Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling

High‐grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to the emergence of treatment‐resistant subclones. We sought to measure the degree of genomic diversity within primary, untreated HGSCs to examine the natural state of tumour evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially and temporally separated HGSC tumour specimens (six patients), including ovarian masses, distant metastases and fallopian tube lesions. We found widespread intratumoural variation in mutation, copy number and gene expression profiles, with key driver alterations in genes present in only a subset of samples (eg PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range 10.2–91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole‐genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology, with common aetiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating that diversity arises at early stages of tumourigenesis. Our results revealed that HGSCs exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug‐resistance mechanisms. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Limits and potentials to deliberative engagement in highly regulated planning systems: Norm development within fixed rules

Planning practice requires ongoing interaction between regulatory “facts” and deliberative “norms”. Played out in local and strategic developments, “norms” are the agreed values and positions developed by advancing deliberative engagement of residents; while “facts” are the more rigid statutory procedures through which planning decisions are typically made. However, conflict arises between residents' groups and local government decision-makers when deliberative norms, now a key tenet of strategic planning processes, struggle to gain traction in the factual spaces provided by statutory planning regulations. A contentious planning process in St Kilda, Melbourne, Australia (concerning the redevelopment of a car park into a commercial and public space) highlights the challenges to deliberative engagement in highly-regulatory planning systems. Drawing on this contested case, this paper examines how the broader formal and relatively fixed framework of regulatory-based decision-making fails to support participatory principles, undermining both the desired communicative ethos and enduring collaborative outcomes and norm development. Specifically, the paper problematises tensions between residents' growing expectations for greater transparency and participation in planning, arising from a growing regard for deliberation in strategic planning, and the hegemonic nature of statutory planning that preserves planning control within the formal domain of government and the private sector.
Single-mode generation of quantum photon states by excited single molecules in a microcavity trap.

The active microcavity is adopted as an efficient source of non-classical light. By this device, excited by a mode-locked laser at a rate of 100 MHz, single-photons are generated over a single field mode with a nonclassical sub-poissonian distribution. The process of adiabatic recycling within a multi-step Franck-Condon molecular optical-pumping mechanism, characterized in our case by a quantum efficiency very close to one, implies a pump self-regularization process leading to a striking n-squeezing effect. By a replication of the basic single-atom excitation process a beam of quantum photon |n> - states (Fock states) can be created. The new process represents a significant advance in the modern fields of basic quantum-mechanical investigation, quantum communication and quantum cryptography.
Endoscopic ultrasound–guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications

OBJECTIVES:The aims of this study were to evaluate the diagnostic accuracy of endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) in patients with suspected pancreatic cancer, and to assess immediate, acute, and 30-day complications related to EUS-FNA.METHODS:All patients with suspected pancreatic cancer were prospectively evaluated. A single gastroenterologist performed all EUS-FNAs in the presence of a cytopathologist. Immediate complications were evaluated in all patients. An experienced nurse called patients 24–72 h and 30 days after the procedure. Reference standard for the classification of the final diagnosis included: surgery (n = 48), clinical or imaging follow-up (n = 63), or death from the disease (n = 47). RESULTS:A total of 158 patients (mean age 62.3 yr) underwent EUS-FNA during the study period. The mean tumor size was 32 × 26 mm. The median number of passes was three (range one to 10). Of these patients, 44% had at least one failed attempt at tissue diagnosis before EUS-FNA. The sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNA in solid pancreatic masses were 84.3%, 97%, 99%, 64%, and 84%, respectively. Immediate self-limited complications occurred in 10 of the 158 EUS-FNAs (6.3%). Of 90 patients contacted at 24–72 h, 78 patients (87%) responded. Of the 90 patients, 20 (22%) reported at least one symptom, all of which were minor except in three cases (one self-limited acute pancreatitis and two emergency room visits, one of which led to admission). In all, 83 patients were contacted at 30 days, and 82% responded. No additional or continued complications were reported.CONCLUSIONS:EUS-FNA is highly accurate in identifying patients with suspected pancreatic cancer, especially when other modalities have failed. Major complications after EUS-FNA are rare, and minor complications are similar to those reported for upper endoscopy. It seems that follow-up at 1 wk might capture all of the adverse events related to EUS-FNA.
Why Firms Purchase Property Insurance?

