Symbol-level fiber-longitudinal power profile estimation.

Symbol-level fiber-longitudinal power profile estimation (PPE) greatly reduces the implementation complexity compared with the waveform-level PPE using oversampled data. However, symbol-rate data cannot account for the inter-sample interaction, which leads to inaccuracy of the absolute power estimation. To realize an accurate symbol-level PPE, we provide an in-depth analysis of the differences between symbol-level and waveform-level perturbation matrices and propose a power calibration method based on the trace of the inverse matrix. Evaluated in the probabilistic constellation shaping (PCS) 64QAM 130 Gbaud 5 × 50 km optical links, the root mean squared error (RMSE) of the symbol-level PPE decreases by 0.98 and 0.62 dB at erbium-doped fiber amplifier (EDFA) positions and all estimated positions with the aid of matrix calibration.

Weakly supervised learning-based 3D bladder reconstruction from 2D ultrasound images for bladder volume measurement.

BACKGROUND: Accurate measurement of bladder volume is necessary to maintain the consistency of the patient's anatomy in radiation therapy for pelvic tumors. As the diversity of the bladder shape, traditional methods for bladder volume measurement from 2D ultrasound have been found to produce inaccurate results. PURPOSE: To improve the accuracy of bladder volume measurement from 2D ultrasound images for patients with pelvic tumors. METHODS: The bladder ultrasound images from 130 patients with pelvic cancer were collected retrospectively. All data were split into a training set (80 patients), a validation set (20 patients), and a test set (30 patients). A total of 12 transabdominal ultrasound images for one patient were captured by automatically rotating the ultrasonic probe with an angle step of 15°. An incomplete 3D ultrasound volume was synthesized by arranging these 2D ultrasound images in 3D space according to the acquisition angles. With this as input, a weakly supervised learning-based 3D bladder reconstruction neural network model was built to predict the complete 3D bladder. The key point is that we designed a novel loss function, including the supervised loss of bladder segmentation in the ultrasound images at known angles and the compactness loss of the 3D bladder. Bladder volume was calculated by counting the number of voxels belonging to the 3D bladder. The dice similarity coefficient (DSC) was used to evaluate the accuracy of bladder segmentation, and the relative standard deviation (RSD) was used to evaluate the calculation accuracy of bladder volume with that of computed tomography (CT) images as the gold standard. RESULTS: The results showed that the mean DSC was up to 0.94 and the mean absolute RSD can be reduced to 6.3% when using 12 ultrasound images of one patient. Further, the mean DSC also was up to 0.90 and the mean absolute RSD can be reduced to 9.0% even if only two ultrasound images were used (i.e., the angle step is 90°). Compared with the commercial algorithm in bladder scanners, which has a mean absolute RSD of 13.6%, our proposed method showed a considerably huge improvement. CONCLUSIONS: The proposed weakly supervised learning-based 3D bladder reconstruction method can greatly improve the accuracy of bladder volume measurement. It has great potential to be used in bladder volume measurement devices in the future.

Deep learning based automatic internal gross target volume delineation from 4D-CT of hepatocellular carcinoma patients.

BACKGROUND: The location and morphology of the liver are significantly affected by respiratory motion. Therefore, delineating the gross target volume (GTV) based on 4D medical images is more accurate than regular 3D-CT with contrast. However, the 4D method is also more time-consuming and laborious. This study proposes a deep learning (DL) framework based on 4D-CT that can achieve automatic delineation of internal GTV. METHODS: The proposed network consists of two encoding paths, one for feature extraction of adjacent slices (spatial slices) in a specific 3D-CT sequence, and one for feature extraction of slices at the same location in three adjacent phase 3D-CT sequences (temporal slices), a feature fusion module based on an attention mechanism was proposed for fusing the temporal and spatial features. Twenty-six patients' 4D-CT, each consisting of 10 respiratory phases, were used as the dataset. The Hausdorff distance (HD95), Dice similarity coefficient (DSC), and volume difference (VD) between the manual and predicted tumor contour were computed to evaluate the model's segmentation accuracy. RESULTS: The predicted GTVs and IGTVs were compared quantitatively and visually with the ground truth. For the test dataset, the proposed method achieved a mean DSC of 0.869 ± 0.089 and an HD95 of 5.14 ± 3.34 mm for all GTVs, with under-segmented GTVs on some CT slices being compensated by GTVs on other slices, resulting in better agreement between the predicted IGTVs and the ground truth, with a mean DSC of 0.882 ± 0.085 and an HD95 of 4.88 ± 2.84 mm. The best GTV results were generally observed at the end-inspiration stage. CONCLUSIONS: Our proposed DL framework for tumor segmentation on 4D-CT datasets shows promise for fully automated delineation in the future. The promising results of this work provide impetus for its integration into the 4DCT treatment planning workflow to improve hepatocellular carcinoma radiotherapy.

