Miracle-dz/UniFAR-FTUs huggingface dataset:
Hemoglobin S gelation and sickle cell disease.

By William A. Eaton and James Hofrichter T HE FUNDAMENTAL cause ofsickle cell disease is the decreased deformability of the sickled red cell produced by gelation of hemoglobin S. Partial inhibition of gelation should therefore reduce clinical severity, while complete inhibition should result in a “cure. ” These basic ideas have stimulated an enormous effort to understand the gelation process in detail and to relate the results of these studies to the pathophysiology of sickle cell disease. Discoveries concerning gelation have also led to new lines of research on a specific therapy. The early finding that fetal hemoglobin inhibits gelation. ”2 has ultimately led to the development of methods to increase the production of F cells in the bone marrow of sickle cell patients,35 while the discovery of the enormous sensitivity of the rate of gelation to hemoglobin concentration6 has stimulated studies on the reduction of intracellular hemoglobin concentration as a means of therapy.6 ’2 Studies on the structure of the hemoglobin S polymer,’3’8 moreover, have guided the development of agents designed to inhibit gelation by interfering with the formation of intermolecular contacts in the polymer. ”2’ The purpose of this article is to review recent developments in the relation between hemoglobin S gelation and sickle cell disease. We first present our current understanding of the major features of the gelation process. Since gelation is a physical rather than a chemical process, its description necessarily requires more physical detail than that of most biological processes. From these studies we are able to develop a more rigorous and comprehensive description of the relation between gelation and the pathophysiology than has been possible up to now. By combining the gelation studies with work on the rheology of sickle cells and blood flow in the microvasculature, a clearer picture emerges of the outstanding issues in understanding the mechanism of vasoocclusion in patients and the resulting cardiovascular response. Finally we discuss the variation in clinical severity and analyze the problem of inhibiting gelation in patients. Throughout this discussion we shall see that the kinetics of gelation is a dominant factor in understanding gelation both in vitro and in vivo, and it will become clear that discussions of the pathophysiobogy that do not include a kinetic analysis22’23 are inadequate. A broader treatment of sickle cell disease, including genetic and clinical aspects, has recently appeared in two excellent books.24’25 Also the structure, physical chemistry, and rheology of hemoglobin S gelation in solution and in red cells is discussed much more extensively in an article that is being published elsewhere.26
Non-lamellar Structure and Negative Charges of Lipopolysaccharides Required for Efficient Folding of Outer Membrane Protein PhoE of Escherichia coli *

Lipopolysaccharides (LPS) are amphiphilic molecules in the outer leaflet of the bacterial outer membrane. Recently, an early role for LPS in the folding of outer membrane porin PhoE was demonstrated in vitro. In order to elucidate the molecular mechanism of LPS-protein interactions, folding of PhoE protein was studied with a large set of well characterized LPS chemotypes. We demonstrate that negative charges in the inner core region contribute to the high efficiency of folding of PhoE protein. In addition, the supramolecular structure of the LPS aggregate seems to be important. LPS with a lipid A part that prefers a lamellar or a direct micellar structure and a high state of order of its acyl chains is much less efficient to support folding as compared with LPS with lipid A that prefers a non-lamellar structure and a low acyl chain order. Thesein vitro data indicate that extensive interactions between the core and lipid A region of LPS with the protein are required to support protein folding. The LPS-PhoE binding might be promoted by the presence of hydroxy fatty acids in the lipid A moiety of LPS.
Supporting Self-Assembly: The IKEA Effect on Mobile Health Persuasive Technology

In this paper, we propose the idea of examining the effect of self-assembly on the success of mobile health persuasive technology. The IKEA effect shows that individuals evaluate products assembled by themselves more positively than pre-assembled products. The IKEA effect has been proven in several domains, e.g., in human robot interaction, where participants who assembled the robot evaluated the robot and the interaction with the robot more favorably than participants who did not assemble the robot themselves. We propose that the IKEA effect exists in the context of mobile health persuasive technology and has high potential for improving users' engagement and long-term user experience of mobile health persuasive applications. In this paper, we describe the IKEA effect and its potential for mobile health applications. In addition, we propose an experimental design to analyze the effect of self-assembly on user engagement and satisfaction.
Measuring Best-in-Class Software Releases

In this research we aimed to identify distinguishing factors in software releases. For this purpose we analyzed the metrics of 26 software projects. These projects were release-based deliveries from two stable, experienced development teams. During the measurement period both teams transformed from a plan-driven delivery model (waterfall) to an agile approach (Scrum). Overall, we observed that these small release-based projects differ largely from non-release-based projects. Our research indicates that a combination of release-based working, a fixed and experienced development team, and a steady heartbeat contribute to performances that can be characterized as best-practice. The main contribution of this paper is that we found five success factors (all reducing development complexity) that result in best-of-class performance for small software releases.
Influence of Intense Light Stimulation on Trigeminal and Cervical Pain Perception Thresholds

