bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical simulation of environmentally induced thin shell deformation
Authors: Chen Hsiao-Yu , Sastry Arnav , van Rees Wim M. , Vouga Etienne
Published: July 2018

We present a physically accurate low-order elastic shell model that incorporates active material response to dynamically changing stimuli such as heat, moisture, and growth. Our continuous formulation of the geometrically non-linear elastic energy derives from the principles of differential geometry, and as such naturally incorporates shell thickness, non-zero rest curvature, and physical material properties. By modeling the environmental stimulus as local, dynamic changes in the rest metric of the material, we are able to solve for the corresponding shape changes by integrating the equations of motions given this non-Euclidean rest state. We present models for differential growth and shrinking due to moisture and temperature gradients along and across the surface, and incorporate anisotropic growth by defining an intrinsic machine direction within the material. Comparisons with experiments and volumetric finite elements show that our simulations achieve excellent qualitative and quantitative agreement. By combining the reduced-order shell theory with appropriate physical models, our approach accurately captures all the physical phenomena while avoiding expensive volumetric discretization of the shell volume.
Example-based turbulence style transfer
Authors: Sato Syuhei , Dobashi Yoshinori , Kim Theodore , Nishita Tomoyuki
Published: July 2018

Generating realistic fluid simulations remains computationally expensive, and animators can expend enormous effort trying to achieve a desired motion. To reduce such costs, several methods have been developed in which high-resolution turbulence is synthesized as a post process. Since global motion can then be obtained using a fast, low-resolution simulation, less effort is needed to create a realistic animation with the desired behavior. While much research has focused on accelerating the low-resolution simulation, the problem controlling the behavior of the turbulent, high-resolution motion has received little attention. In this paper, we show that
style transfer
methods from image editing can be adapted to transfer the turbulent style of an existing fluid simulation onto a new one. We do this by extending example-based image synthesis methods to handle velocity fields using a combination of patch-based and optimization-based texture synthesis. This approach allows us to take into account the incompressibility condition, which we have found to be a important factor during synthesis. Using our method, a user can easily and intuitively create high-resolution fluid animations that have a desired turbulent motion.
Adaptive Process Migrations in Coupled Applications for Exchanging Data in Local File Cache
Authors: Liao Jianwei , Cai Zhigang , Trahay Francois , Zhou Jun , Xiao Guoqiang
Published: July 2018

Many problems in science and engineering are usually emulated as a set of mutually interacting models, resulting in a coupled or multiphysics application. These component models show challenges originating from their interdisciplinary nature and from their computational and algorithmic complexities. In general, these models are independently developed and maintained, so that they commonly employ the global file system for exchanging their data in the coupled application.

To effectively use the local file cache on the compute node for exchanging the data among the processes of such applications, and consequently boosting I/O performance, this article presents a novel mechanism to migrate a process from one compute node to another node on the basis of block I/O dependency. In this newly proposed mechanism, the block I/O dependency between two involved processes running on the different nodes is profiled as block access similarity by taking advantage of the
Cohen’s kappa statistic
. Then, the process is supposed to be dynamically migrated from its source node to the destination node, on which there is another process having heavy block I/O dependency. As a result, both processes can exchange their data by utilizing the local file cache instead of the global file system to reduce I/O time. The experimental results demonstrate that the I/O performance can be significantly improved, and the time required for executing the application can be resultantly decreased, as expected.
The challenges of outreaching
Authors: Guo Jinhong K. , Paradis Rosemary
Published: July 2018

According to Wikipedia,
"outreaching is an activity of providing services to any populations who might not otherwise have access to those services"
. Most people would have been the target of a fund raising campaign at some point, be it public radio during its annual fund raising or an alma mater fund raising event. While some of us may respond because it is a good cause or it aligns with our interests, out-reaching has always been very challenging. We recently met with some ACM groups that have been successful in getting members and outreaching to new people. This short paper summarizes what we learned from the conversations and discovered from our recent activities.
Non-intervention policy for autonomous cars in a trolley dilemma scenario
Authors: Ximenes Bianca Helena
Published: July 2018

This column presents early work on human biases and preferences described in research from Philosophical and Social Sciences, and discusses their impact in AI ethics, especially concerning autonomous vehicles.
Handling delimited continuations with dependent types
Authors: Cong Youyou , Asai Kenichi
Published: July 2018

Dependent types are a powerful tool for maintaining program invariants. To take advantage of this aspect in real-world programming, efforts have been put into enriching dependently typed languages with missing constructs, most notably, effects. This paper presents a language that has two practically interesting ingredients: dependent inductive types, and the delimited control constructs shift and reset. When integrating delimited control into a dependently typed language, however, two challenges arise. First, the dynamic nature of control operators, which is the source of their expressiveness, can break fundamental language properties such as logical consistency and subject reduction. Second, CPS translations, which we often use to define the semantics of control operators, do not scale straightforwardly to dependently typed languages. We solve the former issue by restricting dependency of types, and the latter using answer-type polymorphism of pure terms. The main contribution of this paper is to give a sound type system of our language, as well as a type-preserving CPS translation. We also discuss various extensions, which would make our language more like a full-spectrum proof assistant but pose non-trivial issues.
Mtac2: typed tactics for backward reasoning in Coq
Authors: Kaiser Jan-Oliver , Ziliani Beta , Krebbers Robbert , Régis-Gianas Yann , Dreyer Derek
Published: July 2018

Coq supports a range of built-in tactics, which are engineered primarily to support
backward reasoning
. Starting from a desired goal, the Coq programmer can use these tactics to manipulate the proof state interactively, applying axioms or lemmas to break the goal into subgoals until all subgoals have been solved. Additionally, it provides support for
tactic programming
via OCaml and Ltac, so that users can roll their own custom proof automation routines.

