Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide association study of clinical parameters in immunoglobulin light chain amyloidosis in three patient cohorts

Immunoglobulin light chain (AL) amyloidosis is a progressive plasma cell dyscrasia which is characterized by the deposition of amyloid fibers derived from immunoglobulin light chain or their fragments systemically in many organs. The characteristics of amyloids relate to disease severity and sequelae, including the target organs where amyloids accumulate, such as the heart, kidney, liver, gut and peripheral nerves. Heart failure is usually the critical life-threatening condition; the median survival time may range from months to some years. We have recently characterized ten putative genetic risk loci (at a significance level of <10) for AL amyloidosis using a genome-wide association study (GWAS) approach on a total of 1229 German, UK and Italian patients. In the study herein we carried out a systematic GWAS-based association study on clinical data, including the affected organs and the isotype of serum immunoglobulins (Ig). We hypothesized that clinical profiles may be able to define distinct molecular subtypes. AL amyloidosis and multiple myeloma (MM) patient populations are described in Table 1; more details can be found in the study by da Silva Filho and colleagues. A total of nine clinical profiles were selected based on patient numbers, amyloid organ involvement (heart, kidney, heart + kidney and liver, irrespective of whether other organs were involved) and Ig profiles (intact IgG with l or k, l any, k any, l/k light chain only (LCO), and l LCO). Baseline assessments and procedures included physical examination, amyloid organ involvement and standard laboratory values in addition to serum monoclonal (M)-protein, free light chains, N-terminal pro btype natriuretic peptide (NT-proBNP) and cardiac troponin T (cTNT)/ high-sensitive (hs)TNT analyses. Organ involvement was uniformly assessed according to the consensus criteria agreed on by the three centers involved. The collection of patient samples and associated clinical information was approved by the relevant ethical review boards in accordance with the tenets of the Declaration of Helsinki. Analysis of the GWAS data was performed using imputed data as described. Single-nucleotide polymorphisms (SNPs) possessing a minor allele frequency (MAF) of <1% were excluded. Associations based on imputed SNPs alone were not considered. The association test between SNPs and AL amyloidosis was performed in SNPTEST v2.5. The three data sets were combined in meta-analysis and heterogeneity was assessed by the I statistic (interpreted as low <0.25, moderate 0.50 and high >0.75). For genome-wide significance, a limit of P<5x10 was used. Details of the bioinformatic analyses can be found in the study conducted by da Silva Filho et al. and in the Online Supplementary Material. Z-scores were calculated for SNPs as log odds ratio (OR) divided
EVALUATION OF MARGINAL GAP OF ZIRCONIUM CROWN AFTER AGING CYCLE OF THERMOPLASTIC RESIN CLASP

Statement of problem: Recent materials and techniques for improvement of the esthetic outcome in dentistry have been increasing in the last years. Acetal resin clasp and high strength zirconium crowns and related CAD/CAM techniques have widely used in dentistry. However, there are no studies evaluating the effect of aging cycle of acetal resin clasp on marginal gap of zirconium crown. Objectives: This study was conducted to evaluate the effect of aging cycles of acetal resin clasps on marginal gap of zirconium crowns of abutment teeth. Materials and methods: 10 of zirconium crowns and 10 acetal clasps were constructed. Each testing model with the tooth was attached from its base to the fixed compartment of the universal testing machine. To perform the aging cycle, an insertion/removal test set up (2400) continuous cycles was used, the marginal gap of zirconium crowns before and after removal-insertion aging cycles of the acetal resin clasps were measured using digital-microscope (Electronic Digital Caliper. Instruments-China), magnification X65. Results: Regardless to measured surface, totally it was found that aging recorded higher marginal gap than non-aged, with statistically significant difference between aged and non-aged samples, and the lingual surface recorded the highest marginal gap mean value followed by mesial surface then buccal surface however, the lowest mean value recorded distally. The difference between measured surfaces was statistically non-significant. Conclusion: Marginal gap of zirconium crowns were totally increased after aging cycles of the acetal resin clasps when compared by before aging, and the lowest recorded marginal gap mean value of zirconium crowns was recorded distally after aging.
Robust adaptive beamforming for general-rank signal models

