Miracle-dz/UniFAR-FTUs huggingface dataset:
Potent Spinal Analgesia Elicited through Stimulation of NTS2 Neurotensin Receptors

Intrathecal administration of the neuropeptide neurotensin (NT) was shown previously to exert antinociceptive effects in a variety of acute spinal pain paradigms including hotplate, tail-flick, and writhing tests. In the present study, we sought to determine whether some of these antinociceptive effects might be elicited via stimulation of low-affinity NTS2 receptors. We first established, using immunoblotting and immunohistochemical techniques, that NTS2 receptors were extensively associated with putative spinal nociceptive pathways, both at the level of the dorsal root ganglia and of the superficial layers of the dorsal horn of the spinal cord. We then examined the effects of intrathecal administration of NT or selective NTS2 agonists on acute thermal pain. Both NT and NTS2 agonists, levocabastine and Boc-Arg-Arg-Pro-Tyrψ(CH2NH)Ile-Leu-OH (JMV-431), induced dose-dependent antinociceptive responses in the tail-flick test. The effects of levocabastine and of JMV-431 were unaffected by coadministration of the NTS1-specific antagonist 2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxy-phenyl)pyrazol-3-yl)carboxylamino]tricyclo)3.3. 1.1. 3.7)-decan-2-carboxylic acid (SR48692), confirming that they were NTS2 mediated. In contrast, the antinociceptive effects of NT were partly abolished by coadministration of SR48692, indicating that NTS1 and NTS2 receptors were both involved. These results suggest that NTS2 receptors play a role in the regulation of spinal nociceptive inputs and that selective NTS2 agonists may offer new avenues for the treatment of acute pain.
Corporate leverage and the terms of employment: evidence from French small businesses before and during the global crisis

ABSTRACT Despite the particular importance of corporate leverage and human capital for small businesses, little is surprisingly known about the relationship between these two factors for this category of firms. Accordingly, this article tries to fill this gap by investigating the relationship between leverage and human capital examined through the investment in employee-related expenditure. The analysis focuses on a sample of French listed small businesses before and during the recent global crisis. The empirical findings show that leverage serves as a monitoring mechanism of corporate managers prone to over or underinvest in employee-related expenditure to obtain private benefits. Due notably to the availability of debt, this monitoring is more effective before the crisis period, especially for low growth firms. Overall, these results provide support to the theory that leverage has a disciplining role. Simultaneously, they lead to moderate the strength of this role according to the global crisis. Thus, they should provide useful insights for academics, regulators, managers and credit institutions.
Psikolojik Sahiplenme: Örgütsel Alana İlişkin Bir Model Önerisi

Oz Gunumuzde artan sayida arastirma isgorenlerin orgutlerini ve islerini psikolojik olarak sahiplenmelerinin, olumlu orgutsel ciktilar uzerindeki etkilerini ortaya koymaktadir. Ancak psikolojik sahiplenme olgusunun tam olarak ne oldugu, orgutsel alanda nasil gelistigi, hangi formlarda ortaya ciktigi ve orgutsel ciktilarinin ne oldugu konusunda arastirmalarin yeterli olgunluga erismedigi arastirmacilar tarafindan siklikla dile getirilmektedir. PS (Psikolojik Sahiplenme) olgusunun teorilesmesi yonundeki eksiklige bagli olarak bu calismada PS olgusunun orgutsel alan icerisinde teorilesmesine katki saglanmasi amaclamaktadir. Ozgun bir model uzerinden tasarimlanan calismada model uzerindeki degiskenler arasindaki iliskiler kuramsal analizlere bagli olarak ele alinmistir. Arastirma sonucuna bagli olarak olgunun kavramsallasmasi, orgutsel alan icerisinde ne sekilde gelistigi ve orgutsel alana iliskin ciktilari uzerinde saglam bir teorinin olustugu soylemek zordur. PS olgusunu orgutsel alan icerisinde butuncul bir bakis acisiyla ele alan bu calisma olgunun teorilesmesine iliskin yapilacak ampirik calismalara kuramsal bir altyapi hazirladigi icin onemlidir.
The effect of the orally active platelet-activating factor antagonist WEB 2086 in the treatment of asthma.

