bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fundamental theoretical and practical investigations of the polymorph formation of small amphiphilic molecules, their co-crystals and salts
Authors: Martin Thomas , Niemietz Paul , Greim Dominik , Ectors Philipp , Senker Jürgen , Zahn Dirk , Breu Josef 
Published: September 2016

Abstract
The amphiphilic nature of benzoic acid, benzoates and benzamide causes an unexpected rich polymorphism. Featuring rather rigid and small molecular structures these compounds are ideal model systems for gaining a more fundamental understanding of molecular polymorphism by systematic and concerted investigations. The hydrophilic head allows for hydrogen bonding while the phenyl moiety gives rise to various π-stacking modes. Variations of hydrogen bonding versus π-stacking modes give rise to four polymorphs of benzamide. The central synthon in all phases is a dimer where hydrophilic units form double hydrogen bonds. As suggested by MD simulations of the nucleation process, variations of the crystallization conditions trigger whether the first self-assembly occurs via the hydrophilic head or the hydrophophic tail groups. Based on NMR crystallographic investigations for the co-crystallization of benzamide with benzoic acid, we observed yet another variation of the balance of the two dominating intermolecular interactions leading to the formation of a 1:1 co-crystal. The average crystal structure resembles the packing motive of pure benzoic acid with alternating ribbons of homogenous benzamide and benzoic acid dimers. For alkali-benzoate salts a coordination dilemma arises that is of general importance for many active pharmaceutical ingredients (APIs). A 1:1 stoichiometry requires condensation of coordination polyhedra of small inorganic cations which in turn causes steric stress that varies with the relative volumes of cation and anion. Interestingly, one way of resolving the dilemma is microphase separation which is directly related to the amphiphilic character of benzoate.
New lupan-type triterpenoids
Authors: Mkounga Pierre , Maza Hermine L.D. , Ouahouo Blandine M.W. , Tyon Lydie N. , Ishikawa Hayato , Nishino Hiroshi , Nkengfack Augustin E. 
Published: September 2016

Abstract
Three new lupan-type triterpernoid derivatives, namely globimetulin A (1), B (2) and C (3), were isolated from the shoot of Globimetula dinklagei (Loranthaceae), a hemiparasitic plant growing on Manihot esculenta, along with five known compounds: friedelin (4), friedelan-3-ol (5), 28-hydroxyfriedelin (6), 4-hydroxy-3,5-dimethoxybenzoic acid (7) and (1R,5S,7S)-7-[2-(4-hydroxyphenyl)ethyl]-2,6-dioxabicyclo[3.3.1]nonan-3-one (8). The structures of the new compounds were elucidated by detailed analyses of their MS, IR, 1D and 2D NMR spectral data and chemical evidence. Some of these compounds were evaluated in vitro for their antimicrobial activities against a wide range of microorganisms, but none of them exhibited noticeable activity.
Aging of Cast 35Cr-45Ni Heat Resistant Alloys With Different Carbon Content
Authors: Sustaita-Torres I. A. , Haro-Rodríguez S. , Colás R. 
Published: September 2016

Abstract
The changes in microstructure that took place in two heat-resistant after aging alloys at 750°C for a period of time of up to 1000 h are reported in this work. The alloys selected had a similar composition, with the exception in carbon content that was of 0.15 and 0.50 %. The material was obtained from centrifugal cast pipes and their microstructure was made of an austenitic dendrite matrix with interdendritic primary cabides; light optical and scanning electron microscopy analyses were conducted to identify these carbides as NbC and Cr7C3. Selected area analyses were conducted to quantify the primary carbides in the as-cast and aged conditions; these analyses revealed that their amount was unaffected by aging, but depended on the carbon content, with the predominance of NbC in the alloy with lower carbon content, due to the higher affinity of carbon to niobium. Aging affected the NbC particles, as they transformed into silicides, precipitation of secondary Cr23C6 particles took place, while Cr7C3 remained unaffected. The changes in microstructure that were observed by microscopy were confirmed by X-ray diffraction. The mechanical properties of the materials changed, as hardness and tensile strength increased, while the ductility in both alloys was reduced.
X-Ray and Neutron Diffraction Studies of Quenched and Partitioned (Q&P) Multiphase Steel Microstructures
Authors: Edmonds David , Bigg Timothy 
Published: September 2016

