Miracle-dz/UniFAR-FTUs huggingface dataset:
Two syntaxin homologues in the TGN/endosomal system of yeast

Intracellular membrane traffic is thought to be regulated in part by SNAREs, integral membrane proteins on transport vesicles (v‐SNAREs) and target organelles (t‐SNAREs) that bind to each other and mediate bilayer fusion. All known SNARE‐mediated fusion events involve a member of the syntaxin family of t‐SNAREs. Sequence comparisons identify eight such proteins encoded in the yeast genome, of which six have been characterized. We describe here the remaining two, Tlg1p and Tlg2p. These have the expected biochemical properties of t‐SNAREs, and are located in separable compartments which correspond to a putative early endosome and the yeast equivalent of the TGN, respectively. They co‐precipitate with the v‐SNARE Vti1p, which is implicated in Golgi–endosome traffic and, remarkably, binds to five different syntaxins. Tlg1p also binds the plasma membrane v‐SNARE Snc1p. Both Tlg1p and Tlg2p are required for efficient endocytosis and to maintain normal levels of TGN proteins. However, neither is required for intra‐Golgi traffic. Since no further syntaxins have been identified in yeast, this implies that the Golgi apparatus can function with a single syntaxin, Sed5p.
Sonographic Features of Triple‐Negative and Non–Triple‐Negative Breast Cancer

Triple‐negative breast cancer (TNBC) is known to have unique molecular, clinical, and pathologic characteristics. The growth pattern of this cancer may also affect its appearance on sonography. Our study evaluated the sonographic features of TNBC according to the American College of Radiology Breast Imaging Reporting and Data System sonographic classification system and compared these features with those of non‐TNBC.
Energy and Sampling Constrained Asynchronous Communication

The minimum energy, and, more generally, the minimum cost, to transmit 1 bit of information was recently derived for bursty communication when the information is available infrequently at random times at the transmitter. This result assumes that the receiver is always in the listening mode and samples all channel outputs until it makes a decision. Since sampling is in practice one of the receiver's most energy consuming functions, a natural question is to evaluate capacity per unit cost when the receiver is sampling constrained. This paper investigates such a setting where the receiver can sample only a given fraction ρ ∈ (0, 1] of the channel outputs. It is shown that regardless of ρ > 0, the asynchronous capacity per unit cost is the same as under full sampling, i.e., when ρ = 1. Moreover, a sparse output sampling does not even impact decoding delay-the elapsed time between when information is available and when it is decoded. Hence, surprisingly, it suffices to sample an arbitrarily small fraction of the channel outputs and yet achieve the same (asymptotic) performance as under full output sampling.
Sensory and electrophysiological properties of guinea‐pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel α subunit protein

The TTX‐sensitive Nav1.7 (PN1) Na+ channel α subunit protein is expressed mainly in small dorsal root ganglion (DRG) neurones. This study examines immunocytochemically whether it is expressed exclusively or preferentially in nociceptive primary afferent DRG neurones, and determines the electrophysiological properties of neurones that express it. Intracellular somatic action potentials (APs) evoked by dorsal root stimulation were recorded in L6/S1 DRG neurones at 30 ± 2 °C in vivo in deeply anaesthetised young guinea‐pigs. Each neurone was classified, from its dorsal root conduction velocity (CV) as a C‐, Aδ‐ or Aα/β‐fibre unit and from its response to mechanical and thermal stimuli, as a nociceptive, low threshold mechanoreceptive (LTM) or unresponsive unit. Fluorescent dye was injected into the soma and Nav1.7‐like immunoreactivity (Nav1.7‐LI) was examined on sections of dye‐injected neurones. All C‐, 90 % of Aδ‐ and 40 % of Aα/β‐fibre units, including both nociceptive and LTM units, showed Nav1.7‐LI. Positive units included 1/1 C‐LTM, 6/6 C‐nociceptive, 4/4 C‐unresponsive (possible silent nociceptive) units, 5/6 Aδ‐LTM (D hair), 13/14 Aδ‐nociceptive, 2/9 Aα/β‐nociceptive, 10/18 Aα/β‐LTM cutaneous and 0/9 Aα/β‐muscle spindle afferent units. Overall, a higher proportion of nociceptive than of LTM neurones was positive, and the median relative staining intensity was greater in nociceptive than LTM units. Nav1.7‐LI intensity was clearly positively correlated with AP duration and (less strongly) negatively correlated with CV and soma size. Since nociceptive units tend overall to have longer duration APs, slower CVs and smaller somata, these correlations may be related to the generally greater expression of Nav1.7 in nociceptive units.
Online Tracking by Learning Discriminative Saliency Map with Convolutional Neural Network

