bluuebunny/crossref_metadata_2025 huggingface dataset:
Exponential Lower Bounds for AC
0
-Frege Imply Superpolynomial Frege Lower Bounds
Authors: Filmus Yuval , Pitassi Toniann , Santhanam Rahul
Published: May 2015

We give a general transformation that turns polynomial-size Frege proofs into subexponential-size AC
0
-Frege proofs. This indicates that proving truly exponential lower bounds for AC
0
-Frege is hard, as it is a long-standing open problem to prove superpolynomial lower bounds for Frege. Our construction is optimal for proofs of formulas of unbounded depth.

As a consequence of our main result, we are able to shed some light on the question of automatizability for bounded-depth Frege systems. First, we present a simpler proof of the results of Bonet et al. showing that under cryptographic assumptions, bounded-depth Frege proofs are not automatizable. Second, we show that because our proof is more general, under the right cryptographic assumptions, it could resolve the automatizability question for lower-depth Frege systems.
Low-Level Flexible Architecture with Hybrid Reconfiguration for Evolvable Hardware
Authors: Dobai Roland , Sekanina Lukas
Published: May 2015

Field-programmable gate arrays (FPGAs) can be considered to be the most popular and successful platform for evolvable hardware. They allow one to establish and later reconfigure candidate solutions. Recent work in the field of evolvable hardware includes the use of virtual and native reconfigurations. Virtual reconfiguration is based on the change of functionality by hardware components implemented on top of FPGA resources. Native reconfiguration changes the FPGA resources directly by means provided by the FPGA manufacturer. Both of these approaches have their disadvantages. The virtual reconfiguration is characterized by lower maximal operational frequency of the resulting solutions, and the native reconfiguration is slower. In this work, a hybrid approach is used merging the advantages while limiting the disadvantages of the virtual and native reconfigurations. The main contribution is the new low-level architecture for evolvable hardware in the new Zynq-7000 all-programmable system-on-chip. The proposed architecture offers high flexibility in comparison with other evolvable hardware systems by considering direct modification of the reconfigurable resources. The impact of the higher reconfiguration time of the native approach is limited by the dense placement of the proposed reconfigurable processing elements. These processing elements also ensure fast evaluation of candidate solutions. The proposed architecture is evaluated by evolutionary design of switching image filters and edge detectors. The experimental results demonstrate advantages over the previous approaches considering the time required for evolution, area overhead, and flexibility.
Pebbling, Entropy, and Branching Program Size Lower Bounds
Authors: Komarath Balagopal , Sarma Jayalal
Published: May 2015

We contribute to the program of proving lower bounds on the size of branching programs solving the Tree Evaluation Problem introduced by Cook et al. [2012]. Proving a superpolynomial lower bound for the size of nondeterministic thrifty branching programs would be an important step toward separating NL from P using the tree evaluation problem. First, we show that
Read-Once Nondeterministic Thrifty BPs
are equivalent to whole black-white pebbling algorithms, thus showing a tight lower bound (ignoring polynomial factors) for this model. We then introduce a weaker restriction of nondeterministic thrifty branching programs called
Bitwise Independence
. The best known [Cook et al. 2012] nondeterministic thrifty branching programs (of size
O
(
k

h
/2 + 1

)) for the tree evaluation problem are Bitwise Independent. As our main result, we show that any Bitwise Independent Nondeterministic Thrifty Branching Program solving BT
2
(h, k) must have at least (k2)
h/2
states. Prior to this work, lower bounds were known for nondeterministic thrifty branching programs only for fixed heights
h
= 2, 3, 4 [Cook et al. 2012]. We prove our results by associating a fractional black-white pebbling strategy with any bitwise independent nondeterministic thrifty branching program solving the Tree Evaluation Problem. Such a connection was not known previously, even for fixed heights.

Our main technique is the entropy method introduced by Jukna and Zák [2001] originally in the context of proving lower bounds for read-once branching programs. We also show that the previous lower bounds known [Cook et al. 2012] for deterministic branching programs for the Tree Evaluation Problem can be obtained using this approach. Using this method, we also show tight lower bounds for any
k
-way deterministic branching program solving the Tree Evaluation Problem when the instances are restricted to have the same group operation in all internal nodes.
Hardness of Max-2Lin and Max-3Lin over Integers, Reals, and Large Cyclic Groups
Authors: O’Donnell Ryan , Wu Yi , Zhou Yuan
Published: May 2015

In 1997, Håstad showed NP-hardness of (1 − ϵ, 1/
q
+ δ)-approximating Max-3Lin(Z
q
); however, it was not until 2007 that Guruswami and Raghavendra were able to show NP-hardness of (1 − ϵ, δ)-approximating Max-3Lin(Z). In 2004, Khot--Kindler--Mossel--O’Donnell showed UG-hardness of (1 − ϵ, δ)-approximating Max-2Lin(Z
q
) for
q
=
q
(ϵ, δ) a sufficiently large constant; however, achieving the same hardness for Max-2Lin(Z) was given as an open problem in Raghavendra’s 2009 thesis. In this work, we show that fairly simple modifications to the proofs of the Max-3Lin(Z
q
) and Max-2Lin(Z
q
) results yield optimal hardness results over Z. In fact, we show a kind of “bicriteria” hardness: Even when there is a (1 − ϵ)-good solution over Z, it is hard for an algorithm to find a δ-good solution over Z, R, or Z
m
for any
m
⩾
q
(ϵ, δ) of the algorithm’s choosing.
Effect handlers in scope
Authors: Wu Nicolas , Schrijvers Tom , Hinze Ralf
Published: May 2015

