Miracle-dz/UniFAR-FTUs huggingface dataset:
Minimax and Hamiltonian Dynamics of Excitatory-Inhibitory Networks

A Lyapunov function for excitatory-inhibitory networks is constructed. The construction assumes symmetric interactions within excitatory and inhibitory populations of neurons, and antisymmetric interactions between populations. The Lyapunov function yields sufficient conditions for the global asymptotic stability of fixed points. If these conditions are violated, limit cycles may be stable. The relations of the Lyapunov function to optimization theory and classical mechanics are revealed by minimax and dissipative Hamiltonian forms of the network dynamics.
Speech Reductions Cause a De-Weighting of Secondary Acoustic Cues

The ability of the auditory system to change the perceptual weighting of acoustic cues when faced with degraded speech has long been evidenced. However, the exact changes that occur remain mostly unknown. Here, we proposed to use the Auditory Classification Image (ACI) methodology to reveal the acoustic cues used in natural speech comprehension and in reduced (i.e. noise-vocoded or re-synthesized) speech comprehension. The results show that in the latter case the auditory system updates its listening strategy by de-weighting secondary acoustic cues. Indeed, these are often weaker and thus more easily erased in adverse listening conditions. Furthermore our data suggests that this de-weighting does not directly depend on the actual reliability of the cues, but rather on the expected change in informativeness.
Generic Optimality Conditions for Semialgebraic Convex Programs

We consider linear optimization over a nonempty convex semialgebraic feasible region F. Semidefinite programming is an example. If F is compact, then for almost every linear objective there is a unique optimal solution, lying on a unique “active” manifold, around which F is “partly smooth,” and the second-order sufficient conditions hold. Perturbing the objective results in smooth variation of the optimal solution. The active manifold consists, locally, of these perturbed optimal solutions; it is independent of the representation of F and is eventually identified by a variety of iterative algorithms such as proximal and projected gradient schemes. These results extend to unbounded sets F.
Two-Photon Microscopy Imaging of thy1GFP-M Transgenic Mice: A Novel Animal Model to Investigate Brain Dendritic Cell Subsets In Vivo

Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF) microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP) in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype. With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity) of dendritic cells (DCs), and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions.
On optimal relay selection and subcarrier assignment in OFDMA relay networks with QoS guarantees

This paper investigates QoS-aware relay selection and subcarrier assignment in cooperative OFDMA networks. In contrast to some existing works, which solve the sum-rate maximization problem directly, we first simplify it by exploiting the structure of the optimal solution, then we solve the simplified problem. To characterize the optimal network sum-rate performance, we solve the simplified problem optimally by the branch-and-cut method. In addition to the sum-rate maximization problem, we demonstrate that its two variants can also be similarly simplified and then be solved optimally by the branch-and-cut method. The optimal method serving as the benchmark is particularly suitable for moderate scale problems. Simulations show that the branch-and-cut method can locate the optimal solution effectively, which may in turn provide some insights into the performance of the heuristic method.
Adoptive immunotherapy of advanced solid tumors: an eight year clinical experience.

BACKGROUND Adoptive immunotherapy (AI) of cancer, based upon the injection of in vitro manipulated autologous lymphocytes is still in an experimental phase. Our group started different clinical trials of AI in early 1990, and, at present, some specific targets for this approach seem to have been identified. PATIENTS AND METHODS 296 patients with solid tumors (melanoma, kidney carcinoma, non-small-cell lung cancer, mesothelioma, neoplastic pleural effusion, and liver cancer) were treated with either locoregional or systemic adoptive immunotherapy (AI) using both LAK and TIL cells in combination with s.c. rIL-2. RESULTS The surgery/AI combination resulted in good clinical results, characterized by enhanced survival and long lasting disease free periods in a significant number of patients. CONCLUSIONS AI seems to be efficacious in the treatment of melanoma, lung and hepatic cancers. Further studies will expand the application of the treatment to other malignancies.
Bevacizumab combined with chemotherapy for glioblastoma: a meta-analysis of randomized controlled trials

