Miracle-dz/UniFAR-FTUs huggingface dataset:
Wriggled Lamellar Solutions and Their Stability in the Diblock Copolymer Problem

In a diblock copolymer system the free energy field depends nonlocally on the monomer density field. In addition there are two positive parameters in the constitutive relation. One of them is small, with respect to which we do singular perturbation analysis. The second one is of order 1, with respect to which we do bifurcation analysis. Combining the two techniques we find wriggled lamellar solutions of the Euler--Lagrange equation of the total free energy under a hypothesis regarding the simplicity of the principal eigenvalue, which is generically satisfied. The wriggled lamellar solutions bifurcate from the perfect lamellar solutions. The stability of the wriggled lamellar solutions is reduced to a relatively simple finite dimensional problem, which may be solved accurately by a numerical method. Our tests show that most of them are stable. The existence of such stable wriggled lamellar solutions explains why in reality the lamellar phase is fragile and often exists in distorted forms.
Innate Immune Recognition of Invasive Bacteria Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice

Background—Infectious diseases have emerged as potential risk factors for cardiovascular disease (CVD). Epidemiological studies support a connection between periodontal disease, a chronic inflammatory disease of the supporting tissues of the teeth, and CVD. Methods and Results—To directly test the connection between periodontal disease and atherosclerosis, apoE−/− mice were orally challenged with the periodontal disease pathogen Porphyromonas gingivalis or an invasion-impaired P gingivalis fimbriae-deficient mutant (FimA−). Both wild-type P gingivalis and the FimA− mutant were detected in blood and aortic arch tissue of apoE−/− mice by PCR after challenge. ApoE−/− mice challenged with wild-type P gingivalis presented with increased atherosclerotic plaque and expressed the innate immune response markers Toll-like receptor (TLR)-2 and TLR-4 in aortic tissue. Despite detection of the FimA− mutant in the blood and in aortic arch tissue, apoE−/− mice challenged with the FimA− mutant did not present with periodontal disease, upregulation of TLRs, or accelerated atherosclerosis. Furthermore, we demonstrate that immunization to control P gingivalis–elicited periodontal disease concomitantly prevents P gingivalis–accelerated atherosclerosis. Conclusions—We conclude that invasive P gingivalis accelerates atherosclerosis.
An age of transition: ceramic innovations and social changes in the Mirabello gulf during the Middle Minoan period

This paper offers new insights into the social changes that took place in the Mirabello Gulf in eastern Crete during the Middle Minoan (MM) period (ca. 1900-1700 BC). The most significant change appears to have been the transformation of society from localised chiefdoms to decentralised states for the first time in Greek prehistory, and the archaeological finds from the Mirabello area demonstrate that change. Specifically, the newly examined ceramic material from the site of Mochlos furthers our understanding of this transformation, and is discussed here alongside two other factors that also contributed to the development of states: the population increase and the introduction of the potters’ wheel. The production, distribution and consumption of ceramic material in the Mirabello Gulf demonstrates cultural, economic, and social bonds between sites within the region. The introduction of new standardised ceramic shapes, either local or imported, depicts the common production and consumption habits of a unified socio-cultural regional landscape. Considering the new evidence from the perspective of transitions, this paper discusses the transformation in production technology, as well as in decorative schemata in drinking and storage wares like cups and jars from Mochlos as they relate to other changes taking place in the Mirabello region during this period. It also gives a glimpse of how this transition affected the cultural and economic life of the settlement, such as the intensification of local pottery production, and its relation to the centre’s trends, and offers insight about how a primary material can enrich the present model of a new state level society.
A Fast Multivariate Feature-Selection/Classification Approach for Prediction of Therapy Response in Multiple Sclerosis

