LLukas22/scidocs huggingface dataset:
Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multitarget profile has, however, necessitated the application of combination therapies, which can pose major clinical development challenges. Epigenetic reader domains of the bromodomain family have recently emerged as new targets for cancer therapy. Here we report that several clinical kinase inhibitors also inhibit bromodomains with therapeutically relevant potencies and are best classified as dual kinase-bromodomain inhibitors. Nanomolar activity on BRD4 by BI-2536 and TG-101348, which are clinical PLK1 and JAK2-FLT3 kinase inhibitors, respectively, is particularly noteworthy as these combinations of activities on independent oncogenic pathways exemplify a new strategy for rational single-agent polypharmacological targeting. Furthermore, structure-activity relationships and co-crystal structures identify design features that enable a general platform for the rational design of dual kinase-bromodomain inhibitors.
Influence of alumina oxide nanoparticles on the performance and emissions in a methyl ester of neem oil fuelled direct injection diesel engine

The experimental investigation of the influence of Al2O3 nanoadditive on performance and emissions in a methyl ester of neem oil fueled direct injection Diesel engine is reported in this paper. The Al2O3 nanoparticles are mixed in various proportions (100 to 300 ppm) with methyl ester of neem oil. The performance and emissions are tested in a single cylinder computerized, 4-stroke, stationary, water-cooled Diesel engine of 3.5 kW rated power. Results show that the nanoadditive is effective in increasing the performance and controlling the NO emissions of methyl ester of neem oil fueled Diesel engines.
The Poetics of Portraiture in the Italian Renaissance

1. Dialogue with the beholder 2. 'Familiar colloquium': the recollection and presence of portraits 3. Designing the self Titian's 'Nonautographic' self-portraits 4. 'L'effetto che fa lo specchio' 5. The speaking tomb.
Characterizing 3D Floating Gate NAND Flash

In this paper, we characterize a state-of-the-art 3D floating gate NAND flash memory through comprehensive experiments on an FPGA platform. Then, we present distinct observations on performance and reliability, such as operation latencies and various error patterns. We believe that through our work, novel 3D NAND flash-oriented designs can be developed to achieve better performance and reliability.
How changes affect software entropy: an empirical study

Context Software systems continuously change for various reasons, such as adding new features, fixing bugs, or refactoring. Changes may either increase the source code complexity and disorganization, or help to reducing it. Aim This paper empirically investigates the relationship of source code complexity and disorganization—measured using source code change entropy—with four factors, namely the presence of refactoring activities, the number of developers working on a source code file, the participation of classes in design patterns, and the different kinds of changes occurring on the system, classified in terms of their topics extracted from commit notes. Method We carried out an exploratory study on an interval of the life-time span of four open source systems, namely ArgoUML, Eclipse-JDT, Mozilla, and Samba, with the aim of analyzing the relationship between the source code change entropy and four factors: refactoring activities, number of contributors for a file, participation of classes in design patterns, and change topics. Results The study shows that (i) the change entropy decreases after refactoring, (ii) files changed by a higher number of developers tend to exhibit a higher change entropy than others, (iii) classes participating in certain design patterns exhibit a higher change entropy than others, and (iv) changes related to different topics exhibit different change entropy, for example bug fixings exhibit a limited change entropy while changes introducing new features exhibit a high change entropy. Conclusions Results provided in this paper indicate that the nature of changes (in particular changes related to refactorings), the software design, and the number of active developers are factors related to change entropy. Our findings contribute to understand the software aging phenomenon and are preliminary to identifying better ways to contrast it.
Multicentre double-blind randomized controlled trial of perhexiline as a metabolic modulator to augment myocardial protection in patients with left ventricular hypertrophy undergoing cardiac surgery.

