Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody recognition of the type 14 pneumococcal capsule. Evidence for a conformational epitope in a neutral polysaccharide

Oligosaccharides consisting of one or more tetrasaccharide repeating units were derived from the capsular polysaccharide of type 14 pneumococcus (Pn14) by endo-beta-galactosidase digestion. The relative affinity of anticapsular antibody binding to derivative oligosaccharides of different chain lengths was measured in a Pn 14 ELISA inhibition assay. The concentration of inhibiting antigen required to achieve 50% inhibition of IgG binding increased progressively from 5.6 x 10(-4) M to 7.0 x 10(-11) M as the inhibiting saccharide chain length increased from 1 tetrasaccharide repeating unit to 2,500 repeating units. These data indicate that antibodies directed against the Pn14 polysaccharide recognize a conformational epitope fully expressed only in high molecular weight forms of the antigen. Similar results were found for inhibition of Fab fragment binding, suggesting that recognition of the conformational epitope is largely dependent on the intrinsic affinity of the Fab combining region. Unlike previously reported polysaccharides for which conformational epitopes have been described, the Pn14 polysaccharide does not contain negatively charged residues, indicating that expression of conformational determinants is not limited to acidic polysaccharides. Antibody recognition of conformational epitopes may be a common mechanism by which the host immune response discriminates between bacterial polysaccharides and host oligosaccharides of similar structure.
The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey.

BACKGROUND Psoriasis can have a profound impact on a patient's quality of life. OBJECTIVES To assess patients' perspectives on the impact of psoriasis on their lifestyle and emotional well-being and the social ramifications of living with the disease; to determine the range of therapies available; and to ascertain patients' satisfaction with the management of their disease. DESIGN A 4-page, self-administered questionnaire was mailed on July 13 and 14, 1998, to the entire membership of the National Psoriasis Foundation (N = 40 350), and followed by a telephone survey of responders with severe psoriasis. MAIN OUTCOME MEASURES Patients' perspectives on the psychosocial impact of psoriasis and the effectiveness of the management of their disease. RESULTS Of the 40 350 questionnaires mailed out, a response rate of 43% was realized. The most frequent symptoms experienced by the mail-survey respondents were scaling (94%), itching (79%), and skin redness (71%); 39% reported that psoriasis covered 10% or more of their bodies. A total of 6194 patients with severe psoriasis were entered into the database for the telephone survey. Of these, 79% reported that psoriasis had a negative impact on their lives, 40% felt frustrated with the ineffectiveness of their current therapies, and 32% reported that treatment was not aggressive enough. CONCLUSIONS The unprecedented response to the survey provides compelling evidence that individuals with psoriasis believe that the disease has a profound emotional and social as well as physical impact on their quality of life. Many patients with psoriasis, particularly those with severe disease, are frustrated with the management of their disease and by the perceived ineffectiveness of their therapies. Physicians may need to improve communication with their patients and should reevaluate their management of psoriasis.
A two-stage normalization method for partially degraded mRNA microarray data

MOTIVATION The goal of the study is to obtain genetic information from exfoliated colonocytes in the fecal stream rather than directly from mucosa cells within the colon. The latter is obtained through invasive procedures. The difficulties encountered by this procedure are that certain probe information may be compromised due to partially degraded mRNA. Proper normalization is essential to obtaining useful information from these fecal array data. RESULTS We propose a new two-stage semiparametric normalization method motivated by the features observed in fecal microarray data. A location-scale transformation and a robust inclusion step were used to roughly align arrays within the same treatment. A non-parametric estimated non-linear transformation was then used to remove the potential intensity-based biases. We compared the performance of the new method in analyzing a fecal microarray dataset with those achieved by two existing normalization approaches: global median transformation and quantile normalization. The new method favorably compared with the global median and quantile normalization methods. AVAILABILITY The R codes implementing the two-stage method may be obtained from the corresponding author.
Laparoscopy for Colon and Rectal Cancer

Laparoscopy has emerged as a useful tool in the surgical treatment of diseases of the colon and rectum. Specifically, in the application of colon cancer, a laparoscopic-assisted approach offers short-term benefits to patients while maintaining a long-term oncologic outcome. Hand-assisted laparoscopic surgery may help decrease operative times while preserving the benefits of laparoscopy. The literature on the use of laparoscopy for rectal cancer is still in its early stages. Limited data suggest short-term benefits without compromising oncologic outcome; however, data from large multicenter trials will clarify the role of laparoscopy in the treatment of rectal cancer. Robotic proctectomy is a novel technique that may offer considerable advantage and overcome some limitations laparoscopy creates while working in the confines of the pelvis. The improved magnification and visualization offered with the robot may also assist in preserving bladder and sexual function. Transanal endoscopic microsurgery (TEM) for the treatment of T1 rectal cancers with low-risk features appears to be safe. However, TEM has a significantly higher recurrence rate when used to treat invasive cancer. Endoluminal techniques and equipment are under development and could offer more minimally invasive approaches to the treatment of colon and rectal cancer. Credentialing and training of surgeons and teams involved in the use of laparoscopy is important prior to making these techniques ubiquitous.
Compiling for stream processing

