bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrapulmonary Distribution and Pharmacokinetics of Laninamivir, a Neuraminidase Inhibitor, after a Single Inhaled Administration of Its Prodrug, Laninamivir Octanoate, in Healthy Volunteers
Authors: Ishizuka Hitoshi , Toyama Kaoru , Yoshiba Satoshi , Okabe Hiromi , Furuie Hidetoshi 
Published: April 2012

ABSTRACT
A single inhaled dose of laninamivir octanoate (LO), a long-acting neuraminidase inhibitor, exhibits efficacy in treating both adult and pediatric patients with influenza virus infection. The intrapulmonary pharmacokinetics (PK) of LO and laninamivir, a pharmacologically active metabolite, were investigated by a single-center, open-label study of healthy adult volunteers. Subgroups of five subjects each underwent bronchoalveolar lavage (BAL) 4, 8, 24, 48, 72, 168, and 240 h following a single inhaled administration of LO (40 mg). Plasma, BAL fluid, and alveolar macrophages (AM) were analyzed to determine LO and laninamivir concentrations, using validated liquid chromatography-tandem mass spectrometry methods. The concentrations in epithelial lining fluid (ELF) and AM from the first and subsequent BAL fluid samples were determined separately to explore the drug distribution in airways. Mean laninamivir concentrations in ELF, calculated using the first BAL fluids and BAL fluids collected 4 h after inhaled administration, were 8.57 and 2.40 μg/ml, respectively. The laninamivir concentration in ELF decreased with a longer half-life than that in plasma, and it exceeded the 50% inhibitory concentrations for viral neuraminidases at all time points examined for 240 h after the inhalation. Laninamivir exposure in ELF from the first BAL samples was 3.2 times higher than that in ELF from the subsequent BAL fluid samples. ELF concentration profiles of laninamivir support its long-lasting effect for treatment of patients with influenza virus infection by a single inhaled administration.
Complete Genome Sequence of the Rearranged Porcine Circovirus Type 2
Authors: Wen Libin , He Kongwang , Ni Yanxiu , Zhang Xuehan , Li Bin , Wang Xiaomin , Guo Rong li , Yu Zhengyu , Mao Aihua , Zhou Junming , Lv Lixin , Jiang Jieyuan 
Published: April 2012

ABSTRACT
We first report here the genome sequences of 4 rearranged porcine circovirus type 2 strains, JSTZ, ZJQDH1, ZJQDH2, and JSHM, isolated from porcine sera in China. The complete circular genomes of these isolates are 578, 483, 574, and 772 nucleotides in length, respectively. They are predicted to be defective interfering particles of porcine circovirus type 2. The findings will help us to understand molecular evolution of porcine circovirus type 2 and the relationship between porcine circovirus type 2 and diseases.
Complete Genome Sequences of a Korean Virulent Porcine Epidemic Diarrhea Virus and Its Attenuated Counterpart
Authors: Park Seong-Jun , Kim Hye-Kwon , Song Dae-Sub , An Dong-Jun , Park Bong-Kyun 
Published: April 2012

ABSTRACT
A virulent porcine epidemic diarrhea virus (PEDV) strain, DR13, was obtained from suckling pigs suspected of having porcine epidemic diarrhea in 1999 in Korea, and its attenuated counterpart was derived from virulent strain DR13 by serial propagation in Vero cells. This report describes the first complete genome sequences of virulent PEDV and its attenuated counterpart, which will provide important insights into the molecular basis of the attenuation of PEDV.
Pollination activity affects selection on floral longevity in the autumnal-flowering plant, Narcissus serotinus L.
Authors: Marques Isabel , Draper David 
Published: April 2012