OBJECTIVES
Patients undergoing cardiac surgery require adequate myocardial protection. Manipulating myocardial metabolism may improve the extent of myocardial protection. Perhexiline has been shown to be an effective anti-anginal agent due to its metabolic modulation properties by inhibiting the uptake of free fatty acids into the mitochondrion, and thereby promoting a more efficient carbohydrate-driven myocardial metabolism. Metabolic modulation may augment myocardial protection, particularly in patients with left ventricular hypertrophy (LVH) known to have a deranged metabolic state and are at risk of poor postoperative outcomes. This study aimed to evaluate the role of perhexiline as an adjunct in myocardial protection in patients with LVH secondary to aortic stenosis (AS), undergoing an aortic valve replacement (AVR).


METHODS
In a multicentre double-blind randomized controlled trial of patients with AS undergoing AVR ± coronary artery bypass graft surgery, patients were randomized to preoperative oral therapy with either perhexiline or placebo. The primary end point was incidence of inotrope use to improve haemodynamic performance due to a low cardiac output state during the first 6 h of reperfusion, judged by a blinded end points committee. Secondary outcome measures included haemodynamic measurements, electrocardiographic and biochemical markers of new myocardial injury and clinical safety outcome measures.


RESULTS
The trial was halted early on the advice of the Data Safety and Monitoring Board. Sixty-two patients were randomized to perhexiline and 65 to placebo. Of these, 112 (54 perhexiline and 48 placebo) patients received the intervention, remained in the trial at the time of the operation and were analysed. Of 110 patients who achieved the primary end point, 30 patients (16 perhexiline and 14 placebo) had inotropes started appropriately; there was no difference in the incidence of inotrope usage OR of 1.65 [confidence interval (CI): 0.67-4.06] P = 0.28. There was no difference in myocardial injury as evidenced by electrocardiogram odds ratio (OR) of 0.36 (CI: 0.07-1.97) P = 0.24 or postoperative troponin release. Gross secondary outcome measures were comparable between the groups.


CONCLUSIONS
Perhexiline as a metabolic modulator to enhance standard myocardial protection does not provide an additional benefit in haemodynamic performance or attenuate myocardial injury in the hypertrophied heart secondary to AS. The role of perhexiline in cardiac surgery is limited.
Characteristics of heart failure patients associated with good and poor response to cardiac resynchronization therapy: a PROSPECT (Predictors of Response to CRT) sub-analysis.

AIMS
Predictors of Response to Cardiac Resynchronization Therapy (CRT) (PROSPECT) was the first large-scale, multicentre clinical trial that evaluated the ability of several echocardiographic measures of mechanical dyssynchrony to predict response to CRT. Since response to CRT may be defined as a spectrum and likely influenced by many factors, this sub-analysis aimed to investigate the relationship between baseline characteristics and measures of response to CRT.


METHODS AND RESULTS
A total of 286 patients were grouped according to relative reduction in left ventricular end-systolic volume (LVESV) after 6 months of CRT: super-responders (reduction in LVESV > or =30%), responders (reduction in LVESV 15-29%), non-responders (reduction in LVESV 0-14%), and negative responders (increase in LVESV). In addition, three subgroups were formed according to clinical and/or echocardiographic response: +/+ responders (clinical improvement and a reduction in LVESV > or =15%), +/- responders (clinical improvement or a reduction in LVESV > or =15%), and -/- responders (no clinical improvement and no reduction in LVESV > or =15%). Differences in clinical and echocardiographic baseline characteristics between these subgroups were analysed. Super-responders were more frequently females, had non-ischaemic heart failure (HF), and had a wider QRS complex and more extensive mechanical dyssynchrony at baseline. Conversely, negative responders were more frequently in New York Heart Association class IV and had a history of ventricular tachycardia (VT). Combined positive responders after CRT (+/+ responders) had more non-ischaemic aetiology, more extensive mechanical dyssynchrony at baseline, and no history of VT.