Thirty-three migraineurs and 23 healthy controls were submitted to pressure algometry before and after light-induced discomfort was elicited by progressive light stimulation in a monoblind fashion. Pressure algometries were performed on the emergence of the supraorbital, infraorbital, mental and greater occipital nerves, and over the temporal muscles, always throughout the same sequence and from right to left. Measurements were carried out before and immediately after light stimulation and after 10 min of the second algometry. The final result for each site measured at each time-point was the mean of the three measurements. Light stimulation was carried out progressively until light-induced discomfort was reported, to a maximum of 20 000 lux. A heat-blocking glass protected patients' eyes. Migraineurs presented significant and persistent drops in pain perception thresholds after light stimulation, at all sites tested (P = 0.002 to < 0.0001). These drops were not seen in controls, in whom, conversely, a less significant increase was seen on right infraorbital and left temporal muscle sites. Our results indicate that in migraineurs, light may have a relevant role in trigeminal and cervical pain perception thresholds.
A cross‐cultural study into peer evaluations of women's leadership effectiveness

Purpose – The present paper is based on a cross‐cultural exploration of middle managers in two diverse cultures and aims to focus on how the leadership styles of managerial women are perceived and evaluated. In particular, female and male peer evaluations of leadership effectiveness in Malaysia and Australia are to be explored.Design/methodology/approach – Surveys from 324 middle managers from Malaysia and Australia were quantitatively analysed. The sample for the study was drawn from organisations in four industry types in both countries.Findings – Findings suggest that evaluations of female managers' leadership styles in general, and within the respondent's own organisations, were strongly culture specific, especially in Malaysia. The results reflected the strongly held values, attitudes and beliefs of each country. While this is not unexpected, it does highlight a need to be cautious when interpreting Western research results and attempting to transplant those into other cultures. In Malaysia, female m.
Variational PDE models in image processing

Abstract : Image processing, a traditionally engineering field, has attracted the attention of many mathematicians during the past two decades. From the vision and cognitive science point of view, image processing is a basic tool used to reconstruct the relative order, geometry, topology, patterns, and dynamics of the 3-D world from 2-D images. Therefore, it cannot be merely a historic coincidence that mathematics must meet image processing in this digital technology era. The role of mathematics is also determined by the broad range of applications of image processing in contemporary science and technology. These include astronomy and aerospace exploration, medical imaging, molecular imaging, computer graphics, human and machine vision, telecommunication, auto-piloting, surveillance video, and biometric security identification (such as fingerprints and face identification), etc. All these highly diversified disciplines have made it necessary to develop the common mathematical foundation and frameworks for image analysis and processing. Mathematics at all levels must be introduced to meet the crucial qualities demanded by this new era-genericity, well-posedness, accuracy, and computational efficiency, just to name a few. In return, image processing has created tremendous opportunities for mathematical modeling, analysis, and computation. In this article, we intend to give a broad picture of mathematical image processing through one of the most recent and very successful approaches - the variational PDE method. We first discuss two crucial ingredients for image processing: image modeling or representation, and processor modeling. We then focus on the variational PDE method. The backbone of the article consists of two major problems in image processing - inpainting and segmentation, which we have personally worked on, but by no means do we intend to have a comprehensive review of the entire field of image processing.
Sleep to Remember

Recently, compelling evidence has accumulated that links sleep to learning and memory. Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory. Consolidation is an active process that is presumed to rely on the covert reactivation and reorganization of newly encoded representations. Hippocampus-dependent memories benefit primarily from slow-wave sleep (SWS), whereas memories not depending on the hippocampus show greater gains over periods containing high amounts of rapid eye movement sleep. One way sleep does this is by establishing different patterns of neurotransmitters and neurohormone secretion between sleep stages. Another central role for consolidating memories is played by the slow oscillation, that is, the oscillating field potential change dominating SWS. The emergence of slow oscillations in neocortical networks depends on the prior use of these networks for encoding of information. Via efferent pathways, they synchronize the occurrence of sharp wave ripples accompanying memory reactivations in the hippocampus with thalamocortical spindle activity. Thus, hippocampal memories are fed back into neocortical networks at a time when these networks are depolarized and, because of concurrent spindle activity, can most sensitively react to these inputs with plastic changes underlying the formation of long-term memory representations.
Free and Conjugated Dopamine in Pheochromocytoma, Primary Aldosteronism and Essential Hypertension

