Size-based Selection Research Articles

Advancing passive BCIs: a feasibility study of two temporal derivative features and effect size-based feature selection in continuous online EEG-based machine error detection.

The emerging integration of Brain-Computer Interfaces (BCIs) in human-robot collaboration holds promise for dynamic adaptive interaction. The use of electroencephalogram (EEG)-measured error-related potentials (ErrPs) for online error detection in assistive devices offers a practical method for improving the reliability of such devices. However, continuous online error detection faces challenges such as developing efficient and lightweight classification techniques for quick predictions, reducing false alarms from artifacts, and dealing with the non-stationarity of EEG signals. Further research is essential to address the complexities of continuous classification in online sessions. With this study, we demonstrated a comprehensive approach for continuous online EEG-based machine error detection, which emerged as the winner of a competition at the 32nd International Joint Conference on Artificial Intelligence. The competition consisted of two stages: an offline stage for model development using pre-recorded, labeled EEG data, and an online stage 3 months after the offline stage, where these models were tested live on continuously streamed EEG data to detect errors in orthosis movements in real time. Our approach incorporates two temporal-derivative features with an effect size-based feature selection technique for model training, together with a lightweight noise filtering method for online sessions without recalibration of the model. The model trained in the offline stage not only resulted in a high average cross-validation accuracy of 89.9% across all participants, but also demonstrated remarkable performance during the online session 3 months after the initial data collection without further calibration, maintaining a low overall false alarm rate of 1.7% and swift response capabilities. Our research makes two significant contributions to the field. Firstly, it demonstrates the feasibility of integrating two temporal derivative features with an effect size-based feature selection strategy, particularly in online EEG-based BCIs. Secondly, our work introduces an innovative approach designed for continuous online error prediction, which includes a straightforward noise rejection technique to reduce false alarms. This study serves as a feasibility investigation into a methodology for seamless error detection that promises to transform practical applications in the domain of neuroadaptive technology and human-robot interaction.

Abstract 1681: Single cell RNA sequencing of primary Ewing sarcoma tumors and identification of circulating tumor cells in patient-matched peripheral blood samples

Abstract Ewing sarcoma (ES) is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single-cell RNA sequencing (scRNA-seq) to characterize the transcriptional landscape of primary ES tumors, and to identify circulating tumor cells (CTCs) in peripheral blood at the time of diagnosis in order to further understand ES transcriptional heterogeneity and factors that drive metastasis. Methods: Viably frozen primary tumor and peripheral blood samples were obtained from 7 ES patients at the time of diagnosis and prior to the initiation of treatment. Tumors were dissociated into a single cell suspension and sorted for viability using FACS (fluorescence activated cell sorting) whereas peripheral blood samples were subjected to a size-based selection with the CellSieve microfiltration system. ScRNA-seq was performed using the 10xChromium platform and count matrices were generated using 10x Genomics Cell Ranger software. Quality control, integration, and cluster analysis was performed with Seurat. Results: Cluster analysis of integrated, primary tumor samples demonstrated that candidate ES cell clusters express FLI1 and ES marker NKX2-2 and cluster separately from immune cell populations. Additionally, using inferCNV, ES clusters were demonstrated to harbor chromosomal copy number alterations known to be associated with ES and that were previously identified clinically on preliminary pathology reports for each patient; further GSEA analysis showed significant overlap between published ES gene sets and genes upregulated in ES clusters. Further analysis of ES cells demonstrated that cell-cycle phase determined a cluster enriched in pro-proliferation gene signatures, and overall heterogeneity of expression of previously known therapeutic targets. Candidate ES CTCs were identified among the peripheral blood samples among clusters which corresponded with distinct immune cell populations. The candidate ES CTCs expressed NKX2-2 and demonstrated enrichment in oncogenic gene signatures. Conclusion: ScRNA-seq of primary ES tumors is feasible and demonstrates that ES tumor cells are largely homogeneous in nature; and candidate ES CTCs can be identified in peripheral blood at the time of diagnosis in ES patient and warrant further investigation as to their utility as a biomarker of metastatic disease. Citation Format: Sarah K. Nelson-Taylor, Avery Bodlack, Andrew Goodspeed, Amy Treece, Nathan Donaldson, Carrye Cost, Tim Garrington, Brian Greffe, Sandra Luna-Fineman, Jenna Sopfe, Masanori Hayashi. Single cell RNA sequencing of primary Ewing sarcoma tumors and identification of circulating tumor cells in patient-matched peripheral blood samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1681.

Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer.

IntroductionCirculating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together.MethodsConcurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method via DropCell platform. We performed targeted amplicon sequencing to evaluate the genomic heterogeneity of CTCs and ctDNA in lung cancer and breast cancer patients.ResultsHigher degrees of genomic heterogeneity were observed in CTCs as compared to ctDNA. Several shared alterations present in CTCs and ctDNA were undetected in the primary tumor, highlighting the intra-tumoral heterogeneity of tumor components that were shed into systemic circulation. Accordingly, CTCs and ctDNA displayed higher degree of concordance with the metastatic tumor than the primary tumor. The alterations detected in circulation correlated with worse survival outcome for both lung and breast cancer patients emphasizing the impact of the metastatic phenotype. Notably, evolving genetic signatures were detected in the CTCs and ctDNA samples during the course of treatment and disease progression.ConclusionsA standardized sample processing and data analysis workflow for concurrent analysis of CTCs and ctDNA successfully dissected the heterogeneity of metastatic tumor in circulation as well as the progressive genomic changes that may potentially guide the selection of appropriate therapy against evolving tumor clonality.

Assessing Seed Handling Processes to Facilitate a Community-Engaged Approach to Regional Forest Restoration

In the Midwestern United States, there is a strong management impetus toward reforestation to replace trees lost to due to tree mortality and to establish forests on previously cleared properties. Here, we describe a public outreach and volunteer effort that aimed to generate positive, community-engaged restoration outcomes and report on a practical experiment involving seed handling. We obtained tree seeds that were donated by members of the community to local land managers. We evaluated the size of the seeds collected and tested the influence of common stratification media (none, sand and vermiculite) and seed size on germination success of three tree genera involved in restoration efforts: Quercus, Carya and Juglans (oak, hickory and walnut). We found a species-specific effect of media on germination, such that Carya and Quercus showed little response to their stratification media, but Juglans had higher germination rates when stratified with vermiculite. Further, all genera of seeds germinated faster when stratified with either media than without. Thus, we suggest stratifying these seeds with media to promote germination success. We also tested for seed size as a predictor of mortality during stratification, following the logic that a size-based selection criterion might save time and space during stratification. We found species-specific impacts of seed size on germination, but relationships were highly variable, and we suggest avoiding screening seeds based on their size. In addition to these scientific results, we describe the broader forest restoration project, which may be a useful model for engaging the community in restoration efforts.

Achieving Functionality Through Modular Build-up: Structure and Size Selection of Serine Oligopeptidases.

Enzymes of the prolyl oligopeptidase family (S9 family) recognize their substrates not only by the specificity motif to be cleaved but also by size - they hydrolyze oligopeptides smaller than 30 amino acids. They belong to the serine-protease family, but differ from classical serine-proteases in size (80 kDa), structure (two domains) and regulation system (size selection of substrates). This group of enzymes is an important target for drug design as they are linked to amnesia, schizophrenia, type 2 diabetes, trypanosomiasis, periodontitis and cell growth. By comparing the structure of various members of the family we show that the most important features contributing to selectivity and efficiency are: (i) whether the interactions weaving the two domains together play a role in stabilizing the catalytic triad and thus their absence may provide for its deactivation: these oligopeptidases can screen their substrates by opening up, and (ii) whether the interaction-prone β-edge of the hydrolase domain is accessible and thus can guide a multimerization process that creates shielded entrance or intricate inner channels for the size-based selection of substrates. These cornerstones can be used to estimate the multimeric state and selection strategy of yet undetermined structures.

