bluuebunny/crossref_metadata_2025 huggingface dataset:
Capturing the future by replaying the past (functional pearl)
Authors: Koppel James , Scherer Gabriel , Solar-Lezama Armando
Published: July 2018

Delimited continuations are the mother of all monads! So goes the slogan inspired by Filinski’s 1994 paper, which showed that delimited continuations can implement any monadic effect, letting the programmer use an effect as easily as if it was built into the language. It’s a shame that not many languages have delimited continuations.

Luckily, exceptions and state are also the mother of all monads! In this Pearl, we show how to implement delimited continuations in terms of exceptions and state, a construction we call
thermometer continuations
. While traditional implementations of delimited continuations require some way of ”capturing” an intermediate state of the computation, the insight of thermometer continuations is to reach this intermediate state by replaying the entire computation from the start, guiding it using a recording so that the same thing happens until the captured point.

Along the way, we explain delimited continuations and monadic reflection, show how the Filinski construction lets thermometer continuations express any monadic effect, share an elegant special-case for nondeterminism, and discuss why our construction is not prevented by theoretical results that exceptions and state cannot macro-express continuations.
MoSeL: a general, extensible modal framework for interactive proofs in separation logic
Authors: Krebbers Robbert , Jourdan Jacques-Henri , Jung Ralf , Tassarotti Joseph , Kaiser Jan-Oliver , Timany Amin , Charguéraud Arthur , Dreyer Derek
Published: July 2018

A number of tools have been developed for carrying out separation-logic proofs mechanically using an interactive proof assistant. One of the most advanced such tools is the Iris Proof Mode (IPM) for Coq, which offers a rich set of tactics for making separation-logic proofs look and feel like ordinary Coq proofs. However, IPM is tied to a particular separation logic (namely, Iris), thus limiting its applicability.

In this paper, we propose MoSeL, a general and extensible Coq framework that brings the benefits of IPM to a much larger class of separation logics. Unlike IPM, MoSeL is applicable to both affine and linear separation logics (and combinations thereof), and provides generic tactics that can be easily extended to account for the bespoke connectives of the logics with which it is instantiated. To demonstrate the effectiveness of MoSeL, we have instantiated it to provide effective tactical support for interactive and semi-automated proofs in six very different separation logics.
Build systems à la carte
Authors: Mokhov Andrey , Mitchell Neil , Peyton Jones Simon
Published: July 2018

Build systems are awesome, terrifying -- and unloved. They are used by every developer around the world, but are rarely the object of study. In this paper we offer a systematic, and executable, framework for developing and comparing build systems, viewing them as related points in landscape rather than as isolated phenomena. By teasing apart existing build systems, we can recombine their components, allowing us to prototype new build systems with desired properties.
Functional programming for modular Bayesian inference
Authors: Ścibior Adam , Kammar Ohad , Ghahramani Zoubin
Published: July 2018

We present an architectural design of a library for Bayesian modelling and inference in modern functional programming languages. The novel aspect of our approach are modular implementations of existing state-of-the-art inference algorithms. Our design relies on three inherently functional features: higher-order functions, inductive data-types, and support for either type-classes or an expressive module system. We provide a performant Haskell implementation of this architecture, demonstrating that high-level and modular probabilistic programming can be added as a library in sufficiently expressive languages. We review the core abstractions in this architecture: inference representations, inference transformations, and inference representation transformers. We then implement concrete instances of these abstractions, counterparts to particle filters and Metropolis-Hastings samplers, which form the basic building blocks of our library. By composing these building blocks we obtain state-of-the-art inference algorithms: Resample-Move Sequential Monte Carlo, Particle Marginal Metropolis-Hastings, and Sequential Monte Carlo Squared. We evaluate our implementation against existing probabilistic programming systems and find it is already competitively performant, although we conjecture that existing functional programming optimisation techniques could reduce the overhead associated with the abstractions we use. We show that our modular design enables deterministic testing of inherently stochastic Monte Carlo algorithms. Finally, we demonstrate using OCaml that an expressive module system can also implement our design.
A type and scope safe universe of syntaxes with binding: their semantics and proofs
Authors: Allais Guillaume , Atkey Robert , Chapman James , McBride Conor , McKinna James
Published: July 2018

Almost every programming language’s syntax includes a notion of binder and corresponding bound occurrences, along with the accompanying notions of α-equivalence, capture avoiding substitution, typing contexts, runtime environments, and so on. In the past, implementing and reasoning about programming languages required careful handling to maintain the correct behaviour of bound variables. Modern programming languages include features that enable constraints like scope safety to be expressed in types. Nevertheless, the programmer is still forced to write the same boilerplate over again for each new implementation of a scope safe operation (e.g., renaming, substitution, desugaring, printing, etc.), and then again for correctness proofs.

We present an expressive universe of syntaxes with binding and demonstrate how to (1) implement scope safe traversals once and for all by generic programming; and (2) how to derive properties of these traversals by generic proving. Our universe description, generic traversals and proofs, and our examples have all been formalised in Agda and are available in the accompanying material.

