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1.
Nature ; 558(7708): 60-67, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29875487

RESUMEN

Neural-network training can be slow and energy intensive, owing to the need to transfer the weight data for the network between conventional digital memory chips and processor chips. Analogue non-volatile memory can accelerate the neural-network training algorithm known as backpropagation by performing parallelized multiply-accumulate operations in the analogue domain at the location of the weight data. However, the classification accuracies of such in situ training using non-volatile-memory hardware have generally been less than those of software-based training, owing to insufficient dynamic range and excessive weight-update asymmetry. Here we demonstrate mixed hardware-software neural-network implementations that involve up to 204,900 synapses and that combine long-term storage in phase-change memory, near-linear updates of volatile capacitors and weight-data transfer with 'polarity inversion' to cancel out inherent device-to-device variations. We achieve generalization accuracies (on previously unseen data) equivalent to those of software-based training on various commonly used machine-learning test datasets (MNIST, MNIST-backrand, CIFAR-10 and CIFAR-100). The computational energy efficiency of 28,065 billion operations per second per watt and throughput per area of 3.6 trillion operations per second per square millimetre that we calculate for our implementation exceed those of today's graphical processing units by two orders of magnitude. This work provides a path towards hardware accelerators that are both fast and energy efficient, particularly on fully connected neural-network layers.

2.
Int J Mol Sci ; 23(3)2022 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-35163411

RESUMEN

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.


Asunto(s)
Materiales Biocompatibles/química , Materiales Biomiméticos/química , Hidrogeles/química , Oligopéptidos/química , Poloxámero/química , Animales , Evaluación Preclínica de Medicamentos , Humanos , Células MCF-7 , Ratones , Células 3T3 NIH
3.
Faraday Discuss ; 213(0): 371-391, 2019 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-30357183

RESUMEN

Hardware accelerators based on two-terminal non-volatile memories (NVMs) can potentially provide competitive speed and accuracy for the training of fully connected deep neural networks (FC-DNNs), with respect to GPUs and other digital accelerators. We recently proposed [S. Ambrogio et al., Nature, 2018] novel neuromorphic crossbar arrays, consisting of a pair of phase-change memory (PCM) devices combined with a pair of 3-Transistor 1-Capacitor (3T1C) circuit elements, so that each weight was implemented using multiple conductances of varying significance, and then showed that this weight element can train FC-DNNs to software-equivalent accuracies. Unfortunately, however, real arrays of emerging NVMs such as PCM typically include some failed devices (e.g., <100% yield), either due to fabrication issues or early endurance failures, which can degrade DNN training accuracy. This paper explores the impact of device failures, NVM conductances that may contribute read current but which cannot be programmed, on DNN training and test accuracy. Results show that "stuck-on" and "dead" devices, exhibiting high and low read conductances, respectively, do in fact degrade accuracy performance to some degree. We find that the presence of the CMOS-based and thus highly-reliable 3T1C devices greatly increase system robustness. After studying the inherent mechanisms, we study the dependence of DNN accuracy on the number of functional weights, the number of neurons in the hidden layer, and the number and type of damaged devices. Finally, we describe conditions under which making the network larger or adjusting the network hyperparameters can still improve the network accuracy, even in the presence of failed devices.

4.
Small ; 14(1)2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29194973

RESUMEN

Perovskite quantum dots (PQDs) attract significant interest in recent years because of their unique optical properties, such as tunable wavelength, narrow emission, and high photoluminescence quantum efficiency (PLQY). Recent studies report new types of formamidinium (FA) PbBr3 PQDs, PQDs with organic-inorganic mixed cations, divalent cation doped colloidal CsPb1-x Mx Br3 PQDs (M = Sn2+ , Cd2+ , Zn2+ , Mn2+ ) featuring partial cation exchange, and heterovalent cation doped into PQDs (Bi3+ ). These PQD analogs open new possibilities for optoelectronic devices. For commercial applications in lighting and backlight displays, stability of PQDs requires further improvement to prevent their degradation by temperature, oxygen, moisture, and light. Oxygen and moisture-facilitated ion migration may easily etch unstable PQDs. Easy ion migration may result in crystal growth, which lowers PLQY of PQDs. Surface coating and treatment are important procedures for overcoming such factors. In this study, new types of PQDs and a strategy of improving their stabilities are introduced. Finally, this paper discusses future applications of PQDs in light-emitting diodes.

