bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical utility of a passive immune basophil activation test for the analysis of allergic transfusion reactions
Authors: Yasui Kazuta , Matsuyama Nobuki , Okamura‐Shiki Ikue , Ikeda Takashi , Ishii Kazuyoshi , Furuta Rika A. , Hirayama Fumiya
Published: June 2017

BACKGROUND

In previous studies, we demonstrated that the basophil activation test, which is performed using patient blood and the supernatants from transfused blood components, was able to elucidate not only the causative relationship between allergic transfusion reactions and the transfusion but also the mechanisms behind allergic transfusion reactions. However, for a large number of allergic transfusion reactions, patients are in a state of myelosuppression, and the basophil activation test cannot be performed for these patients because there are insufficient numbers of peripheral blood basophils.

STUDY DESIGN AND METHODS

To overcome this obstacle, we developed a passive immune basophil activation test, in which patient plasma and residually transfused blood are used as the patient's sources of immunoglobulin E and allergen, respectively, whereas healthy volunteer basophils serve as the responder cell source. The passive immune basophil activation test was performed for two patients who had severe allergic transfusion reactions, using supernatants of the residual platelet concentrates and the patients' own immunoglobulin E.

RESULTS

There were no differences in either surface immunoglobulin E or activation in response to allergens between untreated basophils and so‐called quasi‐basophils, in which immunoglobulin E was replaced by a third party's immunoglobulin E. In these patients, the supernatants of the residual platelet concentrates exclusively activated basophils in response to quasi‐basophils onto which the patients' immunoglobulin E, but not a third party's immunoglobulin E, was bound.

CONCLUSION

The passive immune basophil activation test may help clarify the causal relationship between allergic transfusion reactions and transfused blood, even when patients experience myelosuppression.
Picard groups of higher real -theory spectra at height
Authors: Heard Drew , Mathew Akhil , Stojanoska Vesna
Published: June 2017

Using the descent spectral sequence for a Galois extension of ring spectra, we compute the Picard group of the higher real $K$-theory spectra of Hopkins and Miller at height $n=p-1$, for $p$ an odd prime. More generally, we determine the Picard groups of the homotopy fixed points spectra $E_{n}^{hG}$, where $E_{n}$ is Lubin–Tate $E$-theory at the prime $p$ and height $n=p-1$, and $G$ is any finite subgroup of the extended Morava stabilizer group. We find that these Picard groups are always cyclic, generated by the suspension.
Modeling and Analysis of an Efficient Porous Media for a Solar Porous Absorber With a Variable Pore Structure
Authors: Wang P. , Vafai K.
Published: June 2017

A theoretical mathematical model that considers the continuous linear porosity or pore diameter distribution is established to develop a novel porous absorber with variable pore structure, which will result in a thermopressure drop improvement. Efficient performance can be achieved based on reconstruction of the velocity, temperature, and radiation fields. Collimated and diffusive radiative heat fluxes and the heat loss mechanism from the irradiated surface are analyzed in the presence of the volumetric effect. This study analyzes three typical linear pore structure distributions: increasing (I), decreasing (D), and constant (C) types, respectively. In general, the D type porosity (φ) layout combined with the I type pore diameter (dp) distribution would be an excellent pore structure layout for a porous absorber.
Effects of Supersaturated Silicic Acid Concentration on Deposition Rate Around Geological Disposal System
Authors: Sasagawa Tsuyoshi , Chida Taiji , Niibori Yuichi
Published: June 2017

Cementitious materials for the construction of a geological repository of radioactive waste alter the pH of groundwater to a highly alkaline condition (pH ≈ 13). While this alkaline groundwater dissolves silicate minerals, the soluble silicic acid polymerizes or deposits on the surface of rock with the decrease in pH by mixing with the surrounding groundwater (pH = 8). In particular, the deposition of silicic acid leads to a clogging effect in flow-paths, which retards the migration of radionuclides. This study estimated the clogging of silicic acid in flow-paths with the one-dimensional advection–dispersion model considering the deposition rate constants evaluated in our previous study. As some of the most important parameters, these estimations focused on the initial supersaturated concentration of silicic acid and the density of deposited minerals. As a result, the aperture of flow-paths (initial width: 0.1 mm, flow-rate: 5 m/y, initial supersaturated concentration of silicic acid: 0.01, 0.1 and 1.0 mM) was almost clogged within about 200 y by the deposition of silicic acid. The period for the clogging became shorter under the conditions of higher initial supersaturated concentration and lower density of deposited minerals. In other words, the use of cementitious materials for constructing the repository might produce a retardation effect of radionuclide migration by the deposition/clogging processes of the supersaturated silicic acid.
Collagen affinity coating for surface binding of decorin and other biomolecules: Surface characterization
Authors: Sylvester Marisa L. , Ratner Buddy D.
Published: June 2017

