Miracle-dz/UniFAR-FTUs huggingface dataset:
MECHANISMS OF THROMBOTIC MICROANGIOPATHY FOLLOWING XENOGENEIC HEMATOPOIETIC PROGENITOR CELL TRANSPLANTATION1

Introduction. Attempts to induce tolerance though mixed hematopoietic chimerism in the discordant pig-to-baboon xenotransplantation model are sometimes complicated by a potentially fatal thrombotic microangiopathy in the recipient baboons. This state develops immediately after the infusion of porcine mobilized peripheral blood leukocytes, containing progenitor cells (PBPC). In our study, we examined the interaction of infused porcine PBPC with recipient platelets in vivo in baboons and investigated the underlying mechanisms using an in vitro model. Methods. Two naïve baboons and six baboons preconditioned with irradiation and immunosuppression that received porcine PBPC were evaluated in vivo. The interaction of porcine and baboon PBPC with baboon platelets was investigated by an in vitro platelet aggregation assay. Fresh and cryopreserved PBPC were evaluated as well as PBPC obtained from growth-factor mobilized and unmobilized pigs. Furthermore, cellular subsets of PBPC were assessed for potential to induce platelet aggregation. Immunohistochemical staining was performed on platelet-leukocyte aggregates and potential inhibition of aggregation with anti-P-selectin and anti-CD154 mAbs, or eptifibatide (a GPIIb/IIIa receptor antagonist), was tested. Results. All baboons that received porcine PBPC rapidly developed marked thrombocytopenia (<20,000/&mgr;l), elevated serum lactate dehydrogenase (>1,500U/liter), schistocytosis, and platelet aggregates on blood smear. Three baboons died (two untreated and one preconditioned), and substantive platelet aggregates containing porcine leukocytes were observed in the microvasculature of lungs and kidneys. In vitro, porcine, but not baboon, PBPC induced aggregation of baboon platelets in a dose-dependent manner. Immunohistological examination of these aggregates confirmed the incorporation of porcine leukocytes. Cryopreserved PBPC caused less aggregation than fresh PBPC, and growth-factor-mobilized PBPC induced less aggregation than unmobilized PBPC. Aggregation was fully abrogated by the addition of eptifibatide, and modulated by anti-P-selectin and anti-CD154 monoclonal antibodies that recognize adhesion receptors on activated platelets. Purified fractions (granulocytes, CD2+, and CD− cells) of porcine PBPC did not initiate aggregation, whereas addition of exogenous porcine PBPC membranes (erythrocytes, dead cells, and/or platelets) to the purified fractions exacerbated the aggregation response. Conclusions. These data indicate that porcine PBPC mediate aggregation of baboon platelets. This process likely contributes to the thrombotic microangiopathy observed after PBPC transplantation in the pig-to-baboon model. Eptifibatide can fully abrogate platelet aggregation induced by porcine PBPC in vitro. Purification of the progenitor cells from porcine PBPC and/or treatment of baboons with eptifibatide may be beneficial.
Controlling for Compromise Effects Debiases Estimates of Preference Parameters

The compromise effect - a tendency to choose options close to the “middle” of a choice - has been shown to confound measurement of preferences. In an experiment with 550 participants, we study risk preferences elicited with Multiple Price Lists. Following prior work, we manipulate the compromise effect by varying the middle options of each Multiple Price List and find that measured risk-preference estimates are sensitive to this change in the choice set. To eliminate this bias, we incorporate context effects directly into a structural econometric model. We show that this method generates robust estimates of preference parameters.
Role of the cAMP‐dependent protein kinase and protein kinase C in regulating the morphological differentiation of PC12 cells

The cell line A126‐1B2 is a PC12‐derived mutant that is resistance to the toxic effects of dibutyryladenosine 3′:5′‐cyclic monophosphate (dbcAMP) and is deficient in adenosine 3′:5′‐cyclic monophosphate (cAMP)‐dependent protein kinase II (PKAII). This mutant formed neurites in response to nerve growth factor (NGF), but not in response to dbcAMP; and dbcAMP did not increase the rate of NGF‐dependent neurite formation. Thus, while PKAII is essential for process formation in response to agentsw that act through the cAMP‐dependent pathway, activation of PKAII is not essential for NGF‐dependent neurite formation. Unexpectedaly, NGF and phorbol 12‐myristate 13‐acetate (PMA; 10–1,000 nm) synergistically stimulated the formation of shortprocesses that were apparent within 30 min of NGF addition in 85% of these mutant dells. These processes were similar, but not identical, in appearance to the NGF‐dependent neurites that formed only after a period of 24–48 hr. This effect is dependent on the activation of protein kinase C (PKC) because an inactive phorbol ester was without effect. In contrast, therewas only a small effect of NGF and/or PMA on process formation in wiod type cells within the first few hours. The effect of PMA is not augmented by dbcAMP in the A126‐1B2 mutant cells. After several hours, PMA caused a concentration‐dependent decrease in cell adhesion; and higher concetrations of PMA resulted in a transient detachment of the cells and a loss of neurites. These experiments suggest a role for PKC in the regulation of process formation.
T‐cell regulation of neutrophil infiltrate at the early stages of a murine colitis model

