Miracle-dz/UniFAR-FTUs huggingface dataset:
Magnetic Brain Response Mirrors Extraction of Phonological Features from Spoken Vowels

This study further elucidates determinants of vowel perception in the human auditory cortex. The vowel inventory of a given language can be classified on the basis of phonological features which are closely linked to acoustic properties. A cortical representation of speech sounds based on these phonological features might explain the surprisingly inverse correlation between immense variance in the acoustic signal and high accuracy of speech recognition. We investigated timing and mapping of the N100m elicited by 42 tokens of seven natural German vowels varying along the phonological features tongue height (corresponding to the frequency of the first formant) and place of articulation (corresponding to the frequency of the second and third formants). Auditoryevoked fields were recorded using a 148-channel whole-head magnetometer while subjects performed target vowel detection tasks. Source location differences appeared to be driven by place of articulation: Vowels with mutually exclusive place of articulation features, namely, coronal and dorsal elicited separate centers of activation along the posterior-anterior axis. Additionally, the time course of activation as reflected in the N100m peak latency distinguished between vowel categories especially when the spatial distinctiveness of cortical activation was low. In sum, results suggest that both N100m latency and source location as well as their interaction reflect properties of speech stimuli that correspond to abstract phonological features.
Educational level and 5-year all-cause mortality in the Hypertension Detection and Follow-up Program. Hypertension Detection and Follow-up Program Cooperative Group.

Excess mortality in persons of lower socioeconomic status is a finding confirmed in many population studies. Among the nearly 11,000 hypertensive trial participants in the population-based Hypertension Detection and Follow-up Program, lower educational level (an indicator of low socioeconomic status) was associated with a 5-year death rate significantly above that found in those with higher education. This report examines whether this excess was observed uniformly within both treatment groups--stepped care and referred care--or whether the more vigorous antihypertensive program of stepped care was able to reduce the mortality gradient associated with education. In addition, impact on mortality of degree of blood pressure control during the trial was assessed within stepped and referred care groups, taking account also of educational level. Finally, the benefit of stepped care compared with referred care (control group) in reducing mortality was analyzed, controlling for education. Referred care participants with less than a high school education had a 5-year death rate twice as high as those with more than a high school education, whereas no such gradient of mortality was seen in the stepped care group. Level of blood pressure control throughout the trial was better in the stepped than in the referred care group and was significantly (inversely) associated with mortality in the stepped care group, regardless of educational level. In the referred care group as well, the better the control of elevated blood pressure (again, regardless of educational level), the lower the mortality, although this inverse association did not quite reach statistical significance in the referred care group. (ABSTRACT TRUNCATED AT 250 WORDS)
Hypothermia treatment potentiates ERK1/2 activation after traumatic brain injury

Traumatic brain injury (TBI) results in significant hippocampal pathology and hippocampal‐dependent memory loss, both of which are alleviated by hypothermia treatment. To elucidate the molecular mechanisms regulated by hypothermia after TBI, rats underwent moderate parasagittal fluid‐percussion brain injury. Brain temperature was maintained at normothermic or hypothermic temperatures for 30 min prior and up to 4 h after TBI. The ipsilateral hippocampus was assayed with Western blotting. We found that hypothermia potentiated extracellular signal‐regulated kinase 1/2 (ERK1/2) activation and its downstream effectors, p90 ribosomal S6 kinase (p90RSK) and the transcription factor cAMP response element‐binding protein. Phosphorylation of another p90RSK substrate, Bad, also increased with hypothermia after TBI. ERK1/2 regulates mRNA translation through phosphorylation of mitogen‐activated protein kinase‐interacting kinase 1 (Mnk1) and the translation factor eukaryotic initiation factor 4E (eIF4E). Hypothermia also potentiated the phosphorylation of both Mnk1 and eIF4E. Augmentation of ERK1/2 activation and its downstream signalling components may be one molecular mechanism that hypothermia treatment elicits to improve functional outcome after TBI.
Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract

Many neurodegenerative diseases are linked to amyloid aggregation. In Huntington’s disease (HD), neurotoxicity correlates with an increased aggregation propensity of a polyglutamine (polyQ) expansion in exon 1 of mutant huntingtin protein (mHtt). Here we establish how the domains flanking the polyQ tract shape the mHtt conformational landscape in vitro and in neurons. In vitro, the flanking domains have opposing effects on the conformation and stabilities of oligomers and amyloid fibrils. The N-terminal N17 promotes amyloid fibril formation, while the C-terminal Proline Rich Domain destabilizes fibrils and enhances oligomer formation. However, in neurons both domains act synergistically to engage protective chaperone and degradation pathways promoting mHtt proteostasis. Surprisingly, when proteotoxicity was assessed in rat corticostriatal brain slices, either flanking region alone sufficed to generate a neurotoxic conformation, while the polyQ tract alone exhibited minimal toxicity. Linking mHtt structural properties to its neuronal proteostasis should inform new strategies for neuroprotection in polyQ-expansion diseases. DOI: http://dx.doi. org/10.7554/eLife.18065. 001
Confinement effects and tunnelling through quantum dots

