Miracle-dz/UniFAR-FTUs huggingface dataset:
Diabetic Retinopathy: Targeting Vasoregression

Diabetic retinopathy is a clinically well-defined, sight-threatening, chronic microvascular complication that eventually affects virtually all patients with diabetes. Diabetic retinopathy is characterized by gradually progressive alterations in the retinal microvasculature, leading to areas of retinal nonperfusion, increased vasopermeability, and in response to retinal nonperfusion, pathologic intraocular proliferation of retinal vessels (1–3). Most diabetes researchers and clinicians are aware of the major advances made in understanding the pathobiology of proliferative diabetic retinopathy. However mechanisms underlying the progressive alterations in retinal microvessels, which precede and stimulate neovascularization, are less well-known. In this review, current information about the pathogenesis of the primary lesion of diabetic retinopathy, retinal capillary vasoregression (see Fig. 1), is presented. FIG. 1. Phenotype of vasoregression in the diabetic retina. In both experimental diabetic rats and diabetic humans, capillary occlusions occur. Nondiabetic ( A ) and 6-month diabetic rat retina with acellular capillaries (arrows) ( B ). Nondiabetic ( C ) and diabetic ( D ) human retinal digest preparation. Periodic acid-Schiff staining (original magnification ×250). Diabetic retinopathy is often considered as a complication that contrasts with other vascular sequelae of this disease because it is associated with new vessel formation, while diabetic heart disease and diabetic nephropathy are characterized by impaired angiogenesis (4). Diabetic retinopathy is generally grouped with tumor angiogenesis and is presented as a paradigm of a neovascular disease (5). As outlined in this review, the natural history of diabetic retinopathy starts with vasoregression. Recent investigations have brought new insight regarding the primary vasoregressive process that stimulates angiogenesis, provoking new directions of thinking about possible prevention and intervention (1). Diabetic retinopathy starts with the loss of the two cellular components of retinal capillaries: the pericyte, a vessel support cell, and the endothelial cell. The exact sequence of loss in humans is not established because early human retinal samples are not available, but animal …
The Yeast Frataxin Homologue Mediates Mitochondrial Iron Efflux

Mutations in the nuclear gene encoding the mitochondrial protein frataxin are responsible for the neurological disorder Friedreich ataxia (FA). Yeast strains with a deletion in the frataxin homologue YFH1 accumulate excess iron in mitochondria and demonstrate mitochondrial damage. We show that in the absence of YFH1, mitochondrial damage is proportional to the concentration and duration of exposure to extracellular iron, establishing mitochondrial iron accumulation as causal to mitochondrial damage. Reintroduction of YFH1 results in the rapid export of accumulated mitochondrial iron into the cytosol as free, non-heme bound iron, demonstrating that mitochondrial iron in the yeast FA model can be made bioavailable. These results demonstrate a mitochondrial iron cycle in which Yfh1p regulates mitochondrial iron efflux.
Speed/Accuracy Trade-Off between the Habitual and the Goal-Directed Processes

Instrumental responses are hypothesized to be of two kinds: habitual and goal-directed, mediated by the sensorimotor and the associative cortico-basal ganglia circuits, respectively. The existence of the two heterogeneous associative learning mechanisms can be hypothesized to arise from the comparative advantages that they have at different stages of learning. In this paper, we assume that the goal-directed system is behaviourally flexible, but slow in choice selection. The habitual system, in contrast, is fast in responding, but inflexible in adapting its behavioural strategy to new conditions. Based on these assumptions and using the computational theory of reinforcement learning, we propose a normative model for arbitration between the two processes that makes an approximately optimal balance between search-time and accuracy in decision making. Behaviourally, the model can explain experimental evidence on behavioural sensitivity to outcome at the early stages of learning, but insensitivity at the later stages. It also explains that when two choices with equal incentive values are available concurrently, the behaviour remains outcome-sensitive, even after extensive training. Moreover, the model can explain choice reaction time variations during the course of learning, as well as the experimental observation that as the number of choices increases, the reaction time also increases. Neurobiologically, by assuming that phasic and tonic activities of midbrain dopamine neurons carry the reward prediction error and the average reward signals used by the model, respectively, the model predicts that whereas phasic dopamine indirectly affects behaviour through reinforcing stimulus-response associations, tonic dopamine can directly affect behaviour through manipulating the competition between the habitual and the goal-directed systems and thus, affect reaction time.
Real-Time Multiple Refractions Through Deformable Objects