Algebraic effect handlers are a powerful means for describing effectful computations. They provide a lightweight and orthogonal technique to define and compose the syntax and semantics of different effects. The semantics is captured by handlers, which are functions that transform syntax trees.

Unfortunately, the approach does not support syntax for scoping constructs, which arise in a number of scenarios. While handlers can be used to provide a limited form of scope, we demonstrate that this approach constrains the possible interactions of effects and rules out some desired semantics.

This paper presents two different ways to capture scoped constructs in syntax, and shows how to achieve different semantics by reordering handlers. The first approach expresses scopes using the existing algebraic handlers framework, but has some limitations. The problem is fully solved in the second approach where we introduce higher-order syntax.
LiquidHaskell
Authors: Vazou Niki , Seidel Eric L. , Jhala Ranjit
Published: May 2015

Haskell has many delightful features. Perhaps the one most beloved by its users is its type system that allows developers to specify and verify a variety of program properties at compile time. However, many properties, typically those that depend on relationships
between
program values are impossible, or at the very least, cumbersome to encode within the existing type system. Many such properties can be verified using a combination of Refinement Types and external SMT solvers. We describe the refinement type checker liquidHaskell, which we have used to specify and verify a variety of properties of over 10,000 lines of Haskell code from various popular libraries, including containers, hscolour, bytestring, text, vector-algorithms and xmonad. First, we present a high-level overview of liquidHaskell, through a tour of its features. Second, we present a qualitative discussion of the kinds of properties that can be checked -- ranging from generic application independent criteria like totality and termination, to application specific concerns like memory safety and data structure correctness invariants. Finally, we present a quantitative evaluation of the approach, with a view towards measuring the efficiency and programmer effort required for verification, and discuss the limitations of the approach.
Indentation-sensitive parsing for Parsec
Authors: Adams Michael D. , Ağacan Ömer S.
Published: May 2015

Several popular languages including Haskell and Python use the indentation and layout of code as an essential part of their syntax. In the past, implementations of these languages used
ad hoc
techniques to implement layout. Recent work has shown that a simple extension to context-free grammars can replace these
ad hoc
techniques and provide both formal foundations and efficient parsing algorithms for indentation sensitivity.

However, that previous work is limited to bottom-up, LR($k$) parsing, and many combinator-based parsing frameworks including Parsec use top-down algorithms that are outside its scope. This paper remedies this by showing how to add indentation sensitivity to parsing frameworks like Parsec. It explores both the formal semantics of and efficient algorithms for indentation sensitivity. It derives a Parsec-based library for indentation-sensitive parsing and presents benchmarks on a real-world language that show its efficiency and practicality.
Systems demonstration
Authors: Okabe Kiwamu , Muranushi Takayuki
Published: May 2015

Most strongly typed, functional programming languages are not equipped with a reentrant garbage collector. Therefore such languages are not used for operating systems programming, where the virtues of types are most desired. We propose the use of Context-Local Heaps (CLHs) to achieve reentrancy, which also increasing the speed of garbage collection. We have implemented CLHs in Ajhc, a Haskell compiler derived from jhc, rewritten some NetBSD sound drivers using Ajhc, and benchmarked them. The reentrant, faster garbage collection that CLHs provide opens the path to type-assisted operating systems programming.
Safe & Efficient Gradual Typing for TypeScript
Authors: Rastogi Aseem , Swamy Nikhil , Fournet Cédric , Bierman Gavin , Vekris Panagiotis
Published: May 2015

Current proposals for adding gradual typing to JavaScript, such as Closure, TypeScript and Dart, forgo soundness to deal with issues of scale, code reuse, and popular programming patterns. We show how to address these issues in practice while retaining soundness. We design and implement a new gradual type system, prototyped for expediency as a 'Safe' compilation mode for TypeScript. Our compiler achieves soundness by enforcing stricter static checks and embedding residual runtime checks in compiled code. It emits plain JavaScript that runs on stock virtual machines. Our main theorem is a simulation that ensures that the checks introduced by Safe TypeScript (1) catch any dynamic type error, and (2) do not alter the semantics of type-safe TypeScript code.

Safe TypeScript is carefully designed to minimize the performance overhead of runtime checks. At its core, we rely on two new ideas: differential subtyping, a new form of coercive subtyping that computes the minimum amount of runtime type information that must be added to each object; and an erasure modality, which we use to safely and selectively erase type information. This allows us to scale our design to full-fledged TypeScript, including arrays, maps, classes, inheritance, overloading, and generic types.

