Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic Value of Immunohistochemical Staining of p53, bcl-2, and Ki-67 in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is one of the most fatal cancers in humans and many factors are known to be related to its poor prognosis. Immunohistochemical (IHC) stainings were done on SCLC specimens in order to investigate the prognostic value of the apoptosis-related gene expression and the tumor proliferative maker, and the relationships among these IHC results and patients clinical characteristics, chemoresponsiveness, and survival were analyzed. The medical records of 107 patients were reviewed retrospectively. IHC stainings for p53, bcl-2 and Ki-67 expressions were performed in the 66 paraffin-embedded biopsy samples. Sixty-six out of the 107 patients were evaluable for response rate and survival. The overall response rate was 75% (95% Confidence Interval=74-76%) and the median survival time was 14 months. The median survival time of limited stage was 16 months and that of extensive stage was 10 months. The prevalence of p53, bcl-2 and Ki-67 expression was 62%, 70%, and 49%, respectively. There were no correlations among the immunoreactivities of p53, bcl-2 and Ki-67 with clinical stage, chemoresponsiveness or overall survival. The clinical stage was the only prognostic factor influencing survival. The expression rates of p53, bcl-2, and Ki-67 were relatively high in SCLC without any prognostic significance. The exact clinical role of these markers should be defined through further investigations.
C/EBPδ regulates cell cycle and self-renewal of human limbal stem cells

Human limbal stem cells produce transit amplifying progenitors that migrate centripetally to regenerate the corneal epithelium. Coexpression of CCAAT enhancer binding protein δ (C/EBPδ), Bmi1, and ΔNp63α identifies mitotically quiescent limbal stem cells, which generate holoclones in culture. Upon corneal injury, a fraction of these cells switches off C/EBPδ and Bmi1, proliferates, and differentiates into mature corneal cells. Forced expression of C/EBPδ inhibits the growth of limbal colonies and increases the cell cycle length of primary limbal cells through the activity of p27Kip1 and p57Kip2. These effects are reversible; do not alter the limbal cell proliferative capacity; and are not due to apoptosis, senescence, or differentiation. C/EBPδ, but not ΔNp63α, indefinitely promotes holoclone self-renewal and prevents clonal evolution, suggesting that self-renewal and proliferation are distinct, albeit related, processes in limbal stem cells. C/EBPδ is recruited to the chromatin of positively (p27Kip1 and p57Kip2) and negatively (p16INK4A and involucrin) regulated gene loci, suggesting a direct role of this transcription factor in determining limbal stem cell identity.
Common Belief Foundations of Global Games

We study coordination games under general type spaces. We characterize rationalizable actions in terms of the properties of the belief hierarchies and show that there is a unique rationalizable action played whenever there is approximate common certainty of rank beliefs, defined as the probability the players assign to their payoff parameters being higher than their opponents'. We argue that this is the driving force behind selection results for the specific type spaces in the global games literature. (This abstract was borrowed from another version of this item.)
Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants, Prolactin and Breast Cancer

Selective serotonin reuptake inhibitors (SSRIs) are a widely prescribed class of antidepressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003 to 2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with non-users of SSRIs (OR = 1.01, CI = 0.88–1.17 and OR = 0.91, CI = 0.67–1.25 respectively), regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99–3.40) for long-term users of sertraline (≥24 prescriptions), given the small number of exposed cases (n = 12), the borderline statistical significance, and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.
Multiregion sequencing reveals the intratumor heterogeneity of driver mutations in TP53‐driven non‐small cell lung cancer

Intratumor heterogeneity (ITH) in non‐small cell lung cancer (NSCLC) may account for resistance after a period of targeted therapies because drugs destroy only a portion of tumor cells. The recognition of ITH helps identify high‐risk patients to make effective treatment decisions. However, ITH studies are confounded by interpatient heterogeneity in NSCLC and a large amount of passenger mutations. To address these issues, we recruited NSCLC patients carrying TP53 mutations and selected driver mutations within recurrently mutated genes in NSCLC. A total of 12‐paired normal‐tumor tissues were subjected to whole‐genome/whole‐exome sequencing. From these, 367 non‐silent mutations were selected as driver mutations and deeply sequenced in 61 intratumoral microdissections. We identified a universal prevalence of heterogeneity in all 12 tumors, indicating branched evolution. Although TP53 mutations were observed in single biopsy of all 12 tumors, most tumors consist of both TP53 mutated and non‐mutated cells in separate regions within the same tumor. This suggests the late molecular timing of the acquisition of TP53 mutations; therefore, the detection of TP53 mutations in a single biopsy may simply not reflect the early malignant potential. In addition, we identified regions of loss of heterozygosity surrounding TP53 and CDKN2A mutations in tumor 711, which also exhibited heterogeneity in different regional samples. Because the ITH of driver mutations likely has clinical consequences, further efforts are needed to limit the impact of ITH and to improve therapeutic efficiency, which will benefit NSCLC patients receiving targeted treatments.
Test of the Equivalence Principle Using Atomic Vacuum Energy Shifts

