Minor Perturbations Research Articles

Preconditioning by sediment accumulation can produce powerful turbidity currents without major external triggers

Turbidity currents dominate sediment transfer into the deep ocean, and can damage critical seabed infrastructure. It is commonly inferred that powerful turbidity currents are triggered by major external events, such as storms, river floods, or earthquakes. However, basic models for turbidity current triggering remain poorly tested, with few studies accurately recording precise flow timing. Here, we analyse the most detailed series of measurements yet made of powerful (up to 7.2 ms−1) turbidity currents, within Monterey Canyon, offshore California. During 18-months of instrument deployment, fourteen turbidity currents were directly monitored. No consistent triggering mechanism was observed, though flows did cluster around enhanced seasonal sediment supply. We compare turbidity current timing at Monterey Canyon (a sandy canyon-head fed by longshore drift) to the only other systems where numerous (>10-100) flows have been measured precisely via direct monitoring; the Squamish Delta (a sandy fjord-head delta), and the Congo Canyon (connected to the mud-dominated mouth of the Congo River). A common seasonal pattern emerges, leading to a new model for preconditioning and triggering of turbidity currents initiating through slope failure in areas of sediment accumulation, such as canyon heads or river mouths. In this model, rapid or sustained sediment supply alone can produce elevated pore pressures, which may persist, thereby predisposing slopes to fail. Once preconditioned, a range of minor external perturbations, such as moderate storm-waves, result in local pore pressure variation, and thus become effective triggers. Major external triggers are therefore not always a prerequisite for triggering of powerful turbidity currents.

Toward Functional Safety of Systolic Array-Based Deep Learning Hardware Accelerators

High accuracy and ever-increasing computing power have made deep neural networks (DNNs) the algorithm of choice for various machine learning, computer vision, and image processing applications across the computing spectrum. To this end, Google developed the tensor processing unit (TPU) to accelerate the computationally intensive matrix multiplication operation of a DNN on its systolic array architecture. Faults manifested in the datapath of such a systolic array due to latent manufacturing defects or single-event effects may lead to functional safety (FuSa) violation. Although DNNs are known to resist minor perturbations with their inherent fault-tolerant characteristics, we show that the classification accuracy of the model plummets from 97.4% to 7.75% with a minimal fault rate of 0.0003% in the accelerator, implying catastrophic circumstances when deployed across mission-critical systems. Hence, to ensure FuSa of such accelerators, this article provides an extensive FuSa assessment of the accelerator exposed to faults in the datapath, by varying the network parameters, position, and characteristics of the induced error across multiple exhaustive data sets. Furthermore, we propose two novel strategies to obtain a diminutive set of functional test patterns to detect FuSa violation in a DNN accelerator. Our experimental results demonstrate that the obtained test sets can achieve an average of 92.63% (in some cases, up to 100%) fault coverage with cardinality as low as 0.1% of the entire test data set.

Dynamic Analysis of the Switched-Inductor Buck-Boost Converter Based on the Memristor

The direct current (DC)–DC converter presents abundant nonlinear phenomena, such as periodic bifurcation and chaotic motion, under certain conditions. For a switched-inductor buck-boost (SIBB) converter with the memristive load, this paper constructs its state equation model under two operating statuses, investigates its chaotic dynamic characteristics, and draws and analyzes the bifurcation diagrams of the inductive current and phase portraits, under some parameter changing by the MATLAB simulation based on the state equation. Then, by applying certain minor perturbations to parameters, the chaotic phenomenon suppression method is explored by controlling peak current in continuous current mode (CCM) to keep the converter run normally. Finally, the power simulation (PSIM) verifies that the waveforms and the phase portraits controlling the corresponding parameters are consistent with those of the MATLAB simulation.

