Novel Frizzled-specific antibody-based Wnt mimetics and Wnt superagonists selectively activate WNT/ß-catenin signaling in target tissues.

WNTs are essential factors for stem cell biology, embryonic development, and for maintaining homeostasis and tissue repair in adults. Difficulties in purifying WNTs and their lack of receptor selectivity have hampered research and regenerative medicine development. While breakthroughs in WNT mimetic development have overcome some of these difficulties, the tools developed so far are incomplete and mimetics alone are often not sufficient. Here, we developed a complete set of WNT mimetic molecules that cover all WNT/ß-catenin-activating Frizzleds (FZDs). We show that FZD1,2,7 stimulate salivary gland expansion in vivo and salivary gland organoid expansion. We further describe the discovery of a novel WNT-modulating platform that combines WNT and RSPO mimetics' effects into one molecule. This set of molecules supports better organoid expansion in various tissues. These WNT-activating platforms can be broadly applied to organoids, pluripotent stem cells, and in vivo research, and serve as bases for future therapeutic development.

Perceptual averaging of line length: Effects of concurrent digit memory load.

The present experiment investigated performance in perceptual averaging of line ensembles during maintenance of minimal and near-span memory loads of digits. Observers memorized a four-to-seven digit number (high load) or a zero (low load) prior to a brief exposure (500 ms) of an ensemble of nine horizontal lines of various lengths. A subsequent probe line was then classified by observers as greater than or less than the ensemble average length followed by serial recall of the memory load. Slope analysis of the psychometric functions relating p("greater than") and the probe to ensemble-mean-size-ratio showed an advantage (steeper slope and therefore smaller threshold) for averaging under high-load compared with low-load conditions. Reaction time analysis indicated that faster probe responses were more accurate than slower responses.

A selective summary of visual averaging research and issues up to 2000.

Ariely's (2001) "Seeing Sets: Representation by Statistical Properties" (Psychological Science, 12, 157-162) rekindled interest in summary-value estimation for visual ensembles (groups of similar items). Revisiting and reinvigorating research on the "intuitive statistician" has prompted a new set of insights and debates concerning how and why the visual system might benefit from a compact representation of the optic array and how this might relate to crowding, sparse representation, efficiency coding, and processing limits. New research tools and imaging techniques coupled with solid psychophysical work have added substantially to the large base of work done in the 20th century. The present brief review acts as a summary of the ensemble of work prior to Ariely's (2001) landmark paper to encourage a comprehensive continuity of knowledge and reintroduce some of the contemporaneous concerns to help inform ongoing research and modeling.

A timely reminder about stimulus display times and other presentation parameters on CRTs and newer technologies.

Scientific experimentation requires specification and control of independent variables with accurate measurement of dependent variables. In Vision Sciences (here broadly including experimental psychology, cognitive neuroscience, psychophysics, and clinical vision), proper specification and control of stimulus rendering (already a thorny issue) may become more problematic as several newer display technologies replace cathode ray tubes (CRTs) in the lab. The present paper alerts researchers to spatiotemporal differences in display technologies and how these might affect various types of experiments. Parallels are drawn to similar challenges and solutions that arose during the change from cabinet-style tachistoscopes to computer driven CRT tachistoscopes. Technical papers outlining various strengths and limitations of several classes of display devices are introduced as a resource for the reader wanting to select appropriate displays for different presentation requirements. These papers emphasise the need to measure rather than assume display characteristics because manufacturers' specifications and software reports/settings may not correspond with actual performance. This is consistent with the call by several Vision Science and Psychological Science bodies to increase replications and increase detail in Method sections. Finally, several recent tachistoscope-based experiments, which focused on the same question but were implemented with different technologies, are compared for illustrative purposes.

Elucidation of soft tissue flap histologic margins within a canine vocal fold.

