Miracle-dz/UniFAR-FTUs huggingface dataset:
Point Mutations in FimH Adhesin of Crohn's Disease-Associated Adherent-Invasive Escherichia coli Enhance Intestinal Inflammatory Response

Adherent-invasive Escherichia coli (AIEC) are abnormally predominant on Crohn's disease (CD) ileal mucosa. AIEC reference strain LF82 adheres to ileal enterocytes via the common type 1 pili adhesin FimH and recognizes CEACAM6 receptors abnormally expressed on CD ileal epithelial cells. The fimH genes of 45 AIEC and 47 non-AIEC strains were sequenced. The phylogenetic tree based on fimH DNA sequences indicated that AIEC strains predominantly express FimH with amino acid mutations of a recent evolutionary origin - a typical signature of pathoadaptive changes of bacterial pathogens. Point mutations in FimH, some of a unique AIEC-associated nature, confer AIEC bacteria a significantly higher ability to adhere to CEACAM-expressing T84 intestinal epithelial cells. Moreover, in the LF82 strain, the replacement of fimH LF82 (expressing FimH with an AIEC-associated mutation) with fimH K12 (expressing FimH of commensal E. coli K12) decreased the ability of bacteria to persist and to induce severe colitis and gut inflammation in infected CEABAC10 transgenic mice expressing human CEACAM receptors. Our results highlight a mechanism of AIEC virulence evolution that involves selection of amino acid mutations in the common bacterial traits, such as FimH protein, and leads to the development of chronic inflammatory bowel disease (IBD) in a genetically susceptible host. The analysis of fimH SNPs may be a useful method to predict the potential virulence of E. coli isolated from IBD patients for diagnostic or epidemiological studies and to identify new strategies for therapeutic intervention to block the interaction between AIEC and gut mucosa in the early stages of IBD.
Webpage aesthetics, performance and usability: Design variables and their effects

The primary objectives of this research are to identify the underlying clusters of design variables affecting the perceived usability of a webpage and to examine the effects of webpage design variables on webpage performance. Fifty-seven design variables and 10 underlying clusters that conceptualise the structure of user webpage judgement are identified through content analysis on literature and structured interviews, balanced incomplete block user survey administration and cluster analysis. Five clusters are selected to conduct three experiments that quantify the change in user aesthetic preference, perceived ease of interaction and interaction speed as a function of loading speed, image colour, image size, font size, link style, and column width. Results show that user performance alone is not a good indicator of aesthetic judgement and overall effectiveness of a webpage. The value of integrating global construct analysis processes and local controlled experimentation processes in ergonomic interface research is illustrated. Fifty-seven webpage design variables are defined, ranked and clustered according to perceived importance and overall preference. Experimental results illustrate that both technical performance and aesthetic factors are important webpage design considerations.
KDD-Cup 2000 organizers' report: peeling the onion

We describe KDD-Cup 2000, the yearly competition in data mining. For the first time the Cup included insight problems in addition to prediction problems, thus posing new challenges in both the knowledge discovery and the evaluation criteria, and highlighting the need to "peel the onion" and drill deeper into the reasons for the initial patterns found. We chronicle the data generation phase starting from the collection at the site through its conversion to a star schema in a warehouse through data cleansing, data obfuscation for privacy protection, and data aggregation. We describe the information given to the participants, including the questions, site structure, the marketing calendar, and the data schema. Finally, we discuss interesting insights, common mistakes, and lessons learned. Three winners were announced and they describe their own experiences and lessons in the pages following this paper.
An Investigation of Fused Silica Composites for Improvement of Ablation and Rain Erosion Resistance, and an Alternate Method for Manufacture of Fused Silica Radomes

Abstract : The objectives of this program are to develop composite materials based on slip-cast fused silica which have a higher degree of rain erosion resistance and ablation resistance than fused silica itself, and to develop a method other than slip casting for fabrication of rebonded fused silica radomes. Task I of this program studies the effects of small additions of SiC and Si3N4 on the ablation and rain erosion resistance of slip-cast fused silica. The best composites were in the range of 10% SiC and 10% Si3N4. Ablation resistance was improved with both additives, but resistance to rain erosion did not show any improvement under the test conditions used. Task II of this program evaluated isostatic pressing as an alternate radome forming method. Radome shapes were pressed; however, physical properties of the pressed fused silica powders were less than those of slip-cast items. Work so far indicates that the isostatic pressing process has potential, but that further development is still needed.
Phase I evaluation of all-trans-retinoic acid in adults with solid tumors.

