Translational Perturbations Research Articles

Codon optimality, bias and usage in translation and mRNA decay.

The advent of ribosome profiling and other tools to probe mRNA translation has revealed that codon bias - the uneven use of synonymous codons in the transcriptome - serves as a secondary genetic code: a code that guides the efficiency of protein production, the fidelity of translation and the metabolism of mRNAs. Recent advancements in our understanding of mRNA decay have revealed a tight coupling between ribosome dynamics and the stability of mRNA transcripts; this coupling integrates codon bias into the concept of codon optimality, or the effects that specific codons and tRNA concentrations have on the efficiency and fidelity of the translation machinery. In this Review, we first discuss the evidence for codon-dependent effects on translation, beginning with the basic mechanisms through which translation perturbation can affect translation efficiency, protein folding and transcript stability. We then discuss how codon effects are leveraged by the cell to tailor the proteome to maintain homeostasis, execute specific gene expression programmes of growth or differentiation and optimize the efficiency of protein production.

Preparatory cortical and spinal settings to counteract anticipated and non-anticipated perturbations

Little is known about how the central nervous system prepares postural responses differently in anticipated compared to non-anticipated perturbations. To investigate this, participants were exposed to translational and rotational perturbations presented in a blocked (anticipated) and a random (non-anticipated) design. The preparatory setting (‘central set’) was measured by H-reflexes, motor-evoked potentials (MEPs), and short-interval intracortical inhibition (SICI) shortly before perturbation onset in the soleus of 15 healthy adults. Additionally, the behavioral consequences of differential preparatory settings were analyzed by comparing the short- (SLR), medium- (MLR), and long-latency response (LLR) of the soleus after anticipated and non-anticipated rotations and translations. H-reflexes elicited before perturbation were different between conditions (p=0.023) with larger amplitudes in anticipated translations compared to anticipated rotations (37.0%; p=0.048). Reduced SICI was found in the three conditions containing perturbations compared to static standing (p<0.001). Muscular responses assessed after perturbations remained unchanged for the SLR and MLR, whereas the LLR was decreased in anticipated rotations (−36.2%; p=0.002) and increased in anticipated translations (16.7%; p=0.046) compared to the corresponding non-anticipated perturbation. As the SLR and MLR are organized at the spinal and the LLR at the cortical level, the preparatory setting seems to mainly influence cortically mediated postural responses. However, the modulation of the H-reflex before anticipated perturbations indicates that supraspinal centers adjusted Ia-afferent transmission for the soleus in a perturbation-specific manner. Intracortical inhibition was also modulated but differentiates to a lesser extent only between perturbation conditions and unperturbed stance.

Prospect of open-cell solid foams for floating-platform multiphase reactor applications – Maldistribution susceptibility and hydrodynamic behavior

Open-cell solid foams are tested for the first time as prospective structured packings in floating columns to evaluate their potential for offshore multiphase reactor applications. Using a hexapod ship motion simulator and low-intrusive wire-mesh sensors, the effect of floating vessel motions on the hydrodynamic behavior of SiSiC foam packed beds operated with concurrent descending gas-liquid flow was comprehensively investigated. The response of gas-liquid distribution, overall bed pressure drop, and liquid axial dispersion to column tilts as well as translational and rotational motions was acquired and compared to their corresponding stationary (onshore) analog configuration. Maldistribution sensitivity and susceptibility of solid-foam packed beds subject to ship tilts and accelerations were interpreted in terms of fluid uniformity factor. Moreover, a stimulus-response tracer pulse technique and a macro-mixing model were used to estimate the liquid mean residence time and Péclet number. Similar to random packings, fluid maldistribution was found to prevail in solid-foam beds with deviations from uniformity greater for rotational than for translational perturbations. Vessel tilts and oscillations adversely affect open-cell foam bed hydrodynamic performance yielding transient gas-liquid segregated flow regimes, oscillations of pressure drop and uniformity factor, as well as notable deviation from liquid plug flow.