Flower longevity, the period of time that a flower remains open, is a crucial factor in plant reproductive fitness. Though longevity varies substantially among angiosperm species, longer flower longevities may be a selective advantage under unpredictable or scarce pollination activity. This study examined this hypothesis in Narcissus serotinus L. (Amaryllidaceae), a small Mediterranean geophyte that blooms during the autumnal rainy season. Field experiments performed in three natural populations through 3 consecutive years shows that N. serotinus has the ability to expand flower longevity when pollination has not occurred. Flowers that were open longer to pollination have higher reproductive fitness than younger flowers. As N. serotinus flowers age, there was a shift in pollination patterns since flower visits by butterflies became scarcer and are replaced by one small pollen beetle. Given that there was evidence of pollen limitation and that this species produces one single flower, we suggest that extended flower longevity is selected because it assures pollination success under scarce insect visits.
Allelopathic effect of Salix caprea litter on late successional plants at different substrates of post-mining sites: pot experiment studies
Authors: Mudrák Ondřej , Frouz Jan 
Published: April 2012

The willow Salix caprea L. is a common colonizer of post-mining sites including those in the Sokolov coal mining district (Czech Republic) where this study was conducted. In one bioassay and two pot experiments, we investigated the effect of S. caprea litter on three plant species ( Arrhenatherum elatius (L.) P. Beauv. ex J. Presl & C. Presl, Plantago lanceolata L., and Lotus corniculatus L.) that commonly grow in late successional stages on these sites. In a sandy soil, leachate from fresh S. caprea litter reduced the number of germinated individuals (experiment 1) and shoot and root growth (experiment 2). In the clayey substrate originally unaffected by the S. caprea (experiment 3) leachate suppressed germination of all three species, but no reduction of biomass (both aboveground and belowground) was observed. Biomass was enhanced, however, in substrate that was naturally enriched with S. caprea litter (i.e., substrate collected on the same locality as previously mentioned substrate but beneath the S. caprea shrubs). Salix caprea therefore can suppress the establishment of new plants that arrive as seeds, but this suppression may only occur with seeds that directly contact the litter. When S. caprea litter is incorporated into the substrate, it can considerably improve substrate quality and the growth of successional plants.
Model Checking of Recursive Probabilistic Systems
Authors: Etessami Kousha , Yannakakis Mihalis 
Published: April 2012

Recursive Markov Chains (RMCs) are a natural abstract model of procedural probabilistic programs and related systems involving recursion and probability. They succinctly define a class of denumerable Markov chains that generalize several other stochastic models, and they are equivalent in a precise sense to probabilistic Pushdown Systems. In this article, we study the problem of model checking an RMC against an
ω
-regular specification, given in terms of a Büchi automaton or a Linear Temporal Logic (LTL) formula. Namely, given an RMC
A
and a property, we wish to know the probability that an execution of
A
satisfies the property. We establish a number of strong upper bounds, as well as lower bounds, both for
qualitative
problems (is the probability = 1, or = 0?), and for
quantitative
problems (is the probability ≥
p
?, or, approximate the probability to within a desired precision). The complexity upper bounds we obtain for automata and LTL properties are similar, although the algorithms are different.

We present algorithms for the qualitative model checking problem that run in polynomial space in the size |
A
| of the RMC and exponential time in the size of the property (the automaton or the LTL formula). For several classes of RMCs, including single-exit RMCs (a class that encompasses some well-studied stochastic models, for instance, stochastic context-free grammars) the algorithm runs in polynomial time in |
A
|. For the quantitative model checking problem, we present algorithms that run in polynomial space in the RMC and exponential space in the property. For the class of linearly recursive RMCs we can compute the exact probability in time polynomial in the RMC and exponential in the property. For deterministic automata specifications, all our complexities in the specification come down by one exponential.