Bevacizumab, as antibodies, were applied to inhibit tumor angiogenesis by preventing activation of vascular endothelial growth factor receptor. We analyzed four clinical trials, including 607 patients, to investigate the efficacy and safety of bevacizumab when combined with chemotherapy for the treatment of glioblastomas. Results demonstrated that bevacizumab when combined with chemotherapy improved progression-free survival (HR = 0.66; 95% CI 0.56–0.78; p < 0.00001) compared with bevacizumab or chemotherapy alone. Furthermore, overall survival showed insignificant difference between two arms (HR 0.99; 95% CI 0.8–1.21; p = 0.92). However, we found that patients treated with bevacizumab-containing therapy reported increased objective response rate (OR 1.85, 95% CI 1.17–2.93; p = 0.009), but more treatment-related adverse events (OR 1.75; 95% CI 1.09–2.83; p = 0.02).
Expression of the Yersinia enterocolitica pYV-Encoded Type III Secretion System Is Modulated by Lipopolysaccharide O-Antigen Status

ABSTRACT We show that the expression of a Yersinia enterocolitica O:8 pYV-encoded type III secretion system was altered in a rough mutant (YeO8-R) due to elevated levels of FlhDC. H-NS might underlie flhDC upregulation in YeO8-R, and the data suggest a relationship between the absence of O antigen and the expression of H-NS.
Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington's disease brains, associate with membranes, and undergo calpain-dependent proteolysis

The Huntington's disease (HD) mutation is a polyglutamine expansion in the N-terminal region of huntingtin (N-htt). How neurons die in HD is unclear. Mutant N-htt aggregates in neurons in the HD brain; expression of mutant N-htt in vitro causes cell death. Other in vitro studies show that proteolysis by caspase 3 could be important in regulating mutant N-htt function, but there has been no direct evidence for caspase 3-cleaved N-htt fragments in brain. Here, we show that N-htt fragments consistent with the size produced by caspase 3 cleavage in vitro are resident in the cortex, striatum, and cerebellum of normal and adult onset HD brain and are similar in size to the fragments seen after exogenous expression of human huntingtin in mouse clonal striatal neurons. HD brain extracts treated with active caspase 3 had increased levels of N-htt fragments. Compared with the full-length huntingtin, the caspase 3-cleaved N-htt fragments, especially the mutant fragment, preferentially segregated with the membrane fraction. Partial proteolysis of the human caspase 3-cleaved N-htt fragment by calpain occurred in vitro and resulted in smaller N-terminal products; products of similar size appeared when mouse brain protein extracts were treated with calpain. Results support the idea that sequential proteolysis by caspase 3 and calpain may regulate huntingtin function at membranes and produce N-terminal mutant fragments that aggregate and cause cellular dysfunction in HD.
Lensed arc statistics: comparison of Millennium simulation galaxy clusters to Hubble Space Telescope observations of an X-ray selected sample

It has been debated for a decade whether there is a large overabundance of strongly lensed arcs in galaxyclusters, compared to expectations from Λ cold dark matter cosmology. We perform ray tracing through the most massive haloes of the Millennium simulation at several redshifts in their evolution, using the Hubble Ultra Deep Field as a source image, to produce realistic simulated lensed images. We compare the lensed arc statistics measured from the simulations to those of a sample of 45 X-ray selected clusters, observed with the Hubble Space Telescope, that we have analysed in Horesh et al. The observations and the simulations are matched in cluster masses, redshifts, observational effects, and the algorithmic arc detection and selection. At z= 0.6, there are too few massive-enough clusters in the Millennium volume for a proper statistical comparison with the observations. At redshifts 0.3 < z < 0.5, however, we have large numbers of simulated and observed clusters, and the latter are an unbiased selection from a complete sample. For these redshifts, we find excellent agreement between the observed and simulated arc statistics, in terms of the mean number of arcs per cluster, the distribution of number of arcs per cluster and the angular separation distribution. At z≈ 0.2 some conflict remains, with real clusters being ~3 times more efficient arc producers than their simulated counterparts. This may arise due to selection biases in the observed subsample at this redshift, to some mismatch in masses between the observed and simulated clusters or to physical effects that arise at low redshift and enhance the lensing efficiency, but which are not represented by the simulations.
A Multistep, Consensus‐Based Approach to Organ Allocation in Liver Transplantation: Toward a “Blended Principle Model”

Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD‐based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients’ associations and organ‐sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.
Resistance of Human Hepatitis Delta Virus RNAs to Dicer Activity