A wearable vibrotactile biofeedback system improves balance control of healthy young adults following perturbations from quiet stance

Maintaining postural equilibrium requires fast reactions and constant adjustments of the center of mass (CoM) position to prevent falls, especially when there is a sudden perturbation of the support surface. During this study, a newly developed wearable feedback system provided immediate vibrotactile clues to users based on plantar force measurement, in an attempt to reduce reaction time and CoM displacement in response to a perturbation of the floor. Ten healthy young adults participated in this study. They stood on a support surface, which suddenly moved in one of four horizontal directions (forward, backward, left and right), with the biofeedback system turned on or off. The testing sequence of the four perturbation directions and the two system conditions (turned on or off) was randomized. The resulting reaction time and CoM displacement were analysed. Results showed that the vibrotactile feedback system significantly improved balance control during translational perturbations. The positive results of this preliminary study highlight the potential of a plantar force measurement based biofeedback system in improving balance under perturbations of the support surface. Future system optimizations could facilitate its application in fall prevention in real life conditions, such as standing in buses or trains that suddenly decelerate or accelerate.

The Next Step in Understanding Impaired Reactive Balance Control in People With Stroke: The Role of Defective Early Automatic Postural Responses

Background and objective. Postural muscle responses are often impaired after stroke. We aimed to identify the contribution of deficits in very early postural responses to poorer reactive balance capacity, with a particular focus on reactive stepping as a key strategy for avoiding falls. Methods. A total of 34 chronic stroke survivors and 17 controls were subjected to translational balance perturbations in 4 directions. We identified the highest perturbation intensity that could be recovered without stepping (single stepping threshold [SST]) and with maximally 1 step (multiple stepping threshold [MST]). We determined onset latencies and response amplitudes of 7 leg muscles bilaterally and identified associations with balance capacity. Results. People with stroke had a lower MST than controls in all directions. Side steps resulted in a higher lateral MST than crossover steps but were less common toward the paretic side. Postural responses were delayed and smaller in amplitude on the paretic side only. We observed the strongest associations between gluteus medius (GLUT) onset and amplitude and MST toward the paretic side (R2 = 0.33). Electromyographic variables were rather weakly associated with forward and backward MSTs (R2 = 0.10-0.22) and with SSTs (R2 = 0.08-0.15). Conclusions. Delayed and reduced paretic postural responses are associated with impaired reactive stepping after stroke. Particularly, fast and vigorous activity of the GLUT is imperative for overcoming large sideways perturbations, presumably because it facilitates the effective use of side steps. Because people with stroke often fall toward the paretic side, this finding indicates an important target for training.

Sensory and motoric influences on attention dynamics during standing balance recovery in young and older adults.

This study investigated the impact of attention on the sensory and motor actions during postural recovery from underfoot perturbations in young and older adults. A dual-task paradigm was used involving disjunctive and choice reaction time (RT) tasks to auditory and visual stimuli at different delays from the onset of two types of platform perturbations (rotations and translations). The RTs were increased prior to the perturbation (preparation phase) and during the immediate recovery response (response initiation) in young and older adults, but this interference dissipated rapidly after the perturbation response was initiated (<220ms). The sensory modality of the RT task impacted the results with interference being greater for the auditory task compared to the visual task. As motor complexity of the RT task increased (disjunctive versus choice) there was greater interference from the perturbation. Finally, increasing the complexity of the postural perturbation by mixing the rotational and translational perturbations together increased interference for the auditory RT tasks, but did not affect the visual RT responses. These results suggest that sensory and motoric components of postural control are under the influence of different dynamic attentional processes.

Different Applications for CAS in Functional Classification of Protein Interfaces

Protein-protein interactions (PPI) play essential roles in virtually all biological processes. While modern structural determination methods such as x-ray crystallography and NMR provide valuable information that can aid in our understanding of these complexes, they often produce many putative conformations that require further refinement to determine the biological structure. Here, we outline two methods that may aid in the refinement of these potential conformations. Using a manually curated database of both biologically functional and biologically non-functional PPI (FLIPdb), we explore the relationship between binding free energy as determined by computational alanine scanning (CAS) and small translational perturbations of the interacting protein subunits. In short, the interacting protein subunits are translated along a grid that is coplanar with their dividing plane and the interface is subjected to CAS at each point along the grid. The coordinates of the translation are then used in combination with the binding free energy to create an energy landscape that is further analyzed for various features. Analysis of these features by SVM has allowed us to achieve discrimination of biologically functional/biologically non-functional interfaces with an accuracy of seventy-six percent, and suggests that biologically functional interfaces are more sensitive to perturbation than biologically non-functional interfaces. In addition to translational perturbation sensitivity, we analyze the size and distribution of energetic hotspots present in each PPI. Using solvent accessible surface area (SASA) as measured by NACCESS, and binding free energy as determined by CAS, residues are clustered into hotspots using density based clustering. The size and energy density of these hotspots is then analyzed. Analysis of these features by SVM allows us to discriminate between biologically functional and biologically non-functional PPI with an accuracy of approximately eighty percent.

