julilili42/papers huggingface dataset:
P08.48 Combined alterations in MAPK pathway genes, CDKN2A/B and ATRX characterize anaplastic pilocytic astrocytoma
2016-09-21

approximately 15 months following standard of care therapy.However, 10 % survival at 5 years was observed in a randomized phase III study.At GBM recurrence, the addition of bevacizumab (BEV), a humanized monoclonal antibody against circulating vascular endothelial growth factor (VEGF), resulted in a 3-4 month prolongation of progression-free survival (PFS) without improving overall survival (OS).A 45-year-old female who underwent surgery for left fronto-temporal WHO grade II astrocytoma associated with epilepsy in 2005, 125I seed implantation at disease progression in 2009 and seed explantation 9 months later, was diagnosed with MGMT methylated GBM on the occasion of partial tumor resection in 2010 followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) chemotherapy, which was stopped after 4 months due to resection of a left temporal tumor cyst and recurrent cyst within 1 month.TMZ treatment causing prolonged thrombocytopenia was discontinued after 1 additional cycle.Immediately after this cycle, the patient experienced left median cerebral artery stroke resulting in right hemianopia, Broca's aphasia and severe hemiparesis of the right side.Three months later, BEV 10 mg/kg i.v.q14d was initiated, shortly interrupted for abdominal herniotomy in 2012, and continued for 3 years.Since 2014, concurrent low molecular weight heparin was given because of right lower limb deep venous thrombosis suspicion.Whereas GBM progression had not been detected for 2 years during anti-VEGF therapy, methionine PET MRI 6 months after BEV discontinuation revealed left temporal tumor recurrence.Rechallenge with BEV was initiated and the patient remained in stable clinical and radiographical condition for 10 months until now.This case highlights the utility of sequential BEV treatment in a patient being at high risk to develop chemotherapy-induced myelotoxicity.Long-term survival (> 3 years after diagnosis) in GBM has been attributed to patient-derived rather than tumor-derived factors.To our knowledge, this is the first description of effective long-term monotherapy with BEV for GBM and ongoing therapeutic response to single-agent BEV rechallenge in a patient with recurrent secondary GBM.
The Water Load Test As a Measure of Gastric Interoception: Development of a Two-Stage Protocol and Application to a Healthy Female Population
2016-09-22

The sensitivity for one's own internal body signals (i.e., interoception) has been demonstrated to play an important role in the pathogenesis of eating and weight disorders. Most previous measures assessing interoceptive processing have not, or only partly, captured perception of hunger and satiety cues, which is a core aspect of interoceptive deficits in eating disorders. In addition, methods used to measure sensitivity to gastric signals are heterogeneous and findings inconsistent. The primary aim of the present study was to establish a standardised test to measure gastric interoception, and to provide normative data using a non-clinical adult sample. The two-step Water Load Test (WLT-II) involves ingestion of non-caloric water until perceived satiation (step 1) and until maximum fullness (step 2). The WLT-II consists of several variables: Besides volumes of water ingested until satiation and maximum fullness expressed in ml, percentage of satiation to maximum fullness is calculated as an individual index of gastric interoception that is not confounded with stomach capacity. Ninety-nine healthy women participated in the study. Measures included the WLT-II, the heartbeat tracking test, a self-report questionnaire assessing subjective sensations, and the Eating Disorder Inventory-2. Twenty-eight participants underwent test-retest of the WLT-II. Results suggest that the WLT-II is a valid and reliable measure of gastric interoception. Importantly, satiation volume and percentage of satiation to maximum fullness were strongly positively related to self-reported bulimic symptoms, indicating that the WLT-II could emerge as a useful clinical tool to measure interoceptive processing in the field of eating disorders.
Stem cell‐derived organoids to model gastrointestinal facets of cystic fibrosis
2016-09-22

Cystic fibrosis (CF) is one of the most frequently occurring inherited human diseases caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) which lead to ample defects in anion transport and epithelial fluid secretion. Existing models lack both access to early stages of CF development and a coeval focus on the gastrointestinal CF phenotypes, which become increasingly important due increased life span of the affected individuals. Here, we provide a comprehensive overview of gastrointestinal facets of CF and the opportunity to model these in various systems in an attempt to understand and treat CF. A particular focus is given on forward‐leading organoid cultures, which may circumvent current limitations of existing models and thereby provide a platform for drug testing and understanding of disease pathophysiology in gastrointestinal organs.
Synthesis of copper(II) and gold(III) bis(NHC)-pincer complexes
2016-09-22