We consider possible tests of the Einstein equivalence principle for quantum-mechanical vacuum energies by evaluating the Lamb shift transition in a class of nonmetric theories of gravity described by the T H eµ formalism. We compute to lowest-order the associated redshift and time dilation parameters, and discuss how (high-precision) measurements of these quantities could provide new information on the validity of the equivalence principle.
The miraculous survival of an exceptional baby: can a heart manage to function with anomalous origin of both coronary arteries from the pulmonary artery?

The case reported by Ochoa-Ramirez and colleagues1 in this issue brings new light to an exceptionally rare entity—anomalous origin of all the coronary arteries from the pulmonary (AOCAP)—that is usually considered incompatible with survival.2–8 The literature on AOCAP was reviewed in detail by Heifetz and co-authors7 and, more recently, by Heusch and associates,8 who found 30 cases in 1997. The literature is marred by loose definition of the entity. We propose that AOCAP be defined as a cardiac condition in which 2 great vessels are present and the whole of the coronary circulation arises from the pulmonary artery, with any number of coronary ostia. Out of Heusch's 30 cases,8 13 had complex associated anomalies (like common truncus arteriosus and pulmonary atresia) that significantly altered both the clinical presentation and the surgical implications. If those cases are excluded, 17 cases were reviewed by Heusch. For those 17 patients, the mean age at successful surgery or at death was 29.4 days. Only 2 patients had survived surgery at the time that their cases were published.8,9
Template generation from postmarks using cascaded unsupervised learning

Information in historical datasets comes in many forms. We are working with a set of World War I era postcards that contain hand written text, some preprinted text, postage stamps and postmark/cancellation stamps. The postmarks are of considerable interest to collectors looking for images of samples they had not previously seen. The postmarks also provide information on the originating location of the card that complements the information in the address block. The postmarks vary considerably with towns and dates, but also styles. The styles can be grouped into categories. A method for automatically extracting templates for each category of these postmark stamps is described. The problem is complicated by the high levels of degradation present in the cards. The approach uses a cascade of unsupervised learning steps separated with image cleaning. This introduces averaging steps, which reduces noise. It also provides a reduction in the number of comparisons between samples. While merges happen at each stage, the number of times merges are needed within each stage is reduced. The templates once extracted can be used to group the postmarks, and will contribute information about the postmark content to better separate the postmark from the paper and other interfering marks to extract further information about the postmarks and postcards.
The black box of schooling: a cultural history of the classroom

not so much a vocation as a necessity: Vasavi Koka was encouraged at home to enquire about the world and record her observations, and travel, diaspora and diversity also characterise the other stories. On the issue of transferability, it could be said that the initial claims are inferred rather than substantiated with verifiable evidence or reasoned analysis. Perhaps, following the nature of auto-ethnographic methodology (dependent on a rhetoric of authenticity), Hickman’s strategy is to present persuasive models of best practice. In this way he hopes that readers from across the secondary curriculum and beyond will recognise the gap between contributors’ pedagogies and their own, and might apply the book’s recommendations (both implicit and explicit) to those instances where they perceive a lack. Certainly the emergent themes discussed by Hickman and their pedagogical implications raise significant areas for further reflection and research. Despite this reflective turn, the central stories are primarily advocacy, and some of the testimony does indeed convince. As such, the collection is an accessible and engaging account of pedagogic experiences out of which much useful debate could arise. In particular, student teachers will identify with and welcome such narrative-based accounts, as will educators returning to academic study after years of teaching. At their best, and unlike the propositional tenor of much advocacy, these stories recount narratives of possibility that are realised.
Modelling South African grain farmers' preferences to adopt derivative contracts using discrete choice models