Recombinant interferon beta (IFNp) is one of the most commonly prescribed treatments for multiple sclerosis; however, the treatment results in partial success producing no benefit in almost half of the patients. We address the problem of identifying minimal and robust sets of molecular biomarkers that are able to present predictive models of response to treatment in multiple sclerosis patients. To achieve this, we utilize a multivariate feature selection and classification framework; OSeMA (orthogonal search model analysis) integrates fast orthogonal search algorithm for feature selection and discriminant analysis for classification. Feature-selection and classification performance of OSeMA are evaluated through comparative studies with two wrapper-approach feature-selection/classification systems. It is demonstrated that the feature-selection of OSeMA significantly reduces the computational time of exhaustive searches while identifying complex gene-gene relationships. Utilizing OSeMA, we are able to construct classification models that are highly predictive of therapy response in MS patients, based on their gene expression data acquired prior to initiation of IFNp treatment
A prospective, randomised trial of different matching procedures for structured mentoring programmes in medical education

Abstract Background: Spontaneous formation of mentoring relationships can be seen as the gold standard in mentoring. Unfortunately, it happens very infrequently. The purpose of structured mentoring programmes is to facilitate the formation of mentoring relationships. This remains a challenging task, especially for large institutions. Aims: We set out to investigate and compare three methods of matchmaking in the setting of our structured mentoring programme. In a prospective, randomised trial we compared personal matching (PM) by an experienced expert to two different electronic data processing (EDP)-supported matching procedures: “online algorithm” (OA) versus “online search” (OS). Methods: PM was performed after structured interviews of prospective protégés by one founder of our mentoring programme. The OA provides students with a choice of 10 potential mentors based on comparison of online profiles. OS lets students filter and search through all available mentor profiles. One hundred and ninty medical students were randomised into the three groups. One year later, we evaluated the endpoints 1. “establishment of a mentoring relationship” and 2. “satisfaction with the mentoring relationship”. Satisfaction with the mentoring relationship was assessed using Munich-Evaluation-of-Mentoring-Questionnaire (MEMeQ). Results: One hundred sixty-five out of the 190 study participants found a mentor. With regards to endpoint one we found an advantage of PM compared to both EDP-supported matching procedures. There was no significant difference between OA and OS. Concerning endpoint two the differences between the investigated matching procedures were not significant. Conclusion: PM is superior as to the number of mentoring relationships formed per participating student compared to EDP-supported methods. In our data, there was no significant difference in the level of satisfaction. Considering the high investments associated with PM of mentors and protégés, EDP-supported matching procedures seem a viable compromise between effectiveness and efficiency especially for large-scale structured mentoring programmes in medical education.
MicroRNAs Regulate Human Brain Endothelial Cell-Barrier Function in Inflammation: Implications for Multiple Sclerosis

Blood–brain barrier (BBB) dysfunction is a major hallmark of many neurological diseases, including multiple sclerosis (MS). Using a genomics approach, we defined a microRNA signature that is diminished at the BBB of MS patients. In particular, miR-125a-5p is a key regulator of brain endothelial tightness and immune cell efflux. Our findings suggest that repair of a disturbed BBB through microRNAs may represent a novel avenue for effective treatment of MS.
Generalization Bounds for Domain Adaptation

In this paper, we provide a new framework to study the generalization bound of the learning process for domain adaptation. We consider two kinds of representative domain adaptation settings: one is domain adaptation with multiple sources and the other is domain adaptation combining source and target data. In particular, we use the integral probability metric to measure the difference between two domains. Then, we develop the specific Hoeffding-type deviation inequality and symmetrization inequality for either kind of domain adaptation to achieve the corresponding generalization bound based on the uniform entropy number. By using the resultant generalization bound, we analyze the asymptotic convergence and the rate of convergence of the learning process for domain adaptation. Meanwhile, we discuss the factors that affect the asymptotic behavior of the learning process. The numerical experiments support our results.
Modeling the Autonomic and Metabolic Effects of Obstructive Sleep Apnea: A Simulation Study