Abstract
Novel advanced steel developments in recent years have resulted in many steels with complex multiphase microstructures. Foremost currently are steels that contain significant fractions of untransformed parent austenite phase. “Quenched and partitioned” steels, commonly referred to as Q&P steels, important as potential advanced high-strength (AHS) automotive steels, are an example in which the austenite is chemically stabilized by carbon partitioning from martensite following an interrupted quench above the martensite finish temperature, Mf. It is evident that the progress of microstructural change during this novel quenching and partitioning treatment, the volume of untransformed austenite stabilized during partitioning and the behavior of this austenite according to its carbon content should be understood. In relation to these requirements, recent analysis of X-ray powder diffraction (XRD) and neutron diffraction experiments will be considered. Initially, the effect of sample preparation between the two measurement techniques is considered, followed by observation of the partitioning process in real time allowed by specially prepared Mn-containing experimental alloys, with and without a crucial silicon addition required to enable austenite retention during Q&P treatment.
Slow Cholinergic Modulation of Spike Probability in Ultra-Fast Time-Coding Sensory Neurons
Authors: Goyer David , Kurth Stefanie , Gillet Charlène , Keine Christian , Rübsamen Rudolf , Kuenzel Thomas 
Published: September 2016

AbstractSensory processing in the lower auditory pathway is generally considered to be rigid and thus less subject to modulation than central processing. However, in addition to the powerful bottom-up excitation by auditory nerve fibers, the ventral cochlear nucleus also receives efferent cholinergic innervation from both auditory and nonauditory top–down sources. We thus tested the influence of cholinergic modulation on highly precise time-coding neurons in the cochlear nucleus of the Mongolian gerbil. By combining electrophysiological recordings with pharmacological applicationin vitroandin vivo, we found 55–72% of spherical bushy cells (SBCs) to be depolarized by carbachol on two time scales, ranging from hundreds of milliseconds to minutes. These effects were mediated by nicotinic and muscarinic acetylcholine receptors, respectively. Pharmacological block of muscarinic receptors hyperpolarized the resting membrane potential, suggesting a novel mechanism of setting the resting membrane potential for SBC. The cholinergic depolarization led to an increase of spike probability in SBCs without compromising the temporal precision of the SBC outputin vitro.In vivo, iontophoretic application of carbachol resulted in an increase in spontaneous SBC activity. The inclusion of cholinergic modulation in an SBC model predicted an expansion of the dynamic range of sound responses and increased temporal acuity. Our results thus suggest of a top–down modulatory system mediated by acetylcholine which influences temporally precise information processing in the lower auditory pathway.
The Role of Striatal Feedforward Inhibition in the Maintenance of Absence Seizures
Authors: Arakaki Takafumi , Mahon Séverine , Charpier Stéphane , Leblois Arthur , Hansel David 
Published: September 2016

Absence seizures are characterized by brief interruptions of conscious experience accompanied by oscillations of activity synchronized across many brain areas. Although the dynamics of the thalamocortical circuits are traditionally thought to underlie absence seizures, converging experimental evidence supports the key involvement of the basal ganglia (BG). In this theoretical work, we argue that the BG are essential for the maintenance of absence seizures. To this end, we combine analytical calculations with numerical simulations to investigate a computational model of the BG-thalamo-cortical network. We demonstrate that abnormally strong striatal feedforward inhibition can promote synchronous oscillatory activity that persists in the network over several tens of seconds as observed during seizures. We show that these maintained oscillations result from an interplay between the negative feedback through the cortico-subthalamo-nigral pathway and the striatal feedforward inhibition. The negative feedback promotes epileptic oscillations whereas the striatal feedforward inhibition suppresses the positive feedback provided by the cortico-striato-nigral pathway. Our theory is consistent with experimental evidence regarding the influence of BG on seizures (e.g., with the fact that a pharmacological blockade of the subthalamo-nigral pathway suppresses seizures). It also accounts for the observed strong suppression of the striatal output during seizures. Our theory predicts that well-timed transient excitatory inputs to the cortex advance the termination of absence seizures. In contrast with the thalamocortical theory, it also predicts that reducing the synaptic transmission along the cortico-subthalamo-nigral pathway while keeping constant the average firing rate of substantia nigra pars reticulata reduces the incidence of seizures.SIGNIFICANCE STATEMENTAbsence seizures are characterized by brief interruptions of consciousness accompanied by abnormal brain oscillations persisting tens of seconds. Thalamocortical circuits are traditionally thought to underlie absence seizures. However, recent experiments have highlighted the key role of the basal ganglia (BG). This work argues for a novel theory according to which the BG drive the oscillatory patterns of activity occurring during the seizures. It demonstrates that abnormally strong striatal feedforward inhibition promotes synchronous oscillatory activity in the BG-thalamo-cortical network and relate this property to the observed strong suppression of the striatal output during seizures. The theory is compatible with virtually all known experimental results, and it predicts that well-timed transient excitatory inputs to the cortex advance the termination of absence seizures.
Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging
Authors: Sun Felicia W. , Stepanovic Michael R. , Andreano Joseph , Barrett Lisa Feldman , Touroutoglou Alexandra , Dickerson Bradford C. 
Published: September 2016

Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function.SIGNIFICANCE STATEMENTMemory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with youthful memory performance) would exhibit preserved neuroanatomy in key brain networks subserving memory. We found that superagers not only perform similarly to young adults on memory testing, they also do not show the typical patterns of brain atrophy in certain regions. These regions are contained largely within two major intrinsic brain networks: the default mode network, implicated in memory encoding, storage, and retrieval, and the salience network, associated with attention and executive processes involved in encoding and retrieval. Preserved neuroanatomical integrity in these networks is associated with better memory performance among older adults.
DrosophilaNeprilysins Are Involved in Middle-Term and Long-Term Memory
Authors: Turrel Oriane , Lampin-Saint-Amaux Aurélie , Préat Thomas , Goguel Valérie 
Published: September 2016

Neprilysins are type II metalloproteinases known to degrade and inactivate a number of small peptides. Neprilysins in particular are the major amyloid-β peptide-degrading enzymes. In mouse models of Alzheimer's disease, neprilysin overexpression improves learning and memory deficits, whereas neprilysin deficiency aggravates the behavioral phenotypes. However, whether these enzymes are involved in memory in nonpathological conditions is an open question.Drosophila melanogasteris a well suited model system with which to address this issue. Several memory phases have been characterized in this organism and the neuronal circuits involved are well described. The fly genome contains five neprilysin-encoding genes, four of which are expressed in the adult. Using conditional RNA interference, we show here that all four neprilysins are involved in middle-term and long-term memory. Strikingly, all four are required in a single pair of neurons, the dorsal paired medial (DPM) neurons that broadly innervate the mushroom bodies (MBs), the center of olfactory memory. Neprilysins are also required in the MB, reflecting the functional relationship between the DPM neurons and the MB, a circuit believed to stabilize memories. Together, our data establish a role for neprilysins in two specific memory phases and further show that DPM neurons play a critical role in the proper targeting of neuropeptides involved in these processes.SIGNIFICANCE STATEMENTNeprilysins are endopeptidases known to degrade a number of small peptides. Neprilysin research has essentially focused on their role in Alzheimer's disease and heart failure. Here, we useDrosophila melanogasterto study whether neprilysins are involved in memory.Drosophilacan form several types of olfactory memory and the neuronal structures involved are well described. Four neprilysin genes are expressed in adultDrosophila. Using conditional RNA interference, we show that all four are specifically involved in middle-term memory (MTM) and long-term memory (LTM) and that their expression is required in the mushroom bodies and also in a single pair of closely connected neurons. The data show that these two neurons play a critical role in targeting neuropeptides essential for MTM and LTM.
Contributions of Rod and Cone Pathways to Retinal Direction Selectivity Through Development
Authors: Rosa Juliana M. , Morrie Ryan D. , Baertsch Hans C. , Feller Marla B. 
Published: September 2016

Direction selectivity is a robust computation across a broad stimulus space that is mediated by activity of both rod and cone photoreceptors through the ON and OFF pathways. However, rods, S-cones, and M-cones activate the ON and OFF circuits via distinct pathways and the relative contribution of each to direction selectivity is unknown. Using a variety of stimulation paradigms, pharmacological agents, and knockout mice that lack rod transduction, we found that inputs from the ON pathway were critical for strong direction-selective (DS) tuning in the OFF pathway. For UV light stimulation, the ON pathway inputs to the OFF pathway originated with rod signaling, whereas for visible stimulation, the ON pathway inputs to the OFF pathway originated with both rod and M-cone signaling. Whole-cell voltage-clamp recordings revealed that blocking the ON pathway reduced directional tuning in the OFF pathway via a reduction in null-side inhibition, which is provided by OFF starburst amacrine cells (SACs). Consistent with this, our recordings from OFF SACs confirmed that signals originating in the ON pathway contribute to their excitation. Finally, we observed that, for UV stimulation, ON contributions to OFF DS tuning matured earlier than direct signaling via the OFF pathway. These data indicate that the retina uses multiple strategies for computing DS responses across different colors and stages of development.SIGNIFICANCE STATEMENTThe retina uses parallel pathways to encode different features of the visual scene. In some cases, these distinct pathways converge on circuits that mediate a distinct computation. For example, rod and cone pathways enable direction-selective (DS) ganglion cells to encode motion over a wide range of light intensities. Here, we show that although direction selectivity is robust across light intensities, motion discrimination for OFF signals is dependent upon ON signaling. At eye opening, ON directional tuning is mature, whereas OFF DS tuning is significantly reduced due to a delayed maturation of S-cone to OFF cone bipolar signaling. These results provide evidence that the retina uses multiple strategies for computing DS responses across different stimulus conditions.
FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma
Authors: Suryo Rahmanto Aldwin , Savov Vasil , Brunner Andrä , Bolin Sara , Weishaupt Holger , Malyukova Alena , Rosén Gabriela , Čančer Matko , Hutter Sonja , Sundström Anders , Kawauchi Daisuke , Jones David TW , Spruck Charles , Taylor Michael D , Cho Yoon‐Jae , Pfister Stefan M , Kool Marcel , Korshunov Andrey , Swartling Fredrik J , Sangfelt Olle 
Published: September 2016