Abstract Cu II and Au III chlorido complexes bearing the bis(NHC) carbazolide pincer ligand (bimca) were synthesized by transmetallation from the respective lithium complex [Li(bimca)] (NHC=N-heterocyclic carbene). In the case of copper, two different molecular structures were obtained depending on the copper source. With Cu(II) chloride the paramagnetic mononuclear [Cu(bimca)Cl] complex is formed and has been characterized by EPR spectroscopy and X-ray structure analysis, while copper(I) chloride leads under oxidation to a dinuclear structure in which two cationic [Cu II (bimca)] moieties are bridged by one chlorido ligand. The positive charge is compensated by the [CuCl 2 ] − counter ion, as proven by X-ray structure analysis. Transmetallation of [Li(bimca)] with AuCl 3 leads to the [Au(bimca)Cl] + complex with a tetrachloridoaurate counter ion.
Knowledge Contribution in Organizations via Social Media
2016-09-22

Abstract. Knowledge exchange via social media is crucial for organizational success. Yet, many employees only read others’ contributions without actively contributing their knowledge. We thus examined predictors of the willingness to contribute knowledge. Applying social identity theory and expectancy theory to knowledge exchange, we investigated the interplay of users’ identification with their organization and perceived usefulness of a social media tool. In two studies, identification facilitated users’ willingness to contribute knowledge – provided that the social media tool seemed useful (vs. not-useful). Interestingly, identification also raised the importance of acquiring knowledge collectively, which could in turn compensate for low usefulness of the tool. Hence, considering both social and media factors is crucial to enhance employees’ willingness to share knowledge via social media.
Formal Total Synthesis of Amphidinolide Q
2016-09-22

With the preparation of macrolactone 33a we describe a formal total synthesis of amphidinolide Q. The corresponding seco acid 32 originated from an aldol reaction between methyl ketone 6 and methyl (E)-3-methyl-4-oxobut-2-enoate (5). The synthesis of ketone 6 (C5-C16 fragment) started with desymmetrized meso-diol 9. Chain extension reactions involving cyanide, lithium trimethylsilylacetylide, and a Wittig reaction led to aldehyde 22. The two additional stereocenters at C11 and C13 were set by a Noyori transfer hydrogenation on alkynone 14 and a Feringa-Minnaard methyl cuprate addition on enoate 21. The but-1-ene-2-yl subunit on the side chain terminus was created from an unsaturated aldehyde by a substitution reaction on a derived allylic tosylate.
Optimal Control for the Thin Film Equation: Convergence of a Multi-Parameter Approach to Track State Constraints Avoiding Degeneracies
2016-09-22

Abstract We consider an optimal control problem subject to the thin-film equation. The PDE constraint lacks well-posedness for general right-hand sides due to possible degeneracies; state constraints are used to circumvent this problematic issue and to ensure well-posedness. Necessary optimality conditions for the optimal control problem are then derived. A convergent multi-parameter regularization is considered which addresses both, the possibly degenerate term in the equation and the state constraint. Some computational studies are then reported which evidence the relevant role of the state constraint, and motivate proper scalings of involved regularization and numerical parameters.
A bead-based western for high-throughput cellular signal transduction analyses
2016-09-23

Abstract Dissecting cellular signalling requires the analysis of large number of proteins. The DigiWest approach we describe here transfers the western blot to a bead-based microarray platform. By combining gel-based protein separation with immobilization on microspheres, hundreds of replicas of the initial blot are created, thus enabling the comprehensive analysis of limited material, such as cells collected by laser capture microdissection, and extending traditional western blotting to reach proteomic scales. The combination of molecular weight resolution, sensitivity and signal linearity on an automated platform enables the rapid quantification of hundreds of specific proteins and protein modifications in complex samples. This high-throughput western blot approach allowed us to identify and characterize alterations in cellular signal transduction that occur during the development of resistance to the kinase inhibitor Lapatinib, revealing major changes in the activation state of Ephrin-mediated signalling and a central role for p53-controlled processes.
Genetic medicines for CF: Hype versus reality
2016-09-23

Summary Since identification of the CFTR gene over 25 years ago, gene therapy for cystic fibrosis (CF) has been actively developed. More recently gene therapy has been joined by other forms of “genetic medicines” including mRNA delivery, as well as genome editing and mRNA repair‐based strategies. Proof‐of‐concept that gene therapy can stabilize the progression of CF lung disease has recently been established in a Phase IIb trial. An early phase study to assess the safety and explore efficacy of CFTR mRNA repair is ongoing, while mRNA delivery and genome editing‐based strategies are currently at the pre‐clinical phase of development. This review has been written jointly by some of those involved in the various CF “genetic medicine” fields and will summarize the current state‐of‐the‐art, as well as discuss future developments. Where applicable, it highlights common problems faced by each of the strategies, and also tries to highlight where a specific strategy may have an advantage on the pathway to clinical translation. We hope that this review will contribute to the ongoing discussion about the hype versus reality of genetic medicine‐based treatment approaches in CF. Pediatr Pulmonol. 2016;51:S5–S17. © 2016 Wiley Periodicals, Inc.
Depth‐dependence of visual signals in the human superior colliculus at 9.4 T
2016-09-23

