Miracle-dz/UniFAR-FTUs huggingface dataset:
Response Sensitivity in the Yeast Mitogen-Activated Protein Kinase Cascade Permalink

The yeast pheromone response pathway is a canonical three-step mitogen activated protein kinase (MAPK) cascade which requires a scaffold protein for proper signal transduction. Recent experimental studies into the role the scaffold plays in modulating the character of the transduced signal, show that the presence of the scaffold increases the biphasic nature of the signal response. This runs contrary to prior theoretical investigations into how scaffolds function. We describe a mathematical model of the yeast MAPK cascade specifically designed to capture the experimental conditions and results of these empirical studies. We demonstrate how the system can exhibit either graded or ultrasensitive (biphasic) response dynamics based on the binding kinetics of enzymes to the scaffold. At the basis of our theory is an analytical result that weak interactions make the response biphasic while tight interactions lead to a graded response. We then show via an analysis of the kinetic binding rate constants how the results of experimental manipulations, modeled as changes to certain of these binding constants, lead to predictions of pathway output consistent with experimental observations. We demonstrate how the results of these experimental manipulations are consistent within the framework of our theoretical treatment of this scaffold-dependent MAPK cascades, and how future efforts in this style of systems biology can be used to interpret the results of other signal transduction observations. Citation: Thalhauser CJ, Komarova NL (2010) Signal Response Sensitivity in the Yeast Mitogen-Activated Protein Kinase Cascade. PLoS ONE 5(7): e11568. doi:10.1371/journal.pone. 0011568 Editor: Diego Di Bernardo, Fondazione Telethon, Italy Received June 17, 2009; Accepted June 1, 2010; Published July 23, 2010 Copyright: 2010 Thalhauser, Komarova. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the National Institutes of Health/National Science Foundation joint initiative on Mathematical Biology through NIH grant GM75309 and NIH/National Institute of General Medical Sciences grant 1P50GM076516-01A1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: komarova@uci.edu
Air Caloric Stimulation With Tympanic Membrane Perforation

Warm air caloric stimulation in an ear with tympanic membrane perforation or mastoidectomy cavity often causes contralateral nystagmus. Secondary nystagmus is common. Our evidence with squirrel monkeys and patients indicates that the primary “inversion” results from endolymph cooling due to evaporative cooling of the mucus lining the middle ear cavity, by the dry air stimulus. Disconjugate horizontal nystagmus was found in a patient with large eardrum perforation, after cold air caloric stimulation. The effect probably resulted from stimulation of the anterior or posterior vertical semicircular canal. Inverted or disconjugate caloric nystagmus after air stimulation is much more frequently due to tympanic membrane perforation, or moisture in the external ear, than to central nervous system disease.
Head or Tail? An Integrative Analysis of Customer Value and Product Portfolio

In prior e-commerce research, two distinct viewpoints––the customer-based view and the product-basedview––were studied separately to determine optimal consumer marketing strategies. The former focuses oncustomer browsing/searching/purchasing behaviors to discover valuable customers; the latter concentrates onproduct popularity to discover optimal product portfolios. Recent research has shifted the focus from popularitytowards the long-tail phenomenon and its driving factors; however, little is known about efficient and effectivemethods to promote the right (e.g. head- or tail-) products to the right (e.g. VIP or Non-VIP) customers. Thecurrent study integrates these two viewpoints to provide greater insights and thereby develop morecomprehensive marketing strategies. Our findings show that VIP customers make the majority of long-tailpurchases. Moreover, apart from their high number of head- and tail-product purchases, they also display distinctwebsite browsing/searching behaviors compared to Non-VIP customers. Finally, we identify five customersegments and outline corresponding marketing strategies.
Nonlocal cancellation of dispersion.

