Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential mechanisms of tumor progression in clones from a single heterogeneous human melanoma

We used vertical growth phase (VGP) human VMM5 melanoma cells to ask whether the tumor microenvironment could induce matrix metalloproteinase‐1 (MMP‐1) in vivo, and whether this induction correlated with metastasis. We isolated two clones from parental VMM5 cells: a low MMP‐1 producing clone (C4) and high producing clone (C9). When these clones were injected orthotopically (intradermally) into nude mice, both were equally tumorigenic and produced equivalent and abundant amounts of MMP‐1. However, the tumors from the C4 clones displayed different growth kinetics and distinct profiles of gene expression from the C9 population. The C4 tumors, which had low MMP‐1 levels in vitro, appeared to rely on growth factors and cytokines in the microenvironment to increase MMP‐1 expression in vivo, while MMP‐1 levels remained constant in the C9 tumors. C9 cells, but not C4 cells, grew as spheres in culture and expressed higher levels of JARID 1B, a marker associated with melanoma initiating cells. We conclude that VMM5 melanoma cells exhibit striking intra‐tumor heterogeneity, and that the tumorigenicity of these clones is driven by different molecular pathways. Our data suggest that there are multiple mechanisms for melanoma progression within a tumor, which may require different therapeutic strategies. J. Cell. Physiol. 228: 773–780, 2013. © 2012 Wiley Periodicals, Inc.
The 2-Transitive Complex Hadamard Matrices

We determine all possibilities for a complex Hadamard ma- trix H admitting an automorphism group which permutes 2-transitively the rows of H. Our proof of this result relies on the classification theo- rem for finite 2-transitive permutation groups, and thereby also on the classification of finite simple groups.
IL-12 Responsiveness and Expression of IL-12 Receptor in Human Peripheral Blood Monocyte-Derived Dendritic Cells

We analyzed the expression of IL-12Rβ1 and IL-12Rβ2 and the role of IL-12 in the activation of monocyte-derived dendritic cells (DCs) via IL-12Rβ1-mediated signaling events. Flow cytometric analysis revealed that IL-12Rβ1 was expressed in T cells, Con A blasts, and monocyte-derived DCs, but not in monocytes, while its transcript was detected in all of these cell types. Transcriptional expression of IL-12Rβ2 was observed in T cells, Con A blasts, and monocyte-derived DCs, but not monocytes. The ligation of DCs as well as Con A blasts by IL-12 induced the production of GM-CSF, IL-1β, IL-6, TNF-α, and IFN-γ at the transcription levels. Furthermore, stimulation of DCs with IL-12 induced IL-12p40 transcript, but not IL-12p35 transcript, whereas this stimulation caused the expressions of both transcripts in Con A blasts. Stimulation of DCs with IL-12 caused a tyrosine phosphorylation of several intracellular proteins, and the pattern of these events were distinct from those of IL-12-stimulated Con A blasts. IL-12 also induced tyrosine phosphorylation of IL-12Rβ1 as well as recruitment of several tyrosine-phosphorylated proteins to IL-12Rβ1 in DCs and Con A blasts. Receptor engagement of DCs as well as Con A blasts by IL-12 resulted in activation of Janus kinase 2 and Tyk2 kinases and Stat3 and Stat4 transcription factors and the association of these proteins to IL-12Rβ1. Stimulation with IL-12 caused a tyrosine phosphorylation and enzymatic activity of a family of mitogen-activated protein kinases, p38mapk. These results suggest that IL-12 acts directly on DCs to induce their functional activation via IL-12Rβ1-mediated signaling events.
A randomized placebo-controlled trial of a school-based depression prevention program.

