Miracle-dz/UniFAR-FTUs huggingface dataset:
Likelihood functions and confidence bounds for total-least-squares problems

This paper addresses the derivation of likelihood functions and confidence bounds for problems involving over-determined linear systems with noise in all measurements, often referred to as total-least-squares (TLS). It has been shown previously that TLS provides maximum likelihood estimates. But rather than being a function solely of the variables of interest, the associated likelihood functions increase in dimensionality with the number of equations. This has made it difficult to derive suitable confidence bounds, and impractical to use these probability functions with Bayesian belief propagation or Bayesian tracking. This paper derives likelihood functions that are defined only on the parameters of interest. This has two main advantages. First, the likelihood functions are much easier to use within a Bayesian framework; and second it is straightforward to obtain a reliable confidence bound on the estimates. We demonstrate the accuracy of our confidence bound in relation to others that have been proposed. Also, we use our theoretical results to obtain likelihood functions for estimating the direction of 3D camera translation.
Dynamics of the readily releasable pool during post‐tetanic potentiation in the rat calyx of Held synapse

The size of the readily releasable pool (RRP) of vesicles was measured in control conditions and during post‐tetanic potentiation (PTP) in a large glutamatergic terminal called the calyx of Held. We measured excitatory postsynaptic currents evoked by a high frequency train of action potentials in slices of 4–11‐day‐old rats. After a tetanus the cumulative release during such a train was enlarged by approximately 50%, indicating that the size of the RRP was increased. The amount of enhancement depended on the duration and frequency of the tetanus and on the age of the rat. After the tetanus, the size of the RRP decayed more slowly (t1/2= 10 versus 3 min) back to control values than the release probability. This difference was mainly due to a very fast initial decay of the release probability, which had a time constant compatible with an augmentation phase (τ≈ 30 s). The overall decay of PTP at physiological temperature was not different from room temperature, but the increase in release probability (Pr) was restricted to the first minute after the tetanus. Thereafter PTP was dominated by an increase in the size of the RRP. We conclude that due to the short lifetime of the increase in release probability, the contribution of the increase in RRP size during post‐tetanic potentiation is more significant at physiological temperature.
Are GAF scores reliable in routine clinical use?

Objective: The Global Assessment of Functioning (GAF) scale has been considered as a reliable tool. However, most studies of GAF reliability have been based on special conditions, such as prior training and test awareness. This study takes a different approach investigating inter‐rater reliability of GAF scores in a routine clinical context.
WHO‐histological criteria for myeloproliferative neoplasms: reproducibility, diagnostic accuracy and correlation with gene mutations and clinical outcomes

Bone marrow histology is included in the diagnostic criteria of myeloproliferative neoplasms (MPNs). However, some concerns have emerged about its reproducibility. To evaluate the diagnostic accuracy of histology and to assess its correlation with presence of mutations and clinical outcomes, two pathologists reviewed the bone marrow biopsies corresponding to 211 patients with MPN. Despite the low agreement in the evaluation of individual histopathological characteristics, the concordance among pathologists when establishing the diagnosis was good (Kappa index 0·67). The specificity of histology was 100%, 98·5% and 98% in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), respectively, whereas the sensitivity of histological diagnosis was low in PV and ET (32·5% and 54% respectively) and acceptable in PMF (75%). Thirteen out of 146 (9%) patients with clinical ET were diagnosed as prefibrotic PMF. No histological agreement or MPN otherwise unspecified was more frequently observed in JAK2 V617F‐positive ET than in CALR‐mutated cases, whereas megakaryocytic abnormalities and prefibrotic PMF were more frequently observed in CALR‐mutated ET. In conclusion, histological criteria of MPN have a limited diagnostic accuracy due to low sensitivity. Patients with JAK2 V617F‐positive MPN have a heterogeneous histology while CALR‐positive ET is associated with megakaryocyte abnormalities and prefibrotic PMF.
Universal Hough dictionaries for object tracking

Fausto Milletari1 fausto.milletari@tum.de Wadim Kehl1 kehl@in.tum.de Federico Tombari12 tombari@in.tum.de Slobodan Ilic14 slobodan.ilic@in.tum.de Seyed-Ahmad Ahmadi3 ahmadi@cs.tum. edu Nassir Navab1 navab@cs.tum. edu 1 Computer Aided Medical Procedures Technische Universitat Munchen Munchen, Germany 2 Computer Science Department (DISI) University of Bologna Bologna, Italy 3 Department of Neurology Ludwig-Maximilians-Universitat Munchen, Germany 4 Siemens AG Munchen, Germany
SDSS J160531.84+174826.1: A Dwarf Disk Galaxy with an Intermediate-Mass Black Hole

