Targets In Mind Research Articles

Experimental Design and Modeling for Forward-Inverse Maps

In customer-driven design of systems or products, one has performance targets in mind and would like to determine values for product or system parameters that meet such targets. Engineering computer simulation models predict performance given design parameter values; meeting a target is done iteratively through an optimization search procedure, typically by optimizing a regression, neural network or other type of approximation metamodel of the computer model. We pose the thesis that, since forward metamodel construction is a key part of this strategy, constructing an inverse metamodel directly is advantageous. The inverse metamodel obviates the need for optimization in many settings. One can design experiments that allow simultaneous fitting of forward and inverse metamodels. We discuss the potential for this strategy, the connection with the calibration problem, and some of the issues that must be resolved to make the approach practical.

Trends in carbon emissions and renewable energy usage

The purpose of carrying out this study was to explore the trends and inter-linkages between CO2 emission and RE share of total energy between 1990 and 2015. The United Nations’ Sustainable Development Goal 7 is to ensure access to affordable, reliable, sustainable, and modern energy for all. With these targets in mind, we have tried to answer questions like how has the global RE share of total energy changed over time, does the pattern of RE change over time affect CO2 emissions, and has access to clean energy changed significantly over time? The findings of this study has established that there is a general increasing trend in RE and that is associated with diminished trend in CO2. Looking at the access to clean energy between rural and urban sectors and they presented starkly different time trend with almost twice as large a percentage of population with access to clean energy in the urban areas than the rural. Journal of Statistical Research 2024, Vol. 58, No. 1, pp. 221-242.

Chemical and biological versatility of pyrazolo[3,4-d]pyrimidines: one scaffold, multiple modes of action.

Plain language summary Pyrazolo[3,4-d]pyrimidines are chemical compounds possessing remarkable versatility and significance in both biological and chemical contexts. These compounds are composed of specific arrangements of atoms, forming a unique ring structure, which is able to form bonds in a similar way as purines do. In the realm of chemistry, pyrazolo[3,4-d]pyrimidines showcase impressive flexibility due to their ability to easily react with various molecules, opening avenues for the creation of novel compounds with diverse properties for potential applications in medicinal chemistry. In a biological context, pyrazolo[3,4-d]pyrimidines play a crucial role due to their interaction with proteins such as enzymes. In fact, these compounds can impact various biological processes, including cancer cell proliferation, oxidative stress and inflammation. This has led to investigations into their potential as therapeutic agents: by designing pyrazolo[3,4-d]pyrimidines with specific biological targets in mind, new drugs can be developed for the effective treatment of a range of medical conditions. Finally, novel administration tools (e.g., nanomaterials and functionalized liposomes) are being studied as effective ways to overcome the main unwanted characteristics of pyrazolo[3,4-d]pyrimidines (scarce solubility and off-target side effects), thereby increasing their efficacy and specificity toward cell targets. In conclusion, pyrazolo[3,4-d]pyrimidines are fascinating molecules with a dual role in chemistry and biology. Their adaptability in chemical reactions makes them valuable building blocks for designing new compounds with diverse applications. Additionally, their interaction with biological molecules holds promise for the development of innovative medicines. Ongoing research into the properties and behaviors of these compounds could lead to significant advancements in both scientific fields.

Batteries and beyond: Multi-vector energy storage as a tool to decarbonise energy services

With the 2015 Paris Agreement pursuing efforts to limit global temperature increase to below 2°C above pre-industrial levels and the “energy trilemma” goals of energy security, energy equity and environmental sustainability, decarbonisation remains a priority across all of the United Kingdom (United Kingdom) energy system, not just electricity. Electricity and thermal energy storage technologies can offer a host of benefits across the energy value chain through the abilityS to capture, store and then release electricity or thermal energy over a period of time. These benefits include helping capture the full potential of renewable generation and providing services such as frequency response and reserve to Great Britain’s (GB) electricity system. In addition, with the aforementioned climate targets in mind, energy storage can also play a role in facilitating the decarbonisation of other activities and sectors. Here we delve deeper into how energy storage technologies can contribute to both energy sector transformation and more broadly, decarbonisation. Furthermore, we discuss the importance of ensuring a technology-agnostic approach to the development of policy and regulation with relevance to energy storage. This ensures that storage technologies with significant potential to contribute to the ‘energy trilemma’ goals are not precluded from entering the market due to unfavourable policy and regulatory frameworks.