5.
Int J Hyperthermia ; 33(7): 770-778, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28540811

RESUMEN

The gadolinium-doped iron oxide nanoparticles (GdIONP) with greater specific power adsorption rate (SAR) than Fe3O4 was developed and its potential application in tumour therapy and particle tracking were demonstrated in transgenic adenocarcinoma of the mouse prostate C1 (TRAMP-C1) tumours. The GdIONPs accumulated in tumour region during the treatment could be clearly tracked and quantified by T2-weighted MR imaging. The therapeutic effects of GdIONP-mediated hyperthermia alone or in combination with radiotherapy (RT) were also evaluated. A significant increase in the tumour growth time was observed following the treatment of thermotherapy (TT) only group (2.5 days), radiation therapy only group (4.5 days), and the combined radio-thermotherapy group (10 days). Immunohistochemical staining revealed a reduced hypoxia region with vascular disruption and extensive tumour necrosis following the combined radio-thermotherapy. These results indicate that GdIONP-mediated hyperthermia can improve the efficacy of RT by its dual functions in high temperature (temperature greater than 45 °C)-mediated thermal ablation and mild-temperature hyperthermia (MTH) (temperature between 39 and 42 °C)-mediated reoxygenation.


Asunto(s)
Gadolinio/uso terapéutico , Hipertermia Inducida , Campos Magnéticos , Nanopartículas de Magnetita/uso terapéutico , Neoplasias de la Próstata/terapia , Animales , Línea Celular Tumoral , Terapia Combinada , Hipoxia/patología , Hipoxia/radioterapia , Hipoxia/terapia , Masculino , Ratones Endogámicos C57BL , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Carga Tumoral
6.
Angew Chem Int Ed Engl ; 56(44): 13650-13654, 2017 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-28865137

RESUMEN

All inorganic CsPbBr3 perovskite quantum dots (QDs) are potential emitters for electroluminescent displays. We have developed a facile hot-injection method to partially replace the toxic Pb2+ with highly stable Sn4+ . Meanwhile, the absolute photoluminescence quantum yield of CsPb1-x Snx Br3 increased from 45 % to 83 % with SnIV substitution. The transient absorption (TA) exciton dynamics in undoped CsPbBr3 and CsPb0.67 Sn0.33 Br3 QDs at various excitation fluences were determined by femtosecond transient absorption, time-resolved photoluminescence, and single-dot spectroscopy, providing clear evidence for the suppression of trion generation by Sn doping. These highly luminescent CsPb0.67 Sn0.33 Br3 QDs emit at 517 nm. A device based on these QDs exhibited a luminance of 12 500 cd m-2 , a current efficiency of 11.63 cd A-1 , an external quantum efficiency of 4.13 %, a power efficiency of 6.76 lm w-1 , and a low turn-on voltage of 3.6 V, which are the best values among reported tin-based perovskite quantum-dot LEDs.

7.
Nat Commun ; 14(1): 5282, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37648721

RESUMEN

Analog in-memory computing-a promising approach for energy-efficient acceleration of deep learning workloads-computes matrix-vector multiplications but only approximately, due to nonidealities that often are non-deterministic or nonlinear. This can adversely impact the achievable inference accuracy. Here, we develop an hardware-aware retraining approach to systematically examine the accuracy of analog in-memory computing across multiple network topologies, and investigate sensitivity and robustness to a broad set of nonidealities. By introducing a realistic crossbar model, we improve significantly on earlier retraining approaches. We show that many larger-scale deep neural networks-including convnets, recurrent networks, and transformers-can in fact be successfully retrained to show iso-accuracy with the floating point implementation. Our results further suggest that nonidealities that add noise to the inputs or outputs, not the weights, have the largest impact on accuracy, and that recurrent networks are particularly robust to all nonidealities.