The development of biomaterials that promote tissue reconstruction and regeneration can reduce the low level, chronic inflammation and encapsulation that impact the performance of today's medical devices. Specifically, in the case of implantable sensors, the host response often leads to poor device performance that discourages permanent implantation. Our goal is to present on medical implants bioactive molecules that can promote healing rather than scarring. Localized delivery of these molecules would also minimize the possibility of adverse tissue reactions elsewhere in the body. Toward this end, the authors have developed a collagen affinity coating that binds a number of potential healing molecules and can be attached to the surface of an implanted biomaterial. This allows the creation of a wide variety of natural surface coatings that can be evaluated and tailored to promote the desired healing response. To demonstrate the efficacy of this collagen affinity coating to biospecifically bind promising healing molecules to type I collagen in vivo, the antifibrotic proteoglycan decorin was utilized. Decorin binds and renders ineffective the protein transforming growth factor beta (TGFβ) that induces collagen scar production. Thus, an assembled, supramolecular structure of biomaterial-collagen-decorin-TGFβ is formed. A decorin surface coating was created and characterized, illustrating the potential of this type I collagen affinity coating for widespread use with a variety of promising healing molecules. Future studies will test the implant efficacy of this type of coating.
Selective Changes in the Mechanical Capacities of Lower-Body Muscles After Cycle-Ergometer Sprint Training Against Heavy and Light Resistances
Authors: García-Ramos Amador , Torrejón Alejandro , Pérez-Castilla Alejandro , Morales-Artacho Antonio J. , Jaric Slobodan
Published: June 2017

Purpose:To explore the feasibility of the linear force–velocity (F–V) modeling approach to detect selective changes of F–V parameters (ie, maximum force [F0], maximum velocity [V0], F–V slope [a], and maximum power [P0]) after a sprint-training program.Methods:Twenty-seven men were randomly assigned to a heavy-load group (HLG), light-load group (LLG), or control group (CG). The training sessions (6 wk × 2 sessions/wk) comprised performing 8 maximal-effort sprints against either heavy (HLG) or light (LLG) resistances in leg cycle-ergometer exercise. Pre- and posttest consisted of the same task performed against 4 different resistances that enabled the determination of the F–V parameters through the application of the multiple-point method (4 resistances used for the F–V modeling) and the recently proposed 2-point method (only the 2 most distinctive resistances used).Results:Both the multiple-point and the 2-point methods revealed high reliability (all coefficients of variation <5% and intraclass correlation coefficients >.80) while also being able to detect the group-specific training-related changes. Large increments ofF0,a, andP0were observed in HLG compared with LLG and CG (effect size [ES] = 1.29–2.02). Moderate increments ofV0were observed in LLG compared with HLG and CG (ES = 0.87–1.15).Conclusions:Short-term sprint training on a leg cycle ergometer induces specific changes in F–V parameters that can be accurately monitored by applying just 2 distinctive resistances during routine testing.
Errors Associated With Utilizing Prescribed Scapular Kinematics to Estimate Unconstrained, Natural Upper Extremity Motion in Musculoskeletal Modeling
Authors: Richardson R. Tyler , Rapp Elizabeth A. , Quinton R. Garry , Nicholson Kristen F. , Knarr Brian A. , Russo Stephanie A. , Higginson Jill S. , Richards James G.
Published: June 2017

Musculoskeletal modeling is capable of estimating physiological parameters that cannot be directly measured, however, the validity of the results must be assessed. Several models utilize a scapular rhythm to prescribe kinematics, yet it is unknown how well they replicate natural scapular motion. This study evaluated kinematic errors associated with a model that employs a scapular rhythm using 2 shoulder movements: abduction and forward reach. Two versions of the model were tested: the original MoBL ARMS model that utilizes a scapular rhythm, and a modified MoBL ARMS model that permits unconstrained scapular motion. Model estimates were compared against scapulothoracic kinematics directly measured from motion capture. Three-dimensional scapulothoracic resultant angle errors associated with the rhythm model were greater than 10° for abduction (mean: 16.4°, max: 22.4°) and forward reach (mean: 11.1°, max: 16.5°). Errors generally increased with humerothoracic elevation with all subjects reporting greater than 10° differences at elevations greater than 45°. Errors associated with the unconstrained model were less than 10°. Consequently, use of the original MoBL ARMS model is cautioned for applications requiring precise scapulothoracic kinematics. These findings can help determine which research questions are suitable for investigation with these models and assist in contextualizing model results.
Availability of Peripheral Optic Flow Influences Whether Infants Cross a Visual Cliff
Authors: Anderson David I. , Dahl Audun , Campos Joseph J. , Chand Kiren , He Minxuan , Uchiyama Ichiro
Published: June 2017