We propose an online visual tracking algorithm by learning discriminative saliency map using Convolutional Neural Network (CNN). Given a CNN pre-trained on a large-scale image repository in offline, our algorithm takes outputs from hidden layers of the network as feature descriptors since they show excellent representation performance in various general visual recognition problems. The features are used to learn discriminative target appearance models using an online Support Vector Machine (SVM). In addition, we construct target-specific saliency map by backprojecting CNN features with guidance of the SVM, and obtain the final tracking result in each frame based on the appearance model generatively constructed with the saliency map. Since the saliency map reveals spatial configuration of target effectively, it improves target localization accuracy and enables us to achieve pixel-level target segmentation. We verify the effectiveness of our tracking algorithm through extensive experiment on a challenging benchmark, where our method illustrates outstanding performance compared to the state-of-the-art tracking algorithms.
High prevalence of mutations in the EYS gene in Japanese patients with autosomal recessive retinitis pigmentosa.

PURPOSE To screen for disease-causing mutations in the Eyes shut homolog (EYS) gene in Japanese patients with retinitis pigmentosa (RP). Methods. Blood samples were obtained from 68 RP patients and 68 controls. Genomic DNA was extracted from the blood samples and used for screening of mutations in the coding exons by direct sequencing. Each patient underwent a detailed clinical examination. RESULTS Nine nucleotide sequence variations causing amino acid changes were observed in homozygous or heterozygous alleles in 26 patients but not in 68 controls. Seven truncating mutations were found in 21 (32.8%) of 64 patients with nonsyndromic RP composed of 23 autosomal recessive RP (arRP) and 41 sporadic cases. The most abundant mutation was p.S1653Kfs*2, which was generated by a single adenine insertion into exon 26 (c.4957dupA) and was carried by 15 patients. The mutation p.Y2935*, produced by a single nucleotide substitution (c.8805C>A) in the last exon, was carried by five patients. These two truncating mutations were probably founder mutations because each was carried by the particular haplotype. The patients with homozygous or compound heterozygous truncating mutations showed a severe decline in visual acuity, whereas those with a single truncating mutation showed a mild decline. CONCLUSIONS One-third of Japanese patients with nonsyndromic arRP carried probable pathogenic mutations in the EYS gene, including two founder mutations. Because the genotype was correlated with the phenotype, genotyping in the EYS gene could be a valuable tool for predicting long-term prognoses of Japanese patients with arRP and thus could be useful for genetic counseling and future gene therapy.
In Situ Characterization of Splenic Brucella melitensis Reservoir Cells during the Chronic Phase of Infection in Susceptible Mice