Unfortunately, though, these tactic languages share a significant weakness. They do not offer the tactic programmer any static guarantees about the soundness of their custom tactics, making large tactic developments difficult to maintain. To address this limitation, Ziliani et al. previously proposed
Mtac
, a new typed approach to custom proof automation in Coq which provides the static guarantees that OCaml and Ltac are missing. However, despite its name, Mtac is really more of a metaprogramming language than it is a full-blown tactic language: it misses an essential feature of tactic programming, namely the ability to directly manipulate Coq’s proof state and perform backward reasoning on it.

In this paper, we present
Mtac2
, a next-generation version of Mtac that combines its support for typed metaprogramming with additional support for the programming of backward-reasoning tactics in the style of Ltac. In so doing, Mtac2 introduces a novel feature in tactic programming languages—what we call
typed backward reasoning
. With this feature, Mtac2 is capable of statically ruling out several classes of errors that would otherwise remain undetected at tactic definition time. We demonstrate the utility of Mtac2’s typed tactics by porting several tactics from a large Coq development, the Iris Proof Mode, from Ltac to Mtac2.
Synthesizing quotient lenses
Authors: Maina Solomon , Miltner Anders , Fisher Kathleen , Pierce Benjamin C. , Walker David , Zdancewic Steve
Published: July 2018

Quotient lenses
are bidirectional transformations whose correctness laws are “loosened” by specified equivalence relations, allowing inessential details in concrete data formats to be suppressed. For example, a programmer could use a quotient lens to define a transformation that ignores the order of fields in XML data, so that two XML files with the same fields but in different orders would be considered the same, allowing a single, simple program to handle them both. Building on a recently published algorithm for synthesizing plain bijective lenses from high-level specifications, we show how to synthesize bijective quotient lenses in three steps. First, we introduce
quotient regular expressions
(QREs), annotated regular expressions that conveniently mark inessential aspects of string data formats; each QRE specifies, simulteneously, a regular language and an equivalence relation on it. Second, we introduce
QRE lenses
, i.e., lenses mapping between QREs. Our key technical result is a proof that every QRE lens can be transformed into a functionally equivalent lens that canonizes source and target data just at the “edges” and that uses a bijective lens to map between the respective canonical elements; no internal canonization occurs in a lens in this normal form. Third, we leverage this normalization theorem to
synthesize
QRE lenses from a pair of QREs and example input-output pairs, reusing earlier work on synthesizing plain bijective lenses. We have implemented QREs and QRE lens synthesis as an extension to the bidirectional programming language Boomerang. We evaluate the effectiveness of our approach by synthesizing QRE lenses between various real-world data formats in the Optician benchmark suite.
Teaching how to program using automated assessment and functional glossy games (experience report)
Authors: Almeida José Bacelar , Cunha Alcino , Macedo Nuno , Pacheco Hugo , Proença José
Published: July 2018

Our department has long been an advocate of the functional-first school of programming and has been teaching Haskell as a first language in introductory programming course units for 20 years. Although the functional style is largely beneficial, it needs to be taught in an enthusiastic and captivating way to fight the unusually high computer science drop-out rates and appeal to a heterogeneous population of students.

This paper reports our experience of restructuring, over the last 5 years, an introductory laboratory course unit that trains hands-on functional programming concepts and good software development practices. We have been using
game programming
to keep students motivated, and following a methodology that hinges on
test-driven development
and
continuous bidirectional feedback
.

We summarise successes and missteps, and how we have learned from our experience to arrive at a model for comprehensive and interactive functional
game programming assignments
and a general functionally-powered
automated assessment platform
, that together provide a more engaging learning experience for students. In our experience, we have been able to teach increasingly more advanced functional programming concepts while improving student engagement.
Relational algebra by way of adjunctions
Authors: Gibbons Jeremy , Henglein Fritz , Hinze Ralf , Wu Nicolas
Published: July 2018

Bulk types such as sets, bags, and lists are monads, and therefore support a notation for database queries based on comprehensions. This fact is the basis of much work on database query languages. The monadic structure easily explains most of standard relational algebra---specifically, selections and projections---allowing for an elegant mathematical foundation for those aspects of database query language design. Most, but not all: monads do not immediately offer an explanation of relational join or grouping, and hence important foundations for those crucial aspects of relational algebra are missing. The best they can offer is cartesian product followed by selection. Adjunctions come to the rescue: like any monad, bulk types also arise from certain adjunctions; we show that by paying due attention to other important adjunctions, we can elegantly explain the rest of standard relational algebra. In particular, graded monads provide a mathematical foundation for indexing and grouping, which leads directly to an efficient implementation, even of joins.
Partially-static data as free extension of algebras
Authors: Yallop Jeremy , von Glehn Tamara , Kammar Ohad
Published: July 2018

Partially-static data structures are a well-known technique for improving binding times. However, they are often defined in an ad-hoc manner, without a unifying framework to ensure full use of the equations associated with each operation.