We validate the usability and performance of Safe TypeScript empirically by type-checking and compiling around 120,000 lines of existing TypeScript source code. Although runtime checks can be expensive, the end-to-end overhead is small for code bases that already have type annotations. For instance, we bootstrap the Safe TypeScript compiler (90,000 lines including the base TypeScript compiler): we measure a 15% runtime overhead for type safety, and also uncover programming errors as type safety violations. We conclude that, at least during development and testing, subjecting JavaScript/TypeScript programs to safe gradual typing adds significant value to source type annotations at a modest cost.
Runtime Enforcement of Security Policies on Black Box Reactive Programs
Authors: Ngo Minh , Massacci Fabio , Milushev Dimiter , Piessens Frank
Published: May 2015

Security enforcement mechanisms like execution monitors are used to make sure that some untrusted program complies with a policy. Different enforcement mechanisms have different strengths and weaknesses and hence it is important to understand the qualities of various enforcement mechanisms.

This paper studies runtime enforcement mechanisms for reactive programs. We study the impact of two important constraints that many practical enforcement mechanisms satisfy: (1) the enforcement mechanism must handle each input/output event in finite time and on occurrence of the event (as opposed to for instance Ligatti's edit automata that have the power to buffer events for an arbitrary amount of time), and (2) the enforcement mechanism treats the untrusted program as a
black box
: it can monitor and/or edit the input/output events that the program exhibits on execution and it can explore alternative executions of the program by running additional copies of the program and providing these different inputs. It can
not
inspect the source or machine code of the untrusted program.

Such enforcement mechanisms are important in practice: they include for instance many execution monitors, virtual machine monitors, and secure multi-execution or shadow executions.

We establish upper and lower bounds for the class of policies that are enforceable by such black box mechanisms, and we propose a generic enforcement mechanism that works for a wide range of policies. We also show how our generic enforcement mechanism can be instantiated to enforce specific classes of policies, at the same time showing that many existing enforcement mechanisms are optimized instances of our construction.
Faster Algorithms for Algebraic Path Properties in Recursive State Machines with Constant Treewidth
Authors: Chatterjee Krishnendu , Ibsen-Jensen Rasmus , Pavlogiannis Andreas , Goyal Prateesh
Published: May 2015

Interprocedural analysis is at the heart of numerous applications in programming languages, such as alias analysis, constant propagation, etc. Recursive state machines (RSMs) are standard models for interprocedural analysis. We consider a general framework with RSMs where the transitions are labeled from a semiring, and path properties are algebraic with semiring operations. RSMs with algebraic path properties can model interprocedural dataflow analysis problems, the shortest path problem, the most probable path problem, etc. The traditional algorithms for interprocedural analysis focus on path properties where the starting point is
fixed
as the entry point of a specific method. In this work, we consider possible multiple queries as required in many applications such as in alias analysis. The study of multiple queries allows us to bring in a very important algorithmic distinction between the resource usage of the
one-time
preprocessing vs for
each individual
query. The second aspect that we consider is that the control flow graphs for most programs have constant treewidth.

Our main contributions are simple and implementable algorithms that support multiple queries for algebraic path properties for RSMs that have constant treewidth. Our theoretical results show that our algorithms have small additional one-time preprocessing, but can answer subsequent queries significantly faster as compared to the current best-known solutions for several important problems, such as interprocedural reachability and shortest path. We provide a prototype implementation for interprocedural reachability and intraprocedural shortest path that gives a significant speed-up on several benchmarks.
DReX
Authors: Alur Rajeev , D'Antoni Loris , Raghothaman Mukund
Published: May 2015

We present DReX, a declarative language that can express all regular string-to string transformations, and can still be efficiently evaluated. The class of regular string transformations has a robust theoretical foundation including multiple characterizations, closure properties, and decidable analysis questions, and admits a number of string operations such as insertion, deletion, substring swap, and reversal. Recent research has led to a characterization of regular string transformations using a primitive set of function combinators analogous to the definition of regular languages using regular expressions. While these combinators form the basis for the language DReX proposed in this paper, our main technical focus is on the complexity of evaluating the output of a DReX program on a given input string. It turns out that the natural evaluation algorithm involves dynamic programming, leading to complexity that is cubic in the length of the input string. Our main contribution is identifying a consistency restriction on the use of combinators in DReX programs, and a single-pass evaluation algorithm for consistent programs with time complexity that is linear in the length of the input string and polynomial in the size of the program. We show that the consistency restriction does not limit the expressiveness, and whether a DReX program is consistent can be checked efficiently. We report on a prototype implementation, and evaluate it using a representative set of text processing tasks.
K-Java
Authors: Bogdanas Denis , Roşu Grigore
Published: May 2015

