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Can biowarfare agents be defeated with light?
Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious and profoundly virulent diseases may be caused in combat personnel or in civilian populations by the appropriate dissemination of viruses, bacteria, spores, fungi, or toxins. Dissemination may be airborne, waterborne, or by contamination of food or surfaces. Countermeasures may be directed toward destroying or neutralizing the agents outside the body before infection has taken place, by destroying the agents once they have entered the body before the disease has fully developed, or by immunizing susceptible populations against the effects. A range of light-based technologies may have a role to play in biodefense countermeasures. Germicidal UV (UVC) is exceptionally active in destroying a wide range of viruses and microbial cells, and recent data suggests that UVC has high selectivity over host mammalian cells and tissues. Two UVA mediated approaches may also have roles to play; one where UVA is combined with titanium dioxide nanoparticles in a process called photocatalysis, and a second where UVA is combined with psoralens (PUVA) to produce âkilled but metabolically activeâ microbial cells that may be particularly suitable for vaccines. Many microbial cells are surprisingly sensitive to blue light alone, and blue light can effectively destroy bacteria, fungi, and Bacillus spores and can treat wound infections. The combination of photosensitizing dyes such as porphyrins or phenothiaziniums and red light is called photodynamic therapy (PDT) or photoinactivation, and this approach cannot only kill bacteria, spores, and fungi, but also inactivate viruses and toxins. Many reports have highlighted the ability of PDT to treat infections and stimulate the host immune system. Finally pulsed (femtosecond) high power lasers have been used to inactivate pathogens with some degree of selectivity. We have pointed to some of the ways light-based technology may be used to defeat biological warfare in the future
Methods and Instrumentation of Sample Injection for XFEL Experiments
abstract: ABSTRACT
X-Ray crystallography and NMR are two major ways of achieving atomic
resolution of structure determination for macro biomolecules such as proteins. Recently, new developments of hard X-ray pulsed free electron laser XFEL opened up new possibilities to break the dilemma of radiation dose and spatial resolution in diffraction imaging by outrunning radiation damage with ultra high brightness femtosecond X-ray pulses, which is so short in time that the pulse terminates before atomic motion starts. A variety of experimental techniques for structure determination of macro biomolecules is now available including imaging of protein nanocrystals, single particles such as viruses, pump-probe experiments for time-resolved nanocrystallography, and snapshot wide- angle x-ray scattering (WAXS) from molecules in solution. However, due to the nature of the "diffract-then-destroy" process, each protein crystal would be destroyed once
probed. Hence a new sample delivery system is required to replenish the target crystal at a high rate. In this dissertation, the sample delivery systems for the application of XFELs to biomolecular imaging will be discussed and the severe challenges related to the delivering of macroscopic protein crystal in a stable controllable way with minimum waste of sample and maximum hit rate will be tackled with several different development of injector designs and approaches. New developments of the sample delivery system such as liquid mixing jet also opens up new experimental methods which gives opportunities to study of the chemical dynamics in biomolecules in a molecular structural level. The design and characterization of the system will be discussed along with future possible developments and applications. Finally, LCP injector will be discussed which is critical for the success in various applications.Dissertation/ThesisDoctoral Dissertation Physics 201
PROGRAM, THE NEBRASKA ACADEMY OF SCIENCES: One Hundred-Thirty-First Annual Meeting, APRIL 23-24, 2021. ONLINE
AFFILIATED SOCIETIES OF THE NEBRASKA ACADEMY OF SCIENCES, INC.