NB. we recommend printing the paper in colour to benefit from syntax highlighting in code fragments.
Static interpretation of higher-order modules in Futhark: functional GPU programming in the large
Authors: Elsman Martin , Henriksen Troels , Annenkov Danil , Oancea Cosmin E.
Published: July 2018

We present a higher-order module system for the purely functional data-parallel array language Futhark. The module language has the property that it is completely eliminated at compile time, yet it serves as a powerful tool for organizing libraries and complete programs. The presentation includes a static and a dynamic semantics for the language in terms of, respectively, a static type system and a provably terminating elaboration of terms into terms of an underlying target language. The development is formalised in Coq using a novel encoding of semantic objects based on products, sets, and finite maps. The module language features a unified treatment of module type abstraction and core language polymorphism and is rich enough for expressing practical forms of module composition.
Casts and costs: harmonizing safety and performance in gradual typing
Authors: Campora John Peter , Chen Sheng , Walkingshaw Eric
Published: July 2018

Gradual typing allows programmers to use both static and dynamic typing in a single program. However, a well-known problem with sound gradual typing is that the interactions between static and dynamic code can cause significant performance degradation. These performance pitfalls are hard to predict and resolve, and discourage users from using gradual typing features. For example, when migrating to a more statically typed program, often adding a type annotation will trigger a slowdown that can be resolved by adding more annotations elsewhere, but since it is not clear where the additional annotations must be added, the easier solution is to simply remove the annotation. To address these problems, we develop: (1) a static cost semantics that accurately predicts the overhead of static-dynamic interactions in a gradually typed program, (2) a technique for efficiently inferring such costs for all combinations of inferrable type assignments in a program, and (3) a method for translating the results of this analysis into specific recommendations and explanations that can help programmers understand, debug, and optimize the performance of gradually typed programs. We have implemented our approach in Herder, a tool for statically analyzing the performance of different typing configurations for Reticulated Python programs. An evaluation on 15 Python programs shows that Herder can use this analysis to accurately and efficiently recommend type assignments that optimize the performance of these programs without sacrificing the safety guarantees provided by static typing.
Functional programming for compiling and decompiling computer-aided design
Authors: Nandi Chandrakana , Wilcox James R. , Panchekha Pavel , Blau Taylor , Grossman Dan , Tatlock Zachary
Published: July 2018

Desktop-manufacturing techniques like 3D printing are increasingly popular because they reduce the cost and complexity of producing customized objects on demand. Unfortunately, the vibrant communities of early adopters, often referred to as "makers," are not well-served by currently available software pipelines. Users today must compose idiosyncratic sequences of tools which are typically repurposed variants of proprietary software originally designed for expert specialists.

This paper proposes fundamental programming-languages techniques to bring improved rigor, reduced complexity, and new functionality to the computer-aided design (CAD) software pipeline for applications like 3D-printing. Compositionality, denotational semantics, compiler correctness, and program synthesis all play key roles in our approach, starting from the perspective that solid geometry is a programming language.

Specifically, we define a purely functional language for CAD called LambdaCAD and a polygon surface-mesh intermediate representation. We then define denotational semantics of both languages to 3D solids and a compiler from CAD to mesh accompanied by a proof of semantics preservation. We illustrate the utility of this foundation by developing a novel synthesis algorithm based on evaluation contexts to "reverse compile" difficult-to-edit meshes downloaded from online maker communities back to more-editable CAD programs. All our prototypes have been implemented in OCaml to enable further exploration of functional programming for desktop manufacturing.
Refunctionalization of abstract abstract machines: bridging the gap between abstract abstract machines and abstract definitional interpreters (functional pearl)
Authors: Wei Guannan , Decker James , Rompf Tiark
Published: July 2018

Abstracting abstract machines is a systematic methodology for constructing sound static analyses for higher-order languages, by deriving small-step abstract abstract machines (AAMs) that perform abstract interpretation from abstract machines that perform concrete evaluation. Darais et al. apply the same underlying idea to monadic definitional interpreters, and obtain monadic abstract definitional interpreters (ADIs) that perform abstract interpretation in big-step style using monads. Yet, the relation between small-step abstract abstract machines and big-step abstract definitional interpreters is not well studied.

In this paper, we explain their functional correspondence and demonstrate how to systematically transform small-step abstract abstract machines into big-step abstract definitional interpreters. Building on known semantic interderivation techniques from the concrete evaluation setting, the transformations include linearization, lightweight fusion, disentanglement, refunctionalization, and the left inverse of the CPS transform. Linearization expresses nondeterministic choice through first-order data types, after which refunctionalization transforms the first-order data types that represent continuations into higher-order functions. The refunctionalized AAM is an abstract interpreter written in continuation-passing style (CPS) with two layers of continuations, which can be converted back to direct style with delimited control operators. Based on the known correspondence between delimited control and monads, we demonstrate that the explicit use of monads in abstract definitional interpreters is optional.

