VIPMOS-a novel buried injector structure for EPROM applications

A buried injector is proposed as a source of electrons for substrate hot electrons injection. To enhance the compatibility with VLSI processing, the buried injector is formed by the local overlap of the n-well and p-well of a retrograde twin-well CMOS process. The injector is activated by means of punchthrough. This mechanism allows the realization of a selective injector without increasing the latchup susceptibility. The p-well profile controls the punchthrough voltage. The high injection probability and efficient electron supply mechanism lead to oxide current densities up to 1.0 Å.×cm^-2. Programming times of 10 μs have been measured on nonoptimized cells. The realization of a structure for 5-V-only digital and analog applications is viable. A model of the structure for implementation in a circuit simulator, such as SPICE, is presented     

The alternative financialization of the German housing market

While many European countries experienced a global housing boom in the early/mid-2000s, house prices and mortgage debt in Germany stagnated. Therefore, the German housing system is considered to be operating outside financialized capitalism. Despite Germany’s apparent stability, we argue that an alternative trajectory of financialization in the German housing market can be observed. This trajectory has followed three stages or ‘waves’. The first wave started around the time of German unification and is characterized by the failed attempt of West German banks to marketize and liberalize German housing finance. The second wave started in the late 1990s and is characterized by the ‘financialized privatization’ of many public housing associations and the speculative investments of private equity firms and hedge funds. The third wave started during the global financial crisis and is characterized by booming housing prices and the market entry of listed real estate companies.     

Oncological implications of RET gene mutations in Hirschsprung's disease

BACKGROUND: Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may therefore be exposed to a highly increased risk of tumours. AIMS: To define clinical use of RET gene testing in Hirschsprung's disease and related patient management from an oncological point of view. METHODS: Sixty patients with Hirschsprung's disease were screened for RET mutations. In three, MEN2A type RET mutations were detected. Case reports for these three patients are presented. RESULTS AND CONCLUSIONS: Only 22 families or sporadic patients with Hirschsprung's disease and MEN2A type RET mutations have been reported. Therefore, it is difficult to predict tumour risk for patients with familial or sporadic Hirschsprung's disease, and their relatives, who carry these mutations. For these mutation carriers, periodic screening for tumours as in MEN2A is advised, but prophylactic thyroidectomy is offered hesitantly. RET gene testing in familial or sporadic Hirschsprung's disease is not recommended at present outside a complete clinical research setting. In combined MEN2A/Hirschsprung's disease families RET gene testing, tumour screening, and prophylactic thyroidectomy are indicated as in MEN2A.     

Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers.     

The role of macrophages in the induction and regulation of immunity elicited by exogenous antigens

Different delivery vehicles may target to different antigen presenting cells (APC) because of their composition, size and/or physical properties. In this study, we examined the priming of cytotoxic T lymphocyte (CTL) responses to a soluble exogenous protein in vivo, using various delivery vehicles. In addition, we determined the role of macrophages as APC in vivo for each of these delivery vehicles by comparing the induction of antigen-specific CTL and serum antibodies in normal and macrophage-depleted mice. Influenza A virus-derived virosomes, liposomes and monophosphoryl lipid A/squalene (MPLSQ) efficiently induced antigen-specific CTL as well as antibody responses, of which virosomes proved to be the most efficient inducers. In mice that were immunized with cell-associated antigen, strong CTL responses but no antigen-specific antibodies were detectable, while aluminium hydroxide and aluminium phosphate elicited antigen-specific antibodies but no CTL responses. Elimination of macrophages in vivo before immunization abrogated CTL responses induced with liposomes and MPL/SQ, but did not affect induction of antigen-specific CTL with virosomes or cell-associated antigen. Importantly, serum antibody levels were not altered after macrophage depletion, regardless of the delivery vehicle used, suggesting that in the absence of macrophages, other APC may phagocytose the exogenous antigens for major histocompatibility complex (MHC) class II processing and presentation. These results suggest that soluble exogenous antigens delivered in different carrier systems may be processed differently by different APC in vivo for MHC class I- or class II-restricted presentation.     