1.American Association of Physics Teachers, Nebraska Section: Web site: http://www.aapt.org/sections/officers.cfm?section=Nebraska
2.Friends of Loren Eiseley: Web site: http://www.eiseley.org/
3.Lincoln Gem & Mineral Club: Web site: http://www.lincolngemmineralclub.org/
4.Nebraska Chapter, National Council for Geographic Education
5.Nebraska Geological Society: Web site: http://www.nebraskageologicalsociety.org Sponsors of a $50 award to the outstanding student paper presented at the Nebraska Academy of SciencesAnnual Meeting, Earth Science /Nebraska Chapter, National Council Sections
6.Nebraska Graduate Women in Science
7.Nebraska Junior Academy of Sciences: Web site: http://www.nebraskajunioracademyofsciences.org/
8.Nebraska Ornithologistsâ Union: Web site: http://www.noubirds.org/
9.Nebraska Psychological Association: http://www.nebpsych.org/
10.Nebraska-Southeast South Dakota Section Mathematical Association of America: Web site: http://sections.maa.org/nesesd/
11.Nebraska Space Grant Consortium: Web site: http://www.ne.spacegrant.org/
CONTENTS
AERONAUTICS & SPACE SCIENCE
ANTHROPOLOGY
APPLIED SCIENCE & TECHNOLOGY
BIOLOGICAL & MEDICAL SCIENCES
COLLEGIATE ACADEMY: BIOLOGY
COLLEGIATE ACADEMY: CHEMISTRY & PHYSICS
EARTH SCIENCES
ENVIRONMENTAL SCIENCES
GENERAL CHEMISTRY
GENERAL PHYSICS
TEACHING OF SCIENCE & MATHEMATICS
2020-2021 PROGRAM COMMITTEE
2020-2021 EXECUTIVE COMMITTEE
FRIENDS OF THE ACADEMY
NEBRASKA ACADEMY OF SCIENCS FRIEND OF SCIENCE AWARD WINNERS
FRIEND OF SCIENCE AWARD TO DR PAUL KAR
Proceedings of the Thirteenth International Conference on Time-Resolved Vibrational Spectroscopy
The thirteenth meeting in a long-standing series of âTime-Resolved Vibrational Spectroscopyâ (TRVS) conferences was held May 19th to 25th at the Kardinal DĂśpfner Haus in Freising, Germany, organized by the two Munich Universities - Ludwig-Maximilians-Universität and Technische Universität MĂźnchen. This international conference continues the illustrious tradition of the original in 1982, which took place in Lake Placid, NY. The series of meetings was initiated by leading, world-renowned experts in the field of ultrafast laser spectroscopy, and is still guided by its founder, Prof. George Atkinson (University of Arizona and Science and Technology Advisor to the Secretary of State). In its current format, the conference contributes to traditional areas of time resolved vibrational spectroscopies including infrared, Raman and related laser methods. It combines them with the most recent developments to gain new information for research and novel technical applications. The scientific program addressed basic science, applied research and advancing novel commercial applications.
The thirteenth conference on Time Resolved Vibrational Spectroscopy promoted science in the areas of physics, chemistry and biology with a strong focus on biochemistry and material science. Vibrational spectra are molecule- and bond-specific. Thus, time-resolved vibrational studies provide detailed structural and kinetic information about primary dynamical processes on the picometer length scale. From this perspective, the goal of achieving a complete understanding of complex chemical and physical processes on the molecular level is well pursued by the recent progress in experimental and theoretical vibrational studies.
These proceedings collect research papers presented at the TRVS XIII in Freising, German
Molecules in Superfluid Helium Nanodroplets
This open access book covers recent advances in experiments using the ultra-cold, very weakly perturbing superfluid environment provided by helium nanodroplets for high resolution spectroscopic, structural and dynamic studies of molecules and synthetic clusters. The recent infra-red, UV-Vis studies of radicals, molecules, clusters, ions and biomolecules, as well as laser dynamical and laser orientational studies, are reviewed. The Coulomb explosion studies of the uniquely quantum structures of small helium clusters, X-ray imaging of large droplets and electron diffraction of embedded molecules are also described. Particular emphasis is given to the synthesis and detection of new species by mass spectrometry and deposition electron microscopy
Optical characterization of complex mechanical and thermal transport properties
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011.Page 176 blank. Cataloged from PDF version of thesis.Includes bibliographical references (p. 163-175).Time-resolved impulsive stimulated light scattering (ISS), also known as transient grating spectroscopy, was used to investigate phonon mediated thermal transport in semiconductors and mechanical degrees of freedom linked to structural relaxation in supercooled liquids. In ISS measurements, short optical pulses are crossed to produce a periodic excitation profile in or at the surface of the sample. Light from a probe beam that diffracts off the periodic material response is monitored to observe the dynamics of interest. A number of improvements were put into practice including the ability to separate so-called amplitude and phase grating signal contributions using heterodyne detection. This allowed the measurement of thermal transport in lead telluride and gallium arsenide-aluminum arsenide superlattices, and also provided the first direct observation of the initial crossover from diffusive to ballistic thermal transport in single crystal silicon and gallium