bluuebunny/crossref_metadata_2025 huggingface dataset:
The renal molecular clock: broken by aging and restored by exercise
Authors: Schmitt Emily E. , Johnson Evan C. , Yusifova Musharraf , Bruns Danielle R.
Published: August 2019

The mammalian circadian clock governs physiological, endocrine, and metabolic responses coordinated in a 24-h rhythmic pattern by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. The SCN also dictates circadian rhythms in peripheral tissues like the kidney. The kidney has several important physiological functions, including removing waste and filtering the blood and regulating fluid volume, blood osmolarity, blood pressure, and Ca2+ metabolism, all of which are under tight control of the molecular/circadian clock. Normal aging has a profound influence on renal function, central and peripheral circadian rhythms, and the sleep-wake cycle. Disrupted circadian rhythms in the kidney as a result of increased age likely contribute to adverse health outcomes such as nocturia, hypertension, and increased risk for stroke, cardiovascular disease, and end organ failure. Regular physical activity improves circadian misalignment in both young and old mammals, although the precise mechanisms for this protection remain poorly described. Recent advances in the heart and skeletal muscle literature suggest that regular endurance exercise entrains peripheral clocks, and we propose that similar beneficial adaptations occur in the kidney through regulation of renal blood flow and fluid balance.
Urinary extracellular vesicle-associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls
Authors: Chirackal Robin S. , Jayachandran Muthuvel , Wang Xiangling , Edeh Samuel , Haskic Zejfa , Perinpam Majuran , Halling Timothy M. , Mehta Ramila , Rivera Marcelino E. , Lieske John C.
Published: August 2019

Randall’s plaque (RP; subepithelial calcification) appears to be an important precursor of kidney stone disease. However, RP cannot be noninvasively detected. The present study investigated candidate biomarkers associated with extracellular vesicles (EVs) in the urine of calcium stone formers (CSFs) with low (<5% papillary surface area) and high (≥5% papillary surface area) percentages of RP and a group of nonstone formers. RPs were quantitated via videotaping and image processing in consecutive CSFs undergoing percutaneous surgery for stone removal. Urinary EVs derived from cells of different nephron segments of CSFs ( n = 64) and nonstone formers ( n = 40) were quantified in biobanked cell-free urine by standardized and validated digital flow cytometer using fluorophore-conjugated antibodies. Overall, the number of EVs carrying surface monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL) were significantly lower in CSFs compared with nonstone former controls ( P < 0.05) but did not differ statistically between CSFs with low and high RPs. The number of EVs associated with osteopontin did not differ between any groups. Thus, EVs carrying MCP-1 and NGAL may directly or indirectly contribute to stone pathogenesis as evidenced by the lower of these populations of EVs in stone formers compared with nonstone formers. Validation of EV-associated MCP-1 and NGAL as noninvasive biomarkers of kidney stone pathogenesis in larger populations is warranted.
Neural coding and perception of auditory motion direction based on interaural time differences
Authors: Zuk Nathaniel J. , Delgutte Bertrand
Published: August 2019

While motion is important for parsing a complex auditory scene into perceptual objects, how it is encoded in the auditory system is unclear. Perceptual studies suggest that the ability to identify the direction of motion is limited by the duration of the moving sound, yet we can detect changes in interaural differences at even shorter durations. To understand the source of these distinct temporal limits, we recorded from single units in the inferior colliculus (IC) of unanesthetized rabbits in response to noise stimuli containing a brief segment with linearly time-varying interaural time difference (“ITD sweep”) temporally embedded in interaurally uncorrelated noise. We also tested the ability of human listeners to either detect the ITD sweeps or identify the motion direction. Using a point-process model to separate the contributions of stimulus dependence and spiking history to single-neuron responses, we found that the neurons respond primarily by following the instantaneous ITD rather than exhibiting true direction selectivity. Furthermore, using an optimal classifier to decode the single-neuron responses, we found that neural threshold durations of ITD sweeps for both direction identification and detection overlapped with human threshold durations even though the average response of the neurons could track the instantaneous ITD beyond psychophysical limits. Our results suggest that the IC does not explicitly encode motion direction, but internal neural noise may limit the speed at which we can identify the direction of motion.

NEW & NOTEWORTHY Recognizing motion and identifying an object’s trajectory are important for parsing a complex auditory scene, but how we do so is unclear. We show that neurons in the auditory midbrain do not exhibit direction selectivity as found in the visual system but instead follow the trajectory of the motion in their temporal firing patterns. Our results suggest that the inherent variability in neural firings may limit our ability to identify motion direction at short durations.
Tactile angle discriminability improvement: roles of training time intervals and different types of training tasks
Authors: Wang Wu , Yang Jiajia , Yu Yinghua , Wu Qiong , Yu Jiabin , Takahashi Satoshi , Ejima Yoshimichi , Wu Jinglong
Published: August 2019

Perceptual learning, which is not limited to sensory modalities such as vision and touch, emerges within a training session and between training sessions and is accompanied by the remodeling of neural connections in the cortex. However, limited knowledge exists regarding perceptual learning between training sessions. Although tactile studies have paid attention to between-session learning effects, there have been few studies asking fundamental questions regarding whether the time interval between training sessions affects tactile perceptual learning and generalization across tactile tasks. We investigated the effects of different training time intervals on the consecutive performance of a tactile angle discrimination (AD) task and a tactile orientation discrimination (OD) task training on tactile angle discriminability. The results indicated that in the short-interval training group, AD task performance significantly improved in the early stage of learning and nearly plateaued in the later stage, whereas in the long-interval training group, significant improvement was delayed and then also nearly plateaued in the later stage; additionally, improved OD task performance resulted in improved AD task performance. These findings suggest that training time interval affects the early stage of learning but not the later stage and that generalization occurs between different types of tactile tasks.

