Labelled-replica techniques: post-shadow labelling of intramembrane particles in freeze-fracture replicas

Three methods are described for direct post-fracture, post-shadow labelling of individual classes of intramembrane particles (IMPs) in freeze-fracture replicas of biological membranes. The P-face IMPs corresponding to the acetylcholine receptor complexes (AChRs) of vertebrate neuroeffector junctions are identified by post-replication labelling with ferritin-antibody complexes and with neurotoxin-biotin-avidin-colloidal gold affinity ligands. (The freeze-etch nomenclature of Branton et al., 1975, is used in this report.) These post-shadow labelling techniques resemble conventional en bloc labelling techniques except that the labelling reagents must penetrate a thin but discontinuous layer of platinum superimposed on the molecules of interest. In the ‘sectioned labelled-replica technique’, the replicated and labelled tissues are stained, embedded in plastic and sectioned parallel to the replica-tissue interfaces. In the direct ‘labelled-replica techniques’, the replicated and labelled samples are freeze-dried or critical point dried, the labelled surfaces are stabilized by carbon coating, and the underlying tissues are dissolved, allowing the labelled-replicas to be examined as conventional freeze-fracture replicas. The unshadowed side of each AChR IMP is shown to retain sufficient biochemical information to permit both immunospecific and neurotoxin specific labelling despite formaldehyde fixation, freezing, fracturing, platinum shadowing, and thawing in aqueous media. A new mixed ferricyanide-osmium staining method reveals electron opaque structures spanning the membrane bilayer in the same size, number and distribution as the labelled IMPs. These experiments demonstrate the feasibility of identifying individual IMPs in freeze-fracture replicas and may allow the identification of specific membrane lesions in human disease.     

When viewing variations in paintings by Mondrian, aesthetic preferences correlate with pupil size.

Observers consciously prefer Mondrian's paintings in their original orientation compared with a rotated position—the “oblique effect” (Latto, Brain, & Kelly, 2000). However, this finding's premise, that all vertical–horizontal orientations of the thick black lines in Mondrian's oeuvre are preferred, overlooks the fact that the overall balance of these images is also altered when they are reoriented. Thus, balance may regulate the oblique effect, which might influence conscious aesthetic preferences. To address this issue, we explore Hess's (1965, 1972) claim that observers will unconsciously increase their pupil diameter to pleasing images and constrict it to unpleasant images. We overcame Hess's methodological limitation of not keeping his images' luminances and contrast constant across conditions by presenting eight Mondrian paintings (1921–1944) to 30 observers on a CRT for 20 s each in either their original or seven rotated positions. Simultaneously, we measured their pupil size while asking them to report how (dis)pleasing they found each image. We found both evidence for the oblique effect (where image rotation hampers preference) and a correlation between this consciously reported aesthetic preference and unconsciously derived pupil size. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Implications concerning rod bundle crossflow mixing based on measurements of turbulent flow structure

An experimental study was performed to investigate the effect of flow channel geometry on fully developed turbulent flow in “clean” rod bundle flow channels. This information was sought to obtain a better understanding of crossflow mixing between rod bundle subchannels. The experiments were performed in water with a Reynolds number range from 50 000 to 200 000. The experimental flow models considered pitch-to-diameter ratios of 1.25 and 1.125. Axial components of velocity, turbulence intensity and Eulerian autocorrelation function were the primary measurements. The autocorrelation function provided an indication of the dominant frequency of turbulence and an estimate of the longitudinal macroscale by using Taylor's hypothesis. A limited amount of lateral component turbulence intensity data was also obtained.The experimental results show that rod gap spacing (pitch-to-diameter ratio) is the most significant geometric parameter affecting the flow structure. Decreasing the rod gap spacing increases the turbulence intensity, longitudinal macroscale, and the dominant frequency of turbulence. These turbulence parameters are rather insensitive to Reynolds number.The results indicate that macroscopic flow processes exist adjacent to the rod gap. This includes secondary flows and increased scale and frequency of flow pulsations when the rod gap spacing is reduced. When interpreted in terms of crossflow mixing, the results are consistent with present crossflow mixing correlations.     

