julilili42/papers huggingface dataset:
Pressure flaking to serrate bifacial points for the hunt during the MIS5 at Sibudu Cave (South Africa)
2017-04-26

Projectile technology is considered to appear early in the southern African Middle Stone Age (MSA) and the rich and high resolution MSA sequence of Sibudu Cave in KwaZulu-Natal has provided many new insights about the use and hafting of various projectile forms. We present the results of a functional and technological analysis on a series of unpublished serrated bifacial points recently recovered from the basal deposits of Sibudu Cave. These serrated tools, which only find equivalents in the neighbouring site of Umhlatuzana, precede the Still Bay techno-complex and are older than 77 ka BP. Independent residue and use-wear analyses were performed in a phased procedure involving two separate analysts, which allowed the engagement between two separate lines of functional evidence. Thanks to the excellent preservation at Sibudu Cave, a wide range of animal, plant and mineral residues were observed in direct relation with diagnostic wear patterns. The combination of technological, wear and residue evidence allowed us to confirm that the serration was manufactured with bone compressors and that the serrated points were mounted with a composite adhesive as the tips of projectiles used in hunting activities. The suite of technological and functional data pushes back the evidence for the use of pressure flaking during the MSA and highlights the diversity of the technical innovations adopted by southern African MSA populations. We suggest the serrated points from the stratigraphic units Adam to Darya of Sibudu illustrate one important technological adaptation of the southern African MSA and provide another example of the variability of MSA bifacial technologies.
Transcriptional response of Escherichia coli to ammonia and glucose fluctuations
2017-04-26

Summary In large‐scale production processes, metabolic control is typically achieved by limited supply of essential nutrients such as glucose or ammonia. With increasing bioreactor dimensions, microbial producers such as Escherichia coli are exposed to changing substrate availabilities due to limited mixing. In turn, cells sense and respond to these dynamic conditions leading to frequent activation of their regulatory programmes. Previously, we characterized short‐ and long‐term strategies of cells to adapt to glucose fluctuations. Here, we focused on fluctuating ammonia supply while studying a continuously running two‐compartment bioreactor system comprising a stirred tank reactor ( STR ) and a plug‐flow reactor ( PFR ). The alarmone ppGpp rapidly accumulated in PFR , initiating considerable transcriptional responses after 70 s. About 400 genes were repeatedly switched on/off when E. coli returned to the STR . E. coli revealed highly diverging long‐term transcriptional responses in ammonia compared to glucose fluctuations. In contrast, the induction of stringent regulation was a common feature of both short‐term responses. Cellular ATP demands for coping with fluctuating ammonia supply were found to increase maintenance by 15%. The identification of genes contributing to the increased ATP demand together with the elucidation of regulatory mechanisms may help to create robust cells and processes for large‐scale application.
Night sleep in patients with vegetative state
2017-04-26

Summary Polysomnographic recording of night sleep was carried out in 15 patients with the diagnosis vegetative state (syn. unresponsive wakefulness syndrome). Sleep scoring was performed by three raters, and confirmed by means of a spectral power analysis of the electroencephalogram, electrooculogram and electromyogram. All patients but one exhibited at least some signs of sleep. In particular, sleep stage N1 was found in 13 patients, N2 in 14 patients, N3 in nine patients, and rapid eye movement sleep in 10 patients. Three patients exhibited all phenomena characteristic for normal sleep, including spindles and rapid eye movements. However, in all but one patient, sleep patterns were severely disturbed as compared with normative data. All patients had frequent and long periods of wakefulness during the night. In some apparent rapid eye movement sleep episodes, no eye movements were recorded. Sleep spindles were detected in five patients only, and their density was very low. We conclude that the majority of vegetative state patients retain some important circadian changes. Further studies are necessary to disentangle multiple factors potentially affecting sleep pattern of vegetative state patients.
Identification of Genes Controlled by the Essential YycFG Two-Component System Reveals a Role for Biofilm Modulation in Staphylococcus epidermidis
2017-04-26