We present a foundational view of partially-static data structures as free extensions of algebras for suitable equational theories, i.e. the coproduct of an algebra and a free algebra in the category of algebras and their homomorphisms. By precalculating these free extensions, we construct a high-level library of partially-static data representations for common algebraic structures. We demonstrate our library with common use-cases from the literature: string and list manipulation, linear algebra, and numerical simplification.
What’s the difference? a functional pearl on subtracting bijections
Authors: Yorgey Brent A. , Foner Kenneth
Published: July 2018

It is a straightforward exercise to write a program to "add" two bijections---resulting in a bijection between two sum types, which runs the first bijection on elements from the left summand and the second bijection on the right. It is much less obvious how to "subtract" one bijection from another. This problem has been studied in the context of combinatorics, with several computational principles known for producing the "difference" of two bijections. We consider the problem from a computational and algebraic perspective, showing how to construct such bijections at a high level, avoiding pointwise reasoning or being forced to construct the forward and backward directions separately---without sacrificing performance.
Reasonably programmable literal notation
Authors: Omar Cyrus , Aldrich Jonathan
Published: July 2018

General-purpose programming languages typically define literal notation for only a small number of common data structures, like lists. This is unsatisfying because there are many other data structures for which literal notation might be useful, e.g. finite maps, regular expressions, HTML elements, SQL queries, syntax trees for various languages and chemical structures. There may also be different implementations of each of these data structures behind a common interface that could all benefit from common literal notation. This paper introduces
typed literal macros (TLMs)
, which allow library providers to define new literal notation of nearly arbitrary design at any specified type or parameterized family of types. Compared to existing approaches, TLMs are uniquely
reasonable
. TLM clients can reason abstractly, i.e. without examining grammars or generated expansions, about types and binding. The system only needs to convey to clients, via secondary notation, the inferred
segmentation
of each literal body, which gives the locations and types of spliced subterms. TLM providers can reason modularly about syntactic ambiguity and expansion correctness according to clear criteria. This paper incorporates TLMs into Reason, an emerging alternative front-end for OCaml, and demonstrates, through several non-trivial case studies, how TLMs integrate with the advanced features of OCaml, including pattern matching and the module system. We also discuss optional integration with MetaOCaml, which allows TLM providers to be more confident about type correctness. Finally, we establish these abstract reasoning principles formally with a detailed type-theoretic account of expression and pattern TLMs for “core ML”.
Editors opine
Authors: Weikle Dee A. B.
Published: July 2018

The first two articles in this issue are introduced by the Digital Government Area Editor, Carlos Jimenez Gomez. These articles highlight the importance of open innovation and the data scientist for the future of this important area.
The search for the data scientist
Authors: Luna-Reyes Luis Felipe
Published: July 2018

The Internet of Things and Big Data trends are promoting changes in the professional and educational practices of experts in the fields of information, information technologies, computer science and operations management. Although new contents on big data and data analysis are being added to undergraduate and graduate courses, there is still the need of a better understanding of the skills, competencies and values of the Data Scientist. In this essay, I suggest a framework that includes five core sets of competencies to become an effective analyst and decision analysis steward. Skills of the data scientist are so diverse in nature that it is more likely that data science evolve from individual positions into a collective effort involving experts in different domain areas and levels of technical expertise coming from different organizational areas.
Security, privacy'); drop table users; - and forced trust in the information age?
Authors: Hakkala Antti , Heimo Olli I. , Hyrynsalmi Sami , Kimppa Kai K.
Published: July 2018

In this study, we discuss forced trust in the context of information systems, information society and surveillance. Trust definitions and concepts pertinent to the discussion are examined and portrayed with case examples of forced trust in different situations that are central to the information society. As forced trust appears mostly in governmental information systems, we reflect the concept from security and privacy point-of-view, concepts that are important for users of such systems in the current age of information. We portray the trust landscape of critical governmental information systems and discuss forced trust also in the context of Internet infrastructure and mass surveillance. We provide a glimpse of an information society that combines security, trust, and privacy, while also providing discussion on what kind of trust dynamics such a utopia would require.
Narrative technologies meets virtue ethics in alternate reality
Authors: Reijers Wessel , Coeckelbergh Mark
Published: July 2018

