Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific inhibitors of the protein tyrosine phosphatase Shp2 identified by high-throughput docking

The protein tyrosine phosphatase Shp2 is a positive regulator of growth factor signaling. Gain-of-function mutations in several types of leukemia define Shp2 as a bona fide oncogene. We performed a high-throughput in silico screen for small-molecular-weight compounds that bind the catalytic site of Shp2. We have identified the phenylhydrazonopyrazolone sulfonate PHPS1 as a potent and cell-permeable inhibitor, which is specific for Shp2 over the closely related tyrosine phosphatases Shp1 and PTP1B. PHPS1 inhibits Shp2-dependent cellular events such as hepatocyte growth factor/scatter factor (HGF/SF)-induced epithelial cell scattering and branching morphogenesis. PHPS1 also blocks Shp2-dependent downstream signaling, namely HGF/SF-induced sustained phosphorylation of the Erk1/2 MAP kinases and dephosphorylation of paxillin. Furthermore, PHPS1 efficiently inhibits activation of Erk1/2 by the leukemia-associated Shp2 mutant, Shp2-E76K, and blocks the anchorage-independent growth of a variety of human tumor cell lines. The PHPS compound class is therefore suitable for further development of therapeutics for the treatment of Shp2-dependent diseases.
Validation of several types of noxious stimuli for use in determining the minimum alveolar concentration for inhalation anesthetics in dogs and rabbits.

OBJECTIVE To compare 3 types of noxious stimuli applied to various anatomic areas of anesthetized dogs and rabbits for determination of the minimum alveolar concentration (MAC). ANIMALS 10 dogs and 10 rabbits. PROCEDURE Dogs were anesthetized with isoflurane and halothane in a randomized order. Rabbits were anesthetized with isoflurane. The MAC was determined by skin incision on the lateral aspect of the chest; clamping of the tail, paw of the forelimb, and paw of the hind limb; and application of electrical current to the oral mucosa (dogs only), forelimb, and hind limb. The MAC was the end-tidal concentration midway between the value permitting and preventing purposeful movement in response to noxious stimuli. RESULTS In dogs, mean +/- SEM MAC for isoflurane was 1.27 +/- 0.05% for clamping stimuli, 1.36 +/- 0.04% for oral electrical stimulation, 1.35 +/- 0.04% for electrical stimulation to the limbs, and 1.01 +/- 0.07% for surgical incision. The MAC for halothane was 0.97 +/- 0.03% for tail clamping, 0.96 +/- 0.03% for clamping of the limbs, 1.04 +/- 0.03% for electrical stimulation, and 0.75 +/- 0.06% for surgical incision. In rabbits, MAC for isoflurane was 2.08 +/- 0.02% for clamping stimuli, 2.04 +/- 0.02% for electrical stimulation, and 0.90 +/- 0.02% for surgical incision. The MAC for surgical incision was significantly lower than values for the other methods in both species. CONCLUSIONS AND CLINICAL RELEVANCE Use of electrical current and clamping techniques resulted in similar MAC values. Surgical incision underestimated MAC values in dogs and rabbits.
Token Economies and Experimental Economics

The purpose of this note is to extend the discussion begun by Castro and Weingarten (1970) in this Journal on the application of experimental techniques to the study of economic behavior. I report the development of special economic systems for human populations, called token economies, that provide potential laboratories for economic experiments. ' The results of experiments already conducted in these economies show that changes in wages and prices on job selection and consumption patterns are, in general, in agreement with economic theory. Further, the application of designed experiments to token economies avoids most of the problems currently encountered in dealing with human subjects. A brief description of token economies and summaries of several experiments of particular interest to economists follow. I conclude with a discussion of the advantages and potentialities of designed experimentation in token economies.
Preexposure prophylaxis for men who have sex with men and transgender persons in early adopting countries: a narrative review.

