A Cholecystokinin B Receptor-Specific Aptamer Does Not Activate Receptor Signaling

Targeted nanoparticles which deliver effective doses of chemotherapeutic drugs directly to pancreatic tumors could improve treatment efficacy without the toxicities associated with systemic drug administration. One protein on tumor cells that can be targeted by nanoparticles is a G-protein coupled cell surface receptor, the cholecystokinin B receptor (CCKBR). Previously, we had shown that attaching the CCKBR ligand gastrin to the surface of nanoparticles can enhance their up-take by tumors. The drawback of using gastrin is that it can also activate the receptor, causing tumor cell growth. This study shows that a DNA aptamer that binds to the CCKBR and enhances nanoparticle up-take by tumors does not activate this receptor. PANC-1 cells, a cultured human pancreatic cancer cell line, were treated for 24 h with CCKBR aptamer 1153. Cell lysates were run on Bis-Tris gels, transferred to membranes, blocked in 5% BSA and incubated overnight with primary antibodies, including antibodies directly against phosphorylated-Akt (Ser473), total Akt, and beta-actin, a protein loading control. Although the CCKBR aptamer 1153 is internalized by pancreatic cancer cells in a receptor-mediated fashion, it does not stimulate cell proliferation. Because of this, we anticipate that it will not activate CCKBR signaling. If aptamer 1153 does not activate downstream receptor signaling, our future work will test whether the aptamer could be used to specifically direct drug-containing nanoparticles to tumors, making chemotherapy treatments for pancreatic cancer patients more effective with fewer off-target effects and toxicity

A Virtual-system Concept for Exergy Analysis of Flow Network Plant; Part I: Principles

A new type of virtual system, named a flow constraint system (FCS), is proposed to facilitate, clarify, and simplify exergy analyses of plant that involve material flow networks. The need for the virtual system is outlined and the concept is demonstrated by applying it to a CHP steam cycle. The FCS concept allows the physical constraints on the exergy interactions associated with flow streams to be taken into account fully. It also simplifies the treatment of bifurcations in material flows and considerably reduces the need for absolute exergy evaluations. The new concept follows from the work already published by the authors on conceptual devices for exergy analysis and builds on this and the work of other authors relating to exergy and exergoeconomic analysis, especially using matrix methods. A bond graph type of diagram is described as an alternative to the usual Grassmann diagram. A numerical illustration is given in a separate paper — Part II

Quantum Non-Demolition Detection of Polar Molecule Complexes: Dimers, Trimers, Tetramers

The optical nondestructive method for in situ detection of the bound states of ultracold polar molecules is developed. It promises a minimally destructive measurement scheme up to a physically exciting quantum non-demolition (QND) level. The detection of molecular complexes beyond simple pairs of quantum particles (dimers, known, e.g., from the BEC-BCS theory) is suggested, including three-body (trimers) and four-body (tertramers) complexes trapped by one-dimensional tubes. The intensity of scattered light is sensitive to the molecule number fluctuations beyond the mean-density approximation. Such fluctuations are very different for various complexes, which leads to radically different light scattering. This type of research extends "quantum optics of quantum gases" to the field of ultracold molecules. Merging the quantum optical and ultracold gas problems will advance the experimental efforts towards the study of the light-matter interaction at its ultimate quantum level, where the quantizations of both light and matter are equally important.Comment: 6 pages, 2 figure

Prevalence and correlates of substance use in Black, White, and biracial Black–White adolescents: Evidence for a biracial intermediate phenomena.

Most substance-use prevention interventions are based on the implicit assumption that risk and protective factors for substance use are the same for biracial and monoracial youth. However, preliminary research suggests this assumption may be untrue. This study compared the prevalence and correlates of substance use among Black, White, and biracial Black-White youth. Data were derived from the National Longitudinal Study of Adolescent and Adult Health (Add Health), which is a longitudinal investigation using stratified random sampling to study health behaviors. After controlling for sociodemographic factors and using weighted Poisson and logistic regression, we found the substance-use prevalence rates of Black-White youth to be intermediate to the higher rates of Whites and lower rates of Blacks. In addition, Black-White youth’s scores on most covariates were intermediate to those of the monoracial groups. Family factors were more important in explaining higher substance use than other contextual factors. School factors seem to be important in explaining lower substance use for Black-White youth. Correlates of substance use for Black-White youth were not identical to those of either Black or White youth. More research on the observed intermediate phenomena among biracial youth vis-à-vis prevalence, correlates, and causes of substance use is needed

Senator James O. Eastland; Herman E. Talmadge; Bob Dole; George McGovern; James B. Allen; Milton Young; Jesse Helms; Patrick Leahy; Henry Bellmon; S.I. Hayakawa; Carl T. Curtis; Richard Lugar; John Melcher; & Dick Clark to President Jimmy Carter, 14 October 1977

