Target-specific Information Research Articles

Assessing the accuracy of contact predictions in CASP13.

The accuracy of sequence-based tertiary contact predictions was assessed in a blind prediction experiment at the CASP13 meeting. After 4 years of significant improvements in prediction accuracy, another dramatic advance has taken place since CASP12 was held 2 years ago. The precision of predicting the top L/5 contacts in the free modeling category, where L is the corresponding length of the protein in residues, has exceeded 70%. As a comparison, the best-performing group at CASP12 with a 47% precision would have finished below the top 1/3 of the CASP13 groups. Extensively trained deep neural network approaches dominate the top performing algorithms, which appear to efficiently integrate information on coevolving residues and interacting fragments or possibly utilize memories of sequence similarities and sometimes can deliver accurate results even in the absence of virtually any target specific evolutionary information. If the current performance is evaluated by F-score on L contacts, it stands around 24% right now, which, despite the tremendous impact and advance in improving its utility for structure modeling, also suggests that there is much room left for further improvement.

A Photon-Counting Full-Waveform Lidar**Supported by the National Natural Science Foundation of China under Grant Nos 11774095, 11804099 and 11621404, the Shanghai Basic Research Project under Grant No 18JC1412200, and the Program of Introducing Talents of Discipline to Universities under Grant No B12024.

We present the results of using a photon-counting full-waveform lidar to obtain detailed target information with high accuracy. The parameters of the waveforms (i.e., vertical structure, peak position, peak amplitude, peak width and backscatter cross section) are derived with a high resolution limit of 31 mm to establish the vertical structure and scattering properties of targets, which contribute to the recognition and classification of various scatterers. The photon-counting full-waveform lidar has higher resolution than linear-mode full-waveform lidar, and it can obtain more specific target information compared to photon-counting discrete-point lidar, which can provide a potential alternative technique for tomographic surveying and mapping.

Target-Specific Siamese Attention Network for Real-Time Object Tracking

Deep similarity trackers are able to track above real-time speed. However, their accuracy is considerably lower than deep classification based trackers since they avoid valuable online cues. To feed the target-specific information for real-time object tracking, we propose a novel Siamese attention network. Different types of attention mechanisms are used to capture different contexts of target information and then learned knowledge is used to feed target cues at different representation levels of similarity tracking. In addition, an online learning mechanism is employed to utilise the available target-specific data. The proposed tracker reduces the impact of noise in the target template and improves the accuracy of similarity tracking by feeding target cues into the similarity search. Extensive evaluation performed on OTB-2013/50/100 and VOT2018 benchmark datasets demonstrate the proposed tracker outperforms state-of-the-art approaches while maintaining real-time tracking speed.

Provision of target-specific library services for the realization of Sustainable Development Goals (SDGs) in developing countries

This paper examines the Role of Libraries in the Provision of Target-Specific Library Services for the Full Delivery of Sustainable Development Goals (SDGs) in developing countries. The narrative textual case study (NTCS) method was adopted for the study. The paper highlighted on the place of libraries in the actualization of SDGs Agenda. The target-specific library services to be provided by libraries and exact actions that libraries should take in line with the 2030 agenda for realization of sustainable development goals in developing countries were extensively tabulated for ease of understanding. The position of the paper is that libraries are key actors in the attainment of the SDGs and that the different types of libraries irrespective of nomenclature have a place in the 2030 agenda. The paper concludes that SDGs can be actualized if libraries are repositioned to provide target specific information services through partnership with other institutions and agencies. Keywords: Libraries, Sustainable Development Goals (SDGs), Target-Specific Library Services, Developing Countries

CMR-guidance of passively tracked endomyocardial biopsy in an in vivo porcine model.