Several recent theoretical advances concerning semiconductor quantum dots are reviewed. First of all, the effect of the quantum confinement on the energy gap is revisited on the basis of GW and Bethe–Salpeter calculations, showing that the excitonic gap is practically equal to the ordinary eigenvalue gap of single–particle approximations. The second part demonstrates that it is now possible to calculate the conductance peaks for the tunnelling current through a nanostructure. Finally, we discuss in some detail the concept of a macroscopic dielectric constant for nanostructures, showing that, except for a thin surface layer, the local dielectric constant still keeps its bulk value down to pretty small nanostructures.
Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

Complicated intra-abdominal infections (cIAI) represent a large proportion of all hospital admissions and are a major cause of morbidity and mortality in the intensive care unit. Rising rates of multidrug resistant organisms (MDRO), including extended-spectrum β-lactamase producing Enterobacteriaceae and carbapenem-nonsusceptible Pseudomonas spp. , for which there are few remaining active antimicrobial agents, pose an increased challenge to clinicians. Patients with frequent exposures to the health care system or multiple recurrent IAIs are at increased risk for MDRO; however, treatment options have traditionally been limited, in some cases necessitating the utilization of last-line agents with unfavorable side-effect profiles. Ceftolozane/tazobactam and ceftazidime/avibactam are two new cephalosporin and β-lactamase inhibitor combinations with recent US Food and Drug Administration approvals for the treatment of cIAI in combination with metronidazole. Ceftolozane/tazobactam has demonstrated excellent in vitro activity against MDR and extensively drug-resistant Pseudomonas spp. , including carbapenem-nonsusceptible strains, while ceftazidime/avibactam effectively inhibits a broad range of β-lactamases, making it an excellent option for the treatment of carbapenem-resistant Enterobacteriaceae. Both agents were shown to be noninferior to meropenem for treatment of cIAI in Phase III trials; however, reduced responses in patients with renal impairment at baseline highlight the importance of routine serum creatinine monitoring and ongoing dose adjustments. This review highlights in vitro and in vivo data of these two agents and suggests their proper place in cIAI treatment to ensure adequate therapy in our most at-risk patients while sparing unnecessary use in patients without MDRO risk factors.
Bicriteria product design optimization: An efficient solution procedure using AND/OR trees

Competitive imperatives are causing manufacturing firms to consider multiple criteria when designing products. However, current methods to deal with multiple criteria in product design are ad hoc in nature. In this paper we present a systematic procedure to efficiently solve bicriteria product design optimization problems. We first present a modeling framework, the AND/OR tree, which permits a simplified representation of product design optimization problems. We then show how product design optimization problems on AND/OR trees can be framed as network design problems on a special graph—a directed series‐parallel graph. We develop an enumerative solution algorithm for the bicriteria problem that requires as a subroutine the solution of the parametric shortest path problem. Although this parametric problem is hard on general graphs, we show that it is polynomially solvable on the series‐parallel graph. As a result we develop an efficient solution algorithm for the product design optimization problem that does not require the use of complex and expensive linear/integer programming solvers. As a byproduct of the solution algorithm, sensitivity analysis for product design optimization is also efficiently performed under this framework. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 574–592, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/nav.10031
Modelling transcriptional regulation using Gaussian Processes

Modelling the dynamics of transcriptional processes in the cell requires the knowledge of a number of key biological quantities. While some of them are relatively easy to measure, such as mRNA decay rates and mRNA abundance levels, it is still very hard to measure the active concentration levels of the transcription factor proteins that drive the process and the sensitivity of target genes to these concentrations. In this paper we show how these quantities for a given transcription factor can be inferred from gene expression levels of a set of known target genes. We treat the protein concentration as a latent function with a Gaussian process prior, and include the sensitivities, mRNA decay rates and baseline expression levels as hyperparameters. We apply this procedure to a human leukemia dataset, focusing on the tumour repressor p53 and obtaining results in good accordance with recent biological studies.
The Schistosome Oligosaccharide Lacto-N-neotetraose Expands Gr1+ Cells That Secrete Anti-inflammatory Cytokines and Inhibit Proliferation of Naive CD4+ Cells: A Potential Mechanism for Immune Polarization in Helminth Infections