Partial deletion of 18p and partial duplication of 18q caused by a paternal pericentric inversion

The frequency of urinary infection was determined using quantitative microbiology in 172 insulin-dependent diabetic patients repeatedly being tested for microalbuminuria over 18 months on at least six occasions. The point prevalence of urinary infection at first screening for microalbuminuria was 3%. Over the period of study, 20 of the patients (12%) showed evidence of urinary infection, defined as a pure growth of a recognized pathogen > 10(7)I-1. Infection was more common in women than men (20% vs 5%, p < 0.01) and was significantly associated with the presence of peripheral neuropathy (p < 0.05). Infection was not related to patient age, duration of diabetes, glycaemia, blood pressure, retinopathy or autonomic neuropathy. There were no significant within-patient differences in albumin excretion, glycaemic control or blood pressure in relation to the presence and absence of urinary infection. In only one patient (5%) did urinary infection significantly increase the urinary albumin excretion and this was associated with pyuria. We conclude that the presence of urinary infection does not apparently affect the measurement of urinary albumin excretion unless pyuria is present. Unless diabetic patients are symptomatic, examination of the urine for infection is probably unwarranted when testing for microalbuminuria.     

Improved device performance by multistep or carbon co-implants

High-energy ion implantation is used for forming the collector in vertical bipolar transistors in a BiCMOS process. Secondary defects, remaining after annealing the implant damage, give rise to an increased leakage current and to collector-emitter shorts. These shorts reduce the transistor yield. The use of multiple step implants or the introduction of a C gettering layer are demonstrated to avoid dislocation formation. Experimental results show that these schemes subsequently lower the leakage current and dramatically increase device yield. The presence of C can cause increased collector/substrate leakage, indicating that the C profile needs to be optimized with respect to the doping profiles     

New method for determining emitter resistance

A new method is described to determine the emitter resistance of bipolar transistors. With this method the emitter resistance can directly be extracted from the Gummel plot. It is based on the fact that the base current is zero at a certain collector-base voltage due to impact ionisation.<>     

Strongly asymmetric doping profiles at mask edges in high-energyion implantation

The application of high-energy ion implantation is restricted by an asymmetric doping profile at the mask edges. As a result, buried interconnect cannot easily be formed. Moreover, the holding voltage and threshold voltage of CMOS-processes with retrograde wells may be strongly affected by this asymmetry. It arises from the 7° wafer tilt, which is frequently used to avoid channeling, even in the case of nearly perpendicular (82-85°) mask edges. On the mask side, which is incoming to the ion beam, a trunk to the surface has experimentally been observed. According to two-dimensional Gaussian and advanced Monte Carlo simulations, the doping concentration in this trunk is about 20% of the maximum concentration in the case of a 85° mask angle. The simulations predict the experimental results fairly well. The asymmetry effect of high energy ion implantations can also be visualized in photoresist by means of a damaged region     

Caustic injury of the oesophagus. Sixteen years experience, and introduction of a new model oesophageal stent

Caustic ingestion can lead to oesophageal stenosis. We studied 251 patients, 205 of whom were children, in a sixteen-year period. Seventeen patients, of whom one was an adult, acquired deep burns in the oesophagus which had to be treated, to prevent the development of oesophageal strictures. These patients were treated with long-term stenting of the oesophagus with specially designed, silicone rubber stents, impregnated with silicone oil 20 cS, designed by one of us (R.N.P.B.) as the only treatment. Of all models, the twin-tube dilator was the most satisfactory. No corticosteroids were administered. Only one patient developed a mild stenosis. It is therefore our opinion that, when life-saving operations are not indicated, twin-tube stenting of the oesophagus is helpful in treating caustic lesions of the oesophagus and will prevent stricture formation. Corticosteroids were not given in this series, and should be abandoned in the treatment of caustic lesions.