Title of Thesis: Real-Time Multiple Refractions Through Deformable Objects Pankaj Purushottam Chaudhari, M.S. in Computer Science, 2008 Thesis directed by: Dr. Marc Olano, Associate Professor Department of Computer Science and Electrical Engineering Refraction of light is one of the important phenomena that contribute to the perception of realism and is responsible for widely observed effects such as caustics. We describe an image-space algorithm to simulate refraction of light through a dynamic object. Unlike previous approaches, our technique achieves refraction through multiple interfaces at interactive frame-rates and does not require any pre-processing. Each stage of our algorithm runs entirely on the GPU and fits into the existing raster-based pipeline. Multiple refractions are simulated using depth layers obtained from a dynamically voxelized polygonal model and by using an image-space ray tracing technique. We also describe an accurate surface interpolation technique used to obtain surface normals using the depth layers. Our implementation suits the standard rasterization pipeline and achieves visually plausible results at interactive frame rates even for the dynamic scenes involving multiple refractive objects. Real-Time Multiple Refractions Through Deformable Objects by Pankaj Purushottam Chaudhari Thesis submitted to the Faculty of the Graduate School of the University of Maryland in partial fulfillment of the requirements for the degree of M.S. in Computer Science 2008 c © Copyright by Pankaj Purushottam Chaudhari 2008 Dedicated to the inventors of Café Mocha.
Recent Advances in Our Knowledge of Baculovirus Molecular Biology and Its Relevance for the Registration of Baculovirus-Based Products for Insect Pest Population Control

Public demand for safer, environmentally-benign alternatives to synthetic chemical pesticides and more stringent barriers put in place by regulatory agencies worldwide has led to increased interest in microbial pest control agents (MPCA) based on viruses, bacteria, fungi, protozoa and nematodes as the active ingredient. The MPCA market has recently experienced an increase of 47% between 2004/2007 with sales worth $396 million in 2007/2008 (CPL Consultants, 2010). Despite this increase, the microbial biopesticide market still only represents about 1% of the sales of chemical pesticides (CPL Consultants, 2010; Marrone, 2007). Factors impeding the establishment of strong MPCA markets are complex (Chandler et al., 2011; Marrone, 2007; Ravensberg, 2011) but include the burdensome costs associated with the registration of commercial products that are aimed at relatively small niche markets (Chandler et al., 2011; Ehlers, 2011). The main priority of regulatory agencies is to protect human health and safety and the environment from potential risks associated with the use of pest control products. A common feature of MPCA registration processes around the world is that they grew out of registration processes designed for chemical pesticides with adjustments allowing for the reduced risks of MCPAs (Chandler et al., 2011; Ehlers, 2011). Even though public attitudes to the use of biological control agents has been favourable (63%) a large proportion of the public (46%) has expressed concerns about the consumption of food treated with microbial pesticides (Cuddleford, 2006).
Effect of Interlaminar Epidural Steroid Injection in Acute and Subacute Pain Due to Lumbar Disk Herniation: A Randomized Comparison of 2 Different Protocols

In order to assess the efficacy of epidural steroid injections (ESI) in acute and subacute pain due to lumbar spine disk herniation, we conducted a randomized trial, comparing 2 different protocols. Fourty patients with radicular pain due to L4-L5 and L5-S1 disc herniation were assigned to receive either 3 consecutive ESI every 24 hours through a spinal catheter (group A) or 3 consecutive ESI every 10 days with an epidural needle (group B). All patients had improved Oswestry Disabilty Index (ODI) and the Visual Analog Scale (VAS) for pain scores at 1 month of follow-up compared to baseline, while no significant differences were observed between the 2 groups. The scores for group B were statistically significant lower at 2 months of follow-up compared to those of group A. The improvement in the scores of group B was continuous since the mean scores at 2 months of follow up were lower compared to the respective scores at 1 month. Protocol B (3 consecutive ESI every 10 days) was found more effective in the treatment of subacute pain compared to Protocol A (3 consecutive ESI every 24 hours) with statistically significant differences in the ODI and VAS scores at 2 months of follow-up.
The Fusion of Biology, Computer Science, and Engineering: Towards Efficient and Successful Synthetic Biology

Synthetic biology is a nascent field that emerged in earnest only around the turn of the millennium. It aims to engineer new biological systems and impart new biological functionality, often through genetic modifications. The design and construction of new biological systems is a complex, multistep process, requiring multidisciplinary collaborative efforts from "fusion" scientists who have formal training in computer science or engineering, as well as hands-on biological expertise. The public has high expectations for synthetic biology and eagerly anticipates the development of solutions to the major challenges facing humanity. This article discusses laboratory practices and the conduct of research in synthetic biology. It argues that the fusion science approach, which integrates biology with computer science and engineering best practices, including standardization, process optimization, computer-aided design and laboratory automation, miniaturization, and systematic management, will increase the predictability and reproducibility of experiments and lead to breakthroughs in the construction of new biological systems. The article also discusses several successful fusion projects, including the development of software tools for DNA construction design automation, recursive DNA construction, and the development of integrated microfluidics systems.
Phenotypic plasticity and experimental evolution