Abstract The superior colliculus (SC) is a layered structure located in the midbrain. We exploited the improved spatial resolution and BOLD signal strength available at 9.4 T to investigate the depth profile of visual BOLD responses in the human SC based on distortion‐corrected EPI data with a 1 mm isotropic resolution. We used high resolution (350 μm in‐plane) anatomical images to determine regions‐of‐interest of the SC and applied a semi‐automated method to segment it into superficial, intermediate, and deep zones. A greater than linear increase in sensitivity of the functional signal at 9.4 T allowed us to detect a statistically significant depth pattern in a group analysis with a 20 min stimulation paradigm. Descriptive data showed consistent depth profiles also in single individuals. The highest signals were localized to the superficial layers of the right and left SC during contralateral stimulation, which was in good agreement with its functional architecture known from non‐human primates. This study thus demonstrates the potential of 9.4 T MRI for functional neuroimaging even in deeply located, particularly challenging brain structures such as the SC. Hum Brain Mapp 38:574–587, 2017 . © 2016 Wiley Periodicals, Inc.
Stoichiometry determination of macromolecular membrane protein complexes
2016-09-23

Abstract Gaining knowledge of the structural makeup of protein complexes is critical to advance our understanding of their formation and functions. This task is particularly challenging for transmembrane protein complexes, and grows ever more imposing with increasing size of these large macromolecular structures. The last 10 years have seen a steep increase in solved high-resolution membrane protein structures due to both new and improved methods in the field, but still most structures of large transmembrane complexes remain elusive. An important first step towards the structure elucidation of these difficult complexes is the determination of their stoichiometry, which we discuss in this review. Knowing the stoichiometry of complex components not only answers unresolved structural questions and is relevant for understanding the molecular mechanisms of macromolecular machines but also supports further attempts to obtain high-resolution structures by providing constraints for structure calculations.
The Peptidoglycan Pattern of Staphylococcus carnosus TM300—Detailed Analysis and Variations Due to Genetic and Metabolic Influences
2016-09-23

The Gram-positive bacterium Staphylococcus carnosus (S. carnosus) TM300 is an apathogenic staphylococcal species commonly used in meat starter cultures. As with all Gram-positive bacteria, its cytoplasmic membrane is surrounded by a thick peptidoglycan (PGN) or murein sacculus consisting of several layers of glycan strands cross-linked by peptides. In contrast to pathogenic staphylococci, mainly Staphylococcus aureus (S. aureus), the chemical composition of S. carnosus PGN is not well studied so far. UPLC/MS analysis of enzymatically digested S. carnosus TM300 PGN revealed substantial differences in its composition compared to the known pattern of S. aureus. While in S. aureus the uncross-linked stem peptide consists of a pentapeptide, in S. carnosus, this part of the PGN is shortened to tripeptides. Furthermore, we found the PGN composition to vary when cells were incubated under certain conditions. The collective overproduction of HlyD, FtsE and FtsX—a putative protein complex interacting with penicillin-binding protein 2 (PBP2)—caused the reappearance of classical penta stem peptides. In addition, under high sugar conditions, tetra stem peptides occur due to overflow metabolism. This indicates that S. carnosus TM300 cells adapt to various conditions by modification of their PGN.
Advanced System-Level Design for Automated Driving
2016-09-23

Automated driving (A.D.) requires concurrent execution of multiple complex driving functions on automotive embedded platforms. In general, such systems can be partitioned into early stages including sensor processing, individual perception, and cognition functions and into later, more centralized stages that perform data fusion, planning, and decision making. In this chapter, we exemplarily concentrate on automotive embedded processing systems for perception and cognition problems, however, we expect similar problems also on later stages such as data fusion. For perception and cognition, one can observe a wide gap between required processing power and the achievable embedded realizations which have to fulfill non-functional requirements such as low power and small cost. Furthermore, these systems must perform all processing under strict safety requirements that guarantee deadlines and provide high system robustness.
Self-navigated 4D cartesian imaging of periodic motion in the body trunk using partial k-space compressed sensing
2016-09-25

The proposed method provides a clinical feasible setup to capture periodic respiratory motion with a fast acquisition protocol and can be extended by further surrogate signals to capture additional periodic motions. Retrospective parametrization allows for flexible tuning toward the targeted applications. Magn Reson Med 78:632-644, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Hidost: a static machine-learning-based detector of malicious files
2016-09-26

