Functional and representational differences between the bilateral inferior temporal numeral areas

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record The processing of numerals as visual objects is supported by an “Inferior Temporal Numeral Area” (ITNA) in the bilateral inferior temporal gyri (ITG). Extant findings suggest some degree of hemispheric asymmetry in how the bilateral ITNAs process numerals. Pollack and Price (2019) reported such a hemispheric asymmetry by which a region in the left ITG was sensitive to digits during a visual search for a digit among letters, and a homologous region in the right ITG that showed greater digit sensitivity in individuals with higher calculation skills. However, the ITG regions were localized with separate analyses without directly contrasting their digit sensitivities and relation to calculation skills. So, the extent of and reasons for these functional asymmetries remain unclear. Here we probe whether the functional and representational properties of the ITNAs are asymmetric by applying both univariate and multivariate region-of-interest analyses to Pollack and Price’s (2019) data. Contrary to the implications of the original findings, digit sensitivity did not differ between ITNAs, and digit sensitivity in both left and right ITNAs was associated with calculation skills. Representational similarity analyses revealed that the overall representational geometries of digits in the ITNAs were also correlated, albeit weakly, but the representational contents of the ITNAs were largely inconclusive. Nonetheless, we found a right lateralization in engagement in alphanumeric categorization, and that the right ITNA showed greater discriminability between digits and letters. Greater right lateralization of digit sensitivity and digit discriminability in the left ITNA were also related to higher calculation skills. Our findings thus suggest that the ITNAs may not be functionally identical and should be directly contrasted in future work. Our study also highlights the importance of within-individual comparisons for understanding hemispheric asymmetries, and analyses of individual differences and multivariate features to uncover effects that would otherwise be obscured by averages.National Science FoundationNational Science FoundationNanyang Technological University and the Ministry of Education: Singapor

A simple mathematical model of gradual Darwinian evolution: Emergence of a Gaussian trait distribution in adaptation along a fitness gradient

We consider a simple mathematical model of gradual Darwinian evolution in continuous time and continuous trait space, due to intraspecific competition for common resource in an asexually reproducing population in constant environment, while far from evolutionary stable equilibrium. The model admits exact analytical solution. In particular, Gaussian distribution of the trait emerges from generic initial conditions.Comment: 21 pages, 2 figures, as accepted to J Math Biol 2013/03/1

The influence of liver dysfunction on cyclosporine pharmacokinetics -A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs-

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. © 1989 The Japan Surgical Society

Surface structure and frictional properties of the skin of the Amazon tree boa Corallus hortulanus (Squamata, Boidae)

The legless locomotion of snakes requires specific adaptations of their ventral scales to maintain friction force in different directions. The skin microornamentation of the snake Corallus hortulanus was studied by means of scanning electron microscopy and the friction properties of the skin were tested on substrates of different roughness. Skin samples from various parts of the body (dorsal, lateral, ventral) were compared. Dorsal and lateral scales showed similar, net-like microornamentation and similar friction coefficients. Average friction coefficients for dorsal and lateral scales on the epoxy resin surfaces were 0.331 and 0.323, respectively. In contrast, ventral scales possess ridges running parallel to the longitudinal body axis. They demonstrated a significantly lower friction coefficient compared to both dorsal and lateral scales (0.191 on average). In addition, ventral scales showed frictional anisotropy comparing longitudinal and perpendicular direction of the ridges. This study clearly demonstrates that different skin microstructure is responsible for different frictional properties in different body regions

Modular and predictable assembly of porous organic molecular crystals

Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules

Combination of a fusogenic glycoprotein, pro-drug activation and oncolytic HSV as an intravesical therapy for superficial bladder cancer

