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Vegetative propagule pressure may affect the establishment and structure of aquatic plant communities that are commonly dominated by plants capable of clonal growth. We experimentally constructed aquatic communities consisting of four submerged macrophytes (Hydrilla verticillata, Ceratophyllum demersum, Elodea nuttallii and Myriophyllum spicatum) with three levels of vegetative propagule pressure (4, 8 and 16 shoot fragments for communities in each pot) and two levels of water depth (30 cm and 70 cm). Increasing vegetative propagule pressure and decreasing water level significantly increased the growth of the submerged macrophyte communities, suggesting that propagule pressure and water depth should be considered when utilizing vegetative propagules to re-establish submerged macrophyte communities in degraded aquatic ecosystems. However, increasing vegetative propagule pressure and decreasing water level significantly decreased evenness of the submerged macrophyte communities because they markedly increased the dominance of H. verticillata and E. nuttallii, but had little impact on that of C. demersum and M. spicatum. Thus, effects of vegetative propagule pressure and water depth are species-specific and increasing vegetative propagule pressure under lower water level can facilitate the establishment success of submerged macrophyte communities. [ABSTRACT FROM AUTHOR]

Bracts of female cones of extant gymnosperm Ephedra (Joint fir) are either colorful and fleshy (section Ephedra), or dry-winged and membranous (section Alatae), or dry and coriaceous (section Asarca), which have played a crucial role in long- distance seed dispersal that is responsible for a wide distribution of the genus in semiarid and arid areas of Eurasia, North Africa, North America, and South America. Recent molecular systematic studies on Ephedra have suggested that the fleshy bracts in character evolution may be plesiomorphic relative to the dry, membranous and coriaceous bracts. However, little is known about when the fleshy bracts of Ephedra have made their debut in the geological past. Herein, we describe a novel, fleshy bract-bearing female cone macrofossil from the Early Cretaceous (ca. 120--125 Ma) Yixian Formation in Liaoning, northeastern China. This cone bears three ellipsoid seeds subtended by only one whorl of fleshy bracts. Each seed has a thin outer envelope and an inner integument that extends upward and passes through the opening of the outer envelope, forming a thin and straight micropylar tube. Such a syndrome shows the closest similarity to an extant triovulate species Ephedra intermedia in the section Ephedra, but the latter bears a whorl of terminal fertile bracts and more than one whorl of inferior sterile bracts, and a thick outer envelope. Hence, we establish a new fossil species Ephedra carnosa. Our discovery provides the first direct macrofossil evidence for the previous molecular systematics of Ephedra, implying that the origin of fleshy bracts in Ephedra should not have been later than that of the membranous and coriaceous bracts by at least the Early Cretaceous. [ABSTRACT FROM AUTHOR]

In response to ionizing irradiation and certain chemotherapeutic agents, dying tumor cells elicit a potent anticancer immune response. However, the potential effect of wogonin (5,7-dihydroxy-8-methoxyflavone) on cancer immunogenicity has not been studied. Here we demonstrated for the first time that wogonin elicits a potent antitumor immunity effect by inducing the translocation of calreticulin (CRT) and Annexin A1 to cell plasma membrane as well as the release of highmobility group protein 1 (HMGB1) and ATP. Signal pathways involved in this process were studied. We found that wogonininduced reactive oxygen species (ROS) production causes an endoplasmic reticulum (ER) stress response, including the phosphorylation of PERK (PKR-like endoplasmic reticulum kinase)/PKR (protein kinase R) and eIF2α (eukaryotic initiation factor 2α), which served as upstream signal for the activation of phosphoinositide 3-kinase (PI3K)/AKT, inducing calreticulin (CRT)/Annexin A1 cell membrane translocation. P22/CHP, a Ca2+-binding protein, was associated with CRT and was required for CRT translocation to cell membrane. The releases of HMGB1 and ATP from wogonin treated MFC cells, alone or together with other possible factors, activated dendritic cells and induced cytokine releases. In vivo study confirmed that immunization with wogonin-pretreated tumor cells vaccination significantly inhibited homoplastic grafted gastric tumor growth in mice and a possible inflammatory response was involved. In conclusion, the activation of PI3K pathway elicited by ER stress induced CRT/Annexin A1 translocation ("eat me" signal) and HMGB1 release, mediating wogonin-induced immunity of tumor cell vaccine. This indicated that wogonin is a novel effective candidate of immunotherapy against gastric tumor. [ABSTRACT FROM AUTHOR]