NEW & NOTEWORTHY Perceptual learning, which constitutes important foundations of complicated cognitive processes, is learning better perception skills. We demonstrate that training time interval can affect the early stage of learning but not the later stage. Moreover, a tactile orientation discrimination training task can also improve tactile angle discrimination performance. These findings may expand the characteristics of between-session learning and help understand the mechanism of the generalization across tactile tasks.
Role of paroxysmal depolarization in focal seizure activity
Authors: Tryba Andrew K. , Merricks Edward M. , Lee Somin , Pham Tuan , Cho SungJun , Nordli Douglas R. , Eissa Tahra L. , Goodman Robert R. , McKhann Guy M. , Emerson Ronald G. , Schevon Catherine A. , van Drongelen Wim
Published: August 2019

We analyze the role of inhibition in sustaining focal epileptic seizure activity. We review ongoing seizure activity at the mesoscopic scale that can be observed with microelectrode arrays as well as at the macroscale of standard clinical EEG. We provide clinical, experimental, and modeling data to support the hypothesis that paroxysmal depolarization (PD) is a critical component of the ictal machinery. We present dual-patch recordings in cortical cultures showing reduced synaptic transmission associated with presynaptic occurrence of PD, and we find that the PD threshold is cell size related. We further find evidence that optically evoked PD activity in parvalbumin neurons can promote propagation of neuronal excitation in neocortical networks in vitro. Spike sorting results from microelectrode array measurements around ictal wave propagation in human focal seizures demonstrate a strong increase in putative inhibitory firing with an approaching excitatory wave, followed by a sudden reduction of firing at passage. At the macroscopic level, we summarize evidence that this excitatory ictal wave activity is strongly correlated with oscillatory activity across a centimeter-sized cortical network. We summarize Wilson–Cowan-type modeling showing how inhibitory function is crucial for this behavior. Our findings motivated us to develop a network motif of neurons in silico, governed by a reduced version of the Hodgkin–Huxley formalism, to show how feedforward, feedback, PD, and local failure of inhibition contribute to observed dynamics across network scales. The presented multidisciplinary evidence suggests that the PD not only is a cellular marker or epiphenomenon but actively contributes to seizure activity.

NEW & NOTEWORTHY We present mechanisms of ongoing focal seizures across meso- and macroscales of microelectrode array and standard clinical recordings, respectively. We find modeling, experimental, and clinical evidence for a dual role of inhibition across these scales: local failure of inhibition allows propagation of a mesoscopic ictal wave, whereas inhibition elsewhere remains intact and sustains macroscopic oscillatory activity. We present evidence for paroxysmal depolarization as a mechanism behind this dual role of inhibition in shaping ictal activity.
Loose coupling between SK and P/Q-type Ca2+ channels in cartwheel cells of the dorsal cochlear nucleus
Authors: Irie Tomohiko
Published: August 2019

Small-conductance Ca2+-activated K+ (SK) and large-conductance voltage- and Ca2+-activated K+ (BK) channels are Ca2+-activated K+ channels that control action potential firing in diverse neurons in the brain. In cartwheel cells of the dorsal cochlear nucleus, blockade of either channel type leads to excessive production of spike bursts. In the same cells, P/Q-type Ca2+ channels in plasma membrane and ryanodine receptors in endoplasmic reticulum supply Ca2+ to BK channels through Ca2+ nanodomain signaling. In this study, voltage-clamp experiments were performed in cartwheel cells in mouse brain slices to examine the Ca2+ signaling pathways underlying activation of SK channels. As with BK channels, SK channels required the activity of P/Q-type Ca2+ channels. However, this signaling occurred across Ca2+ micro- rather than nanodomain distances and was independent of Ca2+ release from endoplasmic reticulum. These differential modes of activation may lead to distinct time courses of the two K+ currents and therefore control excitability of auditory neurons across different timescales.

NEW & NOTEWORTHY This study has shown for the first time that in cartwheel cells of the dorsal cochlear nucleus, small-conductance Ca2+-activated K+ (SK) channels were triggered by the activation of P/Q-type Ca2+ channels in which SK–P/Q-type coupling is mediated within the Ca2+ microdomains (loose coupling). Although Ca2+-induced Ca2+ release is able to activate large-conductance voltage- and Ca2+-activated K+ (BK) channels in cartwheel cells, it did not contribute to SK activation.
The Needs for Visual Improvement of Patients Presented at Low-Vision Center in Wenzhou, China
Authors: Li Xiaoman , Chen Guofu , Deng Ruzhi , Lin Na , Ni Lingzhi , Jiang Longfei , Lin Haishuang , Thorn Frank , Chen Jie
Published: August 2019