: Pre-exposure prophylaxis (PrEP) is a potent and underutilized HIV prevention tool. In this paper we review the state of knowledge regarding PrEP implementation for men who have sex with men and transgender persons in early adopting countries. We focus on implementation of PrEP in demonstration projects and clinical care, and describe the status of PrEP availability and uptake. We report on approaches to identifying appropriate PrEP candidates in real-world settings and on best practices for clinical monitoring. This includes the exclusion of undiagnosed HIV infection prior to PrEP initiation and longitudinal measurement of renal function, in light of safety data. Since adherence is the primary factor moderating the effectiveness of PrEP, we discuss effective adherence support interventions. Additionally, we review the evidence for risk compensation with PrEP use and opportunities to provide PrEP as part of comprehensive and inclusive preventive health programs. We summarize cost-effectiveness studies, including their variable conclusions because of differing underlying assumptions, and discuss the importance of budgetary impact for public health programs and health care insurers. Further, we emphasize a need for greater engagement of health care providers in PrEP to increase access. We conclude with recommendations for ways to improve future efforts at implementing PrEP.
What Determines EU Decision Making? Needs, Power or Both?

type="main" xml:lang="en"> This paper examines the determinants of power in the Council of the European Union. It argues that quantitative power indices stemming from voting theory provide a good description of the actual distribution of power among EU members. Of course, we cannot directly verify the accuracy of such indices since it is impossible to measure power directly. Instead, we evaluate whether these power measures explain a quantifiable manifestation of the exercise of power, namely members’ shares of EU budget allocation. As an alternative explanation of the EU budget, we also consider a ‘needs view’ of the budget, where members’ allocations are determined by principles of solidarity. Our empirical analysis is based on 1976–2001 data on the patterns of the EU budget shares and on measures of each member state's needs and political power. Our results indicate that at least 60% of the budget expenditures can be attributed to selfish power politics and the remaining 40% to the declared benevolent EU budget policies. However, when we apply specific voting power measures that allow correlated preferences and cooperative voting patterns between the member states, our estimates indicate that the power politics view can explain as much as 90% of the budget shares. We conclude that power politics can explain a major part of the Council decisions and that correlated preferences and voting cooperation between EU countries potentially play significant roles in EU decision making. — Heikki Kauppi and Mika Widgren
Response Variability in Commercial MOSFET SEE Qualification

Single-event effects (SEE) evaluation of five different part types of next generation, commercial trench MOSFETs indicates large part-to-part variation in determining a safe operating area (SOA) for drain-source voltage ( $\text {V}_{\mathrm { {DS}}}$ ) following a test campaign that exposed >50 samples per part type to heavy ions. These results suggest a determination of a SOA using small sample sizes may fail to capture the full extent of the part-to-part variability. An example method is discussed for establishing a Safe Operating Area using a one-sided statistical tolerance limit based on the number of test samples. Burn-in is shown to be a critical factor in reducing part-to-part variation in part response. Implications for radiation qualification requirements are also explored.
Building a sense of home in rented spaces

Purpose – Much of the research into the development of home within the business literature has looked at home as a setting or a construct instead of as a process. Additionally, extant research has explored the process of homebuilding within the context of homeownership, often defining home in terms of a place that is owned by the individual living in it. However, nearly 30 percent of all housing units in which people live are rented spaces that are owned by others not living there. The purpose of this paper is to examine homebuilding as a process that can and often does occur in properties that the individual does not own.Design/methodology/approach – Using a phenomenological approach, in‐depth interviews with renters lead to the development of a conceptual model of how renters build a sense of “home. ”Findings – The paper finds that though ownership does play a part in some individuals' sense of home, apartment dwellers often are able to build a “home” within an apartment context.Research limitations/impl.
Corporate Governance, Auditing, and Reporting Distortions

Conventional wisdom suggests that independent boards limit earnings distortions and promote accurate reporting. In contrast, this study indicates that having insiders on boards enhances reporting integrity. The central result is that strengthening board independence curtails earnings overstatements but heightens the likelihood of understatements. This asymmetry occurs because reinforcing board independence on one hand limits the CEO’s ability to overreport but on the other hand encourages the auditor to rely on the board’s monitoring and consequently economize on effort. The reduced effort impairs the auditor’s ability to verify high earnings and, because auditors favor conservative reports when in doubt, leads to increased incidence of conservative understatements.
[Color pattern reversal visual evoked potentials in primary open angle and angle closure glaucoma].

