In-phase Combination Research Articles

Magnetic multi-fabrics as tools for understanding ignimbrite emplacement processes: An example from late-Variscan Tharandter Wald Caldera, Bohemian Massif

Felsic collapse calderas pose a hazard to our society, thus detailed knowledge of collapse mechanisms and behavior of eruptive products could help us to better understand the active calderas. We present a model of the eruption and collapse of Late Carboniferous Tharandter Wald Caldera (Variscan Bohemian Massif) based on field mapping and a magnetic multi-fabric approach. We investigate intra-caldera rhyolitic ignimbrites using a combination of conventional in-phase and relatively new out-of-phase anisotropy of magnetic susceptibility, along with the anisotropy of anhysteretic remanent magnetization. A two-stage caldera evolution model is proposed. (1) The high-energetic and high-temperature ignimbrites filled the paleo-valleys to form a thick ignimbrite sheet with welded to rheomorphosed central portion. Concurrently, eruptions emptied the source magma chamber triggering the piston caldera collapse. (2) The subsidence caused a monoclinal ductile bending of the still-hot and ignimbrite sheet around the caldera rim towards its center. Caldera activity was terminated by the emplacement of subvolcanic ring and radial dikes associated with hydrothermal activity. The latter likely induced abundant magneto-mineralogical alteration and formed composite fabrics. Hence, the application of the multi-fabric approach may serve as a useful tool to extrapolate reliable geodynamic proxies from the magnetic fabric of old, eroded, or altered caldera ignimbrites.

Different trends of vegetation activity over northern extratropics during two multidecadal warming periods in the 20th century

There have been two periods (1916–1945 and 1982–2014) of rapid and comparable rates (0.054 °C/year vs. 0.055 °C/year) of increase in Global Mean Temperature (GMT). However, little is known about different trends in vegetation activity over the northern extratropics during these two periods, especially for vegetation dynamics in response to the earlier global warming in the 20th century. In this study, we find that although the global warming rates are comparable between the two warming periods, regional warming over the northern extratopics has significant differences. Meanwhile, vegetation greening trends are significantly different, with the latter period being 3–4 times greater than the former. Further analysis of the leading causes reveals that the impacts of the Atlantic Multidecadal Oscillation (AMO) and Pacific Decadal Oscillation (PDO) on regional climate are critical to these differences. In 1916–1945, the in-phase combination of AMO and PDO offsets each other's impact on the climate factors and weakens the greening trend, while in 1982–2014, the effects of AMO and PDO are synergetic for the out-of-phase combination and enhance the greening trend. Our findings highlight the role of internal climate variability in modulating vegetation dynamics under global warming and suggest that future projections of vegetation change may be improved by considering decadal and multidecadal climate oscillations.

Nonlinear and Load-Pulling Effects in an Octave-Bandwidth Transmit Array

This article presents the design and nonlinear analysis of an octave-bandwidth transmit in-phase power combiner feed network. The goal is to evaluate the effect of nonlinearities on the in-phase spatial power combiner figures of merit (FoMs), namely effective isotropically radiated power (EIRP), overall efficiency, and linearity across a wide bandwidth and as a function of active antenna impedance and power amplifier (PA) supply voltage ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$V_{\textrm {DD}}$ </tex-math></inline-formula> ). The analysis is showcased on a 6–12 GHz four-element array implemented with electrically small flared horns fed with microstrip-to ridge waveguide transitions, 2-W commercial gallium nitride (GaN) monolithic microwave integrated circuit (MMIC) amplifiers, and an in-phase Wilkinson power splitter. Over-the-air (OTA) measurements show an EIRP of 50 dBm over the octave bandwidth. Adjacent channel power ratio (ACPR) variation over frequency, power, and supply voltage is also measured through OTA and shows a variation of 10 dB over the considered variables.

Design of a 3-way wide-band in-phase power combiner for UHF applications

ABSTRACT In this work, a three-way wide-band in-phase power combiner for ultra-high frequency band (UHF) applications is presented. The proposed power combiner is a modification of the conventional 3-way Wilkinson power combiner. In the proposed power combiner, the floating isolation-resistors are replaced by coaxial baluns and 50-Ω terminations. This configuration is suitable for high-power applications as flange-mount terminations exhibit superior frequency response and heat conduction compared to floating resistors. The coaxial baluns, connected in the star configuration, help for isolation and input-ports matching. The characteristic impedance of coaxial baluns is 50-Ω and is matched to the terminations. This property serves for a broad bandwidth. Even- and odd-mode methods are employed for the analysis and design of the power combiner. To validate the design method and the theoretical results, a three-way power combiner is fabricated, which consists of microstrip, coaxial-cables and some 50-Ω terminations. The combiner provides 20-dB isolation and summing-port return-loss over an octave bandwidth. The operating frequency is between 470 and 860 MHz, which is used for digital video broadcasting–terrestrial (DVB-T).