Purpose. To characterize the needs for visual improvement of new-visit patients with low vision.Methods. This cross-sectional study collected detailed information of patients presented at low-vision center of the Eye Hospital of Wenzhou Medical University between January 2015 and January 2017. A questionnaire interview, including demographic information and needs for visual improvement, was conducted before ophthalmology examinations.Results. The main need for visual improvement was engagement in hobbies (68.9%), followed by reading (20.9%), engaging in occupation (20.1%), and watching TV or movies (17.1%). Less than 10% of patients mentioned the demand of using public transportation (5.8%), doing housework (3.7%), writing (1.9%), walking on irregular surfaces (1.5%), driving (1.1%), and others (2.4%). Women were significantly associated with a concern for performing hobbies (OR 1.45, 95% CI 1.0–2.0) but associated with lower odds of reading (OR 0.46, 95% CI 0.3–0.7). Older subjects were more willing to choose hobbies (OR 1.35 (per 10-year increase), 95% CI 1.3–1.4), reading (OR 1.11 (per 10-year increase), 95% CI 1.0–1.2), watching TV or movies (OR 1.4 (per 10-year increase), 95% CI 1.3–1.6), and housework (OR 1.21 (per 10-year increase), 95% CI 1.0–1.5) than younger individuals. In comparison with younger participants, older individuals were less likely to choose occupation (OR 0.53 (per 10-year increase), 95% CI 0.5–0.6). No significant association was found between visual acuity and needs for visual improvement.Conclusion. Hobbies, reading, engaging in occupation, and watching TV were the most common needs for visual rehabilitation in patients with visual impairment. Gender and age showed a modest influence on the choice of different needs.
Synthesis and Properties of Bionanocomposites of Polyhydroxybutyrate-Polylactic Acid Doped with Copper and Silver Nanoparticles
Authors: Cárdenas-Triviño Galo , Linares-Bermúdez Nelson , Núñez-Decap Mario
Published: August 2019

Global pollution has caused a real interest on the use of biodegradable materials to the sustainable development. PLA and PHB are interesting materials due to their properties and their biodegradability, and their blends in different ratios are proposed in this study; also, Ag and Cu nanoparticles were incorporated to observe possible enhances and advantages on it. Blends were characterized through FTIR, TGA, tensile, and DMA tests. Theoretically, results obtained were coherent; FTIR spectra showed a characteristic band (around 1740 cm-1) corresponding to the carbonyl bond at different intensities for each blend which is an evidence of the polymers. Likewise, TGA results showed different marked decomposition points (except for PLA/PHB 70/30), which is another indicative parameter. Regarding tensile tests, PLA/PHB/nanoparticle (NP) blends showed higher Young modulus value action improving exponentially some properties and they can act as a powerful complementary component even in small amounts. The NPs incorporated exhibited clustering due to the blending process with ranges from 93.24 nm for Cu to 123.71 nm for Ag.
Dynamic Response Analysis of Planar Multilink Mechanism considering Wear in Clearances
Authors: Jiang Shuai , Chen Xiulong , Deng Yu
Published: August 2019

Clearance wear is one of the factors that affects dynamics for mechanical systems. A numerical methodology suitable for modeling and calculation of wear at multiple revolute clearance pairs in the field of the planar multilink mechanism is proposed. In this paper, the 2‐DOF nine‐bar mechanism considering two revolute clearance joints is regarded as the study object. Normal contact force and friction force models of revolute clearance joints used Lankarani–Nikravesh (L‐N) and LuGre models, respectively. The iterative wear prediction process based upon Archard’s model has been applied to calculate wear characteristics. The wear prediction procedure is integrated with multibody dynamics, wear depths at revolute clearance joints are calculated, and the surface of shaft and bearing is reconstructed twice. The dynamic responses of mechanism considering two nonregular revolute clearances caused by wear are studied in depth. The nonlinear characteristics of the mechanism after wear are studied by the phase diagram and Poincaré map. Influences of different initial constant clearance values and different driving speeds on wear of two revolute joints are also researched. The results show that it is necessary to consider the factor of irregular clearances caused by wear in analysis of dynamics of precision mechanisms. Initial constant clearance values and driving speeds have some influence on wear phenomenon. This research provides a theoretical basis for studying dynamics of the planar multilink mechanism considering wear in multiple clearances.
Social Security and Privacy for Social IoT Polymorphic Value Set: A Solution to Inference Attacks on Social Networks
Authors: Gao Yunpeng , Zhang Nan
Published: August 2019

Social Internet of Things (SIoT) integrates social network schemes into Internet of Things (IoT), which provides opportunities for IoT objects to form social communities. Existing social network models have been adopted by SIoT paradigm. The wide distribution of IoT objects and openness of social networks, however, make it more challenging to preserve privacy of IoT users. In this paper, we present a novel framework that preserves privacy against inference attacks on social network data through ranked retrieval models. We propose PVS, a privacy-preserving framework that involves the design of polymorphic value sets and ranking functions. PVS enables polymorphism of private attributes by allowing them to respond to different queries in different ways. We begin this work by identifying two classes of adversaries, authenticity-ignorant adversary, and authenticity-knowledgeable adversary, based on their knowledge of the distribution of private attributes. Next, we define the measurement functions of utility loss and propose PVSV and PVST that preserve privacy against authenticity-ignorant and authenticity-knowledgeable adversaries, respectively. We take into account the utility loss of query results in the design of PVSV and PVST. Finally, we show that PVSV and PVST meet the privacy guarantee with acceptable utility loss in extensive experiments over real-world datasets.
Intelligent Recognition of Time Stamp Characters in Solar Scanned Images from Film
Authors: Zhang Jiafeng , Lin Guangzhong , Zeng Shuguang , Zheng Sheng , Yang Xiao , Lin Ganghua , Zeng Xiangyun , Wang Haimin
Published: August 2019

