Side-Effect Localization for Lazy, Purely Functional Languages via Aspects

Many side-effecting programming activities, such as profiling and tracing, can be formulated as crosscutting concerns and be framed as side-effecting aspects in the aspect-oriented programming paradigm. The benefit gained from this separation of concerns is particularly evident in purely functional programming, as adding such aspects using techniques such as monadification will generally lead to crosscutting changes. This paper presents an approach to provide side-effecting aspects for lazy purely functional languages in a user transparent fashion. We propose a simple yet direct state manipulation construct for developing side-effecting aspects and devise a systematic monadification scheme to translate the woven code to monadic style purely functional code. Furthermore, we present a static and dynamic semantics of the aspect programs and reason about the correctness of our monadification scheme with respect to them

Efficient System-Enforced Deterministic Parallelism

Deterministic execution offers many benefits for debugging, fault tolerance, and security. Current methods of executing parallel programs deterministically, however, often incur high costs, allow misbehaved software to defeat repeatability, and transform time-dependent races into input- or path-dependent races without eliminating them. We introduce a new parallel programming model addressing these issues, and use Determinator, a proof-of-concept OS, to demonstrate the model's practicality. Determinator's microkernel API provides only “shared-nothing” address spaces and deterministic interprocess communication primitives to make execution of all unprivileged code—well-behaved or not—precisely repeatable. Atop this microkernel, Determinator's user-level runtime adapts optimistic replication techniques to offer a private workspace model for both thread-level and process-level parallel programing. This model avoids the introduction of read/write data races, and converts write/write races into reliably-detected conflicts. Coarse-grained parallel benchmarks perform and scale comparably to nondeterministic systems, on both multicore PCs and across nodes in a distributed cluster

Site-directed in vitro immunization leads to a complete human monoclonal IgG4λ that binds specifically to the CDR2 region of CTLA-4 (CD152) without interfering the engagement of natural ligands

<p>Abstract</p> <p>Background</p> <p>The ability to acquire fully human monoclonal antibodies (mAbs) with pre-defined specificities is critical to the development of molecular tags for the analysis of receptor function in addition to promising immunotherapeutics. Yet most of the arriving affinity maturated and complete human immunoglobulin G (IgG) molecules, which are actually derived from single human B cells, have not widely been used to study the conserved self antigens (Ags) such as CD152 (cytotoxic T lymphocyte antigen-4, CTLA-4) because proper hosts are lacking.</p> <p>Results</p> <p>Here we developed an optimized protocol for site-directed <it>in vitro </it>immunizing peripheral blood mononuclear cells (PBMC) by using a selected epitope of human CD152, an essential receptor involved in down-regulation of T cell activation. The resultant stable trioma cell lines constantly produce anti-CD152 mAb (γ4λhuCD152), which contains variable (V) regions of the heavy chain and the light chain derived from the VH3 and Vλ human germline genes, respectively, and yet displays an unusual IgG4 isotype. Interestingly, γ4λhuCD152 has a basic pI not commonly found in myeloid monoclonal IgG4λs as revealed by the isoelectric focusing (IEF) analysis. Furthermore, γ4λhuCD152 binds specifically, with nanomolar affinity, to an extracellular constituency encompassing the putative second complementarity determining region (CDR2) of CD152, whereby it can react to activated CD3⁺cells.</p> <p>Conclusion</p> <p>In a context of specific cell depletion and conditioned medium,<it>in vitro </it>induction of human Abs against a conserved self Ag was successfully acquired and a relatively basic mAb, γ4λhuCD152, with high affinity to CDR2 of CD152 was thus obtained. Application of such a human IgG4λ mAb with designated CDR2 specificity may impact upon and prefer for CD152 labeling both <it>in situ </it>and <it>ex situ</it>, as it does not affect the binding of endogenous B7 ligands and can localize into the confined immunological synapse which may otherwise prevent the access of whole IgG1 molecules.</p

Type-Directed Weaving of Aspects for Polymorphically Typed Functional Languages

Incorporating aspect-oriented paradigm to a polymorphically typed functional language enables the declaration of type-scoped advice, in which the effect of an aspect can be harnessed by introducing possibly polymorphic type constraints to the aspect. The amalgamation of aspect orientation and functional programming enables quick behavioral adaption of functions, clear separation of concerns and expressive type-directed programming. However, proper static weaving of aspects in polymorphic languages with a type-erasure semantics remains a challenge. In this paper, we describe a type-directed static weaving strategy, as well as its implementation, that supports static type inference and static weaving of programs written in an aspect-oriented polymorphically typed functional language, AspectFun. We show examples of type-scoped advice, identify the challenges faced with compile-time weaving in the presence of type-scoped advice, and demonstrate how various advanced aspect features can be handled by our techniques. Lastly, we prove the correctness of the static weaving strategy with respect to the operational semantics of AspectFun

Fast Distributed Transactions for Partitioned Database Systems.

