Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Back Pain Is Associated with Alterations in Dopamine Neurotransmission in the Ventral Striatum

Back pain is common in the general population, but only a subgroup of back pain patients develops a disabling chronic pain state. The reasons for this are incompletely understood, but recent evidence implies that both preexisting and pain-related variations in the structure and function of the nervous system may contribute significantly to the development of chronic pain. Here, we addressed the role of striatal dopamine (DA) D2/D3 receptor (D2/D3R) function in chronic non-neuropathic back pain (CNBP) by comparing CNBP patients and healthy controls using PET and the D2/D3R-selective radioligand [11C]raclopride. D2/D3R availability was measured at baseline and during a pain challenge, yielding in vivo measures of receptor availability (binding potential, BPND) and DA release (change in BPND from baseline to activated state). At baseline, CNBP patients demonstrated reductions in D2/D3R BPND in the ventral striatum compared with controls. These reductions were associated with greater positive affect scores and pain tolerance measures. The reductions in D2/D3R BPND were also correlated with μ-opioid receptor BPND and pain-induced endogenous opioid system activation in the amygdala, further associated with measures of positive affect, the affective component of back pain and pain tolerance. During the pain challenge, lower magnitudes of DA release, and therefore D2/D3R activation, were also found in the ventral striatum in the CNBP sample compared with controls. Our results show that CNBP is associated with adaptations in ventral striatal D2/D3R function, which, together with endogenous opioid system function, contribute to the sensory and affective-motivational features of CNBP. SIGNIFICANCE STATEMENT The neural systems that underlie chronic pain remain poorly understood. Here, using PET, we provide insight into the molecular mechanisms that regulate sensory and affective dimensions of pain in chronic back pain patients. We found that patients with back pain have alterations in brain dopamine function that are associated with measures of pain sensitivity and affective state, but also with brain endogenous opioid system functional measures. These findings suggest that brain dopamine–opioid interactions are involved in the pathophysiology of chronic pain, which has potential therapeutic implications. Our results may also help to explain individual variation in susceptibility to opioid medication misuse and eventual addiction in the context of chronic pain.
Temporal separation of distinct differentiation pathways by a dual specificity Rap‐Phr system in Bacillus subtilis

In bacterial differentiation, mechanisms have evolved to limit cells to a single developmental pathway. The establishment of genetic competence in Bacillus subtilis is controlled by a complex regulatory circuit that is highly interconnected with the developmental pathway for spore formation, and the two pathways appear to be mutually exclusive. Here we show by in vitro and in vivo analyses that a member of the Rap family of proteins, RapH, is activated directly by the late competence transcription factor ComK, and is capable of inhibiting both competence and sporulation. Importantly, RapH is the first member of the Rap family that demonstrates dual specificity, by dephosphorylating the Spo0F∼P response regulator and inhibiting the DNA‐binding activity of ComA. The protein thus acts at the stage where competence is well initiated, and prevents initiation of sporulation in competent cells as well as contributing to the escape from the competent state. A deletion of rapH induces both differentiation pathways and interferes with their temporal separation. Together, these results indicate that RapH is an integral part of a multifactorial regulatory circuit affecting the cell's decision between distinct developmental pathways.
Community-Based Values for 2009 Pandemic Influenza A H1N1 Illnesses and Vaccination-Related Adverse Events