All transformations properly handle the collecting semantics and nondeterminism of abstract interpretation. Remarkably, we reveal how precise call/return matching in control-flow analysis can be obtained by refunctionalizing a small-step abstract abstract machine with proper caching.
InKeV
Authors: Ahmed Zaafar , Alizai Muhammad Hamad , Syed Affan A.
Published: July 2018

InKeV is a network virtualization platform based on eBPF, an in-kernel execution engine recently upstreamed into linux kernel. InKeV's key contribution is that it enables in-kernel programmability and configuration of virtualized network functions, allowing to create a distributed virtual network across all edges hosting tenant workloads.

Despite high performance demands of production environments, existing virtualization solutions have largely static in-kernel components due to the difficulty of developing and maintaining kernel modules and their years-long feature delivery time. The resulting compromise is either in programmability of network functions that rely on the data plane, such as payload processing, or in performance, due to expensive user-/kernel-space context switching.

InKeV addresses these concerns: The use of eBPF allows it to dynamically insert programmable network functions into a running kernel, requiring neither to package a custom-kernel nor to hope for acceptance in mainline kernel. Its novel
stitching
feature allows to flexibly configure complete virtual networks by creating a graph of network functions inside the kernel. Our evaluation reports on the flexibility of InKeV, and in-kernel implementation benefits such as low-latency and impressive flow creation rate.
Workshop on internet economics (WIE2015) report
Authors: Claffy K C , Clark David
Published: July 2018

On December 16--17 2015, we hosted the 5th interdisciplinary Workshop on Internet Economics (WIE) at the UC San Diego's Supercomputer Center. This workshop series provides a forum for researchers, Internet facilities and service providers, technologists, economists, theorists, policy makers, and other stakeholders to inform current and emerging regulatory and policy debates.

The FCC's latest open Internet order ostensibly changes the landscape of regulation by using Title II as its basis. This year we discussed the implications of Title II (common-carrier-based) regulation for issues we have looked at in the past, or those shaping current policy conversations. Discussion topics included differentiated services on the public Internet, evolving approaches to interconnection across different segments of the ecosystem (e.g., content to access), QoE and QoS measurement techniques and their limitations, interconnection measurement and modeling challenges and opportunities, and transparency. The format was a series of focused sessions, where presenters prepared 10-minute talks on relevant issues, followed by in-depth discussions. This report highlights the discussions and presents relevant open research questions identified by participants.
1
Concomitant Extramedullary Plasmacytoma in the Oropharynx and Hypopharyngeal Squamous Cell Carcinoma
Authors: Sato Hiroki , Yoshimasu Shoko , Okamoto Isaku , Shimizu Akira , Katsube Yasuaki , Tanaka Hideki , Tsukahara Kiyoaki
Published: July 2018

We report a rare case of hypopharyngeal squamous cell carcinoma occurring synchronously with extramedullary plasmacytoma (EPM) of the oropharynx in which radiotherapy was used as the curative treatment. A 73-year-old man presented with a sore throat that had persisted for 6 months. Examination revealed a superficial, smooth tumorous lesion at the base of his tongue with a red hue in the oropharynx. In addition, a protruding tumor was observed on the mucosal surface in the right piriform recess of the hypopharynx, and computed tomography revealed thickening of the pharyngeal wall at the right tongue base and in the right piriform recess of the hypopharynx. Because no definitive diagnosis could be reached for the lesion at the base of the tongue, the entire tongue-base tumor was resected by transoral surgery under endoscopy. Proliferation of plasma cells in the tumor was detected, and a bone marrow puncture test ruled out multiple myeloma leading to a definitive diagnosis of Stage I (cT1N0M0) squamous cell carcinoma in the right piriform recess of the hypopharynx and primary extramedullary plasmacytoma in the oropharynx. Radiotherapy was selected for curative treatment with a complete response for both cancers. No recurrences have been observed as of 12 months postoperatively.
Biochemical Assessment of Renal and Liver Function among Preeclamptics in Lagos Metropolis
Authors: Ekun Oloruntoba Ayodele , Olawumi Oluwatumininu Mary , Makwe Christian Chigozie , Ogidi Nkeiruka Ogochukwu
Published: July 2018

Objectives. Preeclampsia is a pregnancy specific syndrome. Studies have shown that preeclampsia has multiorgan dysfunction effects. This study evaluated biomarkers of renal and liver function among preeclamptic Nigerian women.Study Design. This was a cross-sectional study conducted among 49 preeclamptic women and 50 normotensive healthy pregnant women.Method. The baseline data comprising age, gestational age, and blood pressure were obtained. Venous blood and spot urine samples were collected from each participant. Plasma obtained from blood samples taken into lithium heparinized vacutainer bottles was assayed for electrolytes, urea, creatinine, total protein, albumin, and uric acid, while sera samples from blood samples taken into serum separation tube- (SST-) gel vacutainer were assayed for aspartate transaminase and alanine transaminase using ion selective electrode technique and Cobas autoanalyzer. Spot urine samples were assayed for protein and creatinine using Pyrogallol’s reagent and Jaffe’s methods, respectively. Microalbuminuria (protein/creatinine ratio) was generated from spot urine protein and creatinine data.Result. The plasma sodium, total protein, and albumin in preeclamptic group were significantly decreased (p<0.05) when compared with control. There was statistically significant increase (p<0.05) in microalbuminuria, plasma potassium, urea, creatinine, uric acid levels, serum AST, and ALT activities in preeclamptic group. A positive association (p<0.05) between alanine aminotransferase and biomarkers of renal function was observed.Conclusion. Preeclampsia has deleterious effects on renal and liver function as shown by alteration of these parameters.
In Vitro Weight-Loaded Cell Models for Understanding Mechanodependent Molecular Pathways Involved in Orthodontic Tooth Movement: A Systematic Review
Authors: Janjic Mila , Docheva Denitsa , Trickovic Janjic Olivera , Wichelhaus Andrea , Baumert Uwe
Published: July 2018