Virtue ethics offers a promising starting point for thinking about ethics of technology. Usually, virtue ethics of technology focuses on explaining how we can cultivate our technomoral virtues to cope with technological change. However, it is not clear yet how exactly technologies in turn mediate technomoral virtues, or more precisely how the technological practices that cultivate these virtues do so. Inspired by Ricoeur and MacIntyre, this paper responds to this challenge with an account of technological mediation based on Ricoeur's narrative theory, and explores the possibility of a narrative virtue ethics of technology. We argue that the virtues are technologically mediated because particular technologies configure the practices by which people cultivate their virtues. We demonstrate how this approach could be applied by discussing the example of Pokémon Go: an alternate reality game that enjoyed a brief time of great global popularity and allows players to act through the game in the real world.
TussleOS
Authors: Singh Rayman Preet , Cassell Benjamin , Keshav S. , Brecht Tim
Published: July 2018

Networked sensors and actuators are increasingly permeating our computing devices, and provide a variety of functions for Internet of Things (IoT) devices and applications. However, this sensor data can also be used by applications to extract private information about users. Applications and users are thus in a
tussle
over access to private data. Tussles occur in operating systems when stakeholders with competing interests try to access shared resources such as sensor data, CPU time, or network bandwidth. Unfortunately, existing operating systems lack a principled approach for identifying, tracking, and resolving such tussles. Moreover, users typically have little control over how tussles are resolved. Controls for sensor data tussles, for example, often fail to address trade-offs between functionality and privacy. Therefore, we propose a framework to explicitly recognize and manage tussles. Using sensor data as an example resource, we investigate the design of mechanisms for detecting and resolving privacy tussles in a cyber-physical system, enabling privacy and functionality to be negotiated between users and applications. In doing so, we identify shortcomings of existing research and present directions for future work.
New kid on the block
Authors: Nobach Leonhard , Hohlfeld Oliver , Hausheer David
Published: July 2018

Network management currently undergoes massive changes towards realizing more flexible management of complex networks. Recent efforts include slicing data plane resources by network (link) virtualization and applying operating system design principles to Software Defined Networking to rethink network management. Driven by network operators, network management principles are currently envisioned to be even further improved by virtualizing network (middlebox) functions. The resulting Network Functions Virtualization (NFV) paradigm abstracts network functions from dedicated hardware to virtual machines running on commodity hardware. This change in the design of carrier networks is inspired by the success of virtualization in the server market. By deploying NFV, network operators envision to achieve benefits similar to the server market and elastic cloud services, e.g., flexible and dynamic service provisioning, increased resource utilization, improved energy efficiency, and ultimately decreased operational costs. Despite these efforts, the ability of NFV to satisfy performance demands is often questioned. Tackling these challenges opens a set of research questions that felt short in the current discussion and are of particular relevance to the SIGCOMM community. In this position paper, we therefore provide an overview on the current state-of-the-art and open research questions.
Research and infrastructure challenges for applications and services in the year 2021
Authors: Calyam Prasad , Ricart Glenn
Published: July 2018

The
Applications and Services in the Year 2021
workshop was successfully organized on January 27--28, 2016 in Washington DC through funding support from the National Science Foundation (NSF). The goal of the workshop was to foster discussions that bring together applications researchers in multidisciplinary areas, and developers/operators of research infrastructures at both national, regional, university and city levels. Discussions were organized to identify grand challenge applications and obtain the community voice and consensus on the key issues relating to applications and services that might be delivered by advanced infrastructures in the decade beginning in 2020. The timing and organization for the workshop is significant because today's digital infrastructure is undergoing deep technological changes and new paradigms are rapidly taking shape in both the core and edge domains that pose fundamental challenges. The key outcomes of the discussions were targeted to enhance the quality of peoples' lives while addressing important national priorities, leveraging today's cutting edge applications such as the Internet of Things, Big Data Analytics, Robotics, The Industrial Internet, and Immersive Virtual/Augmented Reality. This report summarizes the workshop efforts to bring together diverse groups for delivering targeted short/long talks, sharing latest advances, and identifying gaps that exist in the community for 'research' and 'infrastructure' needs that require future NSF funding.
Research impacting the practice of congestion control
Authors: Dukkipati Nandita , Cheng Yuchung , Vahdat Amin
Published: July 2018

Many algorithms proposed in networking research papers are widely used in many areas, including Congestion Control, Routing, Traffic Engineering, and Load Balancing. In this paper, we present algorithmic advancements that have impacted the practice of Congestion Control (CC) in datacenters and the Internet. Where possible, we also describe negative examples, ideas that looked promising on paper or in simulations but that performed poorly in practice. We conclude the paper with observations on the characteristics shared by these ideas in taking them from research to impacting practice.
Human Neutrophil Defensin-1, -3, and -4 Are Elevated in Nasal Aspirates from Children with Naturally Occurring Adenovirus Infection
Authors: Priyadharshini V. S. , Ramírez-Jiménez F. , Molina-Macip M. , Renteria-Rosales C. , Santiago-Cruz J. , Zarate-Segura Paola , Lara-Padilla E. , Teran Luis M.
Published: July 2018