Long-term exposure to intermittent hypoxia and sleep fragmentation introduced by recurring obstructive sleep apnea (OSA) has been linked to subsequent cardiovascular disease and Type 2 diabetes. The underlying mechanisms remain unclear, but impairment of the normal interactions among the systems that regulate autonomic and metabolic function is likely involved. We have extended an existing integrative model of respiratory, cardiovascular, and sleep–wake state control, to incorporate a sub-model of glucose–insulin–fatty acid regulation. This computational model is capable of simulating the complex dynamics of cardiorespiratory control, chemoreflex and state-related control of breath-to-breath ventilation, state-related and chemoreflex control of upper airway potency, respiratory and circulatory mechanics, as well as the metabolic control of glucose–insulin dynamics and its interactions with the autonomic control. The interactions between autonomic and metabolic control include the circadian regulation of epinephrine secretion, epinephrine regulation on dynamic fluctuations in glucose and free-fatty acid in plasma, metabolic coupling among tissues and organs provided by insulin and epinephrine, as well as the effect of insulin on peripheral vascular sympathetic activity. These model simulations provide insight into the relative importance of the various mechanisms that determine the acute and chronic physiological effects of sleep-disordered breathing. The model can also be used to investigate the effects of a variety of interventions, such as different glucose clamps, the intravenous glucose tolerance test, and the application of continuous positive airway pressure on OSA subjects. As such, this model provides the foundation on which future efforts to simulate disease progression and the long-term effects of pharmacological intervention can be based.
Methodological and Ethical Issues in Conducting Social Psychology Research via the Internet.

When I set out to recruit highly educated people with specialized training in decision making, I anticipated that it would be a difficult project. The reason I wanted to study this group was that I had been obtaining some very startling results in decision-making experiments with undergraduates (Birnbaum & Navarrete, 1998; Birnbaum, Patton, & Lott, 1999). Undergraduates were systematically violating stochastic dominance, a principle that was considered both rational and descriptive, according to cumulative prospect theory and rank dependent expected utility theory, the most widely accepted theories of decision making at the time (Luce & Fishburn, 1991; Quiggin, 1993; Tversky & Kahneman, 1992). These theories were recognized in the 2002 Nobel Prize in Economics shared by Daniel Kahneman, so these systematic violations required substantial changes in thinking about decision making. The results were not totally unexpected, for they had been predicted by my configural weight models of decision making (Birnbaum, 1997). Nevertheless, I anticipated the challenge that my results might apply only to people who lack the education required to understand the task. I wanted to see if the results I obtained with undergraduates would hold up with people highly trained in decision making, who do not want to be caught behaving badly with respect to rational principles. From my previous experiences in research with special populations, I was aware of the difficulties of such research. In previous work, my students and I had printed and mailed materials to targeted participants C H A P T E R
The homeopathic approach to symptom control in the cancer patient: a prospective observational study

The aims of this study were to describe a population of patients with cancer referred for complementary therapies to an NHS homeopathic hospital, and to explore the homeopathic approach to symptom control and its impact on mood disturbance and quality of life. One hundred consecutive patients attending a designated research cancer clinic were seen for a consultation, lasting up to 60 min, and prescription of a homeopathic remedy. A maximum of three symptoms were identified and rated by the patient as a problem, using a numerical selfrating scale. The effect these symptoms have on daily life and overall sense of well being were recorded using similar scales. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the European Organization for Research and Treatment in Cancer - Quality of Life Questionnaire - Core 30 (EORTC QLQ-30) at the initial consultation and at four to six consultations later. After this time, the patients completed a final assessment questionnaire asking about satisfaction with the homeopathic approach, how helpful they had found the approach for the targeted symptoms and what factors they felt may have contributed to the changes perceived. One hundred patients were entered into the study. Thirty-nine patients had metastatic disease. Nine patients were refusing conventional cancer treatments. The most common symptoms were pain, fatigue and hot flushes. Symptom scores for fatigue and hot flushes improved significantly over the study period but not for pain scores. Side effects included a transient worsening of symptoms in a few cases, which settled on stopping the remedy. Fiftytwo patients completed the study, and in those patients satisfaction was high, and 75% (n=38) rated the approach as helpful or very helpful for their symptoms. Results suggest that further research is warranted to explore the management of hot flushes in women with breast cancer and fatigue in the cancer diagnosis.
A DNA Helicase Required for Maintenance of the Functional Mitochondrial Genome in Saccharomyces cerevisiae

