Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Epidemiology of Metronidazole Resistance in a Population of Trichomonas vaginalis Clinical Isolates

ABSTRACT Trichomonas vaginalis, the causative agent for human trichomoniasis, is a problematic sexually transmitted disease mainly in women, where it may be asymptomatic or cause severe vaginitis and cervicitis. Despite its high prevalence, the genetic variability and drug resistance characteristics of this organism are poorly understood. To address these issues, genetic analyses were performed on 109 clinical isolates using three approaches. First, two internal transcribed spacer (ITS) regions flanking the 5.8S subunit of the ribosomal DNA gene were sequenced. The only variation was a point mutation at nucleotide position 66 of the ITS1 region found in 16 isolates (14.7%). Second, the presence of a 5.5-kb double-stranded RNAT. vaginalis virus (TVV) was assessed. TVV was detected in 55 isolates (50%). Finally, a phylogenetic analysis was performed based on random amplified polymorphic DNA data. The resulting phylogeny indicated at least two distinct lineages that correlate with the presence of TVV. A band-sharing index indicating relatedness was created for different groups of isolates. It demonstrated that isolates harboring the virus are significantly more closely related to each other than to the rest of the population, and it indicated a high level of relatedness among isolates with in vitro metronidazole resistance. This finding is consistent with the hypothesis that drug resistance toT. vaginalis resulted from a single or very few mutational events. Permutation tests and nonparametric analyses showed associations between metronidazole resistance and phylogeny, the ITS mutation, and TVV presence. These results suggest the existence of genetic markers with clinical implications for T. vaginalisinfections.
Treebank-based acquisition of Chinese LFG resources for parsing and generation

This thesis describes a treebank-based approach to automatically acquire robust,wide-coverage Lexical-Functional Grammar (LFG) resources for Chinese parsing and generation, which is part of a larger project on the rapid construction of deep, large-scale, constraint-based, multilingual grammatical resources. I present an application-oriented LFG analysis for Chinese core linguistic phenomena and (in cooperation with PARC) develop a gold-standard dependency-bank of Chinese f-structures for evaluation. Based on the Penn Chinese Treebank, I design and implement two architectures for inducing Chinese LFG resources, one annotation-based and the other dependency conversion-based. I then apply the f-structure acquisition algorithm together with external, state-of-the-art parsers to parsing new text into "proto" f-structures. In order to convert "proto" f-structures into "proper" f-structures or deep dependencies, I present a novel Non-Local Dependency (NLD) recovery algorithm using subcategorisation frames and f-structure paths linking antecedents and traces in NLDs extracted from the automatically-built LFG f-structure treebank. Based on the grammars extracted from the f-structure annotated treebank, I develop a PCFG-based chart generator and a new n-gram based pure dependency generator to realise Chinese sentences from LFG f-structures. The work reported in this thesis is the first effort to scale treebank-based, probabilistic Chinese LFG resources from proof-of-concept research to unrestricted, real text. Although this thesis concentrates on Chinese and LFG, many of the methodologies, e.g. the acquisition of predicate-argument structures, NLD resolution and the PCFG- and dependency n-gram-based generation models, are largely language and formalism independent and should generalise to diverse languages as well as to labelled bilexical dependency representations other than LFG.
Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS

The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin–angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may indicate heterodimerization of these receptors. Therefore, this study investigated the molecular and functional interplay between MAS and the AT2R. Molecular interactions were assessed by fluorescence resonance energy transfer and by cross correlation spectroscopy in human embryonic kidney-293 cells transfected with vectors encoding fluorophore-tagged MAS or AT2R. Functional interaction of AT2R and MAS was studied in astrocytes with CX3C chemokine receptor-1 messenger RNA expression as readout. Coexpression of fluorophore-tagged AT2R and MAS resulted in a fluorescence resonance energy transfer efficiency of 10.8 ± 0.8%, indicating that AT2R and MAS are capable to form heterodimers. Heterodimerization was verified by competition experiments using untagged AT2R and MAS. Specificity of dimerization of AT2R and MAS was supported by lack of dimerization with the transient receptor potential cation channel, subfamily C-member 6. Dimerization of the AT2R was abolished when it was mutated at cysteine residue 35. AT2R and MAS stimulation with the respective agonists, Compound 21 or angiotensin-(1–7), significantly induced CX3C chemokine receptor-1 messenger RNA expression. Effects of each agonist were blocked by an AT2R antagonist (PD123319) and also by a MAS antagonist (A-779). Knockout of a single of these receptors made astrocytes unresponsive for both agonists. Our results suggest that MAS and the AT2R form heterodimers and that—at least in astrocytes—both receptors functionally depend on each other.
Effectiveness of Percutaneous Lumbar Extraforaminotomy in Patients with Lumbar Foraminal Spinal Stenosis: A Prospective, Single-Armed, Observational Pilot Study