This report describes a novel test of the prediction that locomotion-induced changes in an infant’s functional utilization of peripheral lamellar optic flow (PLOF) for postural stability contributes to avoidance of the deep side of a visual cliff. To test the prediction, a corridor, with either low-textured or high-textured walls, was constructed to run the length of a visual cliff. The infants, 9.5-month-olds with varying amounts of hands-and-knees crawling experience, were randomly assigned to the low-texture (n = 30) or the high-texture condition (n = 32). Consistent with predictions, the findings revealed significant interactions between crawling experience and texture condition for the probability of crossing and the latency to venture onto the deep side of the cliff. Most notably, more experienced crawlers, but not less experienced crawlers, were significantly more likely to cross the visual cliff to the parents and ventured onto the cliff faster in the high-texture condition than in the low-texture condition. The availability of PLOF thus had an effect on infants’ crossing behavior on the visual cliff. We interpret these findings as evidence for a three-step process in which locomotor-induced changes in visual proprioception play a central role in the development of wariness of heights.
A Plastid Protein That Evolved from Ubiquitin and Is Required for Apicoplast Protein Import in
Toxoplasma gondii
Authors: Fellows Justin D. , Cipriano Michael J. , Agrawal Swati , Striepen Boris
Published: June 2017

Apicomplexan parasites cause a variety of important infectious diseases, including malaria, toxoplasma encephalitis, and severe diarrhea due to
Cryptosporidium
. Most apicomplexans depend on an organelle called the apicoplast which is derived from a red algal endosymbiont. The apicoplast is essential for the parasite as the compartment of fatty acid, heme, and isoprenoid biosynthesis. The majority of the approximate 500 apicoplast proteins are nucleus encoded and have to be imported across the four membranes that surround the apicoplast. Import across the second outermost membrane of the apicoplast, the periplastid membrane, depends on an apicoplast-specific endoplasmic reticulum-associated protein degradation (ERAD) complex and on enzymes of the associated ubiquitination cascade. However, identification of an apicoplast ubiquitin associated with this machinery has long been elusive. Here we identify a plastid ubiquitin-like protein (PUBL), an apicoplast protein that is derived from a ubiquitin ancestor but that has significantly changed in its primary sequence. PUBL is distinct from known ubiquitin-like proteins, and phylogenomic analyses suggest a clade specific to apicomplexans. We demonstrate that PUBL and the AAA ATPase CDC48
AP
both act to translocate apicoplast proteins across the periplastid membrane during protein import. Conditional null mutants and genetic complementation show that both proteins are critical for this process and for parasite survival. PUBL residues homologous to those that are required for ubiquitin conjugation onto target proteins are essential for this function, while those required for polyubiquitination and preprotein processing are dispensable. Our experiments provide a mechanistic understanding of the molecular machinery that drives protein import across the membranes of the apicoplast.

IMPORTANCE
Apicomplexan parasites are responsible for important human diseases. There are no effective vaccines for use in humans, and drug treatment faces multiple challenges, including emerging resistance, lack of efficacy across the lifecycle, and adverse drug effects. The apicoplast is a promising target for novel treatments: this chloroplast-like organelle is derived from an algal symbiont, is absent from the host, and is essential for parasite growth and pathogenesis. We use
Toxoplasma gondii
as a model to study the apicoplast due to its strong genetic tools and established functional assays. We identify a plastid ubiquitin-like protein (PUBL) which is a novel ubiquitin-like protein and demonstrate its importance and that of the motor protein CDC48
AP
for apicoplast protein import. These findings broaden our understanding of the evolution and mechanistic workings of a unique parasite organelle and may lead to new opportunities for treatments against important human pathogens.
Spontaneous rupture of the bladder during vomiting
Authors: Crawford Ruairidh , Oliver Thomas Richard William , Abboudi Hamid , Shah Shahzad
Published: June 2017

A 46-year-old woman with no urological history or comorbidities presented with an acute abdomen with haematuria after a spell of protracted vomiting. The initial cystogram was negative; however, CT imaging highly suggested an intraperitoneal bladder perforation, which was confirmed during laparotomy and subsequently repaired. Cystoscopic evaluation prior to laparotomy revealed no concurrent bladder pathology, and the ureteric orifices were intact. A cystogram 2 weeks after repair demonstrated no leaks, and her catheters were removed. She recovered well, with expectant postoperative pain and lower urinary tract symptoms settling on 3-month review. Spontaneous bladder rupture is a rare entity, with very few reports in the literature.
Successful repeat ECMO in a patient with AIDS and ARDS
Authors: Horikita Sho , Sanui Masamitsu , Fujimoto Yuki , Lefor Alan Kawarai
Published: June 2017

Veno-venous extracorporeal membrane oxygenation (ECMO) is being more commonly used in patients with acute respiratory distress syndrome (ARDS) due to potentially reversible illnesses. Survival from ARDS using ECMO has been reported even in patients with AIDS. However, the indications for ECMO for ARDS due to immune reconstitution inflammatory syndrome (IRIS) in patients with AIDS are unknown. A 23-year-old man with AIDS andPneumocystis jiroveciipneumonia was admitted to the intensive care unit with severe ARDS refractory to mechanical ventilator support requiring ECMO. Although ECMO was discontinued, a second treatment with ECMO was necessary due to IRIS-associated ARDS, resulting in an excellent patient outcome. This patient’s clinical course suggests two important messages. First, ECMO is a reasonable option for the treatment of patients with ARDS even in a patient with AIDS. Second, ECMO may be effective for the treatment of patients with IRIS.
Heroin-induced acute myelopathy with extreme high levels of CSF glial fibrillar acidic protein indicating a toxic effect on astrocytes
Authors: Sveinsson Olafur , Herrman Lars , Hietala Max Albert
Published: June 2017

