Miracle-dz/UniFAR-FTUs huggingface dataset:
Soil Degradation and Soil Quality in Western Europe: Current situation and future perspectives

The extent and causes of chemical, physical and biological degradation of soil, and of soil loss, vary greatly in different countries in Western Europe. The objective of this review paper is to examine these issues and also strategies for soil protection and future perspectives for soil quality evaluation, in light of present legislation aimed at soil protection. Agriculture and forestry are the main causes of many of the above problems, especially physical degradation, erosion and organic matter loss. Land take and soil sealing have increased in recent decades, further enhancing the problems. In agricultural land, conservation farming, organic farming and other soil-friendly practices have been seen to have site-specific effects, depending on the soil characteristics and the particular types of land use and land users. No single soil management strategy is suitable for all regions, soil types and soil uses. Except for soil contamination, specific legislation for soil protection is lacking in Western Europe. The Thematic Strategy for Soil Protection in the European Union has produced valuable information and has encouraged the development of networks and databases. However, soil degradation is addressed only indirectly in environmental policies and through the Common Agricultural Policy of the European Union, which promotes farming practices that support soil conservation. Despite these efforts, there remains a need for soil monitoring networks and decision-support systems aimed at optimization of soil quality in the region. The pressure on European soils will continue in the future, and a clearly defined regulatory framework is needed.
Approximate Message Passing-Based Joint User Activity and Data Detection for NOMA

This letter focuses on joint user activity and data detection in the uplink grant-free non-orthogonal multiple access systems based on approximate message passing (AMP) and expectation maximization (EM) algorithms. The proposed Joint-EM-AMP detection algorithm consists of three steps in each iteration. First, AMP decouples the superimposed received signal into uncoupled scalar problems. Then, at the denoising step, AMP computes the posterior means and variances of the transmitted symbols with the extended modulation constellation. The third step is to estimate user activity parameters using EM based on the frame-wise joint sparsity of user activity. In contrast to existing state-of-the-art algorithms, the proposed Joint-EM-AMP algorithm demonstrates significant performance gain in terms of bit error rate, which will be verified in simulation results.
Ubiquitin-dependent Degradation of p73 Is Inhibited by PML

p73 has been identified recently as a structural and functional homologue of the tumor suppressor p53. Here, we report that p73 stability is directly regulated by the ubiquitin–proteasome pathway. Furthermore, we show that the promyelocytic leukemia (PML) protein modulates p73 half-life by inhibiting its degradation in a PML–nuclear body (NB)–dependent manner. p38 mitogen-activated protein kinase–mediated phosphorylation of p73 is required for p73 recruitment into the PML-NB and subsequent PML-dependent p73 stabilization. We find that p300-mediated acetylation of p73 protects it against ubiquitinylation and that PML regulates p73 stability by positively modulating its acetylation levels. As a result, PML potentiates p73 transcriptional and proapoptotic activities that are markedly impaired in Pml −/− primary cells. Our findings demonstrate that PML plays a crucial role in modulating p73 function, thus providing further insights on the molecular network for tumor suppression.
Advances in nuclear magnetic resonance for drug discovery

Background: Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exacerbated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project timelines. Recent advances in NMR are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. Objective/method: A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process is presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein–ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by functional annotation screening technology using NMR. Conclusion: NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques and the expansion of NMR amenable targets.
Randomized Phase II Study of Duligotuzumab (MEHD7945A) vs. Cetuximab in Squamous Cell Carcinoma of the Head and Neck (MEHGAN Study)