Platelet-activating factor (PAF) may be a major mediator of asthma and bronchial hyperreactivity through its many proinflammatory actions. Specific antagonism of PAF might offer an alternative anti-inflammatory treatment to inhaled corticosteroids. To test this, we have studied the effect of an orally active PAF antagonist, WEB 2086, on the inhaled steroid requirements of symptomatic atopic asthmatics in a double-blind randomized placebo-controlled parallel group study. The inhaled corticosteroid dose required for symptomatic control of asthma was established and further steroid reduction was attempted after treatment with WEB 2086 40 mg three times daily for 12 wk. Of 106 patients recruited, 68 entered the treatment phase and 65 completed 6 wk of treatment. The mean daily corticosteroid dose (SE) at study entry was 1,257 (75) micrograms which was reduced by 323 (66) micrograms during the run-in period without loss of symptomatic control. A further 416 (57) micrograms reduction in inhaled corticosteroid dosage was possible during the treatment phase but this was almost identical in the WEB 2086 and placebo-treated groups, amounting to 353 (92) and 481 (65) micrograms/day respectively (not significant [NS]). Rate of relapse following corticosteroid reduction was a continuous variable and relapse occurred at different times depending on the variable used to define it. Time to relapse measured by an increase in symptoms correlated with disease duration (r = 0.41, p < 0.01) and with the dose of inhaled corticosteroid at study entry (r = 0.36, p < 0.01) but no other measured variable predicted the time to relapse. (ABSTRACT TRUNCATED AT 250 WORDS)
Water Reclamation and Reuse

A review of the literature published in 2015 on topics relating to water reclamation and reuse is presented. The review is divided into the following sections: (1) General: extent of reuse, research needs, guidelines and monitoring, health effects; (2) Treatment technologies: integrated process design, membrane treatment, membrane bioreactors, electrocoagulation, ion exchange and adsorption, disinfection, wetlands, managed aquifer recharge; (3) Planning and management: public acceptance and education, economics/pricing, water quality planning and management and project/case studies. Much of the water treatment research focuses on membrane treatment, integrated designs, and other innovative technologies.
Parkinson's Disease and Restless Legs Syndrome

Aims: Various sleep-related complications are common in Parkinson's disease (PD). The prevalence of restless legs syndrome (RLS) and its association with other symptoms were studied. Methods: Altogether, 1,447 Parkinson patients, aged 43-89, participated in a questionnaire study. Results: The response rate was 59.0% and of these, 68% returned fully answered questionnaires (n = 577). RLS occurred in 20.3% of the PD subjects. In patients with RLS, the symptoms occurred in 81.9% at least once weekly. The degree of severity was moderate in 42.7%, severe in 23.9% and very severe in 15.4%. Daytime sleepiness, fatigue, chronic insomnia, sleep maintenance insomnia, intense dreaming, and low quality of life were more common in patients with RLS than in patients without RLS. The occurrence of early onset RLS (onset ≤ age of 45 years) was 4.2%. The occurrences of late onset (>45 years) drug naïve RLS and late onset RLS (with dopaminergic medication) were 5.4 and 10.4%, respectively. Conclusion: In patients with PD, the early onset of RLS resembles idiopathic RLS with typical gender distribution and familial trait. Late onset of RLS is more common than idiopathic RLS.
Patients with active relapsing‐remitting multiple sclerosis synthesize antibodies recognizing oligodendrocyte progenitor cell surface protein: Implications for remyelination

In multiple sclerosis (MS), remyelination of demyelinated lesions diminishes with disease progression for unknown reasons. Oligodendrocyte progenitor cells contribute to remyelination; however, antibodies specific for oligodendrocyte progenitor antigens could block remyelination by eliminating or impeding these cells. In myelinating cultures, cell lysis with antibody recognizing a progenitor cell–specific surface glycoprotein (AN2) suppressed the synthesis of myelin proteins. Cerebrospinal fluid from patients with relapsing‐remitting active MS contains antibodies against AN2, whereas cerebrospinal fluid from patients with nonactive disease does not. This is the first report describing antibodies in MS against a progenitor cell–specific antigen that may contribute to the development and progression of chronically demyelinated lesions. Ann Neurol 2000;48:362–371
Protein flexibility is key to cisplatin crosslinking in calmodulin