The effect of weight-bearing asymmetry on dynamic postural stability in people with chronic stroke

After stroke, weight-bearing asymmetry (WBA) towards the non-paretic side is associated with postural instability. It remains unknown whether WBA is a cause or consequence of postural instability, as both phenomena depend on stroke severity. We investigated the effect of WBA on the ability to recover from balance perturbations in people with stroke. Fourteen people in the chronic phase of stroke underwent multidirectional translational perturbations at three levels of initial WBA (0, 10 and 20% of body weight unloading of the paretic leg). We iteratively determined the highest perturbation intensity that could be sustained with a feet-in-place response (i.e. stepping threshold) for each WBA condition and in four perturbation directions (forward, backward, towards paretic and towards non-paretic side). For perturbations above the stepping threshold we determined the choice of stepping leg. WBA increased the stepping threshold for perturbations towards the paretic side, whereas it decreased the stepping threshold for perturbations towards the non-paretic side (p<0.05). No effects of WBA were found on forward or backward stepping thresholds. Yet, the frequency of stepping with the paretic leg in the anteroposterior directions increased with greater WBA. Similarly, greater initial WBA resulted in a larger number of side steps towards the paretic side. In conclusion, the results suggest that people with stroke can benefit from some paretic leg unloading when perturbed towards the paretic side. It remains to be investigated, however, to what extent these benefits outweigh the potentially detrimental effects of WBA that were observed when recovering from perturbations in the other directions.

On the Equilibrium and Stability of a Capillary Liquid with Disconnected Free Surface in an Open Vessel

We consider the problem of stability of the equilibrium state of an ideal liquid placed in a cylindrical vessel containing a hole made in the bottom with regard for the gravity and capillary forces. A spectral criterion for the stability of the equilibrium state of the analyzed liquid is obtained. It is shown that the stability of the equilibrium state is lost if the upper part of the free surface suffers translational perturbations. We propose algorithms for the determination the free surface of liquid and the boundary of the domain of its stability.

Cytoplasmic hGle1A regulates stress granules by modulation of translation.

When eukaryotic cells respond to stress, gene expression pathways change to selectively export and translate subsets of mRNAs. Translationally repressed mRNAs accumulate in cytoplasmic foci known as stress granules (SGs). SGs are in dynamic equilibrium with the translational machinery, but mechanisms controlling this are unclear. Gle1 is required for DEAD-box protein function during mRNA export and translation. We document that human Gle1 (hGle1) is a critical regulator of translation during stress. hGle1 is recruited to SGs, and hGLE1 small interfering RNA-mediated knockdown perturbs SG assembly, resulting in increased numbers of smaller SGs. The rate of SG disassembly is also delayed. Furthermore, SG hGle1-depletion defects correlate with translation perturbations, and the hGle1 role in SGs is independent of mRNA export. Interestingly, we observe isoform-specific roles for hGle1 in which SG function requires hGle1A, whereas mRNA export requires hGle1B. We find that the SG defects in hGle1-depleted cells are rescued by puromycin or DDX3 expression. Together with recent links of hGLE1 mutations in amyotrophic lateral sclerosis patients, these results uncover a paradigm for hGle1A modulating the balance between translation and SGs during stress and disease.

Dopaminergic medication does not improve stepping responses following backward and forward balance perturbations in patients with Parkinson's disease.

In this study, we investigated the effect of dopaminergic medication on reactive stepping responses to forward and backward balance perturbations in patients with moderately severe Parkinson's disease (PD). Twelve PD patients, Hoehn and Yahr stage ranging from 2 to 3, and 15 healthy controls were exposed to multidirectional translational stance perturbations on a moveable platform. Perturbations were unpredictable in terms of amplitude, timing and direction. Patients were tested in the medication ON and OFF (at least 12 h of dopaminergic medication withdrawal) state on two separate days. Forward and backward stepping responses were quantified in terms of (1) presence, onset and amplitude of anticipatory postural adjustments (APAs); (2) spatiotemporal step variables (step onset, length and velocity); and (3) leg inclination angle at first stepping-foot contact. When perturbed forward, patients performed worse than controls in terms of step length (0.32 ± 0.07 vs. 0.38 ± 0.05 m, p = 0.01) and step velocity (1.21 ± 0.16 vs. 1.37 ± 0.13 m/s, p = 0.01), while step onset was not different. The number of steps with an APA was larger in patients in the OFF state than in controls which was, however, only significant after forward perturbations (43 vs. 20%, p = 0.01). Following backward perturbations, leg angles at foot contact were smaller in patients compared to controls (-2.71° ± 4.29° vs. 0.26° ± 2.80°, p = 0.04) reflecting a poorer mechanical efficiency of the step. Dopaminergic medication had no significant effect on any of these outcomes. In conclusion, dopaminergic medication does not improve underscaling of stepping responses in PD. Therefore, other interventions are needed to improve these important defense postural reactions.