The performance of adaptive beamforming methods is known to degrade severely in the presence of even small mismatches between the actual and presumed array responses to the desired signal. Such mismatches may frequently occur in practical situations because of violation of underlying assumptions on the environment, sources, or sensor array. This is especially true when the desired signal components are present in the beamformer "training" data snapshots because in this case, the adaptive array performance is very sensitive to array and model imperfections. The similar phenomenon of performance degradation can occur even when the array response to the desired signal is known exactly, but the training sample size is small. We propose a new powerful approach to robust adaptive beamforming in the presence of unknown arbitrary-type mismatches of the desired signal array response. Our approach is developed for the most general case of an arbitrary dimension of the desired signal subspace and is applicable to both the rank-one (point source) and higher rank (scattered source/fluctuating wavefront) desired signal models. The proposed robust adaptive beamformers are based on explicit modeling of uncertainties in the desired signal array response and data covariance matrix as well as worst-case performance optimization. Simple closed-form solutions to the considered robust adaptive beamforming problems are derived. Our new beamformers have a computational complexity comparable with that of the traditional adaptive beamforming algorithms, while, at the same time, offer a significantly improved robustness and faster convergence rates.
Effects of system variables on surfactant enhanced electrokinetic removal of polycyclic aromatic hydrocarbons from clayey soils

Abstract Numerous polycyclic aromatic hydrocarbon (PAH)‐contaminated sites threaten public health and the environment because PAHs are commonly toxins, mutagens, and/or carcinogens. PAHs are hydrophobic and resistant to degradation; therefore, conventional remediation methods are often costly or inefficient, especially when the PAHs are present in low permeability clayey soils. Electrokinetically enhanced in‐situ soil flushing is an innovative technology that has the potential to greatly increase soil‐solution‐contaminant interaction and remedial efficiency, even under low permeability soil conditions. Although this technique is promising, many system variables may affect remedial efficiency, such as the surfactant concentration, pH control, and voltage gradient. The objective of this investigation was to evaluate the effects of these system variables. Bench‐scale electrokinetic experiments were conducted using various operating conditions, which included deionized water or a 3% or a 5% surfactant concentration flushing solution. Additional tests were also conducted using the 5% surfactant concentration along with a higher pH solution or a larger voltage gradient. The experiments employing the surfactant flushing solution had a lower electroosmotic flow but exhibited greater contaminant desorption, solubilization and migration. The benefits of using a higher pH solution or a larger voltage gradient were difficult to discern because changing these process variables did not significantly improve remedial efficiency. Overall, the results indicated that the surfactant flushing solution was advantageous for treating the soil near the anode region, but contaminant migration was limited by changes in the soil and/or solution chemistry that occurred with time and/or distance from the anode
Intramembrane Proteolysis of Signal Peptides: An Essential Step in the Generation of HLA-E Epitopes1

Signal sequences of human MHC class I molecules are a unique source of epitopes for newly synthesized nonclassical HLA-E molecules. Binding of such conserved peptides to HLA-E induces its cell surface expression and protects cells from NK cell attack. After cleavage from the pre-protein, we show that the liberated MHC class I signal peptide is further processed by signal peptide peptidase in the hydrophobic, membrane-spanning region. This cut is essential for the release of the HLA-E epitope-containing fragment from the lipid bilayer and its subsequent transport into the lumen of the endoplasmic reticulum via the TAP.
TransLISA, a novel quantitative, nonradioactive assay for transcription factor DNA‐binding analyses

