Miracle-dz/UniFAR-FTUs huggingface dataset:
Adiponectin and leptin expression in primary ductal breast cancer and in adjacent healthy epithelial and myoepithelial tissue

typical, 10 atypical and four carcinomas) classiﬁca-tions, we found that both classiﬁcation systems werehighly signiﬁcantly (P < 0.001) correlated with overallsurvival, as well as tumour stage and completeresection (Figure 1). Both classiﬁcations were alsostatistically correlated each other (P < 0.001), butinterobserver agreement was 0.57 and 0.97 within theWHO and Suster ⁄ Moran classiﬁcations respectively.Our results basically overlap with those previouslypublished by Rieker et al.
On the Composition of Public-Coin Zero-Knowledge Protocols

We show that only languages in BPP have public-coin, black-box zero-knowledge protocols that are secure under an unbounded (polynomial) number of parallel repetitions. This result holds both in the plain model (without any set-up) and in the Bare Public-Key Model (where the prover and the verifier have registered public keys). We complement this result by showing the existence of a public-coin black-box zero-knowledge proof that remains secure under any a-priori bounded number of concurrent executions.
Creativity with Building Information Modelling Tools

Whilst the application of BIM continues to be acknowledged and prevailing, design practitioners and academics find themselves in a paradox with an on-going discussion on the impact of BIM tools on design creativity and innovation. Literature suggests that BIM tools can hinder design creativity due to: parametric limitations; interoperability; and the demand for detailed information at preliminary design stages. However, other literature shows that BIM tools increase design creativity, and at some point provide limitless opportunities to be creative. The aim of this paper is to identify and verify the impact of BIM tools on design creativity. It is important for architectural students and practioners to be aware of the impact of BIM tools on the design. A literature review was used to identify the benefits and constraints of BIM tools on design creativity; a questionnaire survey was used to verify its impact. The questionnaire survey was conducted with the top 100 UK architectural firms group one and CNBR Yahoo Group group two. It was found that BIM tools do not affect design creativity and innovation in the opinion of the respondents. This paper enlightens the status-quo of BIM tools on creativity and innovation, but will focus on the impact of BIM tools on architectural design creativity in the early design phase more closely. This research would be important to both academics and architectural designers using BIM in their various applications.
Outcomes in patients with non-ST-elevation acute coronary syndrome randomly assigned to invasive versus conservative treatment strategies: A meta-analysis

OBJECTIVE: The goal of the present study was to compare the prognoses of patients with non-ST-elevation acute coronary syndromes who were treated with invasive or conservative treatment strategies. METHODS: We performed a meta-analysis of studies of patients with non-ST-elevation acute coronary syndromes to assess the benefits of an invasive strategy vs. a conservative strategy for short- and long-term survival. We searched PubMed for studies published from 1990 to November 2012 that investigated the effects of an invasive vs. conservative strategy in patients with non-ST-elevation acute coronary syndromes. The following search terms were used: “non-ST-elevation myocardial infarction”, “unstable angina”, “acute coronary syndromes”, “invasive strategy”, and “conservative strategy”. The primary endpoints were all-cause mortality at 30 days and 1 year. RESULTS: Seven published studies were included in the present meta-analysis. The pooled analyses show that an invasive strategy decreased the risk of death (risk ratio [0.839] [95% confidence interval {0.648-1.086}; I2, 86.46%] compared to a conservative strategy over a 30-day-period. Furthermore, invasive treatment also decreased patient mortality (risk ratio [0.276] [95% confidence interval {0.259-0.294}; I2, 94.58%]) compared to a conservative strategy for one year. CONCLUSION: In non-ST-elevation acute coronary syndromes, an invasive strategy is comparable to a conservative strategy for decreasing short- and long-term mortality rates.
Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan

Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team) and the other from lymph proliferation (Umehara team) supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC) for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP), compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease) and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.
Immunophenotype Discovery, Hierarchical Organization, and Template-Based Classification of Flow Cytometry Samples