A man aged 33 years with previous heroin substance abuse was found unconscious lying in a bush. The patient had been without heroin for some time but had just started to use intravenous heroin again, 0.5–2 g daily. The patient had almost complete paraplegia and a sensory loss for all modalities below the mamillary level and a urine retention of 1.5 L. Acute MRI of the spine revealed an expanded spinal cord with increased intramedullary signal intensity, extending from C7–T9. The cerebrospinal fluid showed extremely high levels of nerve injury markers particularly glial fibrillar acidic protein (GFAP): 2 610 000/ng/L (ref. <750). The patient was empirically treated with intravenous 1 g methylprednisolone daily for 5 days and improved markedly. Very few diseases are known to produce such high levels of GFAP, indicating a toxic effect on astrocytes. Measuring GFAP could possibly aid in the diagnosis of heroin-induced myelopathy.
Carbon Nanotubes, Nanofibers and Nanospikes for Electrochemical Sensing: A Review
Authors: Shanta Aysha S. , Al Mamun Khandakar A. , Islam Syed K. , McFarlane Nicole , Hensley Dale K.
Published: June 2017

The structural and material properties of carbon based sensors have spurred their use in biosensing applications. Carbon electrodes are advantageous for electrochemical sensors due to their increased electroactive surface areas, enhanced electron transfer, and increased adsorption of target molecules. The bonding properties of carbon allows it to form a variety of crystal structures. This paper performs a comparative review of carbon nanostructures for electrochemical sensing applications. The review specifically compares carbon nanotubes (CNT), carbon nanofibers (CNF), and carbon nanospikes (CNS). These carbon nanostructures possess defect sites and oxygen functional groups that aid in electron transfer and adsorption processes.
How important is IT?
Authors: Koutroumpis Pantelis , Leiponen Aija , Thomas Llewellyn D W
Published: June 2017

Information and communication technology patents are more influential on subsequent inventions than are other types of patents.
Efficient Branch and Bound on FPGAs Using Work Stealing and Instance-Specific Designs
Authors: Riebler Heinrich , Lass Michael , Mittendorf Robert , Löcke Thomas , Plessl Christian
Published: June 2017

Branch and bound (B8B) algorithms structure the search space as a tree and eliminate infeasible solutions early by pruning subtrees that cannot lead to a valid or optimal solution. Custom hardware designs significantly accelerate the execution of these algorithms. In this article, we demonstrate a high-performance B8B implementation on FPGAs. First, we identify general elements of B8B algorithms and describe their implementation as a finite state machine. Then, we introduce workers that autonomously cooperate using work stealing to allow parallel execution and full utilization of the target FPGA. Finally, we explore advantages of instance-specific designs that target a specific problem instance to improve performance.

We evaluate our concepts by applying them to a branch and bound problem, the reconstruction of corrupted AES keys obtained from cold-boot attacks. The evaluation shows that our work stealing approach is scalable with the available resources and provides speedups proportional to the number of workers. Instance-specific designs allow us to achieve an overall speedup of 47 × compared to the fastest implementation of AES key reconstruction so far. Finally, we demonstrate how instance-specific designs can be generated just-in-time such that the provided speedups outweigh the additional time required for design synthesis.
Reducing the Performance Gap between Soft Scalar CPUs and Custom Hardware with TILT
Authors: Tili Ilian , Ovtcharov Kalin , Steffan J. Gregory
Published: June 2017

By using resource sharing field-programmable gate array (FPGA) compute engines, we can reduce the performance gap between soft scalar CPUs and resource-intensive custom datapath designs. This article demonstrates that Thread- and Instruction-Level parallel Template architecture (TILT), a programmable FPGA-based horizontally microcoded compute engine designed to highly utilize floating point (FP) functional units (FUs), can improve significantly the average throughput of eight FP-intensive applications compared to a soft scalar CPU (similar to a FP-extended Nios). For eight benchmark applications, we show that: (i) a base TILT configuration having a single instance for each FU type can improve the performance over a soft scalar CPU by 15.8 × , while requiring on average 26% of the custom datapaths’ area; (ii) selectively increasing the number of FUs can more than double TILT’s average throughput, reducing the custom-datapath-throughput-gap from 576 × to 14 × ; and (iii) replicated instances of the most computationally dense TILT configuration that fit within the area of each custom datapath design can reduce the gap to 8.27 × , while replicated instances of application-tuned configurations of TILT can reduce the custom-datapath-throughput-gap to an average of 5.22 × , and up to 3.41 × for the Matrix Multiply benchmark. Last, we present methods for design space reduction, and we correctly predict the computationally densest design for seven out of eight benchmarks.
The IDAR graph
Authors: Overton Mark A.
Published: June 2017

An improvement over UML.
Side effects, front and center
Authors: Helland Pat
Published: June 2017

