Variability in HfO2-based memristors described with a new bidimensional statistical technique.

A new statistical analysis is presented to assess cycle-to-cycle variability in resistive memories. This method employs two-dimensional (2D) distributions of parameters to analyse both set and reset voltages and currents, coupled with a 2D coefficient of variation (CV). This 2D methodology significantly enhances the analysis, providing a more thorough and comprehensive understanding of the data compared to conventional one-dimensional methods. Resistive switching (RS) data from two different technologies based on hafnium oxide are used in the variability study. The 2D CV allows a more compact assessment of technology suitability for applications such as non-volatile memories, neuromorphic computing and random number generation circuits.

Unipolar resistive switching behavior in Al2O3/HfO2 multilayer dielectric stacks: fabrication, characterization and simulation.

In this work, the impact of different HfO2/Al2O3-based multilayer dielectric stack (DS) configurations on the electrical characteristics and on the resistive switching (RS) performance of Ni/Insulator/Silicon devices has been systematically investigated. Significant differences are observed in the electrical characteristics of the fabricated bilayer, trilayer and pentalayer stacks compared to a single HfO2 layer of the same physical thickness. The RS analysis has shown similar low resistance state currents and set voltages for all the DS combinations whereas currents at the high resistance state and reset voltages depend on the DS. The shift of the reset voltage to lower values for HfO2 and Al2O3/HfO2/Al2O3 cases is explained by the results from thermal simulations that reveal that these differences could be associated to the different temperature distributions at the narrowest part of the conductive filament immediately before the thermally triggered reset process occurs.

Removal of Escherichia coli from well water using continuous laminar flow in a channel system containing PPy/Cu modified electrodes.

Polypyrrole (PPy) films modified with copper species were used for disinfection of well water contaminated with Escherichia coli (E. coli). For that purpose a laboratory-scale continuous flow system with a parallel plate flow chamber configuration was implemented operating under laminar flow. Three flow rates were considered. The testing conditions did not affect the morphology of the modified PPy films, even after 5 h of continuous use at the largest flow rate examined. The results show that the bacteria killing process can be described by a first-order kinetic law at all Reynolds numbers. As the flow rate increases, the concentration of Cu species released from the electrodes enhances, accelerating the disinfection process. Re-inoculation and Cu-recharging tests showed bactericidal effects very similar to those displayed by the freshly prepared electrodes. It is concluded that PPy/Cu-modified electrodes installed in the laboratory-scale continuous flow system are effective for the water disinfection process.

Immobilization and release of copper species from a microstructured polypyrrole matrix.

Copper species immobilization in hollow rectangular-sectioned microtubes of polypyrrole (PPy) electrosynthesized on 316L stainless steel was carried out using two different methods. One of them involved the immobilization after the PPy electropolymerization and the other one during the electrosynthesis process. The electrodes modified with copper species were rotated at different speeds in well water under open-circuit potential conditions. The release of copper species from the PPy matrix and the antibacterial activity against Escherichia coli were analyzed. The obtained results demonstrate that the amount of copper species released as well as the bactericidal effects against E. coli increases with rotation speed. The PPy coating modified with copper species after the electropolymerization reaction exhibited the best performance in terms of antibacterial activity and corrosion protection. These electrodes were tested in a lab-scale continuous flow system for well water disinfection.

A novel HEXB mutation and its structural effects in juvenile Sandhoff disease.

Mutations in HEXB, encoding the beta-subunit common to hexosaminidases A and B, cause the neurodegenerative condition, Sandhoff disease. A homozygous missense HEXB mutation (p. D459A) was discovered in six patients with a rare juvenile variant: we show that this disrupts a salt bridge between aspartate D459 and arginine 505 at the subunit interface; R505 mutations are reported in late-onset Sandhoff disease. Identification of D459A contributes to diagnosis and molecular understanding of attenuated Sandhoff disease variants.