Background: Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and ~20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non- invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Methods: Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80°C until analysis. A customised homogeneous sandwich AlphaLISA(R) immunoassay was used to quantify NT-proBNP levels in saliva. Results: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r² = 0.78 (p<0.01, y = 1.7056+1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. Conclusion: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations. [ABSTRACT FROM AUTHOR]

Selective blockade of Kv1.3 channels in effector memory T (TEM) cells was validated to ameliorate autoimmune or autoimmune-associated diseases. We generated the antibody directed against one peptide of human Kv1.3 (hKv1.3) extracellular loop as a novel and possible Kv1.3 blocker. One peptide of hKv1.3 extracellular loop E3 containing 14 amino acids (E314) was chosen as an antigenic determinant to generate the E314 antibody. The E314 antibody specifically recognized 63.8KD protein stably expressed in hKv1.3-HEK 293 cell lines, whereas it did not recognize or cross-react to human Kv1.1(hKv1.1), Kv1.2(hKv1.2), Kv1.4(hKv1.4), Kv1.5(hKv1.5), KCa3.1(hKCa3.1), HERG, hKCNQ1/hKCNE1, Nav1.5 and Cav1.2 proteins stably expressed in HEK 293 cell lines or in human atrial or ventricular myocytes by Western blotting analysis and immunostaining detection. By the technique of whole-cell patch clamp, the E314 antibody was shown to have a directly inhibitory effect on hKv1.3 currents expressed in HEK 293 or Jurkat T cells and the inhibition showed a concentration-dependence. However, it exerted no significant difference on hKv1.1, hKv1.2, hKv1.4, hKv1.5, hKCa3.1, HERG, hKCNQ1/hKCNE1, L-type Ca2+ or voltage-gated Na+ currents. The present study demonstrates that the antibody targeting the E314 peptide of hKv1.3 pore region could be a novel, potent and specific hKv1.3 blocker without affecting a variety of closely related Kv1 channels, KCa3.1 channels and functional cardiac ion channels underlying central nervous systerm (CNS) disorders or drug-acquired arrhythmias, which is required as a safe clinic-promising channel blocker. [ABSTRACT FROM AUTHOR]

Background: Wnts are evolutionarily conserved ligands that signal through b-catenin-dependent and b-catenin- independent pathways to regulate cell fate, proliferation, polarity, and movements during vertebrate development. Dishevelled (Dsh/Dvl) is a multi-domain scaffold protein required for virtually all known Wnt signaling activities, raising interest in the identification and functions of Dsh-associated proteins. Methodology: We conducted a yeast-2-hybrid screen using an N-terminal fragment of Dsh, resulting in isolation of the Xenopus laevis ortholog of Hipk1. Interaction between the Dsh and Hipk1 proteins was confirmed by co-immunoprecipitation assays and mass spectrometry, and further experiments suggest that Hipk1 also complexes with the transcription factor Tcf3. Supporting a nuclear function during X. laevis development, Myc-tagged Hipk1 localizes primarily to the nucleus in animal cap explants, and the endogenous transcript is strongly expressed during gastrula and neurula stages. Experimental manipulations of Hipk1 levels indicate that Hipk1 can repress Wnt/b-catenin target gene activation, as demonstrated by bcatenin reporter assays in human embryonic kidney cells and by indicators of dorsal specification in X. laevis embryos at the late blastula stage. In addition, a subset of Wnt-responsive genes subsequently requires Hipk1 for activation in the involuting mesoderm during gastrulation. Moreover, either over-expression or knock-down of Hipk1 leads to perturbed convergent extension cell movements involved in both gastrulation and neural tube closure. Conclusions: These results suggest that Hipk1 contributes in a complex fashion to Dsh-dependent signaling activities during early vertebrate development. This includes regulating the transcription of Wnt/ß-catenin target genes in the nucleus, possibly in both repressive and activating ways under changing developmental contexts. This regulation is required to modulate gene expression and cell movements that are essential for gastrulation. [ABSTRACT FROM AUTHOR]