CONCLUSION
Sub-analysis of data from PROSPECT showed that gender, aetiology of HF, QRS duration, severity of HF, a history of VT, and the presence of baseline mechanical dyssynchrony influence clinical and/or LV reverse remodelling after CRT. Although integration of information about these characteristics would improve patient selection and counselling for CRT, further randomized controlled trials are necessary prior to changing the current guidelines regarding patient selection for CRT.
Data Parallel Algorithms

Parallel computers with tens of thousands of processors are typically programmed in a data parallel style, as opposed to the control parallel style used in multiprocessing. The success of data parallel algorithms—even on problems that at first glance seem inherently serial—suggests that this style of programming has much wider applicability than was previously thought.
Art and Technics

Lewis Mumford - architectural critic, theorist of technology, urbanologist, city planner, cultural critic, historian, biographer, and philosopher - was the author of more than thirty influential books, many of which expounded his views on the perils of urban sprawl and a society obsessed with "technics." Featuring a new introduction by Casey Nelson Blake, this classic text provides the essence of Mumford's views on the distinct yet interpenetrating roles of technology and the arts in modern culture. Mumford contends that modern man's overemphasis on technics has contributed to the depersonalization and emptiness of much of twentieth-century life. He issues a call for a renewed respect for artistic impulses and achievements. His repeated insistence that technological development take the Human as its measure - as well as his impassioned plea for humanity to make the most of its "splendid potentialities and promise" and reverse its progress toward anomie and destruction - is ever more relevant as the new century dawns.
Low-complexity hybrid form FIR filters using matrix multiple constant multiplication

Hybrid form FIR filters have been shown to provide a trade-off between the direct form and transposed direct form FIR filters resulting in a low power implementation. However, the use of multiple constant multiplication (MCM) techniques is less advantageous as it results in several MCM blocks. In this work a method of implementing low-complexity hybrid form FIR filters using matrix multiple constant multiplication blocks is proposed. The utilized filter structure can be seen as a polyphase decomposition with common delay lines for the subfilters.
End-to-End Interpretation of the French Street Name Signs Dataset

We introduce the French Street Name Signs (FSNS) Dataset consisting of more than a million images of street name signs cropped from Google Street View images of France. Each image contains several views of the same street name sign. Every image has normalized, title case folded ground-truth text as it would appear on a map. We believe that the FSNS dataset is large and complex enough to train a deep network of significant complexity to solve the street name extraction problem “end-to-end” or to explore the design trade-offs between a single complex engineered network and multiple sub-networks designed and trained to solve sub-problems. We present such an “end-to-end” network/graph for Tensor Flow and its results on the FSNS dataset. 1
Definitive treatment of primary vaginal cancer with radiotherapy: multi-institutional retrospective study of the Korean Radiation Oncology Group (KROG 12-09).

OBJECTIVE
To assess the outcome of the treatment of primary vaginal cancer using definitive radiotherapy (RT) and to evaluate the prognostic factors of survival.


METHODS
The medical records of nine institutions were retrospectively reviewed to find the patients with vaginal cancer treated with definitive RT with or without chemotherapy. A total of 138 patients met the inclusion criteria. None had undergone curative excision.


RESULTS
The median follow-up time of the survivors was 77.6 months and the median survival time was 46.9 months. The 5-year overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) rates were 68%, 80%, and 68.7%, respectively. In the survival analysis, the multivariate analysis showed that a lower the International Federation of Gynecology and Obstetrics (FIGO) stage and prior hysterectomy were favorable prognostic factors of CSS, and a lower FIGO stage and diagnosed prior to year 2000 were favorable prognostic factors of PFS. In the subgroup analysis of the patients with available human papillomavirus (HPV) results (n=27), no statistically significant relationship between the HPV status and recurrence or survival was found. Grade 3 or 4 acute and late toxicity were present in 16 and 9 patients, respectively. The FIGO stage and the tumor size were predictors of severe late toxicity.