ABSTRACT The endonuclease dicer cleaves RNAs that are 100% double stranded and certain RNAs with extensive but <100% pairing to release ∼21-nucleotide (nt) fragments. Circular 1,679-nt genomic and antigenomic RNAs of human hepatitis delta virus (HDV) can fold into a rod-like structure with 74% pairing. However, during HDV replication in hepatocytes of human, woodchuck, and mouse origin, no ∼21-nt RNAs were detected. Likewise, in vitro, purified recombinant dicer gave <0.2% cleavage of unit-length HDV RNAs. Similarly, rod-like RNAs of potato spindle tuber viroid (PSTVd) and avocado sunblotch viroid (ASBVd) were only 0.5% cleaved. Furthermore, when a 66-nt hairpin RNA with 79% pairing, the putative precursor to miR-122, which is an abundant liver micro-RNA, replaced one end of HDV genomic RNA, it was poorly cleaved, both in vivo and in vitro. In contrast, this 66-nt hairpin, in the absence of appended HDV sequences, was >80% cleaved in vitro. Other 66-nt hairpins derived from one end of genomic HDV, PSTVd, or ASBVd RNAs were also cleaved. Apparently, for unit-length RNAs of HDV, PSTVd, and ASBVd, it is the extended structure with <100% base pairing that confers significant resistance to dicer action.
A 0.5-Approximation Algorithm for MAX DICUT with Given Sizes of Parts

Given a directed graph $G$ and an arc weight function $w: E(G)\rightarrow\mathbb{R}_+$, the maximum directed cut problem ({\sc max dicut}) is that of finding a directed cut $\delta (X)$ with maximum total weight. In this paper we consider a version of {\sc max dicut}---{\sc max dicut} with given sizes of parts or {\sc max dicut with gsp}---whose instance is that of {\sc max dicut} plus a positive integer $p$, and it is required to find a directed cut $\delta (X)$ having maximum weight over all cuts $\delta (X)$ with $|X|=p$. Our main result is a $0.5$-approximation algorithm for solving the problem. The algorithm is based on a tricky application of the pipage rounding technique developed in some earlier papers by two of the authors and a remarkable structural property of basic solutions to a linear relaxation. The property is that each component of any basic solution is an element of a set $\{0,\delta,1/2,1-\delta,1 \}$, where $\delta$ is a constant that satisfies $0<\delta<1/2$ and is the same for all components.
Status of pretreatment evaluation, treatment and follow‐up regimens for renal cell carcinoma in the Nordic countries

Objective: One prerequisite for performing multicentre studies is that the clinical handling of the patients must be uniform. We therefore evaluated possible differences in pretreatment evaluation, surgical treatment and follow‐up regimes between the Nordic countries and between the different departments that performed nephrectomy due to renal cell carcinoma. Material and Methods: A questionnaire comprising 21 different questions was sent to all hospitals in the five Nordic countries performing nephrectomy. The questionnaires were returned by 195/226 (86%) departments. Results: In total, 24% of the departments performed fewer than five tumour nephrectomies per year. The main differences were as follows. I.v. pyelography was never used in Finland in clinics with urologists while preoperative CT scans were performed by most departments and in most countries. Cytology/biopsy examinations were never used in urological clinics in Finland and Iceland in contrast to 31% of urological clinics in Denmark. In Finland, 69% of the departments performed nephrectomy in patients with multiple distant metastases, compared to only 15% in the other Nordic countries. Follow‐up after nephrectomy was done in 38% of Danish departments and in 96% of departments in the other Nordic countries. Conclusion: There were evident differences between the urological/surgical departments in the five Nordic countries, especially concerning radiological evaluation, treatment of patients with metastases and postoperative follow‐up.
The prosodic licensing of coda consonants in early speech: interactions with vowel length

Abstract English has a word-minimality requirement that all open-class lexical items must contain at least two moras of structure, forming a bimoraic foot (Hayes, 1995). Thus, a word with either a long vowel, or a short vowel and a coda consonant, satisfies this requirement. This raises the question of when and how young children might learn this language-specific constraint, and if they would use coda consonants earlier and more reliably after short vowels compared to long vowels. To evaluate this possibility we conducted an elicited imitation experiment with 15 two-year-old Australian English-speaking children, using both perceptual and acoustic analysis. As predicted, the children produced codas more often when preceded by short vowels. The findings suggest that English-speaking two-year-olds are sensitive to language-specific lexical constraints, and are more likely to use coda consonants when prosodically required.
On Compress-Forward without Wyner-Ziv Binning for Relay Networks

