Carbon Chain Length Modulates MDA-MB-231 Breast Cancer Cell Killing Mechanisms by Mitochondrially Targeted Aryl−Urea Fatty Acids

Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC₅₀s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion.     

Measurements of single chain form factors by small-angle neutron scattering from polystyrene blends containing high concentrations of labelled molecules

A series of small angle neutron scattering measurements on blends of normal polystyrene (PSH) and labelled (deuterated) polystyrene (PSD) have been made with concentrations of PSD from 5 to 50 mol %. It is shown that the single chain form factor of the polymer in bulk can be obtained from a single concentration measurement for any concentration of labelled molecules, providing the molecular weights of the parent and labelled molecules are the same and the molecular weight distributions are narrow.     

Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus: clinical characteristics in a case-control study

Clinical characteristics associated with bacillary angiomatosis and bacillary peliosis (BAP) in patients with human immunodeficiency virus (HIV) infection were evaluated in a case-control study; 42 case-patients and 84 controls were matched by clinical care institution. Case-patients presented with fever (temperature, > 37.8 degrees C; 93%), a median CD4 lymphocyte count of 21/mm3, cutaneous or subcutaneous vascular lesions (55%), lymphadenopathy (21%), and/or abdominal symptoms (24%). Many case-patients experienced long delays between medical evaluation and diagnosis of BAP (median, 4 weeks; range, 1 day to 24 months). Case-patients were more likely than controls to have fever, lymphadenopathy, hepatomegaly, splenomegaly, a low CD4 lymphocyte count, anemia, or an elevated serum level of alkaline phosphatase (AP) (P < .001). In multivariate analysis, a CD4 lymphocyte count of < 200/mm3 (matched odds ratio [OR], 9.9; P < .09), anemia reflected by a hematocrit value of < 0.36 (OR, 19.7; P < .04), and an elevated AP level of > or = 2.6 mukat/L (OR, 23.9; P < .05) remained associated with disease after therapy with zidovudine was controlled for. BAP should be considered an AIDS-defining opportunistic infection and should be included in the differential diagnosis for febrile, HIV-infected patients with cutaneous or osteolytic lesions, lymphadenopathy, abdominal symptoms, anemia, or an elevated serum level of AP.     

Misinterpretation of body sensations in panic disorder

Cognitive accounts of panic predict that panic disorder patients will be particularly prone to misinterpret autonomic sensations. Several studies have produced results consistent with this prediction, but each is open to alternative interpretation. To clarify matters, 2 studies administered the Body Sensations Interpretation Questionnaire (BSIQ) to panic patients and controls. Panic patients were more likely to interpret ambiguous autonomic sensations as signs of immediately impending physical or mental disaster and were more likely than other anxiety disorder patients and nonpatients to believe these interpretations. In a 3rd study, a brief version of the BSIQ was shown to have satisfactory test-retest reliability, to change with treatment, and to discriminate treatments that varied in their effects on panic.     

Fluorescene in situ hybridization establishes homology between human and silvered leaf monkey chromosomes, reveals reciprocal translocations between chromosomes homologous to human Y/5, 1/9, and 6/16, and delineates an X1X2Y1Y2/X1X1X2X2 sex-chromosome system

The adhesive core of the desmosome is composed of cadherin-like glycoproteins of 2 families, desmocollins and desmogleins. The desmosomal cadherins show distinct patterns of expression in adult epidermis, and we have suggested that the desmocollins have a functional role in regulating the differentiation and/or morphogenesis of that epithelium (North et al. [1996] Proc. Natl. Acad. Sci. USA 93:7701-7705.). To examine this hypothesis, we cloned murine desmocollins and examined the induction patterns of desmocollins 1 and 3 during skin and skin appendage development. Desmocollins 3 and 1 were first expressed in epidermis in highly regional patterns at embryonic days 13.0 and 13.5, respectively, and both were up-regulated in general body epidermis at day 14.5. At this stage, epidermis is undifferentiated and the desmocollins showed an unexpected expression pattern. However, by day 18.5 when skin had undergone terminal differentiation, desmocollin 1 and 3 expression resembled that found in the adult. Thus, the establishment of the adult pattern of desmocollin expression corresponds to the adult pattern of epidermal stratification. We suggest that it is the ratio of desmocollin 1 to desmocollin 3 expression at different levels in the epidermis that is fundamental in establishing this pattern of differentiation.     