Objective In lumbar foraminal spinal stenosis (LFSS), numerous ligaments may play an important role in causing radiculopathy by narrowing the exit of the nerve root. In order to achieve effective decompression of lumbar foraminal ligaments, a specially designed instrument for percutaneous lumbar extraforaminotomy (PLEF) was invented. The purpose of this study was to evaluate the effectiveness of PLEF in patients with intractable radiculopathy from LFSS. Design A prospective, single-armed, observational pilot study. Setting A pain center in a tertiary university-based hospital. Methods The PLEF was performed in patients who suffered from radiculopathy with concordant imaging evidence of a mild to severe degree of LFSS. For each patient, an 11-point numerical rating scale (NRS) pain score, the Oswestry Disability Index (ODI), the Roland Morris Disability Questionnaire (RMDQ) score, and any adverse events were evaluated at three-month follow-ups. Successful responder percentage defined as 40% or greater reduction from baseline NRS score with no increase in ODI, and the RMDQ score was assessed at three months. Results Among 26 patients who underwent PLEF, 20 patients completed the study protocol. PLEF was successful in 12 patients (60%). The overall mean pain reduction at three months was 36.3%. Patients who responded well also showed improvement in the ODI (-20%) and RMDQ score (-8.4) at their three-month follow-up. No serious complications were reported in the study. Conclusions The PLEF can be an effective and safe treatment option, as well as a minimally invasive procedure, for the management of patients suffering from refractory radiculopathy caused by LFSS.
Measurement of delay mismatch due to process variations by means of modified ring oscillators

A novel and effective test circuit to measure cell-to-cell delay mismatch due to process variations is presented. A fully digital control circuit that efficiently realizes the technique is also described. The proposed test structure is realized by a series of modified ring oscillators that minimize factors of inaccuracy. The results of a simulation using 0.18 /spl mu/m CMOS technology show the feasibility of the technique. This test structure can be beneficial in thoroughly characterizing the effects of systematical process variations inside the chip.
Simple Finite-Control-Set Model Predictive Control of Grid-Forming Inverters With LCL Filters

Grid-forming inverters (GFI) play an important role as power interfaces for distributed generation units in islanded microgrids, where inductive-capacitive-inductive (LCL) output filters are commonly employed to mitigate the harmonics injected by voltage-source inverters. Due to advantages such as fast dynamic response and straightforward handling of constraints, Finite-control-set model predictive control (FCS-MPC) has become an attractive option for voltage control in GFI systems. However, conventional FCS-MPC algorithms with short prediction horizon have performance limitations in the tracking of ac references in systems with high-order dynamics, such as LCL-filtered GFIs. On the other hand, predictive algorithms with extended prediction horizons suffer from an increased computational burden. This paper proposes a new FCS-MPC algorithm to accurately control the capacitor voltage in an LCL-filtered GFI, using a discrete-time prediction model to dynamically compute the reference for a FCS-MPC inverter-side current controller. The main advantages of the proposed method are its simple implementation without requiring the tuning of weighting factors in its cost function; and its short prediction horizon, which maintains a reduced computational cost. Moreover, active resonance damping elements such as digital filters or ad hoc feedback loops to deal with the LCL filter resonance are not required. Simulation tests and experimental results in a laboratory-scale setup confirm the effectiveness of the proposed control algorithm, yielding lower distortion of output voltage waveforms and increased robustness to modeling errors compared with the conventional FCS-MPC approach.
Predictability of intranasal pharmacokinetics in man using pre-clinical pharmacokinetic data with a dopamine 3 receptor agonist, PF-219061