Noisy network coding is recently proposed for the general multi-source network by Lim, Kim, El Gamal and Chung. This scheme builds on compress-forward (CF) relaying but involves three new ideas, namely no Wyner-Ziv binning, relaxed simultaneous decoding and message repetition. In this paper, using the two-way relay channel as the underlining example, we analyze the impact of each of these ideas on the achievable rate region of relay networks. First, CF without binning but with joint decoding of both the message and compression index can achieve a larger rate region than the original CF scheme for multi-destination relay networks. With binning and successive decoding, the compression rate at each relay is constrained by the weakest link from the relay to a destination; but without binning, this constraint is relaxed. Second, simultaneous decoding of all messages over all blocks without uniquely decoding the compression indices can remove the constraints on compression rate completely, but is still subject to the message block boundary effect. Third, message repetition is necessary to overcome this boundary effect and achieve the noisy network coding region for multi-source networks. The rate region is enlarged with increasing repetition times. We also apply CF without binning specifically to the one-way and two-way relay channels and analyze the rate regions in detail. For the one-way relay channel, it achieves the same rate as the original CF and noisy network coding but has only 1 block decoding delay. For the two-way relay channel, we derive the explicit channel conditions in the Gaussian and fading cases for CF without binning to achieve the same rate region or sum rate as noisy network coding. These analyses may be appealing to practical implementation because of the shorter encoding and decoding delay in CF without binning.
Robust Spectral Analysis

In this paper I introduce quantile spectral densities that summarize the cyclical behavior of time series across their whole distribution by analyzing periodicities in quantile crossings. This approach can capture systematic changes in the impact of cycles on the distribution of a time series and allows robust spectral estimation and inference in situations where the dependence structure is not accurately captured by the auto-covariance function. I study the statistical properties of quantile spectral estimators in a large class of nonlinear time series models and discuss inference both at fixed and across all frequencies. Monte Carlo experiments illustrate the advantages of quantile spectral analysis over classical methods when standard assumptions are violated.
Effects of dopamine on reinforcement learning and consolidation in Parkinson’s disease

Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting. An influential hypothesis posits that dopamine biases reinforcement learning. More recent data also suggest an influence during both consolidation and retrieval. Eighteen Parkinson’s disease patients learned through feedback ON or OFF medication, with memory tested 24 hr later ON or OFF medication (4 conditions, within-subjects design with matched healthy control group). Patients OFF medication during learning decreased in memory accuracy over the following 24 hr. In contrast to previous studies, however, dopaminergic medication during learning and testing did not affect expression of positive or negative reinforcement. Two further experiments were run without the 24 hr delay, but they too failed to reproduce effects of dopaminergic medication on reinforcement learning. While supportive of a dopaminergic role in consolidation, this study failed to replicate previous findings on reinforcement learning. DOI: http://dx.doi. org/10.7554/eLife.26801. 001
Patterns of Autobiographical Memory Loss in Medial-Temporal Lobe Amnesic Patients

The issue of whether the hippocampus and related structures in the medial-temporal lobe (MTL) play a temporary or permanent role in autobiographical episodic memory remains unresolved. One long-standing belief is that autobiographical memory (AM), like semantic memory, is initially dependent on the MTL but ultimately can be retained and recovered independently of it. However, evidence that hippocampal amnesia results in severe loss of episodic memory for a lifetime of personally experienced events suggests otherwise. To test the opposing views, we conducted detailed investigations of autobiographical episodic memory in people with amnesia resulting from MTL lesions of varying extent. By combining precise quantification of MTL and neocortical volumes with sensitive measures of recollection of one's personal past, we show that the severity of episodic, but not semantic, AM loss is best accounted for by the degree of hippocampal damage and less likely related to additional neocortical compromise.
The development of ocular dominance columns in normal and visually deprived monkeys

The main purpose of this study was to examine the normal postnatal development of ocular dominance columns in the striate cortex of the macaque monkey and to determine how this developmental process is influenced by monocular lid‐suture. The physiological pattern of ocular dominance was studied in long, tangential electrode penetrations. For anatomical demonstration of the distribution of afferents we relied principally on the transneuronal transport of [3H]proline injected into one eye, and to a lesser extent on the Liesegang silver method. The effects of deprivation on cell size in the lateral geniculate nucleus (LGN) were also studied. Twenty‐six monkeys, divided into 5 groups (A–E), were used.