Regional and cellular expression of glial (GLT1) and neuronal (EAAC1) glutamate transporter proteins in ovine fetal brain

Glutamate transport is a primary mechanism for regulating extracellular levels of glutamate which can have either neurotrophic or neurotoxic effects in the developing brain, depending on its concentration. Using immunoblotting and immunocytochemistry, we tested the hypotheses that expression of neuronal and glial glutamate transporter proteins was regionally and temporally regulated in the developing ovine brain and that expression of the glial isoform early in development was not cell-type specific. Immunoblots for the neuronal glutamate transporter EAAC1 revealed a major band of immunoreactivity at 69,000 nmol. wt, whereas glial glutamate transporter-1 (GLT1) immunoreactivity was observed as 73,000 and 146,000 mol. wt proteins. EAAC1 and GLT1 are regulated differently during development, with EAAC1 immunoreactivity being most abundant at 60 and 71 days completed gestation (term=145 days) and dissipating thereafter, while GLT1 immunoreactivity was most abundant at 136 days gestation. By immunocytochemistry EAAC1 expression is neuronal throughout gestation with intense labelling of dendrites within the telencephalon evident at 60 days. Neuropil, neuronal cell bodies and processes are EAAC1-immunoreactive throughout gestation with no evidence of astrocytic or oligodendroglial immunoreactivity. In contrast, GLT1 is expressed by neuronal and non-neuronal cell types during midgestation with astrocyte selectivity developing by 136 days. During midgestation, GLT1 is transiently expressed in neurons of the subplate, cranial nerve nuclei, basal ganglia, and cerebellar cortex. The major finding of this study, that GLT1 is transiently expressed in various neuronal populations at midgestation demonstrates that the cell-type specificity of the GLT1 phenotype is developmentally regulated and depends on brain maturity.     

Types and associated type families for hardware simulation and synthesis

In this article we overview the design and implementation of the second generation of Kansas Lava. Driven by the needs and experiences of implementing telemetry decoders and other circuits, we have made a number of improvements to both the external API and the internal representations used. We have retained our dual shallow/deep representation of signals in general, but now have a number of externally visible abstractions for combinatorial and sequential circuits, and enabled signals. We introduce these abstractions, as well as our abstractions for reading and writing memory. Internally, we found the need to represent unknown values inside our circuits, so we made aggressive use of associated type families to lift our values to allow unknowns, in a principled and regular way. We discuss this design decision, how it unfortunately complicates the internals of Kansas Lava, and how we mitigate this complexity. Finally, when connecting Kansas Lava to the real world, the standardized idiom of using named input and output ports is provided by Kansas Lava using a new monad, called Fabric. We present the design of this Fabric monad, and illustrate its use in a small but complete example.     

MET𝔸P: revisiting Privacy-Preserving Data Publishing using secure devices

The goal of Privacy-Preserving Data Publishing (PPDP) is to generate a sanitized (i.e. harmless) view of sensitive personal data (e.g. a health survey), to be released to some agencies or simply the public. However, traditional PPDP practices all make the assumption that the process is run on a trusted central server. In this article, we argue that the trust assumption on the central server is far too strong. We propose Met _??P, a generic fully distributed protocol, to execute various forms of PPDP algorithms on an asymmetric architecture composed of low power secure devices and a powerful but untrusted infrastructure. We show that this protocol is both correct and secure against honest-but-curious or malicious adversaries. Finally, we provide an experimental validation showing that this protocol can support PPDP processes scaling up to nation-wide surveys.     

Performance analysis challenges and framework for high-performance reconfigurable computing

Reconfigurable computing (RC) applications employing both microprocessors and FPGAs have potential for large speedup when compared with traditional (software) parallel applications. However, this potential is marred by the additional complexity of these dual-paradigm systems, making it difficult to identify performance bottlenecks and achieve desired performance. Performance analysis concepts and tools are well researched and widely available for traditional parallel applications but are lacking in RC, despite being of great importance due to the applications’ increased complexity. In this paper, we explore challenges and present new techniques in automated instrumentation, runtime measurement, and visualization of RC application behavior. We also present ideas for integration with conventional performance analysis tools to create a unified tool for RC applications as well as our initial framework for FPGA instrumentation and measurement. Results from a case study are provided using a prototype of this new tool.