This paper presents K-Java, a complete executable formal semantics of Java 1.4. K-Java was extensively tested with a test suite developed alongside the project, following the Test Driven Development methodology. In order to maintain clarity while handling the great size of Java, the semantics was split into two separate definitions -- a static semantics and a dynamic semantics. The output of the static semantics is a preprocessed Java program, which is passed as input to the dynamic semantics for execution. The preprocessed program is a valid Java program, which uses a subset of the features of Java. The semantics is applied to model-check multi-threaded programs. Both the test suite and the static semantics are generic and ready to be used in other Java-related projects.
Abstract Symbolic Automata
Authors: Dalla Preda Mila , Giacobazzi Roberto , Lakhotia Arun , Mastroeni Isabella
Published: May 2015

We introduce a model for mixed syntactic/semantic approximation of programs based on symbolic finite automata (SFA). The edges of SFA are labeled by predicates whose semantics specifies the denotations that are allowed by the edge. We introduce the notion of abstract symbolic finite automaton (ASFA) where approximation is made by abstract interpretation of symbolic finite automata, acting both at syntactic (predicate) and semantic (denotation) level. We investigate in the details how the syntactic and semantic abstractions of SFA relate to each other and contribute to the determination of the recognized language. Then we introduce a family of transformations for simplifying ASFA. We apply this model to prove properties of commonly used tools for similarity analysis of binary executables. Following the structure of their control flow graphs, disassembled binary executables are represented as (concrete) SFA, where states are program points and predicates represent the (possibly infinite) I/O semantics of each basic block in a constraint form. Known tools for binary code analysis are viewed as specific choices of symbolic and semantic abstractions in our framework, making symbolic finite automata and their abstract interpretations a unifying model for comparing and reasoning about soundness and completeness of analyses of low-level code.
Analyzing Program Analyses
Authors: Giacobazzi Roberto , Logozzo Francesco , Ranzato Francesco
Published: May 2015

We want to prove that a static analysis of a given program is complete, namely, no imprecision arises when asking some query on the program behavior in the concrete (ie, for its concrete semantics) or in the abstract (ie, for its abstract interpretation). Completeness proofs are therefore useful to assign confidence to alarms raised by static analyses. We introduce the completeness class of an abstraction as the set of all programs for which the abstraction is complete. Our first result shows that for any nontrivial abstraction, its completeness class is not recursively enumerable. We then introduce a stratified deductive system to prove the completeness of program analyses over an abstract domain A. We prove the soundness of the deductive system. We observe that the only sources of incompleteness are assignments and Boolean tests --- unlikely a common belief in static analysis, joins do not induce incompleteness. The first layer of this proof system is generic, abstraction-agnostic, and it deals with the standard constructs for program composition, that is, sequential composition, branching and guarded iteration. The second layer is instead abstraction-specific: the designer of an abstract domain A provides conditions for completeness in A of assignments and Boolean tests which have to be checked by a suitable static analysis or assumed in the completeness proof as hypotheses. We instantiate the second layer of this proof system first with a generic nonrelational abstraction in order to provide a sound rule for the completeness of assignments. Orthogonally, we instantiate it to the numerical abstract domains of Intervals and Octagons, providing necessary and sufficient conditions for the completeness of their Boolean tests and of assignments for Octagons.
Full Abstraction for Signal Flow Graphs
Authors: Bonchi Filippo , Sobocinski Pawel , Zanasi Fabio
Published: May 2015

Network theory uses the string diagrammatic language of monoidal categories to study graphical structures formally, eschewing specialised translations into intermediate formalisms. Recently, there has been a concerted research focus on developing a network theoretic approach to signal flow graphs, which are classical structures in control theory, signal processing and a cornerstone in the study of feedback. In this approach, signal flow graphs are given a relational denotational semantics in terms of formal power series.

Thus far, the operational behaviour of such signal flow graphs has only been discussed at an intuitive level. In this paper we equip them with a structural operational semantics. As is typically the case, the purely operational picture is too concrete -- two graphs that are denotationally equal may exhibit different operational behaviour. We classify the ways in which this can occur and show that any graph can be realised -- rewritten, using the graphical theory, into an executable form where the operational behavior and the denotation coincides.
Succinct Representation of Concurrent Trace Sets
Authors: Gupta Ashutosh , Henzinger Thomas A. , Radhakrishna Arjun , Samanta Roopsha , Tarrach Thorsten
Published: May 2015

We present a method and a tool for generating succinct representations of sets of concurrent traces. We focus on trace sets that contain all correct or all incorrect permutations of events from a given trace. We represent trace sets as HB-Formulas that are Boolean combinations of happens-before constraints between events. To generate a representation of incorrect interleavings, our method iteratively explores interleavings that violate the specification and gathers generalizations of the discovered interleavings into an HB-Formula; its complement yields a representation of correct interleavings.

We claim that our trace set representations can drive diverse verification, fault localization, repair, and synthesis techniques for concurrent programs. We demonstrate this by using our tool in three case studies involving synchronization synthesis, bug summarization, and abstraction refinement based verification. In each case study, our initial experimental results have been promising.