We report the discovery of a dwarf Seyfert 1 active galactic nucleus (AGN) with a candidate intermediate-mass black hole, hosted by the dwarf galaxy SDSS J160531.84+174826.1 at z = 0.032. A broad component of the Hα line with FWHM = 781 km s-1 is detected in its optical spectrum, and a bright, pointlike nucleus is evident from a Hubble Space Telescope (HST) imaging observation. Nonthermal X-ray emission is also detected from the nucleus. The black hole mass, as estimated from the luminosity and width of the broad Hα component, is about 7 × 104 M☉. The host galaxy appears to be a disk galaxy with a boxy bulge or nuclear bar. With an absolute magnitude of MR = -17.8 (MB = -16.4), it is among the least luminous host galaxies ever identified for a Seyfert 1.
Coordination of groups of mobile autonomous agents using nearest neighbor rules

Vicsek et al. proposed (1995) a simple but compelling discrete-time model of n autonomous agents {i.e., points or particles} all moving in the plane with the same speed but with different headings. Each agent's heading is updated using a local rule based on the average of its own heading plus the headings of its "neighbors". In their paper, Vicsek et al. provide simulation results which demonstrate that the nearest neighbor rule they are studying can cause all agents to eventually move in the same direction despite the absence of centralized coordination and despite the fact that each agent's set of nearest neighbors change with time as the system evolves. This paper provides a theoretical explanation for this observed behavior. In addition, convergence results are derived for several other similarly inspired models. The Vicsek model proves to be a graphic example of a switched linear system which is stable, but for which there does not exist a common quadratic Lyapunov function.
Emotions in Serious Games: From Experience to Assessment

Serious Games represent a global revolution that promises to develop intuitive, affordable, accessible and familiar learning environments for a wide range of educational and training applications. Serious Games are computer or video games in which education is the primary goal, rather than entertainment. Serious Games offer different benefits due to the integration of simulation aspects, game aspects and pedagogical elements at the same time. Among the different assets that Serious Games provide for learning, we will focus in this paper on their ability to leverage the synergy between emotional and learning appropriation processes. We will first outline the specific features of learning opportunities offered by Serious Games considering the involvement of emotions in this learning process. The following part of the paper will be dedicated to the description of the methods for the analysis of the emotional experience of SG users. Finally, we will explore a new promising research direction concerning the use of Affective Computing in Serious Games.
Enhancement of cathepsin G-induced platelet activation by leukocyte elastase: consequence for the neutrophil-mediated platelet activation.

We have focused our interest on the platelet-activating properties of two polymorphonuclear neutrophil (PMN)-derived proteinases, namely elastase (HLE) and cathepsin G (Cat.G). First of all, we observed that whereas HLE was unable to trigger platelet activation by itself, it enhanced platelet activation induced by Cat.G when both proteinases were added simultaneously. It has been recently described that, upon stimulation, PMN released Cat.G, which in turn activated surrounding platelets. Thus, we looked for a combined effect of Cat.G and HLE during this cell-to-cell interaction. When PMN (5 x 10(6)/mL) were stimulated by 0.5 mumol/L N-formyl-Met-Leu-Phe, they released 237.9 +/- 49.1 nmol/L Cat.G and 381.7 +/- 28.0 nmol/L HLE. Such a concentration of purified Cat.G (240 nmol/L) induced only a moderate platelet activation when added to a PMN-platelet mixture. However, when Cat.G (240 nmol/L) and HLE (380 nmol/L) were added together, the resulting platelet activation was strictly comparable to that corresponding to the addition of N-formyl-Met-Leu-Phe (P > .05) in terms of aggregation, dense and alpha granule secretion, and thromboxane B2 production. In fact, Elafin, a specific HLE inhibitor, when added to the PMN-platelet cooperation system triggered by N-formyl-Met-Leu-Phe, prevented platelet activation within the same range of concentrations as for inhibition of HLE activity. In conclusion, we now show that not only Cat.G, but also HLE is involved in the PMN-mediated platelet activation.
A Transmissible Plasmid-Borne Pathogenicity Island Confers Piscibactin Biosynthesis in the Fish Pathogen Photobacterium damselae subsp. piscicida

