Miracle-dz/UniFAR-FTUs huggingface dataset:
Stromelysin‐3 suppresses tumor cell apoptosis in a murine model *

Stromelysin‐3 (STR‐3) is a matrix metalloproteinase with a unique pattern of expression and substrate specificity. During embryogenesis and remodeling of normal adult tissues, STR‐3 is produced by stromal cells in direct contact with epithelial cells undergoing regional apoptosis and selective cell survival. STR‐3 is also overexpressed by interdigitating stromal cells in primary epithelial malignancies. Although STR‐3 does not degrade classic extracellular matrix components, the enzyme promotes the establishment of local tumors in nude mice by as yet undefined mechanisms. STR‐3 is induced when malignant epithelial cells come into contact with surrounding stromal elements; the active stromal cell‐derived 45 kDa enzyme is subsequently processed to a 35 kDa protein without enzymatic activity. We have generated MCF‐7 transfectants expressing wild type or catalytically inactive 45 kDa STR‐3 (STR‐3wt and STR‐3cat‐) or secreted 35 kDa STR‐3 (35 kDa STR‐3sec) and evaluated their implantation and survival in nude mice. Tumors developed significantly more rapidly in animals receiving STR‐3wt, rather than vector‐only, STR‐3cat‐ or 35 kDa STR‐3sec transfectants. Most importantly, STR‐3wt tumors had a significantly lower percentage of apoptotic cells than tumors derived from vector‐only, STR‐3cat‐ or 35 kDa STR‐3sec transfectants. Taken together, these studies suggest that the active STR‐3 enzyme may increase tumor take by suppressing tumor cell apoptosis and that 45 kDa to 35 kDa STR‐3 processing limits STR‐3 activity at the tumor/stromal interface. Because STR‐3 is secreted as an active enzyme rather than a proform, subsequent 45 kDa to 35 kDa STR‐3 processing may represent a novel mechanism for regulating enzymatic activity. J. Cell. Biochem. 82: 549–555, 2001. © 2001 Wiley‐Liss, Inc.
A self-administered technique for the detection of sexually transmitted diseases in remote communities.

The control of sexually transmitted diseases (STDs) in remote rural communities would be enhanced by a sensitive self-administered method for the detection of asymptomatic infection. Results of conventional methods for the detection of STDs were compared with results of tampon-collected specimens analyzed by polymerase chain reaction (PCR) for 480 women. Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis were detected by routine methods in 4 (1%), 14 (3%), and 41 (9%) samples, respectively, while PCR detected these organisms from 52 (11%), 26 (5%), and 75 (16%) tampons, respectively. The detection of each organism was significantly greater by PCR in tampon-collected samples than by routine conventional methods (P < .01). Discrepant results were confirmed by separate primers in 40 of 48 specimens for N. gonorrhoeae, in 11 of 12 specimens for C. trachomatis, and in 31 of 32 specimens for T. vaginalis. Tampons tested by PCR provide an acceptable and sensitive method for detection of STDs in women living in remote areas.
Acute Effect of Caffeine on Arterial Stiffness and Aortic Pressure Waveform

Caffeine acutely increases blood pressure and peripheral vascular resistance, in part because of sympathetic stimulation. Its effects on large artery properties are largely unknown. In a double-blind crossover study, 7 healthy subjects 26±2.6 years of age (mean±SEM) were studied for 90 minutes while in the supine position on 2 occasions separated by a week in random order after ingestion of 250 mL caffeinated (150 mg) and decaffeinated (<2 mg) coffee. Compared with baseline, arterial stiffness measured by carotid femoral pulse wave velocity increased progressively from 7.2±0.41 to 8.0±0.6 m/s (P <0.05) at 90 minutes after caffeine intake, an effect that may be independent of changes in blood pressure. In addition, arterial wave reflection, measured by applanation tonometry from the aortic pressure waveform, also increased from −5.7±7.6% to 5.28%±5.6 (P <0.01). No such changes were seen with decaffeinated coffee intake. Although the integral of the brachial systolic and diastolic blood pressure values over the 90 minutes was larger (P <0.05) after caffeinated than decaffeinated coffee intake, the effect on aortic systolic and diastolic blood pressures was more pronounced (P <0.05) than on the brachial artery. These results show a significant effect of caffeine intake on arterial tone and function and suggest that caffeine acutely increases arterial stiffness.
Electronegative low-density lipoprotein