8.
Materials (Basel) ; 15(12)2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35744191

RESUMEN

The present study is intended to develop and test a cost-effective and efficient printing method for fabricating flexible metamaterial film with high electromagnetic wave absorptivity. The film can be easily applied to the surfaces with curved aspects. Firstly, numerical parametric study of the absorption characteristics of the film is performed for the range of frequency varying from 2.0 to 9.0 GHz based on commercial software package. Secondly, the flexible metamaterial films are fabricated, and experiments are conducted. The flexible metamaterial film consists of a flexible dielectric film made of polyimide (PI) and an array of split-ring resonators. The split-ring resonators of different geometric dimensions are fabricated on the PI film surface by using a silver nanoparticles ink jet printer. The performance of the flexible structure is then measured and dependence of operation frequency with higher absorptivity on the dimensions of the split-ring resonators is investigated. A comparison between the numerical and experimental data shows that the numerical predictions of the operation frequency with higher absorptivity closely agree with the experimental data.

9.
Med Biol Eng Comput ; 60(10): 2841-2849, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35917049

RESUMEN

Nowadays, the physicians usually predict functional outcomes of stroke based on clinical experiences and big data, so we wish to develop a model to accurately identify imaging features for predicting functional outcomes of stroke patients. Using magnetic resonance imaging of ischemic and hemorrhagic stroke patients, we developed and trained a VGG-16 convolutional neural network (CNN) to predict functional outcomes after 28-day hospitalization. A total of 44 individuals (24 men and 20 women) were recruited from Taoyuan General Hospital and China Medical University Hsinchu Hospital to enroll in the study. Based on "modified Rankin Scale (mRS)" and "National Institutes of Health Stroke Scale (NIHSS)" assessments, men, women, and mixed men and women were trained separately to evaluate the differences of the results, and we have shown that VGG-16 demonstrated high accuracy in predicting the functional outcomes of stroke patients. The new deep-learning approach has provided an automated decision support system for personalized recommendations and treatments, assisting the physicians to predict functional outcomes of stroke patients in clinical practice.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Encéfalo/diagnóstico por imagen , Isquemia Encefálica/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Redes Neurales de la Computación , Accidente Cerebrovascular/diagnóstico por imagen
10.
Materials (Basel) ; 15(5)2022 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-35269209

RESUMEN

In this study, we proposed a three-dimensional (3D) printed porous (termed as 3DPP) scaffold composed of bioceramic (beta-tricalcium phosphate (ß-TCP)) and thermoreversible biopolymer (pluronic F-127 (PF127)) that may provide bone tissue ingrowth and loading support for bone defect treatment. The investigated scaffolds were printed in three different ranges of pore sizes for comparison (3DPP-1: 150−200 µm, 3DPP-2: 250−300 µm, and 3DPP-3: 300−350 µm). The material properties and biocompatibility of the 3DPP scaffolds were characterized using scanning electron microscopy, X-ray diffractometry, contact angle goniometry, compression testing, and cell viability assay. In addition, micro-computed tomography was applied to investigate bone regeneration behavior of the 3DPP scaffolds in the mini-pig model. Analytical results showed that the 3DPP scaffolds exhibited well-defined porosity, excellent microstructural interconnectivity, and acceptable wettability (θ < 90°). Among all groups, the 3DPP-1 possessed a significantly highest compressive force 273 ± 20.8 Kgf (* p < 0.05). In vitro experiment results also revealed good cell viability and cell attachment behavior in all 3DPP scaffolds. Furthermore, the 3DPP-3 scaffold showed a significantly higher percentage of bone formation volume than the 3DPP-1 scaffold at week 8 (* p < 0.05) and week 12 (* p < 0.05). Hence, the 3DPP scaffold composed of ß-TCP and F-127 is a promising candidate to promote bone tissue ingrowth into the porous scaffold with decent biocompatibility. This scaffold particularly fabricated with a pore size of around 350 µm (i.e., 3DPP-3 scaffold) can provide proper loading support and promote bone regeneration in bone defects when applied in dental and orthopedic fields.