Positive relationship between seasonal Indo-Pacific Ocean wave power and SST

The influence of increasing sea surface temperatures (SSTs), in response to greenhouse warming, on wave power (WP) remains uncertain. Here, seasonal relationships between SST anomalies and mean and extreme WP over the Indo-Pacific Ocean are examined. Overall, seasonal WP has significantly increased over much of the Pacific, Indian, and Southern Ocean by 1.21–3.10 kW/m dec−1 over 1979–2019. Contributions from wave characteristics, namely significant wave height (SWH) and peak wave period (PWP), to changes in WP show that SWH contributes most in extra-tropical regions, and PWP most in tropical regions. Further, seasonal relationships between SST anomalies and WP indicate that increases in WP are also seen during strong El Niño years in December–February, and in-phase combinations of El Niño and positive Indian Ocean Dipole (IOD) events during June–August and September–November. Results highlight both long-term increasing SSTs and climate variability roles for inducing large-scale seasonal WP changes throughout the Indo-Pacific.

Complex Featuring Two Double Dative Bonds Between Carbon(0) and Uranium

Complex Featuring Two Double Dative Bonds Between Carbon(0) and Uranium

MRI of [2-13 C]Lactate without J-coupling artifacts.

Imaging of [2-13 C]lactate, a metabolic product of [2-13 C]pyruvate, is over considerable interest in hyperpolarized 13 C studies. However, artifact-free imaging of a J-coupled nuclear spin species can be challenging due to the peak-splitting induced by the spin-spin interactions. In this work, two new techniques resolving these J-modulated artifacts are presented. The Product Operator Formalism (POF) of density matrix theory is used to both numerically and analytically derive the coherences arising during radiofrequency excitation and readout of a J-coupled spin system. A combination of computer simulations and experiments with [2-13 C]lactate and 13 C-formate phantoms are then used to verify the performance of two imaging methods. In the first approach, a quadrature imaging technique is used to eliminate scalar coupling artifacts via the combination of in-phase and quadrature images acquired at echo times differing by 1/2J with an echoplanar readout. The second approach employs a highly narrowband RF excitation pulse to image a single peak from the J-coupled doublet. Simulations using a numerical Shepp-Logan phantom, in vitro experiments using thermally polarized [2-13 C]lactate, thermally and hyperpolarized 13 C-formate phantoms, and in vivo imaging of [2-13 C]lactate produced in rat brain following injection of hyperpolarized [2-13 C]pyruvate show artifact-free images and demonstrate potential utility of these methods. The quadrature imaging and the narrowband excitation techniques resolve the J-coupling induced ghosting and blurring artifacts present with conventional MRI of J-coupled signals such as [2-13 C]lactate.

Arbitrary terminated negative group delay circuit using signal interference concept

In this article, we demonstrate signal interference concept based wideband negative group delay (NGD) circuit with an arbitrary termination port impedance. The proposed circuit consists of unequal power division ratio 180° hybrid and in-phase combiner. The NGD can be generated by controlling power division ratios of 180° hybrid and combiner. For experimental verification, the circuit is designed and fabricated at a center frequency of 2 GHz. The experiment results show that the proposed NGD circuit can provide 460 MHz NGD bandwidth (bandwidth of group delay <0 ns) with group delay of −0.8 ns at 2 GHz.

Ab Initio Analysis of Metal-Ligand Bonding in An(COT)2 with An=Th, U in Their Ground- and Core-Excited States.