Effects of supportive hand contact on reactive postural control during support perturbations

There are many everyday situations in which a supportive hand contact is required for an individual to counteract various postural perturbations. By emulating situations when balance of an individual is challenged, we examined functional role of supportive hand contact at different locations where balance of an individual was perturbed by translational perturbations of the support surface. We examined the effects of handle location, perturbation direction and perturbation intensity on the postural control and the forces generated in the handle.There were significantly larger centre-of-pressure (CoP) displacements for perturbations in posterior direction than for perturbations in anterior direction. Besides, the perturbation intensity significantly affected the peak CoP displacement in both perturbation directions. However, the position of the handle had no effects on the peak CoP displacement. On the contrary, there were significant effects of perturbation direction, perturbation intensity and handle position on the maximal force in the handle. The effect of the handle position was significant for the perturbations in posterior direction where the lowest maximal forces were recorded in the handle located at the shoulder height. They were comparable to the forces in the handle at eye height and significantly lower than the forces in the handle located either lower or further away from the shoulder.In summary, our results indicate that although the location of a supportive hand contact has no effect on the peak CoP displacement of healthy individuals, it affects the forces that an individual needs to exert on the handle in order to counteract support perturbations.

Effects of the type and direction of support surface perturbation on postural responses

BackgroundPostural control is organized around a task goal. The two most frequently used types of tasks for postural control research are translational (translation along the anterior-posterior axis) and rotational (rotation in sagittal plane) surface perturbations. These types of perturbations rotate the ankle joint, causing different magnitudes and directions of body sway. The purpose of this study was to investigate the effects of the type (translation vs. rotation) and direction (forward/toe up vs. backward/toe down) of the perturbation on postural responses.MethodNineteen healthy subjects were tested with four perturbations, i.e., forward and backward translation and toe up and toe down rotation. The onset latency and magnitude of muscle activations, angular changes, and COM displacements were measured. In addition, the kinematic data were divided into two phases. The initial phase reflected the balance disturbance induced by the platform movement, and the reversal phase reflected the balance reaction.ResultsThe results showed that, in the initial phase, rotational perturbation induced earlier ankle movement and faster and larger vertical COM displacement, while translational and forward/toe up perturbations induced larger head and trunk angular change and faster and larger horizontal COM displacement. In the reversal phase, balance reaction was attained by multi-joint movements. Translational and forward/toe up perturbations that induced larger upper body instability evoked faster muscle activation as well as faster and larger hip or knee joint movements.ConclusionsThese findings provide insights into an appropriate support surface perturbation for the evaluation and training of balance.

Dynamic Postural Adjustments in Stance in Response to Translational Perturbation in Presence of Visual and Somatosensory Disturbance

Despite many reports on the role of the sensory system in postural control, only a few studies have reported the relationship between sensory disturbance and dynamic postural control. To investigate capabilities for dynamic postural adjustment, this study quantitatively evaluated the response to translational perturbation. Perturbation was experimentally induced in eight subjects (all male, 21.3 ± 1.4 years old) using a platform movable in four directions (forward, backward, right, and left). The response was measured in terms of the center of pressure (COP) using posturography, and electromyography of the trunk and lower extremities, and joint angle using video analysis. The effect of sensory disturbance was examined when wearing translucent goggles and when standing on a soft mat. A significant difference was found in the displacement of COP between the cases with and without sensory disturbance. With disturbance, the medio-lateral and anterior-posterior components of the displacement increased in the posterior and lateral translations, respectively. In addition, postural response against forward translation was not affected by sensory disturbance compared with backward and medio-lateral translation. The results of these analyses provide information useful for the development of balance rehabilitation using translational perturbation.

