A digital pixel sensor array with programmable dynamic range

This paper presents a digital pixel sensor (DPS) array employing a time domain analogue-to-digital conversion (ADC) technique featuring adaptive dynamic range and programmable pixel response. The digital pixel comprises a photodiode, a voltage comparator, and an 8-bit static memory. The conversion characteristics of the ADC are determined by an array-based digital control circuit, which linearizes the pixel response, and sets the conversion range. The ADC response is adapted to different lighting conditions by setting a single clock frequency. Dynamic range compression was also experimentally demonstrated. This clearly shows the potential of the proposed technique in overcoming the limited dynamic range typically imposed by the number of bits in a DPS. A 64 /spl times/ 64 pixel array prototype was manufactured in a 0.35-/spl mu/m, five-metal, single poly, CMOS process. Measurement results indicate a 100 dB dynamic range, a 41-s mean dark time and an average current of 1.6 /spl mu/A per DPS.     

Mechanism of human immunodeficiency virus type 1 localization in CD4-negative thymocytes: differentiation from a CD4-positive precursor allows productive infection

Human immunodeficiency virus (HIV) infection of the thymus could have profound effects on development of the immune response, particularly in children. We and others have established that in addition to infecting and depleting CD4-bearing thymocytes, functional HIV proviruses are found in thymocytes lacking surface CD4 expression. Using in vitro thymocyte cultures, we show that neither HIV-mediated down regulation of CD4 nor CD4-independent infection contributes to the localization of HIV in cells lacking the primary virus receptor. Rather, infection of a CD4-positive precursor cell (CD4 positive/CD8 positive) with subsequent differentiation into a mature CD4-negative phenotype results in productively infected CD4-negative cells. This novel mechanism may contribute to pathogenesis by distributing viral sequences into functional subsets of T cells typically refractory to HIV infection and could account for the presence of viral DNA in CD8-positive lymphocytes recently observed in patients.     

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.     

Two-way Bayesian hierarchical phylogenetic models: An application to the co-evolution of gp120 and gp41 during and after enfuvirtide treatment

Enfuvirtide (ENF) is a fusion inhibitor that prevents the entry of HIV virions into target cells. Studying the characteristics of viral evolution during treatment and after a treatment interruption can lend insight into the mechanisms of viral evolution and fitness. Although interruption of anti-HIV therapy often results in rapid emergence of an archived “wild-type” virus population, previous work from our group indicates that when only ENF is interrupted, viral gp41 continues to evolve forward and resistance mutations are lost due to back-mutation and remodeling of the envelope protein. To examine the co-evolution of gp120 and gp41 during ENF interruption we extend the Bayesian Hierarchical Phylogenetic model (HPM). Current HPMs enforce conditional independence across all outcomes while biologically all gene regions within a patient should return the same tree unless recombination confers an evolutionary selective advantage. A two-way-interaction HPM is proposed that provides middle ground between these two extremes and allows us to test for differences in evolutionary pressures across gene regions in multiple patients simultaneously. When the model is applied to a well-characterized cohort of HIV-infected patients interrupting ENF we find that across patients, the virus continued to evolve forward in both gene regions. Overall, the hypothesis of independence over dependence between the gene regions is supported. Models that allow for the examination of co-evolution over time will be increasingly important as more therapeutic classes are developed, each of which may impact other through novel and complex mechanisms.     

Chemistry of by-product gypsum and plaster III.—Retarder insensitivity in hydrating calcium sulphate β-hemihydrate

A study has been made of the effect of fluoroaluminium ions on the retarded hydration of calcium sulphate β-hemihydrate brought about by amino acid retarders. If sufficient fluoroaluminium ions are present (～0.02–0.03% Al as co-crystalline AlF^2?₅ in the hemihydrate), the hemihydrate becomes insensitive to retarder addition because the latter forms stable chelates with the fluoroaluminate ions. The retarder is thus effectively deactivated because the chelates are not sufficiently strongly adsorbed on to the faces of the growing gypsum crystals to influence the rate of advance of the growth steps.     

Mycotoxins in breakfast cereals from the Canadian retail market: A 3-year survey

One hundred and fifty-six samples of breakfast cereals were collected from the Canadian retail marketplace over a 3-year period. The samples were analysed for the mycotoxins deoxynivalenol, nivalenol, HT-2 toxin, zearalenone, ochratoxin A, and fumonisins B₁ and B₂ to contribute to dietary exposure estimates in support of the development of Canadian guidelines for selected mycotoxins in foods. The samples included corn-, oat-, wheat- and rice-based cereals, as well as mixed-grain cereals, and were primarily from North American processors. Overall, deoxynivalenol was the most frequently detected mycotoxin  — it was detected in over 40% of all samples analysed. Fumonisins and ochratoxin A were each detected in over 30% of all samples. Zearalenone was detected in over 20% of all samples. Nivalenol and HT-2 toxin were each detected in only one sample. The survey clearly demonstrated regular occurrence of low levels of multiple mycotoxins in breakfast cereals on the Canadian market.     

Object-based image similarity computation using inductive learningof contour-segment relations

Describes an efficient and effective image similarity calculation method for object-based image comparison at the level of object classes. It uses probabilistic-prediction voting based on the predicted class distribution of each segment of the contour of an object in an image to determine the class of the object. The C4.5 inductive learning algorithm is used to predict the class distribution of object-contour segments. This method is invariant to rotation, scaling and translation of objects. Experimental results show that the method is effective and efficient. It can be used for object-based image retrieval.     

Changes in structure of the bovine milk fat globule membrane on heating whole milk.

The effects of heat-induced interactions between milk fat globule membrane components and skim milk proteins in whole milk on the structure of the membrane were examined by isopycnic sucrose density gradient centrifugation and by using Triton X-100 as a membrane probe. Skim milk components were incorporated into all the lipoprotein fractions separated by density gradient centrifugation. High density complexes, higher in density than those found in the natural milk fat globule membrane, were formed during the heat treatment. Losses of natural membrane polypeptides from the medium and low density lipoproteins were observed on heating. Heating whole milk also altered the rate of release of membrane components by detergent, with decreases in protein released and an increase in phospholipid constituents released. Studies on washed cream indicated that some of the changes in the membrane on heating whole milk occurred due to the heat treatment alone, independent of the interactions with skim milk proteins.     

Spatial Structure of a Single Mn Impurity State on GaAs (110) Surface

Using a low temperature scanning tunneling microscope (STM), we have manipulated individual Mn adatoms at the GaAs (110) surface to apparently bond with two surface As atoms. In this configuration the Mn atoms, which either are at an interstitial site or have substituted for a surface Ga atom, give rise to strong in-gap levels as probed by spatially resolved STM spectroscopy measurements. Mapping the Mn-induced in-gap bound state shows an unusual spatial structure, with highly anisotropic character. The bound state shares some characteristic features with subsurface Mn and Zn dopants.