Relativistic multireference ab initio wave function calculations with the restricted active space second-order perturbation theory (RASPT2) were performed on thorocene and uranocene to determine the actinide N4,5 -edge and carbon K-edge X-ray absorption near-edge structure (XANES) intensities and the metal-ligand orbital mixing in the ground state and core-excited states. Calculated spectral intensities show very good agreement with the experiments and therefore allow detailed and unambiguous assignment of the observed spectral features. φ-type covalent bonding or antibonding interactions are observed for thorocene in the core-excited states, though not in the ground state. This is because the molecular orbital of φ symmetry, which is the in-phase combination of the ligand Lφ and the Th 5fφ orbitals, can be populated with electrons in core-excited states, whereas it is essentially unoccupied in the ground state. For uranocene, the XANES spectra do not reveal much information beyond multiplet broadening, despite the presence of distinct peaks in the spectra. Every core-excited peak is best characterized by its own set of bond orbitals, as the excited state covalency is clearly different from the ground state covalency.

Thermal cycling effects on the creep-fatigue interaction in type 316LN austenitic stainless steel weld joint

Thermomechanical fatigue (TMF) tests under in-phase temperature-mechanical strain combination were performed on a type 316 LN austenitic stainless steel weld joint using temperature ranges of 573–823 K, 623–873 K and 673–923 K employing a mechanical strain amplitude (Δεmech/2) of ±0.4%. Isothermal low cycle fatigue (designated as IF) tests were also carried out at the maximum temperatures (Tmax) of TMF cycling. The interaction of creep deformation with IF and TMF cycling was assessed by incorporating hold periods of 1 min and 5 min at the maximum tensile strain. TMF cycling resulted in considerably lower lives compared to IF, with the life reduction being more significant under hold conditions. Further, a clear difference in the cyclic stress response (CSR) was observed between creep-TMF and creep-IF cycling, depending on the hold duration and temperature range. The contribution of creep deformation to the overall damage was found to be higher under TMF compared to IF cycling at the Tmax. The observed variations in the cyclic lives under IF and TMF cycling with and without hold times were explained on the basis of the dominant fracture mechanisms identified through detailed microstructural characterization of the crack initiation and propagation modes. The extent of intergranular damage was seen to increase with an increase in the temperature range and the hold period. The role of oxidation in the development of damage was observed to be different under creep-TMF and creep-IF cycling. Numerous grain boundary microvoids and their inter-linkages caused enhanced crack propagation under creep-TMF, compared to creep-IF cycling. A comparison of the deformation behaviour, cyclic life and damage developed in the material under IF and TMF suggested that the performance of the weld joint under TMF cycling cannot be satisfactorily represented through IF tests at the Tmax.

Elucidating the Electronic Structure of the Ligated Cuboctahedral Palladium Cluster [Pd13(μ4-C7H7)6]2+

The electronic structure of the recently reported cuboctahedral [Pd13(μ4-Tr)6]2+ (Tr = C7H7) cluster is analyzed using DFT calculations. Results indicate that the bonding in this cluster can be described from the formal starting point of a [Pd13]2− core interacting with a partly reduced [Tr6]4+ ligand shell. The orbital interactions between the two fragments are strong, owing in particular to the very strong accepting ability of the surrounding ligands. The (moderate) Pd–Pd bonding character is in part due to the occupation of the strongly bonding in-phase combination of the 5s(Pd) orbitals (the 1S jellium level) and for another part from through-bond interactions.

Electronic transport of SiC molecular chains in parallel via first-principles calculations

Motivated by the trend of increasing miniaturization and multifunctional implementation, the electronic transport properties of two silicon carbide (SiC) molecular chains in parallel sandwiched between two semi-infinite Au(100)-3 × 6 electrodes are investigated using the density-functional theory and nonequilibrium Green's function formalism. The π-bonding molecular orbitals resulting from the in-phase combination of two px or py atomic orbitals of the C and Si atoms are found to play a key role in the electronic transport, and the possible electron pathways are summarized. Our results show that changing the separation between the two chains in a certain range can produce remarkable differences in transport properties. When the two chains are in small separation (d = 2.884 Å), their strong electrostatic interaction makes a constructive contribution to the electronic transport properties, in which the underlying physical mechanism has been revealed. We also find that d = 5.768 Å is the critical distance both for the transport difference and for the electrostatic interaction in the top-top configuration. Both the conductance (classical Kirchhoff's superposition law) and the current follow the superposition law well in the atomic scale when d = 5.768 Å, much smaller than the critical distance of 15.5 Å from the result of Zhou et al. [Carbon 95, 503 (2015)]. Additionally, the superposition law is more valid for a larger chain spacing (d ≥ 5.768 Å). Our work demonstrates that the realization of the superposition law and the way of increasing current and rectification effect may lay the foundation for the miniaturization exploration and multifunctional implementation of SiC chain related molecular devices.