Endomyocardial biopsy (EMB) is considered to be the diagnostic gold-standard in detection of myocardial-inflammation. EMB is usually conducted under fluoroscopy without any specific target information. Specific target-information provided by cardiovascular magnetic resonance (CMR) may improve specificity of EMB. The aim was to investigate feasibility and safety of CMR-guided and targeted EMB in a preclinical-model using passively-tracked devices. Procedures were performed on a MRI-System equipped with an Interventional Software-Platform for real-time imaging. Ex vivo experiments were conducted to optimize visibility of the guide-sheath. In vivo experiments were conducted in 2 pigs for technical feasibility assessment and in 4 pigs after acute myocardial infarction to test feasibility of guided and lesion targeted EMB. For anatomical real-time imaging a single-shot-balanced-SSFP-sequence was applied. Myocardial targets were identified under real-time imaging (single-shot-T2 (sshT2) and single-shot Late-Gadolinium-Enhancement (sshLGE) sequences). Ex vivo experiments demonstrated best visibility of continuously labelled guide-sheath. CMR-guided EMB was feasible in all cases without major complications. Likewise, lesion-targeting endomyocardial biopsy was feasible in two cases. Biopsies exhibited appropriate sizes and qualities. Real-time lesion sequences revealed comparable CNR values to clinical-protocols. Real-time imaging of lesions showed following signal- and contrast-to-noise ratios (SNR/CNR): SNR of sshT2- and sshLGE was 124 ± 35 and 67 ± 51 respectively, whereas CNR was 81 ± 30 and 57 ± 44. This study demonstrates feasibility and safety of CMR-guided and basically targeted EMB with passively-tracked devices. Signal-to-noise ratios of real-time sequences is non-inferior to standard sequences for lesion detection. CMR-guidance may improve diagnostic accuracy of EMB since CMR can detect myocardial-targets under real-time-imaging.

Learning domain-shared group-sparse representation for unsupervised domain adaptation

In unsupervised domain adaptation, a key research problem is joint distribution alignment across the source and target domains. However, direct alignment of the source and target joint distributions is infeasible, because the target conditional distribution cannot be known without target labels. Instead of estimating target labels for target conditional distribution approximation, this paper proposes a new criterion of domain-shared group sparsity that is an equivalent condition for conditional distribution alignment. Together with marginal distribution alignment, we develop a domain-shared group-sparse dictionary learning model to learn domain-shared representations with aligned joint distributions. A cross-domain label propagation method is then proposed to train a classifier for the target domain using the domain-shared group-sparse representations and the target-specific information from the target data. The proposed method outperforms eight state-of-the-art unsupervised domain adaptation algorithms for cross-domain face recognition and cross-dataset object recognition with hand-drafted and deep features. Experimental results across multiple sub-domains show that the proposed method also performs well across datasets with large variance. Our results are quantitatively and qualitatively analyzed, and experiments of parameter sensitivity and convergence analysis are performed to show the effectiveness of the proposed method.

Domain-Shared Group-Sparse Dictionary Learning for Unsupervised Domain Adaptation

Unsupervised domain adaptation has been proved to be a promising approach to solve the problem of dataset bias. To employ source labels in the target domain, it is required to align the joint distributions of source and target data. To do this, the key research problem is to align conditional distributions across domains without target labels. In this paper, we propose a new criterion of domain-shared group-sparsity that is an equivalent condition for conditional distribution alignment. To solve the problem in joint distribution alignment, a domain-shared group-sparse dictionary learning method is developed towards joint alignment of conditional and marginal distributions. A classifier for target domain is trained using the domain-shared group-sparse coefficients and the target-specific information from the target data. Experimental results on cross-domain face and object recognition show that the proposed method outperforms eight state-of-the-art unsupervised domain adaptation algorithms.

Online Target Recognition for Time-Sensitive Space Information Networks

The key difficulties of online target recognition task for space information networks lie in the contradiction between time-sensitive response requirement and resource constraints(e.g., computation resource, communication resource, and training samples). To deal with the above problems, an effective online target recognizing approach is proposed, which seamlessly integrates fast online information processing task and efficient target-specific high-rate compression task. The proposed approach begins with enhancing the target-background separability by introducing intraclass and interclass couples, the new model adapted for the hospt spot image is then obtained by capturing the relation between the online target data and the massive historical data. The light-weight target-specific information is efficiently transmitted into the ground system, and the whole scene is capable of being recovered while the details of targets are being preserved. Compared with the traditional target recognition methods, the proposed approach is more promising for time-sensitive space information networks. The experiments demonstrate the effectiveness of the proposed approach.