Bycatch and discarding patterns of dogfish and sharks taken in English and Welsh commercial fisheries.

At-sea observer programmes can provide spatio-temporal data on the sizes and quantities of fish being either discarded or retained, including for species and size categories that may not be sampled effectively during scientific surveys. Such data were analysed for English and Welsh fisheries operating on the continental shelf of the North Sea ecoregion (ICES Divisions 4a-c and 7d) and Celtic Seas ecoregion (ICES Divisions 6a, 7a-c, e-k) for the period (2002-2016). These data were collated for four main gear types: beamtrawl, nephrops and otter trawls, and nets (including gillnets, tangle nets and trammel nets). Beamtrawlers caught proportionally more smaller individuals than otter trawlers, whilst nets were the most size-selective gear for larger sharks. Size-related discarding was observed, with smaller spurdog Squalus acanthias and starry smooth-hound Mustelus asterias (< 60 cm total length, LT ) usually being discarded. Such size-based selection was not evident for lesser-spotted dogfish Scyliorhinus canicula, which was generally landed as bait. Temporal changes in the discard-retention patterns were evident for S. acanthias and porbeagle Lamna nasus, with increased regulatory discarding as management measures became restrictive. A corresponding increase in the proportion of the non-quota M. asterias retained was also observed over the study period. Knowledge of the size-based discard-retention patterns by métier can also help inform on where future studies on discard survival could usefully be undertaken.

Comparison of weight-based and pinna size–based selection of ProSeal laryngeal mask airway in paediatric population – A prospective exploratory trial

Background and Aims:Weight-based selection of ProSeal laryngeal mask airway (PLMA) size may be unreliable in some situations. The aim of this study was to compare the ventilation parameters using PLMA during controlled ventilation between weight-based size selection and pinna size–based selection in children.Methods:A total of 204 patients were randomised to receive either pinna size–based (Group P) or weight-based (Group W) size selection of PLMA. We tested the hypothesis that pinna size–based selection of PLMA was better than weight-based selection of PLMA in paediatric patients during controlled ventilation under general anaesthesia in terms of oropharyngeal sealing pressure (the primary end-point) and Brimacombe score. Cuff pressure was maintained at 60 cm of H2O during the study. Secondary outcomes included the number of attempts for successful placement of PLMA, peak airway pressure, gastric tube placement, traumatic insertion, and complications were also compared. Parametric variables were analysed using unpaired t-test and categorical variables were analysed using Mann–Whitney and Chi-square test.Results:In all, 200 patients were analysed. The mean oropharyngeal sealing pressure in Group P was 25.4 ± 3.5 cmH2O and 24.9 ± 3.8 cmH2O in Group W, (P = 0.34). There was no significant difference between the two groups in any of the secondary outcomes. There were no traumatic insertion or complications reported in both the groups.Conclusion:Pinna-based size selection method can be used in PLMA placement in the paediatric population for positive pressure ventilation and it serves as an alternative method to weight-based selection.

Female American lobster (Homarus americanus) size-at-maturity declined in Canada during the 20th and early 21st centuries

Changes in the environment and fishing have been shown to affect life-history characteristics, such as size or age of maturation, in a number of finfish and invertebrates. The American lobster (Homarus americanus) supports Canada’s most valuable fishery and exploitation rates are high. Female size-at-maturity (SM) is an important parameter in management of this species, as it is used in establishing minimum legal size regulations. In this study, we show with historical and recent data that SM of female American lobsters has declined across most of Canada, in some areas by as much as 30%, over the past 10–80 years. The spatial patterns of these declines are inconsistent with patterns of rising ocean temperature and lobster abundance (density). They are, however, strongly correlated to the strength of size-based fishery selection, and egg-per-recruit modeling indicates a gain in lifetime egg production associated with observed SM declines under a range of realistic harvesting scenarios. These findings suggest that the marked decrease we document in SM of female American lobsters in Canada over the past century represents an evolutionary response to intense exploitation.

