Miracle-dz/UniFAR-FTUs huggingface dataset:
Small Neutral Amino Acid Ester Prodrugs of Acyclovir Targeting Amino Acid Transporters on the Cornea: Possible Antiviral Agents Against Ocular HSV-1 Infections

The aim of this study was to characterize the affinity and permeability patterns of the amino acid ester prodrugs of acyclovir (ACV), L-alanine-ACV (AACV), L-serine-ACV (SACV), L-serine-succinate-ACV (SSACV) and L-cysteine-ACV (CACV) on rabbit primary corneal epithelial cell culture (rPCEC) and on rabbit cornea. Amino acid prodrugs of acyclovir, AACV, SACV, SSACV and CACV were synthesized in our laboratory. Chemical hydrolysis in aqueous buffer, enzymatic hydrolysis in corneal homogenates and transport across freshly excised rabbit cornea of these prodrugs were studied. SSACV inhibited the uptake of [3H] L-alanine on rPCEC and across the intact rabbit cornea. Lineweaver-Burk plot transformation revealed competitive inhibition between L-alanine and SSACV. In corneal tissue homogenate, the half lives of SSACV, SACV and CACV (t1/2) were observed to be 3.5 ± 0.4, 9.2 ± 0.6 and 1.8 ± 0.1 hr respectively, whereas AACV was readily converted to the active parent drug acyclovir exhibiting complete degradation before 5 min. Interestingly translocation of SACV across cornea was inhibited in the presence of 5 mM arginine (~51%), a specific substrate for cationic transport system and in presence of BCH (~38%), a substrate specific for large neutral amino acid transport system (LAT) or cationic and neutral amino acid transport system (B0,+). SACV exhibited higher permeability across cornea along with excellent antiviral activity against herpes simplex virus (HSV-1) and varicella-zoster virus (VZV) in comparison to ACV. Recognition by multiple transporters, stability in corneal homogenate and changes in physico-chemical properties contributed to the increased permeability of SACV across cornea.
Vortex wave interaction theory to understand self sustaining processes in transitional flows

In this work the self-sustaining processes are investigated within a Couette flow developing a method able to apply directly the stress jumps predicted by the vortex wave interaction theory. The challenge of the approach is to implement a technique able to directly implement the stress jumps and to implement a procedure able to deform the mesh to the flow variations. The derivation of the vortex wave interaction theory is also discussed and the numerical formulations of the governing equations are discretized through a spectral/hp element method. The method turns out to agree with the other approaches already utilised in literature and the results reproduce a constraint of the mathematically inviscid flow suggesting that the flow is weakly dependent on the viscosity. The characteristics of the obtained flow are then discussed. These Navier-Stokes solutions are then perturbed by a sinusoidal wall forcing to study the robustness of the self-sustained mechanism by varying the amplitude of the forcing. The results show the possibility to control the behaviour of the flow and the effectiveness of the considered forcing to induce a drag reduction. Overcoming a certain amplitude threshold, a breakdown of the flow occurs in which the vortex core splits into multiple cores. Also after the breakdown the vortex wave interaction theory has been able to generate a self-sustained multiple core flow.
Background factors affecting success in geometry

ix Mathematics plays a key role in bolstering a country’s knowledge economy. Australia’s knowledge economy is negatively affected by the underachievement of Australian school students in geometry. Research indicates a continuing decline in student performance in geometry and a distinct lack of geometrical knowledge and understanding on the part of students and teachers. To address this issue a theory of success in geometry that focussed on background variables and attitude, was developed. In the theory it was hypothesised that success in geometry can be understood in terms of predictor variables and that attitude mediates the effects of the variables on success in geometry. A model of success in geometry was developed to systematically determine the relationships of the variables. Trainee teachers from the University of Western Sydney (n = 224) participated in the survey. Using Confirmatory Factor Analysis the use of one or two attitude scales was determined as were the items in the scales. Using Structural Equation Modeling (SEM) the relationships between the background factors (age, education, gender, left/right brain preference) on success in geometry (van Hiele level) mediated by attitude were determined. When the effects of the factors in the model on success in geometry were controlled for, the effect of gender on van Hiele level (success in geometry), the effect of education on van Hiele level (success in geometry) and the effect of age on van Hiele level (success in geometry) were found to be significant. The
Safety and Efficacy of Allogeneic Cell Therapy in Infarcted Rats Transplanted With Mismatched Cardiosphere-Derived Cells