This paper describes a compiler for stream programs that efficiently schedules computational kernels and stream memory operations, and allocates on-chip storage. Our compiler uses information about the program structure and estimates of kernel and memory operation execution times to overlap kernel execution with memory transfers, maximizing performance, and to optimize use of scarce on-chip memory, significantly reducing external memory bandwidth. Our compiler applies optimizations such as strip-mining, loop unrolling, and software pipelining, at the level of kernels and stream memory operations. We evaluate the performance of our compiler on a suite of media and scientific benchmarks. Our results show that compiler management of on-chip storage reduces external memory bandwidth by 35% to 93% and reduces execution time by 23% to 72% compared to cache like LRU management of the same storage. We show that strip-mining stream applications enables producer-consumer locality to be captured in on-chip storage reducing external bandwidth by 50% to 80%. We also evaluate the sensitivity of performance to the scheduling methods used and to critical resources. Overall, our compiler is able to overlap memory operations and manage local storage so that 78% to 96% of program execution time is spent in running computational kernels.
Diclofenac sodium topical solution with dimethyl sulfoxide, a viable alternative to oral nonsteroidal anti-inflammatories in osteoarthritis: review of current evidence

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may offer a safer alternative to their oral counterparts for the management of osteoarthritis. Diclofenac sodium topical solution with dimethyl sulfoxide (TDiclo) was evaluated in five randomized, controlled trials and is indicated for treatment of the signs and symptoms associated with osteoarthritis of the knee. Three studies showed that TDiclo is superior to placebo and vehicle control with respect to pain, physical function, and perception of osteoarthritis symptoms. Two studies showed that benefits are similar to those of oral diclofenac, with one study demonstrating statistical equivalence. The most common adverse event associated with TDiclo in these studies was dry skin. Incidences of gastrointestinal adverse events and abnormal levels of liver enzymes were lower with TDiclo compared with oral diclofenac in active-controlled studies. Based on these studies, TDiclo represents a practical, evidence-based option for the management of osteoarthritis of the knee.
Gene Expression Levels Are a Target of Recent Natural Selection in the Human Genome

Changes in gene expression may represent an important mode of human adaptation. However, to date, there are relatively few known examples in which selection has been shown to act directly on levels or patterns of gene expression. In order to test whether single nucleotide polymorphisms (SNPs) that affect gene expression in cis are frequently targets of positive natural selection in humans, we analyzed genome-wide SNP and expression data from cell lines associated with the International HapMap Project. Using a haplotype-based test for selection that was designed to detect incomplete selective sweeps, we found that SNPs showing signals of selection are more likely than random SNPs to be associated with gene expression levels in cis. This signal is significant in the Yoruba (which is the population that shows the strongest signals of selection overall) and shows a trend in the same direction in the other HapMap populations. Our results argue that selection on gene expression levels is an important type of human adaptation. Finally, our work provides an analytical framework for tackling a more general problem that will become increasingly important: namely, testing whether selection signals overlap significantly with SNPs that are associated with phenotypes of interest.
Grundy chromatic number of the complement of bipartite graphs

A Grundy k-coloring of a graph G, is a vertex k-coloring of G such that for each two colors i and j with i < j, every vertex of G colored by j has a neighbor with color i. The Grundy chromatic number Γ(G), is the largest integer k for which there exists a Grundy k-coloring for G. In this note we first give an interpretation of Γ(G) in terms of the total graph of G, when G is the complement of a bipartite graph. Then we prove that determining the Grundy number of the complement of bipartite graphs is an NP-Complete problem.
Die Struktur albanischer Rotbuchen-Urwälder – Ableitungen für eine naturnahe Buchenwirtschaft