Size-based fruit selection by a keystone avian frugivore and effects on seed viability

ABSTRACTThe non-random selection of fruits by frugivores can affect plant demography by changing the probability of seedling recruitment. We investigated whether the New Zealand pigeon (Hemiphaga novaeseelandiae) exhibits size-based preference of fruit in two indigenous tree species, Vitex lucens and Prumnopitys ferruginea, that have large fleshy diaspores containing single seeds. We also assessed if there was an advantage for seeds that were actively dispersed since birds may select fruits that have viable seeds (although the cue for such selection remains unclear) and whether a combined scarification–deinhibition advantage was conferred on germination due to seed passage through the gut. Using seed length as a proxy for fruit size, we compared the length of passively dispersed fruits in traps with the estimated fruit length of actively dispersed seeds in six trees of each species across three areas in one fruiting season. For both species, actively dispersed seeds were significantly longer than seeds from passively dispersed fruit, suggesting frugivore preference for larger fruit. Seeds from passively dispersed P. ferruginea fruit had significantly higher viability than actively dispersed seeds and there was no measurable scarification–deinhibition effect. For V. lucens, there was no significant difference in viability between actively and passively dispersed seeds and there was a total lack of seed germination in our trial. Our results show a significant preference by H. novaeseelandiae for larger fruit in both tree species, which was possibly associated with annual fruit production since P. ferruginea trees that had more fruit produced larger fruit on average. That H. novaeseelandiae selected longer fruit in our study is consistent with the prediction that birds will prefer larger fruit when beak gape limitation is absent. However, active dispersal of larger seeds may not always be advantageous since passively dispersed intact fruit germinated equally well and may even have had a viability advantage.

Abstract 2253: Digital sorting and single-cell genomic profile comparison of lung adenocarcinoma CTCs between EpCAM and size-based enrichment methods

Abstract Introduction Several methods are currently available for Circulating Tumor Cells (CTCs) enrichment. Many studies compared CTC counts between FDA-approved CellSearch® system (based on EpCAM enrichment) and size-based selection methods. However, little is known about genomic differences across CTCs obtained from different platforms. For the first time, we report here a genomic characterization of copy-number and sequence variants in single CTCs enriched with different methods from the same patient. Methods Peripheral blood (PB) and FFPE tissue from a pelvis bone metastasis were collected from an advanced lung adenocarcinoma patient, treated with cisplatin-pemetrexed-necitumumab as first line therapy and with carboplatin-gentamicin as second-line. Two PB samples were collected at the same time: one was enriched with CellSearch® System, and one with Parsortix PR1 (size-based selection), followed by Cytokeratin-APC, CD45-PerCp and DAPI staining. Both samples were analyzed with DEPArray™ system and single CTCs along with single WBCs as controls, were isolated. Collected cells were whole genome amplified with Ampli1™ WGA kit and their Genome Integrity Index (GII) was assessed. On IonTorrent™ PGM Platform, we profiled Genome-wide copy-number alterations (CNA) by low-pass whole-genome sequencing with Ampli1™ LowPass Kit, and analyzed cancer-gene sequence variants with Ampli1™ CHP Custom Beta targeted panel. FFPE tissue was disaggregated down to single-cell suspension and labelled with Keratin and Vimentin to distinguish tumor from stromal cells. Aliquots of pure cells were recovered with DEPArray™ system; the analysis of CNVs and mutations on tissue-derived samples is in progress. Results Single CTCs (CK+, CD45-,DAPI), showing GII≥3, either isolated from CellSearch®-enriched or PR1-enriched blood, along with WBC, were selected for NGS. Ampli1™ LowPass Kit data showed several aberrations confirming tumor origin of all CTCs, while WBCs (n = 6) produced balanced profiles. Unsupervised hierarchical clustering segregated PR1-derived (n = 6) from CellSearch®-derived (n = 4) single CTCs in two separate branches. PR1-derived CTCs were very similar to each other, whereas CellSearch®-derived CTCs were more heterogeneous, although certain aberrations were common to all CTCs across platforms. At the sequence level, the targeted panel revealed somatic mutations shared by all CTCs (FLT3), a PTPN11 subclonal mutation (in 3/6 PR1 and 1/4 CellSearch), and other private mutations in single CTCs. Discussion The combination of low-pass whole-genome sequencing and targeted sequencing on single-CTCs sorted from PB enriched with different platforms reveals genetic similarities and diversities. Integration of results with genetic analysis of pure tumor cells isolated from the tumor tissue, will provide further insight of tumor diversity in different compartments. Citation Format: Francesca Fontana, Francesco Gelsomino, Claudio Forcato, Mario Terracciano, Chiara Bolognesi, Annalisa Altimari, Genny Buson, Chiara Mangano, Paola Tononi, Francesco Bacchi, Gianni Medoro, Michelangelo Fiorentino, Nicolò Manaresi, Michele Tognetto, Andrea Ardizzoni. Digital sorting and single-cell genomic profile comparison of lung adenocarcinoma CTCs between EpCAM and size-based enrichment methods. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2253.

