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Interactions with fungi vary among Tripsacum dactyloides genotypes from across a precipitation gradient
Plant-associated microbes, specifically fungal endophytes, augment the ability of many grasses to adapt to extreme environmental conditions. Tripsacum dactyloides (Eastern gamagrass) is a perennial, drought-tolerant grass native to the tallgrass prairies of the central USA. The extent to which the microbiome of T. dactyloides contributes to its drought tolerance is unknown. Ninety-seven genotypes of T. dactyloides were collected from native populations across an east–west precipitation gradient in Kansas, Oklahoma and Texas, and then grown together in a common garden for over 20 years. Root and leaf samples were visually examined for fungal density. Because fungal endophytes confer drought-tolerant capabilities to their host plants, we expected to find higher densities of fungal endophytes in plants from western, drier regions, compared to plants from eastern, wetter regions. Results confirmed a negative correlation between endophyte densities in roots and precipitation at the genotype’s original location (r = −0.21 P = 0.04). Our analyses reveal that the host genotype’s origin along the precipitation gradient predicts the absolute abundance of symbionts in the root, but not the relative abundances of particular organisms or the overall community composition. Overall, these results demonstrate that genetic variation for plant–microbe interactions can reflect historical environment, and reinforce the importance of considering plant genotype in conservation and restoration work in tallgrass prairie ecosystems
Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume
Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to traditional SC delivery systems are therefore needed to support higher-volume biologic formulations and to reduce development time and other risks associated with high-concentration biologic formulations. Here, we outline key considerations for SC biologic drug formulations and delivery and explore a paradigm shift: the flexibility afforded by low-to-moderate-concentration drugs in high-volume formulations as an alternative to the traditionally difficult approach of high-concentration, low-volume SC formulation delivery
Micropolar non-classical continuum theories for solids and fluids with rotational inertial physics
In this thesis, we derive the conservation and balance laws (CBL) and the constitutive theories for micropolar non-classical continuum theories (NCCT) for thermoviscoelastic solids (TVES) without memory in Lagrangian description and thermoviscous (TV) fluids in Eulerian description based on internal or classical rotations (_i\nunezbold{\Theta}) and internal or classical rotation rates (_i^r{\bar{\nunezbold{\Theta}}}) due to skew symmetric part of deformation gradient tensor (\nunezbold{J}) and due to skew symmetric part of the velocity gradient tensor (\bar{\nunezbold{L}}). Thus, these micropolar NCCT for solids and fluids incorporate \nunezbold{J} and \bar{\nunezbold{L}} in their entirety in the derivation of the conservation and balance laws. Both NCCT derived here incorporate rotational inertial physics due to the presence of microconstituents in the derivation of CBL. For micropolar TVES, we consider small deformation, small strain physics. To our knowledge, the inclusion of rotational inertial physics in micropolar NCCT presented here is the first presentation of such a micropolar NCCT.The micropolar NCCT presented in this work for TVES considers two dissipation mechanisms. The first is due to strain rate appearing in the constitutive theory for the deviatoric Cauchy stress tensor. This mechanism is purely due to classical continuum mechanics (CCM). The second dissipation mechanisms is due to the rate of symmetric part of the internal rotation gradient tensor, appearing in the constitutive theory for the symmetric part of the Cauchy moment tensor. The first dissipation mechanisms is viscous. The second dissipation mechanisms is due to the micropolar non-classical physics and it accounts for the drag forces experienced by the microconstituents during deformation of the volume of matter. In the case of micropolar fluids, the dissipation mechanism is due to symmetric part of the velocity gradient tensor appearing in the constitutive theory for the deviatoric Cauchy stress tensor (CCM) and also due to the symmetric part of the rotation rate gradient tensor appearing in the constitutive theory for the symmetric part of the Cauchy moment tensor (NCCM). It is shown that the mathematical models for micropolar TVES and micropolar TV fluids consisting of the conservation and balance laws and constitutive theories have closure.It is established and demonstrated that micropolar NCCT