(R)-3-(4-propylmorpholin-2-yl) phenol (PF-219061) is a potent, selective agonist of the dopamine 3 receptor for the treatment of female sexual dysfunction. In vivo, PF-219061 exhibits liver blood flow clearance in both rat and dog. Oral bioavailability was 0.7% in dog and less than 5% in rat. Intranasal dosing was investigated to improve bioavailability. Pre-clinical assessments in rat and dog demonstrated intranasal bioavailabilities of 16–38% in rat and 54–61% in dog with very rapid absorption. It was predicted that an intranasal dose in man would give approximately 25–50% bioavailability. The clinical data verified the preclinical predictions demonstrating rapid absorption and approximately dose-proportional increases in exposure. The intranasal bioavailability in man was estimated to be 26–38%. These findings indicate the potential utility of intranasal dosing as a route that circumvents the first-pass effects for PF-219061 resulting in high exposures.
Theoretical and Practical Advances in the Assessment of Cross-Cultural Competence

Abstract : Organizations engaged in international operations must navigate complex intercultural dynamics for successful performance, necessitating identification of individuals who are likely to succeed in these environments and training personnel in cross-cultural competence (3C). To do so, adequate competency models of 3C need to be developed and valid 3C assessment instruments must be identified or generated. The present chapter reviews issues and challenges in 3C model development and illustrates these problems in an analysis of the Defense Language Office's Framework for Cross-Cultural Competence. The comparative advantages of competency versus causal models of 3C are discussed and an integration of competency and causal models is suggested. An examination of 34 instruments that have been recommended in the 3C civilian and military literatures for assessing cross-cultural competencies and their antecedent factors showed that existing 3C measures suffer from poor construct validity and have not been empirically linked to important outcome variables. A measurement strategy that eschews self-report methods and broadly assesses KSAOs and behavioral competencies is advocated.
Secretory-IgA Antibodies Play an Important Role in the Immunity to Streptococcus pneumoniae

This study was designed to investigate whether secretory-IgA (S-IgA) Abs induced by a pneumococcal surface protein A (PspA)-based nasal vaccine are necessary for prevention of streptococcal colonization. Mice nasally immunized with PspA plus a plasmid expressing Flt3 ligand (pFL) cDNA as a mucosal adjuvant showed significantly higher levels of PspA-specific S-IgA and IgG Ab responses in both plasma and nasal washes when compared with naive mice. Although IgA−/− mice given nasal PspA plus pFL had significantly high levels of PspA-specific IgG Abs, high numbers of CFUs were detected in nasal washes and nasal passages. In contrast, vaccinated wild-type mice showed essentially no bacteria in the nasal cavity. Further, a nasal vaccine consisting of PspA plus pFL effectively reduced pre-existing Streptococcus pneumoniae in the nasal cavity. These results show that PspA-based vaccine-induced specific S-IgA Abs play a necessary role in the regulation of S. pneumoniae colonization in the nasal cavity.
Prognostic Impact of Micrometastases in Colon Cancer: Interim Results of a Prospective Multicenter Trial