11.
Nat Commun ; 13(1): 3765, 2022 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-35773285

RESUMEN

Analogue memory-based deep neural networks provide energy-efficiency and per-area throughput gains relative to state-of-the-art digital counterparts such as graphics processing units. Recent advances focus largely on hardware-aware algorithmic training and improvements to circuits, architectures, and memory devices. Optimal translation of software-trained weights into analogue hardware weights-given the plethora of complex memory non-idealities-represents an equally important task. We report a generalised computational framework that automates the crafting of complex weight programming strategies to minimise accuracy degradations during inference, particularly over time. The framework is agnostic to network structure and generalises well across recurrent, convolutional, and transformer neural networks. As a highly flexible numerical heuristic, the approach accommodates arbitrary device-level complexity, making it potentially relevant for a variety of analogue memories. By quantifying the limit of achievable inference accuracy, it also enables analogue memory-based deep neural network accelerators to reach their full inference potential.


Asunto(s)
Redes Neurales de la Computación , Programas Informáticos , Computadores
12.
AJR Am J Roentgenol ; 197(3): W471-81, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21862775

RESUMEN

OBJECTIVE: Pulmonary hypertension is a challenge for imagers and clinicians, with a variety of possible underlying causes, each with its own specific treatment. Although the diagnosis is based on physiologic measurements, ECG-gated MDCT can play a vital role in elucidating underlying cardiac, vascular, and pulmonary causes. CONCLUSION: A revised system for pulmonary hypertension, the Dana Point classification, can provide a template for review of the myriad causes of this complex condition.


Asunto(s)
Técnicas de Imagen Sincronizada Cardíacas/métodos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/etiología , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Femenino , Humanos , Hipertensión Pulmonar/clasificación , Masculino , Persona de Mediana Edad , Interpretación de Imagen Radiográfica Asistida por Computador
13.
Pediatr Neonatol ; 62(6): 591-597, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34226155

RESUMEN

BACKGROUND: Optic nerve sheath diameter (ONSD) ultrasound is a noninvasive and repeatable tool to dynamically evaluate intracranial pressure with high diagnostic accuracy; however, data in neonates are scarce. The aim of this study was to determine the reference value of ONSD and potential influencing factors in healthy term neonates. METHODS: We retrospectively reviewed 250 full-term neonates who underwent cranial ultrasound as part of selective newborn screening over a 2-year period. Neonates with any of the following conditions were excluded: using mechanical ventilation, sedatives and/or vasopressors, or signs of infection which needed cerebrospinal fluid analysis and/or intracranial pathologies. Data on sex, gestational age, birth body weight, birth body height, birth head circumference, Apgar score and types of delivery were collected. The neurodevelopmental outcomes were reviewed. RESULTS: A total of 234 neonates (123 girls and 111 boys) were included. The mean ONSD value was 3.30 ± 0.27 mm in the right eye and 3.30 ± 0.23 mm in the left eye, with no significant difference between both eyes (p = 0.797). Male neonates had a larger ONSD than female neonates (3.34 ± 0.22 mm versus 3.26 ± 0.20 mm, p = 0.007), and ONSD was correlated with birth weight in the males. Otherwise, there were no statistically significant associations between ONSD and other birth characteristics in both sexes. Most (63%) cases were followed for at least 12 months, and 98% had normal neurodevelopment. CONCLUSION: The reference value reported in this study may be used to evaluate the ONSD in healthy term neonates. Sex differences should be considered in this age group.