CONCLUSION
The data clearly showed that a higher FIGO stage was correlated with a worse survival outcome and higher severe late toxicity. Therefore, precise RT and careful observation are crucial in advanced vaginal cancer. In this study, the HPV status was not related to the survival outcome, but its further investigation is needed.
Feminism and science—Reason and passion

Abstract Starting with the common roots of feminism and science in the Enlightenment and its distinction of reason and passion, this article briefly summarises the ways this distinction has been used both to defend and oppose women's rights. Current philosophies of science that variously reiterate or question this distinction are then surveyed, it being argued that science involves both reason and passion, particularly the passions and interests of men in male-dominated society such that nothing short of the overthrow of male dominance and the achievement of full equality between the sexes in society generally will suffice to bring about a science that meets the passions and interests of women alike with those of men.
An Extended Authorization Model for Relational Databases

We propose two extensions to the authorization model for relational databases defined originally by Griffiths and Wade. The first extension concerns a new type of revoke operation, called noncascading revoke operation. The original model contains a single, cascading revoke operation, meaning that when a privilege is revoked from a user, a recursive revocation takes place that deletes all authorizations granted by this user that do not have other supporting authorizations. The new type of revocation avoids the recursive revocation of authorizations. The second extension concerns negative authorization which permits specification of explicit denial for a user to access an object under a particular mode. We also address the management of views and groups with respect to the proposed extensions. Index Terms —Database systems, relational database, access control, authorization, security, protection, privacy, revocation of
Finasteride Reduces Risk of Bladder Cancer in a Large Prospective Screening Study.

UNLABELLED
The androgen receptor has been implicated in the development and progression of bladder cancer (BCa), largely based on studies of animal models. We investigated whether finasteride was associated with a reduced incidence of BCa as observed by self-report in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Cox proportional hazard regression analysis was performed to determine the association of finasteride use with time to diagnosis of BCa, controlling for age and tobacco use. Of the 72,370 male participants who met inclusion criteria, 6069 (8.4%) had reported the use of finasteride. BCa was diagnosed in 1.07% (65 of 6069) of those who reported finasteride compared with 1.46% (966 of 66,301) of those who reported no use during the trial. In a multiple Cox regression analysis, self-reported use of finasteride was associated with a decreased risk of development of BCa (hazard ratio: 0.634; 95% confidence interval, 0.493-0.816; p=0.0004), controlling for age and smoking. Limitations of this study include that it is observational and not randomized, that many of the confounding variables for BCa, such as alcohol use, were not available for use in the analysis, and that finasteride use was by annual self-report, which is subject to missing values and error.


PATIENT SUMMARY
Finasteride is a common medication used to reduce the size of the prostate and to promote hair growth by manipulating testosterone in men. Men are more likely than women to develop bladder cancer (BCa), but our study noted that men using finasteride were less likely to have a BCa diagnosis.
An exact formula for "Tooth-to-Tooth" permeance

We present a new, completely original exact method to determine the permeance between two opposing iron teeth. This configuration is important because it is often encountered in electrical machines and apparatus. The method is based on conformal mapping. The given "tooth-to-tooth" configuration is mapped into a simpler one, in which the same permeance can be analytically determined. We derive an explicit formula for this permeance, and confirm our results using the finite-element method.
Assessing the „humorous temperament“: Construction of the facet and standard trait forms of the State-Trait-Cheerfulness-Inventory — STCI

