Stabilizing amplifier with a programmable load line for characterization of nanodevices with negative differential resistance.

Resistive switching devices and other components with negative differential resistance (NDR) are emerging as possible electronic constituents of next-generation computing architectures. Due to the exhibited NDR effects, switching operations are strongly affected by the presence of resistance in series with the memory cell. Experimental measurements useful in the development of these devices use a deliberate addition of series resistance, which can be done either by integrating resistors on-chip or by connecting external components to the wafer probing system. The former approach is considered inflexible because the resistance value attached to a given device cannot be changed or removed, while the latter approach tends to create parasitic effects that impact controllability and interfere with measurements. In this work, we introduce a circuit design for flexible characterization of two-terminal nanodevices that provides a programmatically adjustable external series resistance while maintaining low parasitic capacitance. Experimental demonstrations show the impact of the series resistance on NDR and resistive switching measurements.

Current-limiting amplifier for high speed measurement of resistive switching data.

Resistive switching devices, important for emerging memory and neuromorphic applications, face significant challenges related to the control of delicate filamentary states in the oxide material. As a device switches, its rapid conductivity change is involved in a positive feedback process that would lead to runaway destruction of the cell without current, voltage, or energy limitation. Typically, cells are directly patterned on MOS transistors to limit the current, but this approach is very restrictive as the necessary integration limits the materials available as well as the fabrication cycle time. In this article, we propose an external circuit to cycle resistive memory cells, capturing the full transfer curves while driving the cells in a way that suppresses runaway transitions. Using this circuit, we demonstrate the acquisition of 105 I, V loops per second without using on-wafer current limiting transistors. This setup brings voltage sweeping measurements to a relevant timescale for applications and enables many new experimental possibilities for device evaluation in a statistical context.

The German Infant Nutritional Intervention Study (GINI) for the preventive effect of hydrolyzed infant formulas in infants at high risk for allergic diseases. Design and selected results.

In the complex interaction between certain environmental factors and genetic disposition, the early allergen exposure plays a major role in the development of allergic diseases. In aiming to reduce the allergen burden for the infant at risk during early infancy, cow's milk protein hydrolysate infant formulas (hypoallergenic infant formulas) are appropriate alternatives to breastfeeding for primary allergy prevention. The German Infant Nutritional Intervention-Program (GINI) was supported for the first 3 years by the German Ministry for Education and Research (BMBF) (FKZ 01 EE 9401-4). It is a birth cohort which was primarily scheduled until the children were 3 years old. The aim of the prospective, randomized, double-blind intervention study was to investigate the impact of different cow's milk protein hydrolysate infant formulas in the first 4 - 6 months on the development of allergic diseases in children at risk due to at least one parent or biological sibling with a history of allergic disease. The allocation to one of the 4 intervention formulas (partial whey hydrolysate, extensive whey hydrolysate, extensive casein hydrolysate or standard cow's milk formula) was randomised and stratified by family history (single/biparental) and the respective obstetric clinic. Recruitment was carried out by the three clinical centers (Research Institute Marien-Hospital Wesel, Children's Department, Ludwigs-Maximilians-University Munich and Children's Department Technical University Munich) in 18 obstetric clinics between 01.09.1995 and 30.06.1998. Along with the intervention study a non-interventional, complementary observational cohort of children with or without allergy risk was recruited and followed by annual self-reporting parental questionnaires. The GINI intervention study (GINI-I, N = 2.252) and the non-interventional observation study (GINI-NI, N = 3.739) are combined in the population-based GINIplus study (see article J. Heinrich et al. in this journal). The results of the GINI intervention study confirm that, cow's milk protein hydrolysate infant formulas have a preventive effect on allergic manifestation compared with a standard cow's milk formula, until school age. However, the dimension of the effect is different between the formulas. This effect, which is mainly driven by the effect on atopic eczema, develops in the first months of life and persists without rebound. In the formula groups the cumulative incidence of atopic eczema until school age is reduced between 26% and 45% compared with standard cow's milk formula. A beneficial effect of the hydrolysate formulas on the respiratory manifestations asthma and rhinoconjunctivitis, however, could not be shown. By comparing the GINI intervention and non-intervention arm of the GINIplus study it was demonstrated, that a family history for allergy doubles the risk for eczema in the offspring. Early intervention with cow's milk protein hydrolysate infant formulas is able to substantially compensate this risk for eczema until the age of 6 years. In contrast, by randomization to standard cow's milk formula this risk showed a trend towards a higher incidence compared with children at risk from the non-intervention group. Thus, the results of the GINIplus study have contributed to answer some of the controversially discussed questions.