Objective To evaluate community-based values for avoiding pandemic influenza (A) H1N1 (pH1N1) illness and vaccination-related adverse events in adults and children. Methods Adult community members were randomly selected from a nationally representative research panel to complete an internet survey (response rate = 65%; n = 718). Respondents answered a series of time trade-off questions to value four hypothetical health state scenarios for varying ages (1, 8, 35, or 70 years): uncomplicated pH1N1 illness, pH1N1 illness-related hospitalization, severe allergic reaction to the pH1N1 vaccine, and Guillain-Barré syndrome. We calculated descriptive statistics for time trade-off amounts and derived quality adjusted life year losses for these events. Multivariate regression analyses evaluated the effect of scenario age, as well as respondent socio-demographic and health characteristics on time trade-off amounts. Results Respondents were willing to trade more time to avoid the more severe outcomes, hospitalization and Guillain-Barré syndrome. In our adjusted and unadjusted analyses, age of the patient in the scenario was significantly associated with time trade-off amounts (p-value<0.05), with respondents willing to trade more time to prevent outcomes in children versus adults. Persons who had received the pH1N1 vaccination were willing to trade significantly more time to avoid hospitalization, severe allergic reaction, and Guillain-Barré syndrome, controlling for other variables in adjusted analyses. (p-value<0.05) Conclusions Community members placed the highest value on preventing outcomes in children, compared with adults, and the time trade-off values reported were consistent with the severity of the outcomes presented. Considering these public values along with other decision-making factors may help policy makers improve the allocation of pandemic vaccine resources.
Face-to-Face Interactions of Postpartum Depressed and Nondepressed Mother-Infant Pairs at 2 Months

Depression's influence on mother-infant interactious at 2 months postpartum was studied in 24 depressed and 22 nondepressed mothex-infant dyads. Depression was diagnosed using the SADS-L and RDC. In S's homes, structured interactions of 3 min duration were videotaped and later coded using behavioral descriptors and a l-s time base. Unstructured interactions were described using rating scales. During structured interactions, depressed mothers were more negative and their babies were less positive than were nondepressed dyads. The reduced positivity of depressed dyads was achieved through contingent resixmfiveness. Ratings from unstructured interactions were consistent with these findings. Results support the hypothesis that depression negatively influences motherinfant behaviol; but indicate that influence may vary with development, chronicity, and presence of other risk factors. Ten to 15% of postpartum women develop a moderate, clinically significant depressive reaction that is more prolonged than the "blues" and serious enough to interfere with daily functioning (O'Hara, Neunaber, & Zekosld, 1984). Postpartum depression is thus a potentially important mental health problem for families with young infants. Studies of depression in the postpartum period, however, have focused almost exclusively on the woman herself (see Hopkins, Marcus, & Campbell, 1984, for a review) and have ignored the possible negative effects depression may have on her relationship with her infant and her infant's development. Postpartum depression would be expected to interfere with optimal mothering. The importance of positive expression and responsive caretaking in early infancy has been well documented in numerous studies (e.g., Ainsworth, Blehar, Waters, & Wall, 1978; Belsky, Rovine, & Taylor, 1984), whereas maternal insensitivity and unavailability have been associated with a range of difficulties in adaptation in infancy and early childhood (e.g., Sronfe, 1983). Recent studies have confirmed earlier clinical observations by Weissman and Paykel (1974) about the negative impact of maternal depression on young children's development. Research on the offspring of women with major depressive disorders has indicated a range of cognitive and social problems in toddlers, preschoolers, and school age children (Beardslee, Bemporad, Keller, & Klerman, 1983; Cytryn, McKnew, ZahnWaxier; & Gershon, 1986; Sameroff, Seifer, & Zax, 1982). InThe research reported in this article was supported by National Institute of Mental Health Grant 5R01 MH40867 to Jeffrey E Cohn and
Discovery and Characterization of Triaminotriazine Aniline Amides as Highly Selective p38 Kinase Inhibitors