Prior to the availability of digital cameras, the solar observational images are typically recorded on films, and the information such as date and time were stamped in the same frames on film. It is significant to extract the time stamp information on the film so that the researchers can efficiently use the image data. This paper introduces an intelligent method for extracting time stamp information, namely, the convolutional neural network (CNN), which is an algorithm in deep learning of multilayer neural network structures and can identify time stamp character in the scanned solar images. We carry out the time stamp decoding for the digitized data from the National Solar Observatory from 1963 to 2003. The experimental results show that the method is accurate and quick for this application. We finish the time stamp information extraction for more than 7 million images with the accuracy of 98%.
Optimizing Open‐Pit Truck Route Based on Minimization of Time‐Varying Transport Energy Consumption
Authors: Liu Guangwei , Chai Senlin
Published: August 2019

This paper addresses a special truck routing optimization problem in open‐pit mines based on the minimization of time‐varying transport energy consumption. A mixed‐integer programming model is formulated to clearly describe the engineering problem, and a series of constraints are deduced to strengthen the model. To ensure that the model has time‐varying characteristics, a method to estimate time‐varying parameters is proposed by using pattern recognition and trend surface estimation. This time‐varying resistance coefficient is mainly used to describe the process of road damage caused by frequent rolling of heavy trucks on the road surface. At the same time, in order to make the truck routing converge to the optimal energy consumption solution quickly, some definitions and properties are then provided based on stochastic theory, and a strategy to improve the computational efficiency of the model is proposed using these properties. Finally, an improved genetic algorithm is designed to solve the model. The results of experiments show that the proposed algorithm is effective and efficient.
Reproductive Toxicity of Pomegranate Peel Extract Synthesized Gold Nanoparticles: A Multigeneration Study in C. elegans
Authors: Patel Mahnoor , Siddiqi Nikhat J. , Sharma Preeti , Alhomida Abdullah S. , Khan Haseeb A.
Published: August 2019

C. elegans is a preferential model for testing environmental toxicity of compounds including nanomaterials. The impact of multigeneration exposure of gold nanoparticles (AuNPs) on the lifespan and fertility of C. elegans is not known and therefore is investigated in this study. We used pomegranate (Punica granatum) peel extracts as a reducing agent to synthesize gold nanoparticles (PPE-AuNPs) from chloroauric acid. Nematodes were grown till adult stage and then exposed to 25, 50, and 100 μg/ml of PPE-AuNPs at 20°C for 72 hours and then assessed for lifespan and fertility. The same protocols were followed for subsequent F1, F2, and F3 generations. The results showed that PPE-AuNPs dose-dependently but insignificantly reduced the lifespan of C. elegans. Exposure of PPE-AuNPs significantly and dose-dependently reduced the fertility of C. elegans in terms of the number of eggs produced. The reproductive toxicity of PPE-AuNPs was found to be minimal in parental generation (F0) and maximal in F3 generation. In conclusion, biologically synthesized PPE-AuNPs adversely affect the fertility of C. elegans while the factors responsible for reproductive toxicity are inherited by subsequent generations.
SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes
Authors: Song Xiao , Wan Xuechao , Huang Tianzhi , Zeng Chang , Sastry Namratha , Wu Bingli , James C. David , Horbinski Craig , Nakano Ichiro , Zhang Wei , Hu Bo , Cheng Shi-Yuan
Published: August 2019

Misregulated alternative RNA splicing (AS) contributes to the tumorigenesis and progression of human cancers, including glioblastoma (GBM). Here, we showed that a major splicing factor, serine and arginine rich splicing factor 3 (SRSF3), was frequently upregulated in clinical glioma specimens and that elevated SRSF3 was associated with tumor progression and a poor prognosis for patients with glioma. In patient-derived glioma stem-like cells (GSC), SRSF3 expression promoted cell proliferation, self-renewal, and tumorigenesis. Transcriptomic profiling identified more than 1,000 SRSF3-affected AS events, with a preference for exon skipping in genes involved with cell mitosis. Motif analysis identified the sequence of CA(G/C/A)CC(C/A) as a potential exonic splicing enhancer for these SRSF3-regulated exons. To evaluate the biological impact of SRSF3-affected AS events, four candidates were selected whose AS correlated with SRSF3 expression in glioma tissues, and their splicing pattern was modified using a CRISPR/Cas9 approach. Two functionally validated AS candidates were further investigated for the mechanisms underlying their isoform-specific functions. Specifically, following knockout of SRSF3, transcription factor ETS variant 1 (ETV1) gene showed exon skipping at exon 7, while nudE neurodevelopment protein 1 (NDE1) gene showed replacement of terminal exon 9 with a mutually exclusive exon 9′. SRSF3-regulated AS of these two genes markedly increased their oncogenic activity in GSCs. Taken together, our data demonstrate that SRSF3 is a key regulator of AS in GBM and that understanding mechanisms of misregulated AS could provide critical insights for developing effective therapeutic strategies against GBMs.