Background— Cardiosphere-derived cells (CDCs) are an attractive cell type for tissue regeneration, and autologous CDCs are being tested clinically. However, autologous therapy necessitates patient-specific tissue harvesting and cell processing, with delays to therapy and possible variations in cell potency. The use of allogeneic CDCs, if safe and effective, would obviate such limitations. We compared syngeneic and allogeneic CDC transplantation in rats from immunologically-mismatched inbred strains. Methods and Results— In vitro, CDCs expressed major histocompatibility complex class I but not class II antigens or B7 costimulatory molecules. In mixed-lymphocyte cocultures, allogeneic CDCs elicited negligible lymphocyte proliferation and inflammatory cytokine secretion. In vivo, syngeneic and allogeneic CDCs survived at similar levels in the infarcted rat heart 1 week after delivery, but few syngeneic (and even fewer allogeneic) CDCs remained at 3 weeks. Allogeneic CDCs induced a transient, mild, local immune reaction in the heart, without histologically evident rejection or systemic immunogenicity. Improvements in cardiac structure and function, sustained for 6 months, were comparable with syngeneic and allogeneic CDCs. Allogeneic CDCs stimulated endogenous regenerative mechanisms (cardiomyocyte cycling, recruitment of c-kit+ cells, angiogenesis) and increased myocardial vascular endothelial growth factor, insulin-like growth factor-1, and hepatocyte growth factor equally with syngeneic CDCs. Conclusions— Allogeneic CDC transplantation without immunosuppression is safe, promotes cardiac regeneration, and improves heart function in a rat myocardial infarction model, mainly through stimulation of endogenous repair mechanisms. The indirect mechanism of action rationalizes the persistence of benefit despite the evanescence of transplanted cell survival. This work motivates the testing of allogeneic human CDCs as a potential off-the-shelf product for cellular cardiomyoplasty.
Epidemiological survey and analysis of asthma in children aged 0-14 years old in urban and rural areas of Chengdu region.

OBJECTIVES To investigate the prevalence and incidence of asthma among children aged 0-14 years, with different living environments, economic levels, and sanitary conditions, in the urban and rural areas of Chengdu, China, and their influential factors. METHODS Children aged 0-14 years who were selected from urban, suburban, and rural areas of Chengdu were included in the study. The subjects were selected from all children aged 0-14 years in schools, kindergartens, and communities by random, cluster and non-proportional sampling. Parents were surveyed by questionnaire to find out suspected cases, which were then confirmed by inquiry and physical examination in the departments of respiratory medicine. All the obtained data were analyzed using SPSS statistical software. RESULTS A total of 12,082 children from the urban areas, 5,677 from suburban areas, and 5,590 from the rural areas were included in the study. Of all the subjects, 551 (4.56%) had confirmed asthma, 150 (2.64%) had cough variant asthma (CVA), and 142 (2.54%) had suspected asthma. The prevalence rate of asthma was significantly higher in the urban areas than in the suburban and rural areas. The correct rate of diagnosis of asthma and CVA was highest in the urban areas, followed by the suburban and rural areas. Use of antibiotics and systemic corticosteroids was most common in the rural areas, followed by the suburban and urban areas, but this pattern was reversed for use of inhaled corticosteroids and leukotriene modifier. All the results in the three areas demonstrated that sex, age, age at which the first attack occurred, respiratory tract infection, inhalation/intake of allergens, and genetic factors were significantly associated with asthmatic attack. CONCLUSIONS Population density, living environment, medical and health resources and economic level are associated with the prevalence and treatment of asthma.
A novel approach to remote laboratories

Remote laboratories are becoming widely accepted in universities for providing distance education and for augmenting traditional laboratories. There is a lot of interest in remote laboratories from pedagogical point of view. In this paper, a novel technique for establishing remote laboratories is presented. The technique used and tools developed are extendable for the provision of different laboratory applications. Central to the idea is an experimentation server designed using a core Web technology called the "Web kernel" which provides a common access point for remote experiments. The server supports a number of analog/digital interface cards as well as allowing access to a number of modern laboratory instrumentation including oscilloscopes and signal generators. The Web-kernel provides access to Web sessions over the Internet from remote student workstations and allow fast, reliable and efficient development of applications. It is expected that the realistic facilities provided within the system allows it to be used in engineering education.
Public Medical Care

and a consideration of the procedures of studying atmospheric pollen. A systematic description follows of the principal plants responsible for atopic allergy in North America. The final section is devoted to regional surveys; this is especially useful to the practicing allergist, as well as to the victim seeking relief, since a glance at the tables will reveal to him the situation prevailing in a given area with respect to the nature of the pollens, their quantity, and their seasonal occurrence. The illustrations are most helpful, though some photographs might not have been out of place. The publishers, too, merit special commendation for the unusually distinguished character of the printing and the general construction of the volume.
The Influence of the Internet on the Psychosocial Predictors of Collective Action