Integrated Microfluidic System for Size-Based Selection and Trapping of Giant Vesicles.

Vesicles composed of phospholipids (liposomes) have attracted interest as artificial cell models and have been widely studied to explore lipid-lipid and lipid-protein interactions. However, the size dispersity of liposomes prepared by conventional methods was a major problem that inhibited their use in high-throughput analyses based on monodisperse liposomes. In this study, we developed an integrative microfluidic device that enables both the size-based selection and trapping of liposomes. This device consists of hydrodynamic selection and trapping channels in series, which made it possible to successfully produce an array of more than 60 monodisperse liposomes from a polydisperse liposome suspension with a narrow size distribution (the coefficient of variation was less than 12%). We successfully observed a size-dependent response of the liposomes to sequential osmotic stimuli, which had not clarified so far, by using this device. Our device will be a powerful tool to facilitate the statistical analysis of liposome dynamics.

No Response to Bidirectional Size-Based Selection in the Rotifer Brachionus rotundiformis

Although rotifers have been considered the best feeding option for several species of fishes in aquaculture, they are sometimes larger than appropriate for the early larval stage of some marine fishes. Thus, we aimed to determine whether size-based selection of the parents could affect the average body size of their progeny in two clonal populations of the rotifer Brachionus rotundiformis. From each of the clones, 20 individuals were bi-directionally selected toward both smaller and larger sizes and each individualbased selection was conducted for 10 consecutive generations. The results showed that although there were sometimes differences in mean body size between parents and their progeny, no directional trend was observed in all selected lines of both clones. We demonstrated that artificial selection in a rotifer stock cannot lead to an expected size range although they appear to exhibit a large degree of body size polymorphism.

Coexistence of structured populations with size-based prey selection

Species with a large adult–offspring size ratio and a preferred predator–prey mass ratio undergo ontogenetic trophic niche shift(s) throughout life. Trophic interactions between such species vary throughout life, resulting in different species-level interaction motifs depending on the maximum adult sizes and population size distributions. We explore the assembly and potential for coexistence of small communities where all species experience ontogenetic trophic niche shifts. The life-history of each species is described by a physiologically structured model and species identity is characterised by the trait: size at maturation. We show that a single species can exist in two different states: a ‘resource driven state’ and a ‘cannibalistic state’ with a large scope for emergent Allee effects and bistable states. Two species can coexist in two different configurations: in a ‘competitive coexistence’ state when the ratio between sizes at maturation of the two species is less than a predator–prey mass ratio and the resource level is low to intermediate, or in a ‘trophic ladder’ state if the ratio of sizes at maturation is larger than the predator–prey mass ratio at all resource levels. While there is a large scope for coexistence of two species, the scope for coexistence of three species is limited and we conclude that further trait differentiation is required for coexistence of more species-rich size-structured communities.