Zusammenfassung:Anhand von Vollaufnahmen des lebenden und toten Derbholzbestandes auf mehreren Hektar großen Untersuchungsflächen wird die Waldstruktur von drei albanischen Buchenurwäldern analysiert. Ergänzend werden die Ergebnisse einer stichprobenweisen Verjüngungsinventur vorgestellt. Die Urwälder zeichnen sich durch hohe Derbholzvorräte, eine starke Durchmesserdifferenzierung und hohe Verjüngungsvorräte aus. Sie werden sowohl im Derbholzbestand als auch in der Verjüngung von Buche dominiert. Die Lücken im Kronendach liegen im Mittel unter der Größe einer Altbuchenkrone und entstehen daher überwiegend durch den Ausfall einzelner Bäume. Die kleinflächige Lückenbildung geht mit einem kleinflächigen Wechsel der Waldentwicklungsphasen einher. Ein wichtiges Strukturelement sind Altbäume über 80 cm Brusthöhendurchmesser, die in geklumpter-zufälliger räumlicher Verteilung vorkommen. Auch liegendes und stehendes Totholz ist ein typisches Kennzeichen der Urwälder. Dessen Anteile liegen jedoch am unteren Ende der für naturnahe Laubwälder der gemäßigten Zone bekannten Werte. Dies wird auf die vergleichsweise rasche Zersetzung des Buchentotholzes zurückgeführt. Der Anteil liegenden Totholzes liegt deutlich über dem des stehenden Totholzes. In den Schlussfolgerungen für eine naturnahe Buchenwirtschaft wird die Bedeutung punktueller, an Stelle flächendeckender Eingriffe und die Bedeutung von Altbäumen und Totholz betont. Zielkonflikte können sich aus der Forderung nach gleichzeitig naturnahen und gemischten Buchenwäldern ergeben.Summary:The results of inventories of forest structure and tree regeneration in three Albanian beech (Fagus sylvatica L.) virgin forests are presented and discussed. The data reveal that these forests are characterized by high levels of (1) stand volume of living trees, (2) diameter differentiation and (3) density of saplings and young trees. Beech is the dominant tree species in the upper canopy layers as well as in the regeneration layer. The mean size of canopy gaps is smaller than the mean crown size of old trees. Therefore, gaps are formed mainly by the death of single trees. Subsequently, forest texture is characterized by small-scale changes in development phases. Giant trees, measuring more than 80 cm at breast height, are another prominent feature of the virgin forests examined. These trees show a clumped distribution with a tendency to randomness. Snags and downed logs above 20 cm in diameter amount to 30.3–85.3 m3/ha or 3.9–10.4 % of the living stand above 7 cm DBH. Due to a high rate of decomposition, these values are low compared to other pristine forests of the temperate zone. Forestry can emulate patterns and processes of virgin beech forests by single – group tree cuttings instead of clear cut or homogenous shelterwood systems and a significant amount of old trees and coarse woody debris. Apparently, a high portion of admixed tree species is not a natural feature of beech forests. Therefore, a conflict could arise between the goals of enhancing tree species diversity and of emulating natural patterns.
Testosterone, cuckoldry risk and extra–pair opportunities in the Seychelles warbler

In male birds, testosterone (T) plays an important role in aggressive and mate–attraction behaviour. In the cooperatively breeding Seychelles warbler, Acrocephalus sechellensis, extra–group copulations (EGCs) occur frequently, but are not accompanied by sexual courtship displays as in within–pair copulations. Paternity is nearly always gained by primary males. We investigated whether T levels and sperm storage capability (cloacal protuberance (CP)) in adult primary and subordinate males were related to timing of egg laying, levels of cuckoldry and extra–group paternity (EGP) opportunities. During the sexually active period before egg laying, T levels and CP were only elevated or enlarged (respectively) in primary males, and some suggestion was found that subordinate males do not invest in elevated T levels. The peak in T occurred during the fertile period of the female partner and corresponded to the peak period of male sexual displays and mate guarding, but was independent of cuckoldry risk (density of neighbouring primary males). CP was also enhanced during this period; however, CP but not T remained elevated after egg laying by their mates, and CP but not T was positively related to EGP opportunities (density of neighbouring fertile females). We conclude that T is involved in sexual courtship displays and mate guarding, but not in gaining EGCs. These findings contrast with those in other species where EGP involves elaborate sexual displays.
Genetic Evidence for p75NTR-Dependent Tetraploidy in Cortical Projection Neurons from Adult Mice

A subpopulation of chick retinal projection neurons becomes tetraploid during development, an event prevented by blocking antibodies against p75 neurotrophin receptor (p75NTR). We have used an optimized flow cytometric assay, based on the analysis of unfixed brain cell nuclei, to study whether p75NTR-dependent neuronal tetraploidization takes place in the cerebral cortex, giving rise to projection neurons as well. We show that 3% of neurons in both murine neocortex and chick telencephalic derivatives are tetraploid, and that in the mouse ∼85% of these neurons express the immediate early genes Erg-1 and c-Fos, indicating that they are functionally active. Tetraploid cortical neurons (65–80%) express CTIP2, a transcription factor specific for subcortical projection neurons in the mouse neocortex. During the period in which these neurons are born, p75NTR is detected in differentiating neurons undergoing DNA replication. Accordingly, p75NTR-deficient mice contain a reduced proportion of both NeuN and CTIP2-positive neocortical tetraploid neurons, thus providing genetic evidence for the participation of p75NTR in the induction of neuronal tetraploidy in the mouse neocortex. In the striatum tetraploidy is mainly associated with long-range projection neurons as well since ∼80% of tetraploid neurons in this structure express calbindin, a marker of neostriatal-matrix spiny neurons, known to establish long-range projections to the substantia nigra and globus pallidus. In contrast, only 20% of tetraploid cortical neurons express calbindin, which is mainly expressed in layers II–III, where CTIP2 is absent. We conclude that tetraploidy mainly affects long-range projection neurons, being facilitated by p75NTR in the neocortex.
Quantitative proteomics reveals the dynamics of protein changes during Drosophila oocyte maturation and the oocyte-to-embryo transition