Two classical, coincident light pulses propagating through two different dispersive media will become broadened and their degree of coincidence will be reduced. The width of the coincidence curve can be shown to be proportional to ( β 1 2 + β 2 2 ) x 2 , where β1, and β2 are the dispersion coefficients in the two media and x is the distance traveled. When entangled photon pairs from parametric down conversion are considered instead, it is found that the width of the coincidence curve is then proportional to (β1 + β2)2x2, which gives an interference term of 2β1β1. If β1 = β2, the dispersion experienced by one photon can exactly cancel the dispersion experienced by the other in such a way that their coincidence is maintained.
ClaNC: point-and-click software for classifying microarrays to nearest centroids

SUMMARY ClaNC (classification to nearest centroids) is a simple and an accurate method for classifying microarrays. This document introduces a point-and-click interface to the ClaNC methodology. The software is available as an R package. AVAILABILITY ClaNC is freely available from http://students.washington. edu/adabney/clanc
Chapter 2 Role of Cysteine Cathepsins in Extracellular Proteolysis

Cysteine cathepsins are lysosomal proteases with housekeeping as well as highly specialized functions. Although their activities are optimal at lysosomal acidic and reducing conditions, cathepsins can significantly contribute to the degradation of the extracellular matrix. This may happen under physiological conditions as in cathepsin K-mediated bone resorption or under pathological conditions. Extracellular matrix degradation can occur extracellularly by the secretion of cathepsins or intracellularly following the endocytosis of matrix material. Under physiological conditions, the extracellular matrix is safeguarded against cathepsin activities by its neutral pH, oxidative environment, and high levels of potent endogenous cathepsin inhibitors. However, these barriers can be overcome by pericellular acidification and pathophysiologically reduced anticathepsin concentrations. Whereas matrix metalloproteases are primarily responsible for the homeostasis of the extracellular matrix, cysteine proteases contribute to its destruction under disease conditions. The development of cathepsin inhibitors as anti matrixdegrading drugs appears to be a successful strategy.
Side‐chain entropy effects on protein secondary structure formation

Loss of conformational entropy is one of the primary factors opposing protein folding. Both the backbone and side‐chain of each residue in a protein will have their freedom of motion restricted in the final folded structure. The type of secondary structure of which a residue is part will have a significant impact on how much side‐chain entropy is lost. Side‐chain conformational entropies have previously been determined for folded proteins, simple models of unfolded proteins, α‐helices, and a dipeptide model for β‐strands, but not for polyproline II (PII) helices. In this work, we present side‐chain conformational estimates for the three regular secondary structure types: α‐helices, β‐strands, and PII helices. Entropies are estimated from Monte Carlo computer simulations. β‐Strands are modeled as two structures, parallel and antiparallel β‐strands. Our data indicate that restraining a residue to the PII helix or antiparallel β‐strand conformations results in side‐chain entropies equal to or higher than those obtained by restraining residues to the parallel β‐strand conformation. Side‐chains in the α‐helix conformation have the lowest side‐chain entropies. The observation that extended structures retain the most side‐chain entropy suggests that such structures would be entropically favored in unfolded proteins under folding conditions. Our data indicate that the PII helix conformation would be somewhat favored over β‐strand conformations, with antiparallel β‐strand favored over parallel. Notably, our data imply that, under some circumstances, residues may gain side‐chain entropy upon folding. Implications of our findings for protein folding and unfolded states are discussed. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Genetic interaction between members of the Vangl family causes neural tube defects in mice

Neural tube defects (NTDs) are very frequent congenital abnormalities in humans. Recently, we have documented independent association of Vangl1 and Vangl2 gene mutations with NTDs. In the Looptail mouse, homozygosity (but not heterozygosity) for loss-of-function alleles at Vangl2 causes the severe NTD craniorachischisis, whereas heterozygosity for mutant variants of VANGL1 is associated with NTDs in a human cohort of sporadic and familial cases. To understand the role of Vangl1 in normal development, we created a mouse mutant with an inactivating mutation at Vangl1 (Vangl1gt). Vangl1 shows a dynamic pattern of expression in the developing neural tube and notochord at the time of neural tube closure. Vangl1gt/+ heterozygotes and Vangl1gt/gt homozygotes are viable and fertile, although Vangl1gt/gt display subtle alterations in polarity of inner hair cells of the cochlea. Remarkably, and as opposed to healthy Vangl1gt/+ and Vangl2lp/+ heterozygotes, Vangl1gt/+;Vangl2lp/+ double heterozygotes show profound developmental defects that include severe craniorachischisis, inner ear defects (disorganization of the stereociliary bundles of hair cells of the organ of Corti), and cardiac abnormality (aberrant right subclavian artery). These results show that genetic interaction between Vangl1 and Vangl2 genes causes neural tube defects and raise the possibility that interaction between individual Vangl genes and other genetic loci and/or environmental factors may additionally contribute to the etiology of NTDs.
The role of sprouts in human nutrition. A review

