Miracle-dz/UniFAR-FTUs huggingface dataset:
Policy Contestation over the Ecosystem Services Approach in Sweden

ABSTRACT Ecosystem services (ES) is an important approach to biodiversity protection in political rhetoric and policy practice, but it is also highly contested. This paper analyzes the introduction of ES in Swedish environmental policy and how it is contested by key stakeholders and discusses its implications for biodiversity governance. The results show that although ES is widely accepted on an abstract and conceptual level, critical features and functions are highly contested. These primarily concern the valuation of nature, appropriateness of different policy instruments, and institutional structures. The paper concludes that while the controversy surrounding ES fills an important role by reinvigorating debate and stimulating reflections on biodiversity loss, it also illustrates how ES is used to further particular values and beliefs and to challenge traditional biodiversity-protecting strategies. Understanding these policy controversies is central to addressing the challenges of transforming the promises of ES into practical policies.
Nuclei segmentation in histopathology images using deep neural networks

Analysis and interpretation of stained tumor sections is one of the main tools in cancer diagnosis and prognosis, which is mainly carried out manually by pathologists. The avent of digital pathology provides us with the challenging opportunity to automatically analyze large amounts of these complex image data in order to draw biological conclusions from them and to study cellular and tissular phenotypes at a large scale. One of the bottlenecks for such approaches is the automatic segmentation of cell nuclei from this type of image data. Here, we present a fully automated workflow to segment nuclei from histopathology image data by using deep neural networks trained from a set of manually annotated images and by processing the posterior probability maps in order to split jointly segmented nuclei. Further, we provide the image data set that has been generated for this study as a benchmark set to the scientific community.
Using dynamic voltage drive in a parallel-plate electrostatic actuator for full-gap travel range and positioning

The nonlinear dynamics of the parallel-plate electrostatically driven microstructure have been investigated with the objective of finding a dynamic voltage drive suitable for full-gap operation. Nonlinear dynamic modeling with phase-portrait presentation of both position and velocity of a realistic microstructure demonstrate that instability is avoided by a timely and sufficient reduction of the drive voltage. The simulation results are confirmed by experiments on devices fabricated in an epi-poly process. A 5.5-V peak harmonic drive voltage with frequency higher than 300 Hz allows repetitive microstructure motion up to 70% of gap without position feedback. The results of the analysis have been applied to the design of a new concept for positioning beyond the static pull-in limitation that does include position feedback. The measured instantaneous actuator displacement is compared with the desired displacement setting and, unlike traditional feedback, the voltage applied to the actuator is changed according to the comparison result between two values. The "low" level is below the static pull-in voltage and opposes the motion, thus bringing the structure back into a stable regime, while the "high" level is larger than the static pull-in voltage and will push the structure beyond the static pull-in displacement. Operation is limited only by the position jitter due to the time delay introduced by the readout circuits. Measurements confirm flexible operation up to a mechanical stopper positioned at 2 /spl mu/m of the 2.25 /spl mu/m wide gap with a 30 nm ripple.
CaM kinase II‐dependent mobilization of secretory granules underlies acetylcholine‐induced stimulation of exocytosis in mouse pancreatic B‐cells

1 Measurements of cell capacitance were used to investigate the mechanisms by which acetylcholine (ACh) stimulates Ca2+‐induced exocytosis in single insulin‐secreting mouse pancreatic B‐cells. 2 ACh (250 μM) increased exocytotic responses elicited by voltage‐clamp depolarizations 2.3‐fold. This effect was mediated by activation of muscarinic receptors and dependent on elevation of the cytoplasmic Ca2+ concentration ([Ca2+]i) attributable to mobilization of Ca2+ from intracellular stores. The latter action involved interference with the buffering of [Ca2+]i and the time constant (τ) for the recovery of [Ca2+]i following a voltage‐clamp depolarization increased 5‐fold. As a result, Ca2+ was present at concentrations sufficient to promote the replenishment of the readily releasable pool of granules (RRP; > 0.2 μM) for much longer periods in the presence than in the absence of the agonist. 3 The effect of Ca2+ on exocytosis was mediated by activation of CaM kinase II, but not protein kinase C, and involved both an increased size of the RRP from 40 to 140 granules and a decrease in τ for the refilling of the RRP from 31 to 19 s. 4 Collectively, the effects of ACh on the RRP and τ result in a > 10‐fold stimulation of the rate at which granules are supplied for release.
RNAi functions in cultured mammalian neurons