ABSTRACT A novel DNA helicase, a homolog of several prokaryotic helicases, including Escherichia coli Rep and UvrD proteins, is encoded by the Saccharomyces cerevisiae nuclear genome open reading frame YOL095c on the chromosome XV. Our data demonstrate that the helicase is localized in the yeast mitochondria and is loosely associated with the mitochondrial inner membrane during biochemical fractionation. The sequence of the C-terminal end of the 80-kDa helicase protein is similar to a typical N-terminal mitochondrial targeting signal; deletions and point mutations in this region abolish transport of the protein into mitochondria. The C-terminal signal sequence of the helicase targets a heterologous carrier protein into mitochondria in vivo. The purified recombinant protein can unwind duplex DNA molecules in an ATP-dependent manner. The helicase is required for the maintenance of the functional ([rho+]) mitochondrial genome on both fermentable and nonfermentable carbon sources. However, the helicase is not essential for the maintenance of several defective ([rho −]) mitochondrial genomes. We also demonstrate that the helicase is not required for transcription in mitochondria.
Characterization of Diuron N-Demethylation by Mammalian Hepatic Microsomes and cDNA-Expressed Human Cytochrome P450 Enzymes

Diuron, a widely used herbicide and antifouling biocide, has been shown to persist in the environment and contaminate drinking water. It has been characterized as a “known/likely” human carcinogen. Whereas its environmental transformation and toxicity have been extensively examined, its metabolic characteristics in mammalian livers have not been reported. This study was designed to investigate diuron biotransformation and disposition because metabolic routes, metabolizing enzymes, interactions, interspecies differences, and interindividual variability are important for risk assessment purposes. The only metabolic pathway detected by liquid chromatography/mass spectometry in human liver homogenates and seven types of mammalian liver microsomes including human was demethylation at the terminal nitrogen atom. No other phase I or phase II metabolites were observed. The rank order of N-demethyldiuron formation in liver microsomes based on intrinsic clearance (Vmax/Km) was dog > monkey > rabbit > mouse > human > minipig > rat. All tested recombinant human cytochrome P450s (P450s) catalyzed diuron N-demethylation and the highest activities were possessed by CYP1A1, CYP1A2, CYP2C19, and CYP2D6. Relative contributions of human CYP1A2, CYP2C19, and CYP3A4 to hepatic diuron N-demethylation, based on average abundances of P450 enzymes in human liver microsomes, were approximately 60, 14, and 13%, respectively. Diuron inhibited relatively potently only CYP1A1/2 (IC50 4 μM). With human-derived and quantitative chemical-specific data, the uncertainty factors for animal to human differences and for human variability in toxicokinetics were within the range of the toxicokinetics default uncertainty/safety factors for chemical risk assessment.
Staphylococcus aureus small colony variants in prosthetic joint infection.

BACKGROUND Small colony variants of Staphylococcus aureus tend to persist despite antimicrobial therapy, especially when involved in implant-associated infections. METHODS We analyzed 5 cases of hip prosthesis-associated infections due to small colony variants, including their course prior to identification of the pathogen. Biopsy investigations included microbiological examination and, in 1 case, transmission electron microscopy to detect intracellular bacteria in nonprofessional phagocytes. A treatment concept was elaborated on the basis of a published algorithm and patients were managed accordingly. RESULTS The patients' mean age was 62.2 years. All patients experienced treatment failures prior to isolation of small colony variants, despite as many as 3 surgical revisions and up to 22 months of antibiotics. Transmission electron microscopy performed on biopsy specimens from periprosthetic tissue revealed intracellular cocci in fibroblasts. All prostheses were removed without implanting a spacer, and antimicrobial agents were administered for 5.5-7 weeks. Reimplantation of the prosthesis was performed for 4 patients. Follow-ups were uneventful in all 5 cases. CONCLUSIONS In the case of a poor response to adequate antimicrobial and surgical treatment in implant-associated staphylococcal infections, small colony variants should be considered and actively sought. In our case series, a 2-stage exchange without implantation of a spacer combined with antimicrobial therapy for an implant-free interval of 6-8 weeks was associated with successful outcome, with a mean follow-up of 24 months.
Quality of life in hypertensive patients and concurrent validity of Minichal-Brazil.