Transcription factors are DNA‐binding proteins that regulate key biological processes. Their interactions with DNA are commonly analyzed with gel‐based electrophoretic mobility shift assay (EMSA) using radioactively labeled probes. Within various fields of research, there exists an increasing demand to develop assays with faster sample throughput combined with improved sensitivity, increased analytical range, and precise quantification. Here, we describe the development and performance of a 384‐well plate immunoassay, termed TransLISA, which is a novel homogeneous assay for rapid and sensitive quantification of the DNA‐binding activity of transcription factors in cell and tissue lysates. TransLISA outperforms EMSAs, because it eliminates the need to use radioactive chemicals and allows fast and precise quantification of DNA‐binding activity of transcription factors from large number of samples simultaneously. We have used TransLISA to demonstrate the DNA‐binding activity of heat shock factor 1, representing a well‐known model of inductive transcriptional regulatory responses, but the method is easily adaptable for the study of any transcription factor. Thus, TransLISA can replace EMSAs and may be used in various applications and research fields where quantitative, cost‐effective and large‐scale measurements of the DNA‐binding activity of transcription factors are required, including screening of responses in multiple treatments in cellular and molecular biology, evolutionary research, environmental monitoring, and drug discovery.
Characterization of Demapper EXIT Functions with BEC a priori Information with Applications to BICM-ID

This paper introduces a less is more approach to the modelling of iterative decoding for bit-interleaved coded modulation (BICM). It considers modelling the iterative exchange of soft a priori information between the demapper and decoder with a binary erasure channel model. This simplification, unlike the usual additive white Gaussian noise (AWGN) channel model, allows us to express the extrinsic information transfer (EXIT) chart curves for the demapper with polynomials whose order makes explicit the degrees of freedom available for design. The accuracy of our expressions simplifies the design process enabling us to compare in a more manageable manner the key performance parameters: the BER performance and the convergence threshold. This enabled us to find the pairing of memory-two recursive systematic convolutional (RSC) codes and mappers that achieve the earliest convergence threshold for a target BER floor at convergence: for 8-PSK semi-set partitioning (SSP) was optimal and converged at a signal-to-noise ratio (SNR)= 3.0 dB for a BER target of at least 10-5; two new mappings were the optimal pairings for 16-QAM, where the L4b2 mapping converged at 2.9 dB for a BER floor ≤ 3.46 × 10-4 and the H2b2 mapping converged at 3.1 dB for a BER floor ≤ 2.44 × 10-5.
Cognitive-Behavioural Bibliotherapy for Hypochondriasis: A Pilot Study

Aims: The present study aims to determine whether cognitive-behavioural minimal contact bibliotherapy is acceptable to participants suffering from DSM-IV-TR hypochondriasis, and whether this intervention is able to reduce hypochondriacal complaints, as well as comorbid depressive complaints and trait anxiety. Method: Participants were assigned to either an immediate treatment condition, or subsequently to a waiting list condition. Participants were sent a book, Doctor, I Hope it's Nothing Serious? , containing cognitive behavioural theory and exercises. Measures were taken pre, post and at follow-up (after 3 months). Those in the waiting list group received a second pre-assessment, and were then enrolled in the bibliotherapy. Results: Results showed that participants were accepting of the cognitive-behavioural theory. Furthermore, results showed beneficial effects of the intervention: all effect measures decreased significantly over time, with the largest effect at post-assessment. However, a large amount of questionnaires were not returned. Conclusion: It is concluded that bibliotherapy may be an efficient aid in reducing hypochondriacal and comorbid complaints, but due to data attrition and methodological flaws should first be studied further.
Inverted-FL Antenna With Self-Complementary Structure

An inverted-FL antenna is proposal with a self-complementary structure. This unique design is realized by integrating an inverted-F antenna with a self-complementary structure and an inverted-L element. The proposed antenna with a volume of 10 times 10 times 45 mm3 achieves a constant impedance of 188 Omega without attaching a matching load required since a self-complementary antenna of an axially symmetric type has constant impedance. This antenna acquired broadband and multiband characteristics covering the GSM850/GSM900/DCS/ PCS/UMTS2100/UMTS2600 bands and the 2.5G/3.5G bands for Mobile-WiMAX by simulation and measurement.
Radiation and hydrogen peroxide induced free radical damage to DNA.