Background. Adenoviruses are highly contagious pathogens which cause respiratory disease particularly in children; they may induce severe disease in infants. Human neutrophil peptides (HNPs) have been found to exhibit antiadenoviral activity. Thus, we have investigated HNPs in nasal aspirates (NAs) of children suffering from adenoviral common cold.Objective. To investigate the release of HNP-1–4 in adenovirus infection and the relationship with self-limiting upper respiratory tract infections.Methods. Nasal aspirate samples (n=14) were obtained from children (aged 6–12 years) infected with adenovirus between June 2012 and December 2015. Control samples were taken 4 weeks after infection when the children were asymptomatic. Levels of HNPs were measured using an enzyme-linked immunosorbent assay (ELISA).Results. There were increased levels of HNP-1, -3, and -4, but not HNP-2, in nasal aspirates (NAs) during adenovirus infections compared to healthy specimens (p≤0.01). Moreover, there was also increase in the neutrophil count, which is a known cell source of HNPs.Conclusion. Our finding supports the involvement of HNP-1, -3, and -4 in naturally occurring cold in children infected with adenovirus. Because of their known antiviral properties, it is tempting to hypothesize that HNPs might play a protective role in adenovirus-induced respiratory disease; however, this remains to be shown.
Postnatal Development of Microglia-Like Cells in Mouse Cochlea
Authors: Chen Penghui , Chai Yongchuan , Liu Haijin , Li Gen , Wang Longhao , Yang Tao , Wu Hao
Published: July 2018

Microglial cells are involved in surveillance and cleaning of the central nervous system. Recently, microglial-like cells (MLC) have been found in an adult cochlea and investigated for their role in cochlear inflammation. The presence and potential roles of MLCs during the development of the cochlea, however, remain unclear. In this study, immunostaining was performed using the MLC-specific marker IBA1 to characterize the presence, distribution, and morphology of MLCs in the developing cochlea. From P0 to P14, MLCs were present in a variety of cochlear regions including the modiolus, spiral lamina, spiral ganglion, spiral ligament, and the organ of Corti. Interestingly, the overall number of MLCs in a mouse cochlea steadily increased since P0, peaks at P5, then gradually decreased from P5 to P14. In the spiral ligament, the distribution of the MLCs trends to shift from the type I/II fibrocyte-rich regions to the type III/IV fibrocyte-rich regions during the course of cochlear development, accompanied by the morphological changes of MLCs from the amoeboid, activated form to the ramified, quiescent form. Our results suggested that MLCs experience drastic morphological and distributional changes during postnatal cochlear development, which may play a role in the maturing and remodeling of the cochlea.
Effectiveness of Sequential Viscosupplementation in Temporomandibular Joint Internal Derangements and Symptomatology: A Case Series
Authors: Fonseca Roberta Maria Drumond Furtado Bossi , Januzzi Eduardo , Ferreira Luciano Ambrosio , Grossmann Eduardo , Carvalho Antonio Carlos Pires , Oliveira Pedro Gonçalves de , Vieira Érica Leandro Marciano , Teixeira Antônio Lúcio , Almeida-Leite Camila Megale
Published: July 2018

Viscosupplementation is a minimally invasive technique that replaces synovial fluid by intra-articular injection of hyaluronic acid (HA). Although effective in some joints, there is not conclusive evidence regarding temporomandibular disorders. This case series described the efficacy of a viscosupplementation protocol in intra-articular temporomandibular disorders. Ten patients with a diagnosis of disc displacement and/or osteoarthritis by Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were submitted to four monthly injections of low or medium molecular weight HA. Pain, mandibular function, image analysis by tomography and magnetic resonance, and quality of life were assessed at baseline and follow-ups (1 and 6 months). Pain, jaw range-of-motion, mandibular function, and quality of life improved at follow-up evaluations. Osteoarthritis changes decreased, and 20% of patients improved mandibular head excursion after treatment. Resolution of effusion and improvement in disc morphology were observed for most patients. This viscosupplementation protocol reduced pain and symptoms associated with internal derangement of temporomandibular joint, improved quality of life, and showed benefits from both low and medium molecular weight HA in alternate cycles.
The Place of In Vitro Maturation in PCO/PCOS
Authors: Julania Shital , Walls Melanie L. , Hart Roger
Published: July 2018

In vitro maturation (IVM) of human oocytes is an emerging treatment option for women with polycystic ovary/polycystic ovary syndrome (PCO/PCOS) in addition to the standard in vitro fertilization (IVF) treatment. There has been significant improvements in pregnancy rates with IVM over the last two decades. This article reviews the place of IVM for women with PCO/PCOS, placing an emphasis on the predictors of successful pregnancy, optimization of culture media, IVM protocols, pregnancy rates, and neonatal outcomes following IVM treatment.
In Vitro and In Vivo Characterization of N-Acetyl-L-Cysteine Loaded Beta-Tricalcium Phosphate Scaffolds
Authors: Jang Yong-Seok , Manivong Phonelavanh , Kim Yu-Kyoung , Kim Kyung-Seon , Lee Sook-Jeong , Bae Tae-Sung , Lee Min-Ho
Published: July 2018