Low-complexity clustered polynomial nonlinear filter-based electrical dispersion pre-compensation scheme in IM/DD transmission systems.

A polynomial nonlinear filter (PNLF)-based electrical dispersion pre-compensation (pre-EDC) scheme assisted with Gerchberg-Saxton (GS) algorithm is proposed to compensate the chromatic dispersion (CD) for intensity-modulation and direct-detection (IM/DD) optical transmission systems, where PNLF is utilized to fit the nonlinear transfer function of the iterative GS algorithm-based pre-EDC scheme to realize a low-complexity non-iterative CD pre-compensation. The capability of PNLF to fit the nonlinear iterative process enables the PNLF-based pre-EDC scheme to compensate for CD-induced linear distortions and address CD-induced nonlinear distortions, which are typically captured through iterative approaches. Additionally, to further reduce the computational complexity, we also introduce the k-means clustering algorithm to eliminate the weight redundancy and propose a lower-complexity clustered PNLF-based pre-EDC scheme. Simulation results show that PNLF-based and clustered PNLF-based pre-EDC schemes save 76.0% and 97.5% complexity with only 0.3 dB receiver sensitivity penalty at 20% forward error correction (FEC) threshold, compared with GS-based pre-EDC scheme in C-band 56 GBaud 80-km on-off keying (OOK) system. Furthermore, the effectiveness of PNLF-based and clustered PNLF-based pre-EDC schemes is also evaluated through the experimental demonstration. Experimental results show that under C-band 32 GBaud 80-km OOK system, bit error ratio (BER) satisfying 20% FEC threshold is achieved by applying PNLF-based and clustered PNLF-based pre-EDC schemes, which save 78.3% and 94.2% complexity with only 0.4 dB receiver sensitivity penalty compared with GS-based pre-EDC scheme, respectively. The research results indicate that the (clustered) PNLF-based pre-EDC scheme has the great application potential for CD compensation in high-performance and low-cost IM/DD optical transmission systems.

Low-complexity optimized detection with cluster assisting for C-band 64-Gb/s OOK transmission over 100-km SSMF.

In this paper, a low-complexity optimized detection scheme consisting of a post filter with weight sharing (PF-WS) and cluster-assisted log-maximum a posteriori estimation (CA-Log-MAP) is proposed. Besides, a modified equal-width discrete (MEWD) clustering algorithm is proposed to eliminate the training process during clustering. After channel equalization, optimized detection schemes improve performance by suppressing the in-band noise raised by the equalizers. The proposed optimized detection scheme was experimentally performed in a C-band 64-Gb/s on-off keying (OOK) transmission system over 100-km standard single-mode fiber (SSMF) transmission. Compared with the optimized detection scheme with the lowest complexity, the proposed method saves 69.23% required number of real-valued multiplications per symbol (RNRM) at 7% hard-decision forward error correction (HD-FEC). In addition, when the detection performance reaches saturation, the proposed CA-Log-MAP with MEWD saves 82.93% RNRM. Compared with the classic k-means clustering algorithm, the proposed MEWD has the same performance without a training process. To the best of our knowledge, this is the first time clustering algorithms have been applied to optimize decision schemes.

Retracted: Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats With Reflux Esophagitis.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Jia-Yuan Zhuang, Zhi-Yao Chen, Tao Zhang, Du-Peng Tang, Xiao-Yin Jiang, Ze-Hao Zhuang. Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis. Med Sci Monit, 2017; 23: 542-547. DOI: 10.12659/MSM.898131.

Joint intra and inter-channel nonlinearity compensation based on interpretable neural network for long-haul coherent systems.

