Miracle-dz/UniFAR-FTUs huggingface dataset:
The Anticoagulant Thrombin Mutant W215A/E217A Has a Collapsed Primary Specificity Pocket*

The thrombin mutant W215A/E217A features a drastically impaired catalytic activity toward chromogenic and natural substrates but efficiently activates the anticoagulant protein C in the presence of thrombomodulin. As the remarkable anticoagulant properties of this mutant continue to be unraveled in preclinical studies, we solved the x-ray crystal structures of its free form and its complex with the active site inhibitor H-d-Phe-Pro-Arg-CH2Cl (PPACK). The PPACK-bound structure of W215A/E217A is identical to the structure of the PPACK-bound slow form of thrombin. On the other hand, the structure of the free form reveals a collapse of the 215-217 strand that crushes the primary specificity pocket. The collapse results from abrogation of the stacking interaction between Phe-227 and Trp-215 and the polar interactions of Glu-217 with Thr-172 and Lys-224. Other notable changes are a rotation of the carboxylate group of Asp-189, breakage of the H-bond between the catalytic residues Ser-195 and His-57, breakage of the ion pair between Asp-222 and Arg-187, and significant disorder in the 186- and 220-loops that define the Na+ site. These findings explain the impaired catalytic activity of W215A/E217A and demonstrate that the analysis of the molecular basis of substrate recognition by thrombin and other proteases requires crystallization of both the free and bound forms of the enzyme.
Islamic Law and Finance: Religion, Risk, and Return

1. Introduction. Part I: The Islamic Law of Finance. 2. Islamic Finance as the Application of Islamic Law. 3. Qur'an and Sunna on Contract and Commerce. 4. Islamic Laws of Usury, Risk, and Property. 5. Islamic Law of Contract. 6. The Law of Islamic Financial Institutions and Instruments. Part II: A Financial Analysis of Islamic Banking and Finance. 7. Islamic Financial Instruments: A Primer. 8. The Opportunity Rate of Capital and Islamic Capital Structure. 9. Derivatives in Islamic Finance. Part III: Case Studies: Islamic Financial Innovation. 10. Innovation in Islamic Financial Products. 11. Conclusion. Glossary. Bibliography. Index.
Evaluation of combined transmission and emission tomography for classification of skeletal lesions.

OBJECTIVE This study assessed the benefit of transmission emission tomography (TET) for classification of skeletal lesions in patients with known malignant disease. SUBJECTS AND METHODS The TET technology combines acquisition of SPECT and CT data using the same imaging device, thus allowing perfect overlay of anatomic and functional images. We performed TET in 47 patients with tumors who had a total of 104 focal lesions found on bone scintigraphy. Technetium-99m diphosphonate was used as the radiopharmaceutical in all patients. Findings of bone scintigraphy (planar and SPECT), SPECT + CT or radiography, and TET were compared with regard to the precise location and nature (benign vs malignant) of each lesion. Validation was achieved by radiologic follow-up on CT, MRI, or radiography, especially for the extremities, and using biopsy results in five patients. RESULTS TET could classify 88 (85%) of 104 lesions compared with 37 (36%) of 104 on SPECT. When we counted inconclusive studies as positive for cancer, discrepant findings between SPECT and TET were obtained in 39 lesions. In 38 (97%) of these, TET was correct. Sensitivity for cancer detection was 98% for TET and 94% for SPECT (p = 0.63), and specificity was 81% for TET and 19% for SPECT (p < 0.0001). The highest diagnostic gain was in the spine, thoracic cage, skull, and pelvis. Small osteolytic lesions were missed because of the limited resolution of transmission images. SPECT + CT or radiography and TET were discordant in nine of 104 lesions. TET was false-negative in one lesion and false-positive in another, and SPECT + CT or radiography was false-positive in seven lesions. As a result, sensitivities of TET and SPECT + CT or radiography were nearly the same, but the specificity of TET was significantly higher (p = 0.015). CONCLUSION TET improves the accuracy of bone scintigraphy by correctly classifying equivocal lesions, especially by identifying benign abnormalities in the axial skeleton and thus increasing the specificity of positive findings.
Harness the power of viral marketing in hotel industry: a network discount strategy

Purpose – The purpose of this paper is to focus on the pricing strategy for viral marketing in the context of the hotel industry and propose three typical price‐network size schedules to be tested. The paper further proposes controlled experiments in hotel industry context to examine the performance of those schedules.Design/methodology/approach – A simulated hotel booking web site with basic reservation functions will be constructed. Participants should be randomly drawn and asked to encourage their friends from social networks to book with the participant to achieve a better price. Each participant will be given a special promotion code embedded with different pricing information. The number of customers attracted, total revenue and time to achieve a sell‐out was collected after the experiments.Findings – These were the expected performance differences associated with different network pricing strategies in the viral marketing campaigns.Research limitations/implications – Since participants do not need .
Increased circulating interleukin-18 in patients with congestive heart failure