Beta-tricalcium phosphate bioceramics are widely used as bone replacement scaffolds in bone tissue engineering. The purpose of this study is to develop beta-tricalcium phosphate scaffold with the optimum mechanical properties and porosity and to identify the effect of N-acetyl-L-cysteine loaded to beta-tricalcium phosphate scaffold on the enhancement of biocompatibility. The various interconnected porous scaffolds were fabricated using slurries containing various concentrations of beta-tricalcium phosphate and different coating times by replica method using polyurethane foam as a passing material. It was confirmed that the scaffold of 40 w/v% beta-tricalcium phosphate with three coating times had optimum microstructure and mechanical properties for bone tissue engineering application. The various concentration of N-acetyl-L-cysteine was loaded on 40 w/v% beta-tricalcium phosphate scaffold. Scaffold group loaded 5 mM N-acetyl-L-cysteine showed the best viability of MC3T3-E1 preosteoblastic cells in the water-soluble tetrazolium salt assay test.
Collaborative Filtering Recommendation Algorithm Based on Knowledge Graph
Authors: Mu Ruihui , Zeng Xiaoqin
Published: July 2018

To solve the problem that collaborative filtering algorithm only uses the user-item rating matrix and does not consider semantic information, we proposed a novel collaborative filtering recommendation algorithm based on knowledge graph. Using the knowledge graph representation learning method, this method embeds the existing semantic data into a low-dimensional vector space. It integrates the semantic information of items into the collaborative filtering recommendation by calculating the semantic similarity between items. The shortcoming of collaborative filtering algorithm which does not consider the semantic information of items is overcome, and therefore the effect of collaborative filtering recommendation is improved on the semantic level. Experimental results show that the proposed algorithm can get higher values on precision, recall, and F-measure for collaborative filtering recommendation.
Copper Chelation as Targeted Therapy in a Mouse Model of Oncogenic BRAF-Driven Papillary Thyroid Cancer
Authors: Xu MengMeng , Casio Michael , Range Danielle E. , Sosa Julie A. , Counter Christopher M.
Published: July 2018

Purpose: Sixty percent of papillary thyroid cancers (PTC) have an oncogenic (V600E) BRAF mutation. Inhibitors of BRAF and its substrates MEK1/2 are showing clinical promise in BRAFV600E PTC. PTC progression can be decades long, which is challenging in terms of toxicity and cost. We previously found that MEK1/2 require copper (Cu) for kinase activity and can be inhibited with the well-tolerated and economical Cu chelator tetrathiomolybdate (TM). We therefore tested TM for antineoplastic activity in BRAFV600E-positive PTC.

Experimental Design: The efficacy of TM alone and in combination with current standard-of-care lenvatinib and sorafenib or BRAF and MEK1/2 inhibitors vemurafenib and trametinib was examined in BRAFV600E-positive human PTC cell lines and a genetically engineered mouse PTC model.

Results: TM inhibited MEK1/2 kinase activity and transformed growth of PTC cells. TM was as or more potent than lenvatinib and sorafenib and enhanced the antineoplastic activity of sorafenib and vemurafenib. Activated ERK2, a substrate of MEK1/2, overcame this effect, consistent with TM deriving its antineoplastic activity by inhibiting MEK1/2. Oral TM reduced tumor burden and vemurafenib in a BrafV600E-positive mouse model of PTC. This effect was ascribed to a reduction of Cu in the tumors. TM reduced P-Erk1/2 in mouse PTC tumors, whereas genetic reduction of Cu in developing tumors trended towards a survival advantage. Finally, TM as a maintenance therapy after cessation of vemurafenib reduced tumor volume in the aforementioned PTC mouse model.

Conclusions: TM inhibits BRAFV600E-driven PTC through inhibition of MEK1/2, supporting clinical evaluation of chronic TM therapy for this disease. Clin Cancer Res; 24(17); 4271–81. ©2018 AACR.
Overstaging: A Challenge in Rectal Cancer Treatment
Authors: Scheele Jan , Schmidt Stefan Andreas , Tenzer Sandra , Henne-Bruns Doris , Kornmann Marko
Published: July 2018

Background: Preoperative staging, including computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS), is decisive to envisage the therapeutic concept for rectal cancer (RC). Overstaging may subject the patient to neoadjuvant therapy that does not improve survival but may lead to therapy-associated morbidity. Methods: This study retrospectively compares and values EUS, CT, and MRI in Union Internationale Contre le Cancer (UICC) stage I-III RC with a focus on overstaging. RC patients receiving primary operation only at the University Clinic Ulm were analyzed. The therapeutic relevance of preoperative staging was determined by comparison with postoperative pathological workup. Results: 244 examinations in 184 RC patients (EUS: n = 63, CT: n = 143, MRI: n = 38) revealed therapy-relevant overstaging into the T3/4 category in 10 (16%) EUS, 18 (13%) CT, and 10 (26%) MRI cases. Patients were upgraded to the N+ category in 13 (21%) EUS, 29 (20%) CT, and 11 (29%) MRI cases. As a result, UICC stages II and III turned out to be overstaged in 13 (21%) EUS, 18 (13%) CT, and 10 (26%) MRI cases. Conclusion: More than 10% therapy-relevant overstaging by any method represents a major challenge for modern RC therapy. Physicians should scrupulously consider this fact in their treatment considerations to avoid overtreatment.
Bradycardia and Hypotension from Improper Use of Aconite Root: A Case Report and Brief Review
Authors: Chou Pei-Ying , Wang Ching-Chiung , Tai Chen-Jei , Yang Tsung-Lin , Tang You-Jen
Published: July 2018