In the first case study, we present an algorithm for inferring missing synchronization from an HB-Formula representing correct interleavings of a given trace. The algorithm applies rules to rewrite specific patterns in the HB-Formula into locks, barriers, and wait-notify constructs. In the second case study, we use an HB-Formula representing incorrect interleavings for bug summarization. While the HB-Formula itself is a concise counterexample summary, we present additional inference rules to help identify specific concurrency bugs such as data races, define-use order violations, and two-stage access bugs. In the final case study, we present a novel predicate learning procedure that uses HB-Formulas representing abstract counterexamples to accelerate counterexample-guided abstraction refinement (CEGAR). In each iteration of the CEGAR loop, the procedure refines the abstraction to eliminate multiple spurious abstract counterexamples drawn from the HB-Formula.
A Coalgebraic Decision Procedure for NetKAT
Authors: Foster Nate , Kozen Dexter , Milano Mae , Silva Alexandra , Thompson Laure
Published: May 2015

NetKAT is a domain-specific language and logic for specifying and verifying network packet-processing functions. It consists of Kleene algebra with tests (KAT) augmented with primitives for testing and modifying packet headers and encoding network topologies. Previous work developed the design of the language and its standard semantics, proved the soundness and completeness of the logic, defined a PSPACE algorithm for deciding equivalence, and presented several practical applications.

This paper develops the coalgebraic theory of NetKAT, including a specialized version of the Brzozowski derivative, and presents a new efficient algorithm for deciding the equational theory using bisimulation. The coalgebraic structure admits an efficient sparse representation that results in a significant reduction in the size of the state space. We discuss the details of our implementation and optimizations that exploit NetKAT's equational axioms and coalgebraic structure to yield significantly improved performance. We present results from experiments demonstrating that our tool is competitive with state-of-the-art tools on several benchmarks including all-pairs connectivity, loop-freedom, and translation validation.
Proof Spaces for Unbounded Parallelism
Authors: Farzan Azadeh , Kincaid Zachary , Podelski Andreas
Published: May 2015

In this paper, we present a new approach to automatically verify multi-threaded programs which are executed by an unbounded number of threads running in parallel.

The starting point for our work is the problem of how we can leverage existing automated verification technology for sequential programs (abstract interpretation, Craig interpolation, constraint solving, etc.) for multi-threaded programs. Suppose that we are given a correctness proof for a trace of a program (or for some other program fragment). We observe that the proof can always be decomposed into a finite set of Hoare triples, and we ask
what can be proved from the finite set of Hoare triples using only simple combinatorial inference rules
(without access to a theorem prover and without the possibility to infer genuinely new Hoare triples)?

We introduce a proof system where one proves the correctness of a multi-threaded program by showing that for each trace of the program,
there exists
a correctness proof in the space of proofs that are derivable from a finite set of axioms using simple combinatorial inference rules. This proof system is complete with respect to the classical proof method of establishing an inductive invariant (which uses thread quantification and control predicates). Moreover, it is possible to algorithmically check whether a given set of axioms is sufficient to prove the correctness of a multi-threaded program, using ideas from well-structured transition systems.
Data-Parallel String-Manipulating Programs
Authors: Veanes Margus , Mytkowicz Todd , Molnar David , Livshits Benjamin
Published: May 2015

String-manipulating programs are an important class of programs with applications in malware detection, graphics, input sanitization for Web security, and large-scale HTML processing. This paper extends prior work on BEK, an expressive domain-specific language for writing string-manipulating programs, with algorithmic insights that make BEK both analyzable and data-parallel. By analyzable we mean that unlike most general purpose programming languages, many algebraic properties of a BEK program are decidable (i.e., one can check whether two programs commute or compute the inverse of a program). By data-parallel we mean that a BEK program can compute on arbitrary subsections of its input in parallel, thus exploiting parallel hardware. This latter requirement is particularly important for programs which operate on large data: without data parallelism, a programmer cannot hide the latency of reading data from various storage media (i.e., reading a terabyte of data from a modern hard drive takes about 3 hours). With a data-parallel approach, the system can split data across multiple disks and thus hide the latency of reading the data.

A BEK program is expressive: a programmer can use conditionals, switch statements, and registers--or local variables--in order to implement common string-manipulating programs. Unfortunately, this expressivity induces data dependencies, which are an obstacle to parallelism. The key contribution of this paper is an algorithm which automatically removes these data dependencies by mapping a B EK program into a intermediate format consisting of symbolic transducers, which extend classical transducers with symbolic predicates and symbolic assignments. We present a novel algorithm that we call exploration which performs symbolic loop unrolling of these transducers to obtain simplified versions of the original program. We show how these simplified versions can then be lifted to a stateless form, and from there compiled to data-parallel hardware.