Significance:

SRSF3 is a significant regulator of glioma-associated alternative splicing, implicating SRSF3 as an oncogenic factor that contributes to the tumor biology of GBM.
Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer
Authors: Stover Elizabeth H. , Baco Maria B. , Cohen Ofir , Li Yvonne Y. , Christie Elizabeth L. , Bagul Mukta , Goodale Amy , Lee Yenarae , Pantel Sasha , Rees Matthew G. , Wei Guo , Presser Adam G. , Gelbard Maya K. , Zhang Weiqun , Zervantonakis Ioannis K. , Bhola Patrick D. , Ryan Jeremy , Guerriero Jennifer L. , Montero Joan , Liang Felice J. , Cherniack Andrew D. , Piccioni Federica , Matulonis Ursula A. , Bowtell David D.L. , Sarosiek Kristopher A. , Letai Anthony , Garraway Levi A. , Johannessen Cory M. , Meyerson Matthew
Published: August 2019

High-grade serous ovarian cancer (HGSOC) is often sensitive to initial treatment with platinum and taxane combination chemotherapy, but most patients relapse with chemotherapy-resistant disease. To systematically identify genes modulating chemotherapy response, we performed pooled functional genomic screens in HGSOC cell lines treated with cisplatin, paclitaxel, or cisplatin plus paclitaxel. Genes in the intrinsic pathway of apoptosis were among the top candidate resistance genes in both gain-of-function and loss-of-function screens. In an open reading frame overexpression screen, followed by a mini-pool secondary screen, anti-apoptotic genes including BCL2L1 (BCL-XL) and BCL2L2 (BCL-W) were associated with chemotherapy resistance. In a CRISPR-Cas9 knockout screen, loss of BCL2L1 decreased cell survival whereas loss of proapoptotic genes promoted resistance. To dissect the role of individual anti-apoptotic proteins in HGSOC chemotherapy response, we evaluated overexpression or inhibition of BCL-2, BCL-XL, BCL-W, and MCL1 in HGSOC cell lines. Overexpression of anti-apoptotic proteins decreased apoptosis and modestly increased cell viability upon cisplatin or paclitaxel treatment. Conversely, specific inhibitors of BCL-XL, MCL1, or BCL-XL/BCL-2, but not BCL-2 alone, enhanced cell death when combined with cisplatin or paclitaxel. Anti-apoptotic protein inhibitors also sensitized HGSOC cells to the poly (ADP-ribose) polymerase inhibitor olaparib. These unbiased screens highlight anti-apoptotic proteins as mediators of chemotherapy resistance in HGSOC, and support inhibition of BCL-XL and MCL1, alone or combined with chemotherapy or targeted agents, in treatment of primary and recurrent HGSOC.

Implications:

Anti-apoptotic proteins modulate drug resistance in ovarian cancer, and inhibitors of BCL-XL or MCL1 promote cell death in combination with chemotherapy.
A Bispecific Molecule Targeting CD40 and Tumor Antigen Mesothelin Enhances Tumor-Specific Immunity
Authors: Ye Shiming , Cohen Diane , Belmar Nicole A. , Choi Donghee , Tan Siu Sze , Sho Mien , Akamatsu Yoshiko , Kim Han , Iyer Ramesh , Cabel Jean , Lake Marc , Song Danying , Harlan John , Zhang Catherine , Fang Yuni , Wahl Alan F. , Culp Patricia , Hollenbaugh Diane , Chao Debra T.
Published: August 2019

Agonistic CD40 monoclonal antibodies (mAb) have demonstrated some clinical activity, but with dose-limiting toxicity. To reduce systemic toxicity, we developed a bispecific molecule that was maximally active in the presence of a tumor antigen and had limited activity in the absence of the tumor antigen. LB-1 is a bispecific molecule containing single-chain Fv domains targeting mouse CD40 and the tumor antigen mesothelin. LB-1 exhibited enhanced activity upon binding to cell-surface mesothelin but was less potent in the absence of mesothelin binding. In a mouse model implanted with syngeneic 4T1 tumors expressing cell-surface mesothelin, LB-1 demonstrated comparable antitumor activity as an agonistic CD40 mAb but did not cause elevation of serum cytokines and liver enzymes, as was observed in anti-CD40–treated mice. The results from our study of LB-1 were used to develop a human cross-reactive bispecific molecule (ABBV-428) that targeted human CD40 and mesothelin. ABBV-428 demonstrated enhanced activation of antigen-presenting cells and T cells upon binding to cell-surface mesothelin, and inhibition of cultured or implanted PC3 tumor cell growth after immune activation. Although expression of cell-surface mesothelin is necessary, the bispecific molecules induced immune-mediated antitumor activity against both mesothelin+ and mesothelin− tumor cells. ABBV-428 represents a class of bispecific molecules with conditional activity dependent on the binding of a tumor-specific antigen, and such activity could potentially maximize antitumor potency while limiting systemic toxicity in clinical studies.
STING Signaling in Melanoma Cells Shapes Antigenicity and Can Promote Antitumor T-cell Activity
Authors: Falahat Rana , Perez-Villarroel Patricio , Mailloux Adam W. , Zhu Genyuan , Pilon-Thomas Shari , Barber Glen N. , Mulé James J.
Published: August 2019