Although the influence of the Valsalva maneuver on the heart and circulatory system has been investigated, the mechanism of intrathoracic pressure influencing cardiovascular function is unclear. To test our hypothesis that the interaction between the anatomy-determined partially-intrathoracic system and the fully-intrathoracic system might explain those issues and help to disclose the mechanism, we used the Hitachi dual pulse wave Doppler echocardiographic apparatus to investigate simultaneously the beat-by-beat influence of 40-mmHg Valsalva maneuver on left and right cardiac ventricular filling in 30 male adult volunteers. The mitral and tricuspid blood inflow velocity spectra during the Valsalva maneuver were recorded simultaneously. The peak velocity (PV), velocity--time integral (VTI) and inflow volume (IV) of each cycle were measured or calculated. The PV, VTI and IV of the left heart remained unchanged at the first beat after the Valsalva maneuver onset (compared with those at rest, p>0.1) and then decreased gradually to the lowest at the 11±1.2th beat (range, 9th to 12th beat). Simultaneously, the PV, VTI and IV of the right heart decreased significantly (p<0.05) at the first cycle, decreased rapidly to the lowest at the 6±0.8th beat (range, 4th to 7th beat) and then increased gradually to the 9±1.3th beat (range, 8th to 10th beat). These results suggest that the left heart and right heart have different physiological responses to the Valsalva maneuver. These could be explained by our hypothesis, the interaction between the partially-intrathoracic system and the fully-intrathoracic system, which might help to disclose the mechanism of how intrathoracic pressure influences the heart and circulatory system. [ABSTRACT FROM AUTHOR]

In this study, we examined the expression of osteopontin (OPN), αvβ3 and Pim-1 in non-small cell lung cancer (NSCLC) and investigated the potential clinical implications of their expression patterns in NSCLC. Immunohistochemical assays were used to examine the protein expression of OPN, αvβ3 and Pim-1 in 208 NSCLC samples and their adjacent normal lung tissue specimens. Statistical analyses were performed to evaluate the relationships between OPN, αvβ3 and Pim-1 expression patterns, and their association with the clinical-pathological parameters of NSCLC patients. In NSCLC tissues, the positive rates of OPN, αvβ3 and Pim-1 expression were 67.8% (141/208), 76.0% (158/208) and 58.7% (122/208), respectively. However, in the adjacent normal lung tissues, the positive rates of OPN, αvβ3 and Pim-1 were 20.2% (42/208), 24.0% (50/ 208) and 14.9% (31/208), respectively. The differences in the positive expression rates of OPN, αvβ3 and Pim-1 between NSCLCs and the adjacent normal lung tissues were all significant (P<0.01). Additionally, the positive expression of OPN, αvβ3 and Pim-1 in NSCLCs was associated with an increase in pathological grade, lymph node metastasis and advanced clinical stage (all P<0.01). Furthermore, associations between the expression of OPN and αvβ3, OPN and Pim-1, and αvβ3 and Pim-1 were also observed in our NSCLC cohort (all P<0.01). The OPN, αvβ3 and Pim-1 proteins are frequently overexpressed in NSCLC and are associated with some clinicopathologic variables that are of known prognostic importance in NSCLC, suggesting that they may play an important role in the development and/or progression of NSCLC. [ABSTRACT FROM AUTHOR]

Background: No randomized controlled trial (RCT) has yet been performed to provide the evidence to clarify the therapeutic debate on liver resection (LR) and radiofrequency ablation (RFA) in treating colorectal liver metastases (CLM). The meta-analysis was performed to summarize the evidence mostly from retrospective clinical trials and to investigate the effect of LR and RFA. Methodology/Principal Findings: Systematic literature search of clinical studies was carried out to compare RFA and LR for CLM in Pubmed, Embase and the Cochrane Library Central databases. The meta-analysis was performed using risk ratio (RR) and random effect model, in which 95% confidence intervals (95% CI) for RR were calculated. Primary outcomes were the overall survival (OS) and disease-free survival (DFS) at 3 and 5 years plus mortality and morbidity. 1 prospective study and 12 retrospective studies were finally eligible for meta-analysis. LR was significantly superior to RFA in 3 -year OS (RR 1.377, 95% CI: 1.246-1.522); 5-year OS (RR: 1.474, 95%CI: 1.284-1.692); 3-year DFS (RR 1.735, 95% CI: 1.483-2.029) and 5-year DFS (RR 2.227, 95% CI: 1.823-2.720). The postoperative morbidity was higher in LR (RR: 2.495, 95% CI: 1.881-3.308), but no significant difference was found in mortality between LR and RFA. The data from the 3 subgroups (tumor,3 cm; solitary tumor; open surgery or laparoscopic approach) showed significantly better OS and DFS in patients who received surgical resection. Conclusions/Significances: Although multiple confounders exist in the clinical trials especially the bias in patient selection, LR was significantly superior to RFA in the treatment of CLM, even when conditions limited to tumor,3 cm, solitary tumor and open surgery or laparoscopic (lap) approach. Therefore, caution should be taken when treating CLM with RFA before more supportive evidences for RFA from RCTs are obtained. [ABSTRACT FROM AUTHOR]