To evaluate the efficacy of our approach, we demonstrate up to 8x speedups for a number of real-world, BEK programs, (e.g., HTML encoder and decoder) on data-parallel hardware. To the best of our knowledge, these are the first data parallel implementation of these programs. To validate that our approach is correct, we use an automatic testing technique to compare our generated code to the original implementations and find no semantic deviations.
Rare Head and Neck Benign Mesenchymoma in Close Proximity to Submandibular Gland in a Pediatric Patient: Case Report and Review of the Literature
Authors: Jain Priyanka , Mukerji Shraddha
Published: May 2015

Pediatric head and neck masses are commonly congenital in origin or of infectious etiology. We present a rare case of benign mesenchymoma in close proximity to the submandibular gland in an otherwise asymptomatic child. Computerized tomography (CT) scan of the head and neck area revealed a benign lesion, which was later determined to be a benign mesenchymoma on histopathology. The child did well after surgery without any reported recurrence. We discuss the salient features of a benign mesenchymoma in a child and also discuss relevant imaging and management.
Polyarticular Septic Arthritis Caused byHaemophilus influenzaeSerotype f in an 8-Month-Old Immunocompetent Infant: A Case Report and Review of the Literature
Authors: Ali Raheel Ahmed , Kaplan Sheldon L. , Rosenfeld Scott B.
Published: May 2015

Background. The standard use of vaccinations against pathogens has resulted in a decreased incidence of musculoskeletal infections caused by these previously common bacterial pathogens. Consequently, the incidence of infections caused by atypical bacteria is rising. This report presents a case of septic arthritis caused by non-type bH. influenzaein a pediatric patient.Methods. We report a case of an infant with polyarticular septic arthritis caused byH. influenzaeserotype f. A literature review was conducted with the inclusion criteria of case reports and studies published between 2004 and 2013 addressing musculoskeletalH. influenzaeinfections.Results. An 8-month-old female presented with pain and swelling in her right ankle and left elbow. The patient was diagnosed with septic arthritis and underwent incision and drainage. Wound and blood cultures were positive forHaemophilus influenzaeserotype f. In addition to treatment with IV antibiotics, the patient underwent immunocompetency studies, which were normal. Subsequent follow-up revealed eradication of the infection.Conclusions.Haemophilus influenzaenon-type b may cause serious invasive infections such as sepsis or septic arthritis in children with or without predisposing factors such as immunodeficiency or asplenia. Optimal treatment includes surgical management, culture driven IV antibiotics, and an immunologic workup.
Patients with Fuchs Endothelial Dystrophy and Cataract Undergoing Descemet Stripping Automated Endothelial Keratoplasty and Phacoemulsification with Intraocular Lens Implant: Staged versus Combined Procedure Outcomes
Authors: Sykakis Evripidis , Lam Fook Chang , Georgoudis Panagiotis , Hamada Samer , Lake Damian
Published: May 2015

Purpose. To compare the surgical outcomes of staged and combined phacoemulsification with intraocular lens implant (phaco+IOL) and Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with Fuchs’ endothelial dystrophy and cataract.Setting. Corneoplastic Unit and Eye Bank, Queen Victoria Hospital, East Grinstead, UK.Methods. Retrospective study of patients who had combined phaco+IOL and DSAEK (group 1) or phaco+IOL followed within 2 months by DSAEK (group 2). Patients who had previous eye surgery or any other ocular comorbidities were excluded.Results. There were 28 eyes in group 1 and 31 in group 2. There were no significant differences in the demographics and corneal tissue characteristics of the two groups. The endothelial disc dislocation and rebubbling rate within 1 week in group 1 was 21.42% and in group 2 was 3.2%P=0.04, while the endothelial cell density at 12 months was1510±433for group 1 and1535±482for group 2P=0.89. The mean 12-month logMAR visual acuity was0.28±0.24for group 1 and0.33±0.15for group 2P=0.38.Conclusions. Although the combined procedure seems to be associated with a higher complication rate the final outcomes seem to be similar to both methods.
Role of Hydrogen Sulfide in Ischemia-Reperfusion Injury
Authors: Wu Dongdong , Wang Jun , Li Hui , Xue Mengzhou , Ji Ailing , Li Yanzhang
Published: May 2015

Ischemia-reperfusion (I/R) injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved situation in clinical practice, especially in the field of solid organ transplantation. Hydrogen sulfide (H2S) is the third gaseous signaling molecule and plays a broad range of physiological and pathophysiological roles in mammals. H2S could protect against I/R injury in many organs and tissues, such as heart, liver, kidney, brain, intestine, stomach, hind-limb, lung, and retina. The goal of this review is to highlight recent findings regarding the role of H2S in I/R injury. In this review, we present the production and metabolism of H2S and further discuss the effect and mechanism of H2S in I/R injury.
Effects of Arsenite Resistance on the Growth and Functional Gene Expression ofLeptospirillum ferriphilumandAcidithiobacillus thiooxidansin Pure Culture and Coculture
Authors: Jiang Huidan , Liang Yili , Yin Huaqun , Xiao Yunhua , Guo Xue , Xu Ying , Hu Qi , Liu Hongwei , Liu Xueduan
Published: May 2015

