Miracle-dz/UniFAR-FTUs huggingface dataset:
Ovarian cancer - diagnosis and management.

BACKGROUND Epithelial ovarian cancer presents most often as late stage disease due to a lack of effective screening tests and vagueness of symptoms. OBJECTIVE This article outlines the diagnosis and management of ovarian cancer. DISCUSSION Women with suspected ovarian cancer are best managed in a gynaecological treatment unit offering multidisciplinary care. Surgery is usually needed both to make a diagnosis and for definitive treatment and referral to a specialty trained gynaecological oncologist is appropriate. Most women will also require chemotherapy. Ovarian cancers have good sensitivity to several drugs but relapse rates are high. This means that ovarian cancer is now seen as a chronic disease with often several episodes of remission, relapse and treatment. The psychological impact of this diagnosis both on the woman and her family are significant and best dealt with proactively.
Evidence for Metabolic Domains within the Matrix Compartment of Pea Leaf Mitochondria : Implications for Photorespiratory Metabolism.

The simultaneous oxidation of malate and of glycine was investigated in pea (Pisum sativum) leaf mitochondria. Adding malate to state 4 glycine oxidation did not inhibit, and under some conditions stimulated, glycine oxidation. State 4 oxygen uptake with glycine is restricted because of the control exerted by the membrane potential but reoxidation of NADH by oxaloacetate reduction can still occur. Thus, malate addition stimulates glycine metabolism by producing oxaloacetate. The malate dehydrogenase (EC 1.1.1.37) enzyme fraction remote from glycine decarboxylase (EC 2.1.2.10) oxidizes malate whereas that closely associated with it produces malate, i.e. they function in opposite directions. It is shown that these opposing directions of malate dehydrogenase activity occur within the same mitochondrial matrix compartment and not in different mitochondrial populations. It is concluded that metabolic domains containing different complements of mitochondrial enzymes exist within the one mitochondrial matrix without physical barriers separating them. The differential spatial organization within the matrix may account for the previously reported limited access of some enzymes to the respiratory electron transport chain. The implications for leaf mitochondrial metabolism are discussed.
Integrative biology of an embryonic respiratory behaviour in pond snails: the `embryo stir-bar hypothesis'

SUMMARY Embryos of freshwater snails undergo direct development from single cell to juvenile inside egg masses that are deposited on vegetation and other substratum in pond, lake and stream habitats. Helisoma trivolvis, a member of the Planorbidae family of basommatophoran snails, has served as a model for studying the developmental and physiological roles for neurotransmitters during embryogenesis. Early studies revealed that H. trivolvis embryos from stage E15 to E30, the period between gastrulation and the trochophore–juvenile transition, display a cilia-driven behaviour consisting of slow basal rotation and transient periods of rapid rotation. The discovery of a bilateral pair of early serotonergic neurons, named ENC1, which project an apical process to the embryo surface and basal neurites to ciliated cells, prompted the hypothesis that each ENC1 is a dual-function sensory and motor neuron mediating a physiological embryonic response. This article reviews our past and present studies and addresses questions concerning this hypothesis, including the following. (1) What environmental signal regulates ENC1 activity and rotational behaviour? (2) Does ENC1 function as both a primary sensory and motor neuron underlying the rotational behaviour? (3) What are the sensory transduction mechanisms? (4) How does ENC1 regulate ciliary beating? (5) Do other basommatophoran species have similar neural–ciliary pathways and behavioural responses? (6) How is the behaviour manifest in the dynamic natural environment? In this review, we introduce the `embryo stir-bar hypothesis', which proposes that embryonic rotation is a hypoxia-sensitive respiratory behaviour responsible for mixing the egg capsule fluid, thereby enhancing delivery of environmental oxygen to the embryo.
Transposable element evolution in the allotetraploid Capsella bursa-pastoris.