The p38 mitogen-activated protein (MAP) kinases are a family of serine/threonine protein kinases that play important roles in cellular responses to inflammation and external stress. Inhibitors of the p38 MAP kinase have shown promise for potential treatment of inflammatory disorders such as rheumatoid arthritis, acute coronary syndrome, psoriasis, and Crohn's disease. We identified a novel class of p38 inhibitors via high-throughput screening. PS200981 [3-(4-(1,4-diazepan-1-yl)-6-(((1S,2R,5S)-6,6-dimethylbicyclo[3.1. 1]heptan-2-yl)methylamino)-1,3,5-triazin-2-ylamino)-4-methylbenzamide], a representative compound identified from screening a collection of combinatorial libraries, amounting to 2.1 million compounds, inhibits p38α kinase and the lipopolysaccharide (LPS)-induced increase in tumor necrosis factor (TNF) α levels in cell media of human monocytes with IC50 values of 1 μM. The screening data revealed a preferred synthon, 3-amino-4-methyl benzamide, which is critical for the activity against p38. This synthon appeared almost exclusively in screening hits including PS200981, and slight variations of this synthon including 3-amino benzamide and 2-amino-4-methyl benzamide also contained in the library were inactive. PS200981 is equally potent against the α and β forms of p38 but did not inhibit p38γ and is >25-fold selective versus a panel of other kinases. PS200981 inhibited the LPS-induced increase in TNFα levels when administered at 30 mg/kg to mice. Selectivity and in vivo activity of this class of p38 inhibitors was further demonstrated by PS166276 [(R)-3-(4-(isobutyl(methyl)-amino)-6-(pyrrolidin-3-ylamino)-1,3,5-triazin-2-ylamino)-4-methylbenzamide], a highly structurally related but more potent and less cytotoxic inhibitor, in several intracellular signaling assays, and in LPS-challenged mice. Overall, this novel class of p38 inhibitors is potent, active in vitro and in vivo, and is highly selective.
Structural and Biochemical Studies on ATP Binding and Hydrolysis by the Escherichia coli RNA Chaperone Hfq

In Escherichia coli the RNA chaperone Hfq is involved in riboregulation by assisting base-pairing between small regulatory RNAs (sRNAs) and mRNA targets. Several structural and biochemical studies revealed RNA binding sites on either surface of the donut shaped Hfq-hexamer. Whereas sRNAs are believed to contact preferentially the YKH motifs present on the proximal site, poly(A)15 and ADP were shown to bind to tripartite binding motifs (ARE) circularly positioned on the distal site. Hfq has been reported to bind and to hydrolyze ATP. Here, we present the crystal structure of a C-terminally truncated variant of E. coli Hfq (Hfq65) in complex with ATP, showing that it binds to the distal R-sites. In addition, we revisited the reported ATPase activity of full length Hfq purified to homogeneity. At variance with previous reports, no ATPase activity was observed for Hfq. In addition, FRET assays neither indicated an impact of ATP on annealing of two model oligoribonucleotides nor did the presence of ATP induce strand displacement. Moreover, ATP did not lead to destabilization of binary and ternary Hfq-RNA complexes, unless a vast stoichiometric excess of ATP was used. Taken together, these studies strongly suggest that ATP is dispensable for and does not interfere with Hfq-mediated RNA transactions.
Lifetime assessment for bipolar components under vibration and temperature loading

Electronic devices for automotive applications represent a big market today. The number of these devices per car significantly increased within the last years. At the same time the mounting positions of the devices are close to engine, gear or suspension structures and therefore face harsh use conditions. Nevertheless the expected lifetime of these devices is 25 years or even more. Careful and comprehensive engineering is needed to fulfil the named requirements. To access the reliability of solder joints facing the described conditions an understanding of the damage mechanism driven by vibration and thermal loads need to be gained. To address this situation vibration experiments on as reflowed as well as on isothermally pre-aged (high temperature storage, HTS) ceramic chip capacitors were accomplished at room temperature. In a further set as reflowed specimen were exposed to vibration at 125°C. A strap like PCB as described in [1] was used enabling a defined load introduction. A next generation of these test vehicles including local heater functionality was used to accomplish the vibration at high temperature. Crack growth and failure cycles were investigated. Life time models for the different loading conditions were determined using experimental and simulation results.
Italy and UN peacekeeping: constant transformation

