Miracle-dz/UniFAR-FTUs huggingface dataset:
Amyloid-β and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus.

BACKGROUND Amyloid-β (Aβ1 - 42), total tau (T-tau), and phosphorylated tau (P-tau181) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble Aβ decreases with increasing age and advanced Aβ pathology as seen similarly in CSF. OBJECTIVE To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF). METHODS Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF. RESULTS ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. Aβ1 - 42 and P-tau181 remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while Aβ1 - 42 levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau181 (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF Aβ1 - 42 levels than those six without amyloid pathology. CONCLUSIONS This is the first study to report ISF Aβ and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease.
Learning under signal-to-noise ratio uncertainty

Abstract The paper presents an alternative real time adaptive learning algorithm in the presence of signal-to-noise ratio uncertainty. The main innovation of this algorithm is that it uses a gain which is determined within the model: it continuously depends on the extent of misevaluation of parameters embedded in the forecast error. We show that in the presence of signal-to-noise ratio misevaluation, the usage of the proposed learning algorithm is a significant improvement on the Kalman Filter learning algorithm. In a full information case, the Kalman Filter learning algorithm is still the optimal tool.
Not Dutch Disease, it's China Syndrome

This paper empirically investigates how the Canadian economy has evolved following the rise in commodity prices and appreciation of the Canadian dollar that began in 2003. The adjustment in the manufacturing industry has garnered the greatest attention because it has borne the brunt of job losses. However, the adjustment of the manufacturing industry has not been straightforward. Rather, a complex reallocation has been taking place within manufacturing that has been predominantly due to the integration of emerging nations into the global economy. The increased commodity prices and falling manufactured prices caused by this integration have affected durable and non-durable manufacturing industries differently. Non-durable manufacturers have tended to see their competitiveness eroded and their output has tended to fall. Durable manufacturers, on the other hand, have increased output in response to the resource boom and increased demand in general. The result has been stable manufacturing output overall, accompanied by a re-orientation of manufacturing output away from non-durables and toward durables. The appreciated dollar and higher commodity prices have also led to a more widespread industrial reallocation in Canada. The higher commodity prices have started a resource boom, particularly in Alberta. The boom has led to rising resource industry employment, while manufacturing employment declined, and to rising service-sector employment. It has contributed to inter-provincial migration, and has greatly increased the purchasing power of Canadian incomes as terms of trade have improved.
A stepwise validation of a wearable system for estimating energy expenditure in field-based research

Regular physical activity (PA) is an important contributor to a healthy lifestyle. Currently, standard sensor-based methods to assess PA in field-based research rely on a single accelerometer mounted near the body's center of mass. This paper introduces a wearable system that estimates energy expenditure (EE) based on seven recognized activity types. The system was developed with data from 32 healthy subjects and consists of a chest mounted heart rate belt and two accelerometers attached to a thigh and dominant upper arm. The system was validated with 12 other subjects under restricted lab conditions and simulated free-living conditions against indirect calorimetry, as well as in subjects’ habitual environments for 2 weeks against the doubly labeled water method. Our stepwise validation methodology gradually trades reference information from the lab against realistic data from the field. The average accuracy for EE estimation was 88% for restricted lab conditions, 55% for simulated free-living conditions and 87% and 91% for the estimation of average daily EE over the period of 1 and 2 weeks.
The incidence of visual perceptual impairment in patients with severe traumatic brain injury

Primary objectives: To investigate the incidence of visual perceptual impairments in a sample of patients with traumatic brain injury (TBI) using the Occupational Therapy Adult Perceptual Screening Test (OT-APST), compare incidence rates to a normative sample and explore the relationship between the presence of visual perceptual impairment and the severity of cognitive and functional impairment following TBI. Research design: Cohort study using a convenience sample of patients with TBI and a normative sample. Methods and procedures: Thirty-one patients with severe TBI and 195 healthy people were compared on the OT-APST and measures of cognition and function. Main outcomes and results: The most common impairments in the TBI sample were unilateral neglect (45.2%) and impairments of body scheme (25.8%) and constructional skills (25.8%). Significantly higher incidences of agnosia, apraxia, unilateral neglect and impairments in body scheme and constructional skills were found in the TBI sample compared to the normative sample. No significant relationship was found between the presence of visual perceptual impairments and the level of cognitive and functional impairment after TBI. Conclusions: Visual perceptual changes are evident in patients with severe TBI when compared to a normative sample. Routine use of a screening tool such as the OT-APST may help identify visual perceptual impairments in these patients and the need for more detailed assessment.
Homology of lysosomal enzymes and related proteins: Prediction of posttranslational modification sites including phosphorylation of mannose and potential epitopic and substrate binding sites in the α‐ and β‐subunits of hexosaminidases, α‐glucosidase, and rabbit and human isomaltase