Asunto(s)
Hipertensión Intracraneal , Femenino , Humanos , Recién Nacido , Masculino , Nervio Óptico/diagnóstico por imagen , Estudios Prospectivos , Estudios Retrospectivos , Ultrasonografía
14.
Glob Heart ; 16(1): 45, 2021 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-34211831

RESUMEN

Background: Patients with hyperthyroidism have higher risk of atrial fibrillation (AF). However, the risk of thromboembolic event in patients with hyperthyroidism-related AF is controversial. Objectives: The aim of the study was to examine the risk of thromboembolic events in AF patients with/without hyperthyroidism. Methods: The national retrospective cohort study enrolled AF population was derived from the Taiwan National Health Insurance Research Database. The comparison between the AF patients with clinical hyperthyroidism (HT-AF group) and AF patients without hyperthyroidism (non-thyroid AF group) was made in a propensity score matched cohort and in a real-world setting, of which, the CHA2DS2-VASc level was treated as a stratum variable. The outcomes were ischemic stroke and systemic thromboembolism. Results: There were 3,880 patients in HT AF group and 178,711 in non-thyroid AF group. After propensity score analysis, the incidence of thromboembolism event and ischemic stroke were lower in HT AF patients than non-thyroid AF patients (1.6 versus 2.2 events per 100 person-years; HR, 0.73; 95% CI, 0.64-0.82 and 1.4 versus 1.8 events per 100 person-years; HR, 0.74; 95% CI, 0.64-0.84, respectively) in the 4.3 ± 3.2 year follow up period. The differences persistently existed in those receiving anticoagulants or not. In AF patients without anticoagulants, the incidence densities of ischemic stroke/systemic thromboembolism were significantly lower in HT AF group than those in non-thyroid AF group at CHA2DS2-VASc scores ≤ 4 (HR, 0.41; 95% CI, 0.35-0.48, p < 0.001), while the differences disappeared in case of score ≥ 5 (HR, 0.80; 95% CI, 0.63-1.02, p = 0.071). Conclusion: Patients with HT AF had lower incidence of thromboembolic events as compared to non-thyroid AF patients. The threshold of CHA2DS2-VASc score for anticoagulation in AF patients with clinical hyperthyroidism should be further evaluated. Highlights: The incidence of thromboembolic event was different between hyperthyroidism-related atrial fibrillation (HT-AF) and non-thyroid AF patients.Hyperthyroidism did not confer additional risk of thromboembolic event at CHA2DS2-VASc of ≤ 4.The benefit of anticoagulation strategy in patients with hyperthyroidism-related AF should be further evaluated, especially at low CHA2DS2-VASc score.


Asunto(s)
Fibrilación Atrial , Hipertiroidismo , Accidente Cerebrovascular , Tromboembolia , Anticoagulantes , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Tromboembolia/epidemiología , Tromboembolia/etiología
15.
Front Comput Neurosci ; 15: 675741, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34290595

RESUMEN

Recent advances in deep learning have been driven by ever-increasing model sizes, with networks growing to millions or even billions of parameters. Such enormous models call for fast and energy-efficient hardware accelerators. We study the potential of Analog AI accelerators based on Non-Volatile Memory, in particular Phase Change Memory (PCM), for software-equivalent accurate inference of natural language processing applications. We demonstrate a path to software-equivalent accuracy for the GLUE benchmark on BERT (Bidirectional Encoder Representations from Transformers), by combining noise-aware training to combat inherent PCM drift and noise sources, together with reduced-precision digital attention-block computation down to INT6.

16.
Opt Express ; 18(15): 16014-24, 2010 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-20720986

RESUMEN

We report the imaging of sub-diffraction limited features using an optical probe generated by focusing a round spot at one wavelength, lambda(1) = 405 nm, and a ring-shaped spot at a second wavelength, lambda(2) = 532 nm, onto a thin photochromic layer that coats the nanostructures. Illumination at lambda(2) turns the photochromic layer opaque to lambda(1) everywhere except at the centre of the ring, where the illumination at lambda(1) penetrates and probes the underlying nanostructure. We confirm that this optically confined probe increases image contrast and is able to resolve features smaller than the far-field diffraction limit. Furthermore, by using an array of dual-wavelength diffractive microlenses, we demonstrate the feasibility of parallelizing this approach. Compared to previous approaches, our technique is not limited to fluorescence imaging.