[Progressive multifocal leukoencephalopathy in the province of Cadiz, Spain]. / Leucoencefalopatía multifocal progresiva en la provincia de Cádiz, España.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML), which is caused by the reactivation of an infection due to the JC human polyoma virus, affects immunocompromised patients and more especially those infected by the human immunodeficiency virus. It produces a multifocal neurological clinical picture due to the destruction of oligodendrocytes and the subsequent demyelination. AIMS: To analyse the epidemiological, semiological and radiological characteristics of a sample of patients diagnosed with PML in the province of Cadiz, and to study their rates of survival. PATIENTS AND METHODS: Our sample consisted of 23 patients with PML who presented an unfavourable immunological situation and deficient therapeutic compliance. Factors studied included time to progression of the symptoms, clinical features, neuroimaging and survival. RESULTS: The mean time elapsed between the appearance of symptoms and diagnosis was 30 days. There was a wide range of manifestations: motor symptoms were the most prevalent and cognitive compromise was far less common. All the patients submitted to magnetic resonance imaging of the head and only eight of those who underwent computerised axial tomography displayed multiple insults. The mean survival time was 60 days in the case of the seven deaths and over two years in those who survived. CONCLUSIONS: The symptoms of the patients were similar to those reported in the literature, except for the absence of dementia. Magnetic resonance imaging was better than tomography at detecting multiple, dispersed insults and is more cost-effective for diagnosing PML. The survival time of most of the patients was higher than that reported in previous studies.

Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt's lymphoma. A cytogenetic and comparative genomic hybridization study.

Comparative genomic hybridization (CGH) studies have demonstrated a high incidence of chromosomal imbalances in non-Hodgkin's lymphoma. However, the information on the genomic imbalances in Burkitt's Lymphoma (BL) is scanty. Conventional cytogenetics was performed in 34 cases, and long-distance PCR for t(8;14) was performed in 18 cases. A total of 170 changes were present with a median of four changes per case (range 1-22). Gains of chromosomal material (143) were more frequent than amplifications (5) or losses (22). The most frequent aberrations were gains on chromosomes 12q (26%), Xq (22%), 22q (20%), 20q (17%) and 9q (15%). Losses predominantly involved chromosomes 13q (17%) and 4q (9%). High-level amplifications were present in the regions 1q23-31 (three cases), 6p12-p25 and 8p22-p23. Upon comparing BL vs Burkitt's cell leukemia (BCL), the latter had more changes (mean 4.3 +/- 2.2) than BL (mean 2.7 +/- 3.2). In addition, BCL cases showed more frequently gains on 8q, 9q, 14q, 20q, and 20q, 9q, 8q and 14q, as well as losses on 13q and 4q. Concerning outcome, the presence of abnormalities on 1q (ascertained either by cytogenetics or by CGH), and imbalances on 7q (P=0.01) were associated with a short survival.

Idiopathic monomorphic ventricular tachycardia originating from the left aortic sinus cusp in children: endocardial mapping and radiofrequency catheter ablation.

BACKGROUND: Idiopathic repetitive monomorphic ventricular tachycardia with an inferior axis and left bundle branch block pattern typically originates from the superior right ventricular outflow tract. When indicated, radiofrequency catheter ablation is usually safe and effective. However, a left ventricular origin has been described recently in adult patients in whom ablation attempts in the right ventricular outflow tract were unsuccessful. Experience in pediatric patients is limited. PATIENTS AND METHODS: Since 1998, 13 young patients suffering from symptomatic ventricular tachycardia episodes with an inferior axis and left bundle branch block pattern underwent an electrophysiological study and radiofrequency catheter ablation. In 2 patients, age 13 and 15 years, no endocardial local electrograms preceding the surface ECG QRS complex could be recorded within the right ventricular outflow tract during ventricular ectopy. Detailed mapping within the left ventricular outflow tract and in the aortic root revealed local electrograms 25 and 53 ms earlier than the QRS complex and a 11/12 and 12/12 lead match during pacing inferior and anterior to the ostium of the left main coronary artery in the left aortic sinus cusp. Earliest activation was recorded 10 and 12 mm away from the coronary artery ostium identified angiographically. In each of the patients, one single radiofrequency current application (60 degrees C, 30 W, duration 30 and 60 s, respectively) resulted in complete cessation of ventricular ectopy. Subsequent selective injection into the left coronary artery did not reveal any abnormalities. During follow-up (2 and 34 months) off any antiarrhythmic drugs, both of the patients are in continuous normal sinus rhythm. CONCLUSION: In young patients with symptomatic idiopathic ventricular tachycardia originating from the left aortic sinus cusp, radiofrequency catheter ablation was safe and effective.

Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics.