Verification Design of Moving Based Micro Photoelectric Measuring Device

Photoelectric measuring device miniaturization is conducive to enhance the overall performance of the base on moving base ground system. This paper focuses on the measuring base device miniaturization design verification based on photoelectric for extraction of space target specific spectral information, through the spectrum analysis, achieve the rapid detection of the target. This paper begins with an analysis of the spectral information of target specific band, to determine the basic requirements of the overall design of the instrument, secondly, gives each instrument system design ideas, in the last part of the paper, the instrument with the actual test results and on its performance were test and analysis, basically meet the basic requirements of sky polarization observations of.

Justice Without Borders: The Influence of Psychological Distance and Construal Level on Moral Exclusion.

The present research examines how psychological distance influences the weight given to individuating information about targets of justice judgments. Drawing on construal level theory, which links psychological distance to levels of construal, we hypothesize that increasing psychological distance from justice judgments reduces people's sensitivity to specific features of targets, thereby minimizing the extent to which applications of justice are influenced by target-specific information. Psychological proximity, by contrast, enhances the salience of targets' idiosyncratic characteristics, thereby leading to applications of justice that are more sensitive to targets' identity. Six studies, examining various justice principles, support these conclusions. Studies 1 to 3 show that psychological distancing reduces the weight of target-specific features in justice judgments. Supporting the role of construal level in driving these results, Studies 4 to 6 demonstrate parallel patterns when construal level is manipulated directly. This work offers a novel outlook on the role of construal and target characteristics in moral exclusion.

Two‐ and Three‐dimensional Rings in Drugs

Using small, flat aromatic rings as components of fragments or molecules is a common practice in fragment-based drug discovery and lead optimization. With an increasing focus on the exploration of novel biological and chemical space, and their improved synthetic accessibility, 3D fragments are attracting increasing interest. This study presents a detailed analysis of 3D and 2D ring fragments in marketed drugs. Several measures of properties were used, such as the type of ring assemblies and molecular shapes. The study also took into account the relationship between protein classes targeted by each ring fragment, providing target-specific information. The analysis shows the high structural and shape diversity of 3D ring systems and their importance in bioactive compounds. Major differences in 2D and 3D fragments are apparent in ligands that bind to the major drug targets such as GPCRs, ion channels, and enzymes.

‘Smart’ electronic operation notes in surgery: An innovative way to improve patient care

AimsOperation notes are the only comprehensive account of what took place during surgery. Accurate and detailed documentation of surgical operation notes is crucial, both for post-operative management of patients and for medico-legal clarity.The aims of this study were to compare operation documentation against the Royal College of Surgeons of England guidelines and to compare the before-and-after effect of introducing an electronic operation note system. MethodsFifty consecutive operation notes for inpatients that had undergone emergency orthopaedic trauma surgery were audited.An electronic operation note proforma was then introduced and a re-audit carried out after its implementation. ResultsThe results after implementation of electronic operation notes, demonstrated a marked improvement. All notes contained an operation note (previously 5/6). Seventy five percent included time of surgery and age of patient (vs. 0% previously). A hundred percent included closure details and antibiotic selection at induction (vs. 60% and 69% respectively). Post-operative instructions improved to 100%. All were typed, making for 100% legibility as compared to only 66% of operation notes with legible hand writing in the initial audit. Discussion/conclusionWe used our pilot audit to target specific information that was commonly omitted and we ‘enforced’ these areas using drop-down selections in electronic operation note.This study has demonstrated that implementation of an electronic operation note system markedly improved the quality of documentation, both in terms of information detail and readability. We would recommend this template system as a standard for operation note documentation.

Is Forgetting Caused by Inhibition?