ABSTRACT Many distributed storage systems achieve high data access throughput via partitioning and replication, each system with its own advantages and tradeoffs. In order to achieve high scalability, however, today&apos;s systems generally reduce transactional support, disallowing single transactions from spanning multiple partitions. Calvin is a practical transaction scheduling and data replication layer that uses a deterministic ordering guarantee to significantly reduce the normally prohibitive contention costs associated with distributed transactions. Unlike previous deterministic database system prototypes, Calvin supports disk-based storage, scales near-linearly on a cluster of commodity machines, and has no single point of failure. By replicating transaction inputs rather than effects, Calvin is also able to support multiple consistency levels-including Paxosbased strong consistency across geographically distant replicas-at no cost to transactional throughput

Security Analysis of Accountable Anonymity in Dissent

Users often wish to communicate anonymously on the Internet, for example in group discussion or instant messaging forums. Existing solutions are vulnerable to misbehaving users, however, who may abuse their anonymity to disrupt communication. Dining Cryptographers Networks (DC-nets) leave groups vulnerable to denial-of-service and Sybil attacks, mix networks are difficult to protect against traffic analysis, and accountable voting schemes are unsuited to general anonymous messaging. DISSENT is the first general protocol offering provable anonymity and accountability for moderate-size groups, while efficiently handling unbalanced communication demands among users. We present an improved and hardened DISSENT protocol, define its precise security properties, and offer rigorous proofs of these properties. The improved protocol systematically addresses the delicate balance between provably hiding the identities of well-behaved users, while provably revealing the identities of disruptive users, a challenging task because many forms of misbehavior are inherently undetectable. The new protocol also addresses several non-trivial attacks on the original DISSENT protocol stemming from subtle design flaws

Clonal dissemination of the multi-drug resistant Salmonella enterica serovar Braenderup, but not the serovar Bareilly, of prevalent serogroup C1 Salmonella from Taiwan

<p>Abstract</p> <p>Background</p> <p>Nontyphoidal <it>Salmonella </it>is the main cause of human salmonellosis. In order to study the prevalent serogroups and serovars of clinical isolates in Taiwan, 8931 <it>Salmonellae </it>isolates were collected from 19 medical centers and district hospitals throughout the country from 2004 to 2007. The pulsed-field eletrophoresis types (PFGE) and antibiotic resistance profiles of <it>Salmonella enterica </it>serovars Bareilly (<it>S</it>. Bareilly) and Braenderup (<it>S</it>. Braenderup) were compared, and multi-drug resistance (MDR) plasmids were characterized.</p> <p>Results</p> <p>Over 95% of human salmonellosis in Taiwan was caused by five <it>Salmonella </it>serogroups: B, C1, C2-C3, D1, and E1. <it>S</it>. Typhymurium, <it>S</it>. Enteritidis, <it>S</it>. Stanley and <it>S</it>. Newport were the four most prevalent serovars, accounting for about 64% of isolates. While only one or two major serovars from four of the most prevalent serogroups were represented, four predominant serovars were found in serogroup C1 <it>Salmonellae</it>. The prevalence was decreasing for <it>S</it>. Choleraeuis and <it>S</it>. Braenderup, and S. Virchow and increasing for <it>S</it>. Bareilly. <it>S</it>. Braenderup mainly caused gastroenteritis in children; in contrast, <it>S</it>. Bareiley infected children and elderly people. Both serovars differed by <it>Xba</it>I-PFGE patterns. Almost all <it>S</it>. Bareilly isolates were susceptible to antibiotics of interest, while all lacked plasmids and belonged to one clone. Two distinct major clones in <it>S</it>. Braenderup were cluster A, mainly including MDR isolates with large MDR plasmid from North Taiwan, and cluster B, mainly containing susceptible isolates without R plasmid from South Taiwan. In cluster A, there were two types of conjugative R plasmids with sizes ranging from 75 to 130 kb. Type 1 plasmids consisted of replicons F1A/F1B, <it>bla</it>_TEM, IS<it>26</it>, and a class 1 integron with the genes <it>dfrA12</it>-<it>orfF</it>-<it>aadA2-qacE</it>Δ1-<it>sulI</it>. Type 2 plasmids belonged to incompatibility group Inc<it>I</it>, contained <it>tnpA</it>-<it>bla</it>_CMY-2-<it>blc</it>-<it>sugE </it>genetic structures and lacked both IS<it>26 </it>and class 1 integrons. Although type 2 plasmids showed higher conjugation capability, type 1 plasmids were the predominant plasmid.</p> <p>Conclusions</p> <p>Serogroups B, C1, C2-C3, D1, and E1 of <it>Salmonella </it>caused over 95% of human salmonellosis. Two prevalent serovars within serogroup C1, <it>S</it>. Bareilly and cluster B of S. Braenderup, were clonal and drug-susceptible. However, cluster A of <it>S</it>. Braenderup was MDR and probably derived from susceptible isolates by acquiring one of two distinct conjugative R plasmids.</p

Seminar Report From the 2014 Taiwan Society of Inflammatory Bowel Disease (TSIBD) Spring Forum (May 24th, 2014): Crohn's Disease Versus Intestinal Tuberculosis Infection

Since Taiwan is an endemic area for tuberculosis (TB), differential diagnosis between the intestinal TB and Crohn's disease is an important issue. The steering committee of Taiwan Society of Inflammatory Bowel Disease (TSIBD) has arranged a seminar accordingly on May 24th, 2014 and the different point of views by gastroenterologist, radiologist, pathologist and infectious disease specialist were suggested to help the proper diagnosis and management of these two diseases

miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions

MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system