Background: Adverse reactions associated with Chinese herbal medicines (CHMs) are usually the result of unpredictable active/toxic ingredients, inaccurate or mistaken beliefs, or poor supervision. The herb that most commonly induces severe adverse effects in Hong Kong and China is aconite root. More than 200 species of Aconitum plants are used for medicinal purposes, with aconite roots producing analgesic, anti-inflammatory, cardiotonic, and anti-tumor effects. The active components are alkaloids; these can be toxic, but CHM processing methods lower their toxicity and increase the pharmacological efficacy. However, aconite poisoning can result from inadequate decoction time or exceeding the recommended dose. Case Report: Here we report the case of a 92-year-old woman who presented with life-threatening bradycardia and hypotension. This started 1 h after she inappropriately consumed a herbal decoction containing Fuzi for mood fluctuation and health maintenance; Fuzi, an aconite root, has known cardiotoxicity. Electrocardiography showed supraventricular abnormalities, including sinus bradycardia and low-amplitude P waves. After an infusion of normal saline and inotropic agents for 25 h, the clinical manifestations subsided, her sinus rhythm returned to normal, and she was discharged. At follow-up 2 weeks later, she was in good health and had ceased taking any CHM. Conclusions: Standardized processing methods, stringent regulations, and cooperation between health professions can ensure medication safety and establish a fully-fledged operating process for these valuable drugs. We hope this report will help establish correct attitudes toward CHM and will assist Traditional Chinese Medicine practitioners to become more familiar with Aconitum plants.
Stent Survival and Stent-Adjacent Stenosis Rates following Venous Sinus Stenting for Idiopathic Intracranial Hypertension: A Systematic Review and Meta-Analysis
Authors: Saber Hamidreza , Lewis Whitfield , Sadeghi Mahsa , Rajah Gary , Narayanan Sandra
Published: July 2018

Background: Idiopathic intracranial hypertension (IIH) is characterized by an elevated intracranial pressure without any identifiable causative factor such as an intracranial mass. Dural venous sinus stenosis (DVSS) has been suggested to be associated with IIH. Objective: We performed an updated systematic review and meta-analysis to determine clinical outcomes as well as stent survival and stent-adjacent stenosis rates in patients undergoing DVSS for the management of medically refractory IIH. Methods: We searched PubMed, Embase, and Cochrane databases to identify prospective or retrospective cohorts or case series of patients with IIH treated with DVSS between 2000 and 2017. Results: A total of 473 patients were included from 24 studies. Headache was present in 429 (91.8%) patients and resolved or improved in 319/413 (77.2%) after the procedure. Headache, papilledema, visual acuity, and tinnitus improved in 256/330 (77.6%), 247/288 (85.8%), 121/172 (70.3%), and 93/110 (84.5%) patients following DVSS at the final follow-up (mean of 18.3 months). In a meta-analysis of 395 patients with available follow-up data on stenting outcome (mean of 18.9 months), the stent survival and stent-adjacent stenosis rates were 84% (95% confidence interval [CI] 79–87%) and 14% (95% CI 11–18%), respectively. The rate of major neurological complications was less than 2%. Conclusion: Stent-adjacent stenosis is an important complication following venous stenting in patients with DVSS and IIH. Further studies are needed to identify determinants of stent-adjacent stenosis and stent nonsurvival.
Einseitige pulmonale Fibrose im Oberfeld als Spätfolge nach Thorakotomie
Authors: Lesser Thomas
Published: July 2018

Background: Pleuroparenchymal fibroelastosis (PPFE) is a rare bilateral idiopathic interstitial pneumonia defined by pleural-parenchymal involvement. In clinical practice, we encountered patients with upper lung field pulmonary fibrosis (Upper-PF), which was radiologically consistent with PPFE, but apparently limited to the unilateral lung. Objectives: The purpose of the study was to clarify the clinical characteristics in those patients. Methods: We examined the medical records of all the consecutive patients from 2012 to 2016 to see whether there were patients having unilateral Upper-PF. Results: We found 6 patients with unilateral Upper-PF. The most common symptom was dyspnea, and all patients had a low body mass index and severe restrictive pulmonary impairment. Notably, all patients had a history of thoracotomy for resecting lung or esophageal cancer, and the lesions were limited to the operated side. Dynamic breathing chest MRI showed an impaired thoracic movement in the operated side. Serial chest CT from prethoracotomy to the first visit was obtained in 5 patients: before thoracotomy, only a slight apical cap, defined as a wedge- and triangle-shaped opacity with broad pleural contact, was observed only in the operated side, but progressed into the lesion after a median of 8.4 years following thoracotomy. After the first visit, the unilateral lesion rapidly deteriorated in all patients. Conclusions: Unilateral Upper-PF had some characteristics in common with PPFE. Because the lesion was limited to the operated side, unilateral Upper-PF would be a new disease entity related to thoracotomy. Our results indicate that thoracotomy impairs thoracic movement in the operated side and subsequently triggers unilateral Upper-PF development, especially in patients with an apical cap.
Ist die ambulante Kontrolle der nicht-invasiven Langzeitbeatmung von COPD-Erkrankten möglich?
Authors: Lang Susanne
Published: July 2018