A well-known finding in memory research is the forgetting effect that occurs because of practicing some Item A on the recall of a related Item B. The traditional explanation for such interference effects is based on the notion of competition. According to the inhibition theory of forgetting, however, such forgetting is due to an inhibitory control process that operates whenever the retrieval of specific target information is hindered by competition from related information. The suppression of the related information is a longer lasting phenomenon that may show up on later testing. We report several experiments that were carried out to test 2 fundamental assumptions of the inhibition theory: the interference dependence and retrieval specificity assumptions. The results of these experiments do not support the predictions of the inhibition theory. Instead, the results are more compatible with the standard account that attributes the forgetting to competition at the time of the later testing.

Advances in immuno-positron emission tomography: antibodies for molecular imaging in oncology.

Identification of cancer cell-surface biomarkers and advances in antibody engineering have led to a sharp increase in the development of therapeutic antibodies. These same advances have led to a new generation of radiolabeled antibodies and antibody fragments that can be used as cancer-specific imaging agents, allowing quantitative imaging of cell-surface protein expression in vivo. Immuno-positron emission tomography (immunoPET) imaging with intact antibodies has shown success clinically in diagnosing and staging cancer. Engineered antibody fragments, such as diabodies, minibodies, and single-chain Fv (scFv) -Fc, have been successfully employed for immunoPET imaging of cancer cell-surface biomarkers in preclinical models and are poised to bring same-day imaging into clinical development. ImmunoPET can potentially provide a noninvasive approach for obtaining target-specific information useful for titrating doses for radioimmunotherapy, for patient risk stratification and selection of targeted therapies, for evaluating response to therapy, and for predicting adverse effects, thus contributing to the ongoing development of personalized cancer treatment.

Abstract 3869: Proteomics highlights which G-protein coupled receptors are candidates for ADC development

Abstract Antibody-drug conjugates (ADCs) are a recent and exciting development for targeted therapy of cancer. Their efficacy is governed by ADC-intrinsic characteristics such as avidity, drug load and linker chemistry, and mechanisms of activation and action, which can be controlled or clarified in the early stages of ADC development. In contrast, the properties that define a promising ADC target are still somewhat unclear. OGAP is a unique proteomic database that integrates information at the tissue, disease and protein isoform level across diseases, indications, and normal tissues to clarify protein expression levels and profiles. Specifically, it currently holds information on ∼2,000,000 human protein peptide sequences, ∼16,000 human proteins sequenced, ∼7,000 cancer membrane proteins, ∼50 tissues/organs, and ∼60 diseases. Building on OGAP and a proprietary sample preparation and processing workflow that relies on state-of-the-art high-throughput mass spectrometry and data processing to provide quantitative information on over 4,000 membrane-enriched proteins from ∼ 15,000 unique peptide sequences per analysis, we have established a novel predictive tool to establish each protein's potential to serve as a target for ADC development. The tool considers proteomic and target-specific information on antigenicity, structure, function, expression level, regulation, and tissue distribution in order to highlight the most suitable candidates for ADC development. We will demonstrate the utility of this process for the protein family of G-protein coupled receptors (GPCRs), which according to a recent bioinformatics prediction encompasses 899 distinct members in the human genome. These cell surface receptors are the target of more than one third of conventional drugs, yet their potential for ADCs is largely unexplored. Here we show that proteomics in the context of the OGAP database can highlight which of this large family of receptors have the potential to become true ADC targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3869. doi:1538-7445.AM2012-3869