Abstract This paper applies a discrete choice model to determine specific characteristics that influence South African grain farmers' preferences to hedge against uncertainties. This is the first empirical study on South African grain producers' preferences to adopt derivative contracting and is based on the survey data of Grain South Africa for 2006. With the application of separate binary logit models for each major grain commodity, this paper establishes that different grain farmers are significantly heterogeneous. The results also show that grain farmers' preferences to adopt derivative contracting are mostly influenced by the farmers' prediction of daily grain prices and trends, farm size and various geographic characteristics. From a policy perspective it has been indicated that food and income insecurity will be reduced if farmers can adopt derivative contracting at large scale since it will enable the producers to produce staple food on a continuous basis at a relatively profitable level.
SimB16: Modeling Induced Immune System Response against B16-Melanoma

Immunological therapy of progressive tumors requires not only activation and expansion of tumor specific cytotoxic T lymphocytes (CTLs), but also an efficient effector phase including migration of CTLs in the tumor tissue followed by conjugation and killing of target cells. We report the application of an agent-based model to recapitulate both the effect of a specific immunotherapy strategy against B16-melanoma in mice and the tumor progression in a generic tissue section. A comparison of the in silico results with the in vivo experiments shows excellent agreement. We therefore use the model to predict a critical role for CD137 expression on tumor vessel endothelium for successful therapy and other mechanistic aspects. Experimental results are fully compatible with the model predictions. The biologically oriented in silico model derived in this work will be used to predict treatment failure or success in other pre-clinical conditions eventually leading new promising in vivo experiments.
Cobalt(III) as a Stable and Inert Mediator Ion between NTA and His6-Tagged Proteins**

Don't let go! The Co(3+)-mediated interaction between nitrilotriacetic acid (NTA) and the His6-tag is so stable and inert towards ligand exchange that it has a half-life of 7 days in the presence of imidazole and survives even under strongly chelating as well as reducing conditions, unlike the commonly used Ni(2+) or Co(2+) complexes. Possible applications include the separation of labeled proteins and the stable immobilization of proteins on surfaces.
The Philosophy of Creative Writing

Philosophy concerns asking fundamental questions about practices, concepts and objects: their meaning, how they function, what they presuppose and what makes them distinctive. Within Creative Writing, we often ask about the effectiveness of the workshop, classroom activities or we inquire about our subject's past and present distinctiveness. But the question of a philosophy or philosophies of CW has gone largely unasked. This paper considers a number of questions about how CW articulates itself in terms of its view of teaching, autonomy and the scope of CW research. The paper argues that if CW is to be an autonomous discipline, then various problems need to be addressed. It concludes by identifying two current schools, or philosophies, of CW: integrationism and monarchism. Whereas the latter seeks to rationalise CW as an autonomous discipline, the former seeks to see it as part of a broader education in the humanities. Ultimately, the paper seeks to create a framework for a new area of investigation in CW scholarship.
HybProbes‐based real‐time PCR assay for specific identification of Streptomyces scabies and Streptomyces europaeiscabiei, the potato common scab pathogens

The aim of this study was to develop and validate a HybProbes‐based real‐time PCR assay targeting the trpB gene for specific identification of Streptomyces scabies and Streptomyces europaeiscabiei. Four primer pairs and a fluorescent probe were designed and evaluated for specificity in identifying S. scabies and Streptomyces europaeiscabiei, the potato common scab pathogens. The specificity of the HybProbes‐based real‐time PCR assay was evaluated using 46 bacterial strains, 23 Streptomyces strains and 23 non‐Streptomyces bacterial species. Specific and strong fluorescence signals were detected from all nine strains of S. scabies and Streptomyces europaeiscabiei. No fluorescence signal was detected from 14 strains of other Streptomyces species and all non‐Streptomyces strains. The identification was corroborated by the melting curve analysis that was performed immediately after the amplification step. Eight of the nine S. scabies and S. europaeiscabiei strains exhibited a unique melting peak, at Tm of 69·1°C while one strain, Warba‐6, had a melt peak at Tm of 65·4°C. This difference in Tm peaks could be attributed to a guanine to cytosine mutation in strain Warba‐6 at the region spanning the donor HybProbe. The reported HybProbes assay provides a more specific tool for accurate identification of S. scabies and S. europaeiscabiei strains.
Two directions of change in one corpus: Phonology vs morphosyntax in Tyneside English