For lower bounds, we show that the qualitative model checking problem, even for a fixed RMC, is already EXPTIME-complete. On the other hand, even for simple reachability analysis, we know from our prior work that our PSPACE upper bounds in
A
can not be improved substantially without a breakthrough on a well-known open problem in the complexity of numerical computation.
Annotated Probabilistic Temporal Logic
Authors: Shakarian Paulo , Simari Gerardo I. , Subrahmanian V. S. 
Published: April 2012

Annotated Probabilistic Temporal (APT) logic programs support building applications where we wish to reason about statements of the form “Formula
G
becomes true with a probability in the range [
L
,
U
] within (or in exactly)
Δt
time units after formula
F
became true.” In this paper, we present a sound, but incomplete fixpoint operator that can be used to check consistency and entailment in APT logic programs. We present the first implementation of APT-logic programs and evaluate both its compute time and convergence on a suite of 23 ground APT-logic programs that were automatically learned from two real-world data sets. In both cases, the APT-logic programs contained up to 1,000 ground rules. In one data set, entailment problems were solved on average in under 0.1 seconds per ground rule, while in the other, it took up to 1.3 seconds per ground rule. Consistency was also checked in a reasonable amount of time. When discussing entailment of APT-logic formulas, convergence of the fixpoint operator refers to (
U
−
L
) being below a certain threshold. We show that on virtually all of the 23 automatically generated APT-logic programs, convergence was quick---often in just 2-3 iterations of the fixpoint operator. Thus, our implementation is a practical first step towards checking consistency and entailment in temporal probabilistic logics without independence or Markovian assumptions.
Moment distributions of phase-type (abstract only)
Authors: Bladt Mogens , Nielsen Bo Friis 
Published: April 2012

Both matrix-exponential and phase-type distributions have a number of important closure properties. Among those are the distributions of the age and residual life-time of a stationary renewal process with inter-arrivals of either type. In this talk we show that the spread, which is the sum of the age an residual life-time, is also phase-type distributed. Moreover, we give some explicit representations. The spread is known to have a first order moment distribution. If X is a positive random variable and ?i is its i'th moment, then the function fi(x) = xif(x)/?i is a density function, and the corresponding distribution is called the i'th order moment distribution.
We prove that the classes of matrix-exponential or phase-type distributions are closed under the formation of moment distributions of any order. Other distributions which are closed under the formation of moment distributions are e.g. log-normal, Pareto and gamma distributions. We provide explicit representations for both the matrix-exponential class and for the phase-type distributions, where the latter class may also use the former representations, but for various reasons it is desirable to establish a phase-type representation when dealing with phase-type distributions.
For the first order distribution we present an explicit formula for the related Lorenz curve and Gini index. Moment distributions of orders one, two and three have been extensively used in areas such as economy, physics, demography and civil engineering.
An overview of multivariate gamma distributions as seen from a (multivariate) matrix exponential perspective
Authors: Bladt Mogens , Nielsen Bo Friis 
Published: April 2012

Numerous definitions of multivariate exponential and gamma distributions can be retrieved from the literature [4]. These distribtuions belong to the class of Multivariate Matrix-- Exponetial Distributions (MVME) whenever their joint Laplace transform is a rational function. The majority of these distributions further belongs to an important subclass of MVME distributions [5, 1] where the multivariate random vector can be interpreted as a number of simultaneously collected rewards during sojourns in a the states of a Markov chain with one absorbing state, the rest of the states being transient. We present the corresponding representations for all such distributions. In this way we obtain a unification of the variety of existing distributions as well as a deeper understanding of their probabilistic nature and a clarification of their similarities and differences. In particular one may easily generalize or combine any of the known distributions by modifying the generators adequately. Also, it is straightforward to simulate from this class. Thus, by identifying distributions as belonging to this subclass it becomes apparent how to simulate from most previously discussed distributions with rational Laplace transform. In a longer perspective stochastic and statistical analysis for MVME will in particular apply to any of the previously defined distributions.
Multivariate gamma distributions have been used in a variety of fields like hydrology, [11], [10], [6], space (wind modeling) [9] reliability [3], [7], traffic modeling [8], and, finance [2]. It is our hope that our the paper will assist practitioners in formulating and analyzing models in a much more transparent and easily accessible way.
Relyzer
Authors: Hari Siva Kumar Sastry , Adve Sarita V. , Naeimi Helia , Ramachandran Pradeep 
Published: April 2012