A novel joint intra and inter-channel nonlinearity compensation method is proposed, which is based on interpretable neural network (NN). For the first time, conventional cascaded digital back-propagation (DBP) and nonlinear polarization crosstalk canceller (NPCC) are deep unfolded into an NN architecture together based on their physical meanings. Verified by extensive simulations of 7-channel 20-GBaud DP-16QAM 3200-km coherent optical transmission, deep-unfolded DBP-NPCC (DU-DBP-NPCC) achieves 1 dB and 0.36 dB Q factor improvement at the launch power of -1 dBm/channel compared with chromatic dispersion compensation (CDC) and cascaded DBP-NPCC, respectively. Under the bit error rate threshold of 2 × 10-2, DU-DBP-NPCC extends the maximum transmission reach by 28% (700 km) compared with CDC. Besides, 3 different training schemes of DU-DBP-NPCC are investigated, implying the effective signal-to-noise ratio is not the proper evaluation metric of nonlinearity compensation performance for DU-DBP-NPCC. Moreover, DU-DBP-NPCC costs 26% lower computational complexity compared with DBP-NPCC, providing a better choice for joint intra and inter-channel nonlinearity compensation in long-haul coherent systems.

Comparison of the Dosimetric Influence of Applicator Displacement on 2D and 3D Brachytherapy for Cervical Cancer Treatment.

To compare the dosimetric influence of applicator displacement on two-dimensional brachytherapy (2D-BT) and three-dimensional brachytherapy (3D-BT) for cervical cancer. Nineteen patients who received computed tomography-guided tandem-and-ovoid (T&O) brachytherapy were retrospectively selected. Both 2D (point-based) and 3D (volume-based) plans with and without virtual applicator displacement in the 3 axes were created for each patient. Dose changes at point A, D90 of the high-risk clinical target volume (HR-CTV) and intermediate-risk CTV (IR-CTV), and the D0.1cc, D1cc, D2cc, and D5cc of organs-at-risk (OARs) caused by applicator displacement were evaluated. Both 2D-BT and 3D-BT plans were sensitive to T&O applicator displacement. The D90 of the CTV and the dose at point A were very sensitive to applicator displacement in the right-left direction (X-axis). An applicator shift of >2 mm in the X-axis resulted in a change of >5% in the dose at point A and D90 of HR-CTV and IR-CTV. In addition, the doses to the OARs were mostly affected by applicator displacement in the anterior-posterior direction (Z-axis). A displacement of <1.5 mm in the Z-axis was required to avoid a dose change of >10% for OARs. For both 2D-BT and 3D-BT plans, T&O displacement greater than ± 2 mm in the X-axis or T&O applicator displacement ± 1.5 mm in the Z-axis resulted in significant dose changes to the tumor and OARs. In comparison with 3D-BT plans, 2D-BT plans delivered a higher dose to the tumor, and the OARs received more undesirable doses when applicator displacement occurred. The influence of applicator displacement on the doses to the tumor and OARs differed between 2D-BT and 3D-BT. Physicians should take individual patient differences into account when selecting a brachytherapy plan to mitigate the influence of applicator displacement.

Study on the Appropriate Timing of Postoperative Adaptive Radiotherapy for High-Grade Glioma.

PURPOSE: To investigate the appropriate timing of adaptive radiotherapy (ART) for high-grade glioma. METHODS: Ten patients with high-grade gliomas were selected and underwent CT/MRI (CT1/MRI1, CT2/MRI2, CT3/MRI3, and CT4/MRI4) scans before RT and during 10-, 20- and 30-fraction RT, and the corresponding RT plans (plan1, plan2, plan3 and plan4) were made. The dose of the initial plan (plan1) was projected to CT2 and CT3 using the image registration technique to obtain the projection plans (plan1-2 and plan1-3) and by superimposing the doses to obtain the ART plans (plan10+20 and plan20+10), respectively. The dosimetric differences in the target volume and organs at risk (OARs) were compared between the projection and adaptive plans. The tumor control probability (TCP) for the planning target volume (PTV) and normal tissue complication probability (NTCP) for the OARs were compared between the two adaptive plans. RESULTS: Compared with the projection plan, the D2 to the PTV of ART decreased, the conformity index (CI) to the PTV increased, and the D2/Dmean to the brainstem, optic chiasm and pituitary, as well as the V20, V30, V40 and V50 to the normal brain decreased. The D2 to the pituitary and optic chiasm as well as the V20, V30, V40 and V50 to the normal brain in plan10+20 were lower than those in plan20+10, while the CI to the PTV was higher than that in plan20+10. The TCP of the PTV in plan10+20 was higher than that in plan20+10. CONCLUSION: ART can improve the precision of target volume irradiation and reduce the irradiation dose to the OARs in high-grade glioma. The time point after 10 fractions of RT is appropriate for ART.