Proximity-induced electrodeformation and membrane capacitance coupling between cells

Membrane capacitance and transmembrane potential are sensitive to the proximity of neighboring biological cells which eventually induces anisotropic perturbation of the local electric field distribution in a cell assembly and/or a tissue. The development of robust and reliable multiphysics approaches is essential to solve the challenge of analyzing proximity-induced capacitance coupling (CC) between cells. In this study, we ask to what extent this CC is a minor perturbation on the individual cells or whether it can fundamentally affect bio-electromechanical cues. A key component of our continuum electromechanical analysis is the consideration of elastic models of cells under steady state electric field excitation to characterize electrodeformation (ED). Analyzing the difference between the ED force for a pair of cells and its counterpart for a single reference cell allows us to determine a separation distance-orientation angle diagram providing evidence of a separation distance beyond which the electrostatic interactions between a pair of biological cells become inconsequential for the ED. An attenuation-amplification transition of ED force in this diagram suggests that anisotropy induced by the orientation angle of the cell pair relative to the applied electric field direction has a significant influence on ED and CC. We furthermore observe that the shape of this diagram changes when extracellular conductivity is varied. The results obtained are then contrasted with the corresponding diagrams of similar cell configurations under an oscillating electric field excitation below and above the α-dispersion frequency. This investigation may provide new opportunities for further assessment of electromechanical properties of engineered tissues.

Role of Ligand-Binding and Non-Active Site Residues in the Dynamics, Conformational Integrity, and Catalysis of the Disordered Enzyme Monomeric Chorismate Mutase

The dominant view in enzymology is that an increase in structural disorderedness tends to decrease catalytic efficiency. Surprisingly, engineered monomeric chorismate mutase (mCM), an enzyme with properties of molten globule (intrinsically disordered), efficiently catalyses the conversion of chorismate to prephenate. Therefore, here, we investigate the underlying structural plasticity mechanisms that facilitate this catalysis. We generated rationally designed mutations of mCM and used a battery of spectroscopic tests including Forster resonance energy transfer (FRET) and time-resolved fluorescence anisotropy measurements to probe what influences catalysis. We found that the integrity of the secondary structure, and ligand-induced global compaction (disorder-to-order transition) play a crucial role in catalysis. Intriguingly, we find that even minor perturbation in regions distant from the active site can significantly impact the enzyme efficiency by changing the conformation, segmental dynamics, ligand-induced global compaction, and stability.

Robustness of convolutional neural networks in recognition of pigmented skin lesions

A basic requirement for artificial intelligence (AI)-based image analysis systems, which are to be integrated into clinical practice, is a high robustness. Minor changes in how those images are acquired, for example, during routine skin cancer screening, should not change the diagnosis of such assistance systems. To quantify to what extent minor image perturbations affect the convolutional neural network (CNN)-mediated skin lesion classification and to evaluate three possible solutions for this problem (additional data augmentation, test-time augmentation, anti-aliasing). We trained three commonly used CNN architectures to differentiate between dermoscopic melanoma and nevus images. Subsequently, their performance and susceptibility to minor changes ('brittleness') was tested on two distinct test sets with multiple images per lesion. For the first set, image changes, such as rotations or zooms, were generated artificially. The second set contained natural changes that stemmed from multiple photographs taken of the same lesions. All architectures exhibited brittleness on the artificial and natural test set. The three reviewed methods were able to decrease brittleness to varying degrees while still maintaining performance. The observed improvement was greater for the artificial than for the natural test set, where enhancements were minor. Minor image changes, relatively inconspicuous for humans, can have an effect on the robustness of CNNs differentiating skin lesions. By the methods tested here, this effect can be reduced, but not fully eliminated. Thus, further research to sustain the performance of AI classifiers is needed to facilitate the translation of such systems into the clinic.

Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation

During the late phase of HIV-1 infection, viral Gag polyproteins are targeted to the plasma membrane (PM) for assembly. Gag localization at the PM is a prerequisite for the incorporation of the envelope protein (Env) into budding particles. Gag assembly and Env incorporation are mediated by the N-terminal myristoylated matrix (MA) domain of Gag. Nonconservative mutations in the trimer interface of MA (A45E, T70R, and L75G) were found to impair Env incorporation and infectivity, leading to the hypothesis that MA trimerization is an obligatory step for Env incorporation. Conversely, Env incorporation can be rescued by a compensatory mutation in the MA trimer interface (Q63R). The impact of these MA mutations on the structure and trimerization properties of MA is not known. In this study, we employed NMR spectroscopy, X-ray crystallography, and sedimentation techniques to characterize the structure and trimerization properties of HIV-1 MA A45E, Q63R, T70R, and L75G mutant proteins. NMR data revealed that these point mutations did not alter the overall structure and folding of MA but caused minor structural perturbations in the trimer interface. Analytical ultracentrifugation data indicated that mutations had a minimal effect on the MA monomer–trimer equilibrium. The high-resolution X-ray structure of the unmyristoylated MA Q63R protein revealed hydrogen bonding between the side chains of adjacent Arg-63 and Ser-67 on neighboring MA molecules, providing the first structural evidence for an additional intermolecular interaction in the trimer interface. These findings advance our knowledge of the interplay of MA trimerization and Env incorporation into HIV-1 particles.

Local influence analysis of the 2PL IRT model for binary responses

Detecting influence is an important diagnostic stage in every statistical analysis. This paper examines the local influence of minor perturbations of the model and data for the two-parameter logistic item response model for binary data. By applying Cook's approach in the corresponding EM algorithm used to obtain the maximum likelihood estimate of the model parameters, the normal curvature and the conformal normal curvature - building blocks for obtaining the diagnostic measures – are computed. The methodology is illustrated with two real examples and an artificial one.

Network Re-Wiring During Allostery and Protein-Protein Interactions: A Graph Spectral Approach.

The process of allostery is often guided by subtle changes in the non-covalent interactions between residues of a protein. These changes may be brought about by minor perturbations by natural processes like binding of a ligand or protein-protein interaction. The challenge lies in capturing minute changes at the residue interaction level and following their propagation at local as well as global distances. While macromolecular effects of the phenomenon of allostery are inferred from experiments, a computational microscope can elucidate atomistic-level details leading to such macromolecular effects. Network formalism has served as an attractive means to follow this path and has been pursued further for the past couple of decades. In this chapter some concepts and methods are summarized, and recent advances are discussed. Specifically, the changes in strength of interactions (edge weight) and their repercussion on the overall protein organization (residue clustering) are highlighted. In this review, we adopt a graph spectral method to probe these subtle changes in a quantitative manner. Further, the power of this method is demonstrated for capturing re-ordering of side-chain interactions in response to ligand binding, which culminates into formation of a protein-protein complex in β2-adrenergic receptors.

The impact of ventilation patterns on calcite dissolution rates within karst conduits

Erosion rates in streams vary dramatically over time, as differences in streamflow and sediment load enhance or inhibit erosion processes. Within cave streams, and other bedrock channels incising soluble rocks, changes in water chemistry are an important factor in determining how erosion rates will vary in both time and space. Prior studies in surface streams, springs, and caves suggest that variation in dissolved CO2 is the strongest control on variation in calcite dissolution rates. However, the controls on CO2 variation remain poorly quantified. Limited data suggest that ventilation of karst systems can substantially influence dissolved CO2 within karst conduits. However, the interactions among cave ventilation, air–water CO2 exchange, and dissolution dynamics have not been studied in detail. In this study, three years of time series measurements of dissolved and gaseous CO2, cave airflow velocity, and specific conductance from Blowing Springs Cave, Arkansas, were analyzed and used to estimate continuous calcite dissolution rates and quantify the correlations between those rates and potential physical and chemical drivers. We find that chimney effect airflow creates temperature-driven switches in airflow direction, and that the resulting seasonal changes in airflow regulate both gaseous and dissolved CO2 within the cave. As in previous studies, partial pressure of CO2 (pCO2) is the strongest chemical control of dissolution rate variability. However, we also show that cave airflow direction, rather than streamflow, is the strongest physical driver of changes in dissolution rate, contrary to the typical situation in surface channel erosion where floods largely determine the timing and extent of geomorphic work. At the study site, chemical erosion is typically active in the summer, during periods of cave downdraft (airflow from upper to lower entrances), and inactive in the winter, during updraft (airflow from lower to upper entrances). Storms provide only minor perturbations to this overall pattern. We also find that airflow direction modulates dissolution rate variation during storms, with higher storm variability during updraft than during downdraft. Finally, we compare our results with the limited set of other studies that have examined dissolution rate variation within cave streams and draw an initial hypothesis that evolution of cave ventilation patterns strongly impacts how dissolution rate dynamics evolve over the lifetime of karst conduits.

