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Advances in artificial intelligence (AI) and automated robotics will profoundly influence space operations. By utilising machine learning and deep learning approaches, AI-enabled systems may accomplish tasks as well as improve their own performance. These capabilities are useful in the often-remote settings of outer space and will grow in value as automated space operations become more widespread. As AI extends throughout the space domain, automated algorithms will take on many of the roles that have historically been handled by humans. Artificial intelligence is progressing from theory to implementation in the space environment by exposing new satellites and orbital autonomous vehicles to new data. Even though all initial computational parameters are provided, such systems' outputs can be very unpredictable, putting people, property, and the environment at risk. This paper investigates the application of United Nations space treaties, selected regional AI regulations, and various 'soft-law' instruments and industry initiatives focusing on responsible AI system development to space-based AI systems. Following that, reforms are proposed to clarify the practical relationship between AI systems and the international legal regime that governs space, as well as a 'bottom-up' regulatory approach to better facilitate the future development of regulation governing the use of AI by the global space sector. While this work does not purport to provide a conclusive resolution to these multifaceted matters, its objective is to underscore significant obstacles that arise at the convergence of space law and AI, serving as a preliminary foundation for subsequent discussions on this issue. • Advances in AI and automated robotics will have a profound impact on space operations. Automated algorithms will take on roles traditionally handled by humans as AI becomes more widespread in space. • However, the unpredictable outputs of AI systems can put people, property, and the environment at risk, raising questions about liability. • The paper investigates the application of UN space treaties, regional AI regulations, and industry initiatives to space-based AI systems. • Reforms are proposed to clarify the relationship between AI systems and the international legal regime governing space. • A 'bottom-up' regulatory approach is suggested to facilitate future regulation of AI in the global space sector. [ABSTRACT FROM AUTHOR]

Basketball presents several characteristics that distinguishes it from other contact sports and can influence the manner by which a Team Physician and Hand Surgery Consultant interact. An abbreviated list of pathologies that affect the basketball athlete and the approach to their evaluation and treatment by a Hand Surgeon are described in context of return-to-play. [ABSTRACT FROM AUTHOR]

Golf is unique in this compendium of sports-related hand and wrist injury management. It is the only sport where the ball is stationary and there is no opponent against whom the player is defending. This distinctive sport dates to the 15th century in Scotland and is one of the oldest sports, but it is one where technology has changed many of the fundamental elements—from the "playing field (through advanced in agronomy) and the equipment (club and ball technology). [ABSTRACT FROM AUTHOR]

Recirculating nutrient solutions were treated using dimensionally stable anode (DSA)-based regenerative in situ electrochemical hypochlorination (RisEHc) in a deep water culture hydroponic lettuce (Lactuca sativa) production system. Phytotoxic effects were noted and attributed to the formation of chloramines in treated nutrient solutions containing ammonium. The presence of chloramines resulted in a decrease in overhead biomass by 53% using 2.27 mA/cm² and 83% with 4.55 mA/cm² . Adding ultraviolet light as a tertiary treatment stage allowed the photodecomposition of chloramines, which prevented phytotoxicity in crops and caused no significant differences in growth between treatments. Furthermore, using a nitrate-based fertilizer also served to prevent phytotoxic effects in crops and showed no significant differences in growth between the control and 4.55 mA/cm² . In addition, it was found that the electrochemical flow cell (EFC) treatment resulted in a 13% increase in shoot biomass using 2.27 mA/cm² . The study demonstrated that phytotoxic effects can be prevented with the use of regenerative in situ hypochlorination through proper management and monitoring techniques in recirculating hydroponic systems. [ABSTRACT FROM AUTHOR]

The approach to the care of baseball athletes and organizations is influenced by 2 factors that distinguish it from other sports: the number of contests and the number of players. America's pastime is a marathon that can (if successful in the regular season and postseason play) stretch over a 10-months, 162+-game schedule. In addition, unlike other major North American sports, baseball's "feeder system" is the highly-structured Minor League Baseball. This is in contradistinction to caring for 15 basketball players who arrive at the professional level through collegiate (or even high school) play or 20 hockey players that may have had an NCAA experience or come through the Junior Leagues in Canada. Even though a 53-man football roster can keep a Hand Surgery Consultant busy, it is still a limited professional level cohort that is one-third to one-fourth of the size of baseball's and is played across less than 20 contests. Granted, every sport has its own culture—which is why we have developed this format for this publication—but planning for the scope of baseball care is also influenced by the unique pace and intensity of the interactions, that is why it is called a "clubhouse," rather than a "locker room". With these fundamentals shared, let us expand on what our experience has taught us about the care for athletes that are engaged in batting, throwing, receiving, and colliding on the diamond. [ABSTRACT FROM AUTHOR]