Cells from the mesenchymal lineage in the dental area, including but not limited to PDL fibroblasts, osteoblasts, and dental stem cells, are exposed to mechanical stress in physiological (e.g., chewing) and nonphysiological/therapeutic (e.g., orthodontic tooth movement) situations. Close and complex interaction of these different cell types results in the physiological and nonphysiological adaptation of these tissues to mechanical stress. Currently, different in vitro loading models are used to investigate the effect of different types of mechanical loading on the stress adaptation of these cell types. We performed a systematic review according to the PRISMA guidelines to identify all studies in the field of dentistry with focus on mechanobiology using in vitro loading models applying uniaxial static compressive force. Only studies reporting on cells from the mesenchymal lineage were considered for inclusion. The results are summarized regarding gene expression in relation to force duration and magnitude, and the most significant signaling pathways they take part in are identified using protein-protein interaction networks.
A Multiobjective Scheduling Optimization Model for Multienergy Complementary System Integrated by Wind-Photovoltaic-Convention Gas Turbines considering Demand Response
Authors: Lihui Zhang , He Xin , Liwei Ju
Published: July 2018

To utilize the complementary feature of different power sources, wind power plant (WPP), and solar photovoltaic power (PV), convention gas turbines (CGT) and incentive-based demand response (IBDR) are integrated into a multienergy complementary system (MECS) with the implementation of price-based demand response (PBDR). Firstly, the power output model of WPP, PV, and CGT is constructed and the mathematical model of DR is presented. Then, a multiobjective scheduling model is proposed for MECS operation under the objective functions of the maximum economic benefit, the minimum abandoned energy, and the minimum risk level. Thirdly, the payoff table of objective functions is put forward for converting the multiobjective model into a single objective model by using entropy weight method to calculate weighting coefficients of different objective functions. Finally, the improved IEEE 30 bus system is taken as the simulation system with four simulation scenarios for comparatively analyzing the influence of PBDR and IBDR on MECS operation. The simulation results show the following: (1) The MECS fully utilized the complementarity of different power sources; CGT and IBDR can provide peaking service for WPP and PV to optimize overall system operation. (2) The proposed algorithm can solve the MECS multiobjective scheduling optimization model, and the system scheduling results in the comprehensive optimal mode can take into account different appeal. And the total revenue, abandoned energy capacity, and load fluctuation are, respectively, 108009.30¥, 11.62 MW h, and 9.74 MW. (3) PBDR and IBDR have significant synergistic optimization effects, which can promote the grid connection of WPP and PV. When they are both introduced, the peak-to-valley ratio of the load curve is 1.19, and the abandoned energy is 5.85 MW h. Therefore, the proposed MECS scheduling model and solution algorithm could provide the decision basis for decision makers based on their actual situation.
Finite Element Analysis of Different Double-Plate Angles in the Treatment of the Femoral Shaft Nonunion with No Cortical Support opposite the Primary Lateral Plate
Authors: Zhang Hao , Li Jiantao , Zhou Jianfeng , Li Lianting , Hao Ming , Wang Kun , Xu Gaoxiang , Li Chen , Zhang Wei , Tang Peifu
Published: July 2018

Objectives. We evaluated the biomechanical outcome of different plate fixation strategies (the single plate construct, 45° double-plate construct, 90° double-plate construct, 135° double-plate construct, and 180° double-plate construct) used for the fixation of the femoral shaft nonunion with no cortical support opposite the primary lateral plate. This may help surgeons choose the optimal therapy to the femoral shaft nonunion. Methods. The femoral shaft nonunion with no medial support and the models of lateral plate and medial plate was constructed in 3-matic software and UG-NX software, respectively. We then assembled the single plate and different double plates to the fracture model separately to form the fixation models. After meshing the models’ elements, we used the ABAQUS software to perform the finite element analysis. Values of the von Mises Stress (VMS) distribution of the implant, peak VMS, and model displacement and deformation were used to capture the mechanical factors in this study. Results. Our results indicated that the peak von Mises Stress (VMS) of the lateral plate was concentrated in middle surface of the lateral plate near the fragment of each group. The peak VMS was 5201.0 MPa (the single-plate construct), 3490.0 MPa (45° double-plate construct), 1754.0 MPa (90° double-plate construct), 1123.0 MPa (135° double-plate construct), and 816.5 MPa (180° double-plate construct). The additional short plate dispersed some stress leading to the decrease in the peak VMS of the lateral plate. As angle formed by the double plates increased, the dispersed function of the additional plate was becoming obvious. The bending angles of the lateral plate were 18° versus 12° versus 3° versus 2° versus 1° (the single-plate construct versus 45° double-plate construct versus 90° double-plate construct versus 135° double-plate construct versus 180° double-plate construct). Conclusions. Our study indicated that increasing the angle between the plates in a double-plate construct improves the stability of the construct over a single lateral plate when there is no cortical support opposite to the lateral plate. The strongest fixation occurred when the angle between the two plates was greater than ninety degrees.
Permeability Changes Resulting from Quartz Precipitation and Dissolution around Upper Crustal Intrusions
Authors: Scott Samuel W. , Driesner Thomas
Published: July 2018

