondroma/surgery , Osteotomy/methods , Adult , Bone Neoplasms/diagnosis , Diaphyses , Female , Humans , Magnetic Resonance Imaging , Osteochondroma/diagnosis , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
We report a case of radial palsy of the Frohse arcade type with complete motor deficit due to compression of the posterior interosseous nerve by a fibrous bands in the radial tunnel proximal to the arcade. Simple neurolysis of the posterior interosseous nerve with section of the compressing fibrous bands allowed complete recovery of the motor deficit. We discuss the surgical technique based on our experience with this case and earlier reports in the literature.
Subject(s)
Radial Neuropathy/surgery , Adult , Humans , Male , Radial Neuropathy/complicationsABSTRACT
Higher self-efficacy (SE) is associated with lower pain ratings in chronic pain patients, although longer experience with chronic pain leads to lower SE scores. Self-efficacy in pain patients does not appear to be clearly related to sex or age, however. This study investigated the effects of gender, age, length of pain experience (chronicity) on SE and pain ratings. Archival data from the records of 187 patient's charts were evaluated for demographic information, chronicity, pain ratings and SE. Analyses found a significant inverse relationship between SE and pain ratings (r = -.22) and lower SE for young adult patients. Results support the conclusion that enhanced SE is an important psychosocial intervention in the treatment of chronic pain patients.
ABSTRACT
PURPOSE: To determine the presence and localization of apolipoprotein A-I, a marker for high density lipoprotein, and apolipoprotein B, a marker for low density lipoprotein, in human cornea; to examine the relationship of these lipoprotein markers with areas of lipid accumulation in the cornea. METHODS: A-I and B apolipoproteins were localized in frozen sections of human corneas with specific monoclonal antibodies using avidin-biotin immunoperoxidase labelling. Corneal lipid was colocalized with apolipoproteins by oil red 0 staining of immunostained sections. RESULTS: Staining data showed that apolipoprotein B and lipid accumulated in the extracellular spaces of peripheral corneal stroma. However, their distributions were not coincident. The posterior region of peripheral corneal stroma (including Descemet's membrane) often contained lipid without immunodetectable apolipoprotein B. Unexpectedly, apolipoprotein A-I was associated with many keratocytes throughout the cornea in addition to an extracellular distribution heaviest in peripheral cornea. CONCLUSIONS: Lipid deposits lacking apolipoprotein B in peripheral cornea suggest that if accumulated corneal arcus lipid is derived from extracellular deposition of plasma low density lipoprotein, the low density lipoprotein is altered such that it looses its immunoreactive apolipoprotein B. The unexpected association of apolipoprotein A-I with keratocytes suggests that these cells are either taking up or synthesizing a protein sharing an immunoreactive epitope with apolipoprotein A-I.
Subject(s)
Apolipoprotein A-I/analysis , Apolipoproteins B/analysis , Cornea/chemistry , Aged , Aged, 80 and over , Antibodies, Monoclonal , Biomarkers , Humans , Immunoenzyme Techniques , Lipids/analysis , Lipoproteins, HDL/analysis , Lipoproteins, LDL/analysisABSTRACT
Anterior corneal dystrophies involving Bowman's membrane and anterior stroma include several subtypes of uncertain etiology: the Reis-Bückler, Thiel-Behnke, Grayson-Wilbrandt, and "honeycomb" dystrophies. The clinical and pathologic features of these dystrophies overlap to such a degree that they may represent variations of the same entity. Typically, they all present symptoms beginning in childhood, have a dominant pattern of heredity, and manifest painful, recurrent corneal erosions. Some cases have also been interpreted as representing macular and granular dystrophy. In the present report, we describe a pedigree of affected patients whose corneal dystrophy shared many of the clinical and pathologic features of the Reis-Bücklers and allied subtypes but which differ from all in causing visual symptoms late in life and with minimal signs of recurrent erosion. Histopathology revealed a thickening of the anterior stroma by the addition of a partially disorganized and degenerating tissue in which collagen Type III (fetal or repair collagen) is intermixed with the normal (mature) Type I collagen in the entire stroma. This is accompanied by irregular swelling of the basal epithelial cells and hyperplasia of the basement membrane (collagen Type IV, laminin and fibronectin), suggesting an aberrant influence of the epithelium on collagen synthesis.
Subject(s)
Collagen Diseases/genetics , Collagen/ultrastructure , Corneal Dystrophies, Hereditary/genetics , Aged , Collagen Diseases/pathology , Corneal Dystrophies, Hereditary/pathology , Corneal Stroma/ultrastructure , Epithelium/ultrastructure , Female , Humans , Male , Microscopy, Fluorescence , Middle Aged , PedigreeABSTRACT
Deficiency of lecithin:cholesterol acyltransferase, LCAT disease, is one of the dyslipoproteinemias with characteristic lipid deposits in the cornea. The present report documents the clinicopathologic abnormalities of one case in which a full-thickness corneal specimen was obtained at the time of corneal transplantation. The characteristic clinical abnormality was a progressive corneal opacification with a peripheral arcus that extended into the sclera. The pathologic abnormality consisted of vacuoles prevalent in the anterior corneal stroma by light microscopy and containing extracellular, membranous deposits by electron microscopy. These observations confirm and supplement the previous six pathologic reports of corneal changes in LCAT disease and demonstrate, for the first time, histopathologic evidence of unesterified cholesterol in the corneal stroma of LCAT disease.