In a previous publication (Ward et al., 1985) we examined the production of intracellular DNA damage of the strand break type produced by hydrogen peroxide treatment of mammalian cells. To summarize our findings: V79 and HeLa cells when treated with hydrogen peroxide at 0°C are not readily killed - a treatment with 40mM for 10min is necessary to kill 63% (Figure 1). However the DNA of these cells showed significant levels of single strand breaks (SSB) at micromolar levels of the agent (50micromolar for 10min produced 5 Gray equivalents of damage: 5,000 SSB per cell (Elkind & Redpath, 1977)). This means that, if the yield of SSB produced by hydrogen peroxide is linearly dependent on concentration, 0.4 million SSB are produced per cell per lethal event. In contrast, for ionizing radiation the yield of SSB per cell per lethal event is 1,000 (Elkind & Redpath, 1977). By the use of OH radical scavengers we showed that the species from hydrogen peroxide causing the damage was the OH radical and that the distance travelled by this species prior to reacting with DNA was on average 15 A. This distance is in agreement with the mechanism proposed for the production of OH radicals and their subsequent reaction with DNA:Hydrogen peroxide reacting in a Fenton reaction with a variable valency metal ion bound to the DNA. Subsequent studies brought to anomaly: if the cells were treated at temperature (24°C) or at 37°C, they were killed with lower concentrations of hydrogen peroxide (Figure (DO =35micromolar) (Hofmann We measure the yield of SSB after room temperature treatment. None (less than 100 per cell) were found at concentrations of hydrogen peroxide up to 10mM.
Bivalent Recombinant Vaccine for Botulinum Neurotoxin Types A and B Based on a Polypeptide Comprising Their Effector and Translocation Domains That Is Protective against the Predominant A and B Subtypes

ABSTRACT The botulinum neurotoxins (BoNTs) are a large family of extremely potent, neuroparalytic, dichain proteins which act at the peripheral nervous system. The wide genetic diversity observed with this neurotoxin family poses a significant challenge for the development of an effective botulinum vaccine. The present study describes a vaccine development platform based on protein fragments representing the N-terminal two-thirds of each toxin molecule. These fragments, designated LHN, comprise the light chain and translocation domains of each neurotoxin and are devoid of any neuron-binding activity. Using codon-optimized genes, LHN fragments derived from BoNT serotypes A and B were expressed in Escherichia coli in high yield with >1 g of purified, soluble fragment recoverable from 4.5 liter-scale fermentations. The protective efficacy of LHN/A was significantly enhanced by treatment with formaldehyde, which induced intramolecular cross-linking but virtually no aggregation of the fragment. A single immunization of the modified fragment protected mice from challenge with a 103 50% lethal dose (LD50) of BoNT/A1 with an 50% effective dose (ED50) of 50 ng of the vaccine. In similar experiments, the LHN/A vaccine was shown to protect mice against challenge with BoNT/A subtypes A1, A2, and A3, which is the first demonstration of single-dose protection by a vaccine against the principal toxin subtypes of BoNT/A. The LHN/B vaccine was also highly efficacious, giving an ED50 of ∼140 ng to a challenge of 103 LD50 of BoNT/B1. In addition, LHN/B provided single-dose protection in mice against BoNT/B4 (nonproteolytic toxin subtype).
Rapid sequencing of rDNA from single worms and eggs of parasitic helminths.

The development of highly sensitive diagnostic techniques for the accurate identification of individual eggs of parasite species of medical and veterinary importance is central to the control of the diseases they cause. Sequencing of ribosomal genes provides a powerful molecular tool for species-level diagnosis and phylogenetic studies (1 -3), and is usually based on either of the two original techniques (4, 5). Direct PCR cycle sequencing (6, 7) is an attractive approach, because it is rapid, labour effective, and can be used to generate template from minute quantities of material (8, 9). This is especially important since often only limited specimens are available. This method also enables DNA template to be sequenced at high temperatures, thus reducing artifacts due to local secondary structure. Sequencing techniques rely on pure template DNA. Unfortunately, it is often difficult to isolate sufficient and pure DNA template from some parasitic helminths, because of their tough cuticle (10) and a 'white flocculate' substance found to co-precipitate with DNA during isolation (1 1, 12), which inhibits subsequent enzymatic reactions. In this paper, we describe a DNA isolation method which overcomes these problems and a PCR cycle sequencing technique which is sufficiently sensitive to sequence rDNA from single nematode eggs.
Bacillus gottheilii sp. nov., isolated from a pharmaceutical manufacturing site.