17.
Sci Rep ; 9(1): 7611, 2019 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-31110205

RESUMEN

We have previously identified a novel Aurora-A-mediated Serine 379 (S379) phosphorylation of a poly(C)-binding protein, hnRNPK, the overexpression of which is frequently observed in various cancers. It is known that the oncogenic Aurora-A kinase promotes the malignancy of cancer cells. This study aims to investigate the unexplored functions of hnRNPK S379 phosphorylation using MDA-MB-231 cells, a triple negative breast cancer cell that has amplification of the Aurora-A kinase gene. Accordingly, we established two cell lines in which the endogenous hnRNPK was replaced with either S379D or S379A hnRNPK respectively. Notably, we found that a phosphorylation-mimic S379D mutant of hnRNPK suppressed cell migration and, conversely, a phosphorylation-defective S379A mutant promoted migration. Moreover, Twist was downregulated upon hnRNPK S379 phosphorylation, whereas ß-catenin and MMP12 were increased when there was loss of hnRNPK S379 phosphorylation in MDA-MB-231 cells. Furthermore, S379A hnRNPK increases stability of ß-catenin in MDA-MB-231 cells. In conclusion, our results suggest that hnRNPK S379 phosphorylation regulates migration via the EMT signaling pathway.


Asunto(s)
Movimiento Celular/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Fosforilación/genética , Línea Celular Tumoral , Regulación hacia Abajo/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Serina/genética , Transducción de Señal/genética , Neoplasias de la Mama Triple Negativas/genética , beta Catenina/genética
18.
Brain Dev ; 41(5): 428-435, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30611595

RESUMEN

BACKGROUND: Nitrous oxide (N2O) is a commonly used inhaled anesthetic in outpatient dental procedures. However, the increasing recreational use of N2O may result in vitamin B12 deficiency-related neurologic and psychiatric symptoms. The aim of this study was to demonstrate the clinical features of chronic N2O abuse in pediatric patients. METHODS: Patients under 20 years of age who were diagnosed with N2O-induced subacute combined degeneration of the spinal cord from 2012 to 2018 were enrolled in this study. Clinical presentations, laboratory, imaging, ancillary studies, treatments and outcomes were analyzed. RESULTS: Nine patients were included, all of whom presented with symptoms of myeloneuropathy including limb numbness, limb weakness or unsteady gait. Six patients had low or low-normal vitamin B12 (cyanocobalamin) levels. Eight patients had evidence of subacute combined degeneration of the spinal cord via neuroimaging studies. All of the patients received vitamin B12 supplementation as treatment. All had full recovery of muscle power within 2 months. Five patients had persistent sensory deficits. CONCLUSION: Chronic N2O abuse can cause permanent neurological damage if not treated promptly. Clinical staff should be aware of the various presentations of neurotoxicity related to N2O abuse.


Asunto(s)
Óxido Nitroso/efectos adversos , Evaluación de Resultado en la Atención de Salud , Degeneración Combinada Subaguda/inducido químicamente , Degeneración Combinada Subaguda/fisiopatología , Trastornos Relacionados con Sustancias/complicaciones , Deficiencia de Vitamina B 12/inducido químicamente , Vitamina B 12/farmacología , Complejo Vitamínico B/farmacología , Adolescente , Adulto , Femenino , Humanos , Masculino , Degeneración Combinada Subaguda/tratamiento farmacológico , Vitamina B 12/administración & dosificación , Deficiencia de Vitamina B 12/tratamiento farmacológico , Complejo Vitamínico B/administración & dosificación , Adulto Joven
19.
Biochim Biophys Acta ; 1774(8): 1020-8, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17611171