The role of an experienced Hand Surgery Consultant within the complete care matrix for a professional sports organization has evolved in my 3-decade career. Granted, hand injuries may have been demoted in this population where ACL tears, shoulder dislocations, and Lisfranc injuries seem to have much greater visibility, but our experience has told us that Hand injuries often contribute to the most surgeries per team/per season and can result in significant man-game loss of service. In my 30 years as a Consultant, Team Physician and/or Medical Director in all 4 major North American-based Leagues (as well as for "itinerant" independent contractor sports of golf, tennis, and motorsports), we have cared for well over 2000 athletes. This privilege has provided us with unparalleled exposure to the locker rooms, training rooms, and clubhouses for almost every team in professional-level competition and many elite-level collegiate programs. My goal in assembling this volume was to highlight the skilled and experienced colleagues who have contributed so much to the surgical science of caring for the hand and wrist in the professional athlete and furthering the logic of having a Hand Surgeon on "speed dial" for our fellow Team Physicians who want to provide optimal care for their athletes. Regrettably, until recently, the limited number of us who had significant involvement in this cohort probably fell short of engaging in scientific inquiry and publishing our observations or series. I will accept more than my share of that shortcoming, but as these practices have expanded in number and the exposure went from anecdotal to voluminous, our community started to communicate within Hand Surgery ranks, but now we want to share our knowledge with all professional involved in elite athlete care. This collection is not meant to be an exhaustive review of individual pathologies. Fortunately, valued colleagues have done a laudable job of chronicling the common-to-complex pathologies that we see in sports coverage This publication is styled less from the "what" and "how" standpoint, aimed instead at providing Team Physicians with the "when" and "why" of optimizing their player's outcomes through collaboration with their Hand Specialist. [ABSTRACT FROM AUTHOR]

Single-molecule imaging provides a powerful way to study biochemical processes in live cells, yet it remains challenging to track single molecules while simultaneously detecting their interactions. Here, we describe a novel property of rhodamine dyes, proximity-assisted photoactivation (PAPA), in which one fluorophore (the ‘sender’) can reactivate a second fluorophore (the ‘receiver’) from a dark state. PAPA requires proximity between the two fluorophores, yet it operates at a longer average intermolecular distance than Förster resonance energy transfer (FRET). We show that PAPA can be used in live cells both to detect protein–protein interactions and to highlight a subpopulation of labeled protein complexes in which two different labels are in proximity. In proofof-concept experiments, PAPA detected the expected correlation between androgen receptor selfassociation and chromatin binding at the single-cell level. These results establish a new way in which a photophysical property of fluorophores can be harnessed to study molecular interactions in singlemolecule imaging of live cells. [ABSTRACT FROM AUTHOR]

The article discusses Russian President Valdimir Putin's intention behind invasion of Ukraine. Topics discussed included that Russia considered North Atlantic Treaty Organization (NATO) expansion as threat since the late 1990s, it also discusses Russia's disassociation from NATO was due to democratic expansion in Eurasia and it is discussed that in past two centuries three empires have invaded Russia through Ukraine therefore Russia considers it as a zone of encroachment for foreign invaders.

Hand and Wrist, sports teams, Professional athlete, practice management Sports Medicine and Arthroscopy Review 30.4 - Athletic Injuries to the Hand and Wrist Chapter 2: Preparing Your Practice (and Family) for Your Role in the Care of Professional Sports Teams Keywords: Hand and Wrist; Professional athlete; sports teams; practice management EN Hand and Wrist Professional athlete sports teams practice management 24 26 3 12/27/22 20230301 NES 230301 Although every orthopedist is a "sports doctor" to some degree, special considerations are warranted when preparing to care for professional and other elite athletes. [Extracted from the article]

Re-opening of communities in the midst of the ongoing COVID-19 pandemic has ignited new waves of infections in many places around the world. Mitigating the risk of reopening will require widespread SARS-CoV-2 testing, which would be greatly facilitated by simple, rapid, and inexpensive testing methods. This study evaluates several protocols for RNA extraction and RT-qPCR that are simpler and less expensive than prevailing methods. First, isopropanol precipitation is shown to provide an effective means of RNA extraction from nasopharyngeal (NP) swab samples. Second, direct addition of NP swab samples to RT-qPCRs is evaluated without an RNA extraction step. A simple, inexpensive swab collection solution suitable for direct addition is validated using contrived swab samples. Third, an open-source master mix for RT-qPCR is described that permits detection of viral RNA in NP swab samples with a limit of detection of approximately 50 RNA copies per reaction. Quantification cycle (Cq) values for purified RNA from 30 known positive clinical samples showed a strong correlation (r2 = 0.98) between this homemade master mix and commercial TaqPath master mix. Lastly, end-point fluorescence imaging is found to provide an accurate diagnostic readout without requiring a qPCR thermocycler. Adoption of these simple, open-source methods has the potential to reduce the time and expense of COVID-19 testing. [ABSTRACT FROM AUTHOR]