Purpose of review The occurrence in blood of an electronegatively charged LDL was described in 1988. During the 1990s reports studying electronegative LDL (LDL(-)) were scant and its atherogenic role controversial. Nevertheless, recent reports have provided new evidence on a putative atherogenic role of LDL(-). This review focuses on and discusses these new findings. Recent findings In recent years, LDL(-) has been found to be involved in several atherogenic features through its action on cultured endothelial cells. LDL(-) induces the production of chemokines, such as IL-8 and monocyte chemotactic protein 1, and increases tumor necrosis factor-α-induced production of vascular cell adhesion molecule 1, with these molecules being involved in early phases of leukocyte recruitment. LDL(-) from familial hypercholesterolemic patients also decreases DNA synthesis and intracellular fibroblast growth factor 2 production, which may contribute to impaired angiogenesis and increased apoptosis. In addition, the preferential association of platelet-activating factor acetylhydrolase with LDL(-) has been reported, suggesting a proinflammatory role of this enzyme in LDL(-). Summary Recent findings suggest that LDL(-) could contribute to atherogenesis via several mechanisms, including proinflammatory, proapoptotic and antiangiogenesis properties. Further studies are required to define the role of LDL(-) in atherogenesis more precisely and to clarify mechanisms involved in endothelial cell activation.
A Method for Evaluating the Electro-Mechanical Characteristics of Piezoelectric Actuators during Motion

The electro-mechanical characteristics of piezoelectric actuators which have being driven are evaluated in this paper. The force generated by actuators is measured as an inertial force of a corner cub prism which is attached to the actuators. The Doppler frequency shift of a laser beam, due to the motion of actuator, is accurately measured by a heterodyne interferometer. Subsequently, the mechanical quantities, such as velocity, acceleration, force, power and displacement, are calculated from the Doppler frequency shift. With the measurement results of current and voltage of the actuator, the relationships between electrical and mechanical characteristics are evaluated.
Promises as Commitments

Abstract: We implement a trust game in which the trustee can write a free-form pre-play message for the trustor. The main twist in our design is that there is a 50% probability that the message is delivered to the trustor and a 50% probability that the message is replaced by an empty sheet. We find that even when messages are not delivered trustees who make a promise are significantly more likely to act trustworthy than those who do not make a promise. This suggests that a promise has a commitment value which is independent of its impact on the trustor. Interestingly, we also find that both trustees who make a promise and those who do not make a promise are more likely to be trustworthy if their message is delivered to the trustor. This means that communication increases trustworthiness irrespective of the content of messages.
Two-stent techniques for coronary bifurcation lesions (main vessel first versus side branch first): results from the COBIS (COronary BIfurcation Stenting) II registry.

AIMS It has not been known which two-stent technique is best for treating bifurcation lesions. We aimed to compare the outcomes from main vessel (MV) first and side branch (SB) first techniques for patients with bifurcation lesions requiring a two-stent approach. METHODS AND RESULTS A total of 673 patients with bifurcation lesions were treated with two-stent techniques: MV first (n=250) or SB first (n=423). The rate of a composite of cardiac death, myocardial infarction, or target lesion revascularisation (TLR) was similar in the two groups (SB first versus MV first, 15.1% versus 15.6% in the total population [p=0.90]; 14.3% versus 17.4% in a propensity score-matched population [p=0.80]). There were significant interactions associated with TLR risk between MV and SB first techniques according to angiographic factors. Patients in the MV first group had a lower risk of TLR when they had a lesion with MV diameter stenosis ≥70% (p for interaction=0.04), more severe stenosis of the MV than of the SB (p for interaction=0.008), or MV lesion length ≥18 mm (p for interaction=0.01). CONCLUSIONS Clinical outcomes were similar for patients treated with MV or SB first two-stent techniques. Using "more severe lesion first" two-stent techniques might offer a favourable prognosis.
Multiple deleterious effects of experimentally aged sperm in a monogamous bird

Sperm aging is known to be detrimental to reproductive performance. However, this apparently general phenomenon has seldom been studied in an evolutionary context. The negative impact of sperm aging on parental fitness should constitute a strong selective pressure for adaptations to avoid its effects. We studied the impact of sperm aging on black-legged kittiwakes (Rissa tridactyla), a monogamous seabird. Kittiwakes comprise a model system because (i) of evidence that females eject their mates' sperm to prevent fertilization by sperm that would be old and degraded by the time of fertilization and result in reduced reproductive performance and (ii) the lack of extra-pair fertilization in this species makes cryptic female choice an unlikely explanation of postcopulatory sperm ejection by females. We experimentally manipulated the age of the sperm fertilizing kittiwake eggs by fitting males with anti-insemination rings for variable periods of time preceding egg-laying. We found evidence that sperm aging negatively affected four sequential stages of reproduction: fertilization potential, rate of embryonic development, embryonic mortality, and chick condition at hatching. These results may be produced by a continuum of a single process of sperm aging that differentially affects various aspects of development, depending on the degree of damage incurred to the spermatozoa. The marked impact of sperm age on female fitness may thus drive postcopulatory sperm ejection by females. These results provide experimental evidence of deleterious effects of sperm aging on a nondomestic vertebrate, underlining its taxonomic generality and its potential to select for a wide array of adaptations.
Gating of Shaker-type Channels Requires the Flexibility of S6 Caused by Prolines*