Cheshire et al. (2005) argue that different levels of language do not necessarily follow the same patterns of change over time. In an attempt to test this prediction, this article reports on a comparison between two quantitative corpus studies of Tyneside English which are partly based on the same data. The first study was carried out by Watt and investigated levelling in the phonological variables in the FACE and GOAT lexical set (Watt 2002) based on data collected in 1994. Watt found that speakers were abandoning broad local vernacular variants in favour of more regional or generally Northern forms. The second study was a study of seven morphosyntactic variables based on data collected in the 1960s, 1994 and 2007-2009. This study found that the variables under investigation were either stable over time or used more frequently in the most recent data. Thus, the comparison of the two studies shows support for Cheshire et al. (2005). This difference in the direction of change is sought explained by socio-psychological processes linking linguistic forms, the local Tyneside area and speaker identity. More specifically, it is argued that speakers imbue local vernacular variants with social meaning (Podesva 2006). This means that speakers create a social index (Silverstein 2003) which links linguistic forms and additional non-denotational meanings through processes of enregisterment (Agha 2003). This allows speakers to express an affiliation with their local area and all that it represents to them at a time when this area is undergoing vast changes.
Examining Differences in Kindergarteners’ Mathematics Learning: A Closer Look at Instruction, Socioeconomic Status, and Race

ABSTRACT The author examined whether mathematics instruction provided by kindergarten teachers is related to children's mathematics learning during the kindergarten year based on the children's socioeconomic status and race. Hierarchical linear modeling was employed using a large sample of kindergarten students to estimate relationships between the teacher's instructional approach (e.g., concrete-spatial, interpersonal, linguistic) and children's mathematics skills. Results showed that the teacher's instructional approach was selectively related to children's mathematics learning. Students in classrooms where teachers frequently employed a concrete-spatial instructional approach learned more during the kindergarten year. Students from lower socioeconomic backgrounds benefitted more from teachers who often employed an interpersonal approach, and Black/African American students benefitted less from classrooms where teachers relied more on a linguistic approach. The findings suggest that kindergarten teachers’ instruction needs to employ varied methods that take into account students’ mathematics skills and background characteristics.
Financial Barrier against Access to Diagnostic Procedures among Enteric Fever Suspects in Highly-endemic Areas of China

There is currently no public financial system that fully covers enteric fever suspects in China. This study aimed at documenting the level of access to definitive diagnostic procedures, especially haemoculture, for these patients and examining the effect of health insurance on access to such care. A hospital-based cross-sectional study was conducted in six counties of Yunnan province, using a structured questionnaire and data extraction from medical records. In total, 714 subjects were recruited. Chi-square test and logistic regression were employed for analysis of data. The majority of the subjects were young adults (52%) and farmers (55%) from low-income families (49%). Only 407 (57%) could afford haemoculture routinely advised by their doctors. Of these, 123 (30%) had haemoculture positive for Salmonella Typhi. After adjustment for income, not getting haemoculture was marginally associated with percentage of reimbursement from the insurance (p value for trend=0.047). Illiteracy was also an independent risk factor for this outcome. The poor coverage of haemoculture for patients suspected of having enteric fever in this endemic area was due to financial barrier. The current health-insurance system inadequately relieved the problem. Further financial reform to help patients suspected with enteric fever is required.
Rendering glints on high-resolution normal-mapped specular surfaces

Complex specular surfaces under sharp point lighting show a fascinating glinty appearance, but rendering it is an unsolved problem. Using Monte Carlo pixel sampling for this purpose is impractical: the energy is concentrated in tiny highlights that take up a minuscule fraction of the pixel. We instead compute an accurate solution using a completely different deterministic approach. Our method considers the true distribution of normals on a surface patch seen through a single pixel, which can be highly complex. We show how to evaluate this distribution efficiently, assuming a Gaussian pixel footprint and Gaussian intrinsic roughness. We also take advantage of hierarchical pruning of position-normal space to rapidly find texels that might contribute to a given normal distribution evaluation. Our results show complex, temporally varying glints from materials such as bumpy plastics, brushed and scratched metals, metallic paint and ocean waves.
Vaccines against blood-feeding nematodes of humans and livestock

This paper summarises the progress towards vaccine development against the major blood-feeding nematodes of man and livestock, the hookworms and Haemonchus contortus, respectively. The impact of the diseases and the drivers for vaccine development are summarized as well as the anticipated impact of the host immune response on vaccine design. The performance requirements are discussed and progress towards these objectives using defined larval and adult antigens, many of these being shared between species. Specific examples include the Ancylostoma secreted proteins and homologues in Haemonchus as well as proteases used for digestion of the blood meal. This discussion shows that many of the major vaccine candidates are shared between these blood-feeding species, not only those from the blood-feeding stages but also those expressed by infective L3s in the early stages of infection. Challenges for the future include: exploiting the expanding genome information for antigen discovery, use of different recombinant protein expression systems, formulation with new adjuvants, and novel methods of field testing vaccine efficacy.