We investigate whether corporate finance incentives affect the extent of corporate hedging with property insurance. Using a database that contains detailed insurance information, we document a positive relation between the expected costs of distress and property insurance coverage. We also show that the dividend payout ratio is negatively associated with property insurance coverage, consistent with the view that firms with high payout ratios insure a smaller fraction of properties due to cash flows in excess of investment needs, easy access to capital markets, or both. Different incentives are important for the insurance deductible and limit of coverage, and the deductible and limit of coverage are substitutes.
Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee.

UNLABELLED Wounds penetrating articular cartilage to bone heal with cartilage described variably as either fibrous or hyaline. In the present study, such repair cartilage was induced in the rabbit for biochemical comparison with normal articular cartilage. The main collagen in the repair tissue after three weeks was type I. By six to eight weeks, type II had become predominant and continued to be enriched up to one year; but type I still persisted as a significant constituent of the repair tissue even after a year, so the repair cartilage never fully resembled normal articular cartilage. From radiochemical analysis, type II was determined to be the major collagen synthesized by the repair tissue after three to four weeks. After six months, the repair cartilage contained more collagen and less hexosamine than control cartilage, suggesting that the fibrous texture that often developed was due to a loss of proteoglycans rather than to a change in the type of collagen. CLINICAL RELEVANCE Procedures capable of inducing the differentiation of authentic articular cartilage to resurface degenerated human joints would be invaluable. Surgical methods, such as drilling through to subchondral bone, are often attempted. It is not known, however, whether the cartilage that forms is true articular cartilage or, for example, fibrocartilage. The present experimental study in rabbits compared the properties of such repair cartilage with those of normal articular cartilage.
Hormonal dysfunction in neurocritical patients

Purpose of reviewAcute brain injury results in widespread systemic endocrine dysfunction and affects how we care for patients. We review the existing literature on incidence, type and duration of endocrine dysfunction with special focus on the pituitary dependent function. Recent findingsAcute studies document widespread alterations of the hypothalamic–pituitary–adrenal axis, disruption of the anterior hypothalamus related hormones, and alteration of regulation of sodium and fluid balance. Diagnostic testing and therapeutic intervention are outlined in this review. Relative adrenal insufficiency and cerebral salt wasting are the two main forms of endocrine dysfunction in neurocritical care patients. SummarySurveillance for endocrine dysfunction and early treatment with hormonal replacement may be life-saving in neurologic critically ill patients.
Do Monetary and Non-Monetary Indicators Tell the Same Story About Chronic Poverty? A Study of Vietnam in the 1990s

This paper investigates whether monetary and nonmonetary indicators tell the same story about chronic poverty using a unique panel data from Vietnam in the 1990s. Defining chronic poverty as occurring when an individual is monetarily poor, stunted, malnourished or out of school in both waves of the panel, the overlap and correlation between subgroups of the chronically poor are shown to be modest. Some, but not all, nonmonetary indicators are more persistent and complement monetary indicators of chronic poverty. Taking account of the multiple dimensions of chronic poverty cannot be a simple additive exercise.
Effects of central and peripheral administration of leptin on pain threshold in rats and mice.

OBJECTIVE This study was planned to investigate the effects of exogenous leptin on the pain threshold. METHODS Adult male Wistar rats weighing 250-300 g and mice weighing 25-30 g were used in this study. Leptin was intracerebroventricularly (i. c. v.) injected in a dose of 3.5 micro g/rat. Mice were intraperitoneally (i. p.) injected with leptin in a dose of 25 micro g/mouse. Control animals were injected with the respective vehicle. The pain threshold test was performed using hot plate analgesia meter. The experiments were performed during the day and at night. The data were statistically analysed by Mann-Whitney U test. Level of significance was set at p<0.05. RESULTS During the day, there were no significant changes in hot plate latencies half an hour after i.c. v. injection of vehicle or leptin in the control and leptin-treated rats, respectively. At night, like during the day, i.c. v. injection of neither vehicle nor leptin caused any significant change in pain sensitivity. In mice, i.p. injection of leptin decreased latencies significantly (p<0.05) during the day and at night. Thus, leptin caused an increase in pain sensitivity during the day and at night. CONCLUSION These results clearly demonstrated that leptin has a decreasing-effect on pain threshold if it is peripherally administered in mice.
A Framework for Analyzing Efficiency, Risks, Costs, and Innovations in the Payments System