Copy typed letter signed dated 14 October 1977 from Eastland; Herman E. Talmadge; Bob Dole; George McGovern; James B. Allen; Milton Young; Jesse Helms; Patrick Leahy; Henry Bellmon; S.I. Hayakawa; Carl T. Curtis; Richard Lugar; John Melcher; & Dick Clark to Carter, re: New Orleans strike of International Longshoremens Association, grain exports; 2 pages.https://egrove.olemiss.edu/joecorr_h/1069/thumbnail.jp

A Comparison of Stimulus Presentation Methods in Temporal Discrimination Testing

The temporal discrimination threshold (TDT) is the shortest time interval at which an individual detects two stimuli to be asynchronous (normal  =  30-50 ms). It has been shown to be abnormal in patients with disorders affecting the basal ganglia including adult onset idiopathic focal dystonia (AOIFD). Up to 97% of patients have an abnormal TDT with age- and sex-related penetrance in unaffected relatives, demonstrating an autosomal dominant inheritance pattern. These findings support the use of the TDT as a pre-clinical biomarker for AOIFD. The usual stimulus presentation method involves the presentation of progressively asynchronous stimuli; when three sequential stimuli are reported asynchronous is taken as a participant\u27s TDT. To investigate the robustness of the \u27staircase\u27 method of presentation, we introduced a method of randomised presentation order to explore any potential \u27learning effect\u27 that may be associated with this existing method. The aim of this study was to investigate differences in temporal discrimination using two methods of stimulus presentation. Thirty healthy volunteers were recruited to the study (mean age 33.73  ±  3.4 years). Visual and tactile TDT testing using a staircase and randomised method of presentation order was carried out in a single session. There was a strong relationship between the staircase and random method for TDT values. This observed consistency between testing methods suggests that the existing experimental approach is a robust method of recording an individual\u27s TDT. In addition, our newly devised randomised paradigm is a reproducible and more efficient method for data acquisition in the clinic setting. However, the two presentation methods yield different absolute TDT results and either of the two methods should be used uniformly in all participants in any one particular study. doi: 10.1088/1361-6579/38/2/N5

Prevalence of binary toxin positive Clostridium difficile in diarrhoeal humans in the absence of epidemic ribotype 027

Virulence of Clostridium difficile is primarily attributed to the large clostridial toxins A and B while the role of binary toxin (CDT) remains unclear. The prevalence of human strains of C. difficile possessing only CDT genes (A¯B¯CDT +) is generally low (\u3c 5%), however, this genotype is commonly found in neonatal livestock both in Australia and elsewhere. Zoonotic transmission of C. difficile has been suggested previously. Most human diagnostic tests will not detect A¯B¯CDT + strains of C. difficile because they focus on detection of toxin A and/or B. We performed a prospective investigation into the prevalence and genetic characteristics of A¯B¯CDT + C. difficile in symptomatic humans. All glutamate dehydrogenase or toxin B gene positive faecal specimens from symptomatic inpatients over 30 days (n = 43) were cultured by enrichment, and C. difficile PCR ribotypes (RTs) and toxin gene profiles determined. From 39 culture-positive specimens, 43 C. difficile isolates were recovered, including two A¯B¯CDT + isolates. This corresponded to an A¯B¯CDT + prevalence of 2/35 (5.7%) isolates possessing at least one toxin, 2/10 (20%) A¯B¯+ isolates, 2/3 CDT + isolates and 1/28 (3.6%) presumed true CDI cases. No link to Australian livestock-associated C. difficile was found. Neither A¯B¯CDT + isolate was the predominant A¯B¯CDT + strain found in Australia, RT 033, nor did they belong to toxinotype XI. Previous reports infrequently describe A¯B¯CDT + C. difficile in patients and strain collections but the prevalence of human A¯B¯CDT + C. difficile is rarely investigated. This study highlights the occurrence of A−B−CDT+ strains of C. difficile in symptomatic patients, warranting further investigations of its role in human infection

Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia

The temporal discrimination threshold (TDT) is the shortest time interval at which an observer can discriminate two sequential stimuli as being asynchronous (typically 30-50 ms). It has been shown to be abnormal (prolonged) in neurological disorders, including cervical dystonia, a phenotype of adult onset idiopathic isolated focal dystonia. The TDT is a quantitative measure of the ability to perceive rapid changes in the environment and is considered indicative of the behavior of the visual neurons in the superior colliculus, a key node in covert attentional orienting. This article sets out methods for measuring the TDT (including two hardware options and two modes of stimuli presentation). We also explore two approaches of data analysis and TDT calculation. The application of the assessment of temporal discrimination to the understanding of the pathogenesis of cervical dystonia and adult onset idiopathic isolated focal dystonia is also discussed