One system's side effect is another's meat and potatoes.
Understanding and Exploiting Object Interaction Landscapes
Authors: Pirk Sören , Krs Vojtech , Hu Kaimo , Rajasekaran Suren Deepak , Kang Hao , Yoshiyasu Yusuke , Benes Bedrich , Guibas Leonidas J.
Published: June 2017

Interactions play a key role in understanding objects and scenes for both virtual and real-world agents. We introduce a new general representation for proximal interactions among physical objects that is agnostic to the type of objects or interaction involved. The representation is based on tracking particles on one of the participating objects and then observing them with sensors appropriately placed in the interaction volume or on the interaction surfaces. We show how to factorize these interaction descriptors and project them into a particular participating object so as to obtain a new functional descriptor for that object, its
interaction landscape
, capturing its observed use in a spatiotemporal framework. Interaction landscapes are independent of the particular interaction and capture subtle dynamic effects in how objects move and behave when in functional use. Our method relates objects based on their function, establishes correspondences between shapes based on functional key points and regions, and retrieves peer and partner objects with respect to an interaction.
Cracking the code on DNA storage
Authors: Greengard Samuel
Published: June 2017

Researchers are tapping DNA to create a new and different type of storage media. The technology could prove revolutionary.
Evolution of Mating in the Saccharomycotina
Authors: Wolfe Kenneth H. , Butler Geraldine
Published: June 2017

The fungal phylum Ascomycota comprises three subphyla: Saccharomycotina, Pezizomycotina, and Taphrinomycotina. In many Saccharomycotina species, cell identity is determined by genes at the MAT (mating-type) locus; mating occurs between MATa and MATα cells. Some species can switch between MATa and MATα mating types. Switching in the Saccharomycotina originated in the common ancestor of the Saccharomycetaceae, Pichiaceae, and Metschnikowiaceae families, as a flip/flop mechanism that inverted a section of chromosome. Switching was subsequently lost in the Metschnikowiaceae, including Candida albicans, but became more complex in the Saccharomycetaceae when the mechanism changed from inversion to copy-and-paste between HML/HMR and MAT. Based on their phylogenetic closeness and the similarity of their MTL (mating-type like) loci, some Metschnikowia species may provide useful models for the sexual cycles of Candida species. Conservation of synteny demonstrates that, despite changes in its gene content, a single orthologous locus (MAT/MTL) has controlled cell type throughout ascomycete evolution.
The Critical Roles of Polysaccharides in Gut Microbial Ecology and Physiology
Authors: Porter Nathan T. , Martens Eric C.
Published: June 2017

The human intestine harbors a dense microbial ecosystem (microbiota) that is different between individuals, dynamic over time, and critical for aspects of health and disease. Dietary polysaccharides directly shape the microbiota because of a gap in human digestive physiology, which is equipped to assimilate only proteins, lipids, simple sugars, and starch, leaving nonstarch polysaccharides as major nutrients reaching the microbiota. A mutualistic role of gut microbes is to digest dietary complex carbohydrates, liberating host-absorbable energy via fermentation products. Emerging data indicate that polysaccharides play extensive roles in host–gut microbiota symbiosis beyond dietary polysaccharide digestion, including microbial interactions with endogenous host glycans and the importance of microbial polysaccharides. In this review, we consider multiple mechanisms through which polysaccharides mediate aspects of host-microbe symbiosis in the gut, including some affecting health. As host and microbial metabolic pathways are intimately connected with diet, we highlight the potential to manipulate this system for health.
Intermuscular coherence reflects functional coordination
Authors: Laine Christopher M. , Valero-Cuevas Francisco J.
Published: June 2017

Coherence analysis has the ability to identify the presence of common descending drive shared by motor unit pools and reveals its spectral properties. However, the link between spectral properties of shared neural drive and functional interactions among muscles remains unclear. We assessed shared neural drive between muscles of the thumb and index finger while participants executed two mechanically distinct precision pinch tasks, each requiring distinct functional coordination among muscles. We found that shared neural drive was systematically reduced or enhanced at specific frequencies of interest (~10 and ~40 Hz). While amplitude correlations between surface EMG signals also exhibited changes across tasks, only their coherence has strong physiological underpinnings indicative of neural binding. Our results support the use of intermuscular coherence as a tool to detect when coactivated muscles are members of a functional group or synergy of neural origin. Furthermore, our results demonstrate the advantages of considering neural binding at 10, ~20, and >30 Hz, as indicators of task-dependent neural coordination strategies.