SUMMARY Natural or artificial selection that favors higher values of a particular trait within a given population should engender an evolutionary response that increases the mean value of the trait. For this prediction to hold, the phenotypic variance of the trait must be caused in part by additive effects of alleles segregating in the population, and also the trait must not be too strongly genetically correlated with other traits that are under selection. Another prediction, rarely discussed in the literature, is that directional selection should favor alleles that increase phenotypic plasticity in the direction of selection, where phenotypic plasticity is defined as the ability of one genotype to produce more than one phenotype when exposed to different environments. This prediction has received relatively little empirical attention. Nonetheless, many laboratory experiments impose selection regimes that could allow for the evolution of enhanced plasticity (e.g. desiccation trials with Drosophila that last for several hours or days). We review one example that involved culturing of Drosophila on lemon for multiple generations and then tested for enhanced plasticity of detoxifying enzymes. We also review an example with vertebrates that involves selective breeding for high voluntary activity levels in house mice, targeting wheel-running behavior on days 5+6 of a 6-day wheel exposure. This selection regime allows for the possibility of wheel running itself or subordinate traits that support such running to increase in plasticity over days 1–4 of wheel access. Indeed, some traits, such as the concentration of the glucose transporter GLUT4 in gastrocnemius muscle, do show enhanced plasticity in the selected lines over a 5–6 day period. In several experiments we have housed mice from both the Selected (S) and Control (C) lines with or without wheel access for several weeks to test for differences in plasticity (training effects). A variety of patterns were observed, including no training effects in either S or C mice, similar changes in both the S and C lines, greater changes in the S lines but in the same direction in the C lines, and even opposite directions of change in the S and C lines. For some of the traits that show a greater training effect in the S lines, but in the same direction as in C lines, the greater effect can be explained statistically by the greater wheel running exhibited by S lines (`more pain, more gain'). For others, however, the differences seem to reflect inherently greater plasticity in the S lines (i.e. for a given amount of stimulus, such as wheel running/day, individuals in the S lines show a greater response as compared with individuals in the C lines). We suggest that any selection experiment in which the selective event is more than instantaneous should explore whether plasticity in the appropriate (adaptive) direction has increased as a component of the response to selection.
How Chinese thought can lead the transformation in management practice

Purpose – The purpose of this paper is to explore how the emerging, post‐Newtonian twenty‐first century worldview, integrating elements of holistic Chinese philosophy and individualistic Western Newtonianism, is also driving a new model of organization, the articulation of which Chinese managers and thinkers must take a leadership position.Design/methodology/approach – The author focuses, first, on the similarities between the worldviews of Chinese philosophy and post‐Newtonianism; second, on how those changes in worldview support the emerging model of organization, whose management style one writer refers to as “unmanaging”; and, third, on the benefits available for Chinese business people who apply their acculturated understanding of principles that still seem foreign to Western business people.Findings – This essay asserts that the worldview emerging from twentieth century science – primarily quantum mechanics and complexity theory – will reinforce many of the basic assumptions basic to Chinese culture.
Book Reviews : Social Change and Social Welfare Practice

post-colonial theorising of difference reject both monocultural universalism and pluralistic renderings of difference. Theirs is a new and emergent paradigm. Aggar’s ignorance of this new theorising in the case of feminism is particularly offensive. It is the corollary of a wholesale appropriation of feminism for his representation of critical theory, without any understanding that feminist theorists such as Iris Marion Young and Nancy Fraser have developed important lines of critique of critical theory. Finally, Aggar writes as a U.S. intellectual without any appreciation that his arguments may need modification if they are to be transferred to non-metropolitan con-
Recognition of the polyubiquitin proteolytic signal

Polyubiquitin chains linked through Lys48 are the principal signal for targeting substrates to the 26S proteasome. Through studies of structurally defined, polyubiquitylated model substrates, we show that tetraubiquitin is the minimum signal for efficient proteasomal targeting. The mechanism of targeting involves a simple increase in substrate affinity that is brought about by autonomous binding of the polyubiquitin chain. Assigning the proteasomal signaling function to a specific polymeric unit explains how a single ubiquitin can act as a functionally distinct signal, for example in endocytosis. The properties of the substrates studied here implicate substrate unfolding as a kinetically dominant step in the proteolysis of properly folded proteins, and suggest that extraproteasomal chaperones are required for efficient degradation of certain proteasome substrates.
Multi-modal activity and dominance detection in smart meeting rooms