Effects of deoxynivalenol and fumonisins fed in combination on beef cattle: health and performance indices

Interactions between livestock management practices and toxicological outcomes of mycotoxin exposure may explain the range of tolerable toxin levels reported for various species. In the current study, we investigated the effect of concurrent mycotoxin exposure with a high starch diet in 12 beef steers in a partial cross-over experiment using a 21-day treatment period, followed by a 14-day clearance. During the treatment period, animals were assigned to one of two diets: a low mycotoxin control total mixed ration (TMR) (0.2±0.1 mg deoxynivalenol (DON) and 0.2±0.2 mg fumonisins (FUM)/kg TMR) and a high mycotoxin TMR treatment (1.7±0.2 mg DON and 3.5±0.3 mg FUM/kg TMR). We evaluated the impacts of these mycotoxins on performance, physiology and biochemistry; and the ability of the clearance period to return animals to a naïve state in the cross-over model. The lack of acute ruminal acidosis observed indicates that the animals were able to withstand the physiological stresses of the high starch diet, while toxicological outcomes were manifested in minor perturbations of biochemistry and outright performance of exposed animals. Aspartate aminotransferase, cholesterol, fibrinogen and leukocyte count were increased while sorbitol dehydrogenase, bile acids and mean corpuscular volume were decreased in treatment-fed steers, yet were not significantly different than those from control-fed animals.Fusarium toxin exposure significantly decreased ruminal fluid pH, with the clearance period returning animals to a naïve state, as it did for most of the molecular variables measured. Conversely, treatment-fed animals continued to exhibit significantly lower average weekly body weight throughout the treatment period and the first week of the clearance period. While the risk of adverse health effects to fattening cattle from similar doses of DON or FUM as used in the current study is considered low, additional work should be directed towards minimising production losses due to these feed contaminants.

Introduction of cell‐selectivity in bovine cathelicidin BMAP‐28 by exchanging heptadic isoleucine with the adjacent proline at a non‐heptadic position

AbstractBovine cathelicidin, BMAP‐28 exhibits potent antimicrobial activity without any cell‐selectivity. Considering the role of its C‐terminus amino acid residues in its cytotoxic activities, we envisioned to rearrange the amino acids at its C‐terminus without altering its composition for designing new cell‐selective BMAP‐28‐analog. Thus an isoleucine residue at 20th position, also an “a” position of its previously identified isoleucine zipper sequence, was exchanged with a proline residue at 19th position. As a result, a remarkable reduction in the hemolytic activity of BMAP‐28 toward human red blood cells (hRBCs) was observed without hampering its antibacterial activity in liquid media, and in presence of salts and serum. BMAP‐28‐analog, BMAP‐28M depolarized S. aureus membrane and bacterial membrane‐mimetic, PE/PG lipid vesicles similar to BMAP‐28 but showed weaker efficacy to depolarize hRBC membrane and mammalian membrane‐mimetic, PC/Chol vesicles. Differences in the localization of tryptophan residues of BMAP‐28 and BMAP‐28M were observed only in PC/Chol vesicles. BMAP‐28 induced pores of ~3.4 nm diameter onto hRBCs whereas BMAP‐28M showed minor perturbation onto these cells. BMAP‐28 and BMAP‐28M induced the entry of calcein (size, ~1 nm) and 4.4 kDa FITC‐dextran (size, ~2.8 nm) into B. megaterium but not of higher sized fluorescent‐dextrans indicating toroidal pore formation onto these bacterial membranes.