Dominant Interannual Covariations of the East Asian–Australian Land Precipitation during Boreal Winter

AbstractThe present study applies the empirical orthogonal function (EOF) method to investigate the interannual covariations of East Asian–Australian land precipitation (EAALP) during boreal winter based on observational and reanalysis datasets. The first mode of EAALP variations is characterized by opposite-sign anomalies between East Asia (EA) and Australia (AUS). The second mode features an anomaly pattern over EA similar to the first mode, but with a southwest–northeast dipole structure over AUS. El Niño–Southern Oscillation (ENSO) is found to be a primary factor in modulating the interannual variations of land precipitation over EA and western AUS. By comparison, the Indian Ocean subtropical dipole mode (IOSD) plays an important role in the formation of precipitation anomalies over northeastern AUS, mainly through a zonal vertical circulation spanning from the southern Indian Ocean (SIO) to northern AUS. In addition, the ENSO-independent cold sea surface temperature (SST) anomalies in the western North Pacific (WNP) impact the formation of the second mode. Using the atmospheric general circulation model ECHAM5, three 40-yr numerical simulation experiments differing in specified SST forcings verify the impacts of the IOSD and WNP SST anomalies. Further composite analyses indicate that the dominant patterns of EAALP variability are largely determined by the out-of-phase and in-phase combinations of ENSO and IOSD. These results suggest that in addition to ENSO, IOSD should be considered as another crucial factor influencing the EAALP variability during the boreal winter, which has large implications for improved prediction of EAALP land precipitation on the interannual time scale.

Design of a GaN-on-Si Single-Balanced Resistive Mixer for &lt;italic&gt;Ka&lt;/italic&gt;-band Satcom

Design and performance of a gallium nitride (GaN)-on-Si mixer for the Ka -band satellite telecom applications are presented in this letter. GaN-on-Si offers the advantage of high-volume production even for millimeter-wave applications. A single-balanced architecture is selected as an optimum tradeoff between circuit complexity and rejection of local oscillator (LO) harmonics. An alternative circuit topology is adopted where the in-phase combiner and hybrid quadrature couplers, used to obtain the desired signal phasing at mixer output, are also employed as circuit elements to inject external bias voltages so to optimize the mixer’s conversions loss (CL). The mixer features 11-dB CL, 11- and 22-dBm P1dB and IIP3 respectively, in the 26–31-GHz bandwidth when driven by a 10-dBm LO level. Monolithic microwave integrated circuit area is less than 6 mm2.

Modification of the wintertime Pacific\u2013North American pattern related North American climate anomalies by the Asian\u2013Bering\u2013North American teleconnection

The Pacific–North American (PNA) pattern is closely related to North American climate. In this study, we demonstrate that the PNA associated anomalies of North American surface temperatures and temperature extremes are modified by the extratropical Asian–Bering–North American (ABNA) teleconnection. The temperature and temperature extreme anomalies in association with the combination of the PNA and ABNA patterns are most prominent over the Canadian Prairies, and can be approximated by a linear superposition of the circulation and temperature responses to the two patterns. The various temperature responses result from the corresponding atmospheric circulation anomalies, which are associated with sea surface temperature and precipitation anomalies in the tropical eastern-central Pacific and snow cover anomalies in the Siberian region. In particular, pronounced circulation anomalies are apparent over the Great Lakes/Hudson Bay, and around the Aleutian Islands with opposite sign for the in-phase PNA and ABNA combination. This induces anomalous temperature advection and precipitation, as well as the heating associated variations of vertical motion and clouds, leading to prominent surface temperature anomalies over the Canadian Prairies directly through the variation of the surface energy budget. For the out-of-phase PNA and ABNA combination, the anomalous circulation center tends to be situated along the west coast of North America. This induces weak circulation anomalies over north-central North America and brings weak thermal advection and precipitation anomalies there, leading to insignificant temperature anomalies over the Canadian Prairies. Both the ABNA and PNA can be skillfully predicted on the seasonal time scale, as well as their pattern related North American temperature anomalies. Hence it is important to consider both tropical and extratropical sources of predictability in improving North American climate prediction skill on seasonal to interannual time scales.