Background: T‐cells are a main target for antiinflammatory drugs in inflammatory bowel disease. As the innate immune system is also implicated in the pathogenesis of these diseases, T‐cell suppressors may not only inhibit T‐cell‐dependent production of proinflammatory mediators but also affect innate immune cell function. Specifically, these drugs may impair innate immune cell recruitment and activation through inhibition of T‐cells or act independent of T‐cell modulation. We explored the extent of immune modulation by the T‐cell inhibitor tacrolimus in a murine colitis model. Methods: We assessed the effects of tacrolimus on trinitro‐benzene sulphonic acid (TNBS) colitis in wildtype and Rag2‐deficient mice. The severity of colitis was assessed by means of histological scores and weight loss. We further characterized the inflammation using immunohistochemistry and by analysis of isolated intestinal leukocytes at various stages of disease. Results: Tacrolimus‐treated wildtype mice were less sensitive to colitis and had fewer activated T‐cells. Inhibition of T‐cell function was associated with strongly diminished recruitment of infiltrating neutrophils in the colon at the early stages of this model. In agreement, immunohistochemistry demonstrated that tacrolimus inhibited production of the neutrophil chemoattractants CXCL1 and CXCL2. Rag2‐deficient mice displayed an enhanced baseline level of lamina propria neutrophils that was moderately increased in TNBS colitis and remained unaffected by tacrolimus. Conclusions: Both the innate and the adaptive mucosal immune system contribute to TNBS colitis. Tacrolimus suppresses colitis directly through inhibition of T‐cell activation and by suppression of T‐cell‐mediated recruitment of neutrophils. (Inflamm Bowel Dis 2010)
Generation of Cancelable Iris Template Using Bi-level Transformation

Cancelable biometric system is a transformation technique for securing biometric templates. This work proposes application of bi-level template securing technique at feature-level, and generates revocable templates. The bi-level transformation includes Discrete Fourier Transform and partial Hadamard based transformations on iris features, using user-specific key. The proposed bi-level transformation applied at feature-level provides better robustness and security against correlation attacks. A comprehensive analysis has been performed on the proposed approach to study the non-invertibility, diversity, revocability and matching performance on iris samples. The experimental results show that the proposed approach is promising, and deliver good performance.
A method to enhance the use of interaural time differences for cochlear implants in reverberant environments

The ability of normal-hearing (NH) listeners to exploit interaural time difference (ITD) cues conveyed in the modulated envelopes of high-frequency sounds is poor compared to ITD cues transmitted in the temporal fine structure at low frequencies. Sensitivity to envelope ITDs is further degraded when envelopes become less steep, when modulation depth is reduced, and when envelopes become less similar between the ears, common factors when listening in reverberant environments. The vulnerability of envelope ITDs is particularly problematic for cochlear implant (CI) users, as they rely on information conveyed by slowly varying amplitude envelopes. Here, an approach to improve access to envelope ITDs for CIs is described in which, rather than attempting to reduce reverberation, the perceptual saliency of cues relating to the source is increased by selectively sharpening peaks in the amplitude envelope judged to contain reliable ITDs. Performance of the algorithm with room reverberation was assessed through simulating listening with bilateral CIs in headphone experiments with NH listeners. Relative to simulated standard CI processing, stimuli processed with the algorithm generated lower ITD discrimination thresholds and increased extents of laterality. Depending on parameterization, intelligibility was unchanged or somewhat reduced. The algorithm has the potential to improve spatial listening with CIs.
Human and System Errors, Using Adaptive Turnaround Documents to Capture Data in a Busy Practice