Dosimetric and Radiobiological Comparison of Five Techniques for Postmastectomy Radiotherapy with Simultaneous Integrated Boost.

PURPOSE: To compare five techniques for the postmastectomy radiotherapy (PMRT) with simultaneous integrated boost (SIB). MATERIALS AND METHODS: Twenty patients with left-sided breast cancer were retrospectively selected. Five treatment plans were created for each patient: TomoDirect (TD), unblocked helical TomoTherapy (unb-HT), blocked HT (b-HT), hybrid intensity-modulated radiotherapy (hy-IMRT), and fixed-field IMRT (ff-IMRT). A dose of 50.4 Gy in 28 fractions to PTVtotal and 60.2 Gy in 28 fractions to PTVboost were prescribed. The dosimetric parameters for targets and organs at risk (OARs), the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) for OARs, and the treatment efficiency were assessed and compared. RESULTS: TD plans and hy-IMRT plans had similar good dose coverage and homogeneity for both PTVboost and PTVtotal and superior dose sparing for the lungs and heart. The ff-IMRT plans had similar dosimetric results for the target volumes compared with the TD and hy-IMRT plans, but gave a relatively higher NTCP and SCCP for the lungs. The unb-HT plans exhibited the highest OAR mean dose, highest NTCP for the lungs (0.97 ± 1.25‰) and heart (4.58 ± 3.62%), and highest SCCP for the lungs (3.57 ± 0.05%) and contralateral breast (2.75 ± 0.29%) among all techniques. The b-HT plans significantly outperformed unb-HT plans with respect to the sparing of the lungs and heart. This technique also showed the best conformity index (0.73 ± 0.08) for PTVboost and the optimal NTCP for the lungs (0.03 ± 0.03‰) and heart (0.61 ± 0.73%). Concerning the delivery efficiency, the hy-IMRT and ff-IMRT achieved much higher delivery efficiency compared with TomoTherapy plans. CONCLUSION: Of the five techniques studied, TD and hy-IMRT are considered the preferable options for PMRT with SIB for left-sided breast cancer treatment and can be routinely applied in clinical practice.

Evaluation of Delta4DVH Anatomy in 3D Patient-Specific IMRT Quality Assurance.

PURPOSE: To evaluate the performance of Delta4DVH Anatomy in patient-specific intensity-modulated radiotherapy quality assurance. MATERIALS AND METHODS: Dose comparisons were performed between Anatomy doses calculated with treatment plan dose measured modification and pencil beam algorithms, treatment planning system doses, film doses, and ion chamber measured doses in homogeneous and inhomogeneous geometries. The sensitivity of Anatomy doses to machine errors and output calibration errors was also investigated. RESULTS: For a Volumetric Modulated Arc Therapy (VMAT) plan evaluated on the Delta4 geometry, the conventional gamma passing rate was 99.6%. For a water-equivalent slab geometry, good agreements were found between dose profiles in film, treatment planning system, and Anatomy treatment plan dose measured modification and pencil beam calculations. Gamma passing rate for Anatomy treatment plan dose measured modification and pencil beam doses versus treatment planning system doses was 100%. However, gamma passing rate dropped to 97.2% and 96% for treatment plan dose measured modification and pencil beam calculations in inhomogeneous head & neck phantom, respectively. For the 10 patients' quality assurance plans, good agreements were found between ion chamber measured doses and the planned ones (deviation: 0.09% ± 1.17%). The averaged gamma passing rate for conventional and Anatomy treatment plan dose measured modification and pencil beam gamma analyses in Delta4 geometry was 99.6% ± 0.89%, 98.54% ± 1.60%, and 98.95% ± 1.27%, respectively, higher than averaged gamma passing rate of 97.75% ± 1.23% and 93.04% ± 2.69% for treatment plan dose measured modification and pencil beam in patients' geometries, respectively. Anatomy treatment plan dose measured modification dose profiles agreed well with those in treatment planning system for both Delta4 and patients' geometries, while pencil beam doses demonstrated substantial disagreement in patients' geometries when compared to treatment planning system doses. Both treatment planning system doses are sensitive to multileaf collimator and monitor unit (MU) errors for high and medium dose metrics but not sensitive to the gantry and collimator rotation error smaller than 3°. CONCLUSIONS: The new Delta4DVH Anatomy with treatment plan dose measured modification algorithm is a useful tool for the anatomy-based patient-specific quality assurance. Cautions should be taken when using pencil beam algorithm due to its limitations in handling heterogeneity and in high-dose gradient regions.