In this paper a new approach for activity and dominance modeling in meetings is presented. For this purpose low level acoustic and visual features are extracted from audio and video capture devices. Hidden Markov Models (HMM) are used for the segmentation and classification of activity levels for each participant. Additionally, more semantic features are applied in a two-layer HMM approach. The experiments show that the acoustic feature is the most important one. The early fusion of acoustic and globalmotion features achieves nearly as good results as the acoustic feature alone. All the other early fusion approaches are outperformed by the acoustic feature. More over, the two-layer model could not achieve the results of the acoustic features.
Experimental and Computational Mutagenesis To Investigate the Positioning of a General Base within an Enzyme Active Site

The positioning of catalytic groups within proteins plays an important role in enzyme catalysis, and here we investigate the positioning of the general base in the enzyme ketosteroid isomerase (KSI). The oxygen atoms of Asp38, the general base in KSI, were previously shown to be involved in anion–aromatic interactions with two neighboring Phe residues. Here we ask whether those interactions are sufficient, within the overall protein architecture, to position Asp38 for catalysis or whether the side chains that pack against Asp38 and/or the residues of the structured loop that is capped by Asp38 are necessary to achieve optimal positioning for catalysis. To test positioning, we mutated each of the aforementioned residues, alone and in combinations, in a background with the native Asp general base and in a D38E mutant background, as Glu at position 38 was previously shown to be mispositioned for general base catalysis. These double-mutant cycles reveal positioning effects as large as 103-fold, indicating that structural features in addition to the overall protein architecture and the Phe residues neighboring the carboxylate oxygen atoms play roles in positioning. X-ray crystallography and molecular dynamics simulations suggest that the functional effects arise from both restricting dynamic fluctuations and disfavoring potential mispositioned states. Whereas it may have been anticipated that multiple interactions would be necessary for optimal general base positioning, the energetic contributions from positioning and the nonadditive nature of these interactions are not revealed by structural inspection and require functional dissection. Recognizing the extent, type, and energetic interconnectivity of interactions that contribute to positioning catalytic groups has implications for enzyme evolution and may help reveal the nature and extent of interactions required to design enzymes that rival those found in biology.
Strings in AdS3 and the SL(2,R) WZW model. II: Euclidean black hole

We consider the one-loop partition function for Euclidean BTZ black hole back-grounds or equivalently thermal AdS3 backgrounds which are quotients of H3 (Euclidean AdS3). The one-loop partition function is modular invariant and we can read off the spectrum which is consistent to that found in hep-th/0001053. We see long strings and discrete states in agreement with the expectations.
Minority Student Attrition Research: Higher Education’s Challenge for Human Resource Development

This article addresses higher education’s major challenge for human resource development in the 1990s and beyond—enrolling and retaining to graduation our nation’s racial/ethnic minority students. At the institutional level, this challenge suggests the need for ongoing research and positive intervention. The first section focuses on the interrelationships among human resource development needs, problems associated with the underrepresentation of minorities in higher education, and the subsequent participation of minorities in the skilled labor force. The second section relates these issues to institution-level attrition research as an effective tool with which to more effectively retain students and begin to address the mismatch between future job opportunities and workers’ skill levels. The third section employs the interaction theoretical perspective to warn predominantly White colleges and universities (PWCUs) against basing intervention strategies upon research whose assumptions and recommendations belie the diversity among minority student populations.
CLARET : A Fast Deformable Registration Method Applied to Lung Radiation Therapy

We present a novel 3D-to-2D registration method called CLARET (Correction via Limited-Angle Residues in External Beam Therapy) that has potential application to rapid and accurate image-guided radiotherapy in lung with low-dose imaging. CLARET contains three components: shape modeling, machine learning of regression matrices, and treatment application. It models the patient’s breathing space from the patient’s treatment planning Respiratory-Correlated CTs (RCCTs) through an Large Deformation Diffeomorphic Metric Mapping (LDDMM) / Principal Component Analysis (PCA) framework. The eigenmode weights form the 3D shape parameters. Second, it performs multi-scale linear regressions between selected 3D shape parameters and covariates defined by intensity residues in the 2D projection space. At treatment time, CLARET computes a patient’s lung deformations by iteratively applying the learned regression matrices on the normalized intensity residues between the treatment-time imaging radiographs and corresponding projections of the current estimated CT. Both our synthetic and clinical test results show that CLARET can provide fast and accurate treatment-time 3D shape deformation corrections using a single radiograph for ImageGuided Radiation Therapy (IGRT).