The Internet has emerged as an important communication platform for the support of collective action, but little is known about how it influences the psychosocial motives for participation. Two quantitative studies were conducted within two different mobilizing contexts, in which offline collective actions were launched through computer-mediated communication. We examined whether and how the frequency with which people participated in online political discussions moderated the effects of the psychosocial predictors of collective action, specifically politicized identity, anger, collective efficacy, and morality. Results showed that collective action intention was predicted by politicized identity only when participants reported a higher versus lower frequency of online discussion. However, anger did not predict collective action when people had the chance to express this emotion through a higher versus lower frequency of online discussion. Moreover, collective efficacy and morality supported collective action intention in participants who reported a higher versus lower frequency of online discussion. We theorize on how computer-mediated communication, and its specific features, can be studied as a mobilizing context that influences the psychosocial motives to participate in collective action. Copyright © 2012 John Wiley & Sons, Ltd.
A Steady-state and Pre-steady-state Kinetic Analysis of the NTPase Activity Associated with the Hepatitis C Virus NS3 Helicase Domain*

The helicase domain of hepatitis C virus NS3 (genotype 1b) was expressed in Escherichia coli and purified to homogeneity. The purified protein catalyzed the hydrolysis of nucleoside triphosphates (NTP) and the unwinding of duplex RNA in the presence of divalent metal ion. The enzyme was not selective for the NTP substrate. For example, UTP and acyclovir triphosphate were hydrolyzed efficiently by the enzyme. The rate of NTP hydrolysis was stimulated up to 27-fold by oligomeric nucleic acids (NA). Furthermore, NA bound to the enzyme with concomitant quenching of the intrinsic protein fluorescence. The dissociation constants of the enzyme for selected NA in the absence of NTP were between 10 and 35 μM at pH 7.0 and 25°C. The enzyme had maximal affinity for NA with 12 or more nucleotides. A detailed steady-state and pre-steady-state kinetic analysis of ATP hydrolysis was made with (dU)18 as the effector. The kcat values for ATP hydrolysis in the presence and absence of (dU)18 were 80 s−1 and 2.7 s−1, respectively. The association (dissociation) rate constants for the enzyme and (dU)18 in the presence and absence of ATP were 5.7 μM−1 s−1 (3.9 s−1) and 290 μM−1 s−1 (2.27 s−1), respectively. The association (dissociation) rate constants for the enzyme and ATP in the presence and absence of (dU)18 were 0.4 μM−1 s−1 (<0.5 s−1) and 0.9 μM−1 s−1 (<10−1 s−1), respectively. These data were consistent with a random kinetic mechanism.
Automatic I/O prefetching for out-of-core applications

Automatic I/O Prefetching for Out-of-Core Applications Angela K. Demke Master of Science Graduate Department of Computer Science University of Toronto 1997 In this thesis, we propose and evaluate a fully-automatic technique to manage the I/O requirements of out-of-core scienti c applications. In our scheme, the compiler determines information on future access patterns and inserts prefetch and release operations to initiate I/O before the data is needed and to free pages that are no longer accessed. No modi cations to the original application source code are needed to support our compiler analysis. The operating system provides support for the basic prefetch and release operations and interacts with a run-time layer to accelerate performance by minimizing prefetch overhead. We have implemented our scheme using the SUIF compiler and the Hurricane operating system. Our experimental results demonstrate that our fully-automatic scheme e ectively hides the I/O latency in out-of-core versions of the entire NAS Parallel benchmark suite, thus resulting in speedups of roughly twofold for ve of the eight applications, with one application speeding up by over threefold. ii Acknowledgements The research presented in this thesis could not have been done alone, and I would like to express my sincere thanks to all who have contributed to its success. First of all, I would like to thank my supervisor, Todd Mowry, for his guidance and support throughout the development of the research, and for the many helpful comments on the organization and presentation of this work. I would also like to thank my second reader, Michael Stumm, for further improving the caliber of this thesis. In addition, I wish to gratefully acknowledge the nancial support provided by NSERC for this research. I would also like to acknowledge the entire Hector and Hurricane research teams for developing the research prototypes on which the ideas presented here were evaluated. (Special thanks go to Hector for staying alive and well over the last few years! ) In particular, I would like to thank Orran Krieger for the guided tour of Hurricane and the Hurricane File System, and for his many suggestions. In addition, I would like to thank Ben Gamsa for not only always knowing the answers to my questions about the Hurricane kernel, but also for always being there to provide them. Finally, thanks go out to the many people who have reset Hector for me when I couldn't be there to do it for myself: Ben Gamsa, Karen Reid, Eric Parsons, Paul Lu, Steve Jantzi, and Todd Mowry. I would also like to thank my fellow students at the University of Toronto for contributing to an enjoyable graduate experience. In particular, I would like to thank Ian Maione and Jin Lee for making my life a little more surreal. Finally, I want to thank my partner, Joseph Brown, for putting up with my work habits and my entropic ling system, and for being wonderfully supportive throughout. I also want to thank my cocker spaniel, Smokey, for always making me smile. iii
Rapid Suppression of Growth by Blue Light: OCCURRENCE, TIME COURSE, AND GENERAL CHARACTERISTICS.