Accumulating evidence suggests that proinflammatory cytokines such as tumour necrosis factor (TNF) α, interleukin (IL)-1β, and IL-6 are likely to be involved in the pathogenesis of advanced cardiac failure. Cytokine actions directly identified to date include promotion of systemic catabolism, myocardial depression, cardiac hypertrophy, and apoptosis of myocytes in congestive heart failure (CHF). IL-18, a new member of the IL-1 family, is a proinflammatory cytokine with multiple biologic functions.1 In concert with IL-12, IL-18 stimulates Th1 mediated immune responses; by itself, IL-18 can stimulate Th2 cytokine production. IL-18, originally named as an interferon γ inducing factor (IGIF),2 can induce TNFα and IL-6 in murine macrophages.3 Pomerantz and colleagues demonstrated that IL-18 is expressed in vascular endothelial cells and macrophages in human heart, and that IL-18 binding protein, which is derived from a gene distinct from the IL-18 receptor gene and can neutralise IL-18 actions, reduces human myocardial reperfusion injury after 30 minutes of ischaemia.4,5 We hypothesised that IL-18 might contribute to immune activation and cardiac dysfunction in congestive heart failure. In this study we examined serum concentrations of IL-18 in patients with CHF to examine whether the cytokine was involved in the pathophysiology of this syndrome. Subjects included 34 consecutively recruited patients (20 men and 14 women aged 42–83 years, mean 64 years) who had chronic, stable symptomatic heart failure representing New York Heart Association (NYHA) functional class II–IV for more than two …
Brand Communities and New Product Adoption:The Influence and Limits of Oppositional Loyalty

Abstract Brand communities have been cited for their potential not only to enhance the loyalty of members but also to engender a sense of oppositional loyalty toward competing brands. However, the impact of brand community membership on actual new product adoption behavior has yet to be explored. This study examines the effects of brand community participation and membership duration on the adoption of new products from opposing brands as well as from the preferred brand. Longitudinal data were collected on the participation behavior, membership duration, and adoption behavior of 7506 members spanning four brand communities and two product categories. Using a hazard modeling approach, the authors find that higher levels of participation and longer-term membership in a brand community not only increase the likelihood of adopting a new product from the preferred brand but also decrease the likelihood of adopting new products from opposing brands. However, such oppositional loyalty is contingent on whether a.
Atypical (second generation) antipsychotic treatment response in very late-onset schizophrenia-like psychosis

ABSTRACT Introduction: Symptom amelioration in older patients with very late onset schizophrenia-like psychosis (VLOSLP) is often difficult, with limited psychotropic response reports yielding variable findings. Information about atypical (second generation) antipsychotic use in this population is scant. Methods: A consecutive sample of geriatric psychiatry outpatients and inpatients with psychotic disorders were retrospectively identified over a 31-month period based on systematic information abstraction from an electronic medical record (e-record). After exclusion criteria were applied, 8/138 outpatients and 13/362 inpatients met inclusion criteria for VLOSLP and had been naturalistically treated with an atypical antipsychotic during hospitalization or nine months of outpatient care. Mandatorily completed e-record standardized symptom severity response ratings were converted into positive treatment response thresholds. Results: 38% of outpatients and 77% of inpatients (mean age = 76 years for both groups; mean age of onset of psychosis = 70 years for outpatients and 74 years for inpatients) met criteria for positive treatment response to an atypical antipsychotic (either aripiprazole, olanzapine, quetiapine, or risperidone) with sign/symptom amelioration, rather than eradication. Conclusions: Various atypical antipsychotics at geriatric doses yielded a positive treatment response in nearly two-thirds of VLOSLP patients. Patients with less chronic, more severe symptoms responded at a higher rate. Prospective, double-blind, placebo-controlled trials with representative subject samples are needed to validate these preliminary findings.
Local image segmentation with geometric filters

We propose a mathematical framework for designing filter banks that detect simple geometric features in an image, such as the planarity of the intensity function. Several theoretical results are given on how the geometry of the filters is related to the discriminative power of the filter bank. The experiment results show how the filters can be used to perform a fast segmentation of an image patch into planar segments. © 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 3–13, 2011.
Gender and Organizational Performance: Determinants of Small Business Survival and Success

This research explores the effect of gender on organizational performance. Data used in the analysis was collected from small businesses in South Central Indiana from 1985-1987. The businesses were from the food and drink, computer sales and software, and health industries. Of the businesses surveyed, 312 were headed by men while 99 where headed by women. On average, these individuals were 44-45 years of age. Organizational performance is examined through two different concepts, survival and success. The results indicate that women were not more likely to go out of business than men, and only prior self-employment had different effects for men and women. Further, there was not a difference in this area among the differing industries. The results also indicate that both genders were equally confident and believed they had the ability to influence business outcomes. As for the success of these businesses, there again was no difference between the males and females with respect to earnings growth. These results are contrary to the traditional thinking that men have an advantage over women with respect to entrepreneurship and organizational performance. Since the dataset used in this analysis was limited in scope, further research is necessary to determine if these results will hold true across other industries. (SRD)
Hedging and Taking Risk: On the Role of Derivatives and Stock Options