STING (stimulator of IFN genes) signaling is an innate immune pathway for induction of a spontaneous antitumor T-cell response against certain immunogenic tumors. Although antigen-presenting cells are known to be involved in this process, insight into the participation of tumor cell–intrinsic STING signaling remains weak. In this study, we find diversity in the regulation of STING signaling across a panel of human melanoma cell lines. We show that intact activation of STING signaling in a subset of human melanoma cell lines enhances both their antigenicity and susceptibility to lysis by human melanoma tumor-infiltrating lymphocytes (TIL) through the augmentation of MHC class I expression. Conversely, defects in the STING signaling pathway protect melanoma cells from increased immune recognition by TILs and limit their sensitivity to TIL lysis. Based on these findings, we propose that defects in tumor cell–intrinsic STING signaling can mediate not only tumor immune evasion but also resistance to TIL-based immunotherapies.
The Americanization of Orthodox Christians’ Promotion of Religious Freedom
Authors: Herbel Dellas Oliver
Published: August 2019

Throughout their history in America, Orthodox Christians have promoted their religious freedom primarily through legal changes (e.g., executive orders, court decisions, or legislation). More recently, some Orthodox Christian leaders have begun to respond to the issue of religious freedom by engaging in American political discourse as established by larger conservative religious groups. Orthodox Christians now find themselves utilizing both approaches, exhibiting an Americanization of their faith by accepting the behavior patterns of native-born Americans as valid and authentic. This article explores the three distinct shifts that occurred in this process: self preservation to self-promotion, self-promotion to promoting the religious freedoms of Orthodox overseas, and the adoption of the religious rhetoric and tactics of some American religious conservatives.
Echinoderm Research 2010
Authors: KROH ANDREAS , REICH MIKE
Published: August 2019

Cover & Preface
Tooth morphology and food processing in Ophiothrix fragilis (Abildgaard, in O.F. Müller, 1789) and Ophiura albida Forbes, 1839 (Echinodermata: Ophiuroidea)

Authors: BOOS KARIN
Published: August 2019

Based on the main feeding modes of two common European brittlestars, Ophiothrix fragilis and Ophiura albida, the pre­sent study relates the species’ tooth morphology to their function in processing food items of different structural quality. Clusters of grinding dental papillae in the suspension feeding O. fragilis seem most appropriate for loosening compound food items, i.e., food boli, or potentially for grazing. Large triangular teeth are considered to be used as crushing and cut­ting instruments, most likely for processing loosened or broken up food masses into smaller digestible portions. In the mostly predating and scavenging O. albida, sharp and pointy or broad scale-like oral papillae may serve in gripping and fixing live benthic prey organisms or carrion, while the larger spine-like teeth may be applied as carnassial instruments thrusting into the flesh of a prey organism and tearing off pieces. Designating the two species either as grinders and cutters processing compound and hard structured food or as grippers and tearers handling softer textures, still awaits confirmation through feeding experiments and observational documentation.
Echinoderm conferences and symposia: a concise history and bibliography
Authors: ZIEGLER ALEXANDER , KROH ANDREAS
Published: August 2019

For fifty years, the community of echinoderm researchers has held meetings, symposia, conferences, and workshops deal­ing with their primary objects of research, that is sea stars, sea urchins, and allies. Over the years, a bewildering amount of literature has been published in the course of these gatherings, making it sometimes difficult for the echinoderm novice to see the woods for the trees. In order to facilitate future historic and bibliographic research, we provide a concise summary of echinoderm meetings from 1963 to 2012, together with a detailed list of publications related to these events. This list includes conference proceedings and abstracts compilations complete with ISBN or ISSN numbers. The historical back­ground of several echinoderm conferences is described, and we present information about lesser-known meetings, held for example in the Soviet Union, France, or Japan. In addition, an overview of the evolution of echinoderm conference logos is provided. Finally, we briefly discuss the future of echinoderm conferences and their proceedings.
Reinterpretation of Baltic Ordovician Heckerites multistellatus Rozhnov, 1987 as a possible paracrinoid based on new material*

Authors: ROZHNOV SERGEY V.
Published: August 2019

The monotypic genus Heckerites Rozhnov, 1987, that was found in the Upper Ordovician of Estonia, is redescribed on the basis of new findings. The morphology of the ambulacral system, peristome, the structure and the position of the hydropore, gonopore, and periproct are described in detail. In the morphology of this genus the features of eocrinoids and paracrinoids are unusually combined. Nevertheless, the analysis of these features points to a possible assignment of this genus, and hence the monotypic family Heckeritidae Rozhnov, 1987 based on this genus, to paracrinoids.
Revision of the Early Ordovician (late Tremadocian; Stairsian) cheirurid trilobite Tesselacauda Ross, with species from the Great Basin, western USA
Authors: ADRAIN JONATHAN M. , KARIM TALIA S.
Published: August 2019