Individualized radiation dose control in 256-slice CT coronary angiography (CTCA) in retrospective ECG-triggered helical scans: Using a measure of body size to adjust tube current selection

PurposeTo reduce radiation dose for retrospective ECG-triggered helical 256-slice CTCA by determining an optimal body size index to prospectively adjust tube current. Methods102 consecutive patients with suspected CAD underwent retrospective ECG-triggered CTCA using 256-slice CT scanner. Six body size indexes including BMI, nipple level (NL) bust, thoracic anteroposterior diameter at NL, chest circumference (CC) at NL, left main and right coronary artery (RCA) origin level were measured and their correlation with noise was evaluated using linear regression. An equation was developed to use this index to adjust tube current. Additional 102 consecutive patients were scanned with the index-based mAs adjustment. A t-test for independent samples was used to compare radiation dose levels with and without the index-based mAs selection method. ResultsLinear regression indicated that CC RCA had the best correlation with noise (R2=0.603). Effective radiation dose was reduced from 16.6±0.9 to 9.8±2.7mSv (p<0.01), i.e. 40.9% lower dose with the CC RCA-adapted tube current method. The image quality scores indicated no significant difference with and without the size-based mAs selection method. ConclusionAn accessible measure of body size, such as CC RCA, can be used to adapt tube current for individualized radiation dose control.

Competitive Interactions in Phytotelmata—Breeding Pools of Two Poison-Dart Frogs (Anura: Dendrobatidae) in Costa Rica

Competition and predation are two of the most important factors structuring communities, and these interactions may be exaggerated when two closely related species share similar resource requirements. We studied size-based habitat selection of artificial phytotelmata for deposition of tadpoles in two species of poison-dart frogs, Dendrobates auratus and Oophaga granulifera, in Costa Rica. Dendrobates auratus exhibits male parental care, and its tadpoles are predaceous, whereas O. granulifera exhibits biparental care, and its tadpoles are obligatory trophic egg eaters. These behavioral traits are integral factors in habitat selection for these two species. We found that the predaceous D. auratus selected large- and medium-sized pools, whereas O. granulifera selected all pool sizes but had a preference for small pools. Oophaga granulifera paid a high cost for exploiting large pools experiencing 100% mortality when sharing a pool with D. auratus. The use of small versus large pools in these species is rooted in each species' divergent parental care strategies and tadpole feeding behaviors.

Micrometastasis: Detection methods and clinical importance

Metastatic disease is the most important determinant in the clinical management of patients with cancer. Disseminated tumor cells are regarded as a surrogate for early metastatic spread of disease. These cells can be detected in bone marrow aspirates, lymph nodes and peripheral blood, where we refer to them as circulating tumor cells. Detection of disseminated tumor cells represents a great technical challenge, and many different technologies have been developed to enhance the sensitivity and specificity of the testing for these rare events. Different characteristics of tumor cells have been used to establish enrichment methods, including the differential expression of tumor-specific markers on the surface of the cells, the size-based selection of the cells, and other physical properties. Despite technical obstacles, the detection of circulating tumor cells in particular have emerged in recent years as a biomarker with outstanding predictive and prognostic capacity in a number of malignancies including breast, prostate, lung and colorectal cancer. In this text, we provide a comprehensive review of different approaches for enrichment of disseminated and circulating tumor cells and elucidate additional molecular methods for their detection. Further, the clinical significance of disseminated tumor cells detected in various compartments is discussed. Based on recent findings on the biology and heterogeneity of tumor cells, along with development of robust enrichment techniques, we believe that future research will focus less on pure detection but more importantly on detailed molecular characterization of these rare events with the potential impact on design of novel therapeutics.