ABSTRACT Italy was admitted to the United Nations (UN) in 1955. In a mix of ‘genetic multilateralism’ of Italian society and the ‘institutional multilateralism’ of the Italian Constitution, the UN soon acquired a central position in Italian foreign policy and Italian participation in the UN and its institutions became increasingly active. Italy is the top troop contributor to UN Peacekeeping operations among Western countries. Since the 1960s, Italy has participated in 33 UN Peacekeeping operations. The Italian commitment to the UN faced four main turning points: the launch of the UNOSOM II mission in Somalia (1992), the contribution to the UN Interim Administration Mission in Kosovo (1999), the involvement in Afghanistan and Iraq (2001–05), and the engagement with the UNIFIL II mission (2006). By providing an historical overview of Italy’s approach to UN Peacekeeping and explaining the different engagements and disengagements drive through the shift in the foreign policy priorities of the country and the influence of domestic factors; this article aims to answer to the following questions: ‘How much will Italy be willing to contribute to UN Peacekeeping in the future? ’ and ‘Does Italy see other multilateral options (EU and NATO) as alternatives to the UN? ’
The Impact of Marketing-Induced vs . Word-of-Mouth Customer Acquisition on Customer Equity by

Companies can acquire customers through costly but fast-acting marketing investments, or through slower but cheaper word-of-mouth processes. Their long-term success depends critically on the contribution that each acquired customer makes to overall customer equity. We propose and test an empirical model that captures these long-term effects. An application to a web hosting company reveals that marketing-induced customers add more short-term value, but word-of-mouth customers add nearly twice as much long-term value to the firm. We illustrate our findings with some dynamic simulations of the long-term impact of different resource allocations for acquisition marketing. INTRODUCTION Customers are valuable assets for the firm, but they can be costly to acquire and to retain. Customers’ differences in the course of their relationship with the firm are reflected in their price sensitivity, lifetime duration, purchase volume, and even word-of-mouth generation. This causes differences in customers’ lifetime value (CLV, hereafter), defined as the discounted stream of cash flows generated over the lifetime of a customer. To the extent that different acquisition strategies will bring different “qualities” of customers, the acquisition effort will have an important influence on the long-term profitability of the firm. Indeed, both practitioners and scholars have emphasized that firms should not spend to acquire just any customer, but the “right” kind of customer (Blattberg and Deighton 1996; Blattberg, Getz, and Thomas 2001; Hansotia and Wang 1997; Reichheld 1993). Therefore, the customer acquisition process plays an important role in the newlyemerging paradigm of customer equity (CE). Optimizing the acquisition budget for long-term profitability is particularly relevant for start-ups and for firms competing in growth markets, where acquisition spending is the most important expense in the marketing budget. In these scenarios, the firm could have an illusion of profitable growth, when in fact it is acquiring unprofitable customers. This occurred for many internet start-ups that spent aggressively on acquisition in an effort to maximize ‘eyeballs’, with the hope of locking-in customer revenue later. However, that revenue never materialized for many companies, either because their value proposition was not compelling enough, or because the underlying 1 For a general discussion of the CE concept we refer to Blattberg, Getz and Thomas (2001) and Rust, Zeithaml and Lemon (2000). Though there exist various definitions of CE, it is defined in this paper as the sum of all existing and expected customers’ CLVs.
Centre De Referència En Economia Analítica Barcelona Economics Working Paper Series Working Paper Nº 285 Labor Productivity in Europe: Evidence from a Sample of Regions Labor Productivity in Europe: Evidence from a Sample of Regions

The present paper aims at analyzing the sources of labor productivity in Europe at regional level. We study the productivity performance in a sample of twenty European regions belonging to four countries (France, Germany, Italy and Spain). Exploiting the increasing availability of disaggregated data at regional level, we propose both a descriptive statistics and an econometric analysis of productivity sources since 1995. Our main finding is that the levels and sources of labor productivity are rather heterogeneous across the sample. This heterogeneity is found to be associated with disparities both across sectors and regions.
Defining suffering : African American young men and conduct disorder