BACKGROUND Health-Related Quality of Life Questionnaires (HRQOL) are humanistic outcome measure instruments both in clinical and in pharmacoeconomic studies. However, they should have their psychometric parameters evaluated so as to reflect the individual subjective assessment of quality of life. OBJECTIVES To describe the quality of life profile of hypertensive patients and to assess the concurrent validity of the Minichal-Brazil instrument by comparing it to the generic World Health Organization's (WHO) assessment instrument known as WHOQOL-Bref. METHODS A total of 191 adult patients (72.8% females) with hypertension were interviewed. Approximately one third of these patients had their hypertension controlled. The mean HRQOL as measured by the total Minichal score was 69.7 (SD = 19.2; 95%CI from 66.9 to 72.4); the "mental status" domain and "somatic manifestations" domain scores were 69.1 (95%CI from 66.1 to 72.2), and 69.9 (95%CI from 66.5 to 73.2), respectively. The means for the WHOQOL-Bref instrument were: in the "physical" domain = 61.5 (95%CI from 59.0 to 64.1); in the "psychological" domain = 65.7 (95%CI from 63.2 to 68.2); in the "social" domain = 72.3 (95%CI from 70.0 to 74.5); and in the "environment" domain = 59.7 (95%CI from 57.7 to 61.7). RESULTS Minichal significantly correlated (p<0.001) with WHOQOL-Bref as regards all its domains, except for the "environment" domain, which did not correlate with the "somatic manifestations" domain. CONCLUSION Minichal-Brazil proved to be a useful tool in the assessment of HRQOL in hypertensive patients.
Encapsulation Methods for Transport of Ethernet over MPLS Networks

An Ethernet Pseudowire (PW) allows Ethernet/802.3 Protocol Data Units (PDUs) to be carried over a Packet Switched Network (PSN) such as IP or MPLS. This ability enables service providers to leverage an existing PSN to offer ethernet services. This document addresses the encapsulation of Ethernet/802.3 PDUs within a pseudowire, and issues associated with the point-to-point emulation of ethernet within a PW.
Accuracy of child morbidity data in demographic and health surveys.

BACKGROUND The Demographic and Health Surveys (DHSs) have been used throughout the developing world for the last 20 years to provide data on the distribution of disease in order to inform planning. Data on child illness and death are reported by mothers and are susceptible to error. METHODS We conducted an in-depth study of the Iranian DHS carried out in 2000-2001 and reviewed 110 DHS carried out around the world to check for bias by assessing the social gradient in reported child morbidity and mortality. RESULTS We found that the reported under-5 child morbidity and mortality rates for the 28 Iranian provinces were inversely correlated (r = -0.592, P < 0.001) and that the adjusted social gradient of child morbidity implied increased illness in those who had literate vs illiterate mothers (OR = 1.26, 95% CI 1.20-1.32) compared with a decrease in mortality with increased literacy (OR = 0.52, 95% CI 0.46-0.59). Many of the other DHSs also show increased rates of reported child diarrhoea in households with higher levels of maternal education, access to piped water and urban (vs rural) dwellings, the reverse of what is found with mortality rates. CONCLUSIONS This suggests that there may be significant recall and reporting bias in under-5 childhood morbidity in DHSs. Caution should be used in the interpretation and use of data from DHSs and the survey methods should be reviewed.