The Stairsian genus Tesselacauda Ross, 1951, has historically included two species, the poorly known type, T. depressa Ross, 1951 (Bearriverops loganensis Zone), and the even less well known T. flabella Kobayashi, 1955 (Bearriverops alsacharovi Zone), which may not belong to the genus. The family assignment of the genus has long been in question, with some workers assigning it to Cheiruridae and some to Pliomeridae. New field collections from western Utah and southeastern Idaho yield abundant material of T. depressa, which facilitates revision on the basis of multiple specimens of most exoskeletal parts. Two additional well known species are proposed, T. morrisoni (Rossaspis leboni Zone), and T. kriegerae (Bearriverops alsacharovi Zone). A third new species, very similar to T. depressa, is described in open nomenclature from the Rossaspis leboni Zone. Knowledge of hypostomes from silicified material helps to clarify the basal morphologies of cheirurid versus pliomerid trilobites. Pliomerids have anteroposteriorly elongate hypostomes with a basic pattern of three pairs of lateral hypostomal spines and a single posteromedian spine. Some or all of the spines are reduced or lost in various taxa. Cheirurids either lack paired spines or have only one or two pairs, and never have a posteromedian spine. Cheirurid hypostomes tend to be much shorter and more subquadrate than pliomerids. Other differences between the families are: a small, triangular or trapezoidal rostral plate in pliomerids versus a wide, short plate in cheirurids; a thoracic segment count commonly of 11–13 in Cheiruridae (fewer in one derived subfamily) versus commonly 15 or more in pliomerids (fewer in two derived subfamilies); thoracic pleurae with subequal bands and a prominent furrow in cheirurids versus a much more inflated and rib-like posterior band, reduced anterior band, and short, anteriorly placed furrow; and pygidia with four or fewer segments in cheirurids versus commonly five in pliomerids (again, fewer in two derived subfamilies). On these and other criteria, Tesselacauda is clearly a cheirurid, assigned for the present to the presumptively basal and possibly paraphyletic Subfamily Pilekiinae.
4. Why Should We Protect Biodiversity?
Authors: Wilson John , Primack Richard
Published: August 2019

People value biodiversity in many ways. These reasons vary from person to person, and from region to region. But generally, nature’s contributions to people, also called ecosystem services, are divided into three overlapping and interdependent categories, namely material contributions, regulating services, and nonmaterial contributions. Material contributions include benefits people get from consuming natural resources (e.g. drinking water or burning wood for cooking) or using natural resources in production and trade (e.g. timber to build homes or other structures). Likewise, biodiversity also provides a large variety of regulating services that enable people to benefit from nature’s material contributions. Some of these contributions include ecosystem productivity, water and soil protection, climate regulation, pollination, seed dispersal, and disaster prevention and detection. People attach nonmaterial values to biodiversity which are difficult to quantify, and thus to account for, in modern economic systems. These values include support for inspiration and learning, support for psychological and physical experiences, and support for personal and group identities. Damage to the environment such as pollution caused by industry, are not always fully considered when making political and development decisions, leading to unsustainable economic practices and market failure. The field of environmental economics is a field that highlights this, as it studies the implications of economic transactions, environmental policies, and other decisions that impact the environment. Accounting for negative externalities and perverse subsidies can help policymakers design incentives that promote sustainable practices.
Effects of Rotation on the Multiscale Organization of Convection in a Global 2D Cloud-Resolving Model
Authors: Yang Qiu , Majda Andrew J. , Brenowitz Noah D.
Published: August 2019

Atmospheric convection exhibits distinct spatiotemporal variability at different latitudes. A good understanding of the effects of rotation on the multiscale organization of convection from the mesoscale to synoptic scale to planetary scale is still lacking. Here cloud-resolving simulations with fixed surface fluxes and radiative cooling are implemented with constant rotation in a two-dimensional (2D) planetary domain to simulate multiscale organization of convection from the tropics to midlatitudes. All scenarios are divided into three rotation regimes (weak, order-one, and strong) to represent the idealized ITCZ region (0°–6°N), the Indian monsoon region (6°–20°N), and the midlatitude region (20°–45°N), respectively. In each rotation regime, a multiscale asymptotic model is derived systematically and used as a diagnostic framework for energy budget analysis. The results show that planetary-scale organization of convection only arises in the weak rotation regime, while synoptic-scale organization dominates (vanishes) in the order-one (strong) rotation regime. The depletion of planetary-scale organization of convection as the magnitude of rotation increases is attributed to the reduced planetary kinetic energy of zonal winds, mainly due to the decreasing acceleration effect by eddy zonal momentum transfer from mesoscale convective systems (MCSs) and the increasing deceleration effect by the Coriolis force. Similarly, the maintenance of synoptic-scale organization is related to the acceleration effect by MCSs. Such decreasing acceleration effects by MCSs on both planetary and synoptic scales are further attributed to less favorable conditions for convection provided by weaker background vertical shear of the zonal winds, resulting from the increasing magnitude of rotation.
Subtropical South American Hailstorm Characteristics and Environments
Authors: Bruick Zachary S. , Rasmussen Kristen L. , Cecil Daniel J.
Published: August 2019