PURPOSE Prompted by recent demonstrations that all-trans-retinoic acid (all-trans-RA) had efficacy in acute promyelocytic leukemia, a phase I trial of all-trans-RA was conducted to establish the maximum-tolerated dose (MTD) before phase II testing. PATIENTS AND METHODS Forty patients with a histologic or cytologic diagnosis of malignancy other than leukemia were treated with single daily oral doses of all-trans-RA ranging from 45 mg/m2 to 200 mg/m2. Doses of all-trans-RA were escalated in the next cohort of patients until the MTD was determined if the preceding dose level was not associated with significant toxicity. RESULTS Lung cancer was the most common type of tumor included in the study (26 cases) followed by head and neck squamous cell carcinomas (three cases), and squamous cell carcinoma of the skin (two cases); other miscellaneous solid tumors were also represented. Toxicities included cheilitis, skin reactions, headache, and nausea and vomiting, as well as transient elevations of liver enzymes and triglyceride levels. Skin toxicities, consisting of erythema with desquamation and paronychia, were considered to be the dose-limiting toxicity, and were observed in two of six patients who received 175 mg/m2/d, and in two of five patients who received 200 mg/m2/d. Of the 30 patients with assessable lesions, response was evaluated in 26 patients and no major objective tumor response was observed. Two patients were able to receive the drug for longer than 1 year without significant toxicities. There was considerable variation in individual patients' peak plasma all-trans-RA levels, and a decrease in the area under the curve of all-trans-RA plasma concentration was observed in all four patients evaluated. CONCLUSION For phase II study of adult patients, we recommend 150 mg/m2 of all-trans-RA administered orally once a day. However, for better optimization of drug administration schedules, further studies are needed.
Bacteria Induce Prolonged PMN Survival via a Phosphatidylcholine-Specific Phospholipase C- and Protein Kinase C-Dependent Mechanism

Polymorphonuclear leukocytes (PMNs) are essential for the human innate immune defense, limiting expansion of invading microorganisms. PMN turnover is controlled by apoptosis, but the regulating signaling pathways remain elusive, largely due to inherent differences between mice and humans that undermine use of mouse models for understanding human PMN biology. Here, we aim to elucidate signal transduction mediating survival of human peripheral blood PMNs in response to bacteria, such as Yersinia pseudotuberculosis, an enteropathogen that causes the gastro-intestinal disease yersiniosis, as well as Escherichia coli and Staphylococcus aureus. Determinations of cell death reveal that uninfected control cells undergo apoptosis, while PMNs infected with either Gram-positive or -negative bacteria show profoundly increased survival. Infected cells exhibit decreased caspase 3 and 8 activities, increased mitochondrial integrity and are resistant to apoptosis induced by a death receptor ligand. This bacteria-induced response is accompanied by pro-inflammatory cytokine production including interleukin-8 and tumor necrosis factor-α competent to attract additional PMNs. Using agonists and pharmacological inhibitors, we show participation of Toll-like receptor 2 and 4, and interestingly, that protein kinase C (PKC) and phosphatidylcholine-specific phospholipase C (PC-PLC), but not tyrosine kinases or phosphatidylinositol-specific phospholipase C (PI-PLC) are key players in this dual PMN response. Our findings indicate the importance of prolonged PMN survival in response to bacteria, where general signaling pathways ensure complete exploitation of PMN anti-microbial capacity.
Expression Signatures of Metastatic Capacity in a Genetic Mouse Model of Lung Adenocarcinoma

Background Non-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize. The biologic basis for NSCLC metastasis is not well understood. Methodology/Principal Findings Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-rasG12D and p53R172H. We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature. Conclusions/Significance These findings provide evidence that K-rasG12D; p53R172H mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasis and its prevention by novel agents.
Auditory segmentation based on event detection

Acoustic signals from different sources in a natural environment form an auditory scene. Auditory scene analysis (ASA) is the process in which the auditory system segregates an auditory scene into streams corresponding to different sources. Segmentation is an important stage of ASA where an auditory scene is decomposed into segments, each of which contains signal mainly from one source. We propose a system for auditory segmentation based on analyzing onsets and offsets of auditory events. Our system first detects onsets and offsets, and then generates segments by matching corresponding onsets and offsets. This is achieved through a multiscale approach based on scale-space theory. Systematic evaluation shows that much target speech, including unvoiced speech, is correctly segmented, and target speech and interference are well separated into different segments.
Estimating the Rate of Irreversibility in Protein Evolution