OBJECTIVE To conduct a placebo-controlled study of the effectiveness of a universal school-based depression prevention program. METHOD Three hundred ninety-two students age 13 to 15 from two schools were randomized to intervention (RAP-Kiwi) and placebo programs run by teachers. RAP-Kiwi was an 11-session manual-based program derived from cognitive-behavioral therapy. The placebo was similar but with cognitive components removed. Outcomes were self-rated depression scales, the Reynolds Adolescent Depression Scale (RADS), and the Beck Depression Inventory II (BDI-II). Follow-up was to 18 months. Analysis was done on an intent-to-treat basis. RESULTS Immediately after the intervention, depression scores were reduced significantly more by RAP-Kiwi than by placebo, with a mean difference in change from baseline between groups of 1.5 on BDI-II (CI > 0.38, p =.01) and 2.24 on RADS (CI > 0.22, p =.04). Categorical analysis confirmed significant clinical benefit with an absolute risk reduction of 3% (95% CI, 1-11%, McNemar chi, p =.03), with the "number needed to treat" for short-term benefit of 33. Group differences in depression scores averaged across time to 18 months were significant on RADS but not on BDI-II. Retention rates were 91% at 6 months and 72% at 18 months. CONCLUSIONS The RAP-Kiwi program is a potentially effective public health measure. Confirmation of effectiveness measuring episodes of depressive illness and broader measures of adjustment is warranted.
The relationships between energy balance, milk production and ovulation in postpartum Holstein cows.

Energy balance and serum progesterone concentrations were monitored during early lactation in a group of high producing Holstein cows. The postpartum interval to normal ovulation averaged 36 +/- 6 days (range 6 to 83 days). Average energy balance during the first 20 days of lactation (cumulative daily calculated energy balance divided by days in milk) was inversely related to days to normal ovulation (r = -.60) and to milk production (r = -.80). Milk yield during this period was not closely related to days to ovulation (r = .30). Milk yield was also not significantly related to serum prolactin concentrations over the first 12 weeks of lactation (r = .27). During early lactation, energy balance was maximally negative until peak milk yield and then began returning toward zero, with the magnitude and duration of negative energy balance being quite variable. On the average, ovulation and the initiation of the first normal luteal phase occurred approximately 10 days after energy balance began returning toward zero. During this 10-day interval, a transient elevation in serum progesterone concentrations occurred in eight of 13 cows. These results suggest that energy balance during the first 20 days of lactation is important in determining the onset of ovarian activity following parturition.
Differential Spatial Expression and Subcellular Localization of CtBP Family Members in Rodent Brain

C-terminal binding proteins (CtBPs) are well-characterized nuclear transcriptional co-regulators. In addition, cytoplasmic functions were discovered for these ubiquitously expressed proteins. These include the involvement of the isoform CtBP1-S/BARS50 in cellular membrane-trafficking processes and a role of the isoform RIBEYE as molecular scaffolds in ribbons, the presynaptic specializations of sensory synapses. CtBPs were suggested to regulate neuronal differentiation and they were implied in the control of gene expression during epileptogenesis. However, the expression patterns of CtBP family members in specific brain areas and their subcellular localizations in neurons in situ are largely unknown. Here, we performed comprehensive assessment of the expression of CtBP1 and CtBP2 in mouse brain at the microscopic and the ultra-structural levels using specific antibodies. We quantified and compared expression levels of both CtBPs in biochemically isolated brain fractions containing cellular nuclei or synaptic compartment. Our study demonstrates differential regional and subcellular expression patterns for the two CtBP family members in brain and reveals a previously unknown synaptic localization for CtBP2 in particular brain regions. Finally, we propose a mechanism of differential synapto-nuclear targeting of its splice variants CtBP2-S and CtBP2-L in neurons.
Selection of Nonapoptotic Spermatozoa As a New Tool for Enhancing Assisted Reproduction Outcomes: An In Vitro Model1