The future is going to be a mixture of competition and cooperation, mainly competition, with much of the cooperation aimed at managing it. [ABSTRACT FROM AUTHOR]

Annually, groups of health professionals from high‐income countries are drawn to work in low‐ and middle‐income countries (LMICs) through timed engagements intended to improve the well‐being of people in most disadvantaged communities. The existing evidence on understanding volunteer experience in LMICs often focuses on activities within the medical discipline; whereas little research has been conducted on the experiences of volunteers in other disciplines. This paper focuses on understanding veterinary and public health professional's experiences conducting disease surveillance work in Northern Uganda. Forty US‐based health care professionals were recruited to complete multiple‐choice and open‐ended questions to understand prior and current experiences working in resource‐limited settings. Responses were coded using NVivo 10®, qualitative analysis package. Of the 44 volunteers, 50% completed the questionnaire. Responses were largely positive towards surveillance activities; they reported personal and professional gains, new cultural experiences and mutual learning environment with local colleagues. Nevertheless, respondents highlighted challenges during various stages of program implementation—some difficulty with program logistics, inadequacy of preparation materials, in addition to concerns inherent to working in a resource‐limited environment. This assessment suggests that international volunteer work could positively influence programmatic outcomes, personal experiences, furthering health organizational goals, often achieved in a limited time‐frame. To maximize volunteer impact, these assessments are critical and suggest that volunteer and institutional capacities should be seriously considered when planning placement as it can influence programmatic decision‐making, gauge training needs and volunteer readiness. [ABSTRACT FROM AUTHOR]

Acoustic surface waves are supported at the surface of appropriately structured elastic materials. Here the excitation and propagation of the lowest-order surface mode supported by a square array of open-ended cavities on a metal plate submerged in water is demonstrated. This mode, which has a half-wavelength character in the cavity, arises due to inter-cavity interaction by evanescent diffraction of the pressure field, and forms a band from zero-frequency to an asymptotic limit frequency. The authors perform an acoustic characterization of the pressure field close to the surface of the perforated plate in the 60–100 kHz frequency range; sound is pulsed from a fixed point-like acoustic source, and the evolution of the acoustic field across the sample surface is measured as a function of time and space with a traversing detector. Using Fourier analysis, the dispersion is imaged between points of high-symmetry (Γ , X , M) and at planes in momentum-space at fixed frequencies. Beaming of acoustic energy on the surface over a narrow frequency band was observed, caused by the anisotropic mode dispersion of the acoustic surface wave on the square lattice. The measured dispersion shows good agreement with the predictions of a numerical model. [ABSTRACT FROM AUTHOR]

There is truly no sport that is not hand-intensive. This makes an engaged, experienced, and available Hand Surgery Consultant important to have on the roster of surgical subspecialists for a professional sports organization. It is not infrequent that hand and wrist surgeries top the list of the most commonly performed procedures during a contact sports season. [Extracted from the article]

The influence of light spectral quality on cannabis (Cannabis sativa L.) development is not well defined. It stands to reason that tailoring light quality to the specific needs of cannabis may increase bud quality, consistency, and yield. In this study, C. sativa L. 'WP:Med (Wappa)' plants were grown with either no supplemental subcanopy lighting (SCL) (control), or with red/blue (''Red-Blue'') or red-green-blue (''RGB'') supplemental SCL. Both Red-Blue and RGB SCL significantly increased yield and concentration of total D9-tetrahydrocannabinol (Δ9-THC) in bud tissue from the lower plant canopy. In the lower canopy, RGB SCL significantly increased concentrations of α-pinine and borneol, whereas both Red-Blue and RGB SCL increased concentrations of cis-nerolidol compared with the control treatment. In the upper canopy, concentrations of a-pinine, limonene, myrcene, and linalool were significantly greater with RGB SCL than the control, and cis-nerolidol concentration was significantly greater in both Red-Blue and RGB SCL treated plants relative to the control. Red-Blue SCL yielded a consistently more stable metabolome profile between the upper and lower canopy than RGB or control treated plants, which had significant variation in cannabigerolic acid (CBGA) concentrations between the upper and lower canopies. Overall, both Red-Blue and RGB SCL treatments significantly increased yield more than the control treatment, RGB SCL had the greatest impact on modifying terpene content, and Red-Blue produced a more homogenous bud cannabinoid and terpene profile throughout the canopy. These findings will help to inform growers in selecting a production light quality to best help them meet their specific production goals. [ABSTRACT FROM AUTHOR]

Examines gender differences in coping behavior of competitive athletes. Patterns of coping; Relationships between coping and negative and positive affect; Lack of goal attainment as a measure of stress.