Splenic marginal zone lymphoma (SMZL) has recently been recognized in the World Health Organization classification of hematological diseases as distinct type of non-Hodgkin's lymphoma. In contrast to the well-established chromosomal changes associated with other B-cell non-Hodgkin's lymphoma, few genetic alterations have been found associated with SMZL. The aim of our study was to analyze by comparative genomic hybridization (CGH) the chromosomal imbalances in 29 patients with SMZL and to correlate these findings with clinical and biological characteristics and patient outcome. In 21 cases, cytogenetic studies were simultaneously performed. Most of the patients (83%) displayed genomic imbalances. A total of 111 DNA copy number changes were detected with a median of four abnormalities per case (range, 1 to 12). Gains (n = 92) were more frequent than losses (n = 16), while three high-level amplifications (3q26-q29, 5p11-p15, and 17q22-q25) were observed. The most frequent gains involved 3q (31%), 5q (28%), 12q and 20q (24% each), 9q (21%), and 4q (17%). Losses were observed in 7q (14%) and 17p (10%). SMZL patients with genetic losses had a shorter survival than the remaining SMZL patients (P < 0.05). In summary, chromosomal imbalances in regions 3q, 4q, 5q, 7q, 9q, 12q, and 20q have been detected by CGH in SMZL. Patients with SMZL displaying genetic losses by CGH had a short survival.

Differences in genetic changes between multiple myeloma and plasma cell leukemia demonstrated by comparative genomic hybridization.

To analyze the genomic differences between multiple myeloma (MM) and plasma cell leukemia (PCL), a total of 30 cases were studied by comparative genomic hybridization (CGH). In five cases with a low proportion of plasma cells (PC) in bone marrow, an enrichment of PC was performed by using immunomagnetic beads conjugated with the monoclonal antibody B-B4. In 24 out of the 25 MM (96%) and in all five PCL (100%) patients DNA copy number changes were identified by CGH analysis; in the MM case without chromosomal imbalances, the immunomagnetic enrichment of PC had failed. The most recurrent changes in MM patients were gains at chromosomes 15q (48%), 11q (44%), 3q (40%), 9q (40%) and 1q (36%). By contrast, all PCL patients showed gains in 1q. Losses of chromosomal material were significantly more frequent in PCL than in MM patients (P = 0.03): losses on 13q in 80% of PCL vs 28% of MM; and on chromosome 16 in 80% vs 12%, respectively. In addition, PCL patients showed losses of 2q and 6p that were not present in MM. The CGH data show differences in chromosomal imbalances between MM and PCL.

Detection of inv(16) and t(16;16) by fluorescence in situ hybridization in acute myeloid leukemia M4Eo.

BACKGROUND AND OBJECTIVE: It has been established that cytogenetic findings at the time of diagnosis of acute myeloid leukemia (AML) are powerful prognostic indicators. Pericentric inversion of chromosome 16 and translocation t(16;16) resulting in chimeric fusion of CBFB and MYH11 genes are typically seen in the M4-Eo FAB classification subset of AML and are associated with low-risk disease. These subtle chromosomal abnormalities may be difficult to detect in poor-quality metaphase preparations and if missed could lead to incorrect assignment to risk groups and influence the therapy decision-making process. DESIGN AND METHODS: We prospectively studied, at diagnosis, 10 patients with AML-M4 Eo by cytogenetics and fluorescent in situ hybridization (FISH) with two cosmids (36 and 40). As a control group, 7 patients (5 with a diagnosis of AML other than M4 Eo and two cases of reactive eosinophilia) were analyzed. In addition reverse transcriptase chain reaction (RT-PCR) studies were carried out in 6 cases. RESULTS: Karyotypic analysis detected the inv(16) in all but one of the patients with M4-Eo while none of the control cases showed any abnormality on chromosome 16. FISH studies showed that all 10 patients had abnormalities on chromosome 16; the patient with normal karyotype showed an inv(16) by FISH, while a case with inv(16) by cytogenetics had a t(16;16) by FISH. RT-PCR demonstrated amplification of the CBFB/MYH11 product in all cases analyzed. INTERPRETATION AND CONCLUSIONS: In patients with M4Eo and rearrangements of chromosome 16, FISH studies may afford more complete information than conventional cytogenetics and can be an alternative to RT-PCR studies.

Two cases of myeloid disorders and a t(8;12) (q12;p13).