NEW & NOTEWORTHY It is often unclear whether correlated activity among muscles reflects their neural binding or simply reflects the constraints defining the task. Using the fact that high-frequency coherence between EMG signals (>6 Hz) is thought to reflect shared neural drive, we demonstrate that coherence analysis can reveal the neural origin of distinct muscle coordination patterns required by different tasks.
Idiopathic Bilateral Suprachoroidal Haemorrhage: A Rare Case Presentation
Authors: Saluja Komal , Naik Mayuresh , Vemparala Rajshekhar , Mehta Anuj
Published: June 2017

55-year-old male presented with sudden onset painful diminution of vision in both eyes. On local examination, his visual acuity was FC at 2 metres in right eye and FC at 1 m in left eye. The IOP in right eye was 46 mm Hg and 44 mm Hg in left eye. The patient was admitted and started on injection mannitol, oral syrup glycerol, and oral acetazolamide. Locally, timolol maleate and brimonidine were also started. The next day, his IOP was 17 mm Hg bilaterally but his visual acuity deteriorated to FC 1 m in right eye and hand movement in left eye with inaccurate projection of rays in both eyes. USG B-scan was performed which revealed bilateral choroidal detachment. The echotexture of fluid was suggestive of haemorrhage. As the IOP was controlled, systemic hyperosmotic/antiglaucoma agents were withdrawn in stepwise fashion over next two days. The patient was started on oral prednisolone. At 2 weeks, the visual acuity in both eyes was only perception of light, with inaccurate PR. IOP was 10 mm Hg in both eyes. USG B-scan revealed resorption of the hemorrhage, with partial resolution of the choroidal detachment. The final BCVA was 6/18 and 6/12 in right and left eye.
Dynamic Analysis of Complex Synchronization Schemes between Integer Order and Fractional Order Chaotic Systems with Different Dimensions
Authors: Ouannas Adel , Wang Xiong , Pham Viet-Thanh , Ziar Toufik
Published: June 2017

We present new approaches to synchronize different dimensional master and slave systems described by integer order and fractional order differential equations. Based on fractional order Lyapunov approach and integer order Lyapunov stability method, effective control schemes to rigorously study the coexistence of some synchronization types between integer order and fractional order chaotic systems with different dimensions are introduced. Numerical examples are used to validate the theoretical results and to verify the effectiveness of the proposed schemes.
Influence of Boundary Conditions on the Simulation of a Diamond-Type Lattice Structure: A Preliminary Study
Authors: Terriault Patrick , Brailovski Vladimir
Published: June 2017

Emergent additive manufacturing processes allow the use of metallic porous structures in various industrial applications. Because these structures comprise a large number of ordered unit cells, their design using conventional modeling approaches, such as finite elements, becomes a real challenge. A homogenization technique, in which the lattice structure is simulated as a fully dense volume having equivalent material properties, can then be employed. To determine these equivalent material properties, numerical simulations can be performed on a single unit cell of the lattice structure. However, a critical aspect to consider is the boundary conditions applied to the external faces of the unit cell. In the literature, different types of boundary conditions are used, but a comparative study is definitely lacking. In this publication, a diamond-type unit cell is studied in compression by applying different boundary conditions. If the porous structure’s boundaries are free to deform, then the periodic boundary condition is found to be the most representative, but constraint equations must be introduced in the model. If, instead, the porous structure is inserted in a rigid enclosure, it is then better to use frictionless boundary conditions. These preliminary results remain to be validated for other types of unit cells loaded beyond the yield limit of the material.
Limb Amputation after Multiple Treatments of Tenosynovial Giant Cell Tumour: Series of 4 Dutch Cases
Authors: Mastboom Monique J. L. , Verspoor Floortje G. M. , Gelderblom Hans , Sande Michiel A. J. van de
Published: June 2017

In Tenosynovial Giant Cell Tumours (TGCT), previously named Pigmented Villonodular Synovitis (PVNS), a distinction is made between a single nodule (localized-type) and multiple nodules (diffuse-type). Diffuse-type is considered locally aggressive. Onset and extermination of this orphan disease remain unclear. Surgical resection is the most commonly performed treatment. Unfortunately, recurrences often occur (up to 92%), necessitating reoperations and adjuvant treatments. Once all treatments fail or if severe complications occur, limb amputation may become unavoidable. We describe four cases of above-knee amputation after TGCT diagnosis.
Effect of Varying the Semiconducting/Metallic Tube Ratio on the Performance of Mixed Single-Walled Carbon Nanotube Network Gas Sensors
Authors: Min Sung Joon , Kim Jin Woong , Kim Joon Hyub , Choi Joon Hyock , Park Chan Won , Min Nam Ki
Published: June 2017

The sensing properties of mixed networks consisting of semiconducting and metallic single-walled carbon nanotubes (SWCNTs) have been found to largely vary depending on the ratio of semiconducting to metallic tubes. Solution-deposited 99% semiconductor-enriched nanotube networks exhibited a sensitivity of 1.908%/ppm, whereas the unenriched 66% and 90% enriched samples exhibited a sensitivity of 0.027%/ppm and 0.113%/ppm, respectively. These results suggest that it is extremely important to minimize the metallic pathways to achieve high sensitivity. After an oxygen plasma treatment, the unenriched 66% sample exhibited a 526% increase in sensitivity (0.142%/ppm) compared to the untreated one, whereas the 90% device demonstrated a sensitivity of 1.521%/ppm, which corresponds to an improvement in the sensitivity of 13.5 times the pristine 90% sample. In addition, the plasma-treated sensors exhibited a much faster response time than the untreated one. The significant improvement in the performance of the highly enriched network sensors was explained by the large increase in the anchoring sites for ammonia molecules on the surface of the semiconducting single-walled CNTs and the faster charge transfer from absorbed molecules.
Acquired Immune Resistance Follows Complete Tumor Regression without Loss of Target Antigens or IFNγ Signaling
Authors: Donia Marco , Harbst Katja , van Buuren Marit , Kvistborg Pia , Lindberg Mattias F. , Andersen Rikke , Idorn Manja , Munir Ahmad Shamaila , Ellebæk Eva , Mueller Anja , Fagone Paolo , Nicoletti Ferdinando , Libra Massimo , Lauss Martin , Hadrup Sine Reker , Schmidt Henrik , Andersen Mads Hald , thor Straten Per , Nilsson Jonas A. , Schumacher Ton N. , Seliger Barbara , Jönsson Göran , Svane Inge Marie
Published: June 2017

Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell–based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFNγ signaling, led to impaired recognition by tumor-specific CD8+ T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I–related APM. Loss of target antigens or impaired IFNγ signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted. Cancer Res; 77(17); 4562–6. ©2017 AACR.
Inhibiting p53 Acetylation Reduces Cancer Chemotoxicity
Authors: Zheng Shunsheng , Koh Xin Yu , Goh Hui Chin , Rahmat Siti Aishah B. , Hwang Le-Ann , Lane David P.
Published: June 2017

Chemotoxicity due to unwanted p53 activation in the bone marrow remains an unmet clinical challenge. Doxorubicin, a first-line chemotherapy drug, often causes myelosuppression in patients, thus limiting its effectiveness. In this study, we discovered that C646, a reversible p300 inhibitor, downregulates p53 transcription and selectively protects noncancerous cells from p53-dependent apoptosis. C646 treatment blocked acetylation of specific lysine residues that regulate p53 activity. Exploitation of differential p53 genetic backgrounds between human hematopoietic and colorectal cancer cells improved the therapeutic index of doxorubicin with C646 cotreatment. C646 administration in mice afflicted with p53-mutant tumors protected them from doxorubicin-induced neutropenia and anemia while retaining antitumor efficacy. We deduce that temporary and reversible inhibition of p53 acetylation in cancer subjects, especially those with p53-mutant tumors, may protect them from severe chemotoxicity while allowing treatment regimens to effectively proceed. Cancer Res; 77(16); 4342–54. ©2017 AACR.
Inhibition of Megakaryocyte Differentiation by Antibody–Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC-induced Thrombocytopenia
Authors: Zhao Hui , Gulesserian Sara , Ganesan Sathish Kumar , Ou Jimmy , Morrison Karen , Zeng Zhilan , Robles Veronica , Snyder Josh , Do Lisa , Aviña Hector , Karki Sher , Stover David R. , Doñate Fernando
Published: June 2017

Thrombocytopenia is a common adverse event in cancer patients treated with antibody–drug conjugates (ADC), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MK) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers. Effects of AGS-16C3F, T-DM1, and control ADCs on maturing megakaryocytes were evaluated in an in vitro system in which human hematopoietic stem cells (HSC) were differentiated into MKs. AGS-16C3F, like T-DM1, did not affect platelets directly, but inhibited MK differentiation by the activity of Cys-mcMMAF, its active metabolite. FcγRIIA did not appear to play an important role in ADC cytotoxicity to differentiating MKs. AGS-16C3F, cytotoxic to MKs, did not bind to FcγRIIA on MKs. Blocking the interaction of T-DM1 with FcγRIIA did not prevent the inhibition of MK differentiation and IgG1-mcMMAF was not as cytotoxic to MKs despite binding to FcγRIIA. Several lines of evidence suggest that internalization of AGS-16C3F into MKs is mediated by macropinocytosis. Macropinocytosis activity of differentiating HSCs correlated with cell sensitivity to AGS-16C3F. AGS-16C3F was colocalized with a macropinocytosis marker, dextran-Texas Red in differentiating MKs. Ethyl isopropyl amiloride (EIPA), a macropinocytosis inhibitor, blocked internalization of dextran-Texas Red and AGS-16C3F. These data support the notion that inhibition of MK differentiation via macropinocytosis-mediated internalization plays a role in ADC-induced thrombocytopenia. Mol Cancer Ther; 16(9); 1877–86. ©2017 AACR.

See related article by Zhao et al., p. 1866
Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
Authors: Sadikot Ruxana T. , Kolanjiyil Arun V. , Kleinstreuer Clement , Rubinstein Israel
Published: June 2017

Acute lung injury and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients that continues to have high mortality. Despite the increased understanding of the molecular pathogenesis of ARDS, specific targeted treatments for ARDS have yet to be developed. ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Multiple promising targets have been identified that could lead to the development of potential therapies for ARDS; however, they have been limited because of difficulty with the mode of delivery, especially in critically ill patients. Nanobiotechnology is the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmacodynamics of agents, allowing an increase in the biodistribution of therapeutic agents to target organs and resulting in improved efficacy with reduction in drug toxicity. Although attractive, delivering nanomedicine to lungs can be challenging as it requires sophisticated systems. Here we review the potential of novel nanomedicine approaches that may prove to be therapeutically beneficial for the treatment of this devastating condition.
Natural history of the critically endangered salamander Ambystoma leorae (Caudata: Ambystomatidae) from the Río Tonatzin, Mexico
Authors: Lemos-Espinal Julio A. , Smith Geoffrey R. , Zamora Aline B. Estrella , WoolrichPiña Guillermo , Ayala Raymundo Montoya
Published: June 2017