arsenide at room temperature. Recent first-principles calculations of the thermal conductivity accumulation as a function of phonon mean free path allowed direct comparison to our measured results. In an effort to test theoretical predictions of the prevailing first principles theory of the glass transition, the mode coupling theory (MCT), photoacoustic measurements throughout much of the MHz acoustic frequency range were conducted in supercooled liquids. Longitudinal and shear acoustic waves were generated and monitored in supercooled liquid triphenyl phosphite in order to compare the dynamics. An additional interferometric technique analogous to ISS was developed to probe longitudinal acoustic waves at lower frequencies than was typically accessible with ISS. Lower frequency acoustic data were collected in supercooled tetramethyl tetraphenyl trisiloxane in conjunction with piezotransducer, ISS, and picosecond ultrasonics measurements to produce the first truly broadband mechanical spectra of a viscoelastic material covering frequencies continuously from mHz to hundreds of GHz. This allowed direct testing of the MCT predicted connection between fast and slow relaxation in supercooled liquids. Measurements of the quasi-longitudinal speed of sound in the energetic material cyclotrimethylene trinitramine (RDX) were also performed with ISS and picosecond ultrasonics from 0.5 to 15 GHz in order to resolve discrepancies in published low and high frequency elastic constants.by Jeremy A. Johnson.Ph.D
Acupuncture in Modern Medicine
This book contains four integrated sections: 1) Acupuncture Research; 2) New Developments in Acupuncture; 3) Acupuncture Therapy for Clinical Conditions and 4) Assessment and Accessibility in Acupuncture Therapy. Section 1 provides updates on acupuncture research. From acupuncture effects in modulation of immune system to the role of nitric oxide in acupuncture mechanisms, chapters in this section offer readers the newest trends in acupuncture research. Section 2 summarizes new developments in acupuncture. The included chapters discuss new tools and methods in acupuncture such as laser acupuncture, sham needles, and new technologies. Section 3 discusses acupuncture therapy for clinical conditions. The chapters in this section provide comprehensive and critical views of acupuncture therapy and its application in common clinical practice. Section 4 takes a new look at the issues related to assessment and accessibility in acupuncture therapy. These issues are central to developing new standards for outcome assessment and policies that will increase the accessibility to acupuncture therapy
Prehydrated Electron and Its Role in Ionizing Radiation Induced DNA Damage and Molecular Mechanisms of Action of Halogenated Sensitizers for Radiotherapy of Cancer
Despite advances in technology and understanding of biological systems in the past two decades, modern drug discovery is still a lengthy, expensive, difficult and inefficient process with low rate of new therapeutic discovery. The search for new effective drugs remains a somewhat empirical process. There is compelling need for a more fundamental, mechanistic understanding of human cancers and anticancer drugs to design more appropriate drugs.
Radiotherapy is still the major therapy of cancer. It uses high-energy ionizing radiation such as x-rays and charged particle beams to destroy cancer cells. DNA is well known to be the principal biological target of radiotherapy, but the molecular mechanism of ionizing radiation induced DNA damage was elusive. The conventional thought of the âOH radical as the major origin for ionizing radiation induced DNA damage is questionable. Although various strategies and types of compounds have been designed and developed as potential radiosensitizers to enhance the radiosensitizing efficiency of radiotherapy, none of them have been approved for clinical use. The general outcomes of clinical trials have been disappointing.
This thesis presents an innovative molecular-mechanism-based drug discovery project to develop novel drugs for effective radiotherapy of cancer through the emerging femtomedicine approach. Its ultimate goal is to develop more effective radiosensitizers, based on our unique molecular understandings of ionizing radiation induced DNA damage and halopyrimidines as a family of potential radiosensitizers.
Direct, real-time observation of molecular reactions is of significant importance in diverse fields from chemistry and biology, environmental sciences to medicine. Femtosecond time-resolved laser spectroscopy (fs-TRLS) is a very powerful, direct technique for real-time observation of molecular reactions. Its key strength lies in short duration laser flashes of a time scale at which reactions actually happen - femtoseconds (fs) (1fs = 1015 second). Since the late 1980s, its application to study chemical and biological systems led to the births of new subfields of science, called femtochemistry and femtobiology. Recently, femtomedicine has been proposed as a new transdisciplinary frontier to integrate ultrafast laser techniques with biomedical methods for advances in fundamental understandings and treatments of major human diseases. This the remarkable opportunity afforded through real-time observation of biochemical reactions at the molecular level. Femtomedicine holds the promise of advances in the radiotherapy of cancer.