The recent crystallization of a voltage-gated K+ channel has given insight into the structure of these channels but has not resolved the issues of the location and the operation of the gate. The conserved PXP motif in the S6 segment of Shaker channels has been proposed to contribute to the intracellular gating structure. To investigate the role of this motif in the destabilization of the α-helix, both prolines were replaced to promote an α-helix (alanine) or to allow a flexible configuration (glycine). These substitutions were nonfunctional or resulted in drastically altered channel gating, highlighting an important role of these prolines. Combining these mutations with a proline substitution scan demonstrated that proline residues in the midsection of S6 are required for functionality, but not necessarily at the positions conserved throughout evolution. These results indicate that the destabilization or bending of the S6 α-helix caused by the PXP motif apparently creates a flexible “hinge” that allows movement of the lower S6 segment during channel gating and opening.
Network Discovery Pipeline Elucidates Conserved Time-of-Day–Specific cis-Regulatory Modules

Correct daily phasing of transcription confers an adaptive advantage to almost all organisms, including higher plants. In this study, we describe a hypothesis-driven network discovery pipeline that identifies biologically relevant patterns in genome-scale data. To demonstrate its utility, we analyzed a comprehensive matrix of time courses interrogating the nuclear transcriptome of Arabidopsis thaliana plants grown under different thermocycles, photocycles, and circadian conditions. We show that 89% of Arabidopsis transcripts cycle in at least one condition and that most genes have peak expression at a particular time of day, which shifts depending on the environment. Thermocycles alone can drive at least half of all transcripts critical for synchronizing internal processes such as cell cycle and protein synthesis. We identified at least three distinct transcription modules controlling phase-specific expression, including a new midnight specific module, PBX/TBX/SBX. We validated the network discovery pipeline, as well as the midnight specific module, by demonstrating that the PBX element was sufficient to drive diurnal and circadian condition-dependent expression. Moreover, we show that the three transcription modules are conserved across Arabidopsis, poplar, and rice. These results confirm the complex interplay between thermocycles, photocycles, and the circadian clock on the daily transcription program, and provide a comprehensive view of the conserved genomic targets for a transcriptional network key to successful adaptation.
Learning to create data-integrating queries

The number of potentially-related data resources available for querying --- databases, data warehouses, virtual integrated schemas --- continues to grow rapidly. Perhaps no area has seen this problem as acutely as the life sciences, where hundreds of large, complex, interlinked data resources are available on fields like proteomics, genomics, disease studies, and pharmacology. The schemas of individual databases are often large on their own, but users also need to pose queries across multiple sources, exploiting foreign keys and schema mappings. Since the users are not experts, they typically rely on the existence of pre-defined Web forms and associated query templates, developed by programmers to meet the particular scientists' needs. Unfortunately, such forms are scarce commodities, often limited to a single database, and mismatched with biologists' information needs that are often context-sensitive and span multiple databases. We present a system with which a non-expert user can author new query templates and Web forms, to be reused by anyone with related information needs. The user poses keyword queries that are matched against source relations and their attributes; the system uses sequences of associations (e.g., foreign keys, links, schema mappings, synonyms, and taxonomies) to create multiple ranked queries linking the matches to keywords; the set of queries is attached to a Web query form. Now the user and his or her associates may pose specific queries by filling in parameters in the form. Importantly, the answers to this query are ranked and annotated with data provenance, and the user provides feedback on the utility of the answers, from which the system ultimately learns to assign costs to sources and associations according to the user's specific information need, as a result changing the ranking of the queries used to generate results. We evaluate the effectiveness of our method against "gold standard" costs from domain experts and demonstrate the method's scalability.
Properties of Monoclonal Antibodies Directed against Hepatitis B Virus Polymerase Protein