Background: Tumor antigen (TA)-targeted monoclonal antibody (mAb) immunotherapy can be effective for the treatment of a broad range of cancer etiologies; however, these approaches have demonstrated variable clinical efficacy for the treatment of patients with prostate cancer (PCa). An obstacle currently impeding translational progress has been the inability to quantify the mAb dose that reaches the tumor site and binds to the targeted TAs. The coupling of mAb to nanoparticle-based magnetic resonance imaging (MRI) probes should permit in vivo measurement of patient-specific biodistributions; these measurements could facilitate future development of novel dosimetry paradigms wherein mAb dose is titrated to optimize outcomes for individual patients. Methods: The prostate stem cell antigen (PSCA) is broadly expressed on the surface of prostate cancer (PCa) cells. Antihuman PSCA monoclonal antibodies (mAb 7F5) were bound to Au/Fe3O4 (GoldMag) nanoparticles (mAb 7F5@GoldMag) to serve as PSCA-specific theragnostic MRI probe permitting visualization of mAb biodistribution in vivo. First, the antibody immobilization efficiency of the GoldMag particles and the efficacy for PSCA-specific binding was assessed. Next, PC-3 (prostate cancer with PSCA over-expression) and SMMC-7721 (hepatoma cells without PSCA expression) tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI. MRI probe biodistributions were assessed at increasing time intervals post-infusion; therapy response was evaluated with serial tumor volume measurements. Results: Targeted binding of the mAb 7F5@GoldMag probes to PC-3 cells was verified using optical images and MRI; selective binding was not observed for SMMC-7721 tumors. The immunotherapeutic efficacy of the mAb 7F5@GoldMag in PC-3 tumor-bearing mice was verified with significant inhibition of tumor growth compared to untreated control animals. Conclusion: Our promising results suggest the feasibility of using mAb 7F5@GoldMag probes as a novel paradigm for the detection and immunotherapeutic treatment of PCa. We optimistically anticipate that the approaches have the potential to be translated into the clinical settings. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer represents the leading cause of male death across the world. A recent genome-wide association study (GWAS) identified five novel susceptibility loci for prostate cancer in the Japanese population. This study is to replicate and fine map the potential association of these five loci with prostate cancer in the Chinese Han population. Methods: In Phase I of the study, we tested the five single nucleotide polymorphisms (SNPs) which showed the strongest association evidence in the original GWAS in Japanese. The study sample consists of 1,169 Chinese Hans, comprising 483 patients and 686 healthy controls. Then in phase II, flanking SNPs of the successfully replicated SNPs in Phase I were genotyped and tested for association with prostate cancer to fine map those significant association signals. Results: We successfully replicated the association of rs13385191 (located in the C2orf43 gene, P = 8.60610-5), rs12653946 (P = 1.33610-6), rs1983891 (FOXP4, P = 6.22610-5), and rs339331 (GPRC6A/RFX6, P = 1.42610-5) with prostate cancer. The most significant odds ratio (OR) was recorded as 1.41 (95% confidence interval 1.18-1.68) for rs12653946. Rs9600079 did not show significant association (P = 8.07610-2) with prostate cancer in this study. The Phase II study refined these association signals, and identified several SNPs showing more significant association with prostate cancer than the very SNPs tested in Phase I. Conclusions: Our results provide further support for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in Eastern Asian populations. This study also characterized the novel loci reported in the original GWAS with more details. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Background: There is accumulating epidemiologic evidence that exposure to traffic-related air pollutants, including particulate matter (PM) and polyaromatic hydro carbons (PAHs), plays a role in etiology and prognosis of a large scale of illnesses, although the role of specific causal agents and underlying mechanisms for different health outcomes remains unknown. Objective: Our general objective was to assess the relations between personal exposure to traffic exhausts, in particular ambient PM2.5 and PAHs, and the occurrence of DNA strand breaks by applying personal monitoring of PM and biomarkers of exposure (urinary 1-hydroxypyrene-glucuronide, 1-OHPG) and effect (urinary 8-hydroxydeoxyguanosine, 8-OHdG and DNA strand breaks). Methods: We recruited 91 traffic conductors and 53 indoor office workers between May 2009 and June 2011 in Taipei City, Taiwan. We used PM2.5 personal samplers to collect breathing-zone particulate PAHs samples. Spot urine and blood samples after work shift of 2 consecutive days were analyzed for 1-OHPG, 8-OHdG and DNA strand breaks, respectively. Statistical methods included linear regression and mixed models. Results: Urinary 8-OHdG levels and the occurrence of DNA strand breaks in traffic conductors significantly exceeded those in indoor office workers in mixed models. Particulate PAHs levels showed a positive association with urinary 1-OHPG in the regression model (β = 0.056, p = 0.01). Urinary 1-OHPG levels were significantly associated with urinary 8-OHdG levels in the mixed model (β = 0.101, p = 0.023). Our results provide evidence that exposure to fine particulates causes DNA damage. Further, particulate PAHs could be biologically active constituents of PM2.5 with reference to the induction of oxidative DNA damages. [ABSTRACT FROM AUTHOR]