Malicious software, i.e., malware, has been a persistent threat in the information security landscape since the early days of personal computing. The recent targeted attacks extensively use non-executable malware as a stealthy attack vector. There exists a substantial body of previous work on the detection of non-executable malware, including static, dynamic, and combined methods. While static methods perform orders of magnitude faster, their applicability has been hitherto limited to specific file formats. This paper introduces Hidost, the first static machine-learning-based malware detection system designed to operate on multiple file formats. Extending a previously published, highly effective method, it combines the logical structure of files with their content for even better detection accuracy. Our system has been implemented and evaluated on two formats, PDF and SWF (Flash). Thanks to its modular design and general feature set, it is extensible to other formats whose logical structure is organized as a hierarchy. Evaluated in realistic experiments on timestamped datasets comprising 440,000 PDF and 40,000 SWF files collected during several months, Hidost outperformed all antivirus engines deployed by the website VirusTotal to detect the highest number of malicious PDF files and ranked among the best on SWF malware.
Sex and gender affect the social brain: Beyond simplicity
2016-09-26

As the most fascinating, complex, and dynamic part of our organism, the human brain is shaped by many interacting factors that not only are of neurobiological (including sex hormones) and environmental origin but are also sociocultural in their very nature (such as social roles). Gender is one of these factors. Most neurological, neurodevelopmental, neuropsychiatric, and psychosomatic disorders are characterized by impairments in visual social cognition (primarily body language reading and face perception) and a skewed sex ratio: females and males are affected differently in terms of clinical picture, prevalence, and severity. Is the social brain sex specific? This is still an open question. For a long time and for many reasons, sex differences have been overlooked or entirely ignored in neuroscience and biomedical research: there is a paucity of neuroimaging work examining sex differences in the social brain. However, the pattern of experimental behavioral data in both healthy, typically developing individuals and patients with deficient social cognition is beyond simple interpretation: contrary to popular wisdom, females are not always more proficient in understanding social signals, and their social abilities may be particularly affected by disease. Clarification of how neurobiological sex and sociocultural gender affect the social brain would provide novel insights into understanding gender‐specific vulnerability to neuropsychiatric disorders. This interaction is far beyond simplicity. Although sex differences represent a rather delicate topic, underestimation or exaggeration of possible effects retards progress in the field. © 2016 Wiley Periodicals, Inc.
Cerebellar tDCS Does Not Improve Learning in a Complex Whole Body Dynamic Balance Task in Young Healthy Subjects
2016-09-26

Transcranial direct current stimulation (tDCS) of the cerebellum is of increasing interest as a non-invasive technique to modulate motor performance and learning in health and disease. Previous studies have shown that cerebellar tDCS facilitates reach adaptation and associative motor learning in healthy subjects. In the present study it was tested whether cerebellar tDCS improves learning of a complex whole body motor skill. Because this task involves learning of posture and balance likely including learning of a new motor sequence and cognitive strategies, cerebellar tDCS was applied over midline cerebellar structures and the posterolateral cerebellar hemispheres. 30 young and healthy subjects performed two days of balance training on a Lafayette Instrument 16030 stability platform®. Participants received either anodal, cathodal or sham cerebellar tDCS during training on day 1. The cerebellar electrode (7 cm width by 5 cm height) was centered 2 cm below the inion. Mean platform angle deviation and mean balance time were assessed. All subjects showed significant effects of learning. Learning rate was not different between the three modes of stimulation neither on day 1 nor on day 2. Cerebellar tDCS did not facilitate learning of a complex whole body dynamic balance task in young and healthy subjects. tDCS effects, however, may have been missed because of the small group size. Furthermore, it cannot be excluded that young and healthy subjects learned and performed already at a near optimal level with little room for further improvement. Future work has to evaluate potential benefits of cerebellar tDCS in elderly subjects and subjects with cerebellar deficits, whose motor control and motor learning network is not optimally tuned.
The molecular and phenotypic spectrum of IQSEC2‐related epilepsy
2016-09-26

Summary Objective IQSEC 2 is an X‐linked gene associated with intellectual disability ( ID ) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC 2 pathogenic variants. Methods Forty‐eight patients with IQSEC 2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. Results Six affected individuals had an inherited IQSEC 2 variant and 12 had a de novo one (male‐to‐female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic–clonic ( GTC ) seizures. The electroclinical syndromes could be defined in five patients: late‐onset epileptic spasms (three) and Lennox‐Gastaut or Lennox‐Gastaut–like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging ( MRI ) were prominent features. Significance The phenotypic spectrum of IQSEC 2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC 2 should be evaluated in both male and female patients with an epileptic encephalopathy.