We describe algorithms for discovering immunophenotypes from large collections of flow cytometry samples and using them to organize the samples into a hierarchy based on phenotypic similarity. The hierarchical organization is helpful for effective and robust cytometry data mining, including the creation of collections of cell populations’ characteristic of different classes of samples, robust classification, and anomaly detection. We summarize a set of samples belonging to a biological class or category with a statistically derived template for the class. Whereas individual samples are represented in terms of their cell populations (clusters), a template consists of generic meta-populations (a group of homogeneous cell populations obtained from the samples in a class) that describe key phenotypes shared among all those samples. We organize an FC data collection in a hierarchical data structure that supports the identification of immunophenotypes relevant to clinical diagnosis. A robust template-based classification scheme is also developed, but our primary focus is in the discovery of phenotypic signatures and inter-sample relationships in an FC data collection. This collective analysis approach is more efficient and robust since templates describe phenotypic signatures common to cell populations in several samples while ignoring noise and small sample-specific variations. We have applied the template-based scheme to analyze several datasets, including one representing a healthy immune system and one of acute myeloid leukemia (AML) samples. The last task is challenging due to the phenotypic heterogeneity of the several subtypes of AML. However, we identified thirteen immunophenotypes corresponding to subtypes of AML and were able to distinguish acute promyelocytic leukemia (APL) samples with the markers provided. Clinically, this is helpful since APL has a different treatment regimen from other subtypes of AML. Core algorithms used in our data analysis are available in the flowMatch package at www.bioconductor. org. It has been downloaded nearly 6,000 times since 2014.
Identification of otx2 target genes and restrictions in ectodermal competence during Xenopus cement gland formation.

The homeobox gene otx2 is a key regulator of positional identity in vertebrates, however its downstream target genes and mechanism of action are not known. We have analyzed otx2 function during formation of the Xenopus cement gland, an organ that expresses otx2. The cement gland forms at early neurula from extreme anterior ectoderm and corresponds to the chin primordium of mammals. Previous studies (Blitz, I. and Cho, K. (1995) Development 121, 993-1004; Pannese, M. , Polo, C. , Andreazzoli, M. , Vignali, R. , Kablar, B. , Barsacchi, G. and Boncinelli, E. (1995) Development 121, 707-720) showed that misexpressed otx2 could activate cement gland formation. However, it was not clear whether this was a direct effect of otx2 or a secondary consequence of other tissues induced by otx2. In this study we ask whether otx2 activity is spatially and temporally restricted in the ectoderm and whether cement gland-specific genes are direct targets of otx2. In order to control the timing of otx2 activity, we constructed a dexamethasone-inducible otx2 protein (otx2-GR) by fusion with the ligand-binding domain of the glucocorticoid receptor. We conclude first, that regionally restricted factors regulate otx2 activity since otx2-GR is able to activate the cement gland markers XCG and XAG only in ventrolateral ectoderm, and never in the neural plate. Second, we show that temporal responsiveness of the ectoderm to otx2-GR is limited, beginning only at mid-gastrula but continuing as late as tailbud stages. Third, we show that otx2-GR activates expression of the cement gland differentiation marker XCG in the absence of protein synthesis, identifying a direct target of otx2. otx2-GR can also activate expression of the endogenous otx2 gene, defining an autoregulatory loop. Fourth, we show that otx2-GR is sufficient to overcome the inhibitory effects of retinoic acid on cement gland formation, indicating that this effect is caused by failure to express otx2. Corroboratively, we show that otx2 autoactivation is prevented by retinoic acid. Together, these findings suggest that otx2 directly controls cement gland differentiation, and that spatial and temporal modulation of otx2 activity limits cement gland formation to the front of the embryo.
Guanylyl Cyclase-A Inhibits Angiotensin II Type 1A Receptor-Mediated Cardiac Remodeling, an Endogenous Protective Mechanism in the Heart

Background—Guanylyl cyclase (GC)-A, a natriuretic peptide receptor, lowers blood pressure and inhibits the growth of cardiac myocytes and fibroblasts. Angiotensin II (Ang II) type 1A (AT1A), an Ang II receptor, regulates cardiovascular homeostasis oppositely. Disruption of GC-A induces cardiac hypertrophy and fibrosis, suggesting that GC-A protects the heart from abnormal remodeling. We investigated whether GC-A interacts with AT1A signaling in the heart by target deletion and pharmacological blockade or stimulation of AT1A in mice. Methods and Results—We generated double-knockout (KO) mice for GC-A and AT1A by crossing GC-A-KO mice and AT1A-KO mice and blocked AT1 with a selective antagonist, CS-866. The cardiac hypertrophy and fibrosis of GC-A-KO mice were greatly improved by deletion or pharmacological blockade of AT1A. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, transforming growth factors &bgr;1 and &bgr;3, were also strongly inhibited. Furthermore, stimulation of AT1A by exogenous Ang II at a subpressor dose significantly exacerbated cardiac hypertrophy and dramatically augmented interstitial fibrosis in GC-A-KO mice but not in wild-type animals. Conclusions—These results suggest that cardiac hypertrophy and fibrosis of GC-A-deficient mice are partially ascribed to an augmented cardiac AT1A signaling and that GC-A inhibits AT1A signaling-mediated excessive remodeling.
Genome reduction as the dominant mode of evolution