Background Pain acceptance involves willingness to experience pain and engaging in valued activities while pain is present. Though pain acceptance could limit both headache-related disability and pain interference in individuals with migraine, few studies have addressed this issue. This study evaluated whether higher levels of total pain acceptance and its two subcomponents, pain willingness and activity engagement, were associated with lower levels of headache-related impairment in women who had both migraine and overweight/obesity. Methods In this cross-sectional study, participants seeking weight loss and headache relief in the Women's Health and Migraine trial completed baseline measures of pain acceptance (Chronic Pain Acceptance Questionnaire [CPAQ]), headache-related disability (Headache Impact Test-6), and pain interference (Brief Pain Inventory). Migraine headache frequency and pain intensity were assessed daily via smartphone diary. Using CPAQ total and subcomponent (pain willingness and activity engagement) scores, headache frequency, pain intensity, and body mass index (BMI) as predictors in linear regression, headache-related disability, and pain interference were modeled as outcomes. Results On average, participants (n = 126; age = 38.5 ± 8.2 years; BMI = 35.3 ± 6.6 kg/m2) reported 8.4 ± 4.7 migraine days/month and pain intensity of 6.0 ± 1.5 on a 0-10 scale on headache days. After correcting for multiple comparisons (adjusted α = .008), pain willingness was independently associated with both lower headache-related disability ( P < .001; β = −0.233) and pain interference ( P < .001; β = −0.261). Activity engagement was not associated with headache-related disability ( P = .128; β = −0.138) and pain interference ( P = .042; β = −0.154). CPAQ total score was not associated with headache-related disability ( P = .439; β = 0.066) and pain interference ( P = .305; β = 0.074). Pain intensity was significantly associated with outcomes in all analyses ( Ps < .001; βs 0.343-0.615). Conclusions Higher pain willingness, independent of degree of both migraine severity and overweight, is associated with lower headache-related disability and general pain interference in treatment-seeking women with migraine and overweight/obesity. Future studies are needed to clarify direction of causality and test whether strategies designed to help women increase pain willingness, or relinquish ineffective efforts to control pain, can improve functional outcomes in women who have migraine and overweight/obesity. [ABSTRACT FROM AUTHOR]

The article discusses Ukraine's relations with Russia and the West since the 2014 Ukrainian crisis and whether the country could be a buffer zone or a political flashpoint. It states that the country could succeed as a buffer state by securing its territorial integrity, promoting sustainable economic growth and developing self-determination. It notes that Russia worsen the fissures within the country, while the West aims to shape it into a European Union-leaning free-market democracy.

Capturing and reusing fertigation drainage is a key strategy for maximizing greenhouse production efficiency while minimizing the impact of wastewater discharge on receiving ecosystems. Fertigation drainage, in this regard, refers to irrigation water mixed with fertilizer that has once passed through soilless culture. Although an economically and environmentally prudent practice, recirculating fertigation solutions does pose an increased risk of pathogen proliferation. There are many water disinfection technologies currently available to growers, including ozone (O 3(aq)) and Advanced Oxidation Processes (AOP). Beyond currently available treatment options there are emerging technologies that have yet to be optimized for recirculating hydroponics. Electrochemical systems based on Dimensionally Stable Anodes (DSA) offer a novel method for disinfecting fertigation. Using Cyclamen persicum as a representative greenhouse floriculture crop, fertigation solutions were inoculated with Fusarium oxysporum isolated from a diseased C. persicum sample. Following inoculation, solutions were treated with one of either a DSA electrochemical system, a UV/Ozone AOP system, or ozonation. Solutions were then applied to the crop and disease progression was monitored. The positive control group (F. oxysporum added) exhibited pathogenicity following the recirculation of the fertigation solution, while the negative control (F. oxysporum absent) did not show pathogenicity in C. persicum. All water treatment systems achieved a log-4 reduction in F. oxysporum , which prevented pathogenicity in plants. Furthermore, there were no significant differences in plant physiology between the water treatment methods in comparison to the negative control group. However, all treatments performed significantly better than the positive control group which experienced pathogenicity. Solution nutrient analysis indicated stability across all treatments. Energy consumption was also monitored and demonstrated a two-fold reduction in electricity use with the electrochemical flow cell (EFC) compared to the AOP system. • Recirculating fertigation water is effective for saving water and fertilizer. • Without water treatment, plants are easily decimated from plant pathogens. • All water treatment strategies were effective for inactivating Fusarium oxysporum. • Energy consumption was lowest for electrochemical disinfection. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to importance of better sleep quality and morning chronotype in maintenance of successful weight loss. Topics discussed include association of obesity with poor sleep quality and shorter sleep duration, measurement of duration and sleep quality through Sleep Quality Index (SQI), categorization of individuals with higher success in weight loss as morning type chronotype and prediction of smaller weight losses in evening-type chronotype.