Whether or not evolutionary change is inherently irreversible remains a controversial topic. Some examples of evolutionary irreversibility are known; however, this question has not been comprehensively addressed at the molecular level. Here, we use data from 221 human genes with known pathogenic mutations to estimate the rate of irreversibility in protein evolution. For these genes, we reconstruct ancestral amino acid sequences along the mammalian phylogeny and identify ancestral amino acid states that match known pathogenic mutations. Such cases represent inherent evolutionary irreversibility because, at the present moment, reversals to these ancestral amino acid states are impossible for the human lineage. We estimate that approximately 10% of all amino acid substitutions along the mammalian phylogeny are irreversible, such that a return to the ancestral amino acid state would lead to a pathogenic phenotype. For a subset of 51 genes with high rates of irreversibility, as much as 40% of all amino acid evolution was estimated to be irreversible. Because pathogenic phenotypes do not resemble ancestral phenotypes, the molecular nature of the high rate of irreversibility in proteins is best explained by evolution with a high prevalence of compensatory, epistatic interactions between amino acid sites. Under such mode of protein evolution, once an amino acid substitution is fixed, the probability of its reversal declines as the protein sequence accumulates changes that affect the phenotypic manifestation of the ancestral state. The prevalence of epistasis in evolution indicates that the observed high rate of irreversibility in protein evolution is an inherent property of protein structure and function.
Alternative correction equations in the Jacobi-Davidson method

The correction equation in the Jacobi-Davidson method is effective in a subspace orthogonal to the current eigenvector approximation, whereas for the continuation of the process only vectors orthogonal to the search subspace are of importance. Such a vector is obtained by orthogonalizing the (approximate) solution of the correction equation against the search subspace. As an alternative, a variant of the correction equation can be formulated that is restricted to the subspace orthogonal to the current search subspace. In this paper, we discuss the effectiveness of this variant. Our investigation is also motivated by the fact that the restricted correction equation can be used for avoiding stagnation in case of defective eigenvalues. Moreover, this equation plays a key role in the inexact TRQ method [18].
Creating Directed Double-strand Breaks with the Ref Protein

The bacteriophage P1-encoded Ref protein enhances RecA-dependent recombination in vivo by an unknown mechanism. We demonstrate that Ref is a new type of enzyme; that is, a RecA-dependent nuclease. Ref binds to ss- and dsDNA but does not cleave any DNA substrate until RecA protein and ATP are added to form RecA nucleoprotein filaments. Ref cleaves only where RecA protein is bound. RecA functions as a co-nuclease in the Ref/RecA system. Ref nuclease activity can be limited to the targeted strands of short RecA-containing D-loops. The result is a uniquely programmable endonuclease activity, producing targeted double-strand breaks at any chosen DNA sequence in an oligonucleotide-directed fashion. We present evidence indicating that cleavage occurs in the RecA filament groove. The structure of the Ref protein has been determined to 1.4 Å resolution. The core structure, consisting of residues 77–186, consists of a central 2-stranded β-hairpin that is sandwiched between several α-helical and extended loop elements. The N-terminal 76 amino acid residues are disordered; this flexible region is required for optimal activity. The overall structure of Ref, including several putative active site histidine residues, defines a new subclass of HNH-family nucleases. We propose that enhancement of recombination by Ref reflects the introduction of directed, recombinogenic double-strand breaks.
Effects of energy and protein nutritionin the dam on embryonic development

This review highlights the importance of energy and protein nutrition of the dam on embryo production and embryo development. Fertility is reduced by greater negative energy balance post-partum as manifest by reductions in fertility and embryo quality associated with lower body condition score (BCS) but particularly with greater postpartum loss of BCS. In addition, excessive energy intake, particularly from high carbohydrate diets can reduce fertilization and embryo quality in some but not all circumstances. High protein diets have been found to reduce embryo quality by day 7 after breeding, possibly due to greater blood urea nitrogen, however this negative effect is not observed in all studies. Sufficient circulating concentrations of amino acids, particularly rate-limiting amino acids such as methionine and lysine are critical for optimal milk production. The rate-limiting amino acids may also impact embryonic development, perhaps through improved amino acid profiles in the uterine lumen. Methionine may also have direct epigenetic effects in the embryo by methylation of DNA. Future studies are needed to replicate previously observed positive and negative effects of energy, excess protein, and amino acid supplementation in order to provide further insight into how embryonic development can be rationally manipulated using nutritional strategies.
Effect of Vermicompost on the Growth and Yield of Lettuce Plant (Lactuca sativa L. var. crispa)