In a wide range of organisms, double-stranded RNA triggers posttranscriptional gene silencing or RNA interference (RNAi). Small interfering RNAs, the 21-nt double-stranded RNA intermediates of this natural pathway, have became a powerful tool to knock down specific gene expression in mammalian cell lines and potentially will be useful for the analysis of loss-of-function phenotypes. In mammalian primary neuronal cultures, where genetic manipulations are especially difficult, RNAi might be developed into a highly efficacious tool to study the roles of specific genes in neuron development and functioning. Neurons, however, have been considered the most resistant to RNAi. We report here an application of RNAi to postmitotic primary neuronal cultures. Synthetic siRNA can be readily introduced into neurons and effectively inhibit the expression of endogenous and transfected genes.
Can – and Should – Lawyers Be Considered ‘Appropriate’ Appropriate Adults?

This paper furthers the debate on vulnerable suspects by bringing together research on appropriate adults and criminal defence lawyers. The Police and Criminal Evidence Act (PACE) 1984 forbids all lawyers from acting as appropriate adults. The courts, in very limited case law, have taken a different approach, leaving a space in which lawyers might be considered suitable to fill the gap left by an appropriate adult’s absence. This account is supported by exploring the views of custody officers on the appropriate adult and its use, drawing upon empirical data. Fieldwork with defence lawyers is then explored to highlight how lawyers might have some of the suitable characteristics of the appropriate adult but could not realistically perform such duties in practice (or conceptually). This paper illustrates that lawyers are ill-equipped to deal with a client’s vulnerability and therefore argues that they should never be viewed as an ‘appropriate adult replacement’.
Long‐term follow‐up of a prospective, double‐blind, placebo‐controlled randomized trial of clodronate in multiple myeloma

Oral clodronate (1600 mg/d) has been shown to significantly reduce the incidence of skeletal complications in multiple myeloma. Preliminary analysis of a double‐blind placebo‐controlled trial of this treatment indicated that clodronate might prolong survival in patients without vertebral fractures at presentation. This issue was re‐examined after further follow‐up of the patients recruited into the Medical Research Council (MRC) VIth Myeloma Study. The trial examined the effects of clodronate on the natural history of skeletal disease in multiple myeloma; 619 patients were randomized between June 1986 and May 1992 commencing 15 d after the start of ABCM [adriamycin, BCNU (carmustine), cyclophosphamide, melphalan] chemotherapy or 43 d after ABCMP (ABCM + prenisolone); 535 patients who received clodronate or placebo were included in the analysis. The presence or absence of spinal fractures was assessed centrally from spinal X‐rays; long‐bone fractures were assessed locally. With a median follow‐up of 8·6 years, there was no overall significant difference in survival between the two treatment groups (O/E, χ2 = 0·78, P = 0·38). Among the subgroup of 153 patients with no skeletal fractures at presentation there was a significant survival advantage (O/E, χ2 = 7·52, P = 0·006) in favour of the 73 patients receiving clodronate, with median survivals being, respectively, 59 months (95% CI 43–71 months) and 37 months (95% CI 31–52 months), and 5‐year survivals being 46% and 35%. The original analysis of this study shows that there is a benefit in taking 1600 mg clodronate daily for patients with myelomatosis to prevent the development of new skeletal disease. Bearing in mind the limitations of subgroup analysis, the present study indicates that treatment may prolong survival in patients without overt skeletal disease at diagnosis. These observations, however, require confirmation in prospective clinical trials.
Advances in Multi-Gate MOSFET Circuit Design