Background: There are still no effective treatments for superficial bladder cancer (SBC)/non-muscle invasive bladder cancer. Following treatment, 20% of patients still develop metastatic disease. Superficial bladder cancer is often multifocal, has high recurrences after surgical resection and recurs after intravesical live Bacillus Calmette-Guérin. Oncovex GALV/CD, an oncolytic herpes simplex virus-1, has shown enhanced local tumour control by combining oncolysis with the expression of a highly potent pro-drug activating gene and the fusogenic glycoprotein. Methods: In vitro fusion/prodrug/apoptotic cell-based assays. In vivo orthotopic bladder tumour model, visualised by computed microtomography. Results: Treatment of seven human bladder carcinoma cell lines with the virus resulted in tumour cell killing through oncolysis, pro-drug activation and glycoprotein fusion. Oncovex GALV/CD and mitomycin C showed a synergistic effect, whereas the co-administration with cisplatin or gemcitabine showed an antagonistic effect in vitro. Transitional cell cancer (TCC) cells follow an apoptotic cell death pathway after infection with Oncovex GALV/CD + with or without 5-FC. In vivo results showed that intravesical treatment with Oncovex GALV/CD prodrug (5-FC) reduced the average tumour volume by over 95% compared with controls.Discussion: Our in vitro and in vivo results indicate that Oncovex GALV/CD can improve local tumour control within the bladder, and potentially alter its natural history

Effect of Air Injection Depth on Big-bubble Formation in Lamellar Keratoplasty: an Ex Vivo Study

This study evaluated the effect of air injection depth in the big-bubble (BB) technique, which is used for corneal tissue preparation in lamellar keratoplasty. The BB technique was performed on ex vivo human corneoscleral buttons using a depth-sensing needle, based on optical coherence tomography (OCT) imaging technology. The needle tip, equipped with a miniaturized OCT depth-sensing probe, was inserted for air injection at a specified depth. Inside the corneal tissue, our needle obtained OCT line profiles, from which residual thickness below the needle tip was measured. Subjects were classified into Groups I, II, III, and IV based on injection depths of 75-80%, 80-85%, 85-90%, and > 90% of the full corneal thickness, respectively. Both Type I and II BBs were produced when the mean residual thicknesses of air injection were 109.7 +/- 38.0 mu m and 52.4 +/- 19.2 mu m, respectively. Type II BB (4/5) was dominant in group IV. Bubble burst occurred in 1/16 cases of type I BB and 3/16 cases of type II BB, respectively. Injection depth was an important factor in determining the types of BBs produced. Deeper air injection could facilitate formation of Type II BBs, with an increased risk of bubble bursts

Reading Front to Back: MEG Evidence for Early Feedback Effects During Word Recognition.

Magnetoencephalography studies in humans have shown word-selective activity in the left inferior frontal gyrus (IFG) approximately 130 ms after word presentation (Pammer et al. 2004; Cornelissen et al. 2009; Wheat et al. 2010). The role of this early frontal response is currently not known. We tested the hypothesis that the IFG provides top-down constraints on word recognition using dynamic causal modeling of magnetoencephalography data collected, while subjects viewed written words and false font stimuli. Subject-specific dipoles in left and right occipital, ventral occipitotemporal and frontal cortices were identified using Variational Bayesian Equivalent Current Dipole source reconstruction. A connectivity analysis tested how words and false font stimuli differentially modulated activity between these regions within the first 300 ms after stimulus presentation. We found that left inferior frontal activity showed stronger sensitivity to words than false font and a stronger feedback connection onto the left ventral occipitotemporal cortex (vOT) in the first 200 ms. Subsequently, the effect of words relative to false font was observed on feedforward connections from left occipital to ventral occipitotemporal and frontal regions. These findings demonstrate that left inferior frontal activity modulates vOT in the early stages of word processing and provides a mechanistic account of top-down effects during word recognition

Reading therapy strengthens top-down connectivity in patients with pure alexia

This study tested the efficacy of audio-visual reading training in nine patients with pure alexia, an acquired reading disorder caused by damage to the left ventral occipitotemporal cortex. As well as testing the therapy's impact on reading speed, we investigated the functional reorganization underlying therapy-induced behavioural changes using magnetoencephalography. Reading ability was tested twice before training (t1 and t2) and twice after completion of the 6-week training period (t3 and t4). At t3 there was a significant improvement in word reading speed and reduction of the word length effect for trained words only. Magnetoencephalography at t3 demonstrated significant differences in reading network connectivity for trained and untrained words. The training effects were supported by increased bidirectional connectivity between the left occipital and ventral occipitotemporal perilesional cortex, and increased feedback connectivity from the left inferior frontal gyrus. Conversely, connection strengths between right hemisphere regions became weaker after training