Integrating Through-Wafer Interconnects With Active Devices and Circuits

Through wafer interconnects (TWIs) enable vertical stacking of integrated circuit chips in a single package. A complete process to fabricate TWIs has been developed and demonstrated using blank test wafers. The next step in integrating this technology into 3D microelectronic packaging is the demonstration of TWIs on wafers with preexisting microcircuitry. The circuitry must be electrically accessible from the backside of the wafer utilizing the TWIs; the electrical performance of the circuitry must be unchanged as a result of the TWI processing; and the processing must be as cost effective as possible. With these three goals in mind, several options for creating TWIs were considered. This paper explores the various processing options and describes in detail, the final process flow that was selected for testing, the accompanying masks that were designed, the actual processing of the wafers, and the electrical test results.     

The basilic vein as an in situ bypass for occlusion of the brachial artery

For 30 years we have followed the case of a euthyroid patient who had a goiter diagnosed at age 15. It was originally diffuse and did not shrink during treatment, first with desiccated thyroid extract and then with triiodothyronine. After treatment was stopped, the goiter gradually became nodular and calcified when the patient was in her late teens or early 20s; it then shrank. She remains clinically and chemically euthyroid, with a calcified, multinodular goiter and persistent elevation of the serum PBI concentration which, early in the course of the disease was shown to include a substantial fraction of butanol-insoluble iodine. In a euthyroid patient, the association of an elevated serum PBI concentration (with an abnormally large butanol-insoluble iodine fraction) with a diffuse goiter that became nodular and calcified may be unique.     

Neo-colonial science by the most industrialised upon the least developed countries in peer-reviewed publishing

We are currently experiencing an era that is facing increasing global environmental and societal problems (e.g., climate change, habitat destruction and economic recession). Scientific research projects are often required to emphasize and counter the effects of inequity and globalisation, and prioritise cooperation supported by cooperative research. This paper investigates whether publication of research that is carried out in least developed countries is done in cooperation with research institutes from these countries. The study uses the Current Contents database of peer-reviewed publications from more than 7,000 journals in all sciences (Biology and environmental sciences; Physical, chemical and earth sciences; Engineering, computing and technology; Life sciences; Clinical medicine; Arts and humanities; Social and behavioral sciences) published between 1 January 1999 and 3 November 2000. From a total of 1,601,196 papers published, 2,798 articles of research activities carried out in the 48 least developed countries were selected using title information as an indicator. Collaborative relationships between research institutions involved was then analysed within and between countries and sciences. Our results show that publications of research, carried out in the least developed countries, do not have co-authorship of local research institutes in 70% of the cases, and that a majority of the papers is published by research institutes from the most industrialised countries in the world. We employed the use of questionnaires sent to authors from papers in the above-mentioned database to detect possible causes of this high percentage of lack of authorship in the essential academic currency that 'publications' are. 'Neo-colonial science' is identified as one of them. In addition, there exists a large discrepancy between what the surveyed scientists say they find important in international collaboration and joint publishing, and the way they act to it. However, the interpretation given to the fact that institutional co-authorship is underrepresented for local research institutions in the least developed countries is less important than the fact itself, and future research should concentrate on a scientific way to equilibrate this adverse trend. This revised version was published online in August 2006 with corrections to the Cover Date.     

Infrared A radiation-controlled permeation of tetracaine in vitro and in vivo

The incidence and case fatality rates of meningococcal disease were assessed in the county of Northern Jutland, Denmark, during the 16-year period from 1980 to 1995. A total of 320 patients were identified from the Meningococcal Research Database, which comprises information from the following sources: (i) the Department of Public Health, to whom notification of meningococcal disease is obligatory; (ii) the Regional Hospital Discharge Registry; and (iii) the register of the regional department of clinical microbiology. In order to assess prognostic indicators assessable at admission, information was collected for each patient from hospital records regarding contacts, symptoms and signs on arrival, laboratory data, and course of disease. The mean incidence was 4.3 cases per 100000 persons per year (range, 2.7-7.7). The incidence increased slightly during the period studied. Overall, the case fatality rate was 9.7%, with a significant rise occurring during the period (P=0.016) and a peak occurring in 1992. Advanced age (> or = 50 years), seizures, impaired consciousness, and skin bleeding on arrival at hospital were predictors of death.     

Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas

Uroplakins (UPs) Ia, Ib, II, and III, transmembrane proteins constituting the asymmetrical unit membrane of urothelial umbrella cells, are the first specific urothelial differentiation markers described. We investigated the presence and localization patterns of UPs in various human carcinomas by applying immunohistochemistry (avidin-biotin-peroxidase complex method), using rabbit antibodies against UPs II and III, to paraffin sections. Positive reactions for UP III (sometimes very focal) were noted in 14 of the 16 papillary noninvasive transitional cell carcinomas (TCCs) (88%), 29 of the 55 invasive TCCs (53%), and 23 of the 35 TCC metastases (66%). Different localization patterns of UPs could be distinguished, including superficial membrane staining like that found in normal umbrella cells (in papillary carcinoma), luminal (microluminal) membrane staining (in papillary and invasive carcinoma), and, against expectations, peripheral membrane staining (in invasive carcinoma). Non-TCC carcinomas of various origins (n = 177) were consistently negative for UPs. The presence of UPs in metastatic TCCs represents a prime example of even advanced tumor progression being compatible with the (focal) expression of highly specialized differentiation repertoires. Although of only medium-grade sensitivity, UPs do seem to be highly specific urothelial lineage markers, thus operating up interesting histodiagnostic possibilities in cases of carcinoma metastases of uncertain origin.     

Peyer's patch adherence of enteropathogenic Escherichia coli strains in rabbits

RDEC-1 (serotype O15) is an attaching and effacing strain of rabbit enteropathogenic Escherichia coli (REPEC) that causes diarrhea in postweanling rabbits. It expresses AF/R1 pili that mediate Peyer's patch M-cell adherence. We investigated Peyer's patch adherence, the presence of virulence genes, ileal brush border aggregation, and pilus expression in 9 strains representing several serotypes of REPEC as well as in two commensal strains. Postweanling rabbits were inoculated with 10(6) organisms and sacrificed at 24 h, and tissues were prepared for examination by light microscopy. Strains B10 and RDEC-1 were also studied at 12 and 72 h postinoculation. All REPEC strains were eaeA positive, expressed pili, and adhered to ileal brush borders. Both commensal strains expressed pili, and one strain adhered to brush borders. All REPEC strains demonstrated some degree of Peyer's patch lymphoid follicle adherence, ranging from diffuse coverage to small patches covering two to three dome epithelial cells. Strains C102 and C110 had genes homologous with the structural subunit gene of the AF/R1 pilus (afrA) of RDEC-1, which correlated with greater degrees of lymphoid follicle adherence and lesser degrees of ileal villus adherence. The observation that all REPEC strains adhere to Peyer's patch epithelium suggests the possibility that human strains of enteropathogenic E. coli (EPEC) might do likewise. EPEC strains might thus serve as mucosal vaccine vectors in humans. Better understanding of the molecular mechanism of REPEC adherence should provide a model for the targeting of the Peyer's patch in humans.     

Nonenzymatic lactosylation of bovine beta-lactoglobulin under mild heat treatment leads to structural heterogeneity of the glycoforms

Lactose reacts nonenzymatically with beta-lactoglobulin (beta-LG), the major whey protein, under mild heat treatment and the formation of the complex may be monitored by mass spectrometry. Using Reverse Phase HPLC coupled with Electrospray Ionization MS (ESI-MS) we have measured the global extent of glycosylation and examined the distribution of lactose among the beta-LG glycoforms. Identification of lactosylated sites by trypsinolysis and Tandem MS indicate that, although the glycosylation reaction was non-specific and potentially involved all the reactive sites (alpha- and epsilon-amino groups), beta-LG appeared to have at least two populations of lysine with the distinct ability to react with lactose. These results underline the structural heterogeneity of beta-LG glycoforms, with respect to the number of lactose linked per molecule and to the binding sites involved, which could affect the biological function of beta-LG.