ABSTRACT The fish pathogen Photobacterium damselae subsp. piscicida produces the siderophore piscibactin. A gene cluster that resembles the Yersinia high-pathogenicity island (HPI) encodes piscibactin biosynthesis. Here, we report that this HPI-like cluster is part of a hitherto-uncharacterized 68-kb plasmid dubbed pPHDP70. This plasmid lacks homologs of genes that mediate conjugation, but we found that it could be transferred at low frequencies from P. damselae subsp. piscicida to a mollusk pathogenic Vibrio alginolyticus strain and to other Gram-negative bacteria, likely dependent on the conjugative functions of the coresident plasmid pPHDP60. Following its conjugative transfer, pPHDP70 restored the capacity of a vibrioferrin mutant of V. alginolyticus to grow under low-iron conditions, and piscibactin became detectable in its supernatant. Thus, pPHDP70 appears to harbor all the genes required for piscibactin biosynthesis and transport. P. damselae subsp. piscicida strains cured of pPHDP70 no longer produced piscibactin, had impaired growth under iron-limited conditions, and exhibited markedly decreased virulence in fish. Collectively, our findings highlight the importance of pPHDP70, with its capacity for piscibactin-mediated iron acquisition, in the virulence of P. damselae subsp. piscicida. Horizontal transmission of this plasmid-borne piscibactin synthesis gene cluster in the marine environment may facilitate the emergence of new pathogens.
Constructing Reference Semantic Predictions from Biomedical Knowledge Sources

Semantic tuples are core component of text mining and knowledge extraction systems in biomedicine. The practical success of these systems significantly depends on the correctness and quality of the extracted semantic tuples. The quality and correctness of the semantic predictions can be measured against a benchmark semantic structure. In this article, we presented an approach for constructing a reference semantic tuple structure based on the existing biomedical knowledge sources in which the evaluation is based on the UMLS knowledge sources. In the evaluation, 7400 semantic triples are extracted from UMLS knowledge sources and the semantic predictions are constructed using the proposed approach. In the semantic triples, 87 concepts are found redundantly classified and 207 pair of semantic triples showed hierarchically inconsistent. 128 are found to be non-taxonomically inconsistent. The quality of the semantic triple is also judged using expert evaluators. The Cohen's kappa coefficient is used to measure the degree of agreement between two evaluators and the result is promising (0.9). Construire des prévisions de référence sémantique à partir de sources de connaissances biomédicales Les "tuples sémantiques" forment un élément essentiel à la fouille de texte et aux systèmes d'extraction de connaissances dans le domaine biomédical. Le succès en pratique des systèmes exploitant ces informations sémantique, dépend fortement de l'exactitude et de la qualité des tuples sémantiques. La qualité et l'exactitude des informations sémantiques produites automatiquement peuvent être mesurées par rapport à une structure de référence. Dans cet article, nous présentons une approche pour construire une structure sémantique à base de tuples, basée sur des sources existantes dans le domaine biomédicale. L'approche est évaluée en comparaison du méta-thésaurus UMLS. Dans une évaluation préliminaire, 7400 tuples sémantiques ont été aléatoirement extraits de UMLS et les prédictions de relations on été construites en utilisant l'approche proposée. Dans les triplets sémantiques étudiés, 87 concepts se révèlent être classés de manière redondante et 207 paires de triplets sémantiques ont une relation hiérarchique incompatible, et finalement 128 sont jugées taxonomiquement compatibles. La qualité de la relation sémantique est également jugée en utilisant des évaluateurs, experts du domaine. Le coefficient kappa de Cohen est utilisé pour mesurer le degré d'accord entre deux évaluateurs et le résultat est d'ors et déjà prometteur (0,9).
New insights on NOX enzymes in the central nervous system.

