Optical diagnostic monitoring of resonant-tunneling diode growth

We are employing in situ sensors to monitor and diagnose MBE growth in real-time. Two optical methods, spectroscopic ellipsometry (SE) and laser light scattering (LLS), provide complementary information on strained layer epitaxy. A quantum effect structure, the resonant-tunneling diode (RTD), provides a challenging and important test device vehicle for these studies. The RTD current-voltage characteristics exhibit sensitivities to thickness changes of less than a monoatomic layer. Strain relaxation in vertically-integrated RTD stacks was detected using LLS. Structural data determined using SE was correlated with RTD electrical characteristics (peak current, peak voltage, valley current, asymmetry ratios). Closed-loop control based on SE is being investigated to improve the reproducibility of RTD growth     

Receptor-mediated endocytosis in kidney proximal tubules: recent advances and hypothesis

Preparation of kidney proximal tubules in suspension allows the study of receptor-mediated endocytosis, protein reabsorption, and traffic of endosomal vesicles. The study of tubular protein transport in vitro coupled with that of the function of endosomal preparation offers a unique opportunity to investigate a receptor-mediated endocytosis pathway under physiological and pathological conditions. We assume that receptor-mediated endocytosis of albumin in kidney proximal tubules in situ and in vitro can be regulated, on the one hand, by the components of the acidification machinery (V-type H+-ATPase, Cl(-)-channel and Na+/H+-exchanger), giving rise to formation and dissipation of a proton gradient in endosomal vesicles, and, on the other hand, by small GTPases of the ADP-ribosylation factor (Arf)-family. In this paper we thus analyze the recent advances of the studies of cellular and molecular mechanisms underlying the identification, localization, and function of the acidification machinery (V-type H+-ATPase, Cl(-)-channel) as well as Arf-family small GTPases and phospholipase D in the endocytotic pathway of kidney proximal tubules. Also, we explore the possible functional interaction between the acidification machinery and Arf-family small GTPases. Finally, we propose the hypothesis of the regulation of translocation of Arf-family small GTPases by an endosomal acidification process and its role during receptor-mediated endocytosis in kidney proximal tubules. The results of this study will not only enhance our understanding of the receptor-mediated endocytosis pathway in kidney proximal tubules under physiological conditions but will also have important implications with respect to the functional consequences under some pathological circumstances. Furthermore, it may suggest novel targets and approaches in the prevention and treatment of various diseases (cystic fibrosis, Dent's disease, diabetes and autosomal dominant polycystic kidney disease).     

Robust projected clustering

Projected clustering partitions a data set into several disjoint clusters, plus outliers, so that each cluster exists in a subspace. Subspace clustering enumerates clusters of objects in all subspaces of a data set, and it tends to produce many overlapping clusters. Such algorithms have been extensively studied for numerical data, but only a few have been proposed for categorical data. Typical drawbacks of existing projected and subspace clustering algorithms for numerical or categorical data are that they rely on parameters whose appropriate values are difficult to set appropriately or that they are unable to identify projected clusters with few relevant attributes. We present P3C, a robust algorithm for projected clustering that can effectively discover projected clusters in the data while minimizing the number of required parameters. P3C does not need the number of projected clusters as input, and can discover, under very general conditions, the true number of projected clusters. P3C is effective in detecting very low-dimensional projected clusters embedded in high dimensional spaces. P3C positions itself between projected and subspace clustering in that it can compute both disjoint or overlapping clusters. P3C is the first projected clustering algorithm for both numerical and categorical data.     

Two‐Step Targeted Hybrid Nanoconstructs Increase Brain Penetration and Efficacy of the Therapeutic Antibody Trastuzumab against Brain Metastasis of HER2‐Positive Breast Cancer

Therapeutic antibodies (e.g., trastuzumab, TRA) against human epidermal growth factor receptor 2 (HER2)‐positive breast cancers have shown benefits in controlling primary tumors, yet are ineffective against brain metastases due to their inability to cross the blood‐brain barrier (BBB). A novel hybrid nanoconstruct system is designed to deliver trastuzumab to brain metastasis of HER2‐positive breast cancer via a two‐step sequential targeting approach. Self‐assembly of a polysorbate 80 (PS 80)‐containing polymer, lipid, and polymer‐conjugated TRA forms hybrid nanoconstructs (TRA–terpolymer nanoparticles (TPN)) with high encapsulation efficiency and bioactivity. The PS 80 moiety enables the first‐step targeting and receptor‐mediated trancytosis across BBB is demonstrated in vitro with a 3D human BBB model in healthy and brain tumor‐bearing mice. The subsequent partial dissociation of the nanoconstructs exposes the encapsulated TRA for the second‐step targeting to HER2‐positive cancer cells in the brain. Intravenously injected TRA–TPN delivers 50‐fold TRA compared to free TRA to the brain metastasis of HER2‐positive breast cancer. Treatment with TRA–TPN increases tumor cell apoptosis by 4‐fold, inhibits tumor growth by 43‐fold, and prolongs median survival by >1.3‐fold compared to free TRA, without causing noticeable organ toxicity. These findings suggest the two‐step targeted nanoconstruct system is promising for shuttling therapeutic antibodies to treat central nervous system diseases.     