Molecular Imaging-Guided Theranostics and Personalized Medicine

Molecular imaging agents and a parallel progress in instrumentation ofimaginingtechnology have demonstrated to be effective in improving diagnosis, prognosis, planning, and monitoring of personalized medication. Molecular imaging modalities include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), and optical (Raman, quantum dots, bioluminescence). Among these imaging modalities, PET and SPECT agents could provide target specific information as well as function, pathway activities, and cell migration in the intact organism. Furthermore, the radiotracer could noninvasively assess diseases treatment endpoints which used to rely almost exclusively on biopsies and histopathological assays. New leads on the development of personalized theranostic (image and treat) agents would allow more accuracy in the selection of patients who may respond to treatment. Topics covered in this special issue include advances in biomarkers in preclinical drug discovery, PET/CT and SPECT/CT in disease management, image-guided therapy approach of diseases, imaging technology in drug development, and progress in instrumentation ofimagingtechnology. For instance, upregulation of transporter expressions has often been observed in tumor cells to facilitate their accelerated rates of uptake. Advances in biomarkers in transporter system-based imaging in oncology and neurological diseases such as amino acid (FL. Kong et al.), glucose (YH. Zhang et al.) and dopaminergic (LH. Shen et al.; HF. Hou et al.) transporters were reported. These biomarkers showed that specific uptake in lesions compared to clinic imaging agent. In addition, these biomarkers were capable to be labeled with theranostic isotopes for personalized medication. Most tumors have a considerable proportion of hypoxic cells that are resistant to radio/chemotherapy, with a high propensity to metastasize, and result in worse therapeutic outcome. The contribution by M. Ali et al. and H. Fuji report their newly developed 99mTc-N4-NIM and 125I-IPOS probes for tumor hypoxia. The preclinical findings showed that these biomarkers could image tumor hypoxia by SPECT. The ability to quantify tissue hypoxia would allow the physicians to select patients for additional or alternative treatment regimens that would circumvent the ominous impact of hypoxia. Along this line, L. Jiang and coworkers report the peptide based radiotracer targeting tumor angiogenesis via VEGF integrin alpha(v) beta3. J. Sims-Mourtada and co-workers report 131I-labeled derivatives of the sonic hedgehog (HH) protein for detection of cancer cells via HH receptors. Molecular imaging of cancer stem cell trafficking was reported by T. Xia and co-workers. Hybrid molecular imaging modalities (PET/CT, SPECT/CT) provide high-sensitivity functional and high resolution anatomical imaging, which are important in design personalized treatment. To avoid radiation exposure from multiple slices-CT, K. Tang and co-workers report a reduction of CT tube voltage from 120 kv to 80 kv, the radiation dose could be reduced by 32–42% without losing low-contrast detectability. F. Chao and H. Zhang report the value of using PET/CT in the staging of nonsmall cell lung cancer. Y. Hu and co-workers report the application of PET/CT in assessment of treatment outcome. The application of SPECT/CT in the differential diagnosis of bone metastasis (Y. Zhang et al.) and Parkinson's disease (L. Wang et al.) was reported. Miyake K and co-workers report the application of FDG, MET, and FLT-PET/CT for the management of gliomas. L. Yang and co-workers report the value of using myocardial contrast echocardiography quantitative analysis during adenosine stress over visual analysis before therapy in acute coronary pain. The quantitative analysis correlates well with thrombosis in myocardial infarction. In summary, molecular imaging could integrate metabolomics and chemical biology. Molecular imaging agents could characterize target expressions, understand the disease progression, prediction for drug response and toxicity, staging, grading, and micrometastasis, and support animal studies. This special issue provides a platform of efficacy of personalized medication from molecular imaging technology which may have high impact on drug discovery, delivery, and development. Hong Zhang Mei Tian Enzhong Li Yasuhisa Fujibayashi Lie-Hang Shen David J. Yang