The response of iron-oxidizingLeptospirillum ferriphilumYSK and sulfur-oxidizingAcidithiobacillus thiooxidansA01 to arsenite under pure culture and coculture was investigated based on biochemical characterization (concentration of iron ion and pH value) and related gene expression.L. ferriphilumYSK andAt. thiooxidansA01 in pure culture could adapt up to 400 mM and 800 mM As(III) after domestication, respectively, although arsenite showed a negative effect on both strains. The coculture showed a stronger sulfur and ferrous ion oxidation activity when exposed to arsenite. In coculture, the pH value showed no significant difference when under 500 mM arsenite stress, and the cell number ofAt. thiooxidanswas higher than that in pure culture benefiting from the interaction withL. ferriphilum. The expression profile showed that the arsenic efflux system in the coculture was more active than that in pure culture, indicating that there is a synergetic interaction betweenAt. thiooxidansA01 andL. ferriphilumYSK. In addition, a model was proposed to illustrate the interaction between arsenite and thearsoperon inL. ferriphilumYSK andAt. thiooxidansA01. This study will facilitate the effective application of coculture in the bioleaching process by taking advantage of strain-strain communication and coordination.
Copious Podocyturia without Proteinuria and with Normal Renal Function in a Young Adult with Fabry Disease
Authors: Trimarchi H. , Canzonieri R. , Muryan A. , Schiel A. , Araoz A. , Forrester M. , Karl A. , Lombi F. , Andrews J. , Pomeranz V. , Rengel T. , Zotta E.
Published: May 2015

The time for starting a patient with Fabry disease on enzyme replacement therapy is still a matter of debate, particularly when no overt classical clinical signs or symptoms are present. With respect to Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement infusion until signs of renal disease appear as the appearance of proteinuria or an elevation in serum creatinine and the lack of validated biomarkers of early renal damage. In this regard, proteinuria is nowadays considered as an early and appropriate marker of kidney disease and of cardiovascular morbidity and mortality. However, in this report we demonstrate that podocyturia antedates the classical appearance of proteinuria and could be considered as an even earlier biomarker of kidney damage. Podocyturia may be a novel indication for the initiation of therapy in Fabry disease.
Peritoneal Breach as an Indication for Exploratory Laparotomy in Penetrating Abdominal Stab Injury: Operative Findings in Haemodynamically Stable Patients
Authors: Kevric Jasmina , Aguirre Victor , Martin Kate , Varma Dinesh , Fitzgerald Mark , Pilgrim Charles
Published: May 2015

Introduction. Management of haemodynamically stable patients with penetrating abdominal injuries varies from nonoperative to operative management. The aim was to investigate whether peritoneal breach when used as an indication for exploratory laparotomy appropriately identified patients with intra-abdominal visceral injury.Methods.We conducted retrospective cohort study of all patients presenting with PAI at a major trauma centre from January 2007 to December 2011. We measured the incidence of peritoneal breach and correlated this with intra-abdominal visceral injury diagnosed at surgery.Results. 252 patients were identified with PAI. Of the included patients, 71 were managed nonoperatively and 118 operatively. The operative diagnoses included nonperitoneal-breaching injuries, intraperitoneal penetration without organ damage, or intraperitoneal injury with organ damage. The presenting trauma CT scan was reported as normal in 63%, 34%, and 2% of these groups, respectively. The total negative laparotomy/laparoscopy rate for all patients presented with PAI was 21%, almost half of whom had a normal CT scan.Conclusion. We found that peritoneal breach on its own does not necessarily always equate to intra-abdominal visceral injury. Observation with sequential examination for PAI patients with a normal CT scan may be more important than exclusion of peritoneal breach via laparoscopy.
Prenatal Diagnosis of Central Nervous System Anomalies by High-Resolution Chromosomal Microarray Analysis
Authors: Sun Lijuan , Wu Qingqing , Jiang Shi-Wen , Yan Yani , Wang Xin , Zhang Juan , Liu Yan , Yao Ling , Ma Yuqing , Wang Li
Published: May 2015

The aims of this study were to evaluate the contribution of chromosomal microarray analysis (CMA) in the prenatal diagnosis of fetuses with central nervous system (CNS) anomalies but normal chromosomal karyotype. A total of 46 fetuses with CNS anomalies with or without other ultrasound anomalies but normal karyotypes were evaluated by array-based comparative genomic hybridisation (aCGH) or single-nucleotide polymorphism (SNP) array. The result showed that CNVs were detected in 17 (37.0%) fetuses. Of these, CNVs identified in 5 (5/46, 10.9%) fetuses were considered to be likely pathogenic, and CNVs detected in 3 (3/46, 6.5%) fetuses were defined as being of uncertain clinical significance. Fetuses with CNS malformations plus other ultrasound anomalies had a higher rate of pathogenic CNVs than those with isolated CNS anomalies (13.6% versus 8.3%), but there was no significant difference (Fisher’s exact test,P>0.05). Pathogenic CNVs were detected most frequently in fetuses with Dandy-Walker syndrome (2/6, 33.3%) when compared with other types of neural malformations, and holoprosencephaly (2/7, 28.6%) ranked the second. CMA is valuable in prenatal genetic diagnosis of fetuses with CNS anomalies. It should be considered as part of prenatal diagnosis in fetuses with CNS malformations and normal karyotypes.
Ultrastructural Changes in Human Trabecular Meshwork Tissue after Laser Trabeculoplasty
Authors: SooHoo Jeffrey R. , Seibold Leonard K. , Ammar David A. , Kahook Malik Y.
Published: May 2015