THE MARKET FOR PAYMENT INSTRUMENTS, such as cash, checks, and electronic funds transfers, is one of the largest, most important, and economically interesting markets in the economic system. Virtually every economic transaction requires the use of a payment instrument. Therefore, on a value basis, the demand for payment instruments equals the demand for all other goods, services, assets, and other financial instruments traded in the economy combined. In a monetary economy, the buyers and sellers of any commodity must not only agree on the price and quantity to be exchanged, but must also concur on the payment method that will be employed in the exchange. That is, every commodity buyer takes on the role of a payor and every commodity seller takes on the role of a payee, and they jointly demand a payment instrument of equal value to the commodities exchanged. The size of payments markets is illustrated in Table 1, which shows transactions
Measurement of Tourism Market Potential of Croatia by Use of Delphi Qualitative Research Technique

Abstract The Delphi survey as an effective qualitative marketing research tool was designed to project the future Croatian tourism scenario from 2001 through the year 2020. It is predicted that Croatian tourism industry will grow and prosper substantially over the next decade due to increased tourist demand for non-traditional holiday destinations. There will also be a high demand for activity-based tourism and eco-tourism. Although the tourism demand projections predict positive trends in the coming term, it is subject to a host of uncontrollable factors which make long-term projections difficult and cumbersome. In view of the developments and changes, tourism industry operators and public sector planners need scientifically accepted projection bases for tourism investment and effective operational tourism decisions. In this vein, this research qualitatively forecasts the tourism market potential and identifies the most significant future trends in Croatian tourism and hospitality.
Advertising, Profits, and Corporate Taxes

SOME of the highest profit rates appear in industries that advertise heavily. These high earnings have been attributed to barriers to entry associated with product differentiation [2, 6]. A possible alternative explanation is that the treatment of long-lived advertising as current expenses leads firms that invest heavily in such intangibles to overstate their rates of return since their equity is understated [1, p. 153; 15, p. 167]. The same practice may result in the understatement of their dollar profits so that they pay less tax than other firms whose investments are all tangible. The purpose of this paper is to work out more precisely the overor under-statement of profit and rate of return involved in the "expensing" of advertising and to evaluate the mis-statement in practice. ' Part I develops conceptually the conditions under which overor under-statements can be expected. Part II recomputes dollar profits and rates of return for a variety of industries, estimates the tax avoidance that results, and examines the relationship between recomputed profit rates and advertising. Part III contains a proposal for policy change.
Heterogeneous Preferences, Education Expenditures and Income Distribution

This paper introduces heterogeneous preferences to a growth model that incorporates human capital, accumulated through either public or private education. The implications of heterogeneous preferences for income and its distribution are the focus of the paper. Public education expenditure is determined through a voting mechanism where the median preference rather than median income household is the decisive voter. The paper extends the work of G. Glomm and B. Ravikumar (1992) and shows, first, that heterogeneous preferences increase income inequality in the private education model and, second, public education can overcome the added heterogeneity and reduce income inequality. The results strengthen the arguments for public education as a redistributive mechanism. Copyright 1999 by The Economic Society of Australia.
Lack of Annexin 1 Results in an Increase in Corticotroph Number in Male but not Female Mice

Annexin 1 (ANXA1) is a member of the annexin family of phospholipid‐ and calcium‐binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the pituitary. We have examined corticotrophs in wild‐type and ANXA1 knockout mice to determine the effects of lack of ANXA1 in male and female animals. Anterior pituitary tissue from ANXA1 wild‐type, heterozygote and null mice was fixed and examined (i) by confocal immunocytochemistry to determine the number of corticotrophs and (ii) by electron microscopy to examine the size, secretory granule population and secretory machinery of corticotrophs. No differences in these parameters were detected in female mice. In male ANXA1 null mice, there were approximately four‐fold more corticotrophs than in wild‐type animals. However, the corticotrophs in ANXA1 null mice were smaller and had reduced numbers of secretory granules (the reduction in granules paralleled the reduction in cell size). No differences in the numerical density of folliculo‐stellate, gonadotroph, lactotroph or somatotroph cells were detected in male ANXA1 null mice. Plasma corticosterone, adrenocorticotrophic hormone (ACTH) and pituitary pro‐opiomelanocortin mRNA were unchanged but pituitary ACTH content was increased in male ANXA1 null mice. Interleukin (IL)‐6 pituitary content was significantly elevated in male and reduced in female ANXA1 null mice compared to wild‐type. In conclusion, these data indicate that ANXA1 deficiency is associated with gender‐specific changes in corticotroph number and structure, via direct actions of ANXA1 and/or indirect changes in factors such as IL‐6.
Use of regulated cell lysis in a lethal genetic selection in Escherichia coli: identification of the autoinducer-binding region of the LuxR protein from Vibrio fischeri ATCC 7744