Biofilms play a crucial role in the pathogenicity of <i>Staphylococcus epidermidis</i>, while little is known about whether the essential YycFG two-component signal transduction system (TCS) is involved in biofilm formation. We used antisense RNA (asRNA) to silence the <i>yycFG</i> TCS in order to study its regulatory functions in <i>S. epidermidis</i>. Strain 1457 expressing asRNA <sub><i>yycF</i></sub> exhibited a significant delay (~4-5 h) in entry to log phase, which was partially complemented by overexpressing <i>ssaA</i>. The expression of asRNA <sub><i>yycF</i></sub> and asRNA <sub><i>yycG</i></sub> resulted in a 68 and 50% decrease in biofilm formation at 6 h, respectively, while they had no significant inhibitory effect on 12 h biofilm formation. The expression of asRNA <sub><i>yycF</i></sub> led to a ~5-fold increase in polysaccharide intercellular adhesion (PIA) production, but it did not affect the expression of accumulation-associated protein (Aap) or the release of extracellular DNA. Consistently, quantitative real-time PCR showed that silencing <i>yycF</i> resulted in an increased transcription of biofilm-related genes, including <i>icaA, arlR, sarA, sarX</i>, and <i>sbp</i>. An <i>in silico</i> search of the YycF regulon for the conserved YycF recognition pattern and a modified motif in <i>S. epidermidis</i>, along with additional gel shift and DNase I footprinting assays, showed that <i>arlR, sarA, sarX</i>, and <i>icaA</i> are directly regulated by YycF. Our data suggests that YycFG modulates <i>S. epidermidis</i> biofilm formation in an ica-dependent manner.
Clinical Significance of Intraluminal Contrast Enhancement in Patients with Spontaneous Cervical Artery Dissection: A Black-Blood MRI Study
2017-04-26

Purpose Recent studies have suggested that intraluminal thrombi show contrast enhancement on carotid black-blood T1w MRI. The aim of this study was to evaluate the significance of intraluminal contrast enhancement (iCE) regarding symptom status in patients with spontaneous cervical artery dissection (sCAD). Methods 33 consecutive patients (19 men) with sCAD received a brain MRI (DIFF, T2w, T2*w, FLAIR) and a multi-sequence 3T-MRI with fat-saturated high-resolution black-blood T1w-sequences pre- and post-contrast, contrast-enhanced MR angiography and TOF images of carotid and vertebral arteries. Presence/absence of iCE, vessel occlusion and vessel wall hematoma (hyperintense in T1w pre-contrast) were analysed by two radiologists in consensus decision. Results 44 of 132 analysed vessels had a vessel wall hematoma, consistent with sCAD. In 17 of 44 dissected vessels an acute ischemic stroke was found. 16 of 17 (94.1 %) vessels ipsilateral to ischemic stroke demonstrated iCE, compared to 9 of 44 (20.4 %) dissected vessels without stroke (P&lt; 0.001). The presence/absence of iCE resulted in a sensitivity, specificity, positive and negative predictive value and accuracy for ischemic stroke of 0.94, 0.67, 0.64, 0.95, and 0.77, respectively, and an odds ratio of 32.0. Conclusion iCE, which is suggestive of intraluminal thrombus formation, is strongly correlated with ischemic symptoms in patients with sCAD. Key points Citation Format
The Role of the MAPK Signaling, Topoisomerase and Dietary Bioactives in Controlling Cancer Incidence
2017-04-26

Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and are generated in response to several environmental stress conditions. Some of them play important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are known to be involved in a wide range of human diseases, including cancer. The excessive production of such ROS together with disruption of homeostasis detoxifying mechanisms can mediate a series of cellular oxidative stresses. The oxidative stress of redundant free radicals production can lead to oxidative denaturation of cellular macromolecules including proteins, lipids and DNA. Moreover, oxidative damage is one of the major causes of DNA mutations, replication errors and genomic abnormalities which result in either inhibition or induction of transcription, and end with the disturbance of signal transduction pathways. Among affected signaling pathways are redox-sensitive kinases. The stimulation of these kinases induces several transcription factors through the phosphorylation of their module proteins. The activation of such pathways induces proliferation and cellular transformation. A diet rich in antioxidant compounds has potential health benefits, and there is a growing interest in the role of natural antioxidants in nutrition for prevention and cure of cancer diseases. A controversy has risen regarding the relation between antioxidants and the significant decrease in the risk of cancer incidence. In this review, we will focus on redox-sensitive kinases signaling pathways, highlighting the effects of dietary antioxidant on the prevention, incidence, prognosis or even treatment of human cancers. In addition, we will place emphasis on the chemical classes of pterocarpans as natural anti-oxidants/cancers as well as their underlying mechanisms of action, including their effects on MAPKs and topoisomerase activities.
NFAT5‐sensitive Orai1 expression and store‐operated Ca 2+ entry in megakaryocytes
2017-04-26