Background Duligotuzumab, a novel dual-action humanized IgG1 antibody that blocks ligand binding to epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), inhibits signaling from all ligand-dependent HER dimers, and can elicit antibody-dependent cell-mediated cytotoxicity. High tumor-expression of neuregulin 1 (NRG1), a ligand to HER3, may enhance sensitivity to duligotuzumab. Methods This multicenter, open-label, randomized phase II study (MEHGAN) evaluated drug efficacy in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) progressive on/after chemotherapy and among patients with NRG1-high tumors. Patients received duligotuzumab (1100 mg IV, q2w) or cetuximab (400 mg/m2 load, 250 mg/m2 IV, q1w) until progression or intolerable toxicity. Tumor samples were assayed for biomarkers [NRG1, ERBB3, and human papillomavirus (HPV) status]. Results Patients (N = 121) were randomized (duligotuzumab:cetuximab; 59:62), median age 62 years; ECOG 0–2. Both arms (duligotuzumab vs. cetuximab, respectively) showed comparable progression-free survival [4.2 vs. 4.0 months; HR: 1.23 (90% confidence interval (CI): 0.89–1.70)], overall survival [7.2 vs. 8.7 months; HR 1.15 (90% CI: 0.81–1.63)], and objective response rate (12 vs. 14.5%), with no difference between patients with NRG1-high tumors or ERBB3-low tumors. Responses in both arms were confined to HPV-negative patients. Grade ≥3 adverse events (AEs) (duligotuzumab vs. cetuximab, respectively) included infections (22 vs. 11.5%) and GI disorders (17 vs. 7%), contributing to higher rates of serious AEs (41 vs. 29.5%). Metabolic disorders were less frequent with duligotuzumab (10 vs. 16%); any grade rash-related events were less with duligotuzumab (49 vs. 67%). Conclusion While several lines of preclinical evidence had supported the premise that the blockade of HER3 in addition to that of EGFR may improve outcomes for patients with R/M SCCHN overall or specifically in those patients whose tumors express high levels of NRG1, this study provided definitive clinical evidence refuting this hypothesis. Duligotuzumab did not improve patient outcomes in comparison to cetuximab despite frequent expression of NRG1. These data indicate that inhibition of EGFR alone is sufficient to block EGFR–HER3 signaling, suggesting that HER2 plays a minimal role in this disease. Extensive biomarker analyses further show that HPV-negative SCCHN but not HPV-positive SCCHN are most likely to respond to EGFR blockage by cetuximab or duligotuzumab.
Pulmonary disease in small-vessel vasculitis

Diagnosis of the pulmonary manifestations of small-vessel vasculitis requires attention to detail, judicious use of imaging technology, and awareness of disorders that can mimic or masquerade as pulmonary vasculitis. Treatment should begin with pharmacologic intervention to manage the underlying inflammatory disorder. Dilation procedures and, in rare cases, surgery may be needed to resolve airway stenosis
Development of a Conditional Reasoning Measure of Team Orientation

Abstract : This paper describes a two-year effort to develop a measure of personality-based team orientation using conditional reasoning (CR). A model of team orientation is proposed and the conditional reasoning testing methodology is reviewed. This paper recounts the test development and validation efforts surrounding two CR tests. Although validation efforts indicated that the tests did not achieve acceptable validity and reliability coefficients, individuals who wish to construct CR tests may find the section of "lessons learned" to be particularly helpful.
Imaging Evaluation of Dogs and Cats with Dysphagia

The current literature is reviewed in this paper regarding the application of diagnostic imaging in the evaluation of swallowing disorders of the dog. The applications of radiography, contrast radiography, and contrast videofluoroscopy are discussed with pertinent case examples provided for emphasis. The indications for image-guided interventions are also described.
Rural pharmacy not delivering on its health promotion potential.

OBJECTIVE To investigate the level and perceived quality of health promotion advice received from rural pharmacists. DESIGN Self-administered written survey on access to and quality of pharmacy services in rural Western Australia completed by rural residents. SETTING Rural pharmacy. PARTICIPANTS Four hundred and eighty-three respondents who regularly used a pharmacy. OUTCOME MEASURES Items in the survey included frequency of receiving prevention advice and satisfaction ratings on health and pharmacy services. RESULTS Eighty-eight per cent of respondents had never discussed exercise or diet with their pharmacist and 65% had never discussed preventing health problems. Receiving good prevention advice predicted satisfaction with health services in general but not satisfaction with pharmacy services. CONCLUSION Pharmacies are being underutilised with respect to their capacity to deliver heath prevention advice and ways to capitalise on this potential need to be investigated.
A randomised trial in malignant mesothelioma (M) of early (E) versus delayed (D) chemotherapy in symptomatically stable patients: the MED trial.