OBJECTIVE To investigate the difference in color pattern reversal visual evoked potential (CPR-VEP)between primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) patients. METHODS Vision Monitor visual electrophysiograph made by Metro Vision Inc. in France was used to record CPR-VEP in 17 eyes of 12 POAG patients, 56 eyes of 41 PACG patients, and 26 eyes of 13 age-equivalent normal persons at an ascending series of temporal frequency (1, 2, 4, 8, 16, and 32 Hz) and color stimulation (black/white, red/green, and blue/yellow). P(100) wave amplitudes and latencies of these patients were compared respectively with those of the normal group. RESULTS With black/white stimulation, the P(100) wave amplitudes were reduced with the increase of temporal frequency in the 3 groups. The P(100) wave latencies were extended with the increase of temporal frequency with different color stimulations. The P(100) amplitudes were PACG group > NC group > POAG group and black/white > blue/yellow > red/green. The P(100) wave latencies in the POAG group and the PACG group were extended compared with the NC group, but there was no significant difference between PACG group and POAG group. CONCLUSION CPR-VEP P(100) amplitudes in the PACG group and POAG group have their own characteristics. The P(100) amplitude of PACG is higher, and POAG is lower than normal. The P(100) wave latencies of PACG and POAG are extended.
The determinates of equity portfolio holdings

The investor preference for home assets rather than a diversified portfolio of international assets termed ‘home bias’ remains a puzzle, given recent information and technology improvements, although presumed risk reduction benefits may have been reduced through improved financial market integration. This article investigates the effect of various barriers to international investment on Australian equity portfolio investment and confirms the common view that higher transaction costs impede international investment, although market liquidity, market size and common language are also important factors.
India's Ecocity? Environment, Urbanisation, and Mobility in the Making of Lavasa

In a context of rapid urbanisation in the Global South the potential of ecocities to provide sustainable development is hotly debated within academic and policy circles. This paper will contribute to this debate by referring to Lavasa, India's largest planned ‘hill city’, a fifth of the size of Mumbai. Mentioned in the influential McKinsey report as an emerging global city, Lavasa, the first ‘sustainable’ city developed in the Mumbai—Pune region, attempts to deal with urbanisation, environment, and migration in very particular ways. Yet, it has been riddled with controversies since its inception, and construction has been interrupted by the courts a number of times for alleged environmental violations. Using Lavasa as an example, I will examine the rise and rise of ecocities in India through their legal and policy context. I will argue that future ecocities in India run the danger of prioritising economic development over environmental sustainability in the absence of strong legal enforcement and monitoring of environmental performance. I conclude that strong environmental policy framing and regulation are crucial in this context if new planned cities in India are to have any potential in addressing the challenges of rapid urbanisation and sustainable development.
Distribution of toxic chemicals in particles of various sizes from mainstream cigarette smoke

Abstract To accurately estimate the risk of inhaling cigarette smoke containing toxic chemicals, it is important that the distribution of these chemicals is accurately measured in cigarette smoke aerosol particles of various sizes. In this study, a single-channel smoking machine was directly coupled to an electrical low-pressure impactor. The particles of mainstream cigarette smoke were collected using 12 polyester films, and the particulate matter (PM) was characterized. Nicotine, tobacco-specific N-nitrosamines (TSNAs, including NNN, NAT, NAB, and NNK), polycyclic aromatic hydrocarbons (PAHs, including benzo(a)pyrene (BaP), benzo(a)anthracene, and chrysene), and heavy metals (including Cr, As, Cd, and Pb) present in the particles of different sizes were analyzed by GC, HPLC-MS/MS, GC/MS, or ICP-MS, respectively. The results demonstrated that the nicotine, TSNAs, PAHs, and heavy metals in mainstream cigarette smoke were dispersed over a particle size ranging from 0.1 μm to 2.0 μm, and the concentration of these toxic chemicals initially increased and then decreased the particle size grew. The distribution of nicotine was uniform for the PM in the size ranges of less than 0.1 μm, 0.1–1.0 μm, and 1.0–2.0 μm, TSNAs and heavy metals in particles of less 0.1 μm were more abundant, and PAHs in fine particles were also more abundant.
MEDS and PocR are novel domains with a predicted role in sensing simple hydrocarbon derivatives in prokaryotic signal transduction systems