ABSTRACT The transcription factor nuclear factor of activated T cells 5 (NFAT5) is up‐regulated in several clinical disorders, including dehydration. NFAT5‐sensitive genes include serum and glucocorticoid‐inducible kinase 1 (SGK1). The kinase is a powerful regulator of Orai1, a Ca 2+ channel accomplishing store‐operated Ca 2+ entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca 2+ sensors stromal interaction molecule 1 (STIM1), or STIM2, or both. In the present study, we explored whether nuclear factor of activated T cell (NFAT)‐5 influences Ca 2+ signaling in megakaryocytes. To this end, human megakaryocytic (MEG‐01) cells were transfected with NFAT5 or with siNFAT5. Platelets and megakaryocytes were isolated from wild‐type mice with either access to water ad libitum or dehydration by 36 h of water deprivation. Transcript levels were determined with quantitative RT‐PCR and protein abundance by Western blot analysis and flow cytometry, cytosolic (intracellular) Ca 2+ concentration ([Ca 2+ ] i ) by fura‐2‐fluorescence. SOCE was estimated from the increase of [Ca 2+ ] i following readdition of extracellular Ca 2+ after store depletion with thapsigargin (1 mM). Platelet degranulation was estimated from P‐selectin abundance and integrin activation from α IIb b 3 integrin abundance determined by flow cytometry. As a result, NFAT5 transfection or exposure to hypertonicity (+40 mM NaCl) of MEG‐01 cells increased Orai1, Orai2, STIM1, and STIM2 transcript levels. Orai1 transcript levels were decreased by NFAT5 silencing. NFAT5 transfection and IkB inhibitor BMS 345541 (5 mM) increased SOCE, whereas NFAT5 silencing and SGK1 inhibitor GSK650394 (10 mM) decreased SOCE. In the mice, dehydration increased NFAT5 and Orai1 protein abundance in megakaryocytes and NFAT5, Orai1, and Orai2 abundance in platelets. Dehydration further augmented the degranulation and integrin activation by thrombin and collagen‐related peptide. In summary, NFAT5 is a powerful regulator of Orai1‐expression and SOCE in megakaryocytes.—Sahu, I., Pelzl, L., Sukkar, B., Fakhri, H., al‐Maghout, T., Cao, H., Hauser, S., Gutti, R., Gawaz, M., Lang, F. NFAT5‐sensitive Orai1 expression and store‐operated Ca 2+ entry in megakaryocytes. FASEB J . 31, 3439–3448 (2017). www.fasebj.org
Neolithic nomadism in south‐east Arabia — strontium and oxygen isotope ratios in human tooth enamel from al‐Buhais 18 and Umm al‐Quwain 2 in the Emirates of Sharjah and Umm al‐Quwain (UAE)
2017-04-26

Human skeletal remains from the Neolithic sites BHS 18 in the interior of the Sharjah Emirate and the Neolithic shell midden UAQ 2 (Umm al‐Quwain) on the coast of the Persian Gulf (United Arab Emirates, UAE ) were analysed for their isotope ratios of strontium ( 87 Sr/ 86 Sr) and oxygen ( 18 O/ 16 O). The results are not in agreement with earlier assumptions about a Neolithic nomadism between inland regions and the south‐eastern coast of the Persian Gulf. Existing evidence of nomadic movements of the people from BHS 18 most possibly refers to transhumance within the mountains in the hinterland. The strontium isotope measurements on human skeletons from UAQ 2 on the contrary indicate uninterrupted residence of this population on the coast. Nevertheless, evidence was found of individual mobility between inland regions and the coast.
Post-Learning Sleep Transiently Boosts Context Specific Operant Extinction Memory
2017-04-26