Hybrid infrared focal plane signal and noise model

A signal and noise model is presented for an infrared sensor with an advanced hybrid focal plane that uses a CMOS readout integrated circuit (ROIC). Part of the motivation for this work is to present a clear foundation for some of the well-known practical and useful rules that apply to infrared sensors in use today. The model shows explicitly how a correlated double sampler (CDS) eliminates kTC noise, explains the interesting dependence of output 1/f noise on integration and epoch times, and is generic enough to treat a large class of ROIC preamps. A sensor with a direct injection readout is treated as an example and user-friendly formulas are listed and used to calculate sensor signal and noise     

Oxidation of Starch by Hydrogen Peroxide in the Presence of UV Light-Part II

Various reaction variables in the hydrogen peroxide oxidation of starch in the presence of UV light have been investigated. Higher carboxyl and carbonyl contents of oxystarches were obtained under acidic than under alkaline conditions. Extent of oxidation was found to increase with time. Increasing the concentration of hydrogen peroxide results in an increase in the carboxyl and carbonyl contents. Apparently, air has no effect on the degree of oxidation whereas, oxygen seems to accelerate it.     

Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancers worldwide. More than half of patients with HNSCC eventually experience disease recurrence and/or metastasis, which can threaten their long-term survival. HNSCCs located in the oral cavity and larynx are usually associated with tobacco and/or alcohol use, whereas human papillomavirus (HPV) infection, particularly HPV16 infection, is increasingly recognized as a cause of oropharyngeal HNSCC. Despite clinical, histologic, and molecular differences between HPV-positive and HPV-negative HNSCCs, current treatment approaches are the same. For recurrent disease, these strategies include chemotherapy, immunotherapy with PD-1-inhibitors, or a monoclonal antibody, cetuximab, that targets epidermal growth factor; these therapies can be administered either as single agents or in combination. However, these treatment strategies carry a high risk of toxic side effects; therefore, more effective and less toxic treatments are needed. The landscape of HNSCC therapy is changing significantly; numerous clinical trials are underway to test novel therapeutic options like adaptive cellular therapy, antibody-drug conjugates, new targeted therapy agents, novel immunotherapy combinations, and therapeutic vaccines. This review helps in understanding the various developments in HNSCC therapy and sheds light on the path ahead in terms of further research in this field.     

Neurocognitive signs in prodromal Huntington disease.

Objective: PREDICT-HD is a large-scale international study of people with the Huntington disease (HD) CAG-repeat expansion who are not yet diagnosed with HD. The objective of this study was to determine the stage in the HD prodrome at which cognitive differences from CAG-normal controls can be reliably detected. Method: For each of 738 HD CAG-expanded participants, we computed estimated years to clinical diagnosis and probability of diagnosis in 5 years based on age and CAG-repeat expansion number (Langbehn, Brinkman, Falush, Paulsen, & Hayden, 2004). We then stratified the sample into groups: NEAR, estimated to be ≤9 years; MID, between 9 and 15 years; and FAR, ≥15 years. The control sample included 168 CAG-normal participants. Nineteen cognitive tasks were used to assess attention, working memory, psychomotor functions, episodic memory, language, recognition of facial emotion, sensory–perceptual functions, and executive functions. Results: Compared with the controls, the NEAR group showed significantly poorer performance on nearly all of the cognitive tests and the MID group on about half of the cognitive tests (p = .05, Cohen's d NEAR as large as ?1.17, MID as large as ?0.61). One test even revealed significantly poorer performance in the FAR group (Cohen's d = ?0.26). Individual tasks accounted for 0.2% to 9.7% of the variance in estimated proximity to diagnosis. Overall, the cognitive battery accounted for 34% of the variance; in comparison, the Unified Huntington's Disease Rating Scale motor score accounted for 11.7%. Conclusions: Neurocognitive tests are robust clinical indicators of the disease process prior to reaching criteria for motor diagnosis of HD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)