UNLABELLED We identify two conserved domains in diverse bacterial and archaeal signaling proteins. One of them, the MEDS domain, is typified by the DmcR protein from Methylococcus and the other by the PocR protein of Salmonella typhi. We provide evidence that both these domains are likely to sense simple hydrocarbon derivatives and transduce downstream signals on binding these ligands. The PocR ligand-binding domain is shown to contain a novel variant of the fold found in PAS and GAF domains. The MEDS domain is present in both methylotrophs and complex methanogens, and both the MEDS and PocR domains show a lineage-specific expansion in the latter organisms, suggesting a role in sensing their principle growth substrates. The MEDS domain is also found in the negative regulators of the sigma factor SigB in actinomycetes, including pathogens like Mycobacterium tuberculosis. Hence it is possible that these sigma factors, involved in aerial mycelium development and stress response in the actinomycetes, might be under the regulation of as yet uncharacterized small molecules. CONTACT aravind@ncbi.nlm. nih.gov.
Middle managers' role in transferring person-centered management and care

This paper presents a study of the role of middle managers in the knowledge transfer related to a person-centered management and care approach at a physical rehabilitation center. This qualitative research comprises a multi-case study, representing the six middle managers of the organization studied. The main findings generated by this research indicate that despite top management's efforts to disseminate a person-centered approach throughout the organization, the knowledge transfer process mainly depends on the absorptive capacity of middle managers. When middle managers have the capacity to absorb the person-centered approach, often because it is compatible with their values and current practices, this capacity is expressed mainly through their behavioral exemplarity. The results of the study also engender an intervention model illustrating the key role of middle managers in the transfer of a person-centered management and care approach. The model includes macro- and micro-contextual elements that facilitate the transfer.
The diagnostic and research applications of flow cytometry in cytopathology

Flow cytometry (FCM) is an established ancillary technique applied to the diagnosis of hematological malignancies and for measurement of DNA content. In recent years, the number of fluorochrome‐conjugated antibodies available for immnuofluorescence and FCM has greatly increased, making it possible to evaluate this technique in other diagnostic contexts, as well as to study a range of biological processes. Serous effusions are optimal for studies using FCM as they consist of viable cells in suspension. Molecules that have been studied for their expression and clinical role in effusions in recent years participate in central cellular functions, including adhesion, proliferation, cellular metabolism, and apoptosis, as well as intracellular signaling. FCM can further be applied to quantitative analysis of molecules related to chemotherapy response, which, together with apoptosis, may represent an important tool for evaluating treatment response and prognosis in advanced and/or recurrent cancer. As targeted therapy assumes an ever‐growing role in the treatment of metastatic cancer, the ability to study living cells in effusions or fine‐needle aspirates is becoming more important. This article reviews the currently available data in this area of cytopathology. Diagn. Cytopathol. 2012;40:525–535. © 2012 Wiley Periodicals, Inc.
Impact of the Ottawa Decision Support Framework on the Agreement and the Difference between Patients' and Physicians' Decisional Conflict