Recently developed computer programs, including secondary structure and epitopic site predictions, have been used to align lysosomal proteins for maximum homology, based on conservative interchanges, and the aligned sequences have been searched for potential sites for posttranslational modification, glycosyaltion, and binding and catalysis of substrate. The homology and prediction of the posttranslational modification of the α‐ and β‐subunits of hexosaminidase is in good agreement with previous observations, and an explanation of the differing substrate specificities of the two subunits is advanced. We shows that the striking homology between α‐glucosidase and isomaltase is reflected in that apparent conversation of the active site in both enzymes. Nonhomologous regions have been examined in detail in a search for binding sited for glycogen and maltose, and two such sites have been tentatively identified. A highly redundant consensus sequence for the Phosphorylation of mannose in lysosomal proteins, YXX(Y, W, or F), is suggested.
The relevance of environmental Kuznets curve (EKC) in a framework of broad-based environmental degradation and modified measure of growth – a pooled data analysis

The economic growth and natural environment trajectory has been expressed and interpreted in myriad ways. One hypothesis that is comprehensively used to empirically model the economic growth and environmental degradation relationship is the widely known environmental Kuznets curve (EKC hypothesis). However, the initial EKC formulation has stimulated a large debate around the need for alternative representations of the relationship between economic growth and environment. In this paper, we have introduced some modifications to the standard EKC. In particular, we have changed the dependent variable substituting a pure environmental stress as in the standard EKC with a wider assessment of environmental pressure defined by the environmental degradation index (EDI). Of the two models that we have considered in our study, we have taken gross domestic product (GDP) as the explanatory variable in one model and development balance index (DBI) in another model. The results show an N-shaped pattern for most of the countries considered.
Mammalian protein RAP46: an interaction partner and modulator of 70 kDa heat shock proteins

A ubiquitously expressed nuclear receptor‐associating protein of ∼46 kDa (RAP46) was identified recently. Interaction experiments with in vitro‐translated proteins and proteins contained in cell extracts revealed that a great variety of cellular regulators associate with RAP46. However, in direct interaction tests by the far‐Western technique, only 70 kDa proteins showed up and were identified as members of the 70 kDa heat shock protein (hsp70) family. Interaction is specific since not all members of the hsp70 family bind to RAP46; interaction occurs through their ATP‐binding domain. RAP46 forms complexes with hsp70 in mammalian cells and interacts with hsp70 in the yeast two‐hybrid system. Consistent with the fact that hsp70 can bind a multitude of proteins, we identified heteromeric complexes of RAP46–hsp70 with some selected proteins, most notably c‐Jun. Complex formation is increased significantly by pre‐treatment with alkaline phosphatase, thus suggesting modulation of interactions by protein phosphorylation. We observed that RAP46 interferes with efficient refolding of thermally denatured luciferase. Moreover, ATP‐dependent binding of misfolded proteins to hsp70 was greatly inhibited by RAP46. These data suggest that RAP46 functions as a regulator of hsp70 in higher eukaryotes.
2 . HPV vaccines — Early studies in animal models

First evidence that transmissible agents are involved in the development of cervical cancer dates back to the mid 19th century and is based on investigations of the Italian physi‐ cian Demonico Rigoni-Stern who recognized that cancer of the womb is found most frequently among women in their fourth and fifth decade and that factors such as age of sexual debut and promiscuity attribute to the risk of acquiring this type of cancer [1]. However, only with the advent of molecular biology in the early 1970s, and after ruling out Herpes Simplex Viruses, a link was established between cervical cancer and infec‐ tions by certain types of human papillomaviruses (HPV). After isolation of HPV 6 from a condyloma and subsequently of HPV 11 from a laryngeal papilloma the genomic DNA of these two types allowed tracing of other, novel HPVs in biopsies of cervical tumors [2, 3]. The detection of HPV DNA in tumor cells, including the HeLa cell line, was initially met with much doubt and disbelief in the scientific community but could subsequently be confirmed. In fact, the initial observation by Dürst et al. [4] that 11 out of 18 cervical cancer biopsies from German patients were positive for HPV 16 is consistent with today’s knowledge of HPV 16 being present in more than 50% of malignant tumors from the cervix. In the following years the findings by Harald zur Hausen and his colleagues were confirmed by numerous laboratories worldwide and a causative link between HPV infections and cervical cancer in humans was established due to the vast amount of epidemiological studies and an overwhelming body of data obtained in different in vivo and in vitro models. In 2008 Prof. Harald zur Hausen was awarded the Nobel Prize which recognizes his pioneering findings and fundamental role in HPV research.
Shock-bubble Interaction Near a Compliant Tissue-like Material