This research was done to find out the effect of increasing vermicompost application on yield of lettuce (Lactuca sativa L. var. crispa) plant. For this purpose Lactuca sativa L. var. crispa cv. Bellafiesta lettuce kind and Riverm Company vermicompost were used in this research. Four vermicompost doses (0 kg/ha, 4000 kg/ha, 8000 kg/ha and 12000 kg/ha) were applied to lettuce plant. According to the results, important increases of fresh weight, plant size, number of leaf, length and width of leaf for each plant and dry matter yield of plants were determined with increasing vermicompost applications. But the effects of Vermicopmost applications on some macro element (N, P, K, Ca and Mg) contents of plant were not found significant statistically. Short Research Article Adiloğlu et al.; IJPSS, 21(1): 1-5, 2018; Article no.IJPSS. 37574 2
Dynamics of Ventricular Ejection

Left ventricular ejection in open-chest, anesthetized dogs begins with an abrupt acceleration of blood into the ascending aorta, reaching an average maximum of 4,650 cm. /sec. /sec. Velocity reaches a sharp peak of 88 cm. /sec. (average) within the first one-third to one-half of the ejection period. Deceleration is more gradual and continues to the closure of the aortic valve. The general pattern of the time-course recording is that of a triangle with its peak skewed into early systole and separated from a flat diastolic period of zero flow by a deep notch of backflow attending closure of the aortic valve. Ventricular pressure exceeds aortic pressure only during the brief period between the opening of the valve and peak systolic velocity, a period of approximately 45 per cent of the ejection period. This “positive” (headward) gradient represents the acceleration transient and explains the sharp rise in flow to a maximum in early systole. During the deceleration (terminal) phase of ventricular ejection, the pressure gradient is against the direction of flow. This reversal in pressure gradient brings about a gradual deceleration of flow to zero. These findings are considered experimental proof that the major phenomenon relating pressure and flow in the ascending aorta is that governing mass acceleration.
Can Risk Aversion Explain Schooling Attainments? Evidence from Italy

Using unique Italian panel data, in which individual differences in behavior toward risk are measured from answers to a lottery question, we investigate if (and to what extent) risk aversion can explain differences in schooling attainments. We formulate the schooling decision process as a reduced-form dynamic discrete choice. The model is estimated with a degree of flexibility virtually compatible with semi- parametric likelihood techniques. We analyze how grade transition from one level to the next varies with preference heterogeneity (risk aversion), parental human capital, socioeconomic variables and persistent unobserved (to the econometrician) heterogeneity. We present evidence that schooling attainments decrease with risk aversion, but despite a statistically significant effect, differences in attitudes toward risk account for a modest portion of the probability of entering higher education. Differences in ability(ies) and in parental human capital are much more important. in the most general version of the model, the likelihood function is the joint probability of schooling attainments, and post-schooling wealth and risk aversion.
Cognitive and Motor Loops of the Human Cerebro-cerebellar System

We applied fMRI and diffusion-weighted MRI to study the segregation of cognitive and motor functions in the human cerebro-cerebellar system. Our fMRI results show that a load increase in a nonverbal auditory working memory task is associated with enhanced brain activity in the parietal, dorsal premotor, and lateral prefrontal cortices and in lobules VII–VIII of the posterior cerebellum, whereas a sensory-motor control task activated the motor/somatosensory, medial prefrontal, and posterior cingulate cortices and lobules V/VI of the anterior cerebellum. The load-dependent activity in the crus I/II had a specific relationship with cognitive performance: This activity correlated negatively with load-dependent increase in RTs. This correlation between brain activity and RTs was not observed in the sensory-motor task in the activated cerebellar regions. Furthermore, probabilistic tractography analysis of the diffusion-weighted MRI data suggests that the tracts between the cerebral and the cerebellar areas exhibiting cognitive load-dependent and sensory-motor activity are mainly projected via separated pontine (feed-forward tracts) and thalamic (feedback tracts) nuclei. The tractography results also indicate that the crus I/II in the posterior cerebellum is linked with the lateral prefrontal areas activated by cognitive load increase, whereas the anterior cerebellar lobe is not. The current results support the view that cognitive and motor functions are segregated in the cerebellum. On the basis of these results and theories of the function of the cerebellum, we suggest that the posterior cerebellar activity during a demanding cognitive task is involved with optimization of the response speed.
Financial Pressure and Balance Sheet Adjustment by Firms

This paper examines the financial policies and balance sheet adjustment of companies. Using a large panel of quoted UK firms, we estimate models for dividends, new equity issuance and investment, relating them to debt adjustment. The results suggest that while dividends are sticky in the short run, they are an important means of balance sheet adjustment in the long run. Other evidence supports the idea that companies actively target their balance sheet by variation in dividends, new equity issues and investment. There is evidence for financial pressure effects of debt-servicing costs on investment and dividends but not new equity issuance.