Brucella are facultative intracellular Gram-negative coccobacilli that chronically infect humans as well as domestic and wild-type mammals, and cause brucellosis. Alternatively activated macrophages (M2a) induced by IL-4/IL-13 via STAT6 signaling pathways have been frequently described as a favorable niche for long-term persistence of intracellular pathogens. Based on the observation that M2a-like macrophages are induced in the spleen during the chronic phase of B. abortus infection in mice and are strongly infected in vitro, it has been suggested that M2a macrophages could be a potential in vivo niche for Brucella. In order to test this hypothesis, we used a model in which infected cells can be observed directly in situ and where the differentiation of M2a macrophages is favored by the absence of an IL-12-dependent Th1 response. We performed an in situ analysis by fluorescent microscopy of the phenotype of B. melitensis infected spleen cells from intranasally infected IL-12p40-/- BALB/c mice and the impact of STAT6 deficiency on this phenotype. Most of the infected spleen cells contained high levels of lipids and expressed CD11c and CD205 dendritic cell markers and Arginase1, but were negative for the M2a markers Fizz1 or CD301. Furthermore, STAT6 deficiency had no effect on bacterial growth or the reservoir cell phenotype in vivo, leading us to conclude that, in our model, the infected cells were not Th2-induced M2a macrophages. This characterization of B. melitensis reservoir cells could provide a better understanding of Brucella persistence in the host and lead to the design of more efficient therapeutic strategies.
Bactibilia and Antibiotic Resistance in Elective Cholecysctectomy: An Updated Ecologic Survey.

BACKGROUND The role of bactibilia as a risk factor for an unfavorable outcome during biliary disease or surgical procedures remains obscure. Our aim was to identify possible risk factors for bactibilia and their possible relations to complications after elective cholecystectomy. As secondary aims, composition and antibiotic resistance patterns were studied. METHODS Bile and gallbladder mucosa samples from 358 elective cholecystectomies were collected prospectively between June 2009 and June 2012. Ordinary microbiologic cultures and antibiograms were performed. All pre-operative factors associated with bactibilia were studied by stepwise logistic regression multivariable analysis. RESULTS The bacteria isolated most frequently from 103 positive cultures were Escherichia coli (21.3%), Enterococcus spp. (14.7%), and Enterobacter spp. (14.7%) with a global amoxicillin-clavulanic acid resistance rate of 53.7%. Age >65 y, male gender, previous instrumentation or disease of the biliary tract, and high American Society of Anesthesiologists score were independent risk factors. No correlation was found between bactibilia and surgical complications. CONCLUSIONS Although the influence of bactibilia in developing surgical complications is limited, its composition and the high rate of resistance can be influential enough to modify antibiotic treatment in biliary tract infections, especially in high-risk patients.
Improving Classical Authentication over a Quantum Channel

We propose a quantum protocol to authenticate classical messages that can be used to replace Wegman–Carter’s classical authentication scheme in quantum key distribution (QKD) protocols. We show that the proposed scheme achieves greater conditional entropy of the seed for the intruder given her (quantum) observation than the classical case. The proposed scheme is suitable for situations where the shared symmetric key used in authentication becomes dangerously short (due to noise or eavesdropping), and there is a threat that it might be completely consumed without being replaced. Our protocol is an improvement over a classical scheme by Brassard and takes advantage of quantum channel properties. It is motivated by information-theoretical results. We stress that the proposed authentication protocol can also be used as an independent authentication protocol that is not a part of a QKD. However by adopting it, QKD becomes a fully quantum protocol. We prove that quantum resources can improve both the secrecy of the key generated by the PRG and the secrecy of the tag obtained with a hidden hash function. We conclude that the proposed quantum encoding offers more security than the classical scheme and, by applying a classical result, we show that it can be used under noisy quantum channels.
Essays on framing, free riding, and punishment