RESUMEN

Venoms of Russell's vipers (genus Daboia) are known for their deadly coagulopathic and other effects. We herein studied various isoforms of venom phospholipases A(2) (PLAs) from two Daboia species at their geographic boundary. From Myanmar Daboia siamensis venom (designated as DsM), four PLAs (designated DsM-aI, aI', aII' and bI') were purified, and the cDNAs encoding two acidic (DsM-aI and aII) and two basic PLAs (DsM-bI and S1) were also cloned from its venom-glands. DsM-S1 is identical to the major venom PLA of southern India Daboia russelii, but the protein is absent from the venom. Additionally, four PLAs (designated DrK-aI, aII, bI and bII) were cloned from cDNA obtained from venom glands of a Kolkata D. russelii, and the PLAs were purified from the pooled venom (designated as DrK). The acidic DrK-aI is the most neurotoxic and lethal among these PLAs; DsM-aI which differs from DrK-aI by only the Phe2 substitution shows greatly reduced enzymatic activity and lethality. Both acidic PLAs do not form dimeric complex with basic PLAs in the same venoms. DsM-bI' is neurotoxic and lethal but its orthologous DrK-bI (97% identical to DsM-bI') is a much weaker toxin. Given the fact that most of the orthologous PLAs of DrK and DsM share 97-100% sequence identity, Daboia vipers of Myanmar and Kolkata must be closely related. Molecular phylogenetic analyses on 30 venom PLAs of Eurasian vipers' revealed co-evolution of five subtypes of venom PLAs in both Daboia and Vipera genera. Our results shed light on the intra- and inter-species variations and structure-function relationships of viperid venom PLAs.


Asunto(s)
Daboia/genética , Evolución Molecular , Fosfolipasas A/genética , Filogenia , Venenos de Víboras/genética , Secuencia de Aminoácidos , Animales , Clonación Molecular , India , Datos de Secuencia Molecular , Fosfolipasas A/metabolismo , Daboia/metabolismo , Venenos de Víboras/enzimología
20.
Biochimie ; 90(10): 1486-98, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18554518

RESUMEN

Two homologous P-III hemorrhagic metalloproteinases were purified from Russell's viper venoms from Myanmar and Kolkata (eastern India), and designated as daborhagin-M and daborhagin-K, respectively. They induced severe dermal hemorrhage in mice at a minimum hemorrhagic dose of 0.8-0.9 microg. Daborhagin-M specifically hydrolyzed an Aalpha-chain of fibrinogen, fibronectin, and type IV collagen in vitro. Analyses of its cleavage sites on insulin chain B and kinetic specificities toward oligopeptides suggested that daborhagin-M prefers hydrophobic residues at the P(1), P(1)', and P(2)' positions on the substrates. Of the eight Daboia geographic venom samples analyzed by Western blotting, only those from Myanmar and eastern India showed a strong positive band at 65kDa, which correlated with the high risk of systemic hemorrhagic symptoms elicited by Daboia envenoming in both regions. The full sequence of daborhagin-K was determined by cDNA cloning and sequencing, and then confirmed by peptide mass fingerprinting. Furthermore, molecular phylogenetic analyses based on 27 P-IIIs revealed the co-evolution of two major P-III classes with distinct hemorrhagic potencies, and daborhagin-K belongs to the most hemorrhagic subclass. By comparing the absolute complexity profiles between these two classes, we identified four structural motifs probably responsible for the phylogenetic subtyping and hemorrhagic potencies of P-III SVMPs.


Asunto(s)
Daboia/genética , Daboia/metabolismo , Metaloendopeptidasas/genética , Metaloendopeptidasas/metabolismo , Filogenia , Venenos de Víboras/enzimología , Secuencia de Aminoácidos , Animales , Membrana Basal/metabolismo , Dominio Catalítico , Clonación Molecular , Evolución Molecular , Colorantes Fluorescentes/metabolismo , Insulina/metabolismo , Cinética , Proteínas de la Membrana/metabolismo , Metaloendopeptidasas/química , Metaloendopeptidasas/clasificación , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADN , Especificidad de la Especie
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