Miracle-dz/UniFAR-FTUs huggingface dataset:
New small-molecule inhibitors of mitogen-activated protein kinase kinase

Background: Overexpression of the Ras/Raf/MEK/ERK (extracellular-signal-regulated kinase) pathway is associated with the formation, progression and survival of tumours and has also been implicated in a diverse range of therapeutic areas such as arthritis, organ transplant rejection, asthma and developmental disorders. One approach to down regulation of this pathway is through the inhibition of mitogen-activated protein kinase kinase 1/2 (MEK1/2). Objective: The importance of the mitogen-activated protein kinase (MAPK) pathway, MEK1/2 as a therapeutic target and early MEK1/2 inhibitors is discussed, followed by an overview of recent patent activity in the area. Methods: The patent literature was searched for inhibitors of MEK1/2 published within the last three years; these results are described. Other relevant publications that provide further insight into the discovery and development of these compounds are also discussed. Conclusion: The determination of a crystal structure with inhibitor bound has allowed the design of exquisitely selective and potent inhibitors of MEK1/2. Several allosteric inhibitors have advanced to clinical trial and shown some efficacy in cancer as single agents, but the future application of MEK1/2 inhibitors is likely to be either in combination with other therapies or in disorders which are genetically defined as being dependent on the MAPK pathway.
SIMPLE SHAPE-FROM-SHADING IN THE DENTAL AND MEDICAL MEASUREMENT CONTEXT

Stereo-photogrammetric intra-oral measurement of teeth has been reported previously to be worthwhile to dental research, but inherently difficult because of the lack of optical texture in the dental surfaces. Shape-from-shading (SFS) from single imagery suggests itself as an alternative technique for dental measurement simply because a lack of texture is a fundamental necessity for shape-from-shading measurement. Furthermore, because a number of areas of the human body, notably the back which is of interest in scoliosis studies, can lack strong texture, shape-from-shading is an attractive prospect for various other medical measurement tasks involving human body surfaces. Despite some immediate attractiveness, shape-from-shading has difficulties which may effectively preclude reliable measurement by single images in real medical situations, and the prospective medical user of SFS needs to be aware of certain challenges. Despite these problems, in certain cases where the object is defined by simple shapes, such as may be encountered in incisor teeth and other common external body areas, some three-dimensional results can be achieved. This paper examines some of the possibilities and pitfalls with dental and medical body measurement using simple shape-from-shading, and shows some result from imagery obtained on extracted teeth, on living teeth in the mouth and in other human measurement cases, in which the gaol is to obtain useful, precise, three-dimensional surface data.
Molecular and Physiological Responses to Juvenile Traumatic Brain Injury: Focus on Growth and Metabolism

Traumatic brain injury (TBI), one of the most frequent causes of neurologic and neurobehavioral morbidity in the pediatric population, can result in lifelong challenges not only for patients, but also for their families. Survivors of a brain injury experienced during childhood – when the brain is undergoing a period of rapid development – frequently experience unique challenges as the consequences of their injuries are overlaid on normal developmental changes. Experimental studies have significantly advanced our understanding of the mechanisms and underlying molecular underpinnings of the injury response and recovery process following a TBI in the developing brain. In this paper, normal and TBI-related alterations in growth, development and metabolism are comprehensively reviewed in the postweanling/juvenile age range in the rat (postnatal days 21–60). As part of this review, TBI-related changes in gene expression are presented, with a focus on the injury-induced alterations related to cerebral growth and metabolism, and discussed in the context of existing literature related to physiological and behavioral responses to experimental TBI. Increasing evidence from the existing literature and from our own gene microarray data indicates that molecular responses related to growth, development and metabolism may play a particularly important role in the injury response and the recovery trajectory following developmental TBI. While gene expression analysis shows many of these changes occur at the level of transcription, a comprehensive review of other studies suggests that the control of metabolic substrates may preferentially be regulated through changes in transporters and enzymatic activity. The interrelation between cellular metabolism and activity-dependent neuroplasticity shows great promise as an area for future study for an optimal translation of experimental data to clinical TBI, with the ultimate goal of guiding therapeutic interventions.
Selective Attention and Cerebral Dominance in Perceiving and Responding to Speech Messages