Chemical crosslinking in combination with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) has significant potential for studying protein structures and protein–protein interactions. Previously, cisplatin has been shown to be a crosslinker and crosslinks multiple methionine (Met) residues in apo‐calmodulin (apo‐CaM). However, the inter‐residue distances obtained from nuclear magnetic resonance structures are inconsistent with the measured distance constraints by crosslinking. Met residues lie too far apart to be crosslinked by cisplatin. Here, by combining FTICR MS with a novel computational flexibility analysis, the flexible nature of the CaM structure is found to be key to cisplatin crosslinking in CaM. It is found that the side chains of Met residues can be brought together by flexible motions in both apo‐CaM and calcium‐bound CaM (Ca4‐CaM). The possibility of cisplatin crosslinking Ca4‐CaM is then confirmed by MS data. Therefore, flexibility analysis as a fast and low‐cost computational method can be a useful tool for predicting crosslinking pairs in protein crosslinking analysis and facilitating MS data analysis. Finally, flexibility analysis also indicates that the crosslinking of platinum to pairs of Met residues will effectively close the nonpolar groove and thus will likely interfere with the binding of CaM to its protein targets, as was proved by comparing assays for cisplatin‐modified/unmodified CaM binding to melittin. Collectively, these results suggest that cisplatin crosslinking of apo‐CaM or Ca4‐CaM can inhibit the ability of CaM to recognize its target proteins, which may have important implications for understanding the mechanism of tumor resistance to platinum anticancer drugs.
Trafficking in women: Moldova and Ukraine.

This paper documents the findings of a research study commissioned by the Minnesota Advocates for Human Rights on the problem of trafficking in women in Ukraine and the Republic of Moldova in 2000. The study found that it is a serious problem and is increasing; that it is a complicated phenomenon with many forces impacting womens decisions to work abroad; and that the current laws are not sufficient. A list of recommendations is included.
Why are rods more sensitive than cones?

One hundred and fifty years ago Max Schultze first proposed the duplex theory of vision, that vertebrate eyes have two types of photoreceptor cells with differing sensitivity: rods for dim light and cones for bright light and colour detection. We now know that this division is fundamental not only to the photoreceptors themselves but to the whole of retinal and visual processing. But why are rods more sensitive, and how did the duplex retina first evolve? Cells resembling cones are very old, first appearing among cnidarians; the emergence of rods was a key step in the evolution of the vertebrate eye. Many transduction proteins have different isoforms in rods and cones, and others are expressed at different levels. Moreover rods and cones have a different anatomy, with only rods containing membranous discs enclosed by the plasma membrane. These differences must be responsible for the difference in absolute sensitivity, but which are essential? Recent research particularly expressing cone proteins in rods or changing the level of expression seem to show that many of the molecular differences in the activation and decay of the response may have each made a small contribution as evolution proceeded stepwise with incremental increases in sensitivity. Rod outer‐segment discs were not essential and developed after single‐photon detection. These experiments collectively provide a new understanding of the two kinds of photoreceptors and help to explain how gene duplication and the formation of rod‐specific proteins produced the duplex retina, which has remained remarkably constant in physiology from amphibians to man.
Second-generation method for analysis of chromatin binding with formaldehyde–cross-linking kinetics