In this paper recent advances in multi-gate MOSFET (MuGFET) circuit design are reported. The feasibility of essential parts of low-power mobile SoC applications and large scale integration capability is shown. Excellent short channel control enables undoped metal gate MuGFETs to outperfom their planar counterparts in terms of delay-leakage trade-off. Superior voltage scaling efficiency and competitive performance is demonstrated for a product typical critical path. Design and layout optimization for improved SRAM cell stability is shown. Beneficial analog performance is exemplary demonstrated for an OpAmp. A potential degradation of ADC performance due to transient Vt mismatch is shown, the use of redundancy is proposed as countermeasure. Key RF building blocks are presented, MuGFET specific design issues are outlined. A comparison of different ESD elements yields a potential ESD protection scheme combining planar and MuGFET devices.
Cross‐linking of cell surface immunoglobulins induces epstein‐barr virus in burkitt lymphoma lines

Anti‐human immunoglobulin (Ig) antibodies with single‐chain specificities induced Epstein‐Barr virus (EBV) in various Burkitt lymphoma lines when the corresponding Ig chain was expressed on the cell surface. The F(ab')2 fragments of IgG antibody were as potent as intact Ig, while the Fab and Fc fragments gave no induction, indicating that cross‐linking of surface Ig was required for the induction. Simultaneously with EBV induction, anti‐Ig inhibited the uptake of 3H‐thymidine. This inhibition was also seen in EBV‐genome‐negative Burkitt lymphoma lines. In contrast, no effect on virus induction and cell growth was noted in lymphoblastoid lines of non‐neoplastic origin. The possible relationship between cell differentiation and latency of EBV‐carrier state is discussed.
Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues.

BACKGROUND Trastuzumab has significantly improved the prognosis of breast cancer patients overexpressing the human epidermal growth factor receptor 2 (HER2). This result has been achieved in all disease settings, by increasing overall survival in early stage and advanced disease and by increasing pathological complete responses in neoadjuvant disease. OBJECTIVE Although the greatest impact of this monoclonal antibody has been seen in the adjuvant setting, by increasing disease-free survival and overall survival rates an increased rate of both symptomatic and non-symptomatic cardiac toxicity has also been observed. METHODS In the following review, the different mechanisms of trastuzumab cardiac toxicity are described and, in addition, the clinical data coming from both trials and meta-analyses is discussed. RESULTS While there is strong evidence for the incidence of trastuzumab-related cardiac toxicity, there is still little known on the exact pathogenesis of this toxicity. Interestingly, both experimental and clinical data suggest that trastuzumab may sensitize cardiomyocytes to injuries and stress from administration of anthracyclines. This has led to a proposed novel mechanism of cardiotoxicity that appears to be quite different from the anthracycline-associated cardiotoxicity. Trastuzumab does not seem to cause any overt ultrastructural abnormality; it does, however, lead to myocardial dysfunction. CONCLUSION Most of the proposed hypotheses seems to be related to the activity of trastuzumab in interfering with the ERBB-2 receptor. Indeed, data from clinical trials in the adjuvant setting report increased cardiac toxicity in those patients who previously received anthracyclines.
Identification of glucuronidation and biliary excretion as the main mechanisms for gossypol clearance: in vivo and in vitro evidence