Abstract Magnetic cell sorting (MACS) using annexin V-conjugated microbeads eliminates apoptotic spermatozoa based on the externalization of phosphatidylserine residues. The procedure delivers two sperm fractions: annexin V-negative (nonapoptotic) and annexin V-positive (apoptotic). Our aim was to determine whether the sperm fertilizing potential can be improved by selecting a nonapoptotic fraction using MACS. Semen samples (n = 35) were subjected to separation on a density gradient followed by MACS. Extent of apoptosis was assessed by measuring levels of activated caspase 3 using fluorescein-labeled inhibitors of caspase, alterations in mitochondrial membrane potential (MMP) using a lipophilic cationic dye, and DNA fragmentation using terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling assay. The sperm fertilization potential was assessed using hamster oocyte penetration assay and hamster oocyte-intracytoplasmic sperm injection (ICSI). Annexin V-negative sperm displayed superior quality in terms of high motility, low caspase 3 activation, MMP integrity, and small extent of DNA fragmentation. Annexin V-negative sperm demonstrated higher oocyte penetration capacity but comparable sperm chromatin decondensation (SCD) following ICSI. Conversely, the annexin V-positive sperm presented with poor quality and fertilization potential. The oocyte penetration rate was negatively correlated with apoptotic marker expression, whereas SCD following ICSI was only associated with apoptosis on sperm-damaged membranes. We conclude that apoptosis appears to impact sperm-oocyte penetration rate; however, it does not seem to affect early stages of fertilization such as SCD in spermatozoa of healthy donors. The selection of nonapoptotic sperm by MACS may be used to enhance results of in vitro fertilization by increasing sperm-oocyte penetration.
Liquidity-Based Estimation of Stochastic Volatility under Microstructure Noise ∗

Recent literature on realized volatility suggests that the observed price process of an asset may be decomposed into two parts: the genuine (unobservable) price process and microstructure noise. In this article we present a methodology to estimate stochastic volatility by separating these components. Depending on market liquidity, the source of a move in the transaction price of an asset may be distinguished as a move in the underlying price process or as microstructure noise. To identify the weights of these components we use different (order-based and trade-based) liquidity measures to update expectations on the unobservable price process via Bayesian learning. Depending on these weights we are able to estimate stochastic volatility from noisy data.
Proteus: virtualization for diversified tamper-resistance

Despite huge efforts by software providers, software protection mechanisms are still broken on a regular basis. Due to the current distribution model, an attack against one copy of the software can be reused against any copy of the software. Diversity is an important tool to overcome this problem. It allows for renewable defenses in space, by giving every user a different copy, and renewable defenses in time when combined with tailored updates. This paper studies the possibilities and limitations of using virtualization to open a new set of opportunities to make diverse copies of a piece of software and to make individual copies more tamper-resistant. The performance impact is considerable and indicates that these techniques are best avoided in performance-critical parts of the code.
Cancer Regression and Neurological Toxicity Following Anti-MAGE-A3 TCR Gene Therapy

Nine cancer patients were treated with adoptive cell therapy using autologous anti-MAGE-A3 T-cell receptors (TCR)-engineered T cells. Five patients experienced clinical regression of their cancers including 2 on-going responders. Beginning 1–2 days postinfusion, 3 patients (#’s 5, 7, and 8) experienced mental status changes, and 2 patients (5 and 8) lapsed into comas and subsequently died. Magnetic resonance imagining analysis of patients 5 and 8 demonstrated periventricular leukomalacia, and examination of their brains at autopsy revealed necrotizing leukoencephalopathy with extensive white matter defects associated with infiltration of CD3+/CD8+ T cells. Patient 7, developed Parkinson-like symptoms, which resolved over 4 weeks and fully recovered. Immunohistochemical staining of patient and normal brain samples demonstrated rare positively staining neurons with an antibody that recognizes multiple MAGE-A family members. The TCR used in this study recognized epitopes in MAGE-A3/A9/A12. Molecular assays of human brain samples using real-time quantitative-polymerase chain reaction, Nanostring quantitation, and deep-sequencing indicated that MAGE-A12 was expressed in human brain (and possibly MAGE-A1, MAGE-A8, and MAGE-A9). This previously unrecognized expression of MAGE-A12 in human brain was possibly the initiating event of a TCR-mediated inflammatory response that resulted in neuronal cell destruction and raises caution for clinical applications targeting MAGE-A family members with highly active immunotherapies.
Quantitative structure-activity relationships (QSARs) for inhibitors and substrates of CYP2B enzymes: importance of compound lipophilicity in explanation of potency differences

