Miracle-dz/UniFAR-FTUs huggingface dataset:
Locality Preserving Embedding

Most manifold learning based methods preserve the original neighbor relationships to pursue the discriminating power. Thus, structure information of data distribution might be neglected and destroyed in low-dimensional space in a sense. In this paper, a novel supervised method, called Locality Preserving Embedding (LPE), is proposed to feature extraction and dimensionality reduction. LPE gives a low-dimensional embedding and preserves principal structure information of the local sub-manifolds. The most significant difference from existing methods is that LPE takes the distribution directions of local neighbor data into account and preserves them in low-dimensional subspace instead of only preserving the each local sub-manifold's original neighbor relationships. Therefore, LPE optimally preserves both the local sub-manifold's original neighbor relations and the distribution direction of local neighbors to separate different sub-manifolds as far as possible. The proposed LPE is applied to face recognition on the ORL and Yale face database. The experimental results show that LPE consistently outperforms the-state-of-art linear methods such as Marginal Fisher Analysis (MFA) and Constrained Maximum Variance Mapping (CMVM).
Human Peripheral Blood Eosinophils Express a Functional c-kit Receptor for Stem Cell Factor that Stimulates Very Late Antigen 4 (VLA-4)–mediated Cell Adhesion to Fibronectin and Vascular Cell Adhesion Molecule 1 (VCAM-1)

We evaluated mature peripheral blood eosinophils for their expression of the surface tyrosine kinase, c-kit, the receptor for the stromal cell–derived cytokine, stem cell factor (SCF). Cytofluorographic analysis revealed that c-kit was expressed on the purified peripheral blood eosinophils from 8 of 8 donors (4 nonatopic and 4 atopic) (mean channel fluorescence intensity 2.0– 3.6-fold, average 2.8 ± 0.6-fold, greater than the negative control). The uniform and selective expression of c-kit by eosinophils was confirmed by immunohistochemical analysis of peripheral blood buffy coats. The functional integrity of c-kit was demonstrated by the capacity of 100 ng/ml (5 nM) of recombinant human (rh) SCF to increase eosinophil adhesion to 3, 10, and 30 μg/ml of immobilized FN40, a 40-kD chymotryptic fragment of plasma fibronectin, in 15 min by 7.7 ± 1.4-, 5.3 ± 3.3-, and 5.4 ± 0.2-fold, respectively, and their adhesion to 0.1, 0.5, and 1.0 μg/ml vascular cell adhesion molecule-1 (VCAM-1), by 12.7 ± 9.2-, 3.8 ± 2.5-, and 1.7 ± 0.6-fold, respectively. The SCF-stimulated adhesion occurred without concomitant changes in surface integrin expression, thereby indicating an avidity-based mechanism. rhSCF (100 ng/ml, 5 nM) was comparable to rh eotaxin (200 ng/ml, 24 nM) in stimulating adhesion. Cell adhesion to FN40 was completely inhibited with antibodies against the α4 and β1 integrin subunits, revealing that the SCF/c-kit adhesion effect was mediated by a single integrin heterodimer, very late antigen 4 (VLA-4). Thus, SCF represents a newly recognized stromal ligand for the activation of eosinophils for VLA-4–mediated adhesion, which could contribute to the exit of these cells from the blood, their tissue localization, and their prominence in inflammatory lesions.
Therapeutic targeting of mutant p53 in pediatric acute lymphoblastic leukemia