SUMMARY Since the hypotensive and natrluretic role recently attributed to dopamine (DA) is difficult to test (free DA is usually undetectable in plasma) we measured free and conjugated DA by a newly developed method of hydrolysis of conjugated catecholamlnes in four pheochromocytoma, four primary aldosteronism and 34 essential hypertensive patients subjected to selective venous catheterization or peripheral venous sampling. The 16 control subjects had plasma DA of 0.98 ± 0.1 ng/ml (SE), almost 100% of which was conjugated, and a urinary excretion of 2 ± 03 fig/min of DA, 79% of which was conjugated.Patients with a predominantly norepinephrine-secreting pheochromocytoma had elevated conjugated plasma DA (6 ± 0.S vs 2.5 ± 03 ng/ml in non-pheochromocytoma hypertensive patients) even between paroxysms; in a rare case an alternating DA and epinephrine hypersecretion was detected during predominantly normotensive paroxysms, one of which was associated with the flooding of the peripheral circulation by up to 5.5 ng/ml of free DA.Patients with primary aldosteronism had elevated total plasma DA (3.1 ± 0 3 ng/ml), detectable free DA (0.4 ± 0.2 ng/ml) and an elevated total urinary DA excretion (53 ± 1.5 /ig/min). Following the removal of the aldosteronoma, urinary excretion of total or free DA decreased to normal levels, except in one patient with a bilateral micronodular hyperplasia in whom the hyperaldosteronism persisted after unilateral adrenalectomy. Patients with essential hypertension bad elevated conjugated plasma DA (1.98 ± 03 ng/ml), probably originating in an adrenal outflow of free and conjugated DA, but lower free and total urinary DA excretion than patients with primary aldosteronism (0.19 ± 0.04 vs 0.61 ± 0.01 for free DA and 0.9 ± 0.04 vs 5 3 ± 1.5 Mg/min for total urinary DA). Measurements of conjugated DA, which probably reflects the release of free rapidly conjugated DA, complement the free DA determination in hypertension. Elevated plasma conjugated DA probably mirrors the endogenous autonomous dopamine release in pheochromocytoma and has an adaptive character in primary aldosteronism and essential hypertension. Urinary free and conjugated DA excretion appears to reflect the dopamine modulated natriuresls, modifying the sodium-retaining action of aldosterone.
TRINOCULAR RECTIFICATION FOR VARIOUS CAMERA SETUPS

Convergent stereo images can be rectified such that they correspond to the stereo normal case. The important advantage is that the correspondence analysis is simplified to a linear search along one of the image axes. The proposed method describes a rectification method for three uncalibrated cameras, where the configuration is not generally known. The algorithm automatically determines the best positioning of the cameras and corrects mirroring effects to fit the desired camera setup. Since there is no direct solution for the rectification problem for three cameras, the rectification homographies are linearly determined to within six degrees of freedom from three compatible fundamental matrices. The remaining six parameters are then obtained by enforcing additional constraints.
The necessity of scheduling in compute-and-forward

Compute and Forward (CF) is a promising relaying scheme which, instead of decoding single messages or forwarding/amplifying information at the relay, decodes linear combinations of the simultaneously transmitted messages. The current literature includes several coding schemes and results on the degrees of freedom in CF, yet for systems with a fixed number of transmitters and receivers. It is unclear, however, how CF behaves at the limit of a large number of transmitters. In this paper, we investigate the performance of CF in that regime. Specifically, we show that as the number of transmitters grows, CF becomes degenerated, in the sense that a relay prefers to decode only one (strongest) user instead of any other linear combination of the transmitted codewords, treating the other users as noise. Moreover, the sum-rate tends to zero as well. This makes scheduling necessary in order to maintain the superior abilities CF provides. Indeed, under scheduling, we show that non-trivial linear combinations are chosen, and the sum-rate does not decay, even without state information at the transmitters and without interference alignment.
Graph Regularized Non-negative Matrix Factorization By Maximizing Correntropy

Non-negative matrix factorization (NMF) has proved effective in many clustering and classification tasks. The classic ways to measure the errors between the original and the reconstructed matrix are $l_2$ distance or Kullback-Leibler (KL) divergence. However, nonlinear cases are not properly handled when we use these error measures. As a consequence, alternative measures based on nonlinear kernels, such as correntropy, are proposed. However, the current correntropy-based NMF only targets on the low-level features without considering the intrinsic geometrical distribution of data. In this paper, we propose a new NMF algorithm that preserves local invariance by adding graph regularization into the process of max-correntropy-based matrix factorization. Meanwhile, each feature can learn corresponding kernel from the data. The experiment results of Caltech101 and Caltech256 show the benefits of such combination against other NMF algorithms for the unsupervised image clustering.
The landscape of human STR variation