Summary Repair of DNA double-strand breaks (DSBs) is essential for genomic stability. The most common DSB repair mechanism in human cells, non-homologous end joining (NHEJ), rejoins broken DNA ends by direct ligation. It remains unclear how components of the NHEJ machinery assemble a synaptic complex that bridges DNA ends. Here, we use single-molecule imaging in a vertebrate cell-free extract to show that synapsis of DNA ends occurs in at least two stages that are controlled by different NHEJ factors. DNA ends are initially tethered in a long-range complex whose formation requires the Ku70/80 heterodimer and the DNA-dependent protein kinase catalytic subunit. The ends are then closely aligned, which requires XLF, a non-catalytic function of XRCC4-LIG4, and DNA-PK activity. These results reveal a structural transition in the synaptic complex that governs alignment of DNA ends. Our approach provides a means of studying physiological DNA DSB repair at single-molecule resolution. [ABSTRACT FROM AUTHOR]

DNA interstrand cross-links ( ICLs) are repaired in S phase by a complex, multistep mechanism involving translesion DNA polymerases. After replication forks collide with an ICL, the leading strand approaches to within one nucleotide of the ICL ('approach'), a nucleotide is inserted across from the unhooked lesion ('insertion'), and the leading strand is extended beyond the lesion ('extension'). How DNA polymerases bypass the ICL is incompletely understood. Here, we use repair of a site-specific ICL in Xenopus egg extracts to study the mechanism of lesion bypass. Deep sequencing of ICL repair products showed that the approach and extension steps are largely error-free. However, a short mutagenic tract is introduced in the vicinity of the lesion, with a maximum mutation frequency of ~1%. Our data further suggest that approach is performed by a replicative polymerase, while extension involves a complex of Rev1 and DNA polymerase ζ. Rev1-pol ζ recruitment requires the Fanconi anemia core complex but not FancI-FancD2. Our results begin to illuminate how lesion bypass is integrated with chromosomal DNA replication to limit ICL repair-associated mutagenesis. [ABSTRACT FROM AUTHOR]

Gene activation by mammalian transcription factors (TFs) requires multivalent interactions of their low-complexity domains (LCDs), but how such interactions regulate transcription remains unclear. It has been proposed that extensive LCD-LCD interactions culminating in liquid-liquid phase separation (LLPS) of TFs is the dominant mechanism underlying transactivation. Here, we investigated how tuning the amount and localization of LCD-LCD interactions in vivo affects transcription of endogenous human genes. Quantitative single-cell and single-molecule imaging reveals that the oncogenic TF EWS::FLI1 requires a narrow optimum of LCD-LCD interactions to activate its target genes associated with GGAA microsatellites. Increasing LCD-LCD interactions toward putative LLPS represses transcription of these genes in patient-derived cells. Likewise, ectopically creating LCD-LCD interactions to sequester EWS::FLI1 into a well-documented LLPS compartment, the nucleolus, inhibits EWS::FLI1-driven transcription and oncogenic transformation. Our findings show how altering the balance of LCD-LCD interactions can influence transcriptional regulation and suggest a potential therapeutic strategy for targeting disease-causing TFs. [Display omitted] • EWS::FLI1 requires a narrow optimum of LCD-LCD interactions to activate transcription • Boosting LCD-LCD interactions toward phase separation represses transcription • Sequestering EWS::FLI1 into the nucleolus inhibits its transcription functions • EWS::FLI1 diffuses more slowly within the phase-separated nucleolus It has been proposed that mammalian TFs require phase separation to activate transcription. Using EWS::FLI1 as a model system, Chong et al. show that a TF requires a narrow optimum of LCD-LCD interactions to activate transcription in vivo , and phase separation of TFs represses transcription of its endogenous target genes. [ABSTRACT FROM AUTHOR]