Despite many evidences supporting the concept of ''oncogene addiction'' and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR) associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK) and phosphoinositol- 3 kinase (PI3K)/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1)/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential) due to the elevated level of reactive oxygen species (ROS) is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers. [ABSTRACT FROM AUTHOR]

Development of small molecular kinase inhibitors has recently been the central focus in drug discovery. And type II kinase inhibitors that target inactive conformation of kinases have attracted particular attention since their potency and selectivity are thought to be easier to achieve compared with their counterpart type I inhibitors that target active conformation of kinases. Although mechanisms underlying the interactions between type II inhibitors and their targeting kinases have been widely studied, there are still some challenging problems, for example, how type II inhibitors associate with or dissociate from their targeting kinases. In this investigation, steered molecular dynamics simulations have been carried out to explore the possible dissociation pathways of typical type II inhibitor imatinib from its targeting protein kinases c-Kit and Abl. The simulation results indicate that the most favorable pathway for imatinib dissociation corresponds to the ATP-channel rather than the relatively wider allosteric-pocket-channel, which is mainly due to the different van der Waals interaction that the ligand suffers during dissociation. Nevertheless, the direct reason comes from the fact that the residues composing the ATP-channel are more flexible than that forming the allosteric-pocket-channel. The present investigation suggests that a bulky hydrophobic head is unfavorable, but a large polar tail is allowed for a potent type II inhibitor. The information obtained here can be used to direct the discovery of type II kinase inhibitors. [ABSTRACT FROM AUTHOR]

Background: Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses. Methodology / Principal Findings: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 mg DNA given twice either by intramuscular needle injection or with a needle-free device. Conclusions/Significance: DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates. [ABSTRACT FROM AUTHOR]

Introduction:K-ras gene mutations were common in colorectal patients, but their relationship with prognosis was unclear. Objective:Verify prognostic differences between patient with and without mutant K-ras genes by reviewing the published evidence. Method:Systematic reviews and data bases were searched for cohort/case-control studies of prognosis of colorectal cancer patients with detected K-ras mutations versus those without mutant K-ras genes, both of whom received chemotherapy. Number of patients, regimens of chemotherapy, and short-term or long-term survival rate (disease-free or overall) were extracted. Quality of studies was also evaluated. Principal Findings:7 studies of comparisons with a control group were identified. No association between K-ras gene status with neither short-term disease free-survival (OR=1.01, 95% CI, 0.73-1.38, P=0.97) nor overall survival (OR=1.06, 95% CI, 0.82-1.36, P=0.66) in CRC patients who received chemotherapy was indicated. Comparison of long-term survival between two groups also indicated no significant difference after heterogeneity was eliminated (OR=1.09, 95% CI, 0.85-1.40, P=0.49). Conclusions:K-ras gene mutations may not be a prognostic index for colorectal cancer patients who received chemotherapy. [ABSTRACT FROM AUTHOR]