Alterations of the tumor suppressor gene TP53 are found in different cancers, in particular in carcinomas of adults. In pediatric acute lymphoblastic leukemia (ALL), TP53 mutations are infrequent but enriched at relapse. As in most cancers, mainly DNA-binding domain missense mutations are found, resulting in accumulation of mutant p53, poor therapy response, and inferior outcome. Different strategies to target mutant p53 have been developed including reactivation of p53’s wildtype function by the small molecule APR-246. We investigated TP53 mutations in cell lines and 62 B-cell precursor ALL samples and evaluated the activity of APR-246 in TP53-mutated or wildtype ALL. We identified cases with TP53 missense mutations, high (mutant) p53 expression and insensitivity to the DNA-damaging agent doxorubicin. In TP53-mutated ALL, APR-246 induced apoptosis showing strong anti-leukemia activity. APR-246 restored mutant p53 to its wildtype conformation, leading to pathway activation with induction of transcriptional targets and re-sensitization to genotoxic therapy in vitro and in vivo. In addition, induction of oxidative stress contributed to APR-246-mediated cell death. In a preclinical model of patient-derived TP53-mutant ALL, APR-246 reduced leukemia burden and synergized strongly with the genotoxic agent doxorubicin, leading to superior leukemia-free survival in vivo. Thus, targeting mutant p53 by APR-246, restoring its tumor suppressive function, seems to be an effective therapeutic strategy for this high-risk group of TP53-mutant ALL.
Plasticity and transient binding are key ingredients of the periplasmic chaperone network

SurA, Skp, FkpA, and DegP constitute a chaperone network that ensures biogenesis of outer membrane proteins (OMPs) in Gram‐negative bacteria. Both Skp and FkpA are holdases that prevent the self‐aggregation of unfolded OMPs, whereas SurA accelerates folding and DegP is a protease. None of these chaperones is essential, and we address here how functional plasticity is manifested in nine known null strains. Using a comprehensive computational model of this network termed OMPBioM, our results suggest that a threshold level of steady state holdase occupancy by chaperones is required, but the cell is agnostic to the specific holdase molecule fulfilling this function. In addition to its foldase activity, SurA moonlights as a holdase when there is no expression of Skp and FkpA. We further interrogate the importance of chaperone–client complex lifetime by conducting simulations using lifetime values for Skp complexes that range in length by six orders of magnitude. This analysis suggests that transient occupancy of durations much shorter than the Escherichia coli doubling time is required. We suggest that fleeting chaperone occupancy facilitates rapid sampling of the periplasmic conditions, which ensures that the cell can be adept at responding to environmental changes. Finally, we calculated the network effects of adding multivalency by computing populations that include two Skp trimers per unfolded OMP. We observe only modest perturbations to the system. Overall, this quantitative framework of chaperone–protein interactions in the periplasm demonstrates robust plasticity due to its dynamic binding and unbinding behavior.
The Adjacent Vessel Sign on Breast MRI: New Data and a Subgroup Analysis for 1,084 Histologically Verified Cases

Objective The adjacent vessel sign (AVS) is a descriptor for differentiating malignant from benign breast lesions on breast MRI (bMRI). This investigation was designed to verify the previous reports on the diagnostic accuracy of AVS and to assess correlation between AVS, histopathological diagnosis, lesion size and lesion grade. Materials and Methods This study was approved by the local ethical committee. Experienced radiologists evaluated 1,084 lesions. The exclusion criteria were no histological verification after bMRI and breast interventions that were done up to one year before bMRI (surgery, core biopsy, chemo- or radiation therapy). The native and dynamic contrast-enhanced T1-weighted series were acquired using standardized protocols. The AVS was rated positive if a vessel leading to a lesion could be visualized. Prevalence of an AVS was correlated with the lesions' size, grade and histology using Chi-square-tests. Results The AVS was significantly associated with malignancy (p < 0.001; sensitivity: 47%, specificity: 88%, positive-predictive-value [PPV]: 85%). Malignant lesions > 2 cm more often presented with an AVS than did those malignant lesions < 2 cm (p < 0.0001; sensitivity: 65%, PPV: 90%). There was no correlation of the AVS with the tumor grade. The prevalence of an AVS didn't significantly differ between invasive lobular carcinomas versus ductal carcinomas. In situ cancers were less frequently associated with an AVS (p < 0.001). Conclusion The adjacent vessel sign was significantly associated with malignancy. Thus, it can be used to accurately assess breast lesions on bMRI. In this study, the AVS was particularly associated with advanced and invasive carcinomas.
Institutional Responses to Campus Sexual Assault: Examining the Development and Work of A Multidisciplinary Team