Abstract 1. The natural polyphenol gossypol possesses many therapeutic benefits. Here we aim to determine the elimination pathways of gossypol in vivo and in vitro. 2. Metabolite elucidation of gossypol was performed using UPLC-QTOF/MS coupled with Metabolynx analysis. Clearance of gossypol was evaluated in bile duct cannulated rats and in the single-pass perfused rat intestine model. In vitro glucuronidation of gossypol was characterized using liver and intestine microsomes as well as recombinant UDP-glucuronosyltransferase (UGT) enzymes. 3. Analysis of rat plasma, urine, and feces revealed glucuronidation as the only metabolic pathway for gossypol. In bile duct cannulated rats, considerable amounts of glucuronides (G1, G2 and G3; 58.8–83.2% of dose) and parent compound (5.0–20%) were excreted into bile after IV administration. In the perfused rat intestine model, gossypol was well absorbed with a (the dimensionless effective permeability) value of 4.4. Significant amounts of glucuronides (G1, G2 and G3) were excreted into the gut lumen (2.5%) and into the bile (4.8%). Biliary excretion of unchanged gossypol (6.0%) was comparable to that of glucuronides. Further, gossypol was subjected to rapid glucuronidation by liver and intestine microsomes. Reaction phenotyping showed that multiple UGT1A enzymes (including UGT1A1, 1A3, 1A7 and 1A8) are mainly responsible for gossypol metabolism. 4. In conclusion, glucuronidation was the only metabolic pathway for gossypol in rats. Excretion of unchanged gossypol into bile was also an important clearance mechanism.
Two types of death of poliovirus-infected cells: caspase involvement in the apoptosis but not cytopathic effect.

The death of poliovirus-infected cells may occur in two forms: canonical cytopathic effect (CPE) (on productive infections) or apoptosis (when the viral reproduction is hindered by certain drugs or some other restrictive conditions). Morphological manifestations of the CPE and apoptosis, being distinct, share some traits (e.g., chromatin condensation and nuclear deformation). It was shown here that a permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (zVAD.fmk), prevented the development of the poliovirus-induced apoptosis on abortive infection. The apoptotic pathway could be dissected by an inhibitor of chymotrypsin-like serine proteases, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), which prevented the cleavage of DNA to oligonucleosome-sized pieces and nuclear fragmentation but did not suppress cellular shrinkage, cytoplasmic blebbing, and partial chromatin condensation. These results demonstrate that caspase activation is involved in the execution phase of the viral apoptosis and suggest that a nuclear subset of the apoptotic program is under a separate control, involving a TPCK-sensitive event. Neither zVAD.fmk nor TPCK, at the concentrations affecting the apoptotic response, exerted appreciable influence on the virus growth or cellular pathological changes on productive infection, indicating that the pathways leading to the poliovirus-evoked CPE and apoptosis are different.
On the Profitability of Trade Deflection and the Need for Rules of Origin

When two countries conclude a free trade agreement (FTA), they define rules of origin (RoOs) to determine whether a product is eligible for preferential treatment. RoOs exist to avoid that exports from third countries enter the FTA through the member with the lowest tariff (trade deflection). However, RoOs distort exporters’ sourcing decisions and burden them with red tape. Using a global data set, we show that, for 86% of global trade and 78% of bilateral product-level comparisons, trade deflection is not profitable because external tariffs are rather similar and transportation costs are non-negligible; in the presence of a deep FTA, deflection is significantly less profitable still. We find evidence for both ex post adjustment of external tariffs and ex ante selection effects. The pervasive and unconditional use of RoOs is, therefore, hard to rationalize.
The hidden electoral connection: analysing parliamentary questions in the Chilean Congress

ABSTRACT Legislators in presidential countries use a variety of mechanisms to advance their electoral careers and connect with relevant constituents. The most frequently studied activities are bill initiation, co-sponsoring, and legislative speeches. In this paper, the authors examine legislators’ information requests (i.e. parliamentary questions) to the government, which have been studied in some parliamentary countries but remain largely unscrutinised in presidential countries. The authors focus on the case of Chile – where strong and cohesive national parties coexist with electoral incentives that emphasise the personal vote – to examine the links between party responsiveness and legislators’ efforts to connect with their electoral constituencies. Making use of a new database of parliamentary questions and a comprehensive sample of geographical references, the authors examine how legislators use this mechanism to forge connections with voters, and find that targeted activities tend to increase as a function of electoral insecurity and progressive ambition.
Application of Finite Volume Method for Solving Two-dimensional Navier Stokes Equations