AbstractSOX9 is a master transcription factor that regulates development and stem cell programs. However, its potential oncogenic activity and regulatory mechanisms that control SOX9 protein stability are poorly understood. Here, we show that SOX9 is a substrate of FBW7, a tumor suppressor, and a SCF (SKP1/CUL1/F‐box)‐type ubiquitin ligase. FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is phosphorylated by GSK3 kinase and consequently degraded by SCFFBW7α. Failure to degrade SOX9 promotes migration, metastasis, and treatment resistance in medulloblastoma, one of the most common childhood brain tumors. FBW7 is either mutated or downregulated in medulloblastoma, and in cases where FBW7 mRNA levels are low, SOX9 protein is significantly elevated and this phenotype is associated with metastasis at diagnosis and poor patient outcome. Transcriptional profiling of medulloblastoma cells expressing a degradation‐resistant SOX9 mutant reveals activation of pro‐metastatic genes and genes linked to cisplatin resistance. Finally, we show that pharmacological inhibition of PI3K/AKT/mTOR pathway activity destabilizes SOX9 in a GSK3/FBW7‐dependent manner, rendering medulloblastoma cells sensitive to cytostatic treatment.
Performance Analysis of An Experimental Micro Flexible Manufacturing System (FMS)
Authors: Yildirim Şahin , Yücel Osman 
Published: September 2016

Due to advanced technology, it is very important the performance of FMS for sensivity, production quality, repeatability and energy consumptions. Flexible manufacturing systems (FMSs) are the most automated and technologically sophisticated of the machine cell types used to implement cellular manufacturing. An FMS usually has multiple automated stations and is capable of variable routings among stations, while its flexibility allows it to operate as a mixed model system. The FMS concept integrates many of the advanced technologies that we met in previous units, including flexible automation, CNC machines, distributed computer control, and automated material handling and storage.
In this experimental investigation, vibration and accelerations analysis of an experimental FMS with 5 degrees of freedom robot manipulator are presented. Firstly, experimental measurement of accelerations and vibrations are trained with a vibration measurement system and sensors. However, the process of production of part is a cycle of exact production time.
PROFIL RESISTIVITAS 2D PADA GUA BAWAH TANAH DENGAN METODE GEOLISTRIK KONFIGURASI WENNER-SCHLUMBERGER (STUDI KASUS GUA DAGO PAKAR, BANDUNG)
Authors: Ardi Nanang Dwi , Aryanti Mimin 
Published: September 2016

Makalah ini menampilkan sebuah pendekatan dalam penyelidikan rongga-rongga di bawah tanah. Akuisisi data resistivitas telah dilakukan di Gua Dago Pakar, Bandung. Lintasan resistivitas telah diukur dan dilanjutkan dengan pengukuran secara manual dengan menggunakan tali serta GPS untuk memperkirakan bentuk gua secara akurat. Sistem konfigurasi lintasan resistivitas menggunakan konfigurasi elektroda WennerSchlumberger. Pemrosesan dan pemodelan data menggunakan perangkat lunak Res2DInv dengan metode komputasi kuadrat terkecil. Hasil dari pemodelan inverse 2D menunjukkan bahwa bentuk tubuh gua berlokasi sekitar 10 – 12,4 m di bawah lintasan resistivitas dengan rentang nilai resistivitas 540-600 Ohm meter. Hasil ini dikorelasikan dengan data geologi dan pengukuran secara manual di dalam gua.Kata kunci: Rongga, Resistivitas, Wenner-Schlumberger, Inversi