It has long been recognized that quartz precipitation from circulating hydrothermal fluids may reduce porosity and permeability near intrusions. However, the magnitude of permeability changes and potential feedbacks between flow, heat transfer, and quartz precipitation/dissolution remain largely unquantified. Here, we present numerical simulations of fluid convection around upper crustal intrusions which explicitly incorporate the feedback between quartz solubility and rock permeability. As groundwater is heated to ~350°C, silica dissolves from the host rock, increasing porosity and permeability. Further heating to supercritical conditions leads to intensive quartz precipitation and consequent permeability reduction. The initial host rock permeability and porosity are found to be main controls on the magnitude and timescales of permeability changes. While the permeability changes induced by quartz precipitation are moderate in host rocks with a primary porosity ≥ 0.05, quartz precipitation may reduce rock permeability by more than an order of magnitude in host rocks with a primary porosity of 0.025. Zones of quartz precipitation transiently change locations as the intrusion cools, thereby limiting the clogging effect, except for host rocks with low initial porosity. This permeability reduction occurs in timescales of hundreds of years in host rocks with initial high permeability and thousands of years in host rocks with intermediate permeability.
HBV Upregulates CtBP2 Expression via the X Gene
Authors: Liu Xinghui , Zhu Chengliang , Li Jie , Xu Fengxia , Huang Gang , Xu Limin , Zhang Binghong
Published: July 2018

Background. Hepatitis B virus (HBV) infection causes acute and chronic liver diseases that can eventually develop into cirrhosis and hepatocellular carcinoma (HCC), but the carcinogenesis of HBV is not fully understood. Carboxyl-terminal-binding protein 2 (CtBP2) plays an important role in tumorigenesis and progression. The aim of this study was to investigate the effect of HBV on CtBP2 expression and to explore its mechanism.Methods. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were used to evaluate the CtBP2 mRNA and protein expression levels in tissues and cells. The HBV infectious clone pHBV1.3 and plasmids expressing a single gene of the HBV genome were cotransfected with the CtBP2 gene promoter pGL3-CtBP2 into the human hepatoma cell line HepG2, and luciferase activity was determined using a luminometer.Results. CtBP2 expression was higher in HBV-related HCC tissues than in paracancerous tissues. CtBP2 expression was higher in HepG2.2.15 cells integrated with the HBV genome than in HepG2 cells. pHBV1.3 upregulated CtBP2 mRNA and protein expression. The HBV X gene significantly activated CtBP2 gene promoter activity, and CtBP2 mRNA and protein expression were upregulated by the HBV X gene. This activation effect was enhanced by the increase in the dose of the X gene, showing metrological dependence.Conclusion. HBV may be involved in the occurrence and development of HCC by upregulating CtBP2 expression.
Alzheimer’s Dementia due to Suspected CTE from Subconcussive Head Impact
Authors: Yuan Shauna H. , Wang Sonya G.
Published: July 2018

Chronic traumatic encephalopathy (CTE) has been receiving increasing attention due to press coverage of professional football players. The devastating sequelae of CTE compel us to aim for early diagnosis and treatment. However, by current standards, CTE is challenging to diagnose. Clear clinical diagnostic criteria for CTE have not been established. Only recently, pathological diagnostic criteria have been recognized, but postmortem diagnosis is too late. Reliable biomarkers are not available. By imaging criteria, cavum septum pellucidum has been the only consistent identifiable MRI finding. Because of the imprecise nature of diagnosis based on clinical suspicion, physicians must become cognizant of the broad spectrum of presentations of CTE. With this awareness, appropriate workup can be initiated. CTE can present with early symptoms of emotional changes or late symptoms with memory decline and dementia. Here we present an unusual case of a patient with Alzheimer’s disease secondary to suspected CTE that stems from subconcussive head impacts presenting with severe memory and MRI changes. Clinicians should be aware of this presentation and consider CTE in their differential diagnoses while undergoing workup of memory disorders.
Autoimmune Thyroid Disease and Keratoconus: Is There an Association?
Authors: Alhawari Hussam H. , Khader Yousef S. , Alhawari Hussein H. , Alomari Amal F. , Abbasi Hiba N. , El-Faouri Muhannd S. , Al Bdour Muawyah D.
Published: July 2018