Future microprocessors need low-cost solutions for reliable operation in the presence of failure-prone devices. A promising approach is to detect hardware faults by deploying low-cost monitors of software-level symptoms of such faults. Recently, researchers have shown these mechanisms work well, but there remains a non-negligible risk that several faults may escape the symptom detectors and result in silent data corruptions (SDCs). Most prior evaluations of symptom-based detectors perform fault injection campaigns on application benchmarks, where each run simulates the impact of a fault injected at a hardware site at a certain point in the application's execution (application fault site). Since the total number of application fault sites is very large (trillions for standard benchmark suites), it is not feasible to study all possible faults. Previous work therefore typically studies a randomly selected sample of faults. Such studies do not provide any feedback on the portions of the application where faults were not injected. Some of those instructions may be vulnerable to SDCs, and identifying them could allow protecting them through other means if needed.
This paper presents Relyzer, an approach that systematically analyzes all application fault sites and carefully picks a small subset to perform selective fault injections for transient faults. Relyzer employs novel fault pruning techniques that prune faults that need detailed study by either predicting their outcomes or showing them equivalent to other faults. We find that Relyzer prunes about 99.78% of the total faults across twelve applications studied here, reducing the faults that require detailed simulation by 3 to 5 orders of magnitude for most of the applications. Fault injection simulations on the remaining faults can identify SDC causing faults in the entire application. Some of Relyzer's techniques rely on heuristics to determine fault equivalence. Our validation efforts show that Relyzer determines fault outcomes with 96% accuracy, averaged across all the applications studied here.
Mcl-1 Phosphorylation Defines ABT-737 Resistance That Can Be Overcome by Increased NOXA Expression in Leukemic B cells
Authors: Mazumder Suparna , Choudhary Gaurav S. , Al-harbi Sayer , Almasan Alexandru 
Published: April 2012

Abstract
ABT-737 is a small molecule Bcl-2 homology (BH)-3 domain mimetic that binds to the Bcl-2 family proteins Bcl-2 and Bcl-xL and is currently under investigation in the clinic. In this study, we investigated potential mechanisms of resistance to ABT-737 in leukemia cell lines. Compared with parental cells, cells that have developed acquired resistance to ABT-737 showed increased expression of Mcl-1 in addition to posttranslational modifications that facilitated both Mcl-1 stabilization and its interaction with the BH3-only protein Bim. To sensitize resistant cells, Mcl-1 was targeted by two pan–Bcl-2 family inhibitors, obatoclax and gossypol. Although gossypol was effective only in resistant cells, obatoclax induced cell death in both parental and ABT-737–resistant cells. NOXA levels were increased substantially by treatment with gossypol and its expression was critical for the gossypol response. Mechanistically, the newly generated NOXA interacted with Mcl-1 and displaced Bim from the Mcl-1/Bim complex, freeing Bim to trigger the mitochondrial apoptotic pathway. Together, our findings indicate that NOXA and Mcl-1 are critical determinants for gossypol-mediated cell death in ABT-737–resistant cells. These data therefore reveal novel insight into mechanisms of acquired resistance to ABT-737. Cancer Res; 72(12); 3069–79. ©2012 AACR.
Psychiatric diagnoses are not mental processes: Wittgenstein on conceptual confusion
Authors: Rosenman Stephen , Nasti Julian 
Published: April 2012