The effect of attention on cerebral dominance and the asymmetry between left and right ears was investigated using a selective listening task. Right handed subjects were presented with simultaneous dichotic speech messages; they shadowed one message in either the right or left ear and at the same time tapped with either the right or the left hand when they heard a specified target word in either message. The ear asymmetry was shown only when subjects' attention was focused on some other aspect of the task: they tapped to more targets in the right ear, but only when these came in the non-shadowed message; they made more shadowing errors with the left ear message, but chiefly for non-target words. The verbal response of shadowing showed the right ear dominance more clearly than the manual response of tapping. Tapping with the left hand interfered more with shadowing than tapping with the right hand, but there was little correlation between the degree of hand and of ear asymmetry over individual subjects. The results support the idea that the right ear dominance is primarily a quantitative difference in the distribution of attention to left and right ear inputs reaching the left hemisphere speech areas. This affects both the efficiency of speech perception and the degree of response competition between simultaneous verbal and manual responses.
Free Radicals and Antioxidants in the Year 2000: A Historical Look to the Future

Abstract: In the late 1950's free radicals and antioxidants were almost unheard of in the clinical and biological sciences but chemists had known about them for years in the context of radiation, polymer and combustion technology. Daniel Gilbert, Rebeca Gerschman and their colleagues related the toxic effects of elevated oxygen levels on aerobes to those of ionizing radiation, and proposed that oxygen toxicity is due to free radical formation, in a pioneering paper in 1956. Biochemistry owes much of its early expansion to the development and application of chromatographic and electrophoretic techniques, especially as applied to the study of proteins. Thus, superoxide dismutase (SOD) enzymes (MnSOD, CuZnSOD, FeSOD) were quickly identified. By the 1980's Molecular Biology had evolved from within biochemistry and microbiology to become a dominant new discipline, with DNA sequencing, recombinant DNA technology, cloning, and the development of PCR representing milestones in its advance. As a biological tool to explore reaction mechanisms, SOD was a unique and valuable asset. Its ability to inhibit radical reactions leading to oxidative damage in vitro often turned out to be due to its ability to prevent reduction of iron ions by superoxide. Nitric oxide (NO·) provided the next clue as to how SOD might be playing a critical biological role. Although NO· is sluggish in its reactions with most biomolecules it is astoundingly reactive with free radicals, including superoxide. Overall, this high reactivity of NO· with radicals may be beneficial in vivo, e.g. by scavenging peroxyl radicals and inhibiting lipid peroxidation. If reactive oxygen species are intimately involved with the redox regulation of cell functions, as seems likely from current evidence, it may be easier to understand why attempts to change antioxidant balance in aging experiments have failed. The cell will adapt to maintain its redox balance. Indeed, transgenic animals over‐expressing antioxidants show some abnormalities of function. There must therefore be a highly complex interrelationship between dietary, constitutive, and inducible antioxidants within the body, under genetic control. The challenge for the new century is to be able to understand these relationships, and how to manipulate them to our advantage to prevent and treat disease.
On the Nexus of the Spatial Dynamics of Global Urbanization and the Age of the City

A number of concepts exist regarding how urbanization can be described as a process. Understanding this process that affects billions of people and its future development in a spatial manner is imperative to address related issues such as human quality of life. In the focus of spatially explicit studies on urbanization is typically a city, a particular urban region, an agglomeration. However, gaps remain in spatially explicit global models. This paper addresses that issue by examining the spatial dynamics of urban areas over time, for a full coverage of the world. The presented model identifies past, present and potential future hotspots of urbanization as a function of an urban area's spatial variation and age, whose relation could be depicted both as a proxy and as a path of urban development.
Sex, Age and Height Determination in Asiatic Elephant (Elephas Maximus): A Case Study