This thesis presents an experimental investigation of free riding behaviour and, more particularly, individual responses to it using, as a workhorse, the so called public goods game. This game starkly isolates the conflict between private and collective interest, providing us with a simple measure of the extent of free riding behaviour. The unifying theme of the thesis is elicitation and analysis of different indicators for how subjects perceive free riding under a number of treatment manipulations. Chapter 2 explores how people judge the morality of free riding in a public goods game by eliciting people's moral evaluations in hypothetical scenarios. The scenarios differed with respect to the framing of the game, the order of moves, and the behaviour of the non-judged player. Our findings suggest that free riding is perceived as morally reprehensible, except when the free rider moves second after observing that the other player free rode as well. We also find that moral judgments depend on others' behaviour, on framing and on the order of moves. Chapter 3 analyses the effect of framing on social preferences, as measured by self- reported emotions and punishment. Our findings are that, for a given pattern of contributions, neither punishment nor emotion depends on our framing manipulation. Chapter 4 assesses the behavioural consequences of unfair punishment. In this experiment, we generate an unfair environment by assigning punishment to all group members, irrespective of their first stage behaviour, We find that, although unfair punishment causes a different time profile of contributions, contributions are, on average, little different from in the standard punishment game; and the assignment of punishment in the latter is unaffected by experience of an environment with unfair punishment. However, a history of unfair punishment causes different reactions to helping behaviour and punishment received, respectively.
Treatment of neurosyphilis in HIV-infected patients . A systematic review .

Introduction After a large decrease in the number of cases of syphilis in the past decades, the incidence of syphilis is rising again. (1) At the end of the nineties, a new epidemic of syphilis has been documented in Western-Europe and the United States. (2) Although the number of patients seems to be decreasing again, this disease is still an important infectious disease that is sexually transmitted. Many patients with newly diagnosed syphilis are also HIV-infected. These patients have a higher risk to develop neurosyphilis, an inflammation of the central nerve system. Several case reports have shown that a concurrent infection with HIV may change the natural course of neurosyphilis. (3,4,5) This might mean that patients with HIV respond different on treatment for neurosyphilis. Though, it is not known whether patients with neurosyphilis and concurrent HIV infection really respond different to treatment compared to patients without concurrent HIV-infection. But if they do, what is the best treatment for HIV-infected patients? The purpose of this systematic review is to describe what is already known about treatment of neurosyphilis in HIV-infected patients. Do they respond different and if they do, what is the best treatment option?
Expressive power of the single-object typed access matrix model

The single-object typed access matrix (SOTAM) model was recently introduced in the literature by Sandhu and Suri (1992). It is a special case of Sandhu's typed access matrix (TAM) model (1992). In SOTAM individual commands are restricted to modifying exactly one column of the access matrix (whereas individual TAM commands in general can modify multiple columns). Sandhu and Suri have outlined a simple implementation of SOTAM in a distributed environment using the familiar client-server architecture. In particular the stipulation that each-command modifies a single column of the access matrix, is reflected in the desirable property that each command modifies a single access control list corresponding to that column. In this paper we show that TAM and SOTAM are formally equivalent in their expressive power. This result establishes that SOTAM has precisely the same expressive power as TAM, while having a simple implementation at the same time. In a nutshell, this result tells us that manipulation of access control information can be achieved in its most general form by manipulation of a single access control list (ACL) at a time. <<ETX>>
Medical education as a model for simulation education

Simulation professionals need to see themselves first as systems analysts, i.e., problem solvers, rather than just simulation users. As the networked digital economy develops, systems will become more complex, creating a robust market for experienced systems analysts who use simulation to solve operational problems and manage these complex systems. Physicians solve problems involving a complex biological system, i.e., the human body. The medical education system in the United States is examined and proposed as a model for an education structure for professional systems analysts. The objectives and requirements of simulation education are examined and a curriculum structure is proposed. It is also argued that certifying exams would do much to promote the profession and improve the educational environment.
Misregulation of a DDHD Domain-containing Lipase Causes Mitochondrial Dysfunction in Yeast*