Objective:The 25% rate of recurrence after complete resection of stage II colon cancer (CC) suggests the presence of occult nodal metastases not identified by hematoxylin and eosin staining (H&E). Interim data from our ongoing prospective multicenter trial of sentinel node (SN) biopsy indicate a 29.6% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs in CC. We hypothesized that these MM have prognostic importance. Methods:Between March 2001 and August 2006, 152 patients with resectable colorectal cancer were enrolled in the trial. IHC and quantitative RT-PCR (qRT) assay were performed on H&E-negative SNs. Results were correlated with disease-free survival. Results:The sensitivity of lymphatic mapping was significantly better in CC (75%) than rectal cancer (36%), P < 0.05. Of 92 node-negative CC patients 7 (8%) were upstaged to N1 and 18 (22%) had IHC MM. Four patients negative by H&E and IHC were positive by qRT. At a mean follow-up of 25 months, 15 patients had died from noncancer-related causes, 12 had developed recurrence, 5 had died of CC (2 with macrometastases, 3 with MM), and 7 were alive with disease. The 12 recurrences included 4 patients with SN macrometastases and 6 with SN MM (2 by IHC, 4 by qRT). One of the 2 SN-negative recurrences had other positive lymph nodes by H&E. All patients with CC recurrences had a positive SN by either H&E/IHC or qRT. No CC patient with a negative SN by H&E and qRT has recurred (P = 0.002). Conclusion:This is the first prospective evaluation of the prognostic impact of MM in colorectal cancer. These results indicate that the detection of MM may be clinically relevant in CC and may improve the selection of patients for adjuvant systemic chemotherapy. Patients with CC who are node negative by cumulative detection methods (H&E/IHC and qRT) are likely to be cured by surgery alone.
A dual interior-point distributed algorithm for large-scale data networks optimization

This paper proposes a specialized decomposition algorithm, which incorporates the interior-point method into an augmented Lagrangian decomposition technique, for optimizing the quality of service through a data network. We show that many routing or resource allocation problems from the network literature can be recast into separable problems for which our algorithm can be applied. The proposed algorithm is highly parallelizable and thus suitable for distributively solving large-scale network problems.
An analytic Volterra-series-based model for a MEMS variable capacitor

Microelectromechanical systems (MEMS) components are gradually finding their way in communication applications. To fully understand their behavior in electrical circuits, an interpretable model is required that, in addition, can be simulated efficiently. This paper presents a model for a MEMS variable capacitor (varicap), that can be evaluated much more efficiently and equally accurate during circuit simulation than the differential equations that are normally used to describe this component. The model, based on Volterra series, describes the frequency dependence (e.g., the mechanical resonance) in combination with the nonlinear behavior of the MEMS varicap. The model is simple enough such that it can be interpreted by designers who want to use the MEMS varicap in RF communication circuits.
Endogenous Gene and Protein Expression of Drug-Transporting Proteins in Cell Lines Routinely Used in Drug Discovery Programs

The aim of this study was to investigate the gene and protein expression profiles of important drug-transporting proteins in human cell lines commonly used for studies of drug transport mechanisms. Human cell lines used to transiently or stably express single transporters [HeLa, human embryonic kidney (HEK) 293] and leukemia cell lines used to study drug resistance by ATP-binding cassette transporters (HL-60, K562) were investigated and compared with organotypic cell lines (HepG2, Saos-2, Caco-2, and Caco-2 TC7). For gene expression studies, real-time polymerase chain reaction was used, whereas monospecific polyclonal antibodies were generated and used to investigate protein expression by immunohistochemistry. Thirty-six transporters were studied for gene expression, and nine were studied for protein expression. The antibodies were validated using expression patterns in human tissues. Finally, the function of one ubiquitously expressed transporter, MCT1/SLC16A1, was investigated using [14C]lactic acid as a substrate. In general, the adherent cell lines (HeLa, HEK293) displayed low transporter expression, and the expression patterns were barely affected by transfection. The leukemia cell lines (K562, HL-60) and Saos-2 also had low endogenous transporter expression, whereas the organotypic cell lines (HepG2 and Caco-2) showed higher expression of some transporters. Comparison of gene and protein expression profiles gave poor correlations, but better agreement was obtained for antibodies with a good validation score, indicating that antibody quality was a significant variable. It is noteworthy that the monocarboxylic acid-transporting protein MCT1 was significantly expressed in all and was functional in most of the cell lines, indicating that MCT1 may be a confounding factor when the transport of small anionic drugs is investigated.
Différenciation génétique des populations humaines pour les gènes de la réponse aux médicaments