The present paper outlines the relevance of cheerfulness, seriousness, and bad mood for humor research. A state-trait model of exhtiaratability is presented which incorporates the three concepts äs both states and traits. Definitions of the concepts are undertaken utilizing a facet approach and the relationships among the three concepts are outlined. The construction strategy for the various forms of the German Version of the State-TraitCheerfulness-Inventory (STCI) is outlined and the following versions of the trait form will be elaborated: (a) the pilot form with 122 items (STCI-T<122>); (b) a component (or long) form with 106 items (STCI-T<106>); (c) the Standard form with 60 items (STCI-T<60>) and (d) the international form with 106 items (STCI-T<106i>). The development ofthe twoforms, the replication ofthepsychometric characteristics, and the evaluation of the facet model utilized samples of German and American adults comprising more that 1,300 subjects altogether. The hypothesized facet structure emerged and appeared to be highly generalizable across the samples. The psychometric characteristics ofthe facets and scales appeared to be satisfactory. While there were no sex differences in any of the scales, seriousness increased steadily öfter age 40. Correspondence between seif· and peerevaluation was examinedand turned out to be sufficiently high. The construction seemed to have been successful in promding a reliable Instrument for the assessment ofthe temperamental basis ofthe sense of humor. DOI: 10.1515/humr.1996.9.3-4.303 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: http://doi.org/10.5167/uzh-77696 Published Version Originally published at: Ruch, Willibald; Kohler, G; Van Thriel, Christoph (1996). Assessing the „humorous temperament“: Construction of the facet and standard trait forms of the State-Trait-Cheerfulness-Inventory — STCI. HUMOR: International Journal of Humor Research, 9(3-4):303-339. DOI: 10.1515/humr.1996.9.3-4.303 Assessing the "humorous temperament": Construction of the facet and Standard trait forms of the State-Trait-Cheerfulness-Inventory — STCI* WILLIBALD RUCH, GABRIELE KÖHLER, and CHRISTOPH VAN THRIEL
Evidence for power-law tail of the wealth distribution in India

The higher-end tail of the wealth distribution in India is studied using recently published lists of the wealth of richest Indians between the years 2002-4. The resulting rank distribution seems to imply a power-law tail for the wealth distribution, with a Pareto exponent between 0.81 and 0.92 (depending on the year under analysis). This provides a comparison with previous studies of wealth distribution, which have all been confined to Western advanced capitalist economies. We conclude with a discussion on the appropriateness of multiplicative stochastic process as a model for asset accumulation, the relation between the wealth and income distributions (we estimate the Pareto exponent for the latter to be around 1.5 for India), as well as possible sources of error in measuring the Pareto exponent for wealth. PACS numbers: 89.65.Gh, 89.65.-s, 02.50.-r, 89.75.Da
Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa).

INTRODUCTION
Tumeric is a spice that comes from the root Curcuma longa, a member of the ginger family, Zingaberaceae. In Ayurveda (Indian traditional medicine), tumeric has been used for its medicinal properties for various indications and through different routes of administration, including topically, orally, and by inhalation. Curcuminoids are components of tumeric, which include mainly curcumin (diferuloyl methane), demethoxycurcumin, and bisdemethoxycurcmin.


OBJECTIVES
The goal of this systematic review of the literature was to summarize the literature on the safety and anti-inflammatory activity of curcumin.


METHODS
A search of the computerized database MEDLINE (1966 to January 2002), a manual search of bibliographies of papers identified through MEDLINE, and an Internet search using multiple search engines for references on this topic was conducted. The PDR for Herbal Medicines, and four textbooks on herbal medicine and their bibliographies were also searched.


RESULTS
A large number of studies on curcumin were identified. These included studies on the antioxidant, anti-inflammatory, antiviral, and antifungal properties of curcuminoids. Studies on the toxicity and anti-inflammatory properties of curcumin have included in vitro, animal, and human studies. A phase 1 human trial with 25 subjects using up to 8000 mg of curcumin per day for 3 months found no toxicity from curcumin. Five other human trials using 1125-2500 mg of curcumin per day have also found it to be safe. These human studies have found some evidence of anti-inflammatory activity of curcumin. The laboratory studies have identified a number of different molecules involved in inflammation that are inhibited by curcumin including phospholipase, lipooxygenase, cyclooxygenase 2, leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1 (MCP-1), interferon-inducible protein, tumor necrosis factor (TNF), and interleukin-12 (IL-12).


CONCLUSIONS
Curcumin has been demonstrated to be safe in six human trials and has demonstrated anti-inflammatory activity. It may exert its anti-inflammatory activity by inhibition of a number of different molecules that play a role in inflammation.