Pressure Induced Wetting and Dewetting of the Nonpolar Pocket of Deep-Cavity Cavitands in Water.

Hydrophobic interactions drive the binding of nonpolar ligands to the oily pockets of proteins and supramolecular species in aqueous solution. As such, the wetting of host pockets is expected to play a critical role in determining the thermodynamics of guest binding. Here we use molecular simulations to examine the impact of pressure on the wetting and dewetting of the nonpolar pockets of a series of deep-cavity cavitands in water. The portals to the cavitand pockets are functionalized with both nonpolar (methyl) and polar (hydroxyl) groups oriented pointing either upward or inward toward the pocket. We find wetting of the pocket is favored by the hydroxyl groups and dewetting is favored by the methyl groups. The distribution of waters in the pocket is found to exhibit a two-state-like equilibrium between wet and dry states with a free energy barrier between the two states. Moreover, we demonstrate that the pocket hydration of the cavitands can be collapsed onto a unified adsorption isotherm by assuming the effective pressures within each cavitand pocket differ by a shift pressure that depends on the chemical identity and number of functional groups placed about the portal. These observations support the development of a two-state capillary evaporation model that accurately describes the equilibrium between states and naturally gives rise to the effective shift pressures observed from simulation. This work demonstrates that the hydration of host pockets can be tuned following simple design rules that in turn are expected to impact the thermodynamics of guest complexation.

Spontaneous drying of non-polar deep-cavity cavitand pockets in aqueous solution.

There are many open questions regarding the hydration of solvent-exposed non-polar tracts and pockets in proteins. Although water is predicted to de-wet purely repulsive surfaces and evacuate crevices, the extent of de-wetting is unclear when ubiquitous van der Waals interactions are in play. The structural simplicity of synthetic supramolecular hosts imbues them with considerable potential to address this issue. To this end, here we detail a combination of densimetry and molecular dynamics simulations of three cavitands, coupled with calorimetric studies of their complexes with short-chain carboxylates. Our results reveal the range of wettability possible within the ostensibly identical cavitand pockets-which differ only in the presence and/or position of the methyl groups that encircle the portal to their non-polar pockets. The results demonstrate the ability of macrocycles to template water cavitation within their binding sites and show how the orientation of methyl groups can trigger the drying of non-polar pockets in liquid water, which suggests new avenues to control guest complexation.

Electrostatic Control of Macrocyclization Reactions within Nanospaces.

The intrinsic structural complexity of proteins makes it hard to identify the contributions of each noncovalent interaction behind the remarkable rate accelerations of enzymes. Coulombic forces are evidently primary, but despite developments in artificial nanoreactor design, a picture of the extent to which these can contribute has not been forthcoming. Here we report on two supramolecular capsules that possess structurally identical inner-spaces that differ in the electrostatic potential (EP) field that envelops them: one positive and one negative. This architecture means that only changes in the EP field influence the chemical properties of encapsulated species. We quantify these influences via acidity and rates of cyclization measurements for encapsulated guests, and we confirm the primary role of Coulombic forces with a simple mathematical model approximating the capsules as Born spheres within a continuum dielectric. These results reveal the reaction rate accelerations possible under Coulombic control and highlight important design criteria for nanoreactors.

Simvastatin, but not pravastatin, inhibits the proliferation of esophageal adenocarcinoma and squamous cell carcinoma cells: a cell-molecular study.