SIGNIFICANCE There is increasing evidence that the generation of reactive oxygen species (ROS) in the central nervous system (CNS) involves the NOX family of nicotinamide adenine dinucleotide phosphate oxidases. Controlled ROS generation appears necessary for optimal functioning of the CNS through fine-tuning of redox-sensitive signaling pathways, while overshooting ROS generation will lead to oxidative stress and CNS disease. RECENT ADVANCES NOX enzymes are not only restricted to microglia (i.e. brain phagocytes) but also expressed in neurons, astrocytes, and the neurovascular system. NOX enzymes are involved in CNS development, neural stem cell biology, and the function of mature neurons. While NOX2 appears to be a major source of pathological oxidative stress in the CNS, other NOX isoforms might also be of importance, for example, NOX4 in stroke. Globally speaking, there is now convincing evidence for a role of NOX enzymes in various neurodegenerative diseases, cerebrovascular diseases, and psychosis-related disorders. CRITICAL ISSUES The relative importance of specific ROS sources (e.g., NOX enzymes vs. mitochondria; NOX2 vs. NOX4) in different pathological processes needs further investigation. The absence of specific inhibitors limits the possibility to investigate specific therapeutic strategies. The uncritical use of non-specific inhibitors (e.g., apocynin, diphenylene iodonium) and poorly validated antibodies may lead to misleading conclusions. FUTURE DIRECTIONS Physiological and pathophysiological studies with cell-type-specific knock-out mice will be necessary to delineate the precise functions of NOX enzymes and their implications in pathomechanisms. The development of CNS-permeant, specific NOX inhibitors will be necessary to advance toward therapeutic applications.
Insulation or Patronage: Political Institutions and Bureaucratic Efficiency

Abstract This article presents a model of political insulation of bureaucracies. Political influence can harm competence because it lowers the incentives of bureaucrats to invest in competence. Politicians then want to adopt institutions that insulate the bureaucracy because this establishes a commitment to reward competence. Political leaders insulate the bureaucracy if public good provision is important compared to rent extraction or when political competition forces the political elite to internalize the welfare loss caused by patronage. Through this channel political reforms can lead to reforms of the bureaucracy. The theoretical findings are illustrated with existing empirical studies and data on central bank independence.
Phospholipid Metabolism Regulated by a Transcription Factor Sensing Phosphatidic Acid

Cells regulate the biophysical properties of their membranes by coordinated synthesis of different classes of lipids. Here, we identified a highly dynamic feedback mechanism by which the budding yeast Saccharomyces cerevisiae can regulate phospholipid biosynthesis. Phosphatidic acid on the endoplasmic reticulum directly bound to the soluble transcriptional repressor Opi1p to maintain it as inactive outside the nucleus. After the addition of the lipid precursor inositol, this phosphatidic acid was rapidly consumed, releasing Opi1p from the endoplasmic reticulum and allowing its nuclear translocation and repression of target genes. Thus, phosphatidic acid appears to be both an essential ubiquitous metabolic intermediate and a signaling lipid.
The Bcl-2 Homology Domain 3 Mimetic Gossypol Induces Both Beclin 1-dependent and Beclin 1-independent Cytoprotective Autophagy in Cancer Cells*

Gossypol, a natural Bcl-2 homology domain 3 mimetic compound isolated from cottonseeds, is currently being evaluated in clinical trials. Here, we provide evidence that gossypol induces autophagy followed by apoptotic cell death in both the MCF-7 human breast adenocarcinoma and HeLa cell lines. We first show that knockdown of the Bcl-2 homology domain 3-only protein Beclin 1 reduces gossypol-induced autophagy in MCF-7 cells, but not in HeLa cells. Gossypol inhibits the interaction between Beclin 1 and Bcl-2 (B-cell leukemia/lymphoma 2), antagonizes the inhibition of autophagy by Bcl-2, and hence stimulates autophagy. We then show that knockdown of Vps34 reduces gossypol-induced autophagy in both cell lines, and consistent with this, the phosphatidylinositol 3-phosphate-binding protein WIPI-1 is recruited to autophagosomal membranes. Further, Atg5 knockdown also reduces gossypol-mediated autophagy. We conclude that gossypol induces autophagy in both a canonical and a noncanonical manner. Notably, we found that gossypol-mediated apoptotic cell death was potentiated by treatment with the autophagy inhibitor wortmannin or with small interfering RNA against essential autophagy genes (Vps34, Beclin 1, and Atg5). Our findings support the notion that gossypol-induced autophagy is cytoprotective and not part of the cell death process induced by this compound.
Dilute Semiflexible Polymers with Attraction: Collapse, Folding and Aggregation