Background: Long-term non-invasive ventilation (NIV) is an established and increasingly used treatment option for patients with chronic hypercapnic chronic obstructive pulmonary disease (COPD). Following inpatient NIV establishment, inpatient control visits regularly occur thereafter. However, it remains unclear whether such control visits can also be performed in an outpatient setting, which, in turn, would reduce costs, patient burden and the complications related to hospitalization. Objectives: To investigate an outpatient setting with predefined criteria for hospitalization for patients with chronic hypercapnic COPD. Methods: An outpatient clinic located within the hospital in the vicinity of the respiratory care unit provided predefined criteria for hospitalization of COPD patients receiving long-term NIV therapy. The results of this setting were retrospectively analysed. Results: A total of 130 outpatient visits (80 patients) were analysed. In 93 cases (71.5%), hospital admission was not necessary, while hospitalization was performed in 37 cases (28.5%). Out of these, 7 cases with acute conditions required prompt hospitalization. Patients without hospitalization had better PaCO2 values (45.40 ± 5.27 vs. 50.05 ± 8.04, p = 0.002) and Severe Respiratory Insufficiency Questionnaire Summary scores (55.54 ± 19.74 vs. 41.82 ± 19.59, p = 0.012). Conclusion: Outpatient control of long-term NIV in a hospital setting is feasible and has the capacity to identify stable COPD patients in whom NIV therapy is sufficient according to predefined criteria. These patients may not require hospitalization and may account for more than two thirds of cases.
Lungenkrebs und Rauchen: Risikofaktor und Treiber der Mortalität - die aktualisierte S3-Leitlinie zum Lungenkarzinom
Authors: Schumann Christian
Published: July 2018

Hintergrund: Lungenkrebs zählt zu den häufigen Krebsarten. 2014 erkrankten in Deutschland knapp 35 000 Männer und mehr als 19 000 Frauen daran. Aufgrund der demografischen Entwicklung und steigender Inzidenzraten bei den Frauen prognostizieren Experten einen Anstieg der Erkrankungsfälle bis 2020. Da es für Lungenkrebs kaum Frühsymptome gibt, wird er oft erst im fortgeschrittenen Stadium entdeckt − die späte Diagnose ist mitverantwortlich für die hohe Sterblichkeit bei dieser Krebsart. Die Nutzen-Risiko-Abwägung der zur Verfügung stehenden Früherkennungsverfahren rechtfertigt aus medizinischer Sicht je- doch keine uneingeschränkt positive Empfehlung für ein Lungenkrebs-Screening. In bestimmten Fällen kann laut Leitlinie dennoch eine strahlenarme Computertomographie zur Früherkennung sinnvoll sein, z.B. bei Rauchern ab einem Alter von 50 Jahren, einer langjährigen Raucheranamnese (mehr als 20 Packungsjahre) und bestimmten weiteren Risikofaktoren, etwa, wenn eine chronisch-obstruktive Lungenerkrankung vorliegt oder in der Familie schon einmal Lungenkrebs aufgetreten ist. Die im Februar veröffentlichte aktuelle S3-Leitlinie «Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms» basiert auf der WHO-Klassifikation der Lungentumoren von 2015. Sie greift die neuesten wissenschaftlichen Erkenntnisse auf, u.a. eine neue Klassifikation der Adenokarzinome (Untergruppe der nicht-kleinzelligen Lungenkarzinome), immunpathologische Untersuchungen als Voraussetzung für die Festlegung einer medikamentösen Therapie sowie die neuen immuntherapeutischen Checkpoint-Inhibitoren. Ziele: Ziele der neuen S3-Leitlinie sind: die Unterstützung von Ärzten und von betroffenen Patienten mit einem erhöhten Risiko für ein Lungenkarzinom bei medizinischen Entscheidungen durch evidenzbasierte und formal konsentierte Empfehlungen, die Schaffung einer Grundlage für inhaltlich gezielte ärztliche Aus-, Fort- und Weiterbildungsmaßnahmen, eine flächendeckende Umsetzung einer multidisziplinären, qualitätsgesicherten und sektorübergreifenden Versorgung des Lungenkarzinoms, und die Optimierung der Diagnosekette und der stadiengerechten Therapie sowohl bei der Ersterkrankung als auch beim Rezidiv bzw. bei einer Metastasierung. Durch die Umsetzung dieser Ziele soll mittel- und langfristig die Mortalität der Patienten mit Lungenkarzinomen gesenkt und die Lebensqualität erhöht werden.