BACKGROUND Prior phase II trials have demonstrated the therapeutic activity of cytotoxic chemotherapy in mesothelioma. Currently there are few randomised data assessing the role of chemotherapy versus best supportive care (BSC) in the management of patients with stable symptoms after control of any pleural effusion. A policy of observation is often adopted over initial use of chemotherapy. In this prospective randomised trial we assess the use of early versus delayed cytotoxic therapy. The study opened in 1998, and closed in view of a competing national study (MSO 1) in 2003. METHODS Eligible patients had a performance status<or=2, life expectancy>3 months and had stable symptoms for at least 4 weeks prior to randomisation. Patients were randomised to receive immediate chemotherapy or initial BSC with the addition of chemotherapy at time of symptomatic progression. All patients received the same platinum-based chemotherapy regimen, MVP [mitomycin C 8 mg/m2 cycles 1, 2, 4 and 6, vinblastine 6 mg/m2, maximum 10 mg, and cisplatin 50 mg/m2 (or carboplatin AUC 5)], every 3 weeks for up to six cycles. RESULTS A total of 43 patients were recruited, of which 21 were randomised to the early treatment group and 22 to the delayed treatment group. The median ages were 59 years (range 50-78) and 67 years (range 48-75), respectively (P=0.1); other baseline parameters were well matched between the two groups. All 21 patients in the early group received chemotherapy versus 17 patients in the delayed group. Median time to symptomatic progression was 25 weeks in the early group compared with 11 weeks for the delayed group (P=0.1). Median survival was 14 months (1-year survival 66%) for the early group compared with 10 months (1-year survival 36%) for the delayed group (P=0.1). Quality of life was in general better maintained for early treatment and the health resources use was similar in both arms. CONCLUSIONS In this patient group, presenting with stable symptoms after control of pleural effusion, the early use of chemotherapy provided an extended period of symptom control, and in this small trial a trend to survival advantage.
Versatile Membrane Deformation Potential of Activated Pacsin

Endocytosis is a fundamental process in signaling and membrane trafficking. The formation of vesicles at the plasma membrane is mediated by the G protein dynamin that catalyzes the final fission step, the actin cytoskeleton, and proteins that sense or induce membrane curvature. One such protein, the F-BAR domain-containing protein pacsin, contributes to this process and has been shown to induce a spectrum of membrane morphologies, including tubules and tube constrictions in vitro. Full-length pacsin isoform 1 (pacsin-1) has reduced activity compared to its isolated F-BAR domain, implicating an inhibitory role for its C-terminal Src homology 3 (SH3) domain. Here we show that the autoinhibitory, intramolecular interactions in pacsin-1 can be released upon binding to the entire proline-rich domain (PRD) of dynamin-1, resulting in potent membrane deformation activity that is distinct from the isolated F-BAR domain. Most strikingly, we observe the generation of small, homogenous vesicles with the activated protein complex under certain experimental conditions. In addition, liposomes prepared with different methods yield distinct membrane deformation morphologies of BAR domain proteins and apparent activation barriers to pacsin-1's activity. Theoretical free energy calculations suggest bimodality of the protein-membrane system as a possible source for the different outcomes, which could account for the coexistence of energetically equivalent membrane structures induced by BAR domain-containing proteins in vitro. Taken together, our results suggest a versatile role for pacsin-1 in sculpting cellular membranes that is likely dependent both on protein structure and membrane properties.
Alteration of Serum Biochemical Markers and Malondialdehyde Levels in Patients with Thyroid Gland Dysfunction Receiving Interferon Therapy

Thyroid dysfunction is the most frequent autoimmune reaction to interferon therapy. Thyroid diseases are frequently associated with liver injuries and abnormal results for biochemical tests, such as increased levels of alanine transaminase (ALT), aspartate transaminase (AST) and other liver-specific enzymes. In the present study, serum levels of AST, ALT, alkaline phosphatase (ALP), total bilirubin and malondialdehyde (MDA) were investigated as markers of liver injuries in patients with thyroid dysfunction. The focus of the present study was to assess the biochemical markers and MDA status in cases of interferon-induced thyroid gland dysfunctions. Interferon (IFN) therapy leads to an increase in liver enzymes such as AST, ALT, ALP and total bilirubin in patients with thyroid dysfunction. MDA, which is an important biochemical parameter and one of the products of lipid peroxidation, was also found to be significantly increased in patients with interferon-induced thyroid dysfunction. The estimation of these circulating biochemical parameters indicated that in cases of interferon-induced thyroid dysfunctions, some liver enzymes and the oxidative status of the cells were imbalanced, which is related to hepatic injury. IFN therapy leads to an increase in liver enzyme levels, particularly AST, ALT, ALP and MDA, in patients with thyroid dysfunction. Therefore, patients treated with IFN therapy should be informed of their risk of developing thyroid dysfunction, and screening of thyroid function should be conducted before and during treatment for HCV.
A directionally adaptive edge anti-aliasing filter