The finite volume method combines the advantage of the finite element method and the finite difference method, while overcoming their shortcomings. This paper describes the development of the finite volume method and the process of using finite volume method for fluid calculations. Finally, this paper introduces the process of using improved finite volume method for solving the flow equations of NS.
Surface electromyography features in manual workers affected by carpal tunnel syndrome

Introduction: Alterations in surface electromyographic (sEMG) signals of the abductor pollicis brevis muscle were evaluated in 24 non‐manual workers and 40 manual workers (25 asymptomatic and 15 reporting CTS symptoms). Methods: The initial value (IV) and the normalized rate of change (NRC) of average rectified value (ARV), mean frequency of the power spectrum (MNF), and muscle fiber conduction velocity (MFCV) were calculated during contractions at 20% and 50% of maximal voluntary contraction (MVC). Neuromuscular efficiency (NME) and kurtosis of the sEMG amplitude distribution were estimated. Results: With respect to controls, manual workers showed higher NME, lower ARV IV, and reduced myoelectric manifestations of fatigue (lower MNF NRC for both contraction levels, and lower MFCV NRC at 50% MVC). Kurtosis at 20% MVC showed higher values in symptomatic manual workers than in the other two groups. Conclusions: Kurtosis seems to be a promising parameter for use in monitoring individuals who develop CTS. Muscle Nerve 45: 873–882, 2012
MOS voltage reference based on polysilicon gate work function difference

A voltage reference in CMOS technology is based upon transistor pairs of the same type except for the opposite doping type of their polysilicon gates. At identical drain currents, the gate voltage difference, close to the silicon bandgap, is 1.2 V/spl plusmn/0.06 V. Circuits for a positive and for a negative voltage reference are presented. Digital voltage tuning improves accuracy. Temperature compensation is provided by proper choice of current ratio or by means of an auxiliary circuit. Voltage drift is about 300 ppm//spl deg/C without compensation, and can be reduced to /spl plusmn/30 ppm//spl deg/C. The circuits work with a supply voltage of 2-10 V and draw a current that is less than 1 /spl mu/A.
Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder affecting children worldwide. The male bias in the prevalence of the disorder, suggests that some susceptibility genes may lie on the X chromosome. In this study we present evidence for a role of the X‐linked steroid sulfatase (STS) gene and neurosteroids in the development of ADHD. Previously it has been observed that probands with ADHD have lower serum concentrations of the neurosteroids DHEA, which is synthesized from DHEA‐S by STS. In further support, boys that suffer from XLI, a skin disorder caused by the deletion of the STS gene, have higher rates of ADHD, in particular the inattentive subtype. In a moderately sized sample of ADHD families (N = 384), we genotyped seven single nucleotide polymorphisms, tagging the entire gene. TDT analysis of the data yielded two polymorphisms that were significantly associated with ADHD (rs2770112—Transmitted: 71 Not Transmitted; 48; rs12861247—Transmitted: 43 Not Transmitted: 21), located towards the 5′ end of the gene (P < 0.05). We conclude that the STS gene may play a role in susceptibility for ADHD, and that the neurosteroids pathways should be investigated further to access their potential contribution in susceptibility to the disorder. © 2008 Wiley‐Liss, Inc.
Clinical protein science and bioanalytical mass spectrometry with an emphasis on lung cancer.

6. Tissue Degradation Biomarkers 3284 6.1. Elastin and Collagen Degradation Biomarkers 3284 7. Cancer 3285 7.1. Lung Cancer 3285 7.2. Lung Cancer and Epidermal Growth Factor 3285 7.3. Epidermal Growth Factor and Drug Treatment 3286 7.4. Additional Studies on Lung Cancer 3288 8. Absolute Quantitation of Proteins 3289 8.1. Assay Principles 3289 8.2. Assay Design 3290 8.3. In Silico Processing 3290 8.4. Isotope Labeled Internal Standard Peptides 3291 8.5. Bioanalytical Assays for Candidate Biomarker Validation 3291