The inhibition of stem elongation in dark-grown seedlings by blue light was studied with marking techniques and with a high-resolution, growth-measuring apparatus. Blue light rapidly suppresses growth in a variety of cultivated species. In some species, the inhibition persists only during the period of irradiation, after which time growth quickly returns to the high dark rate, whereas, in other species, the light response has an additional long-term component which lasts for at least several hours in the dark. The long-term inhibition may be mediated by phytochrome, whereas the rapid, short-term component is specific to a blue-light receptor.The rapid inhibition of growth in cucumber (Cucumis sativus L.) requires high-energy blue irradiation, which is perceived directly by the growing region of the hypocotyl and inhibits all regions below the hook to the same extent. Detailed investigation of the kinetics of the inhibition in cucumber and in sunflower (Helianthus annuus L.) shows that, after a short lag period (20 to 30 seconds in cucumber, 60 to 70 seconds in sunflower), the growth rate declines in an exponential fashion to a lower rate, with a half-time of 15 to 25 seconds in cucumber and 90 to 150 seconds in sunflower. Excision of the hypocotyl greatly reduces the sensitivity of the growth rate to blue-light inhibition. Because of the rapid kinetics, the blue-light photoreceptor cannot affect cell enlargement by altering the supply of growth hormone or the sensitivity to hormones but probably operates more directly either on the biochemical process which loosens cell walls or on cell turgor.
Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection

Significance Patients with compromised T-cell function are at risk for opportunistic fungal infections. We have developed a novel approach to restore immunity by using a fungal pattern-recognition receptor Dectin-1 to redirect T-cell specificity to carbohydrate antigen in the fungal cell wall. We did so by genetically modifying T cells using the nonviral Sleeping Beauty gene-transfer system to enforce expression of a chimeric antigen receptor (CAR) that recapitulates the specificity of Dectin-1 (D-CAR). The D-CAR+ T cells can be electroporated and propagated on artificial activating and propagating cells in a manner suitable for human application, enabling this immunology to be translated into immunotherapy. This approach has implications for genetically modifying T cells to express CARs with specificity for carbohydrate and thus broadening their application in the investigational treatment of pathogens and malignancies. Clinical-grade T cells are genetically modified ex vivo to express chimeric antigen receptors (CARs) to redirect their specificity to target tumor-associated antigens in vivo. We now have developed this molecular strategy to render cytotoxic T cells specific for fungi. We adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-ζ (designated “D-CAR”) upon binding with carbohydrate in the cell wall of Aspergillus germlings. T cells genetically modified with the Sleeping Beauty system to express D-CAR stably were propagated selectively on artificial activating and propagating cells using an approach similar to that approved by the Food and Drug Administration for manufacturing CD19-specific CAR+ T cells for clinical trials. The D-CAR+ T cells exhibited specificity for β-glucan which led to damage and inhibition of hyphal growth of Aspergillus in vitro and in vivo. Treatment of D-CAR+ T cells with steroids did not compromise antifungal activity significantly. These data support the targeting of carbohydrate antigens by CAR+ T cells and provide a clinically appealing strategy to enhance immunity for opportunistic fungal infections using T-cell gene therapy.
Timing of transcription during the cell cycle: Protein complexes binding to E2F, E2F/CLE, CDE/CHR, or CHR promoter elements define early and late cell cycle gene expression

A central question in cell cycle control is how differential gene expression is regulated. Timing of expression is important for correct progression through the cell cycle. E2F, CDE, and CHR promoter sites have been linked to transcriptional repression in resting cells and activation during the cell cycle. Further, the DREAM complex binds CHR or CDE/CHR elements of G2/M genes resulting in repression during G0/G1. Here, we show that DREAM also binds to E2F sites of S phase genes in quiescence and upon p53 activation. Furthermore, we describe a novel class of promoter sites, the CHR-like elements (CLE), which can support binding of DREAM to E2F elements. Activation of such S phase genes is achieved through binding of E2F1-3/DP complexes to E2F sites. In contrast, the activating MuvB complexes MMB and FOXM1-MuvB bind to CHR elements and mediate peak expression in G2/M. In conclusion, data presented here in combination with earlier results leads us to propose a model that explains how DREAM can repress early cell cycle genes through E2F or E2F/CLE sites and late genes through CHR or CDE/CHR elements. Also p53-dependent indirect transcriptional repression through the p53-p21-Cyclin/CDK-DREAM-E2F/CLE/CDE/CHR pathway requires DREAM binding to E2F or E2F/CLE sites in early cell cycle genes and binding of DREAM to CHR or CDE/CHR elements of late cell cycle genes. Specific timing of activation is achieved through binding of E2F1-3/DP to E2F sites and MMB or FOXM1-MuvB complexes to CHR elements.