Molecular Image‐Guided Theranostic and Personalized Medicine

The growing use of molecular imaging helps to control and monitor dosage for increased safety and effectiveness. Molecular imaging agents become the scientific tools for moving a concept from bench work to clinic product development. This special issue provides original research and review of new trends in molecular imaging agent development. Among clinic molecular imaging modalities, radionuclide imaging technique is the most sensitive and could provide target-specific information. The radiotracer could non-invasively assess disease treatment endpoints which used to rely almost exclusively on biopsies and histopathological assays. L.-H. Shen et al. (Taiwan) reviewed molecular imaging in the diagnosis and management of CNS disorders. F.-L. Kong et al. (USA), N. Tsao et al. (USA), and C.-L. Ho et al. (Taiwan) report pharmacokinetics and dosimetry of molecular imaging compounds in oncology. M.-H. Liao et al. (Taiwan), X. Wang et al. (China), C. Wu et al. (China) and M. Tian et al. (USA) reported that molecular imaging techniques play a major role in the development of novel therapies since they measure target expressions (apoptosis, glycolysis) as well as function, pathway activities, and cell migration in the intact organism. Y.-F. Wang et al. and M.-Y. Chao et al. (Taiwan) described the kit probe for 99mTc-labeling which is crucial for centralized drug process. The kit probe may allow theranostic concept. A theranostic agent would be more accurate in the evaluation of patient response to treatment. The radiotracer could also be used for radionuclide therapy as reported by C. Wang et al. (China). Hybrid molecular imaging modalities (PET/CT, SPECT/CT) provide high-sensitivity functional and high-resolution anatomical imaging which are important in design-personalized treatment. M.-C. Chen et al. (Taiwan) reported the value of using I-131 NP-59 SPECT/CT to diagnose patients with subclinical or atypical features of primary aldosteronism. To proof of concept for molecular biology findings using different imaging modalities (optical, sonography) were described by Z. Pu et al. (China). In summary, molecular imaging enables the comprehensive characterization of therapeutic intervention and can be used in preclinical studies, pharmacokinetic studies, dose-finding studies, and proof-of-concept studies. Molecular imaging technologies promote the discovery and development of personalized medicine. Hong Zhang Mei Tian Carrio Ignasi Zhen Cheng Lie-Hang Shen David J. Yang

Multiple-Person Tracking by Multiple Cameras and Laser Range Scanners in Indoor Environments

In this paper, we propose a method for multiple-person tracking using cameras and laser range scanners. Our method estimates 3D positions of human body and head, and labels them with their identities. Individual particle filters track person correctly by integrating information from laser range scanners and target-specific information from cameras, thus compensating for weak points of each. We also develop a particle filter framework that tracks the human head simultaneously using the estimated body position. Results of experiments demonstrate the effectiveness and robustness of the proposal in tracking multiple persons with multiple scanners and cameras.

Category-based errors and the accessibility of unbiased spatial memories: A retrieval model.

Studies have consistently shown a spatial memory bias such that a target location is remembered toward the prototypical location of the region to which the target belongs, indicating a blending between the target's specific information and the generic information of its region. The authors investigated whether people retain a veridical representation of a target location after a delay by determining the locus of the blending (during encoding, delay, or retrieval). To examine accessibility to the original target location, they used a recognition task, which is less demanding than the traditional reproduction procedure. The results showed that participants were able to recognize the original position of a target over their own biased recalled position after both a short (1,500 ms) and a longer (5,000 ms) delay. These findings reveal that spatial memories can be undistorted despite distorted recall responses. Results are discussed in terms of J. Huttenlocher, L. V. Hedges, and S. Duncan's (1991) category adjustment model.

Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007

The 10th St Gallen (Switzerland) expert consensus meeting in March 2007 refined and extended a target-oriented approach to adjuvant systemic therapy of early breast cancer. Target definition is inextricably intertwined with the availability of target-specific therapeutic agents. Since 2005, the presence of HER2 on the cell surface has been used as an effective target for trastuzumab much as steroid hormone receptors are targets for endocrine therapies. An expert Panel reaffirmed the primary importance of determining endocrine responsiveness of the cancer as a first approach to selecting systemic therapy. Three categories were acknowledged: highly endocrine responsive, incompletely endocrine responsive and endocrine non-responsive. The Panel accepted HER2-positivity to assign trastuzumab, and noted that adjuvant trastuzumab has only been assessed together with chemotherapy. They largely endorsed previous definitions of risk categories. While recognizing the existence of several molecularly-based tools for risk stratification, the Panel preferred to recommend the use of high-quality standard histopathological assessment for both risk allocation and target identification. Chemotherapy, although largely lacking specific target information, is the only option in cases which are both endocrine receptor-negative and HER2-negative. Chemotherapy is conventionally given with or preceding trastuzumab for patients with HER2-positive disease, and may be used for patients with endocrine responsive disease in cases where the sufficiency of endocrine therapy alone is uncertain. Recommendations are provided not as specific therapy guidelines but rather as a general guidance emphasizing main principles for tailoring therapeutic choice.