In Mexico, many species of Ambystoma are endangered, but unfortunately little is known about their natural history and ecology. We report on aspects of the natural history of A. leorae, a critically endangered endemic salamander, from the Río Tonatzin, State of México, Mexico. We observed egg masses, which were attached to vegetation, from April to June, with a mean of 7.28 eggs per egg mass. Larval A. leorae were found in sections of the Río Tonatzin with muddy bottoms and submerged aquatic vegetation. We observed adult and juvenile salamanders throughout the year except September, but with a peak from May to July. The use of sites along the Río Tonatzin by adult and juvenile A. leorae was driven primarily by vegetation type and substrate type of the site, with mud or sand substrate with grass roots and submerged aquatic vegetation being the most used site types. We found no evidence of sexual dimorphism in A. leorae. Our results suggest that adult and juvenile A. leorae use a variety of stream sites, although larvae appear to be more limited in their use of stream sites. These observations indicate that to maintain this population of A. leorae, the general conditions existing in the Río Tonatzin should be protected, especially the sections with muddy bottoms and aquatic vegetation where larvae, juveniles, and adults are found
Optimal Transport Destination for Ischemic Stroke Patients With Unknown Vessel Status
Authors: Schlemm Eckhard , Ebinger Martin , Nolte Christian H. , Endres Matthias , Schlemm Ludwig
Published: June 2017

Background and Purpose—

Patients with acute ischemic stroke (AIS) and large vessel occlusion may benefit from direct transportation to an endovascular capable comprehensive stroke center (mothership approach) as opposed to direct transportation to the nearest stroke unit without endovascular therapy (drip and ship approach). The optimal transport strategy for patients with AIS and unknown vessel status is uncertain. The rapid arterial occlusion evaluation scale (RACE, scores ranging from 0 to 9, with higher scores indicating higher stroke severity) correlates with the National Institutes of Health Stroke Scale and was developed to identify patients with large vessel occlusion in a prehospital setting. We evaluate how the RACE scale can help to inform prehospital triage decisions for AIS patients.

Methods—

In a model-based approach, we estimate probabilities of good outcome (modified Rankin Scale score of ≤2 at 3 months) as a function of severity of stroke symptoms and transport times for the mothership approach and the drip and ship approach. We use these probabilities to obtain optimal RACE cutoff scores for different transfer time settings and combinations of treatment options (time-based eligibility for secondary transfer under the drip and ship approach, time-based eligibility for thrombolysis at the comprehensive stroke center under the mothership approach).

Results—

In our model, patients with AIS are more likely to benefit from direct transportation to the comprehensive stroke center if they have more severe strokes. Values of the optimal RACE cutoff scores range from 0 (mothership for all patients) to >9 (drip and ship for all patients). Shorter transfer times and longer door-to-needle and needle-to-transfer (door out) times are associated with lower optimal RACE cutoff scores.

Conclusions—

Use of RACE cutoff scores that take into account transport times to triage AIS patients to the nearest appropriate hospital may lead to improved outcomes. Further studies should examine the feasibility of translation into clinical practice.
Picturing Saul’s Vision on the Road to Damascus: A Question of Authority
Authors: Prince Deborah Thompson
Published: June 2017

Saul’s vision of the risen Jesus on the road to Damascus (Acts 9:1-9) has been a popular theme for artists over the centuries because it expresses something meaningful to both the artists and their audiences. Meaning, however, changes over time. My aim in this article is to explore how and why the narrative of Acts asserts the authority of Saul’s vision and how audience perception of this authority evolved over time, as evident in artistic representations of Saul’s vision. By employing literary and rhetorical analysis, I will clarify the claim that the author of Acts employs this vision as a reliable message from God by exploring two related issues: (1) the centrality of the life of the community to the function of the vision; and (2) the establishment of credibility by means of the shared visionary experiences of unrelated corroborative witnesses. However, as many visual interpretations of Saul’s vision indicate, the conception of this vision encounter as divine guidance for a whole community did not continue to be a central part of its value for later Christians. On the contrary, Paul’s personal authority and/or transformation become(s) the significant outcome of the vision for later audiences. Therefore, this article will also engage in the study of reception history to show how perception of the authority granted to this vision changed over time and ultimately reframed the power of the vision by elevating the transformation of the individual over the transformation of the community.
The Igor’ Tale and the Origins of Conspiracy Theory
Authors: Ingham † Norman W.
Published: June 2017

In his 2004 lecture delivered at Harvard, Norman W. Ingham critiques Edward L. Keenan’s controversial book Joseph Dobrovský and the Origins of the Igor’ Tale (Slovo o polku Igoreve) and argues that Keenan’s claims against the poem’s authenticity are not convincing.