Based on the data of the literature it can be stated that the original composition of the seeds essentially changes during germination. The quantity of the protein fractions changes, the proportion of the ni- trogen containing fractions shifts towards the smaller protein fractions, oligopeptides and free amino acids. Beyond this changes the quantity of the amino acids (some of them increase, others decrease or do not alter) during germination, and nonprotein amino acids also are produced. In consequence of these changes, the biological value of the sprout protein increase, and greater digestibility was established in animal experiments. The composition of the triglycerides also changes, owing to hydrolysis free fatty acids originate, that can be considered as a certain kind of prediges- tion. Generally, the ratio of the saturated fatty acids increases compared
Interleukin-4 Blood Concentrations in Early and Metastatic Human Solid Neoplasms

Blood levels of the immunosuppressive cytokines IL-6 and IL-10 are often abnormally high in patients with advanced cancer. However, since IL-6 and IL-10 may be produced by macrophages and TH2 cells, the evidence of abnormally high values of IL-6 and/or IL-10 may reflect hyperactivation either of the macrophage system or of TH2 cell functions. In contrast, IL-4 is almost completely produced by the TH2 lymphocytes. Therefore, evaluation of IL-4 levels could help to differentiate macrophage from TH2 cell hyperactivation. This study was performed to investigate IL-4 serum levels in a group of cancer patients in relation to the stage of disease and to the secretion of other cytokines. The study included 50 patients, 28 of whom showed distant organ metastases. Lung cancer and gastrointestinal cancers were the most frequent neoplasms in our patients. The control group consisted of 60 healthy subjects. IL-4 was measured by the Elisa method. No patient showed high levels of IL-4. No significant differences were seen between controls and cancer patients, nor between metastatic and non-metastatic patients. In addition, no significant differences in IL-4 mean values were found between patients with normal or high levels of IL-6 and IL-10, or between patients with normal or low IL-2 concentrations. This preliminary study seems to exclude cancer-related abnormally high secretion of IL-4. Therefore, the high levels of IL-6 and/or IL-10 often occurring in advanced neoplastic disease would mainly depend on macrophage production.
A review of language learning motivation theories

This paper traces in brief the history of language learning motivation (LLM) by reviewing the main motivation theories and models that have affected its development. The paper commences with a brief discussion on the definition of the concept of motivation and on the emergence of the interest in LLM. It examines the complexity of LLM in light of the bulk of research in the field. Finally, the paper refers to some of the most recent perspectives on the nature of this concept. Introduction It is a well established belief among most researchers that motivation is crucial in students' learning. However, the concept of` motivation, as will be illustrated below, proves complex since it takes a respectable number of different disciplines to arrive at a reasonable understanding of its different facets. General, educational, social, and cognitive psychology, as well as general educational and social theories and sociolinguistic theories have something to contribute for understanding LLM (language learning motivation) within a formal school context. The concept of motivation involves, in addition, neurobiological and physiological explanations. The complexity of the concept of motivation resides in its endeavours to explain individuals’ actions and behaviour (Dörnyei, 2000 & 2001) which cannot be accounted for by one panaceic approach. Research on students’ LLM has recently mushroomed (see Dörnyei, 2001, 2005 and Dörnyei & Schmidt, 2001 for extensive reviews) and it remains a fertile area (Spolsky, 2000). The problem, as Dörnyei (1996) asserts, is not the lack of theories to explain motivation but rather the abundance of theories and models. However, the long history of research into LLM and the plenty of research and theorisation did not bring an end to the confusion
EXPERIMENTAL INFECTION OF PONIES WITH SARCOCYSTIS FAYERI AND DIFFERENTIATION FROM SARCOCYSTIS NEURONA INFECTIONS IN HORSES