Formaldehyde-cross-linking underpins many of the most commonly used experimental approaches in the chromatin field, especially in capturing site-specific protein–DNA interactions. Extending such assays to assess the stability and binding kinetics of protein–DNA interactions is more challenging, requiring absolute measurements with a relatively high degree of physical precision. We previously described an experimental framework called the cross-linking kinetics (CLK) assay, which uses time-dependent formaldehyde–cross-linking data to extract kinetic parameters of chromatin binding. Many aspects of formaldehyde behavior in cells are unknown or undocumented, however, and could potentially affect CLK data analyses. Here, we report biochemical results that better define the properties of formaldehyde–cross-linking in budding yeast cells. These results have the potential to inform interpretations of “standard” chromatin assays, including chromatin immunoprecipitation. Moreover, the chemical complexity we uncovered resulted in the development of an improved method for measuring binding kinetics with the CLK approach. Optimum conditions included an increased formaldehyde concentration and more robust glycine-quench conditions. Notably, we observed that formaldehyde–cross-linking rates can vary dramatically for different protein–DNA interactions in vivo. Some interactions were cross-linked much faster than the in vivo macromolecular interactions, making them suitable for kinetic analysis. For other interactions, we found the cross-linking reaction occurred on the same time scale or slower than binding dynamics; for these interactions, it was sometimes possible to compute the in vivo equilibrium-binding constant but not binding on- and off-rates. This improved method yields more accurate in vivo binding kinetics estimates on the minute time scale.
Changes in cartilage composition and physical properties due to stromelysin degradation.

OBJECTIVE To determine the effects of stromelysin treatment on biochemical, histologic, and swelling characteristics of intact cartilage explants and to correlate these effects with changes in the functional physical properties of the tissue. METHODS Bovine articular cartilage explants were cultured for up to 3 days in the presence or absence of recombinant human stromelysin (SLN). Damage to matrix proteoglycans and collagens was assessed and characterized by N-terminal sequencing and Western blot analysis, respectively. Explants were mechanically tested to assess the ability of the tissue to withstand cyclic and static compressive loads. RESULTS Treatment with SLN resulted in a time- and dose-dependent loss of proteoglycans from cartilage explants, with significant loss seen after 3 days of exposure to 20 nM SLN: Histology indicated that initial loss of proteoglycans occurred in regions near the tissue surface and proceeded inward with increasing time of SLN exposure. SLN treatment resulted in degradation of matrix collagen types IX and II, and a concomitant increase in tissue swelling. This matrix degradation resulted in severe alterations in functional physical properties of the tissue, including compressive stiffness. The initial, focal loss of proteoglycans that resulted from SLN treatment was most accurately detected with high-frequency streaming potential measurements. CONCLUSION Exposure of intact cartilage to SLN caused specific, molecular-level degradation of matrix molecules, which resulted in changes in the swelling behavior and marked deterioration of functional physical properties of the tissue.
Self-induction by erythromycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450.

Erythromycin, 0.3 mM, elicited a small reverse type I binding spectrum with, and was slowly demethylated by, cytochrome P-450 from control rats. No absorption peak at 456 nm could be detected upon incubation of 0.3 mM erythromycin with NADPH and control microsomes. No complex formed in vivo could be detected in microsomes isolated 2 hr after a single dose of erythromycin, 2 mmol.kg-1 p.o. Repeated administration of erythromycin, 2 mmol.kg-1 p.o. daily for 4 days increased hepatic microsomal protein concentration, NADPH-cytochrome c reductase activity, the amplitude of the reverse type I binding spectrum of erythromycin and erythromycin demethylase activity. Microsomes isolated from rats treated with repeated doses of erythromycin exhibited a marked absorption peak at 456 nm. The absorption at 456 nm was further increased upon incubation with erythromycin and NADPH. It disappeared upon addition of 50 muM potassium ferricyanide. Disruption of the complex with potassium ferricyanide markedly increased the CO-binding capacity of dithionite-reduced microsomes. It further increased the amplitude of the reverse type I binding spectrum of erythromycin and erythromycin demethylase activity and increased ethylmorphine N-demethylase and benzo[a]pyrene hydroxylase activities. It is concluded that erythromycin induces its own transformation into a metabolite which forms a inactive 456-nm absorbing complex with the iron (II) of cytochrome P-450.
Anterior Lumbar Interbody Fusion for Treatment of Failed Back Surgery Syndrome: An Outcome Analysis