Bifurcation of magnetorheological film–substrate elastomers subjected to biaxial pre-compression and transverse magnetic fields

This work investigates the primary sinusoidal bifurcation wrinkling response of single- and multi-layered magnetorheological elastomer (MRE) film–substrate systems subjected to combined transverse applied magnetic fields and in-plane biaxial pre-compression. A recently proposed continuum model that includes the volume fraction of soft-magnetic particles is employed to analyze the effect of the magnetic properties upon the bifurcation response of the system. The analysis is built in a highly versatile manner using a finite-element discretization approach along the direction of the applied magnetic field and Fourier expansions along the infinite in-plane layer directions. This allows for a seamless investigation of various multi-layered structures. First, we analyze the effect of biaxial pre-compression upon the critical magnetic field for a film–substrate system and for various mechanical stiffness ratios. We observe a kink in the critical magnetic curves and a reflection in the corresponding wave numbers as they cross the equi-biaxial pre-compression regime. Subsequently, we consider a MRE film bonded to a MRE substrate and study the effect of the particle volume fraction ratios in those two parts. As a result, we obtain sharp pattern transitions, i.e., long-to-short wavelength changes with only minor perturbations of the applied pre-compression. The presence of a magnetic substrate changes qualitatively and quantitatively the bifurcation response of the film–substrate system. Finally, we carry out a data-mining exercise to minimize the critical magnetic field at bifurcation by using three different topologies, i.e., a monolayer, a bilayer and a sandwich film. We find that the topologies resembling closely the monolayer one lead to the lowest critical magnetic fields for a given biaxial pre-compression.

Intensified mid-Holocene floods recorded by archeomalacological data and resilience of first farming groups of the Carpathian Basin

One of the most significant cultural transformations in European prehistory occurred in the middle of the 6th millennium BC in the heart of the Carpathian Basin. The northward expansion of Mediterranean farming groups (Starčevo-Körös-Criş cultural complex) halted and underwent a complete transformation giving rise to a new cultural group carrying an altered form of Neolithic traditions onward to Europe. This transformation is restricted to sites along a boundary found in the heart of the basin, north of which unfavorable ecological conditions hampered a long-term engagement in a Mediterranean type of agriculture. The majority of Early Neolithic Körös sites in eastern Hungary are confined to the alluvial plain of the Tisza River prone to natural biannual flooding. These wetland conditions were marginal for early farmers as it contained several elements that were hostile for herded animals and these groups were not adopted to cope with. Körös Culture pastoralists responded to these challenges posed by the new environment by complementing their diet with opportunistically exploited wild resources. This type of resilience of the first farmers seen in the alteration of traditional subsistence strategies was simply attributed to the static hostile conditions of the environment alone. Influence of dynamic changes in the hydrology has not been studied and documented so far. This paper presents a multiproxy archeomalacological approach to establish a mid-Holocene flood record in Southern Central Europe and assess the potential impacts of flood frequencies, climate change-induced higher floods on economic, societal development of the first farming groups from the heart of the Carpathian Basin. Based on our findings, intensified use of second-line subsistence resources marking resilience is coeval with intensified flooding during the second phase of cultural evolution preceding transformation. This marked transformation could have been traced regionally as well along the referred northern distribution line and is coeval with the initial phase of a minor climatic perturbation refered to as the IRD 5.b event. The southward expansion of cold waters in the North Atlantic yielded intensive cyclonic activity bringing more rain and cold weather to W Europe. In Hungary, higher continentality provided by the basin setting preserved warmer conditions. Nevertheless, increased rainfall onto the watershed of major rivers triggered heightened floods.

Stability of the Atlantic overturning circulation under intermediate (MIS3) and full glacial (LGM) conditions and its relationship with Dansgaard-Oeschger climate variability