In this work, we present numerical simulation results for shock-induced bubble collapse dynamics near tissue-like compliant gelatin phase. We use a sharp-interface model for multiple materials to represent the ambient liquid (water), the non-condensable gas phase (air) and the gelatin phase. Employing multi-resolution techniques, we investigate the complex interface dynamics and compare the results with experimental data from literature. Our aim is to understand and quantify the mechanisms observed during extracorporeal shock-wave lithotripsy or sonoporation. Therefore, latestage dynamics of the bubble collapse and tissue penetration are presented.
Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population‐based study – the HUNT study

We studied the impact of genetic and traditional risk factors for type 2 diabetes in a large, population‐based study from Nord‐Trøndelag county in Norway (HUNT), in both cross‐sectional and prospective design. Material and methods. 65,905 individuals participated in the HUNT study. We studied a randomly selected group of 869 individuals with self‐reported diabetes or non‐fasting serum glucose ⩾11.1 mmol/L and 2,080 non‐diabetic control subjects with non‐fasting serum glucose <5.5 mmol/L. Four candidate polymorphisms in the three genes TCF7L2 (rs12255372 and rs7903146), PPARG (rs1801282), KCNJ11 (rs5219) and traditional risk factors were studied. Results. Risk alleles of the TCF7L2 gene showed increased risk of diabetes even when controlled for traditional diabetes risk factors (diabetes in family, waist circumference, physical activity, BMI, SBP and total and HDL‐cholesterol) in both a cross‐sectional and prospective setting (cross‐sectional: rs12255372 OR 1.61 (1.31–1.99), rs7903146 OR 1.48 (1.20–1.83) and prospective: rs12255372 OR 1.59 (1.22–2.07), rs7903146 OR 1.47 (1.11–1.93)). The risk alleles of TCF7L2 indicated impaired β‐cell function in patients and control subjects. The population attributable risks for diabetes with TCF7L2 risk alleles were 15 % and with diabetes in a first‐degree relative 31 %. Conclusion. The risk alleles of the TCF7L2 gene (rs12255372 and rs7903146) were strongly associated with type 2 diabetes, even after controlling for traditional risk factors in both a cross‐sectional and prospective setting. These risk alleles were associated with indices of reduced β‐cell function.
Increased olfactory sensitivity in euthymic patients with bipolar disorder with event-related episodes compared with patients with bipolar disorder without such episodes.

OBJECTIVE Some patients with bipolar disorder experience mood episodes following emotional life events, whereas others do not. There is evidence that orbitofrontal hypoactivity may be related to this, because the orbitofrontal cortex is involved in the regulation of emotional and behavioural responses to external events. The close anatomical and functional connection between the orbitofrontal cortex and olfactory processing suggests that patients with bipolar disorder and heightened emotional reactivity may exhibit altered olfactory function compared with patients with bipolar disorder who do not exhibit this sensitivity. METHODS In this pilot study, olfactory function was assessed in patients with bipolar disorder and a history of event-triggered episodes (n = 7) and in patients with bipolar disorder without such a history (n = 9) at the Department of Psychiatry and the Taste and Smell Clinic of the University of Dresden, Germany. Each patient's bipolar disorder was in remission at study entry, and they were on monotherapy with mood stabilizers. Assessment included olfactory event-related potentials (ERP) and psychophysical tests for odour threshold, odour identification and olfactory quality discrimination. RESULTS Odour thresholds were lower in patients with bipolar disorder and event-triggered episodes compared with the other patient group. In addition, patients with event-triggered episodes exhibited shorter N1 peak latencies of the olfactory ERP. CONCLUSIONS Our findings indicate disinhibition of orbitofrontal areas involved in the processing of emotional events in a subset of patients with bipolar illness.
Simple sequence repeat DNA markers in alfalfa and perennial and annual Medicago species.

Simple sequence repeat (SSR) or microsatellite DNA markers have been shown to function well in plant and mammalian species for genetic map construction and genotype identification. The objectives of the work reported here were to search GenBank for the presence of SSR-containing sequences from the genus Medicago, to assess the presence and frequency of SSR DNA in the alfalfa (Medicago sativa (L.) L. &L. ) genome, and to examine the function of selected markers in a spectrum of perennial and annual Medicago species. The screening of an alfalfa genomic DNA library and sequencing of clones putatively containing SSRs indicated approximately 19 000 (AT)n + (CT)n + (CA)n + (ATT)n SSRs in the tetraploid genome. Inheritance was consistent with Mendelian expectations at four selected SSR loci with different core motifs. Additionally, genotypes of a range of Medicago species, including 10 perennial subspecies of the M. sativa complex and other perennial and annual Medicago species, were analyzed at each of the loci to ascertain the presence, number, and size of SSR alleles at each locus in each genotype. These studies indicate that SSR markers can function in alfalfa for the construction of genetic maps and will also be useful in a range of Medicago species for purposes of assessing genetic relatedness and taxonomic relationships, and for genotype identification.
Fundamentals for a Theory of Policy Instruments