Significant advances in controlled-environment (CE) plant production lighting have been made in recent years, driven by rapid improvements in light-emitting diode (LED) technologies. Aside from energy efficiency gains, LEDs offer the ability to customize the spectrum delivered to a crop, which may have untold benefits for growers and researchers alike. Understanding how these specific wavebands are attenuated by plant tissue is important if lighting engineers are to fully optimize systems for CE plant production. In this study, seven different greenhouse and field crops (radish, Raphanus sativus 'Cherry Bomb II'; red romaine lettuce, Lactuca sativa 'Outredgeous', green leaf lettuce, Lactuca sativa 'Waldmann's Green'; pepper, Capsicum attnuum 'Fruit Basket'; soybean, Glycine max 'Hovt'; cucumber, Cucumis sativus 'Spacemaster'; canola, Brassica napus 'Westar') were grown in CE chambers under two different light intensities (225 and 420 µmol⋅m-2⋅s-1). Intact, fully expanded upper canopy leaves w ere used to determine the level of light transmission, at two to three different plant ages, across seven different wavebands with peaks at 400, 450, 530, 595, 630, 655, and 735 nm. The photosynthetic photon flux (PPF) environment that plants were grown in affected light transmission across the different LED wavelengths in a crop-dependent manner. Plant age had no effect on light transmission at the time intervals examined. Specific waveband transmission from the seven LED sources varied similarly across plant types with low transmission of blue and red wavelengths, intermediate transmission of green and amber wavelengths, and the highest transmission at the far-red wavelengths. Higher native PPF increased anthocyanin levels in red romaine lettuce compared with the lower native PPF treatment. Understanding the differences in light transmission will inform the development of novel, energy-saving lighting architectures for CE plant growth. [ABSTRACT FROM AUTHOR]

Tree fruits (e.g., apples, plums, cherries) are appealing constituents of a crew menu for longduration exploration missions (i.e., Mars), both in terms of their nutritive and menu diversity contributions. Although appealing, tree fruit species have long been precluded as candidate crops for use in plant-based bioregenerative life support system designs based on their large crown architecture, prolonged juvenile phase, and phenological constraints. Recent advances by researchers at the United States Department of Agriculture (USDA) have led to the development of plum (Prunus domestica) trees ectopically over-expressing the Flowering Locus T-1 (FT1) gene from Populus trichocarpa (poplar). The transformed plants exhibit atypical phenotypes that seemingly eliminate the aforementioned obstacles to spaceflight. Here we demonstrate the FT1 expression system (FasTrack) and the resultant dwarf growth habits, early flowering, and continuous fruit production. The potential contribution of P. domestica as a countermeasure to microgravity-induced bone loss is also discussed. [ABSTRACT FROM AUTHOR]

The parABS system is a widely employed mechanism for plasmid partitioning and chromosome segregation in bacteria. ParB binds to parS sites on plasmids and chromosomes and associates with broad regions of adjacent DNA, a phenomenon known as spreading. Although essential for ParB function, the mechanism of spreading remains poorly understood. Using single-molecule approaches, we discovered that Bacillus subtilis ParB (Spo0J) is able to trap DNA loops. Point mutants in Spo0J that disrupt DNA bridging are defective in spreading and recruitment of structural maintenance of chromosomes (SMC) condensin complexes in vivo. DNA bridging helps to explain how a limited number of Spo0J molecules per parS site (~20) can spread over many kilobases and suggests a mechanism by which ParB proteins could facilitate the loading of SMC complexes. We show that DNA bridging is a property of diverse ParB homologs, suggesting broad evolutionary conservation. [ABSTRACT FROM AUTHOR]

Herein, we describe an operationally straightforward radiosynthesis of a chiral transition metal fluoride catalyst, [18F](salen)CoF, and its use for late-stage enantioselective aliphatic radiofluorination. We demonstrate the utility of the method by preparing single enantiomer experimental and clinically validated PET tracers that contain base-sensitive functional groups, epimerizable stereocenters, and nitrogen-rich motifs. Unlike the conventional radiosyntheses of these targets with [18F]KF, labeling with (salen)CoF is possible in the last step and under exceptionally mild conditions. These results constitute a rare example of a nucleophilic radiofluorination using a transition metal fluoride and highlight the potential of such reagents to enhance traditional methods for labeling aliphatic hydrocarbons. [ABSTRACT FROM AUTHOR]