Paleoclimatic records reveal that millennial-scale climate variability during the Pleistocene was most pronounced during intermediate glacial conditions, like Marine Isotope Stage 3 (MIS3), rather than during interglacial and fully glaciated climates, like the Last Glacial Maximum (LGM). The rapid transitions between cold stadials and warm interstadials recorded in Greenland ice cores during MIS3, referred to as Dansgaard–Oeschger (D-O) events, have been correlated with millennial-scale climate variations worldwide. Although the origin of D-O events is a matter of controversy, striking evidence shows that variations in the strength of the Atlantic meridional overturning circulation (AMOC) were involved. Therefore, understanding the stability properties of the ocean circulation under different background climate conditions is key to understanding D-O millennial-scale climate variability. In the present study, the stability of the AMOC to northern high-latitude freshwater perturbations under MIS3 and LGM boundary conditions is investigated by using the coupled climate model CCSM3. Stability diagrams constructed from a large set of equilibrium experiments reveal a nonlinear dependence of AMOC strength on freshwater forcing under both MIS3 and LGM conditions. The MIS3 baseline state is close to an AMOC stability threshold, which makes the MIS3 climate unstable with respect to minor perturbations. A similar threshold behavior in AMOC stability is observed under LGM conditions; however, larger freshwater perturbations are necessary to pass the threshold and weaken the AMOC. The threshold’s displacement relative to the MIS3 background climate is attributable to differences in the atmospheric hydrologic cycle and North Atlantic sea ice transport. Different atmospheric moisture transports are attributable to thermodynamic and dynamic processes related to differences in greenhouse gas forcing and ice-sheet height between MIS3 and the LGM. We conclude that the higher stability of the AMOC during the LGM is a physically plausible explanation for millennial-scale D-O-type climate variability being suppressed under full glacial conditions, whereas minor perturbations in freshwater fluxes could have triggered D-O climate shifts during MIS3.

Thermodynamics of Huntingtin Aggregation

Amyloid aggregates are found in many neurodegenerative diseases, including Huntington’s, Alzheimer’s, and prion diseases. The precise role of the aggregates in disease progression has been difficult to elucidate because of the diversity of aggregated states they can adopt. Here, we study the formation of fibrils and oligomers by exon 1 of huntingtin protein. We show that the oligomer states are consistent with polymer micelles that are limited in size by the stretching entropy of the polyglutamine region. The model shows how the sequences flanking the amyloid core modulate aggregation behavior. The N17 region promotes aggregation through weakly attractive interactions, whereas the C38 tail opposes aggregation via steric repulsion. We also show that the energetics of cross-β stacking by polyglutamine would produce fibrils with many alignment defects, but minor perturbations from the flanking sequences are sufficient to reduce the defects to the level observed in experiment. We conclude with a discussion of the implications of this model for other amyloid-forming molecules.

Adversarial machine learning for cybersecurity and computer vision: Current developments and challenges

AbstractWe provide a comprehensive overview of adversarial machine learning focusing on two application domains, that is, cybersecurity and computer vision. Research in adversarial machine learning addresses a significant threat to the wide application of machine learning techniques—they are vulnerable to carefully crafted attacks from malicious adversaries. For example, deep neural networks fail to correctly classify adversarial images, which are generated by adding imperceptible perturbations to clean images. We first discuss three main categories of attacks against machine learning techniques—poisoning attacks, evasion attacks, and privacy attacks. Then the corresponding defense approaches are introduced along with the weakness and limitations of the existing defense approaches. We notice adversarial samples in cybersecurity and computer vision are fundamentally different. While adversarial samples in cybersecurity often have different properties/distributions compared with training data, adversarial images in computer vision are created with minor input perturbations. This further complicates the development of robust learning techniques, because a robust learning technique must withstand different types of attacks.This article is categorized under: Statistical Learning and Exploratory Methods of the Data Sciences > Clustering and Classification Statistical Learning and Exploratory Methods of the Data Sciences > Deep Learning Statistical and Graphical Methods of Data Analysis > Robust Methods

MCPH1 Lack of Function Enhances Mitotic Cell Sensitivity Caused by Catalytic Inhibitors of Topo II.