BACKGROUND AND OBJECTIVE: Long-term statin therapy has been shown to protect against several cancers, including esophageal cancer (EC). While the mechanisms underlying this effect are not clear. We investigated the effect of hydrophobic simvastatin and hydrophilic pravastatin on the proliferation of EC cells and sought to explore the underlying mechanisms. METHODS: Esophageal adenocarcinoma OE-19 cells and esophageal squamous cell carcinoma Eca-109 cells were treated with different concentrations of simvastatin or pravastatin for 24 h and 48 h. Cell proliferation was assessed by Cell Counting Kit-8 assay. Malondialdehyde (MDA) levels were measured by thiobarbituric acid (TBA) assay. mRNA and protein expression of COX-2 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively; The expression of prostaglandin E2 (PGE2) was measured by ELISA. RESULTS: Simvastatin, but not pravastatin, significantly inhibited the proliferation of OE-19 and Eca-109 cells in a dose- and time-dependent manner, accompanying with the increasing of the MDA level. Moreover, simvastatin suppressed the expression of COX-2 and PGE2 in both OE-19 and Eca-109 cells in a dose-dependent manner. CONCLUSIONS: Lipophilic simvastatin, but not hydrophilic pravastatin, had significant inhibitory effects on the proliferation of Eca-109 and OE-19 cells. The reduction of COX-2 and PGE2 by simvastatin suggested that the inhibitory effect of simvastatin on the proliferation of EC cells may be independent of its lipid-lowering effect. Simvastatin may be a promising agent for the prevention and treatment of EC.

Alkane guest packing drives switching between multimeric deep-cavity cavitand assembly states.

Alkane guest transfer into aqueous dimeric, tetrameric, hexameric, and octameric assemblies of the deep-cavity cavitand TEMOA is examined using molecular simulations. The experimental transitions between aggregation states strongly correlate with calculated alkane transfer free energy minima, demonstrating the guiding role of guest packing on stabilizing multimeric complexes. The predictive simulation approach described affords a salient rationale as to why octameric assemblies have yet to be experimentally observed.

Note: Second osmotic virial coefficients of short alkanes and their alcohol counterparts in water as a function of temperature.

While molecular-scale hydrophobic interactions are readily evaluable from molecular simulations, it is challenging to compare these predictions against experiment as a result of the sparing solubility of purely non-polar species. Recent theoretical and simulation advances have enabled the determination of second osmotic virial coefficients for solutes in aqueous solution, providing an alternate route for experimental validation. Here we report simulation predictions for the second osmotic virial coefficients for methane and ethane as well as those for their alcohol counterparts, methanol and ethanol, in water over a broad temperature range. The results for the alcohols quantitatively agree with available experimental results, providing support for simulation predictions for molecular-scale hydrophobic interactions.

The Thermodynamics of Anion Complexation to Nonpolar Pockets.

The interactions between nonpolar surfaces and polarizable anions lie in a gray area between the hydrophobic and Hofmeister effects. To assess the affinity of these interactions, NMR and ITC were used to probe the thermodynamics of eight anions binding to four different hosts whose pockets each consist primarily of hydrocarbon. Two classes of host were examined: cavitands and cyclodextrins. For all hosts, anion affinity was found to follow the Hofmeister series, with associations ranging from 1.6-5.7 kcal mol-1. Despite the fact that cavitand hosts 1 and 2 possess intrinsic negative electrostatic fields, it was determined that these more enveloping hosts generally bound anions more strongly. The observation that the four hosts each possess specific anion affinities that cannot be readily explained by their structures, points to the importance of counter cations and the solvation of the "empty" hosts, free guests, and host-guest complexes, in defining the affinity.

Guest Controlled Nonmonotonic Deep Cavity Cavitand Assembly State Switching.

Octa-acid (OA) and tetra-endo-methyl octa-acid (TEMOA) are water-soluble, deep-cavity cavitands with nanometer-sized nonpolar pockets that readily bind complementary guests, such as n-alkanes. Experimentally, OA exhibits a progression of 1:1 to 2:2 to 2:1 host/guest complexes (X:Y where X is the number of hosts and Y is the number of guests) with increasing alkane chain length from methane to tetradecane. Differing from OA only by the addition of four methyl groups ringing the portal of the pocket, TEMOA exhibits a nonmonotonic progression of assembly states from 1:1 to 2:2 to 1:1 to 2:1 with increasing guest length. Here we present a systematic molecular simulation study to parse the molecular and thermodynamic determinants that distinguish the succession of assembly stoichiometries observed for these similar hosts. Potentials of mean force between hosts and guests, determined via umbrella sampling, are used to characterize association free energies. These free energies are subsequently used in a reaction network model to predict the equilibrium distributions of assemblies. Our models accurately reproduce the experimentally observed trends, showing that TEMOA's endo-methyl units constrict the opening of the binding pocket, limiting the conformations available to bound guests and disrupting the balance between monomeric complexes and dimeric capsules. The success of our simulations demonstrate their utility at interpreting the impact of even simple chemical modifications on supramolecular assembly and highlight their potential to aid bottom-up design.