This paper empirically examines the relation between the use of derivatives and the risk level of firms in a sample of 431 large Japanese nonfinancial firms. Previous studies investigating whether firms systematically reduce or increase their risk with derivatives show that firms reduce their risk. By contrast, this paper shows that the use of derivatives increases total risk and firm-specific risk. However, the magnitude of the increase is not economically significant. Further analysis provides some evidence on the association between derivatives and stock options. The results show that there is a positive relation between the use of derivatives and stock options. In addition, firms introducing stock options invest in R&D activities to a greater extent than firms that do not introduce stock options. These findings suggest that Japanese firms use derivatives to hedge homogeneous risk and adopt stock option compensation to take core-business risk.
Modeling Consumers’ Choices of Multiple Items

Contemporary choice models focus on choice opportunities in which consumers purchase a quantity of a single item in a product category. However, failing to recognize the possibility of assortments of multiple-Item purchases can lead to incorrect conclusions about the impact of past purchase behavior on current choices. The authors propose a model that allows for multiple-item shopping trips and apply it to scanner data for powdered soft drinks. The model provides descriptions about the influence of (1) consumer's prior behavior across previous shopping trips, (2) behavior within the same shopping trip, (3) the in-store shelf assortment available at the time of purchase, and (4) marketing mix variables on multiple-item shopping trip choices. The authors’ model provides better choice predictions in a holdout sample at the aggregate and assortment composition levels than a traditional, single-purchase choice model. Using the model, they present simulation and naturally occurring experiment results in the powdered soft drinks category. Finally, they discuss the value of their results for understanding the consequences of consumers’ choices and their implications for manufacturers.
Effect of Adrenergic Agents on Salivary Composition

Goodman and Gillman's classical textbook of pharmacology,' in dealing with salivary glands, considers the sympathetic system as affecting the submaxillary but not the parotid gland and operating via alpha rather than beta adrenergic stimulation. Surprisingly, this view is not based on direct observations on human subjects, which are limited, but rather on extrapolation from experiments on the cat.2 Quite different results have been noted in the rat and rabbit where direct sympathetic stimulation or introduction of beta adrenergic agents affect the parotid gland to a greater extent than the submaxillary gland.3,4 In the dog, the submaxillary gland is strongly affected by beta (not alpha) adrenergic agents5; the situation in the dog parotid gland is not clear.6 Obviously, differences among species are so great that one cannot readily extrapolate from animals to man. The most comparable species to man seems to be the rat.7 In view of the increasing use of adrenergic drugs in the treatment of a number of diseases and the paucity of direct data on the role of the sympathetic system in human salivary secretion, there is need for systematic examination of the effects of adrenergic drugs on human salivary secretion and composition. This report is concerned with the effect of intravenously administered isoproterenol as compared to effects observed with administration of epinephrine, norepinephrine, and phenylephrine. The agonists are used alone and after alpha or beta adrenergic blockade, or both. In addition to the human studies, experiments were conducted with rats to compare the effects on saliva of high doses of isopro-
International Transmission Effects of Monetary Policy Shocks: Can Asymmetric Price Setting Explain the Stylized Facts?

How does an unexpected domestic monetary expansion affect the foreign economy? Does it induce an increase or a decline in foreign production? In the traditional two-country Mundell-Fleming model, monetary policy has "beggar-thy-neighbor" effects. Yet, empirical evidence from VARs indicates that U.S. monetary policy has positive international transmission effects on both foreign (non-U.S. G-7) output and aggregate demand. In this paper, I will show that a two-country dynamic general equilibrium model with sticky prices can account for these "stylized facts" if we allow for international asymmetries in the price-setting behavior of firms. If U.S. firms set export prices in their own currency only (producer-currency pricing), whereas producers in the rest of the world price their exports to the U.S. in the local currency of the export market (local-currency pricing), a U.S. monetary expansion is found to increase output and aggregate demand abroad.
Novel tretinoin formulations: a drug-in-cyclodextrin-in-liposome approach