PREMISE OF THE STUDY Shifts in ploidy affect the evolutionary dynamics of genomes in a myriad of ways. Population genetic theory predicts that transposable element (TE) proliferation may follow because the genomewide efficacy of selection should be reduced and the increase in gene copies may mask the deleterious effects of TE insertions. Moreover, in allopolyploids, TEs may further accumulate because of hybrid breakdown of TE silencing. However, to date the evidence of TE proliferation following an increase in ploidy is mixed, and the relative importance of relaxed selection vs. silencing breakdown remains unclear. METHODS We used high-coverage whole-genome sequence data to evaluate the abundance, genomic distribution, and population frequencies of TEs in the self-fertilizing recent allotetraploid Capsella bursa-pastoris (Brassicaceae). We then compared the C. bursa-pastoris TE profile with that of its two parental diploid species, outcrossing C. grandiflora and self-fertilizing C. orientalis. KEY RESULTS We found no evidence that C. bursa-pastoris has experienced a large genomewide proliferation of TEs relative to its parental species. However, when centromeric regions are excluded, we found evidence of significantly higher abundance of retrotransposons in C. bursa-pastoris along the gene-rich chromosome arms compared with C. grandiflora and C. orientalis. CONCLUSIONS The lack of a genomewide effect of allopolyploidy on TE abundance, combined with the increases TE abundance in gene-rich regions, suggests that relaxed selection rather than hybrid breakdown of host silencing explains the TE accumulation in C. bursa-pastoris.
BEYOND HIERARCHICAL REPRESENTATIONS OF THE FORMAL/INFORMAL EMPLOYMENT DUALISM

ABSTRACT This paper evaluates critically the conventional hierarchical representation of the formal/informal employment dualism, which depicts formal employment as extensive and positively contributing to economic development and social cohesion, and the separate realm of informal employment as weaker, inhabiting the margins and impairing progress and development. Although the discourses of informal employment as weak, marginal and separate from formal employment have been previously put under the spotlight, there has been little questioning of whether informal employment is a negative phenomenon. Through a study of Ukraine, however, this paper finds evidence that informal employment positively contributes to not only economic development as a seedbed for enterprise and entrepreneurship but also social cohesion as a primary vehicle for delivering community self-help. The outcome is a call for a finer-grained understanding of informal (and ultimately also formal) employment that recognises its plurality of forms and their varying consequences for economic development and social cohesion.
SOCIAL PRISMS: AN INTERNATIONAL COMPARISON OF CHILDREARING MANUALS

Abstract This paper presents findings from a comparative study of childrearing values and practices in four countries–Japan, People's Republic of China, France, and United States–based upon a content analysis of the ten best-selling childrearing manuals in each country during the last decade of the twentieth century. A uniform set of procedures was used to classify and analyze the content of the manuals. Selected findings are discussed regarding: (1) management of the child's body and bodily functions: 12) management and shaping of the child's behavior; and (3) roles and role relationships within the family and outside. While cultural differences remain, two general trends emerge from the analysis. One is a trend toward more flexible child care practices and greater sensitivity to the character and needs of the individual child. The second is a convergence of opinion on many aspects of children's upbringing. Global trends that are affecting the production and dissemination of childrearing advice are also discussed.
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Subproblems have become an important object of NP-completeness theory since its beginning. In this paper, we show some undesirable consequences for subproblems deduced by the standard foundation of the theory, which are di fferent from the practical viewpoint of computation. By the consequences, we clarify further the range in which the standard foundation is applicable to decision problems.
Pathology of Encapsulating Peritoneal Sclerosis