Abstract: Bioisosteres are integral components of modern pharmaceutical research that allow structural optimization to maximize in vivo efficacy and minimize adverse effects by selectively modifying pharmacodynamic, pharmacokinetic and physicochemical properties. A recent medicinal chemistry campaign focused on identifying small molecule inhibitors of prolylcarboxypeptidase (PrCP) initiated an investigation into the use of pyrazoles as bioisosteres for amides. The results indicate that pyrazoles are suitable bioisosteric replacements of amide functional groups. The study is an example of managing bioisosteric replacement by incorporating subsequent structural modifications to maintain potency against the selected target. A heuristic model for an embedded pharmacophore is also described. [Copyright &y& Elsevier]

Abstract: The synthesis, SAR, binding affinities and pharmacokinetic profiles are described for a series of cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors discovered by high throughput screening. Compounds show high levels of ex vivo target engagement in mouse plasma 20h post oral dose. [Copyright &y& Elsevier]

The author discusses the role of professional health professional in promoting food and nutrition safety. The author mentions that livestock support human health by providing nutrient cycling, nutrients and transport. The author further highlights the role of various organizations in the U.S. including the Department of Agriculture, the Department of Education and the Department of Homeland Security.

Possible chemical methods for the treatment of ammonia in the air of livestock holding facilities, with particular focus on poultry production, are reviewed in the context of eliminating ammonia by oxidation to elemental nitrogen. Gas phase catalytic oxidation processes are incompatible with the needs of the poultry industry on grounds of both capital cost and energy intensiveness. Most chemical oxidants convert ammonia principally to nitrate rather than N2. So-called advanced oxidation processes are unsuited to ammonia oxidation because the hydroxyl radicals that characterize these oxidations react poorly with both NH3 and NH4 +. One promising option is electrochemical oxidation, which does not require the purchase of stoichiometric amounts of chemical oxidants. Among possible electrochemical methods, we favour electrochemical hypochlorination, whereby the denitrification of ammonia to elemental nitrogen is mediated by hypochlorous acid, which is formed reversibly from chloride ion. This technique is compatible with currently available scrubbing technology, with the modification of using acidic brine as the scrubbing solution. Because electrochemical hypochlorination can be applied without costly and complicated pH adjustment of the scrubbed solution with chemical additives, it constitutes an example of best available technology. [ABSTRACT FROM AUTHOR]

Objective--To determine whether vaccination with a monovalent vaccine against Leptospi-ra borgpetersenii serovar Hardjo strain hardjobovis would improve reproductive efficiency in Holstein cattle in a commercial dairy setting. Design--Randomized controlled trial. Animals--1,894 Holstein cows and heifers from a Central California dairy. Procedures--Cattle were assigned to undergo SC administration of a monovalent vaccine against Leptospira borgpetersenii serovar Hardjo strain hardjobovis (n = 986) or a placebo (lac-tated Ringer's solution; 908). At the end of their lactation period, cows received 2 doses of the vaccine or placebo, 28 to 35 days apart, with the initial dose administered in conjunction with oxytetracycline. Heifers received the same treatments, with the second dose administered at least 2 weeks before their entrance into the heifer breeding pen. Urine and blood samples were collected from randomly selected cattle immediately before and 1 year after the trial began and submitted for fluorescent antibody and microscopic agglutination testing to identify any infect-ing Leptospira serovar. Results--The initial herd prevalence of active infection with strain hardjobovis was 13% (6/46 tested cattle), followed by 15% (6/40) 1 year after the trial began. The odds of heifers conceiving over the period at risk for conception, regardless of vaccination, was approximately 2.8 times as high as for primiparous and pluriparous cows. Survival analysis of days from parturition to conception revealed that the vaccine protocol had no effect on the probability of conception between the vaccinated and control groups. The vaccine protocol had no impact on pregnancy loss. Conclusions and Clinical Relevance--The evaluated vaccination protocol against Leptospira strain hardjobovis was not effective in improving reproductive efficiency in commercial Holstein dairy cows or in decreasing urine shedding of leptospires. [ABSTRACT FROM AUTHOR]

The ability to monitor and control plant nutrient ions in fertigation solutions, on an ion-specific basis, is critical to the future of controlled environment agriculture crop production, be it in traditional terrestrial settings (e.g., greenhouse crop production) or as a component of bioregenerative life support systems for long duration space exploration. Several technologies are currently available that can provide the required measurement of ion-specific activities in solution. The greenhouse sector has invested in research examining the potential of a number of these technologies to meet the industry's demanding requirements, and although no ideal solution yet exists for on-line measurement, growers do utilize technologies such as high-performance liquid chromatography to provide off-line measurements. An analogous situation exists on the International Space Station where, technological solutions are sought, but currently on-orbit water quality monitoring is considerably restricted. This paper examines the specific advantages that on-line ion-selective sensors could provide to plant production systems both terrestrially and when utilized in space-based biological life support systems and how similar technologies could be applied to nominal on-orbit water quality monitoring. A historical development and technical review of the various ion-selective monitoring technologies is provided. [ABSTRACT FROM AUTHOR]