GENETIC IDENTITY DETERMINES RISK OF POST-SETTLEMENT MORTALITY OF A MARINE FISH

Longitudinal sampling of four cohorts of Neopomacentrus filamentosus, a common tropical damselfish from Dampier Archipelago, Western Australia, revealed the evolution of size structure after settlement. Light traps collected premetamorphic individuals from the water column ("settlers") to establish a baseline for each cohort. Subsequently, divers collected benthic juveniles ("recruits") at 1-3-month intervals to determine the relative impacts of post-settlement mortality during the first three months. Growth trajectories for individual fish were back-calculated from otolith records and compared with nonlinear mixed-effects models. Size-selective mortality was detected in all cohorts with the loss of smaller, slower growing individuals. Three months after settlement, recruits showed significantly faster growth as juveniles, faster growth as larvae, and larger sizes as hatchlings. The timing and intensity of post-settlement selection differed among cohorts and was correlated with density at settlement. The cohort with the greatest initial abundance experienced the strongest selective mortality, with most of this mortality occurring between one and two months after settlement when juveniles began foraging at higher positions in the water column. Significant genetic structure was found between settlers and three-month-old recruits in this cohort as a result of natural selection that changed the frequency of mtDNA haplotypes measured at the control region. The extent of this genetic difference was enlarged or reduced by artificially manipulating the intensity of size-based selection, thus establishing a link between phenotype and haplotype. Sequence variation in the control region of the mitochondrial genome has been linked to mitochondrial efficiency and weight gain in other studies, which provides a plausible explanation for the patterns observed here.

Automatic and Efficient Decomposition of Two-Dimensional Structures of Small Molecules for Fragment-Based High-Throughput Docking

The computer program DAIM (Decomposition and Identification of Molecules) has been developed to automatically break up compounds in small-molecule libraries for fragment-based docking as well as database analysis. Here, DAIM is evaluated on 130 ligands derived from known crystal structures of ligand-protein complexes. The decomposition and a new fingerprint-based identification technique are used to select anchor fragments for docking. The docking results show that the DAIM selection is superior to size-based or random selection of fragments. To evaluate the usefulness for analyzing the fragment composition of a large library, DAIM is applied to a collection of about 1.85 million commercially available compounds. Interestingly, it is found that the set of most frequent cyclic and acyclic fragments originating from the decomposition of the 1.85 million molecules shows a large overlap with the most frequent fragments in a library of 5120 known drugs. DAIM has been successfully used in the in silico screening for inhibitors of beta-secretase and EphB4 kinase by fragment-based high-throughput docking. Possible future applications for de novo ligand design are briefly discussed.

Experimental trial for diagnosis of pancreatic ductal carcinoma based on gene expression profiles of pancreatic ductal cells

Pancreatic ductal carcinoma (PDC) remains one of the most intractable human malignancies, mainly because of the lack of sensitive detection methods. Although gene expression profiling by DNA microarray analysis is a promising tool for the development of such detection systems, a simple comparison of pancreatic tissues may yield misleading data that reflect only differences in cellular composition. To directly compare PDC cells with normal pancreatic ductal cells, we purified MUC1-positive epithelial cells from the pancreatic juices of 25 individuals with a normal pancreas and 24 patients with PDC. The gene expression profiles of these 49 specimens were determined with DNA microarrays containing >44 000 probe sets. Application of both Welch's analysis of variance and effect size-based selection to the expression data resulted in the identification of 21 probe sets corresponding to 20 genes whose expression was highly associated with clinical diagnosis. Furthermore, correspondence analysis and 3-D projection with these probe sets resulted in separation of the transcriptomes of pancreatic ductal cells into distinct but overlapping spaces corresponding to the two clinical classes. To establish an accurate transcriptome-based diagnosis system for PDC, we applied supervised class prediction algorithms to our large data set. With the expression profiles of only five predictor genes, the weighted vote method diagnosed the class of samples with an accuracy of 81.6%. Microarray analysis with purified pancreatic ductal cells has thus provided a basis for the development of a sensitive method for the detection of PDC.

Size-based fruit selection of Calophyllum brasiliense (Clusiaceae) by bats of the genus Artibeus (Phyllostomidae) in a Restinga area, southeastern Brazil

Size-based fruit selection of Calophyllum brasiliense (Clusiaceae) by bats of the genus Artibeus (Phyllostomidae) in a Restinga area, southeastern Brazil