Background. The Ottawa Decision Support Framework (ODSF) provides a process that facilitates shared decision making. Objective. To assess the impact of implementing the ODSF on the agreement and the difference between patients' and physicians' decisional conflict scores. Design. In total, 120 physicians and 903 patients enrolled in this before-and-after study. Implementation of the ODSF was composed of an interactive workshop, feedback, and a reminder at the point of care. The Decisional Conflict Scale (DCS) was completed by physicians and patients after a clinical encounter. Results. The intraclass correlation coefficient was–0.205 ± 0.096 (95% confidence interval [CI]= – 0.224 to –0.186) before implementing the ODSF and– 0.013 ± 0.114 (95% CI = – 0.036 to 0.009) after. At the patient level, the following factors were significantly associated with the difference between the patients' and physicians' DCS: unemployed (P = 0.023), implementing the ODSF (P = 0.008), high school degree (P = 0.04), male (P = 0.03), and unilateral role in decision making (P = 0.03). At the physician level, provincial committee (P = 0.001), national committee (P = 0.045), clinical site (P = 0.016), reluctance to share uncertainty (P = 0.023), and anxiety due to uncertainty (P = 0.017) were significantly associated with this outcome. Conclusion. After implementing the ODSF, there was less dissimilarity between patients' and physicians' DSC than expected by chance than before. Implementing the ODSF was also found to be associated with the difference between patients' and physicians' DSC. The physician level explained a significant amount of the variance in this outcome, thus emphasizing the importance of an intervention at this level.
Modulation of ‘A’-type K+ current by rodent and human forms of amyloid &bgr; protein

The Alzheimer's disease related peptide amyloid &bgr; (A&bgr;) might have a physiological role in upregulating K+ channel currents in neurones. Earlier studies used the human form of A&bgr;1−40 on rat neurones. We sought to confirm our hypothesis by use of rat A&bgr;, which has no Alzheimer's association. In rat cerebellar granule neurones and HEK293 cells expressing Kv4.2 subunits, whole-cell patch clamp of K+ currents revealed that preincubation of cells with recombinant human or rat A&bgr;1−40 (10 nM for 24 h) significantly increased K+ channel current density. This was accompanied by increased mRNA levels for Kv4.2. These data indicate that rodent and human A&bgr; are effective in modulating K+ currents. The effectiveness of nonaggregating rat A&bgr; also strongly supports a physiological role for the peptide.
Insider Trading in Credit Derivatives

Insider trading in the credit derivatives market has become a significant concern for regulators and participants. This paper attempts to quantify the problem. Using news reflected in the stock market as a benchmark for public information, we report evidence of significant incremental information revelation in the credit default swap (CDS) market under circumstances consistent with the use of non-public information by informed banks. Specifically, the information revelation occurs only for negative credit news and for entities that subsequently experience adverse shocks. Moreover the degree of advance information revelation increases with the number of banks that have lending/monitoring relations with a given firm, and this effect is robust to controls for non-informational trade. We find no evidence, however, that the degree of asymmetric information adversely affects prices or liquidity in either the equity or credit markets. If anything, with regard to liquidity, the reverse appears to be true.
Social Capital in Voluntary Associations

ABSTRACT Associations are likely to recruit resource rich individuals and they are places where individuals interact, and thus, are likely to exchange social resources. The paper asks which kinds of associations embed individuals holding many social resources. According to theoretical considerations, I distinguish between bridging and bonding associations. Bridging associations are likely to embed heterogeneous individuals while bonding associations embed homogeneous individuals. Therefore, the range of social resources available inside associations may be higher in bridging than in bonding associations. Thinking about the resource exchanging environment inside the associations, a further distinction of bonding associations seems reasonable: some aim at political goals outside the group (e.g., trade unions or professional organizations) and others focus on developing a nice atmosphere inside the group (apolitical bonding associations like elderly leisure associations). I analyze data from Eurobarometer 62.2 using multilevel analyses. Descriptive analyses indicate that active individuals have access to more social resources than inactive individuals. This relation varies for apolitical and political bonding associations according to the European countries. The multilevel analyses controlling for individual characteristics and country variables indicate that potential resources accessible to individuals active in associations depend on the focus of the associations. While bridging and apolitical bonding associations embed individuals accessing more social resources than non-active individuals, political bonding associations are not likely to embed resource rich individuals.