Perspectives on low voltage transmission electron microscopy as applied to cell biology

Low voltage transmission electron microscopy (LVTEM) with accelerating voltages as low as 5 kV was applied to cell biology. To take advantage of the increased contrast given by LVTEM, tissue preparation was modified omitting all heavy metals such as osmium, uranium, and lead from the fixation, on block staining and counterstaining. Nonstained ultra‐thin tissue sections (40 nm thick) generated highly contrasted images. While the aspect of the cells remains similar to that obtained by conventional TEM, some new substructures were revealed. The pancreatic acinar cells granules present a heterogeneous matrix with partitions corresponding to segregation of their different secretory proteins. Microvilli display their core of microfilaments anchored to the dense top membrane. Mitochondria revealed the presence of distinct particles along their cristea membranes that may correspond to the ATP synthase complexes or oxysomes. The dense nuclear chromatin displays a honey‐comb appearance while distinct beads aligned along thin threads were seen in the dispersed chromatin. These new features revealed by LVTEM correlate with structures described or predicted through other approaches. Masking effects due to thickness of the tissue sections and to the presence of heavy metals must have prevented their observation by conventional TEM. Furthermore, the immunogold was adapted to LVTEM revealing nuclear lamin‐A at the edge of the dense chromatin ribbons. Combining cytochemistry with LVTEM brings additional advantages to this new approach in cell biology. Microsc. Res. Tech. 77:999–1004, 2014. © 2014 Wiley Periodicals, Inc.     

Is progression of coronary artery disease occurring at bouts or as a continuous process? Serial cineangiographic studies in 44 patients

In order to assess if coronary artery disease progression occurs as a slow, continuous process or at bouts, the coronary angiograms of 44 patients catheterized three times were reviewed. A previously developed logistic model, taking into account time interval between the angiograms, age, occurrence of unstable angina, and extent score of coronary artery disease, was used to compute a probability of progression from the second to the third angiogram. Two groups of patients were considered: those with (n = 15) and those without (n = 29) progression from the first to the second angiogram (PROGRESSION 1-2). A simulation provided in each group the distribution of the expected number of patients with progression from the second to the third catheterization. In the group without PROGRESSION 1-2, the observed number of progressions from the second to the third angiogram was in agreement with the expected one. However, in the group with PROGRESSION 1-2, the progression from the second to the third angiogram was more frequent than expected (p = 0.068). These results suggest that, in many patients, coronary artery disease progression is continuous over several years.     

Hydrogen bonding in poly(styrene-mono-ethyl-maleate)

This paper studies the styrene-(mono-ethyl-maleate) copolymer using IR spectroscopy. The copolymer was obtained by styrene copolymerization with maleic anhydride, in ethanol as the reaction medium. The IR spectra recorded give information concerning the physico-chemical structure, the monomer ratio and emphasize the intermolecular interactions corresponding to the hydrogen bond associations. The elevated temperature studies (90–130°C) allowed us to establish the equilibrium constants, the enthalphy and entropy variation, values of –4.2 kcal mol^-1 and –3.7 e.u. mol^-1, respectively, being obtained.     

Heterogeneous sympathetic innervation in German shepherd dogs with inherited ventricular arrhythmia and sudden cardiac death

BACKGROUND: Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation to the heart. METHODS AND RESULTS: We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/-16.5% denervation, whereas the group without ventricular tachycardia showed 12+/-5.6% denervation (P<.02). CONCLUSIONS: Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.     

Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios sequence

A mass balance for lead for the year 1989 in the South Coast Air Basin has inputs to the atmosphere of 600 +/- 190 kg/day and outputs of 580 +/- 160 kg/day, showing rough agreement. Stationary sources are responsible for only about 5% of the total lead emissions. The bulk of the lead is emitted from vehicles using leaded gasoline (37%) and unleaded gasoline (15%), as well as from resuspension of previously deposited lead on roads (43%). Over half of the total emitted lead deposits on roads and nearby soil, while about one-third is carried out the basin by wind. A small amount, less than 10%, is deposited on surfaces throughout the basin. These percentages are approximately the same as those in a mass balance for the same region calculated for 1972, when lead emissions from leaded gasoline were about a factor of 70 greater than leaded gas emissions in 1989. When the lead emissions are used as inputs to a simple continuously stirred flow reactor model for the basin, reasonable agreement is obtained between calculated and measured concentrations.     

Fetal RhD typing by polymerase chain reaction in pregnancies complicated by rhesus alloimmunization

OBJECTIVE: To review the specificity and sensitivity of diagnostic techniques using the polymerase chain reaction (PCR) on amniotic fluid (AF) samples for the determination of fetal RhD status. DATA SOURCES: A MEDLINE computerized search was conducted for January 1991 through March 1996 using the key terms "polymerase chain reaction," "rhesus," and "RhD typing." METHODS OF STUDY SELECTION: All articles describing the use of PCR in AF for RhD typing were reviewed. Only cases in which the results of PCR testing were confirmed by fetal or neonatal serology were included in the final analysis. TABULATION, INTEGRATION, AND RESULTS: The results of PCR typing were compared with serology to determine the sensitivity, specificity, and positive and negative predictive values of DNA-based techniques. A total of 500 cases were reviewed, in which four different sets of oligonucleotide primers were used. The sensitivity and specificity of PCR typing were 98.7% and 100%, respectively, and the positive and negative predictive values were 100% and 96.9%, respectively. In five cases, an RhD-positive fetus was incorrectly diagnosed: Two fetuses died, one neonate needed exchange transfusions, and another neonate needed phototherapy in conjunction with a simple transfusion. The remaining infant was lost to follow-up. A theoretical model indicated that amniocentesis with PCR-based techniques for fetal RhD typing would be associated with a fourfold reduction in perinatal loss compared with funipuncture and serology for fetal typing. CONCLUSIONS: This lower rate of procedure-related loss makes RhD typing using AF the preferred method for assessing the fetal Rh status in cases of a heterozygous paternal genotype.