Scientific theories on the effects of various policy instruments are often formulated without accounting for the circumstances under which these instruments are applied. Also the implementation process is often neglected. Economic theory formulation often concentrates solely on the influence of the instrument‐as‐intended on the cost‐benefit relationship of various behavioural alternatives. Theories based on the joint influence of possible combinations of circumstances rather than the isolated influences of individual circumstances tend to become tremendously complex. Consequently, attempts to formulate such theories are few. Nevertheless, precisely that combined perspective offers invaluable insights when it comes to making choices concerning practical policy issues. This holds true regardless of whether the choice is part of a,more or less rational and conscious decision‐making process or, alternatively, involves a more personal and intuitive decision which is later to be tabled as the subject of political or administrative debate. This article deals with some fundamentals which provided the groundwork for formulating a scientific theory on the effects of policy instruments by the authors. The complexity of the matter will be reduced without affecting either the number or the diversity of circumstances that can be discussed simultaneously. In addition, attention will be focused on the role and influence of the implementation process which acts as an intermediary between the “paper” policy instruments and the actual policy measures.
RT-qPCR analysis of the tumor antigens TOMM34 and RNF43 in samples extracted from paraffin-embedded specimens of colorectal cancer

Comprehensive genetic analysis of colorectal malignant tumors by microarrays has identified translocase of the outer mitochondrial membrane 34 (TOMM34) and ring finger protein 43 (RNF43) as highly expressed oncogenes in malignant colorectal tumors. Vaccine therapy using cancer peptides synthesized using the amino acid sequences of tumor antigens is currently undergoing clinical trials. Since it is important to perform vaccine therapy based on the oncogene expression levels in individual tumors, analysis of tumor antigen expression is necessary for this therapy. However, the quality of the messenger RNA extracted from formalin-fixed and paraffin-embedded specimens is generally considered insufficient for gene quantification. The present study examined whether it could be possible to quantify the expression of TOMM34 and RNF43 in colorectal cancer and liver metastasis samples prepared from paraffin blocks. The formalin-fixed and paraffin-embedded specimens were sliced for slides and the colorectal cancer and normal mucosal tissues were obtained from the slides. Total RNA was extracted from the tissue samples, and quantitative polymerase chain reaction (qPCR) was performed using the Universal ProbeLibrary as a PCR probe. Quantification of TOMM34 and RNF43 gene expression in several-year-old paraffin-embedded colorectal cancer specimens was possible by qPCR using the Universal ProbeLibrary. qPCR revealed that TOMM34 expression was elevated in 78.9% (15 of 19 cases) of the primary tumors and in 73.7% (14 of 19 cases) of the liver metastasis samples. RNF43 expression was elevated in 63.2% (12 of 19 cases) of the primary tumors and in 73.7% (14 of 19 cases) of the liver metastasis samples.
Titration Microcalorimetry

Isothermal titration calorimetry (ITC) is perhaps the most rigorous commercially available method for characterizing protein‐ligand interactions. In this method, interactions are detected by the intrinsic heat (binding enthalpy) change of the reaction. The technique is applicable to native, unmodified proteins in solution. This is important for proteins that lose or change their functional behavior when chemically modified or attached to a surface. ITC is also useful for evaluating qualitative questions such whether a proposed binding interaction occurs at all, or for quantitatively measuring the concentration of functionally active protein. Finally, if executed with proper control experiments, ITC can be a rich source of thermodynamic information about the molecular binding mechanism.
A BAYESIAN APPROACH TO STOCHASTIC COST-EFFECTIVENESS ANALYSIS

The aim of this paper is to discuss the use of Bayesian methods in cost-effectiveness analysis (CEA) and the common ground between Bayesian and traditional frequentist approaches. A further aim is to explore the use of the net benefit statistic and its advantages over the incremental cost-effectiveness ratio (ICER) statistic. In particular, the use of cost-effectiveness acceptability curves is examined as a device for presenting the implications of uncertainty in a CEA to decision makers. Although it is argued that the interpretation of such curves as the probability that an intervention is cost-effective given the data requires a Bayesian approach, this should generate no misgivings for the frequentist. Furthermore, cost-effectiveness acceptability curves estimated using the net benefit statistic are exactly equivalent to those estimated from an appropriate analysis of ICERs on the cost-effectiveness plane. The principles examined in this paper are illustrated by application to the cost-effectiveness of blood pressure control in the U.K. Prospective Diabetes Study (UKPDS 40). Due to a lack of good-quality prior information on the cost and effectiveness of blood pressure control in diabetes, a Bayesian analysis assuming an uninformative prior is argued to be most appropriate. This generates exactly the same cost-effectiveness results as a standard frequentist analysis.