We review the current state on the thermodynamic behavior and structural phases of self- and mutually-attractive dilute semiflexible polymers that undergo temperature-driven transitions. In extreme dilution, polymers may be considered isolated, and this single polymer undergoes a collapse or folding transition depending on the internal structure. This may go as far as to stable knot phases. Adding polymers results in aggregation, where structural motifs again depend on the internal structure. We discuss in detail the effect of semiflexibility on the collapse and aggregation transition and provide perspectives for interesting future investigations.
Identification of New Antileishmanial Leads from Hits Obtained by High-Throughput Screening

ABSTRACT A previous screen of ∼200,000 compounds from the PubChem database identified 70 compounds possessing 50% effective concentrations (EC50s) below 1 μM against Leishmania major promastigotes that were not toxic to mammalian epithelial cancer cells at this concentration (E. Sharlow et al., PLoS Negl. Trop. Dis. 3:e540, 2009). Based on availability and chemical exclusion criteria, 31 of these compounds were purchased from commercial suppliers and evaluated for in vitro activity against intracellular L. donovani and L. amazonensis parasites. Benzothiazole cyanine compounds (PubChem 16196319 and 16196223) displayed potent activity against intracellular amastigotes, prompting a search for commercially available compounds that were structurally related. Pubchem 123859 (the cyanine dye thiazole orange) showed exceptionally potent activity against intracellular L. donovani in vitro (50% inhibitory concentration [IC50] = 21 ± 12 nM) and low cytotoxicity against Vero cells (IC50 = 7,800 ± 200 nM). Administration of 123859 and 16196319 at a dose of 1 mg/kg of body weight intraperitoneally (i.p.) daily for 5 days resulted in 44% ± 4% and 42% ± 3% suppression of liver parasitemia in L. donovani-infected BALB/c mice, respectively, compared to the untreated control group (the reductions in liver parasitemia were 30% ± 5% and 27% ± 4%, respectively, compared to the (2-hydroxypropyl)-β-cyclodextrin solution (HPβCD) vehicle control, which itself displayed some antileishmanial activity). Benzothiazole-containing cyanine dyes are thus potential lead compounds for the discovery of novel antileishmanial agents.
Plasmid-Mediated Beta-Lactamase Production in Neisseria gonorrhoeae

Several β-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae were examined for R plasmids. Penicillin-resistant strains isolated from men returning from the Far East and their contacts contained a 4.4 × 106-dalton plasmid in common. Transformation studies and the isolation of a spontaneous penicillin-susceptible segregant showed that the structural gene for β-lactamase was part of the 4.4 × 106-dalton plasmid. An additional penicillin-resistant gonococcal strain isolated in London was found to harbor a 3.2 × 106-dalton R plasmid. Deoxyribonucleic acid (DNA)-DNA duplex studies revealed that the penicillin-resistant gonococcal isolates contained a significant portion (about 40%) of the transposable DNA sequence, TnA, which includes the β-lactamase gene commonly found on R plasmids of the Enterobacteriaceae and Haemophilus influenzae.
A Novel Rabbit Immunospot Array Assay on a Chip Allows for the Rapid Generation of Rabbit Monoclonal Antibodies with High Affinity

Antigen-specific rabbit monoclonal antibodies (RaMoAbs) are useful due to their high specificity and high affinity, and the establishment of a comprehensive and rapid RaMoAb generation system has been highly anticipated. Here, we present a novel system using immunospot array assay on a chip (ISAAC) technology in which we detect and retrieve antigen-specific antibody-secreting cells from the peripheral blood lymphocytes of antigen-immunized rabbits and produce antigen-specific RaMoAbs with 10–12 M affinity within a time period of only 7 days. We have used this system to efficiently generate RaMoAbs that are specific to a phosphorylated signal-transducing molecule. Our system provides a new method for the comprehensive and rapid production of RaMoAbs, which may contribute to laboratory research and clinical applications.
The Unemployment Volatility Puzzle: A Note on the Role of Reference Points

This theoretical note aims at studying the role of reference points in generating unemployment volatility. For this purpose, I introduce the notion of reference points in a standard Mortensen-Pissarides model. I obtain two results. First, I find that the obtained model is similar to the one found by Pissarides (2009) with matching costs. Second, I show that the introduction of reference points can increase significantly unemployment volatility through a mechanism a la Hagerdorn and Manovskii (2008).