ABSTRACT Responding to campus sexual assault can involve complex processes and procedures that span campus, criminal justice, and community-based institutions, particularly when there are co-occurring Title IX and criminal investigations. This study investigated the development of a multidisciplinary team (MDT) that involved campus, criminal justice, and community-based institutions seeking to improve coordinated responses to campus sexual assault. Data included observations of MDT monthly meetings over 16 months as well as individual interviews with MDT members. Transcripts of the MDT meetings and individual interviews were coded to capture major themes. The MDT meetings were dynamic and flexible with a structure that involved intentional agenda setting along with responsiveness to current events and collaborative processes. The MDT invested more time during the meetings addressing the complexity of navigating existing procedures than developing new protocols. Individual interviews with MDT members highlighted logistical challenges that were relevant to MDT effectiveness, such as consistent attendance, supervisor legitimacy, and differences in stakeholder priorities. Implications for future MDT work are discussed.
Exploring the Impact of Formal Internships on Biomedical Graduate and Postgraduate Careers: An Interview Study

Graduate students and postdocs in science, technology, engineering, and math fields are faced with a wide range of career paths to employment, but they are often not trained to effectively pursue these opportunities. The lack of career management skills implies long tenures in graduate school for many students, especially as tenure-track positions in academia dwindle. At our university, we used a cohort model in which graduate students and postdocs were encouraged to apply to the Broadening Experiences in Scientific Training program (BEST under the aegis of the National Institutes of Health) that provided opportunities to gain career management skills, engage in career exploration, and complete at least one formal internship. In this interview study of the BEST trainees, we investigated the efficacy of internships as career exploration tools and associated outcomes. Our findings show that internships were seen as effective career exploration and self-development vehicles that influenced participants’ long-term career goals. Graduate students and postdocs reported gaining transferable knowledge and skills, in addition to receiving valuable industry mentoring and networking opportunities.
Improving the real-time performance of heterogeneous extremely large datasets

The POWDER protocol is a Semantic Web technology --and W3C Recommendation- that takes advantage of natural groupings of URIs, as identifiers as well as navigational paths, to annotate all the resources in a regular expression-delineated sub-space of the URI space. POWDER was designed as a mechanism for accreditation, trustmarking and resource discovery, emphasizing the publishing of attributed metadata by third parties and trusted authorities. However, its versatility allows the application of POWDER in different use cases such as repository compression. In this paper, we present the POWDER protocol, briefly discuss current implementations and use cases and present how POWDER can be implemented over existing well-tested and robust semantic storage systems. Furthermore, we discuss a novel solution for the scalable storing data summaries in the form of metadata for the purposes of source selection and source schema coordination in large-scale, heterogeneous federations of semantic querying endpoints. Our solution takes advantage of POWDER's ability to exploit naming conventions and other natural groupings of URIs in order to compress instance-level metadata about the nodes of a data service federation, especially in situations where URI hashing cannot be used to efficiently resolve the sources that hold statements regarding a given URI resource.
A novel block-level continuous data protection system

Continuous Data Protection (CDP) techniques have received great interest both from academia and industry in recent years. Aiming at the challenges to design and implement a CDP system, this paper proposes GSP_BCDP: a novel continuous data protection architecture at block level. Compared with other approaches, it uses a global shared storage pool to actually store all the versions of data contents, and each version of each logical volume bonded with a restore index table. The recovery of GSP_BCDP is per volume basis, rather than per block basis in other schemes, so GSP_BCDP can provide a much faster version restore than others. Furthermore, through global data de-duplication techniques, GSP_BCDP can not only reduce the duplications along the history of the same data stream, but also de-duplicate the redundancies among data streams or identities between different users. Experimental results demonstrate that GSP_BCDP can improve the recovery time up to more than 10 times, and with storage space compression ratio of 1.2 times in average.
A Data-driven Approach to Internet-based Business Collaboration

Traditional business process modeling approaches focus on the activities, data flows are an afterthought. Concerning cross-organizational collaboration on the Internet, data flow is still far from optimal, causing resource contention and unnecessary data exchanges. In this paper, a data-driven approach to Internet based business collaboration is proposed, which treats data as a centerpiece as data objects and associates activities with the data objects. The data objects hold information structures pertinent to global context to support logic data flow, both the resource contention and data exchanges can be alleviated. A case study shows that the approach works efficiently.
Mobidev: a tool for creating apps on mobile phones