Background: Empirical explanation and treatment repeatedly fail for psychiatric diagnoses. Diagnosis is mired in conceptual confusion that is illuminated by Ludwig Wittgenstein’s later critique of philosophy ( Philosophical Investigations). This paper examines conceptual confusions in the foundation of psychiatric diagnosis from some of Wittgenstein’s important critical viewpoints. Argument: Diagnostic terms are words whose meanings are given by usages not definitions. Diagnoses, by Wittgenstein’s analogy with ‘games’, have various and evolving usages that are connected by family relationships, and no essence or core phenomenon connects them. Their usages will change according to the demands and contexts in which they are employed. Diagnoses, like many psychological terms, such as ‘reading’ or ‘understanding’, are concepts that refer not to fixed behavioural or mental states but to complex apprehensions of the relationship of a variety of behavioural phenomena with the world. A diagnosis is a sort of concept that cannot be located in or explained by a mental process. Conclusion: A diagnosis is an exercise in language and its usage changes according to the context and the needs it addresses. Diagnoses have important uses but they are irreducibly heterogeneous and cannot be identified with or connected to particular mental processes or even with a unity of phenomena that can be addressed empirically. This makes understandable not only the repeated failure of empirical science to replicate or illuminate genetic, neurophysiologic, psychic or social processes underlying diagnoses but also the emptiness of a succession of explanatory theories and treatment effects that cannot be repeated or stubbornly regress to the mean. Attempts to fix the meanings of diagnoses to allow empirical explanation will and should fail as there is no foundation on which a fixed meaning can be built and it can only be done at the cost of the relevance and usefulness of diagnosis.
Paroxysmal sneezing after hypothalamic deep brain stimulation for cluster headache
Authors: Maniyar Farooq H , Starr Philip , Goadsby Peter J 
Published: April 2012

Background: Cluster headache (CH) is the most common of the trigeminal autonomic cephalalgias (TAC), presenting with excruciatingly severe, short-lasting, unilateral headache accompanied by cranial autonomic symptoms. Chronic CH occurs in 10–15% of patients. Deep brain stimulation in the posterior hypothalamic region (hDBS) is successful in treating about 60% of patients otherwise refractory to medical treatment. Case: A 28-year-old man had hDBS for medically refractory left-sided chronic CH, with a resultant reduction in frequency and severity of his attacks. He developed recurrent paroxysms of sneezing soon after the stimulation was started that have reduced after increasing the pulse width from 60 to 90 µs. Discussion: Stimulation of the brain in the region of the posterior hypothalamus could produce sneezing from activation of facial nerve parasympathetic or trigeminal afferent pathway activation through the trigeminohypothalamic tract, or through other central mechanisms. DBS in general offers the opportunity to illuminate our understanding of brain function and for CH offers particular opportunities to understand a devastating primary headache syndrome.
Differences in clinical characteristics and frequency of accompanying migraine features in episodic and chronic cluster headache
Authors: Gaul C , Christmann N , Schröder D , Weber R , Shanib H , Diener HC , Holle D 
Published: April 2012

Introduction: Data on clinical differences between episodic (eCH) and chronic cluster headache (cCH) and accompanying migraine features are limited. Methods: History and clinical features of 209 consecutive cluster headache patients (144 eCH, 65 cCH; male:female ratio 3.4 : 1) were obtained in a tertiary headache centre by face-to-face interviews. Relationship between occurrence of accompanying symptoms, pain intensity, comorbid migraine, and circannual and circadian rhythmicity was analysed. Results: 99.5% of patients reported a minimum of one ipsilateral cranial autonomic symptom (CAS); 80% showed at least three CAS. A seasonal rhythmicity was observed in both eCH and cCH. A comorbid headache disorder occurred in 25%. No significant difference was detected between patients with comorbid migraine and without regarding occurrence of phonophobia, photophobia or nausea during cluster attacks. Patients with comorbid migraine reported allodynia significantly ( p = 0.022) more often during cluster attacks than patients without comorbid migraine. Conclusion: Occurrence of CAS and attack frequency, as well as periodic patterns of attacks, are relatively uniform in eCH and cCH. Multiple CAS are not related to pain intensity. Allodynia during cluster attacks is a frequent symptom. The unexpectedly high rate of accompanying migrainous features during cluster attacks cannot be explained by comorbid migraine.