Tous les individus ne repondent pas de la meme facon a un meme traitement medicamenteux, tant sur le plan pharmacologique (efficacite) que sur le plan toxicologique (effets indesirables). Des facteurs genetiques affectant la pharmacocinetique et la pharmacodynamie des medicaments jouent un role determinant dans cette variabilite interindividuelle de reponse. Certains de ces facteurs sont distribues de maniere heterogene entre les populations humaines. Ces differences s’expliquent en partie par des phenomenes d’adaptation locale des populations a leur environnement. Au cours de son histoire, l’homme a du en effet faire face a des changements de son environnement chimique, qui ont entraine des pressions de selection naturelle sur les genes intervenant dans la reponse de l’organisme aux xenobiotiques. Ce sont ces memes genes qui, aujourd’hui, influencent la reponse aux medicaments.La formidable acceleration des progres de la genetique donne acces aujourd’hui a la variabilite genetique des populations humaines sur l’ensemble du genome, facilitant la decouverte et la comprehension des mecanismes genetiques a l’origine des traits complexes comme la reponse aux medicaments. Les outils de la genetique des populations permettent notamment d’identifier des variants affichant un niveau de differenciation genetique inhabituel entre les populations humaines et de determiner dans quelle mesure la selection naturelle a joue un role dans les profils atypiques observes.Dans cette these, nous avons applique ces outils a des donnees de genotypage et de sequencage pour analyser les profils de differenciation genetique des populations humaines pour les genes de la reponse aux medicaments. Nous avons ainsi demontre qu’une selection positive recente en Asie de l’Est dans la region genomique du gene VKORC1 etait responsable d’une heterogeneite de distribution du variant fonctionnel de VKORC1, a l’origine des differences de sensibilite genetique aux anticoagulant oraux de type antivitamine K entre les populations humaines. Puis, en etendant notre analyse a l’ensemble des pharmacogenes majeurs, nous avons identifie de nouveaux variants potentiellement interessants en pharmacogenetique pour expliquer les differences de reponse aux medicaments entre les populations humaines et les individus. Enfin, l’etude approfondie du gene NAT2 nous a permis de reveler un processus de selection homogeneisante ciblant un variant fonctionnel associe a un phenotype d’acetylation tres lent. Ces resultats soulignent l’influence determinante de la selection naturelle dans la variabilite de reponse aux medicaments entre les populations et les individus. Ils montrent l’apport de la genetique des populations pour une meilleure comprehension de la composante genetique de la reponse aux medicaments et des traits complexes.
CPMF: A collective pairwise matrix factorization model for upcoming event recommendation

Due to the rapid growth of event-based social networks (EBSNs), event recommendation which helps users find their preferred events has become a popular topic. Different from movies or books in conventional recommendation problem, events usually have recommendation lifetimes and almost all the events to be recommended are upcoming, which brings a severe cold start problem. To achieve better event recommendation performance, we formulates multiple interactions among users, events, groups and locations into an unified framework and propose a collective pairwise matrix factorization (CPMF) model to estimate users' pairwise preferences on events, groups and locations. We further develop an efficient stochastic gradient descent algorithm for the model learning. We conduct experiments on real-world Meetup datasets and the experimental results demonstrate that our CPMF model can outperform the state-of-the-art methods.
Integrin β1‐chain residues involved in substrate recognition and specificity of binding to invasin

A highly conserved 14‐amino‐acid region of the chicken β1 integrin chain (β1chk residues 151–168) hypothesized to be involved in divalent cation co‐ordination was analysed to determine whether invasin uses the same structural determinants as fibronectin (Fn) to recognize receptors. For the most part, both proteins required similar β1 chain residues for integrin recognition, although the relative preference of the integrin for the two substrates could be inverted mutationally. Substitution mutations in the amino terminal residues of this region resulted in defective binding to both substrates by the receptor, while substitutions at the carboxyl‐terminal end of this region were better tolerated. A derivative carrying the double substitution (KDD160RDV) had the unique phenotype of maintaining Fn binding while abolishing invasin binding, indicating that this region of the receptor may determine substrate specificity. These data indicate that the integrin β1 chain possesses a ligand binding site shared by invasin and Fn that can be altered by mutation to allow greater preference for the normally lower affinity substrate Fn than for invasin. It was also established that the region analysed has the ability to bind divalent cations.