ABSTRACT Hepadnavirus polymerases are multifunctional enzymes that play critical roles during the viral life cycle but have been difficult to study due to a lack of a well-defined panel of monoclonal antibodies (MAbs). We have used recombinant human hepatitis B virus (HBV) polymerase (Pol) expressed in and purified from baculovirus-infected insect cells to generate a panel of six MAbs directed against HBV Pol protein. Such MAbs were subsequently characterized with respect to their isotypes and functions in analytical and preparative assays. Using these MAbs as probes together with various deletion mutants of Pol expressed in insect cells, we mapped the B-cell epitopes of Pol recognized by these MAbs to amino acids (aa) 8 to 20 and 20 to 30 in the terminal protein (TP) region of Pol, to aa 225 to 250 in the spacer region, and to aa 800 to 832 in the RNase H domain. Confocal microscopy and immunocytochemical studies using various Pol-specific MAbs revealed that the protein itself appears to be exclusively localized to the cytoplasm. Finally, MAbs specific for the TP domain, but not MAbs specific for the spacer or RNase H regions of Pol, appeared to inhibit Pol function in the in vitro priming assay, suggesting that antibody-mediated interference with TP may now be assessed in the context of HBV replication.
A catalog of stream processing optimizations

Various research communities have independently arrived at stream processing as a programming model for efficient and parallel computing. These communities include digital signal processing, databases, operating systems, and complex event processing. Since each community faces applications with challenging performance requirements, each of them has developed some of the same optimizations, but often with conflicting terminology and unstated assumptions. This article presents a survey of optimizations for stream processing. It is aimed both at users who need to understand and guide the system’s optimizer and at implementers who need to make engineering tradeoffs. To consolidate terminology, this article is organized as a catalog, in a style similar to catalogs of design patterns or refactorings. To make assumptions explicit and help understand tradeoffs, each optimization is presented with its safety constraints (when does it preserve correctness? ) and a profitability experiment (when does it improve performance? ). We hope that this survey will help future streaming system builders to stand on the shoulders of giants from not just their own community.
Impact of a New Reimbursement Program on Hepatitis B Antiviral Medication Cost and Utilization in Beijing, China

Background Hepatitis B virus (HBV) infection is a significant clinical and financial burden for chronic hepatitis B (CHB) patients. In Beijing, China, partial reimbursement on antiviral agents was first implemented for the treatment of CHB patients in July 1, 2011. Aims In this study, we describe the medical cost and utilization rates of antiviral therapy for CHB patients to explore the impact of the new partial reimbursement policy on the medical care cost, the composition, and antivirals utilization. Methods Clinical and claims data of a retrospective cohort of 92,776 outpatients and 2,774 inpatients with non-cirrhotic CHB were retrieved and analyzed from You'an Hospital, Beijing between February 14, 2008 and December 31, 2012. The propensity score matching was used to adjust factors associated with the annual total cost, including age, gender, medical insurance type and treatment indicator. Results Compared to patients who paid out-of-pocket, medical cost, especially antiviral costs increased greater among patients with medical insurance after July 1, 2011, the start date of reimbursement policy. Outpatients with medical insurance had 16% more antiviral utilization; usage increased 3% among those who paid out-of-pocket after the new partial reimbursement policy was implemented. Conclusions Direct medical costs and antiviral utilization rates of CHB patients with medical insurance were higher than those from paid out-of-pocket payments, even after adjusting for inflation and other factors. Thus, a new partial reimbursement program may positively optimize the cost and standardization of antiviral treatment.
Influence of Partial Liquid Ventilation on Bacterial Growth and Alveolar Expansion in Newborn Rabbits with Group B-Streptococcal Pneumonia

Partial liquid ventilation (PLV) with perfluorocarbons has been considered as an alternative therapy for severe inflammatory lung disease. The present study was performed to test whether PLV influences bacterial growth and lung histology in a rabbit model of congenital pneumonia caused by group B streptococci. Near-term newborn rabbits were tracheotomized, inoculated via the airways with group B streptococci, and subsequently ventilated for 5 h with either PLV or conventional ventilation. At 30 min after group B streptococci administration, animals in the PLV group (n = 16) received 30 mL/kg body weight of perfluorocarbon (PF 5080) via the tracheal tube. Evaporative losses were substituted with 20 mL/kg perfluorocarbon at hourly intervals. Identical volumes of air were injected in control animals at the same times (n = 15). The number of colony-forming units in left lung homogenate, evaluated at the end of the experiments, tended to be lower in PLV-treated animals than in controls (6.8 × 109versus 6.4 × 1010 colony-forming units/g body weight; p = 0.06). Comparison of these numbers with the colony-forming units injected at the beginning of the experiments revealed a reduction in bacterial number in the PLV group and proliferation in the controls (−2.2 × 108versus +5.6 × 1010 colony-forming units/g body weight; p < 0.05). Histologic examination demonstrated less inflammation and more homogeneous lung expansion in PLV-treated animals. Two animals in the PLV group had focal interstitial emphysema. Our results suggest that PLV with PF 5080 reduces bacterial proliferation in experimental group B streptococcal pneumonia.