The mRNA Secondary Structure Impact on Translation of the KCNH2 Channel Protein

The gene KCNH2 encodes the K+ channel responsible for the repolarizing IKr current essential for normal cardiac physiology. Genetic, translational and post-translational perturbation of KCNH2 causes hereditary (Locus LQT2) and acquired Long QT Syndrome. Over 600 deleterious mutations have been identified as causes of LQT2, most leading to protein trafficking or assembly malfunction. Investigation has focused on the impact the changed amino acids have on the protein product, but little is known about mutational effects on mRNA function. KCNH2 is unusual in that its GC content is ∼66% and there is increased use of rare codons when compared to other human mRNA. Previous studies from our lab have shown that KCNH2 channel translation and trafficking efficiencies are dependent on “extra-coding” elements in the mRNA sequence. CM-KCNH2, a codon modified version of the KCNH2 mRNA, was made with reduced GC content (51%) and decreased use of rare codons, while maintaining the exact amino acid sequence. CM-KCNH2 protein product was a more efficiently trafficked protein, but was translated less efficiently when compared to native KCNH2 (NT-KCNH2). Whether codon-usage, GC content or mRNA 2° structure controls these processes is unknown. To address this, we employ a combined approach of ribosomal profiling to analyze precisely where translational slowing/pausing occurs, and RNA SHAPE analysis to investigate the secondary structure of the KCNH2 mRNA. We hypothesize that the indicated sites of ribosomal pausing, caused by secondary mRNA structure and rare codon placement, allow for correct secondary and tertiary structure formation of the KCNH2 protein, indicating that mRNA impacts not only the primary structure of a protein, but through ‘extra-coding’ features, impacts the folding efficiency and function of the protein product. Ongoing studies will have implications for evaluation and treatment of hereditary and acquired arrhythmias.

Ankle Joint Stiffness and Damping Pattern under Different Frequency of Translation Perturbation

The change of effective stiffness and damping characteristic of ankle joint are able to indicate degeneration of balance ability due to ageing effect. This paper will discuss the ankle joint stiffness and damping pattern along repeated translation perturbation. Six young healthy subjects were exposed to five trials of five different frequencies of perturbation (quiet standing, 0.2 Hz, 0.4 Hz, 0.6 Hz and 0.8 Hz). The result showed that the mean of effective stiffness was reduced with the increase of frequency applied; meanwhile the mean of damping value increased with increasing frequency. Additionally, a cubic polynomial curve (u-shape) was estimated to represent stiffness pattern when using curve fitting method with correlation R2&gt;0.5. These estimations also suggested that ankle joint does not oscillate like spring-damper system which is based on inverted pendulum model; however, it applied a different strategy to maintain balance, in particular during initiation, middle and termination of perturbation. These also indicate the influence of sensory processing and adaptation to maintain balance under a long period of disturbance. On the other hand, damping pattern seems to be similar over different frequencies and under repeated perturbation. Besides, the change of stiffness pattern at higher frequency of perturbation (0.8 Hz) recommends the change in posture strategy from ankle to hip strategy. These findings indicated that stiffness and damping are able to describe adaptation of human posture strategy to keep balance and motor learning under repeated perturbation.

Theoretical and experimental indicators of falls during pregnancy as assessed by postural perturbations

Throughout pregnancy, women experience physical, physiological, and hormonal alterations that are often accompanied by decreased postural control. According to one study, nearly 27% of pregnant women fell while pregnant. This study had two objectives: (1) to characterize the postural responses of pregnant fallers, nonfallers, and controls to surface perturbations, and (2) to develop a mathematical model to gain insights into the postural control strategies of each group. This retrospective analysis used experimental data obtained from 15 women with a fall history during pregnancy, 14 women without a fall history during pregnancy, and 40 nonpregnant controls. Small, medium, and large translational support surface perturbations in the anterior and posterior directions were performed during the pregnant participants’ second and third trimesters. A two-segmented mathematical model of bipedal stance was developed and parameterized, and optimization tools were used to identify ankle and hip stiffness, viscosity, and the feedback time delay by searching for the best fits to experimental COP data. The peak differences between the center of pressure and center of gravity (COP-COG) values were significantly smaller for the pregnant fallers compared with the pregnant nonfallers and controls (p<0.01). Perturbation magnitude was a significant factor (p<0.01), but perturbation direction was not (p=0.24). Model fits were obtained with a mean goodness of fit value of R2=0.92. Theoretical results indicated that pregnant nonfallers had higher ankle stiffness compared with the pregnant fallers and the controls, which suggests that ankle stiffness itself may be the dominant reason for the different dynamic response characteristics (e.g., peak COP–COG) observed. We conclude that increasing ankle stiffness could be an important strategy to prevent falling by pregnant women.