The present investigation was carried out on the skeletal remains of a dead Asian elephant (Elephas maximus) presented to the Centre for Wildlife Health, OUAT, Bhubaneswar by the District Forest Officer, Chandaka suspected of dying due to burning to determine the sex, tentative age and height of the animal. Basing on the morphology of skull, i.e rounded and convex parieto-occipital crest, absence of temporal line in the postero medial wall of the temporal fossa and thin, short and pointed lip bone, it was confirmed that the suspected elephant was a female one. The tentative age of the animal was found to be about 6 years basing on the number of lamellae present on the table surface of molar tooth. The tentative height of the animal was ascertained from the shoulder height or height of the fore limb, which was found to be about 6 feet. This study will help explore new avenues in the forensic wild life science in dealing with the vetero legal cases.
COMPACT ARTIFICIAL MAGNETIC CONDUCTOR DESIGNS USING PLANAR SQUARE SPIRAL GEOMETRIES

Compact spiral artificial magnetic conductors (AMC) have been investigatedin this paper. First, single andd ouble spirals are examinedto achieve an in-phase reflection at a lower frequency comparedto a conventional patch element of the same size. However, these two designs generate a large cross polarization. The cross polarization affects the operating frequency and bandwidth. In order to eliminate the cross polarization effect, a four-arm spiral element is introduced. This geometry does not generate a cross polarization, and an operating frequency that is 49.45% lower than the reference patch element has been achieved.
Structure of β-galactosidase at 3.2-Å resolution obtained by cryo-electron microscopy

Significance Atomic resolution models for proteins and protein complexes are usually obtained using X-ray crystallography or NMR spectroscopy, and in selected instances, by cryo-electron microscopy (cryo-EM) of ordered protein assemblies. The vast majority of high-resolution structures obtained using cryo-EM have been typically restricted to large, well-ordered entities such as helical or icosahedral assemblies or two-dimensional crystals. We show here that emerging methods in single-particle cryo-EM now allow structure determination at near-atomic resolution, even for much smaller protein complexes with low symmetry, by determining the structure of the 465-kDa enzyme β-galactosidase. In addition, by quantitative comparison of density maps obtained at different electron dosages, we demonstrate preferential sensitivity of residues such as Asp and Glu to damage upon irradiation with electrons. We report the solution structure of Escherichia coli β-galactosidase (∼465 kDa), solved at ∼3.2-Å resolution by using single-particle cryo-electron microscopy (cryo-EM). Densities for most side chains, including those of residues in the active site, and a catalytic Mg2+ ion can be discerned in the map obtained by cryo-EM. The atomic model derived from our cryo-EM analysis closely matches the 1.7-Å crystal structure with a global rmsd of ∼0.66 Å. There are significant local differences throughout the protein, with clear evidence for conformational changes resulting from contact zones in the crystal lattice. Inspection of the map reveals that although densities for residues with positively charged and neutral side chains are well resolved, systematically weaker densities are observed for residues with negatively charged side chains. We show that the weaker densities for negatively charged residues arise from their greater sensitivity to radiation damage from electron irradiation as determined by comparison of density maps obtained by using electron doses ranging from 10 to 30 e−/Å2. In summary, we establish that it is feasible to use cryo-EM to determine near-atomic resolution structures of protein complexes (<500 kDa) with low symmetry, and that the residue-specific radiation damage that occurs with increasing electron dose can be monitored by using dose fractionation tools available with direct electron detector technology.
An Abstraction Technique for the Verification of Artifact-Centric Systems

We explore the paradigm of artifact-centric systems from a knowledge-based perspective. We provide a semantics based on interpreted-systems to interpret a first-order temporal-epistemic language with identity in a multi-agent setting. We consider the model checking problem for this language and provide abstraction results. We isolate a natural subclass of artifact-systems for which the model checking problem is decidable. We give an upper bound on the complexity of the model checking problem.
Daily oscillations in liver function: diurnal vs circadian rhythmicity