A Wideband Linear &lt;inline-formula&gt; &lt;tex-math notation="LaTeX"&gt;$I/Q$ &lt;/tex-math&gt; &lt;/inline-formula&gt;-Interleaving DDRM

This paper presents a wideband linear direct-digital RF modulator (DDRM) in 40-nm CMOS technology. An innovative $I/Q$ -interleaving RF digital-to-analog converter (DAC) is proposed to enable the combination of in-phase ( $I$ ) and quadrature ( $Q$ ) signals in a more digital fashion, thereby improving the linearity performance at large bandwidths. The DDRM also features an advanced second-order hold digital interpolation filter to suppress the sampling spectral replicas in the presence of large bandwidth signals. Moreover, the harmonic rejection technique in the context of RF DAC operation is adopted and implemented. The $2 \times 9$ -bit DDRM core occupies 0.21 mm2 and consumes 110 and 146 mW at 1 and 3 GHz, respectively, with the peak power of +9.2 dBm. The error vector magnitude (EVM) and adjacent channel power ratio (ACPR) at 3 GHz for a 57-MHz 64-QAM signal are better than −30 and −45 dB, respectively, and ACPR remains as low as −44 dBc up to a wide bandwidth of 113 MHz.

Unraveling substituent effects on frontier orbitals of conjugated molecules using an absolutely localized molecular orbital based analysis.

It is common to introduce electron-donating or electron-withdrawing substituent groups into functional conjugated molecules (such as dyes) to tune their electronic structure properties (such as frontier orbital energy levels) and photophysical properties (such as absorption and emission wavelengths). However, there lacks a generally applicable tool that can unravel the underlying interactions between orbitals from a substrate molecule and those from its substituents in modern electronic structure calculations, despite the long history of qualitative molecular orbital theory. In this work, the absolutely localized molecular orbitals (ALMO) based analysis is extended to analyze the effects of substituent groups on the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of a given system. This provides a bottom-up avenue towards quantification of effects from distinct physical origins (e.g. permanent electrostatics/Pauli repulsion, mutual polarization, inter-fragment orbital mixing). For the example case of prodan (a typical dye molecule), it is found that inter-fragment orbital mixing plays a key role in narrowing the HOMO-LUMO gap of the naphthalene core. Specifically, an out-of-phase mixing of high-lying occupied orbitals on the naphthalene core and the dimethylamino group leads to an elevated HOMO, whereas an in-phase combination of LUMOs on the naphthalene core and the propionyl group lowers the LUMO energy of the entire molecule. We expect this ALMO-based analysis to bridge the gap between concepts from qualitative orbital interaction analysis and quantitative electronic structure calculations.

Combined effect of the East Atlantic/West Russia and Western Pacific teleconnections on the East Asian winter monsoon

This study investigates the individual effects of the East Atlantic/West Russia (EATL/WRUS) and Western Pacific (WP) teleconnection patterns and their combined effect on the East Asian winter monsoon (EAWM). The contributions of the respective EATL/WRUS and WP teleconnection patterns to the EAWM are revealed by removing the dependence on the Arctic Oscillation (AO) and the El Nino-Southern Oscillation (ENSO) using a linear regression, which are named as N_EATL/WRUS and N_WP, respectively. This is because the EATL/WRUS (WP) is closely linked to the Arctic (tropics) region. A significant increase (decrease) in temperature over East Asia (EA) corresponding to a weak (strong) EAWM is associated with the N_EATL/WRUS and N_WP teleconnection patterns during the positive (negative) phases. In order to examine impacts of these two teleconnections on the EAWM, three types of effects are reconstructed on the basis of ± 0.5 standard deviation: 1) Combined effect, 2) N_EATL/WRUS effect, and 3) N_WP effect. The positive N_EATL/WRUS teleconnection induces to a weakened Siberian High and a shallow EA trough at the mid-troposphere through wave propagation, leading to the weak EAWM. During the positive N_WP pattern, warm air from the tropics flows toward the EA along western flank of an anomalous anticyclone over the North Pacific that is relevant to the meridional shift of the Aleutian Low. When the two mid-latitude teleconnections have the in-phase combination, the increase in temperature over EA appears to be more pronounced than the individual effects by transporting warm air from tropics via strong southeasterly wind anomalies induced by anomalous zonal pressure gradient between the Siberian High and Aleutian Low. Therefore, the impact of the mid-latitude teleconnections on the EAWM becomes robust and linearly superimposed, unlike a nonlinear in-phase combined effect of the AO and ENSO.