Dual-Targeted Textfooler Attack on Text Classification Systems

Deep neural networks provide good performance on classification tasks such as those for image, audio, and text classification. However, such neural networks are vulnerable to adversarial examples. An adversarial example is a sample created by adding a small adversarial noise to an original data sample in such a way that it will be correctly classified by a human but misclassified by a deep neural network. Studies on adversarial examples have focused mainly on the image field, but research is expanding into the text field as well. Adversarial examples in the text field that are designed with two targets in mind can be useful in certain situations. In a military scenario, for example, if enemy models A and B use a text recognition model, it may be desirable to cause enemy model A tanks to go to the right and enemy model B self-propelled guns to go to the left by using strategically designed adversarial messages. Such a dual-targeted adversarial example could accomplish this by causing different misclassifications in different models, in contrast to single-target adversarial examples produced by existing methods. In this paper, I propose a method for creating a dual-targeted textual adversarial example for attacking a text classification system. Unlike the existing adversarial methods, which are designed for images, the proposed method creates dual-targeted adversarial examples that will be misclassified as a different class by each of two models while maintaining the meaning and grammar of the original sentence, by substituting words of importance. Experiments were conducted using the SNLI dataset and the TensorFlow library. The results demonstrate that the proposed method can generate a dual-targeted adversarial example with an average attack success rate of 82.2% on the two models.

A Framework for Modifying Orchestral Qualities in Computer-Aided Orchestration

Abstract This article introduces the Orchidea Orchestral Qualities framework (OOQ), an extension of the Orchidea environment for computer-aided orchestration. Traditional target-based orchestration generally reconstructs a target sound “as faithfully as possible” with a collection of samples. But more often than not, composers do not have specific targets in mind while performing orchestration tasks. A large class of orchestration practices deal with the transformation of musical material to enhance or reduce certain of its qualities (such as making a score more “brilliant,” “blurry,” “dense,” and so on). The OOQ framework implements this idea by making use of an analogy with digital signal processing. Scores and sounds are no longer used as targets, but rather as “sources” to be processed, not unlike what happens within a channel strip of a modern digital audio workstation. This article presents the rationale behind the OOQ framework, describes the behavior of its modules, and traces a path for future research on the subject.

Evaluating the Magnitude of VIIRS Out-of-Band Response for Varying Earth Spectra

Prior evaluations of Visible Infrared Imaging Radiometer Suite (VIIRS) out-of-band (OOB) contribution to total signal revealed specification exceedance for multiple key solar reflective and infrared bands that are of interest to the passive remote-sensing community. These assessments are based on laboratory measurements, and although highly useful, do not necessarily translate to OOB contribution with consideration of true Earth-reflected or Earth-emitted spectra, especially given the significant spectral variation of Earth targets. That is, although the OOB contribution of VIIRS is well known, it is not a uniform quantity applicable across all scene types. As such, this article quantifies OOB contribution for multiple relative spectral response characterization versions across the S-NPP, NOAA-20, and JPSS-2 VIIRS sensors as a function of varied SCIAMACHY- and IASI-measured hyperspectral Earth-reflected and Earth-emitted scenes. For instance, this paper reveals measured radiance variations of nearly 2% for the S-NPP VIIRS M5 (~0.67 μm) band, and up to 5.7% for certain VIIRS M9 (~1.38 μm) and M13 (~4.06 μm) bands that are owed solely to the truncation of OOB response for a set of spectrally distinct Earth scenes. If unmitigated, e.g., by only considering the published extended bandpass, such variations may directly translate to scene-dependent scaling discrepancies or subtle errors in vegetative index determinations. Therefore, knowledge of OOB effects is especially important for inter-calibration or environmental retrieval efforts that rely on specific or multiple categories of Earth scene spectra, and also to researchers whose products rely on the impacted channels. Additionally, instrument teams may find this evaluation method useful for pre-launch characterization of OOB contribution with specific Earth targets in mind rather than relying on general models.

Mobility policy through the lens of policy mobility: The post-political case of introducing free transit in Luxembourg

This viewpoint paper addresses the issue of fare-free public transport (FFPT) in the context of policy mobility, the strand of urban studies literature that examines how policy formulations developed in one place tend to ‘travel’ and inform and inspire plans elsewhere as good or best practices. We argue that the promotion of policies may not reflect a serious attempt to solve a sustainability or socio-economic issue. Rather, the institutions in charge have different targets in mind. FFPT in Luxembourg is thus more a reflection of a post-political process where politics are severed from the political.

Synergy-Based Gaussian Process Estimation of Ankle Angle and Torque: Conceptualization for High Level Controlling of Active Robotic Foot Prostheses/Orthoses.