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).

The WST survival assay: an easy and reliable method to screen radiation-sensitive individuals.

An easy, fast and reliable method was developed to screen hundreds of Epstein-Barr virus-transformed cell lines (lymphoblastoid cell lines, LCLs) for radiation sensitivity that were generated from lymphocytes isolated from young lung cancer patients. The WST-1 test explores the metabolic activity of the mitochondria as an indicator for the vital status of cells. Cell proliferation as well as indirect cell death can be quantified by this method on a large scale in microtiter plates. Cell survival was measured at 24- and 48-h post-irradiation with 10 Gy ((137)Cs source) by the WST-1 assay and Trypan blue staining. To set up the experimental screening conditions and to establish a positive and a negative control, an ATM-mutated cell line from a radiation-sensitive ATM patient and an ATM proficient cell line from a healthy brother were compared. An optimal differentiation between the two cell lines was demonstrated for 10 Gy and 24- and 48-h cell growth after irradiation. Upon screening 120 LCLs of young lung cancer patients under these conditions, 5 of them were found to be radiation sensitive to a high degree of statistical significance. The results have been confirmed by a second laboratory by means of Trypan blue testing. The WST-1 test represents an efficient and reliable method by means of screening for radiation-sensitive cell lines.

Histologic types of lung carcinoma and age at onset.

BACKGROUND: Previous research has demonstrated that adenocarcinoma is the leading cell type among patients with early age onset lung carcinoma. An increase in adenocarcinoma at the expense of squamous cell carcinoma in general was observed in recent years and may be due to the smoking of filtered cigarettes. METHODS: To rule out whether shifts in smoking patterns or other etiologic factors are responsible for the high rates of adenocarcinoma in young patients, personal interviews regarding smoking, occupation, and family history of cancer were conducted in 251 young patients (age < or =45 years) and 2009 older patients (ages 55-69 years) with histologically confirmed lung carcinoma from selected study clinics in Germany between 1990 and 1996. RESULTS: Young male patients were found to have significantly more adenocarcinomas (41%) than older male patients (28%), whereas adenocarcinomas were dominant in young and older women (43% and 47%, respectively). Because smoking patterns were different between young and older patients, the authors stratified for comparable levels of smoking exposure. Histology did not differ in never smokers (dominance of adenocarcinomas in both age groups) and in male heavy smokers (dominance of squamous cell carcinomas in both age groups), whereas young male low dose smokers showed significantly more cases of adenocarcinoma than older low dose smokers. A family history of lung carcinoma was significantly higher in young patients compared with older patients, but no association with histologic type was observed. CONCLUSIONS: The results of the current study show that differences in the histologic type of lung carcinoma based on age at onset can be explained in part by differences in smoking patterns. However, there still are unknown factors that appear to favor the development of adenocarcinoma in the young.

Effect of cadmium body burden on immune response of school children.

The effects of cadmium on measures of immune-system function were determined from a health survey of school children in heavily polluted regions of eastern Germany. A representative sample of 842 students, aged 5-14 y, was included in logistic regression analyses in which the relationship between urinary cadmium content and blood immunoglobulin levels was examined. Investigators further evaluated a subsample of 807 students to determine cadmium's effect on the immediate hypersensitivity reactions elicited by skin-prick challenges with 12 common aeroallergens. Several potentially confounding factors were controlled for, after which investigators found that increasing body burdens of cadmium were associated consistently with dose-dependent suppression of immediate hypersensitivity and of immunoglobin G, but not immunoglobulins M, A, or E levels. The immunoglobulin pattern observed in exposed children led investigators to suggest that secondary humoral responses were impaired by cadmium.