Purpose.The association between autoimmune diseases and keratoconus (KC) has been proposed based on previous retrospective studies and case reports. The aim of our study is to investigate whether KC is associated with autoimmune thyroid disease. Methods.A comparative study was conducted on 131 adult subjects from September 2015 to May 2017 at Jordan University Hospital, Amman, Jordan. Subjects were classified into 2 groups: subjects with autoimmune thyroid disease, including Graves’ disease and Hashimoto’s thyroiditis (n=68), and a healthy group for comparison (n=63). Subjects with any other conditions known to be associated with KC were excluded. The diagnosis of KC was based on clinical and corneal topographic findings utilizing the Oculus-Pentacam machine. In addition, TSH and total T4 levels as well as thyroid peroxidase antibodies were measured in all study participants. Antithyroglobulin antibodies, thyroid stimulating immunoglobulin, thyroid ultrasound, and thyroid uptake and scan were also selectively performed in some participants.Results.This study included a total of 131 participants (101 females and 30 males), including patients and controls. In the multivariate analysis, autoimmune disease was not significantly associated with keratoconus (OR = 1.1; 95% confidence interval: 0.3, 3.8;pvalue = 0.353) after adjusting for age and gender.Conclusion.This study did not show a statistically significant association between autoimmune thyroid disease and KC.
Isolated Intraventricular Hemorrhage Associated with Cerebral Vasospasm and Delayed Cerebral Ischemia following Arteriovenous Malformation Rupture
Authors: Amuluru Krishna , Al-Mufti Fawaz , Romero Charles E. , Gandhi Chirag D.
Published: July 2018

Background: Although it is well characterized in aneurysmal subarachnoid hemorrhage, vasospasm is exceedingly rare following cerebral arteriovenous malformation (AVM) rupture. Subsequently, this complication is poorly characterized with regard to delayed cerebral ischemia (DCI). We review cases of ruptured AVM to assess the frequency and severity of vasospasm on cerebral angiography, and DCI. Summary: We reviewed our institutional database of acute intracranial hemorrhages between 2005 and 2014. We identified patients with cerebral AVM rupture and evidence of vasospasm, which was confirmed with digital subtraction angiography (DSA). Cerebral angiograms were evaluated by 2 blinded neurointerventionalists for vasospasm. Statistical analyses were conducted on the angiographic results and variables of interest to determine predictors and associations of vasospasm and DCI. Thirty-six patients with acute intracranial hemorrhage due to ruptured cerebral AVM subsequently underwent cerebral angiography. The interrater reliability for vasospasm was 0.81. The incidence of vasospasm was 13.9% and the incidence of subsequent DCI was 11.1%. A significant relationship existed between isolated intraventricular hemorrhage and vasospasm (p = 0.001) and subsequent DCI (p = 0.006). Radiographic vasospasm was associated with DCI in 80% of the patients (p < 0.0001). No statistical significance existed between subarachnoid hemorrhage and the development of vasospasm or DCI (p = 1.000 and p = 0.626, respectively). All differences were significant at a 99% level of significance. Key Message: In cases of ruptured AVM, isolated intraventricular hemorrhage appears to be an independent risk factor for vasospasm and DCI. Vasospasm must be considered during late neurological deterioration following AVM hemorrhage, especially in the setting of isolated intraventricular hemorrhage.
The Kyoto Collection of Human Embryos and Fetuses: History and Recent Advancements in Modern Methods
Authors: Yamaguchi Yutaka , Yamada Shigehito
Published: July 2018

The Kyoto Collection of Human Embryos and Fetuses, the largest collection of human embryos worldwide, was initiated in the 1960s, and the Congenital Anomaly Research Center of Kyoto University was established in 1975 for long-term storage of the collection and for the promotion of research into human embryonic and fetal development. Currently, the Kyoto Collection comprises approximately 45,000 specimens of human embryonic or fetal development and is renowned for the following unique characteristics: (1) the collection is considered to represent the total population of fetal specimens nationwide in Japan, (2) it comprises a large number of specimens with a variety of external malformations, and (3) for most specimens there are clinical and epidemiological data from the mothers and the pregnancies concerned. Therefore, the specimens have been used extensively for morphological studies and could potentially be used for epidemiological analysis. Recently, several new approaches such as DNA extraction from formalin-fixed specimens or geometric morphometrics have been adopted and it is to be expected that further technological advances will facilitate new studies on the specimens of the Kyoto Collection as well as of other human embryo collections worldwide. Permanent preservation of the Kyoto Collection is, therefore, of paramount importance so that it will continue to contribute to human embryological studies in the future.
Targeting Regulatory T Cells for Transplant Tolerance: New Insights and Future Perspectives
Authors: Shaban Eman , Bayliss George , Malhotra Deepak K. , Shemin Douglas , Wang Li Juan , Gohh Reginald , Dworkin Lance D. , Gong Rujun
Published: July 2018