BACKGROUND: Histologic identification of implanted soft tissues in experimental animal models can be challenging, as donor tissue often strongly resembles the recipient bed. We have encountered this dilemma following implantation of a Composite Thyroid Ala Perichondrium flap (CTAP) into a vocal fold. The CTAP procedure is the first to utilize a vascularized flap for vocal fold reconstruction, making data to confirm or refute its viability critical. The current study evaluated several tissue stains to define precisely the histologic margins of CTAPs at two weeks post-implantation in a canine model. METHODS: Initial testing exposed canine cadaveric tissues to four stains (tattoo ink, Congo red, 4'6-diamidino-2-phenylindole, and henna) across four time periods. Tattoo ink alone withstood histologic processing. An exposure of 1 minute adequately delineated CTAP boundaries. The study concluded with a canine in vivo evaluation of a CTAP exposed to tattoo ink for 1 minute. After a two-week recovery period, vocal folds were harvested and evaluated histologically. RESULTS: Tattoo ink proved to be a safe and effective histologic marker in vivo, where the histologic margins of the implanted CTAP were clearly demarcated by a thin band of tattoo ink, soft tissue reactions were minimal, and interference with standard, special, or immunohistochemical stain assessments did not occur. CONCLUSIONS: Tattoo ink provides a reliable means of demarcating a CTAP within a vocal fold and demonstrated that CTAPs survive transplantation. Further, tattoo ink demarcation may serve as a useful histologic marker for those wishing to assess tissue implants in other in vivo models.

Technical refinements to the minithyrotomy procedure.

OBJECTIVES/HYPOTHESIS: Although the minithyrotomy (MT) procedure was introduced in 1999, it has not been widely used for voice restoration. Its limited dissemination is due in part to lack of appropriate implants and in part due to technical challenges. The 2011 introduction of the composite thyroid ala perichondrium flap (CTAP) into a vocal fold through an MT was designed to supply an appropriate implanted tissue. However, technical difficulties persisted. Noted impediments have included limited surgical access, potential CTAP pedicle constriction during healing, lack of specialized surgical instrumentation, and potential retraction or extrusion of CTAPs. This study was performed to address these technical challenges with or without the use of CTAP reconstruction. STUDY DESIGN: Experimental. Cadaveric and in vivo canine model. METHODS: Experimentation on canine cadaveric larynges yielded MT and CTAP alterations, instrument creation, and implant affixation procedures. These refinements were applied in vivo using canine subjects. Two weeks post-CTAP repair, subjects were humanely euthanized, followed by laryngeal harvest and histologic analysis of the vocal folds. RESULTS: Refinements to CTAP modification, MT, instrumentation, and CTAP affixation are successful in vivo, just as in preliminary cadaveric trials. CONCLUSIONS: The proposed refinements were designed to improve the outcomes achieved via a CTAP specifically but have utility for any MT approach. Continued improvements to specialized instrumentation are necessary. Enhanced affixation of a CTAP, with improved accuracy and easier deployment are also essential. Further refinements should allow more reliable implementation of the MT by a growing number of laryngeal surgeons.

Phantom arcs: now you see them...

A new visual illusion is reported and illustrated. The illusion, dubbed 'phantom arcs', survives manipulations of contrast, scale, and hue. The arcs can be seen in printed versions as well as in images displayed on CRT or LCD monitors. Data collected in an undergraduate perception class reveal that the illusion can be seen by untrained observers.

The danger of trial-by-trial knowledge of results in perceptual averaging studies.

Revived interest in "intuitive statistics" (Peterson & Beach, 1967) is evident in recent studies concerning the ability of observers to estimate mean size for ensembles of lines or of circles. To put the recent studies in context, and to highlight a potential danger in providing trial-by-trial knowledge of results (KOR), brief contact with previous research is made and a new experiment is presented demonstrating the malleability of responding to KOR. Together, these suggest two perils of KOR. First, given that the nature and even the existence of a molar size-averaging operator are both controversial, the proper criterion average for determining KOR is unclear. Second, whatever the operation observers use in this task, its scope and algorithm need to emerge from data unbiased by KOR. A corollary scaling concern is noted for averaging of areal stimuli (perceived as a compression function of physical area) as an instance of the more general concern that perceptual scaling factors must be taken into account when psychological averaging processes are studied.

Recovering data from scanned graphs: performance of Frantz's g3data software.

Recovering data points from scanned or photocopied graphs by hand is time consuming, prone to error, and it requires patience and a steady hand. An alternative is to use g3data-a program that reads many common image file types and allows accurate estimation of data point coordinates from the graphs contained in these files. Limits of the software are discussed, and validation of its accuracy using graphs with known data values is presented.