Short Tandem Repeats are among the most polymorphic loci in the human genome. These loci play a role in the etiology of a range of genetic diseases and have been frequently utilized in forensics, population genetics, and genetic genealogy. Despite this plethora of applications, little is known about the variation of most STRs in the human population. Here, we report the largest-scale analysis of human STR variation to date. We collected information for nearly 700,000 STR loci across over 1,000 individuals in phase 1 of the 1000 Genomes Project. This process nearly saturated common STR variations. After employing a series of quality controls, we utilize this call set to analyze determinants of STR variation, assess the human reference genome’s representation of STR alleles, find STR loci with common loss-of-function alleles, and obtain initial estimates of the linkage disequilibrium between STRs and common SNPs. Overall, these analyses further elucidate the scale of genetic variation beyond classical point mutations. The resource is publicly available at http://strcat.teamerlich. org/ both in raw format and via a graphical interface.
cNEUPRO: Novel Biomarkers for Neurodegenerative Diseases

“clinical NEUroPROteomics of neurodegenerative diseases” (cNEUPRO) is a Specific Targeted Research Project (STREP) within the sixth framework program of the European Commission dedicated to the search for novel biomarker candidates for Alzheimer's disease and other neurodegenerative diseases. The ultimate goal of cNEUPRO is to identify one or more valid biomarker(s) in blood and CSF applicable to support the early and differential diagnosis of dementia disorders. The consortium covers all steps required for the discovery of novel biomarker candidates such as acquisition of high quality CSF and blood samples from relevant patient groups and controls, analysis of body fluids by various methods, and finally assay development and assay validation. Here we report the standardized procedures for diagnosis and preanalytical sample-handling within the project, as well as the status of the ongoing research activities and some first results.
Cocaine Alters Proliferation, Migration, and Differentiation of Human Fetal Brain-Derived Neural Precursor Cells

Maternal use of cocaine during pregnancy is associated with sustained morphological brain abnormalities and sustained cognitive deficits in the offspring. Here, we use a cell culture model of highly enriched human fetal brain-derived neural precursor cells (NPCs) to assess the effects of cocaine treatment on their proliferation, migration, and differentiation. Our data show that cocaine treatment markedly inhibited the proliferation of NPCs, a phenomenon that was associated with cell cycle arrest, possibly because of increased expression of the cyclin-dependent kinase inhibitor p21. In addition, treatment of NPCs with cocaine inhibited their migratory response to CXCL12 (stromal cell-derived factor-1α), a finding that correlated with cocaine-induced down-regulation of CXCR4 on NPCs. Finally, these data demonstrated that NPCs exposed to cocaine underwent differentiation into cells expressing neuronal markers that was associated with an inhibition of SOX2 (SRY-related HMG-box gene 2), a transcription factor that inhibits NPC differentiation. Taken together, these results point to several cellular mechanisms whereby exposure of human neural stem cells to cocaine in utero could contribute to subsequent neurodevelopmental and neurocognitive deficits.
Neighbourhood food environment and dietary intakes in adolescents: sex and perceived family affluence as moderators.

OBJECTIVE To examine the effects of perceived availability of fast-food shops, restaurants, and convenience stores on adolescent dietary intakes. METHODS Survey data from 34 369 students in 42 Hong Kong secondary schools were collected in 2006-7. Respondents reported the availability of fast-food shops, restaurants and convenience stores in the neighbourhood, and their intakes of fruit, vegetables, high-fat foods and junk food/soft drinks. For intakes of high-fat foods and junk food/ soft drinks, ≤ once a week was defined as low consumption and the rest moderate/high consumption. At least three servings of vegetables and two servings of fruit daily were defined as sufficient consumption. Logistic regression yielded adjusted odds ratios (OR) for each dietary intake in relation to the reported food shops. Potential effect modifications by socio-demographic factors were also examined. RESULTS Perceived availability of fast-food shops and convenience stores were positively associated with moderate/high consumptions of high-fat foods (OR(fast) =1.10 and OR(con) =1.15) and junk food/soft drinks (OR(fast)=1.10 and OR(con) =1.10). Significant negative associations of the perceived availability of restaurants with intakes of vegetables and fruit were observed (OR(veg) =0.87 and OR(fruit) =0.83). The positive relationship between reporting fast-food shops with intake of junk food/soft drinks were observed only in boys and those with low perceived family affluence. The negative association of reporting restaurants with fruit consumption was found in those with low and middle perceived family affluence only. CONCLUSIONS Perceived availability of neighbourhood fast-food shops, restaurants, and convenience stores may have a negative impact on adolescent dietary intakes particularly for those from poorer families.