with rotational inertial physics derived here permits coexistence of translational waves (deviatoric Cauchy stress waves) and rotational waves (Cauchy moment waves). In the case of micropolar TV fluids with rotational inertial physics, neither translational nor rotational waves can exist. This is due to the lack of elasticity in classical as well as non-classical physics, as a consequence the balance of linear momenta and balance of angular momenta are time dependent diffusion equations in translational and rotational velocities and are not wave equations.Simple model problems describing evolutions (IVPs) in micropolar TVES and micropolar TV fluids are considered and their numerical solutions are presented (computed using space-time coupled finite element method) to specifically illustrate the influence of rotational inertial physics on the resulting evolutions
The Anti-Cancer Activity of the Naturally Occurring Dipeptide Carnosine: Potential for Breast Cancer
Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine, possessing a multimodal pharmacodynamic profile that includes anti-inflammatory and anti-oxidant activities. Carnosine has also shown its ability to modulate cell proliferation, cell cycle arrest, apoptosis, and even glycolytic energy metabolism, all processes playing a key role in the context of cancer. Cancer is one of the most dreaded diseases of the 20th and 21st centuries. Among the different types of cancer, breast cancer represents the most common non-skin cancer among women, accounting for an estimated 15% of all cancer-related deaths in women. The main aim of the present review was to provide an overview of studies on the anti-cancer activity of carnosine, and in particular its activity against breast cancer. We also highlighted the possible advantages and limitations involved in the use of this dipeptide. The first part of the review entailed a brief description of carnosine’s biological activities and the pathophysiology of cancer, with a focus on breast cancer. The second part of the review described the anti-tumoral activity of carnosine, for which numerous studies have been carried out, especially at the preclinical level, showing promising results. However, only a few studies have investigated the therapeutic potential of this dipeptide for breast cancer prevention or treatment. In this context, carnosine has shown to be able to decrease the size of cancer cells and their viability. It also reduces the levels of vascular endothelial growth factor (VEGF), cyclin D1, NAD+, and ATP, as well as cytochrome c oxidase activity in vitro. When tested in mice with induced breast cancer, carnosine proved to be non-toxic to healthy cells and exhibited chemopreventive activity by reducing tumor growth. Some evidence has also been reported at the clinical level. A randomized phase III prospective placebo-controlled trial showed the ability of Zn–carnosine to prevent dysphagia in breast cancer patients undergoing adjuvant radiotherapy. Despite this evidence, more preclinical and clinical studies are needed to better understand carnosine’s anti-tumoral activity, especially in the context of breast cancer
Species Delimitation, Phylogenomics, and Biogeography of Sulawesi Flying Lizards: A Diversification History Complicated by Ancient Hybridization, Cryptic Species, and Arrested Speciation
The biota of Sulawesi is noted for its high degree of endemism and for its substantial levels of in situ biological diversification. While the island’s long period of isolation and dynamic tectonic history have been implicated as drivers of the regional diversification, this has rarely been tested in the context of an explicit geological framework. Here, we provide a tectonically informed biogeographical framework that we use to explore the diversification history of Sulawesi flying lizards (the Draco lineatus Group), a radiation that is endemic to Sulawesi and its surrounding islands. We employ a framework for inferring cryptic speciation that involves phylogeographic and genetic clustering analyses as a means of identifying potential species followed by population demographic assessment of divergence-timing and rates of bi-directional migration as means of confirming lineage independence (and thus species status). Using this approach, phylogenetic and population genetic analyses of mitochondrial sequence data obtained for 613 samples, a 50-SNP data set for 370 samples, and a 1249-locus exon-capture data set for 106 samples indicate that the current taxonomy substantially understates the true number of Sulawesi Draco species, that both cryptic and arrested speciations have taken place, and that ancient hybridization confounds phylogenetic analyses that do not explicitly account for reticulation. The Draco lineatus Group appears to comprise 15 species—9 on Sulawesi proper and 6 on peripheral islands. The common ancestor of this group colonized Sulawesi ~11 Ma when proto-Sulawesi was likely composed of two ancestral islands, and began to radiate ~6 Ma as new islands formed and were colonized via overwater dispersal. The enlargement and amalgamation of many of these proto-islands into modern Sulawesi, especially during the past 3 Ma, set in motion dynamic species interactions as once-isolated lineages came into secondary contact, some of which resulted in lineage merger, and others surviving to the present