OBJECTIVEAnterior lumbar interbody fusion (ALIF) has gained popularity for the treatment of degenerative disease of the lumbar spine. In this report, we present our experience with the ALIF procedure for treatment of failed back surgery syndrome (FBSS) in a noncontrolled prospective cohort. METHODSIn a 2-year period, we treated patients diagnosed with FBSS with ALIF. Clinical and radiological outcomes were recorded in a prospective, nonrandomized, longitudinal manner. Neurological, pain, and functional outcomes were measured preoperatively and 12 months after surgery. Operative data, perioperative complications, and radiological and clinical outcomes were recorded. RESULTSThirty-three patients with a preoperative diagnosis of FBSS, with degenerative disc disease (n = 17), postsurgical spondylolisthesis (n = 13), or pseudarthrosis (n = 3), underwent ALIF. Back pain, leg pain, and functional status improved significantly, by 76% (P < 0.01), 80% (P < 0.01), and 67% (P < 0.01), respectively. CONCLUSIONOn the basis of our results, we found ALIF to be a safe and effective procedure for the treatment of FBSS for selected patients.
The relation between foreign direct investments and some economic indicators. The case of Romanian economy

Foreign direct investments (FDI) are a force that shapes the world economy. Stocks and flows of FDI (inward and outward) are indicators followed with great attention by national and international entities and they are correlated with other macroeconomic indicators to detect trends at regional, national and international levels and to determine the degree of development of a country. The dramatically changes that occurred in world economy in the last 30 years have generated major changes on the motivations of foreign investors, the emergence of new types of economic agents that generate foreign direct investments and new international regulations regarding FDI. In this article, the authors analyzed the relations between FDI, import, export and GDP for Romania economy for the period 1990-2014. The research methodology applied is based on the Augmented Dickey-Fuller statistic test and the Granger causality test, the datasets for the variables included in the study have been drawn from official data sources, the UNCTAD database and the National Statistics Institute of Romania’s database (TEMPO). To present their results, the authors have used graphical and table-based instruments, which provides better understanding of the research outputs. Also, the study is placed within the context and historical landmarks of the Romanian economy, the results and conclusions emphasize the effects of certain actions and events on the indicators and correlations analyzed.
Measuring Social Capital in Adult Education Projects

This theoretical research analyzes the measurement of social capital in adult education and community development projects that seek to strengthen democratic processes and develop local leadership. It analyzes two different methodologies—in depth interviews and Web-based questionnaires—used to measure social capital. Introduction This theoretical research analyzes the measurement of social capital in adult education and community development projects that seek to strengthen democratic processes and develop local leadership. While most of the intellectual discussion and case study research into social capital is occurring in the fields of community development, sociology, and political science, there is growing awareness of social capital’s importance within adult education (Waites, 2005; Zacharakis & Flora, 2005). Conceptually, understanding and defining social capital is relatively straightforward. Measuring social capital is far more complex and requires creative latitude that reflects the community or organization you are working with rather than a set of rigid rules that are applied to all situations. This research reports on an analysis of two different methodologies—in-depth interviews and Web-based questionnaires—used to measure social capital. The theoretical void in adult education is the problem of measuring project impact and success. Social capital measurement allows the adult educator or community developer to identify barriers that limit the development of new leadership, and thereby develop strategies that encourage participation by new leadership. If strengthening social capital is a barometer of project success, then the question is “How do we measure social capital? ” This paper is divided into three parts: (a) defining social capital relative to the adult education project of building community, (b) case-study literature on measuring social capital, and (c) an analysis to two methodologies to measure social capital used independently in two projects directed by the author. This research on analyzing these two methodologies is new. Social capital is defined (The World Bank, n.d.) by communication and collective action within groups, organizations, or communities. It is based on trust, networks, and shared interests and values. Social capital can be invested and reinvested in the same way that financial, human, physical, and environmental capitals are invested. And social capital is inherently connected to these other forms of capital. For example, it is difficult to imagine how financial or environmental capital can grow without strong social capital. It takes time to develop social capital, yet it can be destroyed relatively quickly (Flora, 1997). While the assumption is that communities and organizations should strive to develop strong social capital, strong social capital can be either positive or negative (Zacharakis & Flora, 2005). Weak social capital is usually considered to be negative and strong social capital is usually positive, yet when social capital is too strong it can have a negative impact on a project.