Subject(s)
Corneal Opacity/pathology , Lecithin Cholesterol Acyltransferase Deficiency/pathology , Corneal Stroma/pathology , Corneal Transplantation , Female , Humans , Middle Aged , Vacuoles/pathologySubject(s)
Awards and Prizes , Ophthalmology , Florida , History, 20th Century , Minnesota , Ophthalmology/history , Societies, ScientificABSTRACT
Monkeys made hemiparkinsonian by infusion of a solution of MPTP into one carotid artery appeared to ignore food presented from the contralateral side. Initial observations suggested neglect of visual stimuli presented as fruit treats by automated delivery system in the half-field contralateral to MPTP treatment. Further studies in which fruit treats were left in the 'neglected' visual field indicated that this apparent neglect, unlike neglect attending cortical lesions, was rather a marked delay in initiating movements (unilateral hypokinesia). These observations may explain apparent subcortical neglect and are consistent with the known role of nigrostriatal dopaminergic neurones in movement regulation. This is a useful animal model in which difficulties in initiation of movement (hypokinesia). a cardinal symptom of Parkinson's disease, can be studied separately from other deficits in motor performance.
Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Attention , Motor Activity/physiology , Parkinson Disease, Secondary/psychology , Visual Perception/physiology , Animals , Behavior, Animal/physiology , Female , Levodopa/pharmacology , Macaca fascicularis , Macaca mulatta , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/physiopathology , Reaction TimeABSTRACT
A 72-year-old woman developed recurrent blindness on exposure to bright light (sunlight). Examination revealed total achromatopsia; bilateral central scotomas, predominant suppression of the cone response by electroretinography, and narrowing of the retinal arteries on ophthalmoscopy. The general examination revealed a pelvic tumor that later proved to be a pleomorphic carcinoma of presumed uterine origin. The patient died of metastatic disease 9 months after the ocular symptoms developed. Histopathologic examination of the eyes revealed loss of the photoreceptors, most extensive in the macular regions, and selective loss of the cones from the rest of the retinas. No ocular metastases of inflammation were found. The changes described are interpreted as paraneoplastic retinopathy of autoimmune origin.
Subject(s)
Autoimmune Diseases/immunology , Paraneoplastic Syndromes/pathology , Photoreceptor Cells/pathology , Retinal Degeneration/pathology , Uterine Neoplasms/pathology , Aged , Autoantibodies/analysis , Female , Humans , Microscopy, Electron , Pigment Epithelium of Eye/pathology , Retina/immunologyABSTRACT
Analysis of the neurologic symptomatology in 22 patients with Niemann-Pick disease type C revealed 3 phenotypes: (1) an early-onset, rapidly progressive form associated with severe hepatic dysfunction and psychomotor delay during infancy and later with supranuclear vertical gaze paresis, ataxia, marked spasticity, and dementia; (2) a delayed-onset, slowly progressive form heralded by the appearance, usually in early childhood, of mild intellectual impairment, supranuclear vertical gaze paresis, and ataxia, and later associated with dementia and, variably, seizures and extrapyramidal deficits; (3) a late-onset slowly progressive form distinguished from the 2nd pattern by later age of onset (adolescence or adulthood) and a much slower rate of progression. The existence of the 1st and 2nd phenotypes within the same sibship suggests that they are variant expressions of the same clinicopathologic disorder. Niemann-Pick disease type C should be considered not only in infants and children who present with organomegaly and a progressive neurodegenerative course, but also in adolescents and adults who have insidiously progressive neurologic dysfunction and only slight organomegaly. Associated with the disease is a marked deficiency in the ability of cultured fibroblasts to esterify exogenously supplied cholesterol. Assay of this deficiency is particularly useful for confirming the diagnosis in patients with atypical presentation.
Subject(s)
Niemann-Pick Diseases/classification , Adolescent , Adult , Age Factors , Child , Child, Preschool , Electroencephalography , Female , Humans , Infant , Male , Niemann-Pick Diseases/diagnosis , Niemann-Pick Diseases/genetics , PhenotypeABSTRACT
Proliferative interstitial pneumonia of undetermined cause was diagnosed in 2 dogs. The clinical signs in both dogs consisted primarily of acute onset, rapid breathing, and raspy lung sounds. Radiography revealed a diffuse increase in pulmonary alveolar density. In both dogs, the primary pathologic process was diffuse alveolar pneumocyte injury, and the pulmonary lesions were similar. Proliferation of type II pneumocytes (some of which were atypical mononucleated, and others multinucleated) was a prominent feature of the interstitial pneumonia. Because of the atypical features of some pneumocytes in such cases, biopsy findings may suggest a neoplastic process. Proliferative interstitial pneumonia should be included in the differential diagnosis of a diffuse pulmonary disease that is poorly responsive to medical treatment.