Abstract Purpose: The aims of this experimental work were the incorporation and full characterization of the system Tretinoin-in-dimethyl-beta-cyclodextrin-in-ultradeformable vesicles (Tretinoin-CyD-UDV) and Tretinoin-in-ultradeformable vesicles (Tretinoin-UDV). Methods: The Tretinoin-CyD complex was prepared by kneading and the UDV by adding soybean phosphatidylcholine (SPC) to Tween® 80 followed by an appropriate volume of sodium phosphate buffer solution to make a 10%–20% lipid suspension. The resulting suspension was brought to the final mean vesicles size, of approximately 150 nm, by sequential filtration. The physicochemical characterization was based on: the evaluation of mean particle size and polydispersity index (PI) measured by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM) topographic imaging; zeta potential (ζ-potential) and the SPC concentration determined by Laser–Doppler anemometry and an enzymatic-colorimetric test, respectively. The quantification of the incorporated Tretinoin and its chemical stability (during preparation and storage) was assayed by a HPLC at 342 nm. Results: It was possible to obtain the system Tretinoin-CyD-UDV. The mean vesicle size was the most stable parameter during experiments time course. AFM showed that Tretinoin-CyD-UDV samples were very heterogeneous in size, having three distinct subpopulations, while Tretinoin-UDV samples had only one homogeneous size population. The results of the ζ-potential measurements have shown that vesicle surface charge was low, as expected, presenting negative values. The incorporation efficiency was high, and no significant differences between Tretinoin-CyD-UDV and Tretinoin-UDV were observed. However, only Tretinoin-UDV with 20% lipid concentration formulation remained chemically stable during the evaluation period. Conclusion: According to our results, Tretinoin-UDV with 20% lipid concentration seems to be a better approach than Tretinoin-CyD-UDV, attending to the higher chemical stability.
Volunteer Science

Experimental research in traditional laboratories comes at a significant logistic and financial cost while drawing data from demographically narrow populations. The growth of online methods of research has resulted in effective means for social psychologists to collect large-scale survey-based data in a cost-effective and timely manner. However, the same advancement has not occurred for social psychologists who rely on experimentation as their primary method of data collection. The aim of this article is to provide an overview of one online laboratory for conducting experiments, Volunteer Science, and report the results of six studies that test canonical behaviors commonly captured in social psychological experiments. Our results show that the online laboratory is capable of performing a variety of studies with large numbers of diverse volunteers. We advocate for the use of the online laboratory as a valid and cost-effective way to perform social psychological experiments with large numbers of diverse subjects.
Silvia Formenti on the promise of combining radiotherapy and immunotherapy to treat cancer.

During the past decade, scientific evidence has emerged that shows that radiotherapy can induce: A) immunogenic cell death, a form of cancer cell death that is effectively signaling to the immune system; and B) a series of “danger” and pro-immunogenic signals that are sensed by the host’s immune system, and can be harnessed to reject the tumor.
Service Quality: : Students′ Assessment of Banks and Building Societies

Investigates service quality in the student market for financial services. Reports empirical work in which students′ attitudes towards the service provided by their banks and building societies were assessed, with emphasis on loan and overdraft arrangements. The students′ expectations and perceptions were measured using a graphic positioning scale and a number of service quality shortfalls were identified which have implications for organizations providing financial services to the student market. Highlights opportunities for further research in the area of measuring service quality.
Cosmetic surgery training in Canadian plastic surgery residencies: are we training competent surgeons?

BACKGROUND With the demand for cosmetic surgery continuing to rise, it is necessary to reevaluate the current state of cosmetic surgery training during plastic surgery residency. An evaluation of cosmetic surgery training in US plastic surgery residency programs in 2006 identified several areas for improvement, resulting in changes to both the duration and content of training. OBJECTIVES The authors assess the current state of cosmetic surgery training in Canadian plastic surgery residency programs. METHODS A paper survey of all graduating Canadian plastic surgery residents eligible to complete the 2009 Royal College of Physicians and Surgeons of Canada fellowship examinations was performed (N = 29). The survey was conducted primarily at the Canadian Plastic Surgery Review Course in February 2009, with surveys collected from absent residents by e-mail within 1 month after the course. The survey covered 2 broad areas: (1) specifics regarding resident cosmetic surgery training and (2) confidence and satisfaction associated with this experience. RESULTS Of the 29 residents surveyed, 28 responded (96%). The majority of Canadian plastic surgery residency programs (75%) have a designated cosmetic surgery rotation, but 90% of respondents felt it has become increasingly difficult to gain exposure to cosmetic procedures as most are performed at private surgery centers. Elective rotations at cosmetic surgery practices and resident cosmetic clinics were considered the most beneficial for cosmetic surgery education. Residents considered cosmetic surgery procedures of the face (such as rhinoplasty and facelift) more challenging, but they had more confidence with breast and body contouring procedures. CONCLUSIONS Canadian plastic surgery residency programs need to ensure that residents continue to receive comprehensive exposure to both surgical and nonsurgical cosmetic procedures to ensure our specialty's continued leadership in this evolving and highly competitive field. A multidimensional approach utilizing a variety of readily available resources will ensure that the current and future cosmetic surgery educational needs of Canadian plastic surgery residents are met.