Several important findings were made in this thesis. First, our results of careful and high-quality fs-TRLS measurements have resolved the long existing controversies about the physical nature and lifetimes of a novel ultrashort-lived electron species (epre) generated in radiolysis of water. These results have not only resolved the large discrepancies existing in the literature but provided new insights into electron hydration dynamics in bulk water. Such information is important for quantitative understanding and modeling of the role of non-equilibrium epre in electron-driven reactions in diverse environmental and biological systems, from radiation chemistry and radiation biology to atmospheric ozone depletion.
Second, our fs-TRLS results have unraveled how epre plays a crucial role in ionizing radiation induced DNA damage. We found that among DNA bases, only T and especially G are vulnerable to a dissociative electron transfer (DET) reaction with epre leading to bond breaks, while the electron can be stably trapped at C and especially A to form stable anions. The results not only challenge the conventional notion that damage to the genome by ionizing radiation is mainly induced by the oxidizing â˘OH radical, but provide a deeper fundamental understanding of the molecular mechanism of the DNA damage caused by a reductive agent (epre). Our findings have led to a new molecular mechanism of reductive DNA damage.
Third, halopyrimidines, especially BrdU and IdU, have passed Phase I to II clinical trials as potential hypoxic radiosensitizers, but the outcome of Phase III clinical trials was disappointing. Our results of fs-TRLS studies have provided a new molecular mechanism of action of halopyrimidines (XdUs, X=F, Cl, Br and I) in liquid water under ionizing radiation. We found that it is the ultrashort-lived epre, rather than the long-lived ehyd, that is responsible for DET reactions of XdUs. This reaction leads to the formation of the reactive dU⢠radical, which then causes DNA strand breaks and cancer cell death. Our results have challenged a long accepted mechanism that long-lived ehyd would be responsible for the radical formation from halogenated molecules. Furthermore, we found that the DET reaction efficacy leading to the formation of the reactive dU⢠radical is in the order of FdU << CldU < BrdU < IdU. Thus, only BrdU and IdU could be explored as potential radiosensitizers, in agreement with the results of bioactivity tests and clinical trials.
Fourth, our fs-TRLS studies have provided a molecular mechanism for the DNA sequence selectivity of BrdU and IdU in radiosensitization. We found the DET reactions of BrdU/ IdU with dAMP* and dGMP* formed by attachment of epre generated by radiolysis of water in aqueous BrdU-dAMP/dGMP and IdU-dAMP/dGMP complexes under ionizing radiation. This new mechanistic insight into the interaction of BrdU and IdU with DNA provides clues to improve the halogen familty as potential radiosensitizers and to develop more effective radiosensitizers for clinical applications.
Fifth, based on our molecular mechanistic understandings of DNA damage induced by ionizing radiation and halopyrimidines as potential radiosensitizers, we develop more effective new radisensitizing drug candidates through the femtomedicine approach. We have performed a fs-TRLS study of the DET reaction of a candidate compound (RS-1) with epre, and found that the DET reaction of epre with RS-1 is much stronger than that of IdU (and certainly BrdU and CldU). Moreover, we have tested the radiosensitizing effect of RS-1 against human cervical cancer (HeLa) cells exposed to various doses of x-ray irradiation through DNA damage measurements by gel electrophoresis and cell viability/death assays by MTT. Our results have confirmed that RS-1 can largely enhance the radiosensitivity of treated human cervical cancer (HeLa) cells to x-ray (ionizing) radiation. It is clearly demonstrated that RS-1 has a much better radiosensitizing effect than IdU. Although these are just preliminary results, our results have shown promise of developing more effective radiosensitizers.
In summary, our studies have demonstrated the potential of femtomedicine as an exciting new frontier to bring breakthroughs in understanding fundamental biological processes and to provide an efficient and economical strategy for development of new anticancer drugs.1 yea
Photodetectors
In this book some recent advances in development of photodetectors and photodetection systems for specific applications are included. In the first section of the book nine different types of photodetectors and their characteristics are presented. Next, some theoretical aspects and simulations are discussed. The last eight chapters are devoted to the development of photodetection systems for imaging, particle size analysis, transfers of time, measurement of vibrations, magnetic field, polarization of light, and particle energy. The book is addressed to students, engineers, and researchers working in the field of photonics and advanced technologies
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