Intervju. Dijalekti čuvaju vrijedne informacije o prošlosti
Interview in Bosnian of Marc L. Greenberg, professor of Slavic languages at the University of Kansas, conducted by Prof. Halid Bulić, University of Sarajevo, for Lingvazin, a publication of the Institute for Bosnian Language and Literature in Tuzla, Bosnia and Herzegovina. Topics include the Encyclopedia of Slavic Languages and Linguistics (Brill), dialectology, open access, and the history of Slavic linguistics in the United States
A pilot study evaluating the prefeasibility of a behavioral weight loss program in people with multiple sclerosis
Weight loss interventions seldom include individuals with neurologic disease. The aims of the present study were to: 1) develop and assess the prefeasibility of a 6-month telehealth behavioral weight loss program for people with multiple sclerosis (MS) and obesity and 2) examine changes in weight loss (primary outcome), physical activity, and fruit/vegetable consumption at follow-up. Participants with obesity and MS engaged in a 24-week weight loss program. Participants followed established diet, exercise, and self-monitoring guidelines and attended weekly online group meetings. Median percentage weight loss was 10.54 % (SD = 7.19). Participants who adhered more closely to the self-monitoring guidelines (r = 0.81, p =.02), and who averaged higher weekly active minutes (r = 0.91, p =.002) achieved greater percentage weight loss. Six of the eight pilot participants achieved clinically meaningful weight loss (>5%) after 6-months
ANCHORAGE OF HIGH-STRENGTH REINFORCING BARS IN CONCRETE
Hooked and headed reinforcing bars are commonly used as a means of shortening development length of reinforcing bars, but a limited amount of previous research has resulted in restrictions on their use in practice. This study included two phases: In the first phase, 31 tests of simulated column-foundation joints were conducted to investigate the anchorage strength and behavior of large and high-strength headed bars as functions of the distance between the anchored headed bar and the compression reaction, number of headed bars tested simultaneously (1 or 2), size of the headed bars (No. 11 or No. 14), center-to-center spacing between headed bars loaded simultaneously (3.2 or 8.2db), amount of confining reinforcement within the joint region (zero to six No. 4 closed stirrups), and concrete compressive strength (5,060 to 14,470 psi). The embedment length of the headed bars ranged from 125/8 to 14 in., and the stresses in the headed bars at failure ranged from 41,800 to 144,400 psi. The test results are compared with anchorage strengths based on the descriptive equations for headed bars developed at the University of Kansas, ACI 318-19 Code provisions, and proposed Code provisions. Recommended changes to Chapters 17 and 25 of ACI 318-19 are presented. In the second phase of the study, descriptive equations for beam-column joints tested under monotonic loading are investigated their applicability to predict the anchorage strength of hooked bars anchored in members subjected to reversed cyclic loading. Comparisons are made with test results from 24 studies of 146 exterior beam-column joint specimens subjected to reversed cyclic loading in which the beam bars are anchored by hooks. Key variables include embedment lengths of the hooked bars (6 to 21 in.), concrete compressive strength (3,140 to 13,700 psi), center-to-center spacing between the hooked bars (1.75 to 6.5 in.), bar size (No. 3 to No. 9), and confining reinforcement within the joint region parallel to the straight portion of the hooked bars (none to nine hoops spaced at 1.25 to 6.0 in.). The yield strength of the hooked bars ranged from 42,900 to 103,000 psi. Proposed changes to Chapters 18 of ACI 318-19 are presented.The results of the experimental study show that the anchorage strength of headed bars anchored in column-foundation joints is improved by parallel tie reinforcement located on all sides of the headed bars, a contribution that is not included in the provisions of ACI 318-19. Similar to observations for beam-column joints, the anchorage strength of headed bars anchored in simulated column-foundation joints decreases as the center-to-center spacing decreases below 8db. The