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The human hand is a complex biological system. Humans have evolved a unique ability to use the hand for a wide range of tasks, including activities of daily living such as successfully grasping and manipulating objects, i.e., lifting a cup of coffee without spilling. Despite the ubiquitous nature of hand

The human hand is a complex biological system. Humans have evolved a unique ability to use the hand for a wide range of tasks, including activities of daily living such as successfully grasping and manipulating objects, i.e., lifting a cup of coffee without spilling. Despite the ubiquitous nature of hand use in everyday activities involving object manipulations, there is currently an incomplete understanding of the cortical sensorimotor mechanisms underlying this important behavior. One critical aspect of natural object grasping is the coordination of where the fingers make contact with an object and how much force is applied following contact. Such force-to-position modulation is critical for successful manipulation. However, the neural mechanisms underlying these motor processes remain less understood, as previous experiments have utilized protocols with fixed contact points which likely rely on different neural mechanisms from those involved in grasping at unconstrained contacts. To address this gap in the motor neuroscience field, transcranial magnetic stimulation (TMS) and electroencephalography (EEG) were used to investigate the role of primary motor cortex (M1), as well as other important cortical regions in the grasping network, during the planning and execution of object grasping and manipulation. The results of virtual lesions induced by TMS and EEG revealed grasp context-specific cortical mechanisms underlying digit force-to-position coordination, as well as the spatial and temporal dynamics of cortical activity during planning and execution. Together, the present findings provide the foundation for a novel framework accounting for how the central nervous system controls dexterous manipulation. This new knowledge can potentially benefit research in neuroprosthetics and improve the efficacy of neurorehabilitation techniques for patients affected by sensorimotor impairments.
ContributorsMcGurrin, Patrick M (Author) / Santello, Marco (Thesis advisor) / Helms-Tillery, Steve (Committee member) / Kleim, Jeff (Committee member) / Davare, Marco (Committee member) / Arizona State University (Publisher)
Created2017
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Description

The human hand has so many degrees of freedom that it may seem impossible to control. A potential solution to this problem is “synergy control” which combines dimensionality reduction with great flexibility. With applicability to a wide range of tasks, this has become a very popular concept. In this review,

The human hand has so many degrees of freedom that it may seem impossible to control. A potential solution to this problem is “synergy control” which combines dimensionality reduction with great flexibility. With applicability to a wide range of tasks, this has become a very popular concept. In this review, we describe the evolution of the modern concept using studies of kinematic and force synergies in human hand control, neurophysiology of cortical and spinal neurons, and electromyographic (EMG) activity of hand muscles. We go beyond the often purely descriptive usage of synergy by reviewing the organization of the underlying neuronal circuitry in order to propose mechanistic explanations for various observed synergy phenomena. Finally, we propose a theoretical framework to reconcile important and still debated concepts such as the definitions of “fixed” vs. “flexible” synergies and mechanisms underlying the combination of synergies for hand control.

ContributorsSantello, Marco (Author) / Baud-Bovy, Gabriel (Author) / Jorntell, Henrik (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-04-08
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Description

The heat-labile toxins (LT) produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the

The heat-labile toxins (LT) produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB) in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV) envelope glycoprotein domain III (EDIII), which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.

Created2017-09-25
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Description

Pure coconut oil, lanolin, and acetaminophen were vaporized at rates of 1–50 mg/min, using a porous network exhibiting a temperature gradient from 5000 to 5500 K/mm, without incurring noticeable chemical changes due to combustion, oxidation, or other thermally-induced chemical structural changes. The newly coined term “ereptiospiration” is used here to

Pure coconut oil, lanolin, and acetaminophen were vaporized at rates of 1–50 mg/min, using a porous network exhibiting a temperature gradient from 5000 to 5500 K/mm, without incurring noticeable chemical changes due to combustion, oxidation, or other thermally-induced chemical structural changes. The newly coined term “ereptiospiration” is used here to describe this combination of thermal transpiration at high temperature gradients since the process can force the creation of thermal aerosols by rapid heating in a localized zone. Experimental data were generated for these materials using two different supports for metering the materials to the battery powered coil: namely, a stainless steel fiber bundle and a 3-D printed steel cartridge. Heating coconut oil, lanolin, or acetaminophen in a beaker to lower temperatures than those achieved at the surface of the coil showed noticeable and rapid degradation in the samples, while visual and olfactory observations for ereptiospiration showed no noticeable degradation in lanolin and coconut oil while HPLC chromatograms along with visual observation confirm that within the limit of detection, acetaminophen remains chemically unaltered by ereptiospiration.

ContributorsWoolley, Christine (Author) / Garcia, Antonio (Author) / Santello, Marco (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2017-04-12
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Description
Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading to a median survival period of two to five years. B cells in the bone marrow are responsible for generating

Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading to a median survival period of two to five years. B cells in the bone marrow are responsible for generating antigen-specific antibodies, but in MM the B cells express mutated, non-specific monoclonal antibodies. Therefore, it is hypothesized that antibody-based assay and therapy may be feasible for detecting and treating the disease. In this project, 330k peptide microarrays were used to ascertain the binding affinity of sera antibodies for MM patients with random sequence peptides; these results were then contrasted with normal donor assays to determine the "immunosignatures" for MM. From this data, high-binding peptides with target-specificity (high fluorescent intensity for one patient, low in all other patients and normal donors) were selected for two MM patients. These peptides were narrowed down to two lists of five (10 total peptides) to analyze in a synthetic antibody study. The rationale behind this originates from the idea that antibodies present specific binding sites on either of their branches, thus relating high binding peptides from the arrays to potential binding targets of the monoclonal antibodies. Furthermore, these peptides may be synthesized on a synthetic antibody scaffold with the potential to induce targeted delivery of radioactive or chemotherapeutic molecular tags to only myelomic B cells. If successful, this would provide a novel alternative to current treatments that is less invasive, has fewer side effects, more specifically targets the cause of MM, and reliably diagnoses the cancer in the presymptomatic stage.
ContributorsBerry, Jameson (Co-author) / Buelt, Allison (Co-author) / Johnston, Stephen (Thesis director) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Since its inception in the early 1990s, the concept of gene vaccines, particularly DNA vaccines, has enticed researchers across the board due to its simple design, flexible modification, and overall inexpensive cost of manufacturing. However, the past three decades have proven to be less fruitful than anticipated as scientists have

Since its inception in the early 1990s, the concept of gene vaccines, particularly DNA vaccines, has enticed researchers across the board due to its simple design, flexible modification, and overall inexpensive cost of manufacturing. However, the past three decades have proven to be less fruitful than anticipated as scientists have yet to tackle the issue of inducing a strong enough response in humans and non-human primates to protect against foreign pathogens, an issue that has since been coined as the “simian barrier.” This appears to be a human/primate barrier as protective vaccines have been produced for other mammals. Despite millions of dollars in research along with some of the world’s brightest minds chipping in to resolve this, there has yet to be any truly viable solution to overcoming this barrier. With current research illustrating effective applications of RNA vaccines in humans, these studies may be uncovering the solution to the largely unsolved simian barrier dilemma. If vaccines using RNA, the transcribed version of DNA, are effective in humans, the problem may be inefficient transcription of the DNA. This may be attributable to a DNA promoter that has insufficient activity in primates. Additionally, with DNA vaccines being even cheaper and easier to manufacture than RNA vaccines, along with having no required cold chain for distribution, this concept remains more promising than RNA vaccines that are further along in clinical trials.
ContributorsWillis, Joshua Aaron (Author) / Johnston, Stephen (Thesis director) / Sykes, Kathryn (Committee member) / Shen, Luhui (Committee member) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12