Capturing coded clinical data for clinical decision support can improve care, but cost and disruption of clinic workflow present barriers to implementation. Previous work has shown that tailored, scannable paper forms (adaptive turnaround documents, ATDs) can achieve the benefits of computer-based clinical decision support at low cost and minimal disruption of workflow. ATDs are highly accurate under controlled circumstances, but accuracy in the setting of busy clinics with untrained physician users is untested. We recently developed and implemented such a system and studied rates of errors attributable to physician users and errors in the system. Prompts were used in 63% of encounters. Errors resulting from incorrectly marking forms occurred in 1.8% of prompts. System errors occurred in 7.2% of prompts. Most system errors were failures to capture data and may represent human errors in the scanning process. ATDs are an effective way to collect coded data from physicians. Further automation of the scanning process may reduce system errors.
Reduced activity of TAFI (thrombin‐activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia

Acute promyelocytic leukaemia (APL) is a disease that is distinguished from other leukaemias by the high potential for early haemorrhagic death. Several processes are involved, such as disseminated intravascular coagulation and hyperfibrinolysis. Recently, TAFI (thrombin‐activatable fibrinolysis inhibitor) was identified as a link between coagulation and fibrinolysis. TAFI can be activated by thrombin, and in its activated form potently attenuates fibrinolysis by removing C‐terminal lysine and arginine residues that are important for the binding and activation of plasminogen. Activation of TAFI by the coagulation system results in a down‐regulation of fibrinolytic activity and, thereby, prevents a rapid dissolution of the fibrin clot. To establish whether TAFI was involved in the severity of the bleeding complications in APL, the TAFI antigen and activity levels were determined in a group of 15 patients. The TAFI antigen concentration was normal, but the activity of TAFI was severely reduced in APL by ≈ 60%. The reduction of TAFI activity was most probably caused by the action of plasmin on TAFI because in vitro experiments revealed that plasmin slightly reduced antigen levels but severely reduced TAFI activity. The acquired functional TAFI deficiency in APL may contribute to the severity of the haemorrhagic diathesis because of the impaired capacity of the coagulation system to protect the fibrin clot from fibrinolysis.
Tenecteplase–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion

Background and Purpose— Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK–tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population. Methods— TNK–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK–tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ⩽5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0–1). Results— Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01–20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0–1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0–1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09–2.5; P=0.026). Conclusions— Administration of TNK–tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT01654445.
A Framework For Long-Term Actuarial Projections Of Health Care Costs

Abstract Ever-expanding life expectancy is increasing the size of elderly populations with profound social and economic consequences for developed nations, including future cost of their health care systems. Most existing long-term health care cost projections are driven mainly by changing demographics (aging populations). This simplified approach fails to recognize the many variables, and complicated interactions among them, affecting the future of health, health care, and health care costs. This study presents a framework incorporating key health care cost drivers. Using the framework, the study then introduces three plausible futures for health care along with broad, nonmodeled estimates of their costs that point to a very wide range of potential future costs. By taking the next step and building actuarial models based on the framework presented in this study, actuaries and health economists can create a powerful tool for health policymakers and health officials to better understand the long-term consequences of decisions taken during their stewardship of health care systems.
A Political-Economic Analysis of the Antidumping Procedure in the European Union

In this paper we present spatial, complete and incomplete information models of the EU antidumping procedure. We identify the key players and study interest groups’, member states’ and institutions’ optimal strategies. We find that in the complete information model the Commission sets the duty it prefers most from among the duties a simple majority of member states prefer to the status quo. In the incomplete information model the industry affected by dumping has private information. It lobbies the Commission at the proposal stage and the pivotal member state at the vote stage. Furthermore, we analyze a scenario in which the European Parliament (EP) becomes involved as a veto player. We find that giving the EP such a role only affects the outcome if the EP is more reluctant to impose antidumping duties than is the pivotal member state. Subsequently, we present an empirical analysis and use Bayesian item response models to compare the positions of the Council and the EP on trade issues between December 2009 and June 2014. We find that the EP is indeed less protectionist than the Council. This suggests that the member states may be reluctant to give the EP more power on antidumping issues, because it would veto duties as high as those the Council currently imposes. † Christophe Crombez is Professor at the University of Leuven, Belgium, and Consulting Professor at the Freeman Spogli Institute for International Studies at Stanford University, U.S.A. ‡ Pieterjan Vangerven is Doctoral Candidate at the University of Leuven, Belgium, and Research Fellow at the Research Foundation Flanders (FWO), Belgium.
Hip strength in females with and without patellofemoral pain.