This paper will discuss the disproportionate overrepresentation of African American young men among those diagnosed with Conduct Disorder. Existing research attributes this disproportionality to a variety of factors but does not incorporate historical or social analysis. This project will endeavor to consider how the historical and enduring stereotype of black men as “criminal” impacts this diagnosing pattern, and explores alternate ways to define and treat behavioral symptomology among young black men. This paper will discuss how stereotypes as well as the fear of being stereotyped impact both client and clinician and affect their interaction, thereby influencing psychological assessment and diagnosis. This paper will also argue that in general clinicians may not adequately account for the environment with which African American young men contend, and that historical and ongoing oppression must be considered in the assessing and diagnosing process. The way in which a client’s problem is defined leads to specific treatment, and thus it is necessary to explore varying ways to define the problem that manifests in behavioral symptoms for African American young men. This analysis will aim to examine the ways in which slavery and its legacy impact psychological assessment and diagnosis today, and how diagnosing clinicians may inadvertently contribute to the criminalization of young African American men when assigning Conduct Disorder diagnoses. The purpose of this project is to encourage social workers to critically consider the ways in which they define the healing and suffering of their clients. DEFINING SUFFERING: AFRICAN AMERICAN YOUNG MEN AND CONDUCT DISORDER A project based upon an investigation, submitted in partial fulfillment of the requirements for the degree of Master of Social Work. Sascha Atkins-Loria Smith College School for Social Work Northampton, MA 01063 2014
Type safety from the ground up

Type safety is the most common mechanism for securely running untrusted code from the Internet. When the untrusted code is written in a type-safe language like JavaScript, Java, or C#, the language's type system guarantees that the code cannot damage the user's computer (without the user's permission). This guarantee, however, rests on the correct enforcement of type safety, and a typical computer system has many components that must be trusted to enforce type safety. A bug in any one of these components could break security entirely: a buggy compiler could emit unsafe code, a buggy garbage collector could turn integers into unsafe pointers, a buggy operating system could overwrite a thread's context with untyped data, and a buggy device driver could instruct a device to overwrite typed memory with untyped data. This talk will describe work on the Verve operating system [8]{verve:pldi10}, which uses typed assembly language (TAL)[6] and automated theorem proving to ensure type safety across all components of a computer system, including the garbage collector, the operating system, the device drivers, and all compiler-generated assembly language code. Verve consists of about 35,000 lines of safe C# code, compiled to typed assembly language, running on top of 1500 lines of assembly language, verified with the Z3 automated theorem [2]. For example, the operating system's scheduler is C# code compiled to TAL, while the operating system's low-level context switching and interrupt handling is verified assembly language code. Similarly, the Ethernet driver's packet processing is C# compiled to TAL, while the verified assembly language ensures that devices are managed safely (via verified interaction with PCI) and device memory access is safe (via verified programming of an I/O memory management unit). Finally, the run-time system is split into components that the TAL type system can express (including array-store checks and run-time casts), and components that are verified with theorem proving (in particular, the garbage collector). This splitting is similar to other operating systems designed for high assurance [1, 4, 5, 7], but Verve adds a higher degree of static safety verification: every assembly language instruction is statically verified, either with type checking or theorem proving, to preserve type safety. Because Verve relies on two separate static checkers (TAL and Z3), it does not yet achieve the goal of unified, foundational certification as pursued by the FLINT project [3]. This talk will discuss ongoing work to move closer to this goal, by expressing both Verve's low-level state and a TAL type system in a unified language (Coq). Although this work is preliminary, it has already uncovered several bugs in the specification used to verify Verve's 1500 lines of assembly language. (These bugs were too-strong preconditions and too-weak postconditions; luckily, the specification bugs didn't result in bugs in the code itself.) Verve's source code is available at the following URL (in the "verify" directory): http://www.codeplex. com/singularity