Abstract: Aqueous ozone is increasingly used to treat irrigation source water in greenhouse and nursery operations; however, the ozone is typically removed prior to crop application. Until recently, this was appropriate as there was a paucity of data to suggest any other course of action. Recent research examining the application of aqueous ozone, through drip irrigation, to a mineral wool grown hydroponic tomato crop suggests that ozone can remain in solution during distribution to the crop without negative effect. What is not known from this recent work is the upper limit or phytotoxic threshold for aqueous ozone application, beyond which crop damage would occur. The present study examined the effects of high aqueous ozone concentrations applied daily in this same production system. Suppression of some growth metrics was observed at 6.0mgL−1. The ancillary effect of enhanced oxygenation of the irrigation solution, as a result of the ozonation process, was also examined to disentangle the oxygen/aeration effects from the ozone effects. No significant productivity effects were observed at elevated dissolved oxygen levels relative to the fully aerated control, therefore any productivity influence was attributed to aqueous ozone. The degree to which aqueous ozone penetrated the mineral wool substrate was also examined to aid in the development of horticultural management protocols. Even at volumetric ratios well in excess of typical commercial irrigation events, aqueous ozone still did not penetrate the mineral wool medium beyond 4cm, with most of the ozone being lost in the upper 2cm. Only after excessive volumes of aqueous ozone solution had been applied was a residual observed past 4cm. Based on the results of this study and previous work, an upper limit of 3.0mgL−1 for this type of production system is recommended until further research is completed. [Copyright &y& Elsevier]

Abstract: A series of potent inhibitors of prolylcarboxypeptidase (PrCP) was developed by modifying a lead structure that was discovered by high-throughput screening. The tert-butyl pyrrolidine was replaced by an aminocyclopentane to reduce the metabolic liabilities of the original lead. The compounds demonstrated sub-nanomolar in vitro IC50 values, minimal activity shifts in pure plasma and improved pharmacokinetics. Complete ex vivo plasma target engagement was achieved with low brain exposure at the 20h time point following p.o. dosing in a mouse. The results indicate that the aminocyclopentanes are useful tools for studying the therapeutic potential of peripheral (non-CNS) PrCP inhibition. [Copyright &y& Elsevier]

Abstract: A new structural class of potent prolylcarboxypeptidase (PrCP) inhibitors was discovered by high-throughput screening. The series possesses a tractable SAR profile with sub-nanomolar in vitro IC50 values. Compared to prior inhibitors, the new series demonstrated minimal activity shifts in pure plasma and complete ex vivo plasma target engagement in mouse plasma at the 20h post-dose time point (po). In addition, the in vivo level of CNS and non-CNS drug exposure was measured. [Copyright &y& Elsevier]

Marchantia polymorpha L. (a thalloid liverwort) is a common plant pest in nursery and greenhouse production systems. The rapid growth and dissemination of this pest can result in heavy mats of thallus tissue on the surface of pots, which restrict water penetration, compete for nutrients, and provide a habitat for other pests and disease vectors. The sensitivity of liverwort to aqueous ozone was examined to determine if routine use of ozone, as a component of an irrigation water remediation strategy, could provide ancillary services in the form of liverwort management. Three experiments were performed to evaluate contact time (CT) thresholds and application frequencies suitable for liverwort management applications. The first two experiments confirmed that CT is a suitable process control parameter with a base liverwort management threshold occurring between CT 0.84 and 1.68 mg⋅L-1.min under the conditions used. The third experiment examined the effect of application frequency at a CT of 3.75 mg⋅L-1.min, which was previously determined to be compatible with select woody perennial species. Three and five applications per week resulted in reduced liverwort growth and fecundity. [ABSTRACT FROM AUTHOR]

Abstract: Novel prolylcarboxypeptidase (PrCP) inhibitors with nanomolar IC50 values were prepared by replacing the previously described dichlorobenzimidazole-substituted pyrrolidine amides with a variety of substituted benzylamine amides. In contrast to prior series, the compounds demonstrated minimal inhibition shift in whole serum and minimal recognition by P-glycoprotein (P-gp) efflux transporters. The compounds were also cell permeable and demonstrated in vivo brain exposure. The in vivo effect of compound (S)-6e on weight loss in an established diet-induced obesity (eDIO) mouse model was studied. [Copyright &y& Elsevier]