Millimeter-Wave Sources at 60 and 140 GHz by Magnetic-Plasmon-Waveguide-Based In-Phase Coupled Oscillator Network in 65-nm CMOS

High output power density millimeter-wave (mm-wave) signal sources are demonstrated at 60 and 140 GHz by a magnetic plasmon waveguide (MPW) based in-phase coupled oscillator network (CON) in 65-nm CMOS. Each oscillator unit-cell is designed by an MPW-based low-loss inter-digital zero-phase coupler (ZPC). With multiple in-phase coupled ZPC unit-cells, a high output power mm-wave signal is generated at the center of the CON by an in-phase power combination. A 60-GHz CON-based signal source is implemented with four in-phase CON unit-cells at 60 GHz in a compact core chip area of ${\text {0.11 mm}}^{2}$ . It is measured with 2-mW peak differential output power, 2.2% power efficiency, ${\text {18.2-mW/mm}}^{2}$ output power density, $-{\text {113.9-dBc/Hz}}$ phase noise at 10-MHz offset, and 15.8% frequency tuning range (FTR) centered at 63.1 GHz. Moreover, a 140-GHz signal source is implemented by the combination of second-order harmonics of four in-phase coupled ZPC unit-cells at 70 GHz in a compact core chip area of ${\text {0.13 mm}}^{2}$ . It is measured with 3.5-mW peak output power, 2.4% power efficiency, ${\text {26.9-mW/mm}}^{2}$ output power density, $-{\text {104.9-dBc/Hz}}$ phase noise at 25-MHz offset, and 9.7% FTR centered at 133.5 GHz.

Abstract 4520: Biological coupling: Drug synergy, cross-resistance, and schedule effects in combination therapy

Abstract Introduction Combination therapy promises to enhance and extend benefit to oncology patients, but development of drug combinations engenders challenges beyond those of single agents. In this work, we use theoretical models of combination efficacy to demonstrate a potential link between drug interactions, cross-resistance, and dosing schedule effects. Methods First, we investigated the relationship between efficacy interaction and schedule effects by building a dynamic pharmacokinetic (PK)/efficacy (E) model to generate theoretical tumor volume trajectories in response to exposure to two drugs. We used a single compartment PK model to simulate the plasma exposure to each drug following various dosing schedules, and exponential tumor growth was inhibited by a drug effect model consisting of the sum of single agent effects and their product with an interaction coefficient. Simulations of this PK/E model for 1000 pairs of drugs with randomized properties and interaction strengths were compared for dosing schedules with high or low concomitance, respectively. Next, we used a Moran simulation to study the effect of interaction strength on sensitivity loss in a heterogeneous population. For a tumor initially comprising 1000 subclones (either doubly sensitive, singly resistant to either drug, or doubly resistant), we simulate based on relative subclone fitnesses the time steps until fixation of a resistant population. We then apply the PK/E model assuming a multi-clone tumor to elucidate the relationship between synergy, dosing schedule, and the rise of cross-resistance by comparing response to in-phase and off-phase combination dosing and across a range of interaction strengths. Results Simulation of the PK/E model demonstrates that tumor growth inhibition of in-phase and off-phase dosing schedules diverges in a linear relationship with the interaction strength. Moran simulations show synergistic compounds are more likely to lead to fixation of a doubly resistant subclone within a population of tumor cells, and that it will happen faster than with nonsynergistic combinations. Comparing the tumor volume and sensitive fraction trajectories in response to either in-phase or off-phase dosing of a synergistic combination revealed prolonged sensitivity and reduced tumor load when dosing out of phase to avoid the synergistic interaction. Sweeping the interaction strength shows a minimum in long-term tumor growth rate when the combination exerts its effect additively. Conclusions While synergistic drug combinations may provide increased efficacy beyond additive effects of the drugs, this theoretical framework predicts that positive interactions will lead to scheduling challenges and faster resistance emergence. Counter-intuitively, it suggests the best strategy for long-term patient benefit is to use drugs with additive efficacy or non-concomitant dosing to avoid synergistic interactions. Citation Format: Andrew Chen, Christopher J. Zopf, Jing-Tao Wu, Wen Chyi Shyu, Arijit Chakravarty. Biological coupling: Drug synergy, cross-resistance, and schedule effects in combination therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4520. doi:10.1158/1538-7445.AM2015-4520