Immunomodulatory oligosaccharides found on helminths also are found in human milk, and both helminths and milk have been shown to be immunosuppressive. We have been examining the immunomodulatory capabilities of two oligosaccharides expressed in milk and on helminth parasites, lacto-N-fucopentaose III and lacto-N-neotetraose (LNnT). In an attempt to dissect mechanisms that lead to Th2 polarization and immune suppression, we examined the early response in mice to the glycoconjugate LNnT-Dextran (LNnT-Dex). We found that injection of LNnT-Dex expanded a cell population, phenotypically defined as Gr1+/CD11b+/F4/80+, as early as 2 h after injection. Examination of spontaneous cytokine production showed that this Gr1+/F4/80+ population of cells spontaneously produced low levels of proinflammatory cytokines, but higher levels of IL-10 and TGF-β ex vivo, compared to peritoneal cells from mice injected with Dex. Gr1+ cells adoptively suppressed naive CD4+ T cell proliferation in vitro in response to anti-CD3/CD28 Ab stimulation. Suppression of naive CD4+ cells involved cell contact and was dependent on IFN-γ and NO, with a discrete role played by IL-10. Coculture of naive CD4+T cells with Gr1+ suppressor cells did not lead to CD4+ T cell apoptosis, although it did imprint on naive CD4+ T cells a response characterized by lower levels of IFN-γ, coincident with increased IL-13 production. Our results suggest that both human milk and helminth parasites may share a ligand-specific mechanism involved in the generation of anti-inflammatory mediators that suppress Th1-type and inflammatory responses.
ACUTE CHEMICAL TOXICITY OF URANIUM WITH APPLICATION TO 10 CFR 70.61

Requirements for licensure of special nuclear material applicable to uranium are specified in Title 10 Code of Federal Regulations Part 70 (10 CFR 70) and include three levels of specific risk criteria defined by biological effects and whether the exposed individual is a worker or a member of the public; these are in order of decreasing severity life endangerment, irreversible or serious long lasting effects, and mild transient health effects. The Executive Summary should indicate why this paper was written. It should explain how the three levels of risk criteria mentioned above are used in ensuring safety and what affects new criteria would have on the design and operation of a plant. This report provides a brief overview and necessary background of the properties, distribution, biokinetics and chemical toxicity of uranium and recommends threshold levels or standards for accidental acute inhalation and ingestion of levels for application to acute accidental exposure to uranium to comply with 10 CFR 70. The proposed threshold levels were primarily based on human exposure experience as reported in the peer reviewed scientific and medical literature and correlated with kidney concentrations calculated with a generally accepted biokinetic model . For life endangerment, the proposed thresholds are 2500 mg and 500 mg, respectively, for acute oral and inhalation intakes, although the former could be increased by a factor of 3 based on peak kidney concentration. Acute intake thresholds for irreversible or serious long lasting health effects are 1400 mg and 100 mg, respectively, for ingestion and inhalation and 410 and 30 mg, respectively for ingestion and inhalation for minor transient health effects. Based on peak kidney concentration, 3 μ g U per gram of kidney is considered to be the threshold for measurable kidney effects and 50 μ g U per gram of kidney is conservatively selected as having life endangerment possibilities. This last section of the report is quite confusing. For example, it is not clear why there are two numbers for intakes by inhalation
Patient experiences of adjusting to life in the first 2 years after bariatric surgery: a qualitative study

There is currently little research into the experiences of those who have undergone bariatric surgery, or how surgery affects their lives and social interactions. Adopting a constructivist grounded theory methodological approach with a constant comparative analytical framework, semi‐structured interviews were carried out with 18 participants (11 female, 7 male) who had undergone permanent bariatric surgical procedures 5‐24 months prior to interview. Findings revealed that participants regarded social encounters after bariatric surgery as underpinned by risk. Their attitudes towards social situations guided their social interaction with others. Three profiles of attitudes towards risk were constructed: Risk Accepters, Risk Contenders and Risk Challengers. Profiles were based on participant‐reported narratives of their experiences in the first two years after surgery. The social complexities which occurred as a consequence of bariatric surgery required adjustments to patients' lives. Participants reported that social aspects of bariatric surgery did not appear to be widely understood by those who have not undergone bariatric surgery. The three risk attitude profiles that emerged from our data offer an understanding of how patients adjust to life after surgery and can be used reflexively by healthcare professionals to support both patients pre‐ and post‐operatively.
The MACHO Project Large Magellanic Cloud Variable Star Inventory. XI. Frequency Analysis of the Fundamental-Mode RR Lyrae Stars