Currently, the development of mobile applications heavily relies on using conventional computers as development platform. MobiDev enables people in emerging countries without access to a computer but to a cell phone to develop their own locally relevant applications. The goal of the Mo-biDev project is to simplify development and deployment of applications directly on mobile phones. As a first step, we focus on the design of applications and try to support the computer science curriculum in developing countries to bootstrap the mobile developer culture and community. MobiDev allows the creation of graphical user interfaces (GUI) using various concepts. We present the results of a first system evaluation that show how people perceive the concepts for UI creation of MobiDev.
Global analysis of a continuum model for pulse-coupled oscillators

We consider phase oscillators on the circle interacting through an impulsive instantaneous coupling. In contrast with previous studies on related pulse-coupled models, global stability results are obtained in the continuum limit. For the nonlinear transport equation governing the evolution of the oscillators, we propose (under technical assumptions) a global Lyapunov function which is induced by a total variation distance between quantile densities. The monotone time evolution of the Lyapunov function completely characterizes the dichotomic behavior of the oscillators: either the oscillators converge in finite time to a synchronous state or they asymptotically converge to an asynchronous state uniformly spread on the circle. The results of the present paper apply to various popular phase oscillators models (e.g. the well-known leaky integrate-and-fire model) and provide a novel approach for the (global) analysis of pulse-coupled oscillators.
Magellan: Charting Large-Scale Peer-to-Peer Live Streaming Topologies

Live peer-to-peer (P2P) streaming applications have been successfully deployed in the Internet. With relatively simple peer selection protocol design, modern live P2P streaming applications are able to provide millions of concurrent users adequately satisfying viewing experiences. That said, few existing research has provided sufficient insights on the time-varying internal characteristics of P2P topologies in live streaming. With 120 GB worth of traces in late 2006 from a commercial P2P live streaming system of UUSee Inc. in Beijing, this paper represents the first attempt in the research community to explore topological properties in practical P2P streaming, and how they behave over time. Starting from classical graph metrics, such as degree, clustering coefficient, and reciprocity, we explore and extend them in specific perspectives of streaming applications. We also compare our findings with existing insights from topological studies of P2P file sharing applications, which shed new and unique insights specific to streaming. Our characterization reveals the scalability of the commercial P2P streaming application even in case of large flash crowds, the clustering phenomenon of peers in each ISP, as well as the reciprocal behavior among peers, all of which play important roles in achieving its current success.
Detection of changes in mitochondrial hydrogen sulfide in vivo in the fish model Poecilia mexicana (Poeciliidae)

ABSTRACT In this paper, we outline the use of a mitochondria-targeted ratiometric mass spectrometry probe, MitoA, to detect in vivo changes in mitochondrial hydrogen sulfide (H2S) in Poecilia mexicana (family Poeciliidae). MitoA is introduced via intraperitoneal injection into the animal and is taken up by mitochondria, where it reacts with H2S to form the product MitoN. The MitoN/MitoA ratio can be used to assess relative changes in the amounts of mitochondrial H2S produced over time. We describe the use of MitoA in the fish species P. mexicana to illustrate the steps for adopting the use of MitoA in a new organism, including extraction and purification of MitoA and MitoN from tissues followed by tandem mass spectrometry. In this proof-of-concept study we exposed H2S tolerant P. mexicana to 59 µM free H2S for 5 h, which resulted in increased MitoN/MitoA in brain and gills, but not in liver or muscle, demonstrating increased mitochondrial H2S levels in select tissues following whole-animal H2S exposure. This is the first time that accumulation of H2S has been observed in vivo during whole-animal exposure to free H2S using MitoA. This article has an associated First Person interview with the first author of the paper. Summary: We established the mitochondria-targeted mass spectrometry probe MitoA for H2S detection in vivo in the animal model Poecilia mexicana for the first time.
Circular RNA rno_circ_0004002 regulates cell proliferation, apoptosis, and epithelial‐mesenchymal transition through targeting miR‐342‐5p and Wnt3a in anorectal malformations