A common belief is that evolution generally proceeds towards greater complexity at both the organismal and the genomic level, numerous examples of reductive evolution of parasites and symbionts notwithstanding. However, recent evolutionary reconstructions challenge this notion. Two notable examples are the reconstruction of the complex archaeal ancestor and the intron‐rich ancestor of eukaryotes. In both cases, evolution in most of the lineages was apparently dominated by extensive loss of genes and introns, respectively. These and many other cases of reductive evolution are consistent with a general model composed of two distinct evolutionary phases: the short, explosive, innovation phase that leads to an abrupt increase in genome complexity, followed by a much longer reductive phase, which encompasses either a neutral ratchet of genetic material loss or adaptive genome streamlining. Quantitatively, the evolution of genomes appears to be dominated by reduction and simplification, punctuated by episodes of complexification.
The Expresso Microarray Experiment Management System: The Functional Genomics of Stress Responses in Loblolly Pine

Conception, design, and implementation of cDNA microarray experiments present a variety of bioinformatics challenges for biologists and computational scientists. The multiple stages of data acquisition and analysis have motivated the design of Expresso, a system for microarray experiment management. Salient aspects of Expresso include support for clone replication and randomized placement; automatic gridding, extraction of expression data from each spot, and quality monitoring; flexible methods of combining data from individual spots into information about clones and functional categories; and the use of inductive logic programming for higher-level data analysis and mining. The development of Expresso is occurring in parallel with several generations of microarray experiments aimed at elucidating genomic responses to drought stress in loblolly pine seedlings. The current experimental design incorporates 384 pine cDNAs replicated and randomly placed in two specific microarray layouts. We describe the design of Expresso as well as results of analysis with Expresso that suggest the importance of molecular chaperones and membrane transport proteins in mechanisms conferring successful adaptation to long-term drought stress.
Sensor-based computation of transitional flows using wall-modeled large eddy simulation

To be applicable to complex aerodynamic flows at realistic Reynolds numbers, large eddy simulation (LES) must be combined with a model for the inner part of the boundary layer. Aerodynamic flows are, in general, very sensitive to the location of boundary layer transition. While traditional LES can predict the transition location and process accurately, existing wall-modeled LES approaches can not. Simply put, wall-models are derived assuming a fully developed turbulent boundary layer; hence wall-modeled LES grossly overestimates the friction and momentum losses in locations where the boundary layer is laminar. Aside from leading to erroneously predicted overall friction, it also leads to an artificially thick boundary layer that has a different sensitivity to an adverse pressure gradient. Therefore, wall-modeled LES will only ever be useful in airfoil-type flows once the wall model correctly distinguishes between laminar and turbulent regions and allows for prediction of transition. Moreover, this should be accomplished in a way that can be applied to arbitrary geometries; most notably, any proposed method must not rely on the presence of homogeneous directions. In the present work, the behavior of the wall model is adapted locally by sensing the turbulent kinetic energy in the outer part of the boundary layer that is resolved by the LES. The sensor is defined for arbitrary geometries and does rely on any homogeneous direction. The full proposed method (i.e., the sensor coupled to a wall model in an LES) is tested first in a very controlled setting: transition over a flat plate induced by blowing and suction. It is then applied to compute the flow around the MD 30P/30N multi-element airfoil at the realistic chord Reynolds number of 9 million. It is important to note that the transition on the slat of the MD 30P/30N (at the 19◦ angle of attack that is considered here) occurs immediately after a small laminar separation bubble, which effectively determines the transition location for the airfoil case. In this scenario, existing wall-models can overestimate the skin friction in the laminar region, thus leading to slightly thicker boundary layers. This situation is, obviously, highly dependent on the airfoil, Reynolds number, and angle of attack. The purpose of the first test case (flat plate boundary layer transition) is to directly test the ability of the proposed method to predict the transition location.
Rheumatoid Factors: Clinical Applications

Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.
Metal Transport across Biomembranes: Emerging Models for a Distinct Chemistry*

Transition metals are essential components of important biomolecules, and their homeostasis is central to many life processes. Transmembrane transporters are key elements controlling the distribution of metals in various compartments. However, due to their chemical properties, transition elements require transporters with different structural-functional characteristics from those of alkali and alkali earth ions. Emerging structural information and functional studies have revealed distinctive features of metal transport. Among these are the relevance of multifaceted events involving metal transfer among participating proteins, the importance of coordination geometry at transmembrane transport sites, and the presence of the largely irreversible steps associated with vectorial transport. Here, we discuss how these characteristics shape novel transition metal ion transport models.
On-line identification of hidden Markov models via recursive prediction error techniques