Abstract: The rodent suprachiasmatic nucleus (SCN), a site in the brain that contains a light‐entrained biological (circadian) clock, has been thought of as the master oscillator, regulating processes as diverse as cell division, reproductive cycles, sleep, and feeding. However, a second circadian system exists that can be entrained by meal feeding and has an influence over metabolism and behavior. Recent advances in the molecular genetics of circadian clocks are revealing clock characteristics such as rhythmic clock gene expression in a variety of non‐neural tissues such as liver. Although little is known regarding the function of these clock genes in the liver, there is a large literature that addresses the capabilities of this organ to keep time. This time‐keeping capability may be an adaptive function allowing for the prediction of mealtime and therefore improved digestion and energy usage. Consequently, an understanding of these rhythms is of great importance. This review summarizes the results of studies on diurnal and circadian rhythmicity in the rodent liver. We hope to lend support to the hypothesis that there are functionally important circadian clocks outside of the brain that are not light‐ or SCN‐dependent. Rather, these clocks are largely responsive to stimuli involved in nutrient intake. The interaction between these two systems may be very important for the ability of organisms to synchronize their internal physiology.
SPLAT: A System for Self-Plagiarism Detection

This paper presents a system for self-plagiarism detection, SPLAT. The system uses a WebL web spider that crawls through the web sites of the top fifty Computer Science departments, downloading research papers and grouping them by author. Next a text-comparison algorithm is used to search for instances of textual reuse. Instances of potential selfplagiarism for each author are reported in an HTML document so that they can be considered in more detail, in order to determine if they are truly self-plagiarized papers. The system discovered a number of pairs of papers of questionable originality.
Miuz: measuring the impact of disconnecting a node

In this article we present Miuz, a robustness index for complex networks. Miuz measures the impact of disconnecting a node from the network while comparing the sizes of the remaining connected components. Strictly speaking, Miuz for a node is defined as the inverse of the size of the largest connected component divided by the sum of the sizes of the remaining ones. We tested our index in attack strategies where the nodes are disconnected in decreasing order of a specified metric. We considered Miuz and other well-known centrality measures such as betweenness, degree, and harmonic centrality. All of these metrics were compared regarding the behavior of the robustness (R- index) during the attacks. In an attempt to simulate the Internet backbone, the attacks were performed in complex networks with power-law degree distributions (scale-free networks). Preliminary results show that attacks based on disconnecting a few number of nodes Miuz are more dangerous (decreasing the robustness) than the same attacks based on other centrality measures. We believe that Miuz, as well as other measures based on the size of the largest connected component, provides a good addition to other robustness metrics for complex networks.
Long-Term Trends in First Hospitalization for Heart Failure and Subsequent Survival Between 1986 and 2003: A Population Study of 5.1 Million People

Background— We examined whether population-level hospitalization rates for heart failure (HF) and subsequent survival have continued to improve since the turn of the century. We also examined trends in the prescribing of evidence-based pharmacological treatment for HF. Methods and Results— All patients in Scotland hospitalized with a first episode of HF between 1986 and 2003 were followed up until death or the end of 2004. Prescriptions of evidence-based treatments issued from 1997 to 2003 by a sample of primary care practices were also examined. A total of 116 556 individuals (52.6% women) had a first hospital discharge for HF. Age-adjusted first hospitalization rates for HF (per 100 000; 95% CI in parentheses) rose from 124 (119 to 129) in 1986 to 162 (157 to 168) in 1994 and then fell to 105 (101 to 109) in 2003 in men; in women, they rose from 128 (123 to 132) in 1986 to 160 (155 to 165) in 1993, falling to 101 (97 to 105) in 2003. Case-fatality rates fell steadily over the period. Adjusted 30-day case-fatality rates fell after discharge (adjusted odds [2003 versus 1986] 0.59 [95% CI 0.45 to 0.63] in men and 0.77 [95% CI 0.67 to 0.88] in women). Adjusted 1- and 5-year survival improved similarly. Median survival increased from 1.33 to 2.34 years in men and from 1.32 to 1.79 years in women. Age-adjusted prescribing rates for angiotensin-converting enzyme inhibitors, β-blockers, and spironolactone increased from 1997 to 2003 (all P<0.0001 for trend). Conclusions— After rising between 1986 and 1994, rates of first hospitalization for HF declined. Case-fatality rates also fell. Prescribing rates for HF therapies increased from 1997 to 2003. These findings suggest that improvements in the prevention and treatment of HF may have had progressive, sustained effects on outcomes at the population level; however, prognosis remains poor in HF.
Early Recovery of Salmonella from Food Using a 6-Hour Non-selective Pre-enrichment and Reformulation of Tetrathionate Broth