The results of quantitative structure-activity relationship (QSAR) studies on inhibitors and substrates of cytochrome P450 2B (CYP2B) subfamily enzymes are reported. It was found that lipophilicity (in the form of log P) is the most important property for explaining the variations in inhibitory activity, and there are similarities between QSARs for both substrates and inhibitors for CYP2B6 (human), and also between those of other CYP2B enzymes, such as CYP2B1 (rat) and CYP2B4 (rabbit). Both linear and quadratic lipophilicity relationships are evidenced in human and other mammalian species, and the particular type of expression found is probably due to the nature of the compounds under investigation, as it is usually the homologous series which tend to show quadratic relationships in log P. The findings from QSAR studies can be rationalized by molecular modelling of the active site interactions with both P450 crystal structures and homology models of CYP2B subfamily enzymes.
SParseval: Evaluation Metrics for Parsing Speech

While both spoken and written language processing stand to benefit from parsing, the standard Parseval metrics (Black et al., 1991) and their canonical implementation (Sekine and Collins, 1997) are only useful for text. The Parseval metrics are undefined when the words input to the parser do not match the words in the gold standard parse tree exactly, and word errors are unavoidable with automatic speech recognition (ASR) systems. To fill this gap, we have developed a publicly available tool for scoring parses that implements a variety of metrics which can handle mismatches in words and segmentations, including: alignment-based bracket evaluation, alignment-based dependency evaluation, and a dependency evaluation that does not require alignment. We describe the different metrics, how to use the tool, and the outcome of an extensive set of experiments on the sensitivity.
Detecting Data Stream Dependencies on High Dimensional Data

Intelligent production in smart factories or wearable devices that measure our activities produce on an ever growing amount of sensor data. In these environments, the validation of measurements to distinguish sensor flukes from significant events is of particular importance. We developed an algorithm that detects dependencies between sensor readings. These can be used for instance to verify or analyze large scale measurements. An entropy based approach allows us to detect dependencies beyond linear correlation and is well suited to deal with high dimensional and high volume data streams. Results show statistically significant improvements in reliability and on-par execution time over other stream monitoring systems.
Medication-Assisted Treatment in Criminal Justice Agencies Affiliated with the Criminal Justice-Drug Abuse Treatment Studies (CJ-DATS): Availability, Barriers, and Intentions

Medication-assisted treatment (MAT) is underutilized in the treatment of drug-dependent, criminal justice populations. This study surveyed criminal justice agencies affiliated with the Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) to assess use of MAT and factors influencing use of MAT. A convenience sample (N = 50) of criminal justice agency respondents (e.g., jails, prisons, parole/probation, and drug courts) completed a survey on MAT practices and attitudes. Pregnant women and individuals experiencing withdrawal were most likely to receive MAT for opiate dependence in jail or prison, whereas those reentering the community from jail or prison were the least likely to receive MAT. Factors influencing use of MAT included criminal justice preferences for drug-free treatment, limited knowledge of the benefits of MAT, security concerns, regulations prohibiting use of MAT for certain agencies, and lack of qualified medical staff. Differences across agency type in the factors influencing use and perceptions of MAT were also examined. MAT use is largely limited to detoxification and maintenance of pregnant women in criminal justice settings. Use of MAT during the community reentry period is minimal. Addressing inadequate knowledge and negative attitudes about MAT may increase its adoption, but better linkages to community pharmacotherapy during the reentry period might overcome other issues, including security, liability, staffing, and regulatory concerns. The CJ-DATS collaborative MAT implementation study to address inadequate knowledge, attitudes, and linkage will be described.
ε-Equilibrium in LQ differential games with bounded uncertain disturbances: robustness of standard strategies and new strategies with adaptation