Human gait is the result of a complex and fascinating cooperation between different joints and segments in the lower extremity. This study aims at investigating the existence of this cooperation or the so-called synergy between the shank motion and the ankle motion. One potential use of this synergy is to develop the high level controllers for active foot prostheses/orthoses. The central point in this paper is to develop a high level controller that is able to continuously map shank kinematics (inputs) to ankle angles and torques (outputs). At the same time, it does not require speed determination, gait percent identification, switching rules, and look-up tables. Furthermore, having those targets in mind, an important part of this study is to determine which input type is required to achieve such targets. This should be fulfilled through using minimum number of inputs. To do this, the Gaussian process (GP) regression has been used to estimate the ankle angles and torques for 11 subjects at three walking speeds (0.5, 1, and 1.5 m/s) based on the shank angular velocity and angle. The results show that it is possible to estimate ankle motion based on the shank motion. It was found that the estimation achieved less quality with only shank angular velocity or angle, whereas the aggregated angular velocity and angle resulted in much higher output estimation quality. In addition, the estimation quality was acceptable for the speeds that there was a training procedure before and when it was tested for the untrained speeds, the estimation quality was not as acceptable as before. The pros and cons of the proposed method are investigated at different scenarios.

Superoxide Dismutases in Pancreatic Cancer.

The incidence of pancreatic cancer is increasing as the population ages but treatment advancements continue to lag far behind. The majority of pancreatic cancer patients have a K-ras oncogene mutation causing a shift in the redox state of the cell, favoring malignant proliferation. This mutation is believed to lead to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and superoxide overproduction, generating tumorigenic behavior. Superoxide dismutases (SODs) have been studied for their ability to manage the oxidative state of the cell by dismuting superoxide and inhibiting signals for pancreatic cancer growth. In particular, manganese superoxide dismutase has clearly shown importance in cell cycle regulation and has been found to be abnormally low in pancreatic cancer cells as well as the surrounding stromal tissue. Likewise, extracellular superoxide dismutase expression seems to favor suppression of pancreatic cancer growth. With an increased understanding of the redox behavior of pancreatic cancer and key regulators, new treatments are being developed with specific targets in mind. This review summarizes what is known about superoxide dismutases in pancreatic cancer and the most current treatment strategies to be advanced from this knowledge.

Modeling of ribonucleic acid–ligand interactions

Computational methods play a pivotal role in the early stages of small molecule drug discovery and are widely applied in virtual screening, structure optimization, and compound activity profiling. Over the past half century in medicinal chemistry, almost all the attention has been directed to protein–ligand binding and computational tools were created with such targets in mind. However, with growing discoveries of functional RNAs and their possible applications, RNA macromolecules have gained considerable attention as possible drug targets. This flow of discovery was followed by adapting existing computational tools for RNA applications as well as active development of new RNA‐tailored methods. However, due to the different nature of RNA, especially its tendency to use morphological plasticity (conformational change in ligand binding) this remains a challenging task. The evolution of ‘protein‐based’ drug discovery and related computational methods offers some clues on possible future directions and developments in modeling RNA interactions with small molecule ligands. WIREs Comput Mol Sci 2015, 5:425–439. doi: 10.1002/wcms.1226This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Computer and Information Science > Chemoinformatics Molecular and Statistical Mechanics > Molecular Interactions

Tail-ion transport and Knudsen layer formation in the presence of magnetic fields

Knudsen layer losses of tail fuel ions could reduce significantly the fusion reactivity of highly compressed cylindrical and spherical targets in inertial confinement fusion (ICF). With the class of magnetized ICF targets in mind, the effect of embedded magnetic fields on Knudsen layer formation is investigated for the first time. The modified energy scaling of ion diffusivity in magnetized hot spots is found to suppress the preferential losses of tail-ions perpendicular to the magnetic field lines to a degree that the tail distribution can be at least partially, if not fully, restored. Two simple threshold conditions are identified leading to the restoration of fusion reactivity in magnetized hot spots. A kinetic equation for tail-ion transport in the presence of a magnetic field is derived, and solutions to the equation are obtained numerically in simulations. Numerical results confirm the validity of the threshold conditions for restored reactivity and identify two different asymptotic regimes of the fusion fuel. While Knudsen layer formation is shown to be suppressed entirely in strongly magnetized cylindrical hot spot cavities, uniformly magnetized spherical cavities demonstrate remnant, albeit reduced, levels of tail-ion depletion.

How should regional biodiversity be monitored?

We consider quantification of biodiversity in the context of targets set by the Convention on Biological Diversity. Implicit in such targets is a requirement to monitor biodiversity at a regional level. Few monitoring schemes are designed with these targets in mind. Monitored sites are typically not selected to be representative of a wider region, and measures of biodiversity are often biased by a failure to account for varying detectability among species and across time. Precision is often not adequately quantified. We review methods for quantifying the biodiversity of regions, consider issues that should be addressed in designing and evaluating a regional monitoring scheme, and offer a practical guide to what types of survey are appropriate for addressing different objectives for biodiversity monitoring.