Hailstorms in subtropical South America are known to be some of the most frequent anywhere in the world, causing significant damage to the local agricultural economy every year. Convection in this region tends to be orographically forced, with moisture supplied from the Amazon rain forest by the South American low-level jet. Previous climatologies of hailstorms in this region have been limited to localized and sparse observational networks. Because of the lack of sufficient ground-based radar coverage, objective radar-derived hail climatologies have also not been produced for this region. As a result, this study uses a 16-yr dataset of TRMM Precipitation Radar and Microwave Imager observations to identify possible hailstorms remotely, using 37-GHz brightness temperature as a hail proxy. By combining satellite instruments and ERA-Interim reanalysis data, this study produces the first objective study of hailstorms in this region. Hailstorms in subtropical South America have an extended diurnal cycle, often occurring in the overnight hours. In addition, they tend to be multicellular in nature, rather than discrete. High-probability hailstorms (≥50% probability of containing hail) tend to be deeper by 1–2 km and horizontally larger by greater than 15 000 km2 than storms having a low probability of containing hail (<25% probability of containing hail). Hailstorms are supported synoptically by strong upper- and lower-level jets, anomalously warm and moist low levels, and enhanced instability. The findings of this study will support the forecasting of these severe storms and mitigation of their damage within this region.
Measurement and Implications of Perfectionism in South Korea and the United States
Authors: Rice Kenneth G. , Park Hyun-joo , Hong Jihee , Lee Dong-gwi
Published: August 2019

We evaluated the Short Almost Perfect Scale (SAPS; Rice et al., 2014) in South Korean ( N = 306) and United States ( N = 259) samples. Results supported partial metric invariance for the standards (perfectionistic strivings) and discrepancy (perfectionistic concerns) factors, and for depression and self-esteem. Item responses were unaffected by gender- or age-related bias. Differential item functioning analyses and tests of scalar invariance revealed noninvariance for several items that might reflect culturally relevant issues. There were no differences in SAPS factor means based on invariance tests using the alignment method. For both samples, the standards factor was positively and comparably associated with self-esteem and inversely predicted depression; the discrepancy factor yielded effects in the opposite direction. Results generally supported the use of the SAPS for United States–Korean correlational comparisons. Future work could develop and evaluate additional indicators of perfectionistic concerns for cross-national studies, and increase representation in the samples and breadth of criterion factors.
Access to Subsidised Packing Credit for Financing Export: Who are the Gainers?
Authors: Sanati Gargi
Published: August 2019

This study examines the packing credit or pre-shipment credit (PC) as a key determinant factor for the export growth in India. PC is considered to be an important means of financing export if advance payment is not received by the exporter prior to the shipment of goods. The Government of India’s (GoI) scheme of interest subsidy in PC is mostly to boost the export growth in India. In this backdrop, this article is having threefold objectives: (a) to examine the distribution pattern of PC across various exporting sectors; (b) to analyse the availability of export financing at different interest rate range; and (c) to estimate the sensitivity of export growth of India to its utilisation of PC in small, medium and large exporting sectors. Our preliminary analysis reveals that natural elimination takes place, and the present practice of disbursing PC is not able to fulfil the goal of establishing a level playing field for the exporters. Per capita utilisation of PC shows highly skewed preference of the banks to large borrowers, even if they are not subject to the benefit of interest subvention. This study also reveals that small exporters hold the maximum number of PC account, although having the least outstanding amount per account. On the contrary, our Arellano–Bond Dynamic panel analysis for the period 1996–1997 to 2015–2016 shows that the utilisation of PC by medium and small exporters respectively are more sensitive to boost the export growth of India. This study also finds that the effect of the interest subvention scheme was dampened due to the financial crisis and concludes that the export growth would have been much worse affected in the absence of the subvention scheme. Our empirical examination concludes that interest subvention plays a positive and significant role to boost the export growth and additional reduction in the cost of production may add to the export growth of India. This study recommends that the government may introduce a differential interest subsidy for different creditworthy exporters within the entitled sectors to reduce the cost of fund effectively for more needy and sensitive exporters. Given the resource constraint, it may be ensured that large exporters are restricted from receiving the subsidised export finance.

JEL: F49, F30, G01, G18, G32
Microstructure characterization and evaluation of mechanical properties of stir rheocast AA2024/TiB2 composite
Authors: Cheneke Semegn , Karunakar D Benny
Published: August 2019

In this research, microstructure and mechanical properties of stir rheocast AA2024/TiB2 metal matrix composite have been investigated. The working temperature was 640℃, which was the selected semisolid temperature that corresponds to 40% of the solid fraction. Two weight percentage, 4 wt%, and 6 wt% of the TiB2 reinforcements were added to the matrix. The field emission scanning electron microscope micrographs of the developed composites showed a uniform distribution of the particles in the case of the 2 wt% and 4 wt% of the reinforcements. However, the particles agglomerated as the weight percentages of the reinforcement increases to 6%. The optical microscope of the liquid cast sample showed the dendritic structure, whereas the rheocast samples showed a globular structure. The X-ray diffraction analysis confirmed the distribution of the reinforcements in the matrix and the formation of some intermetallic compounds. Mechanical properties significantly improved by the addition of the reinforcements in the matrix. An increase in tensile strength of 13.3%, 40%, 28%, and 5% was achieved for the unreinforced rheocast sample, 2 wt%, 4 wt%, and 6 wt% reinforced rheocast samples respectively, compared to the liquid cast sample. An increase in 20% of hardness was attained for the composite with 2 wt% TiB2 compared to the liquid cast sample. According to the fractography analysis, small dimples were observed on the fractured surface of the unreinforced rheocast sample, whereas small and large voids were dominant on the fractured surface of the 2 wt% composite, which shows the ductile fracture mode.