Background: Organ transplantation is considered the ultimate therapy for end-stage organ disease. While pharmacologic immunosuppression is the mainstay of therapeutic strategies to prolong the survival of the graft, long-term use of immunosuppressive medications carries the risk of organ toxicity, malignancies, serious opportunistic infections, and diabetes. Therapies that promote recipient tolerance in solid organ transplantation are able to improve patient outcomes by eliminating the need for long-term immunosuppression. Summary: Establishing tolerance to an allograft has become an area of intense study and would be the ideal therapy in clinical practice. The discovery of a subset of T cells naturally committed to perform immunoregulation has led to further investigation into their role in the immunopathogenesis of transplantation. Evidence suggests that regulatory T cells (Tregs) are fundamentally involved in promoting allograft tolerance. Efforts to characterize specific markers for Tregs, while challenging, have identified Foxp3 gene expression as a crucial step in promoting the tolerance-inducing features of Tregs. A number of approaches, including those based on targeting the glycogen synthase kinase 3β signaling pathway or activating the melanocortinergic pathway, have been tested as a way to promote Treg lineage commitment and maintenance as well as to facilitate immune tolerance. In order to be effective in clinical practice, Tregs must be allospecific and possess a specific phenotype to avoid suppression of other aspects of the immune system or increasing the risk of malignancy or infections. Multiple experimental and clinical studies have demonstrated the impact of currently used immunosuppressants on the immunoregulatory activities of Tregs and their Foxp3 expression status. Pharmacological induction of tolerogenic Tregs for inducing transplant tolerance, including epigenetic therapies, is in the ascendant. Key Messages: Therapies that promote Treg function and survival may represent a novel strategy for achieving immune tolerance in transplant patients.
Functional and Structural Study of the Amino Acid Substitution in a Novel Familial Androgen Receptor Mutation (W752G) Responsible for Complete Androgen Insensitivity Syndrome
Authors: Paris Françoise , Boulahtouf Abdelhay , Kalfa Nicolas , Guibal Marie P. , Gaspari Laura , Servant Nadège , Bourguet William , Sultan Charles , Balaguer Patrick
Published: July 2018

Mutations of the androgen receptor (AR) gene are the most frequent cause of 46,XY disorders of sex development. They are associated with a variety of phenotypes, ranging from phenotypic women (complete androgen insensitivity syndrome, CAIS) to milder degrees of undervirilization (partial forms) or men with only infertility (mild form). We identified a new W752G AR mutation responsible for a familial case of CAIS and performed an in vitro study and structural analysis of this mutation and the only other reported substitution affecting the same amino acid (W752R). Although sex assignment is not discussed in cases of CAIS, we show how the phenotype-genotype correlation can be refined by in vitro and structural studies according to the nature of the amino acid substitution, which in turn may have interesting impacts on the follow-up of these patients.
Zedoarondiol Attenuates Endothelial Cells Injury Induced by Oxidized Low-Density Lipoprotein via Nrf2 Activation
Authors: Mao Huimin , Tao Tianqi , Wang Xiaoren , Liu Mi , Song Dandan , Liu Xiuhua , Shi Dazhuo
Published: July 2018

Background/Aims: Zedoarondiol, a sesquiterpene lactone compound, showed an anti-proliferative activity on vascular smooth muscle cells in our previous study. However, whether it has a beneficial effect on endothelial cells injury induced by oxidized low-density lipoprotein (ox-LDL) remains unclear. This study was designed to investigate the protective effect of zedoarondiol on ox-LDL-induced injury of endothelial cells and explored its underlying mechanism. Methods: The protective effect of zedoarondiol on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injury were evaluated by Cell Counting Kit-8 (CCK-8) assay and released lactic dehydrogenase (LDH) activity assay. Oxidative stress was determined by malonedialdehyde (MDA) content and superoxide dismutase (SOD) activity. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The culture supernatant was collected for enzyme linked immune-sorbent assays (ELISA) of interleukine-1β (IL-1β), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Immunofluorescence staining was used to observe NF-E2-related factor 2 (Nrf2) translocation. Western blotting was performed to determine the expression of IL-1β, TNF-α, MCP-1, Kelch-like ECH associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and Nrf2. Results: Zedoarondiol attenuated HUVECs injury, up-regulated SOD activity, suppressed formation of MDA and ROS, and secretion and protein expression of IL-1β, TNF-α, and MCP-1 in injured HUVECs induced by ox-LDL. Zedoarondiol induced nuclear Nrf2 translocation from cytoplasm into nucleus and up-regulated expression of HO-1, NQO1, and Nrf2 in nucleus. All-trans-retinoic acid (ATRA), an inhibitor of Nrf2, abolished zedoarondiol-mediated anti-oxidative effect. Conclusion: Zedoarondiol attenuates ox-LDL-induced endothelial cells injury by inhibiting oxidative stress and inflammation via Nrf2/HO-1 pathway, suggesting that zedoarondiol might be meaningful on prevention and treatment of atherosclerosis.
Verbal Paired Associates and the Hippocampus: The Role of Scenes
Authors: Clark Ian A. , Kim Misun , Maguire Eleanor A.
Published: July 2018