descriptive equations developed based on tests of beam-column joints are suitable for predicting the anchorage strength of headed bars anchored in column-foundation joints. Chapter 17 of ACI 318-19 does not accurately predict the anchorage strength of headed bars tested when parallel tie/anchor reinforcement is used and should be modified to combine the contributions of concrete strength and parallel tie reinforcement. The descriptive equations developed for beam-column joints apply to column-foundation joints and could serve as a basis for the anchorage provisions in Chapter 17 of ACI 318. The provisions in Chapter 25 of ACI 318-19 should be updated to include the effect of parallel tie reinforcement in connections other than beam-column joints. The descriptive equations for the anchorage strength of hooked bars in beam-column joints tested under monotonic loading are suitable for predicting the anchorage strength of hooked bars anchored in members subjected to reversed cyclic loading. The ACI Code provisions for the development length of hooked bars in tension in beam-column joints in special moment frames (Section 18.8.5.1 of ACI 318-19), derived from the development length provisions for non-seismic loading in earlier Codes, permit development lengths that are shorter needed for gravity load by Chapter 25. Changes in Chapter 18 of ACI 318-19 are proposed that require the use of the provisions in Chapter 25 to establish the minimum development length for hooked bars anchored in joints for frames subjected to seismic loading
Particle filter-based parameter estimation algorithm for prognostic risk assessment of progression in non-small cell lung cancer
Non-small cell lung cancer (NSCLC) is a malignant tumor that threatens human life and health. The development of a new NSCLC risk assessment model based on electronic medical records has great potential for reducing the risk of cancer recurrence. In this process, machine learning is a powerful method for automatically extracting risk factors and indicating impact weights for NSCLC deaths. However, when the number of samples reaches a certain value, it is difficult for machine learning to improve the prediction accuracy, and it is also challenging to use the characteristic data of subsequent patients effectively. Therefore, this study aimed to build a postoperative survival risk assessment model for patients with NSCLC that updates the model parameters and improves model accuracy based on new patient data. The model perspective was a combination of particle filtering and parameter estimation. To demonstrate the feasibility and further evaluate the performance of our approach, we performed an empirical analysis experiment. The study showed that our method achieved an overall accuracy of 92% and a recall of 71% for deceased patients. Compared with traditional machine learning models, the accuracy of the model estimated by particle filter parameters has been improved by 2%, and the recall rate for dead patients has been improved by 11%. Additionally, this study outcome shows that this method can better utilize subsequent patients' characteristic data, be more relevant to different patients, and help achieve precision medicine
Cutaneous Hypervascularization Treatment Using Photo-Mediated Ultrasound Therapy
Photo-mediated ultrasound therapy (PUT) is a cavitation-based, highly selective antivascular technique. In this study, the effectiveness and safety of PUT on cutaneous vascular malformation was examined through in vivo experiments in a clinically relevant chicken wattle model, whose microanatomy is similar to that of port-wine stain and other hypervascular dermal diseases in humans. Assessed by optical coherence tomography angiography, the blood vessel density in the chicken wattle decreased by 73.23% after one session of PUT treatment in which 0.707 J/cm2 fluence laser pulses were applied concurrently with ultrasound bursts (n = 7, P < .01). The effectiveness of removing blood vessels in the skin at depth up to 1 mm was further assessed by H&E-stained histology at multiple time points, which included days 1, 3, 7, 14, and 21 after treatment. Additional immunohistochemical analyses with CD31, caspase-3, and Masson’s trichrome stains were performed on day 3 after treatment. The results show that the PUT-induced therapeutic effect was confined and specific to blood vessels only, whereas unwanted collateral damage in other skin tissues such as collagen was avoided. The findings from this study demonstrate that PUT can efficiently and safely remove hypervascular dermal capillaries using laser fluence at a level that is orders of magnitude smaller than that used in conventional laser treatment of vascular lesions, thus offering a safer alternative technique for clinical management of cutaneous vascular malformations