The latest generation of graphics hardware provides direct access to multisample anti-aliasing (MSAA) rendering data. By taking advantage of these existing pixel subsample values, an intelligent reconstruction filter can be computed using programmable GPU shader units. This paper describes an adaptive anti-aliasing (AA) filter for real-time rendering on the GPU. Improved quality is achieved by using information from neighboring pixel samples to compute both an approximation of the gradient of primitive edges and the final pixel color.
TOPCONS: consensus prediction of membrane protein topology

TOPCONS (http://topcons.net/) is a web server for consensus prediction of membrane protein topology. The underlying algorithm combines an arbitrary number of topology predictions into one consensus prediction and quantifies the reliability of the prediction based on the level of agreement between the underlying methods, both on the protein level and on the level of individual TM regions. Benchmarking the method shows that overall performance levels match the best available topology prediction methods, and for sequences with high reliability scores, performance is increased by ∼10 percentage points. The web interface allows for constraining parts of the sequence to a known inside/outside location, and detailed results are displayed both graphically and in text format.
New Chronic EEG Electrode for Critical/Intensive Care Unit Monitoring

The main limiting factor of EEG monitoring in the critical/intensive care environments is, and always has been, the recording electrode. The electrode and its application to the scalp has changed very little since EEG was first discovered and developed as a clinical tool. However, the evolution of amplifiers and data acquisition systems have made tremendous strides. Modern-day EEG recording systems now have the capability to record for days and weeks with little intervention, whereas the EEG electrode requires constant attention and skilled adjustment every 10 to 24 hours. If one surveys the vast array of electrodes used now and in the past, the only electrode that, once placed, never needed any further adjustment for days and weeks on end, was the chronic silver-silver/chloride (Ag-Ag/Cl) sphenoidal (Sp) electrode. This Sp electrode has now been modified to permit it to be placed subdermally, similar to that of a subdermal needle electrode, but now the needle is removed to leave in place a fine, flexible, durable, chronic Ag-Ag/Cl electrode. Once placed, this subdermal wire electrode (SWE, patent pending) starts to record immediately with a low impedance of 3 to 4 K&OHgr;. This electrode can record any biopotential, in humans and in animals, and in most recording environments; it never needs adjustment, and records high-quality biopotential signals for as long as it is left in place. The SWE is also MRI and computed-tomography compatible. It takes less than half the time to place the SWE, and placement can now be performed by any medically trained personnel to obtain a low-maintenance, high-quality EEG recording.
Nutritional modulation of the carcinogenesis process: targets and examples.

1 The ultimate goal of carcinogenesis research is to achieve an understanding of the processes involved in the induction of human cancer to an extent that will allow intervention to prevent the disease, either in the general population or in susceptible sub-populations. Humans are exposed to a wide variety of carcinogenic insults, including chemicals, viruses, radiation, and physical agents [1]. In addition, it has become increasingly apparent that an individual’s genetic background can dramatically affect the level of susceptibility to carcinogenic exposure [2–4]. The objective of this chapter is to examine the basic mechanisms and stages of the carcinogenesis process, with an emphasis on the ways in which food components can modify those mechanisms.
Experimental fault-tolerant control of a PMSM drive

The paper describes the study and experimental verification of remedial strategies against failures occurring in the inverter power devices of a PM synchronous motor drive. The basic idea for designing a fault-tolerant drive consists in incorporating a fourth leg into the inverter stage, which has the same topology and capabilities of the other conventional ones. This represents a minimal redundancy that, when appropriately connected and controlled, allows the drive to face a power device fault condition with smooth torque. The proposed control strategy also fits interior permanent magnet motor drives, which can operate even above the base speed, where a proper flux-weakening current control is adopted.
Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

Background People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed. Methods and Findings We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade. Conclusion Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID.
Development of a Polyclonal-Antibody-Based Immunohistochemical Method for the Detection of Type 2 Porcine Circovirus in Formalin-Fixed, Paraffin-Embedded Tissue

An immunohistochemical method for the detection of type 2 porcine circovirus (PCV2) in paraffin-embedded tissue was developed. Rabbits were inoculated with purified PCV2 to obtain a polyclonal antiserum. Antiserum was applied to sections of porcine tissue that contained lesions consistent with post-weaning multisystemic wasting syndrome and in which PCV2 genome had been demonstrated by in situ hybridization. In all cases (18/18), the density and distribution of positive cells detected by in situ hybridization or immunohistochemistry were identical. The immunohistochemical method is more rapid and less expensive than in situ hybridization and is thus more suitable for routine diagnostic use.