We have frequency-analyzed 6391 variables classified earlier as fundamental-mode RR Lyrae (RR0) stars in the MACHO database on the Large Magellanic Cloud (LMC). The overwhelming majority (i.e., 96%) of these variables have been proved to be indeed RR0 stars, whereas the remaining ones have fallen into one of the following categories: single- and double-mode Cepheids, binaries, first-overtone and double-mode RR Lyrae stars, and nonclassified variables. Special attention has been paid to the properties of the amplitude- and phase-modulated RR0 stars (the Blazhko stars). We found altogether 731 Blazhko variables showing either a doublet or an equidistant triplet pattern at the main pulsation component in their frequency spectra. This sample overwhelmingly exceeds the number of Blazhko stars known in all other systems combined. The incidence rate of the Blazhko variables among the RR0 stars in the LMC is 11.9%, which is 3 times higher than their rate among the first-overtone RR Lyrae stars. No difference is found in the average brightness between the single-mode and Blazhko variables. However, the latter ones show a somewhat lower degree of skewness in their average light curves and a concomitant lower total amplitude in their modulation-free light curves. From the frequency spectra we found that variables with larger modulation amplitudes at the higher frequency side of the main pulsation component are 3 times more common than the ones showing the opposite amplitude pattern. A search for a modulation component with the Blazhko period in the average brightness of the individual variables showed the existence of such a modulation with an overall amplitude of ≈0.006 mag. On the other hand, a similar search for quadruple modulation patterns around the main pulsation component has failed to clearly detect such components at the ≈0.004 mag level. This means that the amplitudes of the quadruple components (if they exist) should be, on average, at least 10 times smaller than those of the triplet components. This finding and the existence of Blazhko variables with highly asymmetric modulation amplitudes not only question the validity of the magnetic oblique rotator model but also put stringent constraints on models based on mode-coupling theories.
Social and ecological benefits of restored wolf populations

Our relationship with, treatment ofand scientific understanding about the wolf (formally, the gray wolf, Canis lupus) have always been a reflection of humankind's beliefs about our own place in the universe. From at least the 18th century until the first part ofthe 20 century, western civilization, in particular the United States, based its perspective of the earth and of its natural resources, forests, wildlife, rivers and oceans on viewpoints developed in that period of human history known as the Enlightenment. Humans were at the center of a mechanical, rational universe. Using rational powers ofthe mind, newly developed science and modern technologies, western civilization set out to conquer the rest of the world, to spread its enlightenment and to convert the natural resources ofthe world into wealth and power that would continue to fuel its progress. This was viewed as a social good that would benefit humankind. The wolf was an unfortunate beneficiary of this enlightenment. When Europeans arrived in North America in the 1500s, perhaps 2 million wolves
Design and implementation of the AEGIS single-chip secure processor using physical random functions

Secure processors enable new applications by ensuring private and authentic program execution even in the face of physical attack. In this paper, we present the AEGIS secure processor architecture, and evaluate its RTL implementation on FPGAs. By using physical random functions, we propose a new way of reliably protecting and sharing secrets that is more secure than existing solutions based on non-volatile memory. Our architecture gives applications the flexibility of trusting and protecting only a portion of a given process, unlike prior proposals which require a process to be protected in entirety. We also put forward a specific model of how secure applications can be programmed in a high-level language and compiled to run on our system. Finally, we evaluate a fully functional FPGA implementation of our processor, assess the implementation tradeoffs, compare performance, and demonstrate the benefits of partially protecting a program.
Selective influences of oxytocin on the evaluative processing of social stimuli

The neuropeptide oxytocin has been implicated in a wide range of social processes, such as pair bonding, affiliation, and social judgments that may contribute to normal adjustment and psychiatric states. The present experimental study sought to elucidate potential underlying mechanisms by which oxytocin may impact social processes by examining the effects of intranasal oxytocin on basic evaluative processes. Subjects rated slide stimuli from the International Affective Picture System, varying across multiple categories (pleasant, neutral, unpleasant) and social content. Separate ratings for arousal and for the positive and negative components of valence were obtained in the context of a bivariate evaluative space model. Oxytocin did not have an independent significant effect on positivity or negativity ratings, but instead oxytocin treatment altered the interaction between these component processes for social, relative to non-social stimuli regardless of valence conditions. Specifically, oxytocin, relative to vehicle, significantly decreased arousal ratings to threatening human stimuli without altering ratings of threatening animal stimuli. These results indicate that oxytocin may exert its effects through dynamic alterations in the partially separable neural substrates mediating arousal as well as positive and negative evaluations of social stimuli.