Linear and nonlinear stability criteria for compressible MHD flows in a gravitational field

AbstractThe equilibrium and stability properties of ideal magnetohydrodynamics (MHD) of compressible flow in a gravitational field with a translational symmetry are investigated. Variational principles for the steady-state equations are formulated. The MHD equilibrium equations are obtained as critical points of a conserved Lyapunov functional. This functional consists of the sum of the total energy, the mass, the circulation along field lines (cross helicity), the momentum, and the magnetic helicity. In the unperturbed case, the equilibrium states satisfy a nonlinear second-order partial differential equation (PDE) associated with hydrodynamic Bernoulli law. The PDE can be an elliptic or a parabolic equation depending on increasing the poloidal flow speed. Linear and nonlinear Lyapunov stability conditions under translational symmetric perturbations are established for the equilibrium states.

Precision grip responses to unexpected rotational perturbations scale with axis of rotation

It has been established that rapid, pulse-like increases in precision grip forces (“catch-up responses”) are elicited by unexpected translational perturbations and that response latency and strength scale according to the direction of linear slip relative to the hand as well as gravity. To determine if catch-up responses are elicited by unexpected rotational perturbations and are strength-, axis-, and/or direction-dependent, we imposed step torque loads about each of two axes which were defined relative to the subject's hand: the distal–proximal axis away from and towards the subject's palm, and the grip axis which connects the two fingertips. Precision grip responses were dominated initially by passive mechanics and then by active, unimodal catch-up responses. First dorsal interosseous activity, marking the start of the catch-up response, began 71–89ms after the onset of perturbation. The onset latency, shape, and duration (217–231ms) of the catch-up response were not affected by the axis, direction, or magnitude of the rotational perturbation, while strength was scaled by axis of rotation and slip conditions. Rotations about the grip axis that tilted the object away from the palm and induced rotational slip elicited stronger catch-up responses than rotations about the distal–proximal axis that twisted the object between the digits. To our knowledge, this study is the first to investigate grip responses to unexpected torque loads and to show characteristic, yet axis-dependent, catch-up responses for conditions other than pure linear slip.

Quantitative probabilistic functional diffusion mapping in newly diagnosed glioblastoma treated with radiochemotherapy

Functional diffusion mapping (fDM) is a cancer imaging technique that uses voxel-wise changes in apparent diffusion coefficients (ADC) to evaluate response to treatment. Despite promising initial results, uncertainty in image registration remains the largest barrier to widespread clinical application. The current study introduces a probabilistic approach to fDM quantification to overcome some of these limitations. A total of 143 patients with newly diagnosed glioblastoma who were undergoing standard radiochemotherapy were enrolled in this retrospective study. Traditional and probabilistic fDMs were calculated using ADC maps acquired before and after therapy. Probabilistic fDMs were calculated by applying random, finite translational, and rotational perturbations to both pre-and posttherapy ADC maps, then repeating calculation of fDMs reflecting changes after treatment, resulting in probabilistic fDMs showing the voxel-wise probability of fDM classification. Probabilistic fDMs were then compared with traditional fDMs in their ability to predict progression-free survival (PFS) and overall survival (OS). Probabilistic fDMs applied to patients with newly diagnosed glioblastoma treated with radiochemotherapy demonstrated shortened PFS and OS among patients with a large volume of tumor with decreasing ADC evaluated at the posttreatment time with respect to the baseline scans. Alternatively, patients with a large volume of tumor with increasing ADC evaluated at the posttreatment time with respect to baseline scans were more likely to progress later and live longer. Probabilistic fDMs performed better than traditional fDMs at predicting 12-month PFS and 24-month OS with use of receiver-operator characteristic analysis. Univariate log-rank analysis on Kaplan-Meier data also revealed that probabilistic fDMs could better separate patients on the basis of PFS and OS, compared with traditional fDMs. Results suggest that probabilistic fDMs are a more predictive biomarker in terms of 12-month PFS and 24-month OS in newly diagnosed glioblastoma, compared with traditional fDM analysis.