A lethal genetic selection utilizing the bacteriophage lambda lysis genes (S, R, RZ) has been developed and used in conjunction with a luminescence screen to allow the isolation and characterization of six missense mutations and two nonsense mutations in the luxR gene from Vibrio fischeri ATCC 7744. A transcriptional fusion of the lysis genes in operonR downstream of a truncated luxI gene allows control of cell lysis by the addition of synthetic autoinducer to the growth medium. The six missense mutations isolated resulted in changes in the LuxR protein of Asp at position 79 to Asn (hereafter designated as D79N), V82I, V109L, L118F, S123I, and H217Y. Variant LuxR proteins with amino acid changes of D79N, V82I, V82L, and H127Y were shown to require higher concentrations of autoinducer to elicit a certain amplitude response than is required by the wild-type protein. We believe that the clustering of a total of seven randomly generated missense mutations in a 49-amino-acid region of the LuxR primary sequence defines a critical portion of the LuxR protein. The observation that proteins with lesions in this region responded to elevated levels of autoinducer suggests that the autoinducer-binding site is constructed, at least in part, from several amino acid residues within the 79-to-127 region of the LuxR protein.
Blood Group Antigen Studies of Four Chibchan Tribes

THE four tribes whose various blood group frequencies constitute the principal subject matter of the present paper are found associated here because they speak languages of the same phylum; i.e. Chibchan. Chibchanspeaking tribes have been distributed throughout the area between Honduras in the North and Colombia and Ecuador in the South, and according to recent investigations they are also supposed to have penetrated into such distant eastern territories as the Orinoco Delta and southern Venezuela. Generally speaking, however, the Chibcha are highland people who occupied the mountainous regions of the above mentioned territories, where they developed a formative type of culture with chiefdoms, relying on a stable surplus production of agricultural goods for the maintenance of their political and religious institutions. From several points of view the Chibcha represent one of the more important indigenous populations of our continent, the study of which can greatly advance our knowledge of American anthropology and which should actually be accelerated by all priority measures available. Unfortunately, however, they have never been studied comprehensively from the different angles of our specialization, so that there exists considerable confusion as to the definite cultural and genetic identification of the various ethnic entities they comprise.
Virtual access point to the Cloud

Adapting virtualization concepts to satisfy many of today's network telecommunication challenges receives more and more attention. We have developed virtual environment design to allow the coexistence of virtual networks and their respective operators. In our approach, virtualized wireless access equipment are deployed to provide users more flexibility to access their services delivered by Cloud providers. In this demo, we demonstrate how we improved virtual network urbanization by including virtualized access point equipment. We have developed this approach to support wireless network advantages such as mobility, coverage areas, installation speed and simplicity. Each virtual access point is also conceived and adapted to guarantee the convenient access to the provided Cloud computing services.
A Note on a Framework to Assess the Required Equity Risk Premium Using Cumulative Prospect Theory

We provide a framework to ascertain the required equity risk premium (ERP) within the setting of Cumulative Prospect Theory (CPT) over arbitrary investment time periods. Once accounting for behavioral biases in estimating distributions (generated by using a simulation of asset returns based on a sampling procedure) and using a CPT utility function, it becomes apparent that the key determinant of the required ERP is an investor’s time horizon.
Obesity in older persons

Purpose of reviewThere is an increasing number of reports suggesting that indicators of obesity for the general adult population may need to be modified; that the magnitude of risk is attenuated or that adiposity may even be protective; and that additional adverse outcomes specific to older persons need to be considered. Finally, there are benefits and adverse effects of weight loss programmes for older persons. This article reviews publications addressing these issues from 2013 to March 2014. Recent findingsBMI was not considered to be as good an indicator of obesity because of loss of muscle mass with age. Higher body weight seems to be protective among older persons with chronic diseases or geriatric syndromes. Increased adiposity together with decreased muscle mass (sarcopenic obesity) is associated with adverse outcomes, although there is no consensus regarding the definition. Intentional weight loss has health benefits but is accompanied by muscle and bone loss, and therefore programmes should include components to counteract these changes. SummaryThe magnitude of health risk associated with obesity is attenuated with age, and mild increase in adiposity may be beneficial for those who are frail and/or with chronic diseases. Weight loss programmes should include resistance exercises to counteract muscle loss.
The Sharpe Ratio and the Information Ratio

The Sharpe ratio and the information ratio are routinely used in performance assessment; they are among the original risk-adjusted performance measures. Though they are simple metrics, practitioners should take care not to use them naively. This article highlights shortcomings of the two ratios and provides a framework for evaluating each ratio each within the appropriate context.