STUDY DESIGN Cross-sectional. OBJECTIVES To determine if females with anterior knee pain are more likely to demonstrate hip abduction or external rotation weakness than a similar, asymptomatic, age-matched control group. BACKGROUND Diminished hip strength has been implicated as being contributory to lower-extremity malalignment and patellofemoral pain. The identification of reliable and consistent patterns of weakness in this population may assist health care professionals establish a more effective treatment plan. METHODS AND MEASURES Hip abduction and external rotation isometric strength measurements were recorded for the injured side of 15 female subjects with patellofemoral joint pain (mean +/- SD age, 15.7 +/- 2.7 years; age range, 12-21 years). These were compared with strength measurements from the corresponding hip of 15 age-matched female control subjects (mean +/- SD age, 15.7 +/- 2.7 years; age range, 12-21 years). All strength measurements were made using hand-held dynamometers. RESULTS Subjects with patellofemoral pain demonstrated 26% less hip abduction strength (P<.001) and 36% less hip external rotation strength (P<.001) than similar age-matched controls. CONCLUSIONS The results indicate that young women with patellofemoral pain are more likely to demonstrate weakness in hip abduction as well as external rotation than age-matched women who are not symptomatic.
Measures of Shame and Conflict Tactics: Effects of Questionnaire Order

In the context of a theory of the intrapsychic dynamics of violent spousal relationships, in which abuse serves to replace shame with guilt, the effect of the order of presentation of questionnaires assessing shame, guilt, narcissism and conflict tactics was considered. Among 122 male and 133 female students, a shame score was significantly higher if the student had responded first to the Conflict Tactics Scale.
MC-2D: An Efficient and Scalable Multicoupon Scheme

Electronic multicoupons are the digital version of paper-based booklet of coupons, which allow a customer to obtain goods or services from a merchant typically with discounts or gifts. In this paper, we propose a multicoupon scheme for multi-merchant environments that enhances the security and the efficiency as regards the previous solution that deals with this kind of scenario. On one hand, our scheme meets basic security requirements (unforgeability, reuse detection), but also unsplittability. This fact will help to increase the trust on the part of merchants. On the other hand, we focus on achieving a high degree of privacy for customers (anonymity, unlinkability, confidentiality) that will contribute to gaining the trust of the involved customers. Moreover, we provide measures to protect honest parties from dishonest participants, keeping in mind the scalability and efficiency of the multicoupon scheme, to attract customers and merchants. In addition, we show by implementation that our proposal outperforms previous solutions of this kind.
Estimation Risk, Learning and the Equity Premium

We examine the effects of estimation risk and Bayesian learning on equilibrium asset prices when there is uncertainty about both the first and second moments of consumption and dividend growth rates. For the 1891-2007 period, our model generates a sizable average annual equity premium, relatively low average risk-free rate and a high mean Sharpe ratio that approximates the data average with (1) low risk aversion, (2) non-persistent (i.i.d.) growth rates, (3) power utility, (4) diffuse (or non-pessimistic) priors, and (5) finite posterior moments. Learning does not produce a monotonically declining equity premium and shocks to growth rates can induce sharp fluctuations in the market returns even after one hundred years of data. For reducing the discrepancy between the equilibrium outcomes and the data, variations in the prior estimation risk with respect to consumption --- but not dividend --- growth are at least as effective as variations in risk aversion, or in the inter-temporal elasticity of substitution, or in the persistence of growth rates.
Characterization of a Murine Monoclonal Antibody toCryptococcus neoformans Polysaccharide That Is a Candidate for Human Therapeutic Studies

ABSTRACT The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(κ)] is in preclinical development for treatment ofCryptococcus neoformans infections. In anticipation of its use in humans, we defined the serological and biological properties of MAb 18B7 in detail. Structural comparison to the related protective MAb 2H1 revealed conservation of the antigen binding site despite several amino acid differences. MAb 18B7 was shown by immunofluorescence and agglutination studies to bind to all four serotypes of C. neoformans, opsonize C. neoformans serotypes A and D, enhance human and mouse effector cell antifungal activity, and activate the complement pathway leading to deposition of complement component 3 (C3) on the cryptococcal capsule. Administration of MAb 18B7 to mice led to rapid clearance of serum cryptococcal antigen and deposition in the liver and spleen. Immunohistochemical studies revealed that MAb 18B7 bound to capsular glucuronoxylomannan in infected mouse tissues. No reactivity of MAb 18B7 with normal human, rat, or mouse tissues was detected. The results show that both the variable and constant regions of MAb 18B7 are biologically functional and support the use of this MAb in human therapeutic trials.