Pathology findings of encapsulating peritoneal sclerosis (EPS) are reviewed to establish histologic criteria for a diagnosis of EPS. The typical macroscopic finding is a cocoon-like encapsulation of the entire intestine. This encapsulation is frequently accompanied by fibrin deposition, focal bleeding on the peritoneum, and various quantities of bloody ascites. A thin membrane on the visceral peritoneum contributes to the formation of the intestinal encapsulation. Histologically, the membrane is composed mainly of organized fibrin, probably derived from plasma exudation from the peritoneal microvasculature. The peritoneal fibroblasts appear swollen and exhibit an increased level of cellularity, accompanied by expression of various activation and proliferation markers. According to the “two-hit” theory of EPS pathogenesis, deterioration of the peritoneum as a result of the peritoneal dialysis (PD) procedure (the first “hit”) and superimposition of inflammatory stimuli such as infectious peritonitis (the second “hit”) are thought to play key roles in the pathogenesis of EPS. Based on histologic examination of peritoneal biopsy specimens, the detection of fibrin deposition and fibroblast phenotypic alteration were proposed as important findings for early diagnosis of EPS. Persistent inflammatory changes are also predictive of the future onset of EPS. Careful histologic evaluation of peritoneal biopsy specimens, combined with laparoscopic observations after withdrawal of PD, is required for the early diagnosis and treatment of EPS.
Neurodegeneration and Clinical Disease in Prion-Infected Mice Oral Treatment Targeting the Unfolded Protein Response Prevents

possibly other neurodegenerative diseases as well. data suggest that the UPR may represent a new therapeutic target for drug development to treat prion disease and emergence of clinical disease in prion-infected mice, whereas untreated animals all succumbed to disease. These pharmacological inhibition would be neuroprotective. The compound prevented neurodegeneration and the used a newly described specific inhibitor of a key UPR kinase mediating translational shutdown to test if long-term translational inhibition, causing a critical decline in key proteins needed for neuronal survival. The authors misfolded prion protein in mice with prion disease causes sustained overactivation of this pathway. This results in . now report that the buildup of et al load in a number of ways including transiently switching off translation. Moreno dealing with misfolded proteins called the unfolded protein response (UPR). The UPR deals with the misfolded protein brains of patients with these neurodegenerative diseases show overactivation of a cellular defense pathway for misfolded disease-specific proteins in the brain, leading to neuronal loss, which is ultimately fatal. In addition, the Parkinson's disease (PD), and prion disease. These diseases share common features, including the accumulation of There are no effective treatments for neurodegenerative disorders such as Alzheimer's disease (AD), Perking Up Prion Disease Therapy
A Half Century of Mate Preferences: The Cultural Evolution of Values

The qualities people believe are important in selecting a marriage partner afford one domain for assessing human values. We examined the cultural evolution of these values over more than half a century. Building on existing data on mate preferences collected in 1939 (N= 628), 1956 (N= 120), 1967 (N= 566), and 1977 (N= 316), we collected data using the same instrument in 1984/1985 (N= 1,496) and in 1996 (N= 607) at geographically diverse locations. Several changes in values were documented across the 57-year span. Both sexes increased the importance they attach to physical attractiveness in a mate. Both sexes, but especially men, increased the importance they attach to mates with good financial prospects. Domestic skills in a partner plummeted in importance for men. Mutual attraction and love climbed in importance for both sexes. The sexes converged in the ordering of the importance of different mate qualities, showing maximum similarity in 1996. Discussion speculates about causes of the cultural evolution of values.
Native-like attainment in L2-syntax

In this study, we test the prediction, derived from the Critical Period Hypothesis, that a native-level of attainment in L2 grammar cannot be reached by learners who start acquiring a second language after the onset of puberty. We selected 30 very advanced German and French late learners (age of arrival less than or equal to 12 years) of Dutch and compared their performance on a grammar test with that of 44 (highly educated) native speakers of Dutch. The test consisted of two tasks: an elicited imitation task and a relative grammaticality judgement task. In these tasks, participants were tested on their knowledge of dummy subject constructions. These construction types were chosen because they are known to be very hard to acquire for learners of Dutch as a second language. The results show that it is possible to attain a native level of proficiency for learners who start acquiring a second language (long) after puberty.
Treatment strategies for osteoarthritis patients with pain and hypertension

Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP), which is more marked in patients with established hypertension. NSAIDs and COX-2 inhibitors attenuate the antihypertensive effect of several antihypertensive agents. Frequent BP controls are needed in treated hypertensive patients who are concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase in BP may be associated with an important rise in the risk of major cardiovascular complications. In meta-analyses, an increase in systolic BP of 5 mmHg was associated with a 25% higher risk of cardiovascular events. These data have been confirmed in randomized studies with rofecoxib and celecoxib, where a modest increase in BP was associated with a significantly higher risk of cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric oxide donator (CINOD) class is promising in the treatment of patients with OA. Naproxcinod, the first CINOD investigated in clinical trials, is composed of the traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise in normotensive and hypertensive patients observed with naproxen. The BP benefit of naproxcinod over naproxen was greater in patients concomitantly receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. These investigational data suggest that naproxcinod is a valuable alternative to NSAIDs and COX-2 inhibitors for treatment of OA patients.
Genome to Phenome Mapping in Apple Using Historical Data

Apple (Malus X. domestica Borkh.) is one of the world's most valuable fruit crops. Its large size and long juvenile phase make it a particularly promising candidate for marker‐assisted selection (MAS). However, advances in MAS in apple have been limited by a lack of phenotype and genotype data from sufficiently large samples. To establish genotype‐phenotype relationships and advance MAS in apple, we extracted over 24,000 phenotype scores from the USDA‐Germplasm Resources Information Network (GRIN) database and linked them with over 8000 single nucleotide polymorphisms (SNPs) from 689 apple accessions from the USDA apple germplasm collection clonally preserved in Geneva, NY. We find significant genetic differentiation between Old World and New World cultivars and demonstrate that the genetic structure of the domesticated apple also reflects the time required for ripening. A genome‐wide association study (GWAS) of 36 phenotypes confirms the association between fruit color and the MYB1 locus, and we also report a novel association between the transcription factor, NAC18.1, and harvest date and fruit firmness. We demonstrate that harvest time and fruit size can be predicted with relatively high accuracies (r > 0.46) using genomic prediction. Rapid decay of linkage disequilibrium (LD) in apples means millions of SNPs may be required for well‐powered GWAS. However, rapid LD decay also promises to enable extremely high resolution mapping of causal variants, which holds great potential for advancing MAS.
Low-cost technologies for medical diagnostics in low-resource settings.

INTRODUCTION Medical diagnostics is a critical element of effective medical treatment. However, many modern and emerging diagnostic technologies are not affordable or compatible with the needs and conditions found in low- and middle-income countries. Resource-poor countries require low-cost, robust, easy-to-use, and portable diagnostic devices compatible with telemedicine that can be adapted to meet diverse medical needs. AREAS COVERED The most suitable devices are likely those that will be based on optical technologies, which are used for many types of biological analyses. This manuscript describes several prototypes of low-cost optical technologies and their application developed at the FDA's Office of Science and Engineering laboratories including a webcam-based multiwavelength fluorescence plate reader, a webcam-based fluorescence microscope demonstrated for colonic mucosa tissue pathology analysis, a lens-free optical detector used for the detection of Botulinum A neurotoxin activity, and a lab-on-a-chip which enables the performance of enzyme-linked immunosorbent assay and other immunological or enzymatic assays without the need of dedicated laboratories and complex equipment demonstrated for the detection of the toxin staphylococcal enterotoxin B. EXPERT OPINION Sensitive and effective optical detection devices can be developed using readily available consumer electronics components such as webcams, charge-coupled device cameras, and LEDs. There are challenges in developing devices with sufficient sensitivity and specificity. Several optical and computational approaches were developed to overcome these challenges to create optical detectors that can serve as low-cost medical diagnostics in resource-poor settings.
The Gab1 PH Domain Is Required for Localization of Gab1 at Sites of Cell-Cell Contact and Epithelial Morphogenesis Downstream from the Met Receptor Tyrosine Kinase