Sarcocystis neurona and Sarcocystis fayeri infections are common in horses in the Americas. Their antemortem diagnosis is important because the former causes a neurological disorder in horses, whereas the latter is considered nonpathogenic. There is a concern that equine antibodies to S. fayeri might react with S. neurona antigens in diagnostic tests. In this study, 4 ponies without demonstrable serum antibodies to S. neurona by Western immunoblot were used. Three ponies were fed 1 × 105 to 1 × 107 sporocysts of S. fayeri obtained from dogs that were fed naturally infected horse muscles. All ponies remained asymptomatic until the termination of the experiment, day 79 postinoculation (PI). All serum samples collected were negative for antibodies to S. neurona using the Western blot at the initial screening, just before inoculation with S. fayeri (day 2) and weekly until day 79 PI. Cerebrospinal fluid samples from each pony were negative for S. neurona antibodies. Using the S. neurona agglutination test, antibodies to S. neurona were not detected in 1:25 dilution of sera from any samples, except that from pony no. 4 on day 28; this pony had received 1 × 107 sporocysts. Using indirect immunofluorescence antibody tests (IFATs), 7 serum samples were found to be positive for S. neurona antibodies from 1:25 to 1:400 dilutions. Sarcocystis fayeri sarcocysts were found in striated muscles of all inoculated ponies, with heaviest infections in the tongue. All sarcocysts examined histologically appeared to contain only microcytes. Ultrastructurally, S. fayeri sarcocysts could be differentiated from S. neurona sarcocysts by the microtubules (mt) in villar protrusions on sarcocyst walls; in S. fayeri the mt extended from the villar tips to the pellicle of zoites, whereas in S. neurona the mt were restricted to the middle of the cyst wall. Results indicate that horses with S. fayeri infections may be misdiagnosed as being S. neurona infected using IFAT, and further research is needed on the serologic diagnosis of S. neurona infections.
Immunoglobulin and Lymphocyte Responses Following Silica Exposure in New Zealand Mixed Mice

Epidemiological studies have shown strong associations between silica exposure and several autoimmune diseases, including scleroderma and systemic lupus erythematosus.We previously reported that the New Zealand mixed (NZM) mouse develops silicosis and exacerbated autoimmunity following crystalline silica exposure, including increased levels of autoantibodies, proteinuria, circulating immune complexes, pulmonary fibrosis, and glomerulonephritis. In this study, the NZM mouse was used to examine changes in immune activation following silica exposure by measuring levels of immunoglobulin, cytokines and lymphocyte populations. Levels of immunoglobulin (Ig) G1 were significantly decreased from 1124 ± 244 µg/ml in saline exposed mice to 614 ± 204 µg/ml in silica-exposed mice, suggesting a decrease in the Th2 response. The levels of tumor necrosis factor (TNF)-α were significantly increased (1.5-fold) in the bronchoalveolar lavage fluid of the silica-exposed mice as compared to the saline-exposed mice. The number of B1a B cells were significantly increased sixfold within the superficial cervical lymph nodes of silica-exposed mice as compared with saline-exposed mice. Following silica exposure, CD4+T cells significantly increased threefold within the superficial cervical lymph nodes. During this increase in the number of CD4+T cells, the number of CD4+CD25+ regulatory T cells was not significantly changed, altering the ratio of regulatory T cells to T helper cells from 1:5 to 1:8 following silica exposure. Therefore, the silica-induced alterations in immunoglobulin levels, increased TNF-α, increased B1a B cells and CD4+ T cells, with decreased regulatory T cells, may provide an environment that allows for increased autoreactivity. These studies begin to provide possible mechanisms for environmentally induced autoimmune diseases that have been reported in many epidemiological studies.
Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies

Editors’ Note: In reference to “Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy,” Dr. Papanicolaou et al. discuss whether functional MRI (fMRI) evaluation for language dominance in epilepsy surgery can be considered reliable given the high rate of false-positives inherent in fMRI data processing. In support, guideline editors Gloss et al. cite the high concordance between fMRI and amobarbital testing and explain how the method of analysis used in hemispheric language assessment has been shown to be less prone to statistical error. Drs. Zack and Kobau bring up several questions in regards to “Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies,” including the exclusion of at least 2 relevant references and the suitability of the statistical methodology chosen. Authors Jette et al. further explain their statistical approach but agree that one reference was omitted. A correction appears on page 642. —Megan Alcauskas, MD, and Robert C. Griggs, MD
Rare variants of Cutaneous Leishmaniasis: Whitlow, paronychia, and sporotrichoid

Cutaneous Leishmaniasis is endemic in certain areas of Pakistan, with the wet form of the disease being the most prevalent. It has a number of morphological variants, which are dependant on the immune status of the host, the subspecies of the Leishmania, and also, to some extent, on the site of involvement. We describe here a case of Leishmaniasis showing two very rare variants, whitlow and paronychial lesions, occurring concurrently with sporotrichoid spread. The patient responded to intramuscular sodium stibogluconate with resolution of the skin lesions.
Effect of a Topical Vasodilator on Tumor Hypoxia and Tumor Oxygen Guided Radiotherapy using EPR Oximetry

Abstract We sought to reduce tumor hypoxia by topical application of a vasodilator, benzyl nicotinate (BN), and investigated its effect on the growth of tumors irradiated at times when tumor pO2 increased. EPR oximetry was used to follow the changes in the tissue pO2 of subcutaneous radiation-induced fibrosarcoma (RIF-1) tumors during topical applications of 1.25–8% BN formulations for 5 consecutive days. The RIF-1 tumors were hypoxic with a tissue pO2 of 4.6–7.0 mmHg. A significant increase in tumor pO2 occurred 10–30 min after BN application. The formulation with the minimal BN concentration that produced a significant increase in tumor pO2 was used for the radiation study. The tumors were irradiated (4 Gy × 5) at the time of the maximum increase in pO2 observed with the 2.5% BN formulation. The tumors with an increase in pO2 of greater than 2 mmHg from the baseline after application of BN on day 1 had a significant growth inhibition compared to the tumors with an increase in pO2 of less than 2 mmHg. The results indicate that the irradiation of tumors at the time of an increase in pO2 after the topical application of the 2.5% BN formulation led to a significant growth inhibition. EPR oximetry provided dynamic information on the changes in tumor pO2, which could be used to identify responders and non-responders and schedule therapy during the experiments.
Loss of blood group A in acute leukemia: Morphologic and biochemical studies of red cells

A patient with blood type A had acute myelomonocytic leukemia; his red cells (RBCs) typed as O and his serum had anti‐B. RBC membranes were isolated from the patient as well as from controls with group A and O red cells. The membranes were incubated with uridine diphosphate (UDP)‐ N‐acetyl‐D‐14C galactosamine in plasma from the patient and controls with group A and O red cells. RBC membranes from the patient behaved normally in that they incorporated the terminal carbohydrate responsible for blood group A activity. Scanning electron microscopy showed that the patient's RBCs had striking morphologic changes, with marked crenation and numerous knisocytes and dacryocytes. It was concluded that loss of the A antigen in this patient was not due to an abnormality of the enzyme required to convert H substance to A substance. It was postulated that weakening of the A antigen in some patients with leukemia may be related to a steric modification associated with abnormal red cell morphology.
Noncollinear intra-atomic magnetism.

An intra-atomic noncollinear magnetization density has been calculated for the case of ferromagnetic fcc Pu, by means of a newly implemented general-local-spin-density-approximation method which treats the magnetization density as a continuous vector quantity. The presence of noncollinearity is a general effect, not specific to Pu, which is shown to rise due to the interplay of the local exchange and the spin-orbit coupling. The form of the noncollinear part of the magnetization density is very sensitive to the space group symmetry as is demonstrated by calculations with the average spin moment along [001] and [111], respectively. {copyright} {ital 1996 The American Physical Society. }