A novel Gram-staining-positive, rod-shaped, motile, strictly aerobic, endospore-forming bacterium, designated WCC 4585(T), was isolated from a pharmaceutical production line. The organism grew optimally at 30 °C, at pH 8 and in the presence of 0.5 % (w/v) NaCl. Oval endospores were formed subterminally and terminally in swollen sporangia. The cell-wall diamino acid was meso-diaminopimelic acid (type A1γ) and the genomic DNA G+C content was 38.7 mol%. The major menaquinone was MK-7. The cellular fatty acid profile contained major amounts of iso-C15 : 0, anteiso-C15 : 0 and anteiso-C17 : 0, and the cellular phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and aminophospholipid. The isolate was most closely related to Bacillus oceanisediminis H2(T), Bacillus infantis SMC 4352-1(T), Bacillus firmus NCIMB 9366(T), Bacillus circulans ATCC 4513(T) and Bacillus horneckiae DSM 23495(T) with which it shared less than 98.0 % 16S rRNA gene sequence similarity. DNA-DNA relatedness values between strain WCC 4585(T) and five type strains of related species were ≤27 % and sequence similarity values based on groEL sequences were ≤88.7 %. On the basis of the characteristics presented, strain WCC 4585(T) is proposed to represent a novel species, Bacillus gottheilii sp. nov. The type strain is WCC 4585(T)( = DSM 23668(T) = CCUG 59876(T) = LMG 25856(T)).
AC Electrical Arcs with Graphite Electrodes

In order to improve the safety of potentially hazardous situations such as "hot" disconnections of equipment or deteriorated connections, a deeper knowledge of the characteristics of the arcs thus produced and their subsequent damage to contact materials, insulating and wiring, is needed. Numerous studies have been performed on DC arcs as they appear in automotive applications. There is however, a strong need to study arcs in the domain of alternating current, in order to understand their consequences to safety and reliability in domestic applications. The purpose of this study is to extend our knowledge of AC-arc characteristics and consequences (e.g. risk of fire ignition) in order to improve the reliability of security devices such as arc fault circuit interrupters (AFCI). Conditions when arcs could initiate and reinitiate are determined, for a voltage of 220V (50Hz), a current from 1A to 4A, electrodes made with copper or graphite and gaps from 10µm to 1000µm. The conclusion of this work is that arcs produced by graphite electrodes present some characteristics which differ significantly from metallic electrode arcs, especially regarding ignition and re-ignition capability. This behavior should be taken into count for safety considerations.
Delineation of the GPRC6A Receptor Signaling Pathways Using a Mammalian Cell Line Stably Expressing the Receptor

The GPRC6A receptor is a recently “deorphanized” class C G protein–coupled receptor. We and others have shown that this receptor is coactivated by basic l-α-amino acids and divalent cations, whereas other groups have also suggested osteocalcin and testosterone to be agonists. Likewise, the GPRC6A receptor has been suggested to couple to multiple G protein classes albeit via indirect methods. Thus, the exact ligand preferences and signaling pathways are yet to be elucidated. In the present study, we generated a Chinese hamster ovary (CHO) cell line that stably expresses mouse GPRC6A. In an effort to establish fully the signaling properties of the receptor, we tested representatives of four previously reported GPRC6A agonist classes for activity in the Gq, Gs, Gi, and extracellular-signal regulated kinase signaling pathways. Our results confirm that GPRC6A is activated by basic l-α-amino acids and divalent cations, and for the first time, we conclusively show that these responses are mediated through the Gq pathway. We were not able to confirm previously published data demonstrating Gi- and Gs-mediated signaling; neither could we detect agonistic activity of testosterone and osteocalcin. Generation of the stable CHO cell line with robust receptor responsiveness and optimization of the highly sensitive homogeneous time resolved fluorescence technology allow fast assessment of Gq activation without previous manipulations like cotransfection of mutated G proteins. This cell-based assay system for GPRC6A is thus useful in high-throughput screening for novel pharmacological tool compounds, which are necessary to unravel the physiologic function of the receptor.