High‐throughput screening and evaluation of anti‐cancer compounds

Early drug discovery for cancer treatment was based on targeting known proliferation mechanisms and the disruption of essential cellular functions. These therapies, although specific, were shown to have a wide range of toxicities. In contrast, therapies targeted to non essential functions were less toxic and less effective. Currently, the discovery phase has shifted to identify targeted therapies without specific molecular targets in mind. This approach allows for the identification of compounds against multiple targets or cancer pathway specific molecules. Furthermore, the identification of compounds that are efficacious and safe, particularly at the level of the immune system, will result in overall better therapies being developed. In this proposal various genomic and proteomic tools will be used to advance the identification of novel therapeutic compounds. A 150,000 molecule chemical library has been pre‐screened at various levels and narrowed down to 8 lead compounds. These compounds have minimal toxic effects on the immune system and will be further evaluated to identify the genomic and proteomic signatures for safety, efficacy and dose. We will also elucidate the molecular pathways that are targeted as they relate to cancer. This research is supported by funding to JX She.

The Management of Pain in Metastatic Bone Disease

Metastatic bone disease is a common cause of pain in cancer patients. A multidisciplinary approach to treatment is often necessary because simplified analgesic regimens may fail in the face of complex pain generators, especially those involved in the genesis of neuropathic pain. From the origins of formalized guidelines by the World Health Organization (WHO) to recent developments in implantable therapies, great strides have been made to meet the needs of these patients. The authors review the existing literature on the pathophysiology and treatment options for pain generated by metastatic bone disease and summarize classic and new approaches. Relatively recent animal models of malignant bone disease have allowed a better understanding of the intimate mechanisms involved in the genesis of pain, resulting in a mechanistic approach to its treatment. Analgesic strategies can be developed with specific targets in mind to complement the classic, opioid-centered WHO analgesic ladder obtaining improved outcomes and quality of life. Unfortunately, high-quality evidence is difficult to produce in pain medicine, and these concepts are evolving slowly. Treatment options are expanding for the challenging clinical problem of painful metastatic bone disease. Efforts are concentrated on developing alternative nonopioid approaches that appear to increase the success rate and improve patients' quality of life.

Abstract CN02-03: Prospects for targeted reduction of ovarian cancer risk

Abstract CN02-03 The 5 year survival for patients diagnosed with Stage 3 and 4 epithelial ovarian cancer (EOC) is less than 40% in spite of overall benefit from primary treatment with debulking surgery and chemotherapy. For advanced EOC, even clinical complete responses are usually time-limited, a situation that supports a strategy for earlier intervention. Efforts to establish a screening program with ultrasound and CA-125 have been encumbered by false positive results. The absence of demonstrated benefit in a definitive trial precludes the implementation of widespread screening in the general population. For high risk women like those with BRCA or HNPCC mutations, prophylactic salpingo-oophorectomy is available for risk reduction. Otherwise, the identification of specific risk markers and precursor lesions in the general population remains a challenging goal for EOC prevention research. Because access to human tissues of interest is limited, many questions about the natural history of EOC remain to be answered, and translational efforts have focused on preclinical models and animal studies. In spite of the difficulties, there are promising leads and methodology that can be pursued to make ovarian cancer risk reduction a broader reality. From epidemiologic studies, a major result in risk modification is the association of oral contraceptive use with EOC risk reduction. The literature is replete with studies that also link EOC with a variety of other hormonal and reproductive factors. These results have been used to support a number of etiologic hypotheses including risk related to 1) incessant ovulation, 2) gonadotropins, 3) hormones (estrogen/androgen/progesterone, and 4) inflammation. These hypotheses are interrelated and support a systems biology approach that integrates changes in the tumor microenvironment along with changes in the epithelium to identify targeted opportunities for preventive modulation. At this point, the translational research process may be well served by small clinical trials that are carefully designed to reconcile inconsistencies in existing data and to test mechanistic leads from preclinical studies as well as from investigations with therapeutics like bevacizumab and anti-Mullerian hormone. Pathways of interest include those related to aromatase and prostaglandins. With specific targets in mind, biomarker comparison in controls using placebo versus subjects using chemopreventive agents as mechanistic probes should allow an improved definition of risk and response. Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN02-03.

New chemotherapy options for the treatment of malignant gliomas.

Chemotherapy remains part of the treatment triad that includes surgery and radiation therapy for the management of malignant gliomas. In recent years there has been an increased understanding of the molecular pathways of malignant transformation. Based on this research, new drugs have been evaluated, with specific cellular targets in mind that can be modified or inhibited. Many of these agents are now being tested in phase I and II clinical trials and have shown some promising results. Clearly, not all patients with malignant gliomas respond equally to chemotherapy. Recent evidence suggests that certain molecular markers may predict chemosensitivity in some tumor types, particularly anaplastic oligodendroglioma. This article reviews recent trends in the use of chemotherapy and clinical trials of new therapies for adults with malignant gliomas.