Culture based methods are commonly employed to detect pathogens in food and environmental samples. These methods are time consuming and complex, requiring multiple non-selective and selective enrichment broths, and usually take at least 1 week to recover and identify pathogens. Improving pathogen detection in foods is a primary goal for regulatory agencies and industry. Salmonella detection in food relies on a series of culture steps in broth formulations optimized to resuscitate Salmonella and reduce the abundance of competitive bacteria. Examples of non-selective pre-enrichment broths used to isolate Salmonella from food include Lactose, Universal Pre-enrichment, BPW, and Trypticase Soy broths. Tetrathionate (TT) and Rappaport–Vassiliadis (RV) broths are employed after a 24-h non-selective enrichment to select for Salmonella and hamper the growth of competitive bacteria. In this study, we tested a new formulation of TT broth that lacks brilliant green dye and has lower levels of TT . We employed this TT broth formulation in conjunction with a 6-h non-selective pre-enrichment period and determined that Salmonella recovery was possible one day earlier than standard food culture methods. We tested the shortened culture method in different non-selective enrichment broths, enumerated Salmonella in the non-selective enrichments, and used 16S rRNA gene sequencing to determine the proportional abundances of Salmonella in the TT and RV selective enrichments. Together these data revealed that a 6-h non-selective pre-enrichment reduces the levels of competitive bacteria inoculated into the selective TT and RV broths, enabling the recovery of Salmonella 1 day earlier than standard culture enrichment methods.
Control-loop bandwidth limitations for multiphase interleaving buck converters

To investigate the relationship between the control-loop bandwidth and the switching frequency, this paper introduces a multi-frequency small-signal model for multiphase interleaving buck converters. Including the influences from the frequency components generated by the pulse-width modulation schemes, this model is applicable beyond half the switching frequency, which is where the average model loses its validity. For voltage-mode control, both cases of trailing-edge modulation and of double-edge modulation are analyzed. Control-loop bandwidth limitations are clearly illustrated. In addition, peak current-mode control is discussed. Simulation and experimental results prove the analysis.
A Feasible Direction Method for Optimization Problem with Orthogonal Constraint in Feature Selection

Feature selection, as a fundamental component of building robust models, plays an important role in many machine learning and data mining tasks. Since acquiring labeled data is particularly expensive in both time and effort, unsupervised feature selection on unlabeled data has recently gained considerable attention. Without label information, unsupervised feature selection needs alternative criteria to define feature relevance. We propose a novel unsupervised feature selection model, which embeds feature selection into nonnegative spectral clustering. A tailored optimization algorithm based on Alternating Direction Method of Multipliers (ADMM) is designed to solve the proposed model. Many previous unsupervised feature selection methods used singular value decompose (SVD) to handle the subproblem with orthogonal constraint. Generally, the scale of the matrix in feature selection is significantly big, the computation of SVD will be very slow or even infeasible. To address this issue, we propose to use a feasible direction method to efficiently solve the subproblem with orthogonal constraint. The experimental study shows that we can obtain better performance compared with the state of the art methods.