The DDHD domain-containing proteins, which belong to the intracellular phospholipase A1 (iPLA1) family, have been predicted to be involved in phospholipid metabolism, lipid trafficking, membrane turnover, and signaling. Defective cardiolipin (CL), phosphatidylethanolamine, and phosphatidylglycerol remodeling cause Barth syndrome and mitochondrial dysfunction. Here, we report that Yor022c is a Ddl1 (DDHD domain-containing lipase 1) that hydrolyzes CL, phosphatidylethanolamine, and phosphatidylglycerol. Ddl1 has been implicated in the remodeling of mitochondrial phospholipids and CL degradation. Our data also suggested that the accumulation of monolysocardiolipin is deleterious to the cells. We show that Aft1 and Aft2 transcription factors antagonistically regulate the DDL1 gene. This study reveals that the misregulation of DDL1 by Aft1/2 transcription factors alters CL metabolism and causes mitochondrial dysfunction in the cells. In humans, mutations in the DDHD1 and DDHD2 genes cause specific types of hereditary spastic paraplegia (SPG28 and SPG54, respectively), and the yeast DDL1-defective strain produces similar phenotypes of hereditary spastic paraplegia (mitochondrial dysfunction and defects in lipid metabolism). Therefore, the DDL1-defective strain could be a good model system for understanding hereditary spastic paraplegia.
GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo

Ex vivo-expanded, allogeneic natural killer (NK) cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP) conditions. After a single step of magnetic depletion of CD3+ T cells, the depleted peripheral blood mononuclear cells (PBMCs) were stimulated and expanded with irradiated autologous PBMCs in the presence of OKT3 and IL-2 for 14 days, resulting in a highly pure population of CD3−CD16+CD56+ NK cells which is desired for allogeneic purpose. Compared with freshly isolated NK cells, these expanded NK cells showed robust cytokine production and potent cytolytic activity against various cancer cell lines. Of note, expanded NK cells selectively killed cancer cells without demonstrating cytotoxicity against allogeneic non-tumor cells in coculture assays. The anti-tumor activity of expanded human NK cells was examined in SCID mice injected with human lymphoma cells. In this model, expanded NK cells efficiently controlled lymphoma progression. In conclusion, allogeneic NK cells were efficiently expanded in a GMP-compliant facility and demonstrated potent anti-tumor activity both in vitro and in vivo.
Unified developmental model of maps, complex cells and surround modulation in the primary visual cortex

For human and animal vision, the perception of local visual features can depend on the spatial arrangement of the surrounding visual stimuli. In the earliest stages of visual processing this phenomenon is called surround modulation, where the response of visually selective neurons is influenced by the response of neighboring neurons. Surround modulation has been implicated in numerous important perceptual phenomena, such as contour integration and figure-ground segregation. In cats, one of the major potential neural substrates for surround modulation are lateral connections between cortical neurons in layer 2/3, which typically contains ”complex” cells that appear to combine responses from ”simple” cells in layer 4C. Interestingly, these lateral connections have also been implicated in the development of functional maps in primary visual cortex, such as smooth, well-organized maps for the preference of oriented lines. Together, this evidence suggests a common underlying substrate the lateral interactions in layer 2/3—as the driving force behind development of orientation maps for both simple and complex cells, and at the same time expression of surround modulation in adult animals. However, previously these phenomena have been studied largely in isolation, and we are not aware of a computational model that can account for all of them simultaneously and show how they are related. In this thesis we resolve this problem by building a single, unified computational model that can explain the development of orientation maps, the development of simple and complex cells, and surround modulation. First we build a simple, single-layer model of orientation map development based on ALISSOM, which has more realistic single cell properties (such as contrast gain control and contrast invariant orientation tuning) than its predecessor. Then we extend this model by adding layer 2/3, and show how the model can explain development of orientation maps of both simple and complex cells. As the last step towards a developmental model of surround modulation, we replace Mexican-hat-like lateral connectivity in layer 2/3 of the model with a more realistic configuration based on long-range excitation and short-range inhibitory cells, extending a simpler model by Judith Law. The resulting unified model of V1 explains how orientation maps of simple and complex cells can develop, while individual neurons in the developed model express realistic orientation tuning and various surround modulation properties. In doing so, we not only offer a consistent explanation behind all these phenomena, but also create a very rich model of V1 in which the interactions between various V1 properties can be studied. The model allows us to formulate several novel predictions that relate the