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that have regulatory functions in varieties of diseases. The purpose of this study was to investigate the potential role of circRNAs in anorectal malformations (ARM). With sequencing analysis, 78 circRNAs were identified to be differentially expressed on gestational day (GD) 19 in ARM and normal anorectal tissues, including 41 upregulated and 37 downregulated circRNAs. Among the downregulated circRNAs, rno_circ_0004002 was selected as the candidate circRNA. Functionally, silencing of rno_circ_0004002 was correlated with suppression of proliferation, and promotion of apoptosis and epithelial‐mesenchymal transition (EMT) in anorectal development. For the mechanism investigation, bioinformatic prediction and luciferase reporter assay revealed that rno_circ_0004002 was proved to be a sponge of miR‐342‐5p, and miR‐342‐5p could target 3'‐UTR of Wnt3a to negatively regulate its expression. The quantitative reverse transcription polymerase chain reaction (qRT‐PCR) results showed that the expression of miR‐342‐5p was significantly increased in ARM anorectal tissues compared with normal tissues on GD19 and GD21, and the expression of Wnt3a demonstrated the opposite on GD21. In addition, rescue assays disclosed that miR‐342‐5p inhibitor could reverse the role of rno_circ_0004002 knockdown on the repression of anorectal development. In summary, our study shed light on the regulatory mechanism of rno_circ_0004002 in cell proliferation, apoptosis, and EMT via sponging miR‐342‐5p, which downregulated the Wnt3a expression in anorectal development. We also suggested that GD19 and GD21 was the crucial time in the progression of ARM, and rno_circ_0004002/miR‐342‐5p/Wnt3a might serve as potential therapeutic targets for ARM.
Machine Learning: The High Interest Credit Card of Technical Debt

Machine learning offers a fantastically powerful toolkit for building complex systems quickly. This paper argues that it is dangerous to think of these quick wins as coming for free. Using the framework of technical debt, we note that it is remarkably easy to incur massive ongoing maintenance costs at the system level when applying machine learning. The goal of this paper is highlight several machine learning specific risk factors and design patterns to be avoided or refactored where possible. These include boundary erosion, entanglement, hidden feedback loops, undeclared consumers, data dependencies, changes in the external world, and a variety of system-level anti-patterns. 1 Machine Learning and Complex Systems Real world software engineers are often faced with the challenge of moving quickly to ship new products or services, which can lead to a dilemma between speed of execution and quality of engineering. The concept of technical debt was first introduced by Ward Cunningham in 1992 as a way to help quantify the cost of such decisions. Like incurring fiscal debt, there are often sound strategic reasons to take on technical debt. Not all debt is necessarily bad, but technical debt does tend to compound. Deferring the work to pay it off results in increasing costs, system brittleness, and reduced rates of innovation. Traditional methods of paying off technical debt include refactoring, increasing coverage of unit tests, deleting dead code, reducing dependencies, tightening APIs, and improving documentation [4]. The goal of these activities is not to add new functionality, but to make it easier to add future improvements, be cheaper to maintain, and reduce the likelihood of bugs. One of the basic arguments in this paper is that machine learning packages have all the basic code complexity issues as normal code, but also have a larger system-level complexity that can create hidden debt. Thus, refactoring these libraries, adding better unit tests, and associated activity is time well spent but does not necessarily address debt at a systems level. In this paper, we focus on the system-level interaction between machine learning code and larger systems as an area where hidden technical debt may rapidly accumulate. At a system-level, a machine learning model may subtly erode abstraction boundaries. It may be tempting to re-use input signals in ways that create unintended tight coupling of otherwise disjoint systems. Machine learning packages may often be treated as black boxes, resulting in large masses of “glue code” or calibration layers that can lock in assumptions. Changes in the external world may make models or input signals change behavior in unintended ways, ratcheting up maintenance cost and the burden of any debt. Even monitoring that the system as a whole is operating as intended may be difficult without careful design.