It is widely agreed that patients with bilateral hippocampal damage are impaired at binding pairs of words together. Consequently, the verbal paired associates (VPA) task has become emblematic of hippocampal function. This VPA deficit is not well understood and is particularly difficult for hippocampal theories with a visuospatial bias to explain (e.g., cognitive map and scene construction theories). Resolving the tension among hippocampal theories concerning the VPA could be important for leveraging a fuller understanding of hippocampal function. Notably, VPA tasks typically use high imagery concrete words and so conflate imagery and binding. To determine why VPA engages the hippocampus, we devised an fMRI encoding task involving closely matched pairs of scene words, pairs of object words, and pairs of very low imagery abstract words. We found that the anterior hippocampus was engaged during processing of both scene and object word pairs in comparison to abstract word pairs, despite binding occurring in all conditions. This was also the case when just subsequently remembered stimuli were considered. Moreover, for object word pairs, fMRI activity patterns in anterior hippocampus were more similar to those for scene imagery than object imagery. This was especially evident in participants who were high imagery users and not in mid and low imagery users. Overall, our results show that hippocampal engagement during VPA, even when object word pairs are involved, seems to be evoked by scene imagery rather than binding. This may help to resolve the issue that visuospatial hippocampal theories have in accounting for verbal memory.
Dynamics of Feature-based Attentional Selection during Color–Shape Conjunction Search
Authors: Lee Jeongmi , Leonard Carly J. , Luck Steven J. , Geng Joy J.
Published: July 2018

Feature-based attentional selection is accomplished by increasing the gain of sensory neurons encoding target-relevant features while decreasing that of other features. But how do these mechanisms work when targets and distractors share features? We investigated this in a simplified color–shape conjunction search task using ERP components (N2pc, PD, and SPCN) that index lateralized attentional processing. In Experiment 1, we manipulated the presence and frequency of color distractors while holding shape distractors constant. We tested the hypothesis that the color distractor would capture attention, requiring active suppression such that processing of the target can continue. Consistent with this hypothesis, we found that color distractors consistently captured attention, as indexed by a significant N2pc, but were reactively suppressed (indexed by PD). Interestingly, when the color distractor was present, target processing was sustained (indexed by SPCN), suggesting that the dynamics of attentional competition involved distractor suppression interlinked with sustained target processing. In Experiment 2, we examined the contribution of shape to the dynamics of attentional competition under similar conditions. In contrast to color distractors, shape distractors did not reliably capture attention, even when the color distractor was very frequent and attending to target shape would be beneficial. Together, these results suggest that target-colored objects are prioritized during color–shape conjunction search, and the ability to select the target is delayed while target-colored distractors are actively suppressed.
Decision-making Increases Episodic Memory via Postencoding Consolidation
Authors: Murty Vishnu P. , DuBrow Sarah , Davachi Lila
Published: July 2018

The ability for individuals to actively make decisions engages regions within the mesolimbic system and enhances memory for chosen items. In other behavioral contexts, mesolimbic engagement has been shown to enhance episodic memory by supporting consolidation. However, research has yet to investigate how consolidation may support interactions between decision-making and episodic memory. Across two studies, participants encoded items that were covered by occluder screens and could either actively decide which of two items to uncover or an item was preselected by the experimenter. In Study 1, we show that active decision-making reduces forgetting rates across an immediate and 24-hr memory test, a behavioral marker of consolidation. In Study 2, we use functional neuroimaging to characterize putative neural markers of memory consolidation by measuring interactions between the hippocampus and perirhinal cortex (PRC) during a postencoding period that reexposed participants to elements of the decision-making context without exposing them to memoranda. We show that choice-related striatal engagement is associated with increased postencoding hippocampal–PRC interactions. Finally, we show that a previous reported relationship between choice-related striatal engagement and long-term memory is accounted for by these postencoding hippocampal–PRC interactions. Together, these findings support a model by which actively deciding to encode information enhances memory consolidation to preserve episodic memory for outcomes, a process that may be facilitated by reexposure to the original decision-making context.
Tangible Tetris
Authors: Wang Meng , Mi Haipeng
Published: July 2018

Tangible Tetris is a mixed-reality interactive game allowing play with a physical transformable tetromino in a virtual playfield. The extension from game world to the physical brings plenty of new characteristics, strategies and fun to the classic game, as well as more possibilities in interactive art.
The Trouble with Calasiris
Authors: Kim Lawrence
Published: July 2018

In this article, I take a new look at the problem of Calasiris’ ‘duplicity’ as depicted in the long autobiographical narrative he delivers to Cnemon in Books 2-5 of Heliodorus’ Aethiopica. A close parallel for Calasiris’ self-presentation can be found in an unlikely source: the medical case histories of the doctor Galen. Through a comparison of Calasiris’ narrative with those of Galen, I demonstrate that both narrators employ similar ‘deceptive’ strategies to showcase their observational and deductive skills to their audience. Calasiris’ foregrounding of such ‘rational’ methods and his downplaying of the prophetic power that others attribute to him suggest that, despite the Aethiopica’s religious trappings, its ideal reader is a secular one.
Public Theology: Its Pastoral, Apologetic, Scientific, Political, and Prophetic Tasks
Authors: Peters Ted
Published: July 2018

This blueprint for a constructive public theology assumes that Christian theology already includes public discourse. Following David Tracy’s delineation of three publics—church, academy, culture—further constructive work leads to a public theology conceived in the church, reflected on critically in the academy, and meshed with the wider culture. Public reflection on classic Christian doctrines in a post-secular pluralistic context takes the form of pastoral illumination, apologetic reason, a theology of nature, political theology, and prophetic critique.