Significance Oogenesis aberrations are an important cause of birth defects. During oocyte development, meiotic divisions are coordinated with intense transcription and translation, which produce maternally encoded RNAs and proteins that drive early embryonic development. Oocyte maturation and egg activation result in eggs competent for fertilization and embryogenesis, respectively, and these events occur in the absence of transcription or RNA degradation. Therefore, it is likely that changes in protein levels or activity govern these developmental transitions. By providing the first proteome-wide overview, to our knowledge, of the proteins whose levels change during oocyte maturation and combining these data with our previous description of proteome remodeling at egg activation, we describe critical events and factors driving the development of immature oocyte into an embryogenesis-competent egg. The onset of development is marked by two major, posttranscriptionally controlled, events: oocyte maturation (release of the prophase I primary arrest) and egg activation (release from the secondary meiotic arrest). Using quantitative mass spectrometry, we previously described proteome remodeling during Drosophila egg activation. Here, we describe our quantitative mass spectrometry-based analysis of the changes in protein levels during Drosophila oocyte maturation. This study presents the first quantitative survey, to our knowledge, of proteome changes accompanying oocyte maturation in any organism and provides a powerful resource for identifying both key regulators and biological processes driving this critical developmental window. We show that Muskelin, found to be up-regulated during oocyte maturation, is required for timely nurse cell nuclei clearing from mature egg chambers. Other proteins up-regulated at maturation are factors needed not only for late oogenesis but also completion of meiosis and early embryogenesis. Interestingly, the down-regulated proteins are predominantly involved in RNA processing, translation, and RNAi. Integrating datasets on the proteome changes at oocyte maturation and egg activation uncovers dynamics in proteome remodeling during the change from oocyte to embryo. Notably, 66 proteins likely act uniquely during late oogenesis, because they are up-regulated at maturation and down-regulated at activation. We find down-regulation of this class of proteins to be mediated partially by APC/CCORT, a meiosis-specific form of the E3 ligase anaphase promoting complex/cyclosome (APC/C).
Analysis of the p16INK4A, p15INK4B and p18INK4C genes in multiple myeloma

To study the structural integrity of the cyclin‐dependent kinase inhibitors known as INK4A (p16), INK4B (p15) and INK4C (p18) in multiple myeloma, we examined 20 primary myeloma samples (including one case of plasma cell leukaemia) using polymerase chain reaction–single strand conformation polymorphism, and 17 samples were examined by Southern blot analysis. The plasma cell leukaemia sample had homozygous deletions of the p15 and p16 genes (6%). One myeloma case had a p15 gene homozygous deletion (6%) with an intact p16 gene. This sample also had a p18 homozygous deletion, suggesting that the deletion of both genes may be important in either the development or progression of myeloma. No point mutations of these INK4 genes were found in the 20 samples. This is the first report that indicates that deletions of p15, p16 and p18 genes occur in some individuals with multiple myeloma (2/17 cases).
Family Material Hardship and Chinese Adolescents’ Problem Behaviors: A Moderated Mediation Analysis

In the current study, we examined a moderated mediation model using the risk and resilience framework. Specifically, the impact of family material hardship on adolescent problem behaviors was examined in a Chinese sample; we used the family stress model framework to investigate parental depression and negative parenting as potential mediators of the relation between family material hardship and adolescents’ problem behaviors. In addition, based on resilience theory, we investigated adolescents’ resilience as a potential protective factor in the development of their internalizing and externalizing problems. Participants included 1,419 Chinese adolescents (mean age = 15.38 years, SD = 1.79) and their primary caregivers. After controlling for covariates (age, gender, location of family residence, and primary caregiver), we found that parental depression and negative parenting mediated the association between family material hardship and adolescents’ problem behaviors. Furthermore, the adolescent resilience moderated the relationship between negative parenting and internalizing problems in a protective-stabilizing pattern; in addition, a protective-reactive pattern also emerged when adolescent resilience was examined as a moderator of the relationship between negative parenting and externalizing problems. These findings contribute to a comprehensive understanding of the mechanisms of risk and resilience in youth development. Moreover, the findings have important implications for the prevention of adolescent problem behaviors.