A finite time multi-persons linear-quadratic differential game (LQDG) with bounded disturbances and uncertainties is considered. When players cannot measure these disturbances and uncertainties, the standard feedback Nash strategies are shown to yield to an ε-(or quasi) Nash equilibrium depending on an uncertainty upper bound that confirms the robustness property of such standard strategies. In the case of periodic disturbances, another concept, namely adaptive concept, is suggested. It is defined an “adaptation period” where all participants apply the standard feedback Nash strategies with the, so-called, “shifting signal” generated only by a known external exciting signal. Then, during the adaptation, the readjustment (or correction) of the control strategies is realized to estimate the effect of unknown periodic disturbances by the corresponding correction of the shifting vector. After that adaptation period, the complete standard strategies including the recalculated shifting signal are activated allowing the achievement of pure (ε = 0) Nash equilibrium for the rest of the game. A numerical example dealing with a two participants game shows that the cost functional for each player achieves better values when the adaptive approach is applied.
Bridges into the Unknown: Personalizing Connections to Little-known Countries

How are you related to Malawi? Do recent events on the Comoros effect you in any subtle way? Who in your extended social network is in Croatia? We seldom ask ourselves these questions, yet a "long tail" of content beyond our everyday knowledge is waiting to be explored. In this work we propose a recommendation task of creating interest in little-known content by building personalized "bridges" to users. We consider an example task of interesting users in little-known countries, and propose a system which aggregates a user's Twitter profile, network, and tweets to create an interest model, which is then matched to a library of knowledge about the countries. We perform a user study of 69 participants and conduct 11 in-depth interviews in order to evaluate the efficacy of the proposed approach and gather qualitative insight into the effect of multi-faceted use of Twitter on the perception of the bridges. We find the increase in interest concerning little-known content to greatly depend on the pre-existing disposition to it. Additionally, we discover a set of vital properties good bridges must possess, including recency, novelty, emotiveness, and a proper selection of language. Using the proposed approach we aim to harvest the "invisible connections" to make explicit the idea of a "small world" where even a faraway country is more closely connected to you than you might have imagined.
ProtoTalk: A Generative Software Engineering Framework for Prototyping Protocols in Smalltalk

Network protocols are complex systems implemented by collections of equally complex software components. In many cases, the realization of such protocols requires extensive prototyping and experimentation with different alternative implementations.In this paper, we present ProtoTalk, a generative, domain-specific software framework that utilizes model driven software engineering principles for prototyping state and message driven protocols with emphasis on telecommunication and network protocols. The framework allows first, for modeling a variety of common protocol features by using mappings from state machines, sequence diagrams and packet encodings to ProtoTalk models, and second, for the consequent automatic generation of prototype Smalltalk code from the aforementioned ProtoTalk models. In this respect, the paper attempts to shed light on the use of generative model driven programming techniques within reflective object oriented programming languages and environments. As a proof of concept, we have specified in ProtoTalk and consequently generated in Smalltalk, several core features of the Session Initiation Protocol.
A Quantitative Study on the Communication Performance of Myrinet Network Interfaces

This paper presents a series of experiments for evaluating the communication performance of Myrinet network adaptors. In particular, this paper studies the impact that arises from the interactions between the Myrinet network adaptors and host computer systems on communications performance. We report and analyze the communication performances of GM, the low-level messaging API for Myrinet, and other network protocols such as IP and MPI that are built on top of GM. All the performance results are obtained using a Pentium-based cluster running the Linux operating systems and interconnected by the Myricom’s LANai9 (M3M-PCI64B) host adapters. ABSTRACT. 1
Automatic data capture for geographic information systems

We present a map interpretation system for automatic extraction of high level information from the scanned images of Chinese land register maps. Our map interpretation system consists of three main components: text/graphics separation, parcel extraction, and rotated character recognition. Our approach to text/graphics separation is based on a simple yet effective rule: the feature points of characters are more compact than those of graphics. In the parcel extraction process, the proposed algorithm traces the branches between feature points to extract polygon structure from line drawings. Our character recognition method is based on the matching of extracted strokes using a neural network. The techniques of text/graphics separation and character recognition are robust to the rotation and writing style of characters. Another advantage of our separation algorithm is that it can successfully extract a character connected to a graphical line. Experimental results have shown that the proposed system is effective for the data capture of geographic information systems.