ABSTRACT Stimulation of the hepatocyte growth factor (HGF) receptor tyrosine kinase, Met, induces mitogenesis, motility, invasion, and branching tubulogenesis of epithelial and endothelial cell lines in culture. We have previously shown that Gab1 is the major phosphorylated protein following stimulation of the Met receptor in epithelial cells that undergo a morphogenic program in response to HGF. Gab1 is a member of the family of IRS-1-like multisubstrate docking proteins and, like IRS-1, contains an amino-terminal pleckstrin homology domain, in addition to multiple tyrosine residues that are potential binding sites for proteins that contain SH2 or PTB domains. Following stimulation of epithelial cells with HGF, Gab1 associates with phosphatidylinositol 3-kinase and the tyrosine phosphatase SHP2. Met receptor mutants that are impaired in their association with Gab1 fail to induce branching tubulogenesis. Overexpression of Gab1 rescues the Met-dependent tubulogenic response in these cell lines. The ability of Gab1 to promote tubulogenesis is dependent on its pleckstrin homology domain. Whereas the wild-type Gab1 protein is localized to areas of cell-cell contact, a Gab1 protein lacking the pleckstrin homology domain is localized predominantly in the cytoplasm. Localization of Gab1 to areas of cell-cell contact is inhibited by LY294002, demonstrating that phosphatidylinositol 3-kinase activity is required. These data show that Gab1 is an important mediator of branching tubulogenesis downstream from the Met receptor and identify phosphatidylinositol 3-kinase and the Gab1 pleckstrin homology domain as crucial for subcellular localization of Gab1 and biological responses.
Acute variations in extracellular pH modulate transduction pathways of PTH in rat proximal tubule.

An increase in circulating parathyroid hormone (PTH) has been shown to enhance the capacity for the kidney to excrete an acid as well an alkaline load, which suggests that changes in systemic acid-base status may modulate the effect of the hormone on bicarbonate absorption in proximal tubule. In the present study, we tested the possibility that acute variations in extracellular pH (pHe), obtained by modifying bicarbonate concentration at constant PCO2 (40 mmHg), may modulate the responses of intracellular messengers coupled to PTH receptors in a preparation of freshly isolated proximal tubule fragments. Variations in pHe, which induced parallel variations in intracellular pH (pHi), did not affect unstimulated values for adenosine 3',5'-cyclic monophosphate (cAMP) production, inositol trisphosphate accumulation, or cytosolic free Ca2+ concentration. In contrast, reducing pHe from 7.4 to 7.2 elicited a decrease of the PTH-induced cAMP production, whereas increasing pHe from 7.4 to 7.6 enhanced it. The ability for cholera toxin and forskolin (which both bypass PTH receptors) to stimulate cAMP formation was diminished at pHe 7.2 and enhanced at pHe 7.6 (the increase did not achieve statistical significance in the presence of forskolin), suggesting that variations in pHe and/or pHi may affect per se adenylyl cyclase activity. Conversely, reducing pHe from 7.4 to 7.2 enhanced the PTH-induced inositol trisphosphate accumulation and rise in cytosolic free Ca2+ whereas increasing pHe from 7.4 to 7.6 had opposite effects. (ABSTRACT TRUNCATED AT 250 WORDS)
Toward effectively generating environment maps

We explore a cost-effective approach to creating envi- ronment maps. Unlike other environment map generating systems that use specially designed mirrors or sensing devices, our system uses off-the-shelf digital cameras. This makes our system poten- tially acquirable by average consumers. In our design, the two digital cameras are displaced vertically with parallel optical axes, and the rotation axis passes through the focal points of the two cameras. This vertical displacement arrangement overcomes the problem of having inconsistent occlusions in two adjacent stereo image sets that happen in a horizontally displaced stereo camera system. To obtain dense spatial images, our system uses color-information- based algorithms to propagate disparity values from matched fea- ture points to unmatched feature points and featureless areas. Schemes of transforming local 3-D (X,Y,Z) data to a world coordi- nate system are also devised to smoothly stitch 3-D data from indi- vidual frames for virtual reality modeling language graphics display.