Operant extinction is learning to supress a previously rewarded behavior. It is known to be strongly associated with the specific context in which it was acquired, which limits the therapeutic use of operant extinction in behavioral treatments, e.g., of addiction. We examined whether sleep influences contextual memory of operant extinction over time, using two different recall tests (Recent and Remote). Rats were trained in an operant conditioning task (lever press) in context A, then underwent extinction training in context B, followed by a 3-h retention period that contained either spontaneous morning sleep, morning sleep deprivation, or spontaneous evening wakefulness. A recall test was performed either immediately after the 3-h experimental retention period (Recent recall) or after 48 h (Remote), in the extinction context B and in a novel context C. The two main findings were: (i) at the Recent recall test, sleep in comparison with sleep deprivation and spontaneous wakefulness enhanced extinction memory but, only in the extinction context B; (ii) at the Remote recall, extinction performance after sleep was enhanced in both contexts B and C to an extent comparable to levels at Recent recall in context B. Interestingly, extinction performance at Remote recall was also improved in the sleep deprivation groups in both contexts, with no difference to performance in the sleep group. Our results suggest that 3 h of post-learning sleep transiently facilitate the context specificity of operant extinction at a Recent recall. However, the improvement and contextual generalization of operant extinction memory observed in the long-term, i.e., after 48 h, does not require immediate post-learning sleep.
Explorative Saccade Training in Children with Homonymous Hemianopia
2017-04-26

Background/Purpose: In adult patients with homonymous hemianopia, computer-based saccade training can lead to significant improvements of visual search.1 Here, we developed and tested a child-adapted training program.
Bohmian Mechanics
2017-04-26

Bohmian mechanics, also known as pilot-wave theory or de Broglie-Bohm theory, is a formulation of mechanics whose fundamental axioms are not about what observers will see if they perform an experiment but about what happens in reality. It is therefore called a quantum theory without observers, alongside with collapse theories and many-worlds theories and in contrast to orthodox mechanics. It follows from these axioms that in a universe governed by Bohmian mechanics, observers will see outcomes with exactly the probabilities specified by the usual rules of mechanics for empirical predictions. Specifically, Bohmian mechanics asserts that electrons and other elementary particles have a definite position at every time and move according to an equation of motion that is one of the fundamental laws of the theory and involves a wave function that evolves according to the usual Schr\\odinger equation. Bohmian mechanics is named after David Bohm (1917-1992), who was, although not the first to consider this theory, the first to realize (in 1952) that it actually makes correct predictions.
Recommendations for Diagnostic Genetic Testing in Epilepsies
2017-04-26

Background/Purpose: Childhood epilepsies are frequently caused by genetic alterations. During the last years, research initiatives identified multiple genes and genetic anomalies that are responsible for various epilepsy syndromes. Especially in the group of severe, early-onset epilepsies and epileptic encephalopathies, the number of possibly causal genes is increasing continuously. At the same time, new diagnostic methods become widely available, but need to be reviewed critically with respect to possibilities and pitfalls.
Remarkable Genetic Finding in a Girl with Phenotype of Classic Pelizäus-Merzbacher Disease: Xq22.2 Microdeletion Including PLP1 and Other Genes
2017-04-26

Background: PLP1-related disorders are X-linked and include a range of clinical and neuro-radiological phenotypes from severe connatal and classic Pelizäus-Merzbacher disease (PMD), PLP1 null-syndrome to spastic paraplegia (SPG2). Most individuals with classic PMD have PLP1 duplications. Deletions of PLP1 are scarce. Female carriers may show mild neurological signs. Severely affected females with Xq22.2 microdeletions including PLP1 and skewed X-inactivation are reported; GLRA4, which in some cases also was deleted, is a novel candidate gene for X-linked intellectual disability.
Congenital Myasthenic Syndrome Caused by Isolated PREPL Deficiency
2017-04-26

Background: Mutations in PREPL are a rare cause of congenital myasthenic syndrome. PREPL encodes the prolyl endopeptidase-like enzyme, which plays an important role for vesicular transport of the acetylcholine receptor. So far, only a single case of isolated PREPL deficiency has been reported in the literature. The child presented as a floppy baby and showed developmental delay.
Evaluation of the Accelerate Pheno System for Fast Identification and Antimicrobial Susceptibility Testing from Positive Blood Cultures in Bloodstream Infections Caused by Gram-Negative Pathogens
2017-04-27