An on-line state and parameter identification scheme for hidden Markov models (HMMs) with states in a finite-discrete set is developed using recursive prediction error (RPE) techniques. The parameters of interest are the transition probabilities and discrete state values of a Markov chain. The noise density associated with the observations can also be estimated. Implementation aspects of the proposed algorithms are discussed, and simulation studies are presented to show that the algorithms converge for a wide variety of initializations. In addition, an improved version of an earlier proposed scheme (the Recursive Kullback-Leibler (RKL) algorithm) is presented with a parameterization that ensures positivity of transition probability estimates. >
Survival following Non–Small Cell Lung Cancer among Asian/Pacific Islander, Latina, and Non-Hispanic White Women Who Have Never Smoked

Background: Lung cancer is the leading cause of cancer death among U.S. Asian/Pacific Islander (API) and Latina women despite low smoking prevalence. This study examined survival patterns following non–small cell lung cancer in a population-based sample of lung cancer cases from the San Francisco Bay Area Lung Cancer Study (SFBALCS). Methods: Women diagnosed with lung cancer from 1998 to 2003 and 2005 to 2008 and identified through the Greater Bay Area Cancer Registry were telephone-screened for eligibility for the SFBALCS. The screener data were linked to the cancer registry data to determine follow-up. This analysis included 187 non-Hispanic (NH) white, 23 U.S.-born Latina, 32 foreign-born Latina, 30 U.S.-born API, and 190 foreign-born API never-smokers diagnosed with lung cancer and followed through 2008. Results: All-cause survival was poorer among APIs [HR = 1.7 (95% CI: 1.0–2.8) among U.S.-born APIs and HR = 1.2 (95% CI: 0.9–1.5) among foreign-born APIs] and Latinas [HR = 2.1 (95% CI: 1.2–3.6) among U.S.-born Latinas; HR = 1.4 (95% CI: 0.9–2.3) among foreign-born Latinas] relative to NH whites. These survival differences were not explained by differences in selected sociodemographic or clinical factors. Conclusions: Further research should focus on factors such as cultural behaviors, access to or attitudes toward health care, and genetic variations as possible explanations for these striking racial/ethnic differences. Impact: Latina and API female never-smokers diagnosed with lung cancer were up to two times more likely to die than NH whites, highlighting the need for additional research to identify the underlying reasons for the disparities and heightened clinical awareness. Cancer Epidemiol Biomarkers Prev; 20(3); 545–54. ©2011 AACR.
The Necessity and Sufficiency of Anytime Capacity for Stabilization of a Linear System Over a Noisy Communication Link&#8212;Part I: Scalar Systems

In this paper, we review how Shannon's classical notion of capacity is not enough to characterize a noisy communication channel if the channel is intended to be used as part of a feedback loop to stabilize an unstable scalar linear system. While classical capacity is not enough, another sense of capacity (parametrized by reliability) called "anytime capacity" is necessary for the stabilization of an unstable process. The required rate is given by the log of the unstable system gain and the required reliability comes from the sense of stability desired. A consequence of this necessity result is a sequential generalization of the Schalkwijk-Kailath scheme for communication over the additive white Gaussian noise (AWGN) channel with feedback. In cases of sufficiently rich information patterns between the encoder and decoder, adequate anytime capacity is also shown to be sufficient for there to exist a stabilizing controller. These sufficiency results are then generalized to cases with noisy observations, delayed control actions, and without any explicit feedback between the observer and the controller. Both necessary and sufficient conditions are extended to continuous time systems as well. We close with comments discussing a hierarchy of difficulty for communication problems and how these results establish where stabilization problems sit in that hierarchy
A virtual tabletop workspace for upper-limb rehabilitation in Traumatic Brain Injury (TBI): A multiple case study evaluation

Deficits in upper limb function are common among patients with traumatic brain injury (TBI). Accordingly, new technologies, such as virtual reality (VR), are being developed to further upper limb rehabilitation. The study described here successfully trialed a table-top VR-based system (called Elements). Two patients with TBI participated in case-studies using a multiple-baseline, AB time-sequence design; the intervention consisted of 12 1-hour sessions. Performance was measured on both system-rated measures and standardized tests of functional skill. Time-sequence plots for each patient were first sight inspected for trends; this was followed by split-middle trend analysis. Participants demonstrated significant improvements in their movement accuracy, efficiency, and bimanual dexterity; and mixed improvement on speed and other measures of movement skill. Taken together, these findings demonstrate that the Elements system facilitated motor learning in both TBI patients. Larger scale clinical trials are now deemed a viable step in further validating the system.