Purpose. To compare morphologic changes in human trabecular meshwork (TM) after selective laser trabeculoplasty (SLT) and argon laser trabeculoplasty (ALT).Design. Laboratory evaluation of ex vivo human eye TM after laser trabeculoplasty.Methods. Corneoscleral rims from human cadaver eyes were sectioned and treated with varying powers of either SLT or ALT. Specimens were examined using light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).Results. TEM of SLT at all powers resulted in disrupted TM cells with cracked and extracellular pigment granules. SEM of SLT samples treated at high power revealed tissue destruction with scrolling of trabecular beams. SEM of ALT-treated tissue showed increasing destruction with exposure to higher power. The presence or absence of “champagne” bubbles during SLT did not alter the histologic findings.Conclusions. SLT-treated human TM revealed disruption of TM cells with cracked, extracellular pigment granules, particularly at higher treatment powers. Tissue scrolling was noted at very high SLT energy levels. ALT-treated tissue showed significant damage to both the superficial and deeper TM tissues in a dose-dependent fashion. Further studies are needed to guide titration of treatment power to maximize the IOP-lowering effect while minimizing both energy delivered and damage to target tissues.
Long-Term Effect of Surgery in Graves’ Disease: 20 Years Experience in a Single Institution
Authors: Sung Tae-Yon , Lee Yu-mi , Yoon Jong Ho , Chung Ki-Wook , Hong Suck Joon
Published: May 2015

The present study compared the long-term outcome of subtotal thyroidectomy (ST) to that of total thyroidectomy (TT) in Graves’ disease (GD). Patients with GD requiring surgery were divided between two groups: ST and TT. Postoperative thyroid function (PoTF) changes, including hypothyroidism, euthyroidism, and hyperthyroidism, and surgical complications were analyzed 3 months and 2 years after surgery. During the study period, 350 GD patients underwent surgery, of whom 254 underwent ST and 96 underwent TT. In the ST group, the rates of hypothyroidism, euthyroidism, and hyperthyroidism were 92.5%, 6.7%, and 0.4%, respectively, after 3 months, and 86.1%, 8.6%, and 5.3%, respectively, after 2 years. No difference in the rate of surgical complication was observed between the ST and TT groups(p=0.089). Most of the ST patients showed hypothyroidism after surgery, and euthyroidism was rare. The long-term outcome of ST included noticeable PoTF changes and recurrence of GD. These results suggest that TT should be considered as a treatment option in GD requiring surgery.
Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Insulin-Producing Cells: Evidence for Further Maturation In Vivo
Authors: Gabr Mahmoud M. , Zakaria Mahmoud M. , Refaie Ayman F. , Khater Sherry M. , Ashamallah Sylvia A. , Ismail Amani M. , El-Halawani Sawsan M. , Ghoneim Mohamed A.
Published: May 2015

The aim of this study was to provide evidence for further in vivo maturation of insulin-producing cells (IPCs) derived from human bone marrow-derived mesenchymal stem cells (HBM-MSCs). HBM-MSCs were obtained from three insulin-dependent type 2 diabetic volunteers. Following expansion, cells were differentiated according to a trichostatin-A/GLP protocol. One million cells were transplanted under the renal capsule of 29 diabetic nude mice. Blood glucose, serum human insulin and c-peptide levels, and glucose tolerance curves were determined. Mice were euthanized 1, 2, 4, or 12 weeks after transplantation. IPC-bearing kidneys were immunolabeled, number of IPCs was counted, and expression of relevant genes was determined. At the end of in vitro differentiation, all pancreatic endocrine genes were expressed, albeit at very low values. The percentage of IPCs among transplanted cells was small (≤3%). Diabetic animals became euglycemic8±3days after transplantation. Thereafter, the percentage of IPCs reached a mean of ~18% at 4 weeks. Relative gene expression of insulin, glucagon, and somatostatin showed a parallel increase. The ability of the transplanted cells to induce euglycemia was due to their further maturation in the favorable in vivo microenvironment. Elucidation of the exact mechanism(s) involved requires further investigation.
What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
Authors: Bárcia R. N. , Santos J. M. , Filipe M. , Teixeira M. , Martins J. P. , Almeida J. , Água-Doce A. , Almeida S. C. P. , Varela A. , Pohl S. , Dittmar K. E. J. , Calado S. , Simões S. I. , Gaspar M. M. , Cruz M. E. M. , Lindenmaier W. , Graça L. , Cruz H. , Cruz P. E.
Published: May 2015

MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroboratedin vivoin a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression ofHLA-DRA,HO-1,IGFBP1, 4 and 6,ILR1,IL6RandPTGESand increased expression ofCD200,CD273,CD274,IL1B,IL-8,LIFandTGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1β, IL-8, LIF and TGFβ2.