ABSTRACT Bloodstream infections (BSI) are an important cause of morbidity and mortality. Increasing rates of antimicrobial-resistant pathogens limit treatment options, prompting an empirical use of broad-range antibiotics. Fast and reliable diagnostic tools are needed to provide adequate therapy in a timely manner and to enable a de-escalation of treatment. The Accelerate Pheno system (Accelerate Diagnostics, USA) is a fully automated test system that performs both identification and antimicrobial susceptibility testing (AST) directly from positive blood cultures within approximately 7 h. In total, 115 episodes of BSI with Gram-negative bacteria were included in our study and compared to conventional culture-based methods. The Accelerate Pheno system correctly identified 88.7% (102 of 115) of all BSI episodes and 97.1% (102 of 105) of isolates that are covered by the system's identification panel. The Accelerate Pheno system generated an AST result for 91.3% (95 of 104) samples in which the Accelerate Pheno system identified a Gram-negative pathogen. The overall category agreement between the Accelerate Pheno system and culture-based AST was 96.4%, the rates for minor discrepancies 1.4%, major discrepancies 2.3%, and very major discrepancies 1.0%. Of note, ceftriaxone, piperacillin-tazobactam, and carbapenem resistance was correctly detected in blood culture specimens with extended-spectrum beta-lactamase-producing Escherichia coli ( n = 7) and multidrug-resistant Pseudomonas aeruginosa ( n = 3) strains. The utilization of the Accelerate Pheno system reduced the time to result for identification by 27.49 h ( P &lt; 0.0001) and for AST by 40.39 h ( P &lt; 0.0001) compared to culture-based methods in our laboratory setting. In conclusion, the Accelerate Pheno system provided fast, reliable results while significantly improving turnaround time in blood culture diagnostics of Gram-negative BSI.
Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study
2017-04-27

Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients.
Optimizing Contrast Media Injection Protocols in Computed Tomography Angiography at Different Tube Voltages: Evaluation in a Circulation Phantom
2017-04-27

Objectives The aim of this study was to investigate the minimum iodine delivery rate (IDR) and contrast media (CM) volume required for diagnostic contrast enhancement of 350 HU (Hounsfield units) in the ascending aorta at different kV settings. Methods Dynamic computed tomography acquisitions from 70 to 150 kV were performed in a circulation phantom. First, injections with IDR ranging from 0.1 to 2.0 g I/s were tested for each kV. In the second part, the IDR was held constant, whereas the CM volume was reduced from 50 to 10 mL. Diagnostic aortic peak enhancement for each kV was compared using the Kruskal-Wallis test. P &lt; 0.05 was considered statistically significant. Results The mean aortic peak enhancement for all diagnostic IDRs was 368.7 ± 11.1 HU. Diagnostic IDRs returned similar aortic peak enhancement values for all protocols (all P ≥ 0.18). For the second part of the study, a diagnostic enhancement was yielded by using a minimum of 30 mL of CM for 110 kV, 25 mL for 100 and 90 kV, and 15 mL for 80 and 70 kV. Conclusion Our study suggests that a differentiated approach reducing the CM volume for tube voltages of less than 120 kV and increasing the IDR for higher kV settings seems to be the most effective approach.
Application and Implementation of Incorporating Local Boundary Conditions into Nonlocal Problems
2017-04-27

We study nonlocal equations from the area of peridynamics, an instance of nonlocal wave equation, and nonlocal diffusion on bounded domains whose governing equations contain a convolution operator based on integrals. We generalize the notion of convolution to accommodate local boundary conditions. On a bounded domain, the classical operator with local boundary conditions has a purely discrete spectrum, and hence, provides a Hilbert basis. We define an abstract convolution operator using this Hilbert basis, thereby automatically satisfying local boundary conditions. The main goal in this paper is twofold: apply the concept of abstract convolution operator to nonlocal problems and carry out a numerical study of the resulting operators. We study the corresponding initial value problems with prominent boundary conditions such as periodic, antiperiodic, Neumann, and Dirichlet. To connect to the standard convolution, we give an integral representation of the abstract convolution operator. For discretization, we use a weak formulation based on a Galerkin projection and use piecewise polynomials on each element which allows discontinuities of the approximate solution at the element borders. We study convergence order of solutions with respect to polynomial order and observe optimal convergence. We depict the solutions for each boundary condition.