BACKGROUND AND OBJECTIVE: Rearrangements of the short arm of chromosome 12 have been described in different hematologic malignancies. Some of these abnormalities showed a rearrangement of the ETV6 gene. We studied the 12p region in one case with a t(8;12)(q12;p13) by fluorescence in situ hybridization (FISH). DESIGN AND METHODS: We have identified a chromosome translocation, t(8;12)(q12;p13) in two patients with myeloid disorders; one with acute myelogenous leukemia (AML) and one with refractory anemia (RA). FISH studies with specific probes (cosmids and YACs) for the 12p region were used to investigate one case. RESULTS: FISH studies demonstrated hemizygous loss of the ETV6 and CDKN1B regions and two copies of the CCDN2 locus, as a result of the balanced translocation and an additional copy of the der(8). INTERPRETATION AND CONCLUSIONS: Myeloid diseases with t(8;12)(q12;p13) have an interstitial deletion of 12p, including the ETV6 and CDKN1B regions. A duplication of CCDN2 locus can also be found.

The hairless gene of the mouse: relationship of phenotypic effects with expression profile and genotype.

Various mutations of the hairless (hr) gene of mice result in hair loss and other integument defects. To examine the role of the hr gene in mouse development, the expression profile of hr has been determined by in situ hybridisation and correlated to the nature of genetic changes and morphological abnormalities in different mutant animals. Four variant alleles have been characterised at the molecular level. hr/hr mice produce reduced, but significant, levels of hr mRNA whereas other alleles contain mutations which would be expected to preclude the synthesis of functional product, demonstrating a correlation between allelic variation at the hr locus and phenotypic severity. hr expression was shown to be widespread and temporally regulated. It was identified in novel tissues such as cartilage, developing tooth, inner ear, retina, and colon as well as in skin and brain. Analysis of mice homozygous for the rhino allele of hairless revealed that, although no morphological defects were detectable in many tissues normally expressing hr, previously undescribed abnormalities were present in several tissues including inner ear, retina, and colon. These findings indicate that the hairless gene product plays a wider role in development than previously suspected. Dev Dyn 1999;216:113-126.

The effect of major depression on functional status in patients with coronary artery disease.

OBJECTIVE: To examine the effect of major depression on reported functional status in a group of patients with coronary artery disease (CAD). SETTING: An inpatient cardiology service. PARTICIPANTS: Three hundred thirty-five inpatients with coronary artery disease who were free of dementia, Parkinson's disease, and other primary neurological illnesses. MEASUREMENTS: Duke Depression Evaluation Schedule, a structured psychiatric interview which included the Diagnostic Interview Schedule depression subscale, the Cumulative Illness Rating Scale, and two scales for measuring instrumental and self-maintenance activities of daily living. RESULTS: Twenty-seven subjects met DSM-IV criteria for major depression. Compared with subjects without major depression, depressed subjects were more than twice as likely to report a self-maintenance ADL deficit and were significantly more likely to report an IADL deficit than were nondepressed subjects (93 vs 71%). In regression models, female gender, older age, greater medical illness severity, and presence of major depression were significant predictors of self-maintenance ADL disability; and female gender, older age, greater medical severity, and presence of major depression significantly predicted greater IADL impairment. CONCLUSION: The presence of major depression was associated with functional disability in patients with CAD. Further research is needed to clarify whether antidepressant treatment significantly impacts both affective symptoms and functional status in patients with coronary heart disease.

Neurobiology of chronic fatigue syndrome.

1. Chronic fatigue syndrome (CFS) is characterized by a new onset of significant fatigue for a period of six months or longer usually following an infection, injury or period of high stress. 2. The exact etiology of CFS is not known and a diagnostic test is not available. Hence, the diagnosis is made by exclusion of other explanations for the patient's symptoms and by meeting the CDC research case definitions. Early studies supported an infectious or immune dysregulation hypothesis for the pathophysiology of CFS. 3. Subsequent studies documented that neurological, affective and cognitive symptoms also occur at high rates in CFS patients. Neuropsychological, neuroendocrine studies and brain imaging have now confirmed the occurrence of neurobiological abnormalities in most patients with CFS. 4. In this article, the authors review these findings in relation to the clinical neurobiology of CFS and their potential relevance to biological psychiatry.

Depression in patients with coronary artery disease.

Depression is more prevalent in patients with coronary artery disease (CAD) than in the general elderly population. Although CAD patients with depression have higher mortality rates, depression is often not recognized and treated in these patients. We administered structured psychiatric diagnostic interviews to 99 inpatients with CAD and diagnosed 23% with a major depressive episode (MDE) by DSM-IV criteria. Severity of medical illness and family history of psychopathology were indicators for increased risk for MDE. These findings may facilitate the recognition of CAD patients at greater risk for MDE.