The capacity of Topoisomerase II (Topo II) to remove DNA catenations that arise after replication is essential to ensure faithful chromosome segregation. Topo II activity is monitored during G2 by a specific checkpoint pathway that delays entry into mitosis until the chromosomes are properly decatenated. Recently, we demonstrated that the mitotic defects that are characteristic of cells depleted of MCPH1 function, a protein mutated in primary microcephaly, are not a consequence of a weakened G2 decatenation checkpoint response. However, the mitotic defects could be accounted for by a minor defect in the activity of Topo II during G2/M. To test this hypothesis, we have tracked at live single cell resolution the dynamics of mitosis in MCPH1 depleted HeLa cells upon catalytic inhibition of Topo II. Our analyses demonstrate that neither chromosome alignment nor segregation are more susceptible to minor perturbation in decatenation in MCPH1 deficient cells, as compared with control cells. Interestingly, MCPH1 depleted cells were more prone to mitotic cell death when decatenation was perturbed. Furthermore, when the G2 arrest that was induced by catalytic inhibition of Topo II was abrogated by Chk1 inhibition, the incidence of mitotic cell death was also increased. Taken together, our data suggest that the MCPH1 lack of function increases mitotic cell hypersensitivity to the catalytic inhibition of Topo II.

Welcome to Raman Spectroscopy: Successes, Challenges, and Pitfalls

Geoscientists quickly recognized the broad applicability of Raman micro-probe spectroscopy to the Earth and planetary sciences, especially after commercially built microprobe instruments became available in the early 1980s. Raman spectra are sensitive to even minor (chemical or structural) perturbations within chemical bonds in (even amorphous) solids, liquids, and gases and can, thus, help identify, characterize, and differentiate between individual minerals, fluid inclusions, glasses, carbonaceous materials, solid solution phases, strain in minerals, and dissolved species in multi-component solutions. The articles in this issue explore how Raman spectroscopy has deepened and broadened our understanding of geological and extraterrestrial materials and processes.

Microbiota Stability and Gastrointestinal Tolerance in Response to a High-Protein Diet with and without a Prebiotic, Probiotic, and Synbiotic: A Randomized, Double-Blind, Placebo-Controlled Trial in Older Women

BackgroundHigher protein intakes may help reduce sarcopenia and facilitate recovery from illness and injury in older adults. However, high-protein diets (HPDs) including animal-sourced foods may negatively perturb the microbiota, and provision of probiotics and prebiotics may mitigate these effects. ObjectiveThe aim of this study was to examine the effects of HPD, with and without a probiotic and/or prebiotic, on gut microbiota and wellness in older women. DesignWe conducted an 18-week, double-blind, placebo-controlled, crossover study. Participants/settingParticipants were healthy, older women (mean age±standard deviation=73.7±5.6 years; n=26) recruited from Florida. InterventionParticipants received a weight-maintenance HPD for 2-week periods and the following, in random order: HPD alone (1.5 to 2.2 g/kg/day protein); HPD plus multistrain probiotic formulation (1.54×109Bifidobacterium bifidum HA-132, 4.62×109Bifidobacterium breve HA-129, 4.62×109Bifidobacterium longum HA-135, 4.62×109Lactobacillus acidophilus HA-122, and 4.62×109Lactobacillus plantarum HA-119), HPD plus prebiotic (5.6 g inulin), and HPD plus synbiotic (probiotic plus inulin), separated by 2-week washouts. Stools were collected per period for quantitative polymerase chain reaction (strain recovery) and 16S ribosomal RNA gene amplicon sequencing analyses (microbiota profile). Measures of gastrointestinal and general wellness were assessed. Main outcome measuresMicrobiota composition and probiotic strain recovery were measured. Statistical analysesMicrobiota composition was analyzed by Wilcoxon signed-rank test and t test. Secondary outcomes were analyzing using generalized linear mixed models. ResultsThe microbiota profile demonstrated relative stability with the HPD; representation of Lactobacillus, Lactococcus, and Streptococcus were enhanced, whereas butyrate producers, Roseburia and Anaerostipes, were suppressed. Lactococcus was suppressed with synbiotic vs other HPD periods. Recovery was confirmed for all probiotic strains. Indicators of wellness were unchanged, with the exception of a minimal increase in gastrointestinal distress with inulin. Fat-free mass increased from baseline to study end. ConclusionsAn HPD adhering to the recommended acceptable macronutrient distribution ranges maintains wellness in healthy older women and exerts minor perturbations to the microbiome profile, a group that may benefit from a higher protein intake. ClinicalTrials.gov ID: NCT #02445560.