Forward Mode Research Articles

Quantum communication through devices with indefinite input-output direction

Certain quantum devices, such as half-wave plates and quarter-wave plates in quantum optics, are bidirectional, meaning that the roles of their input and output ports can be exchanged. Bidirectional devices can be used in a forward mode and a backward mode, corresponding to two opposite choices of the input-output direction. They can also be used in a coherent superposition of the forward and backward modes, giving rise to new operations with indefinite input-output direction. In this work we explore the potential of input-output indefiniteness for the transfer of classical and quantum information through noisy channels. We first formulate a model of communication from a sender to a receiver via a noisy channel used in indefinite input-output direction. Then, we show that indefiniteness of the input-output direction yields advantages over standard communication protocols in which the given noisy channel is used in a fixed input-output direction. These advantages range from a general reduction of noise in bidirectional processes, to heralded noiseless transmission of quantum states, and, in some special cases, to a complete noise removal. The noise reduction due to input-output indefiniteness can be experimentally demonstrated with current photonic technologies, providing a way to investigate the operational consequences of exotic scenarios characterised by coherent quantum superpositions of forward-time and backward-time processes.

CHAD for expressive total languages

AbstractWe show how to apply forward and reverse mode Combinatory Homomorphic Automatic Differentiation (CHAD) (Vákár (2021). ESOP, 607–634; Vákár and Smeding (2022). ACM Transactions on Programming Languages and Systems44 (3) 20:1–20:49.) to total functional programming languages with expressive type systems featuring the combination of •tuple types;•sum types;•inductive types;•coinductive types;•function types.We achieve this by analyzing the categorical semantics of such types in $\Sigma$ -types (Grothendieck constructions) of suitable categories. Using a novel categorical logical relations technique for such expressive type systems, we give a correctness proof of CHAD in this setting by showing that it computes the usual mathematical derivative of the function that the original program implements. The result is a principled, purely functional and provably correct method for performing forward- and reverse-mode automatic differentiation (AD) on total functional programming languages with expressive type systems.

BER Performance of Co-operative Relay NOMA-assisted PS Protocol with Imperfect SIC and CSI

Objective: Wireless networks and devices are consuming a significant amount of energy as wireless communication is rapidly expanding, radio frequency (RF) energy harvesting has been envisioned as a feasible technology for powering low-power wireless systems. Aims: This paper investigates a bit error rate (BER) of the non-orthogonal multiple access with cooperative relay-assisted power splitting (CR-NOMA-PS) based energy harvesting (EH). Methods: We consider that the relay works in the decode and forward (DF) mode. For more practical scenarios, we consider the imperfect successive interference cancellation (SIC) and channel state information (CSI) are available. Results: We obtain the end-to-end (e2e) BER expressions for the CR-NOMA-PS with imperfect CSI. Under different scenarios of PS, we evaluate and discuss the BER performance of the users with imperfect SIC and CSI. We validate the derivation of the BER expressions by simulation results. Conclusion: The results indicated that the high values of the PS factor reduce the users' performance. Furthermore, in the high signal-to-noise ratio (SNR), the CSI error degrade BER performance and produced an error floor.

Thermal assessment of a new planar thermal diode integrated collector storage solar water heater in different partial vacuums: An experimental study

Thermal diodes are novel mechanisms with high thermal resistance in one direction and low thermal resistance in the other. The current study introduces a new planar thermal diode integrated collector storage (ICSs) system and analyzes its transient dynamics and performance under field conditions in several scenarios, including operating at atmospheric pressure and partial vacuums: Ptotal = 0.7 atm and 0.5 atm. The acquired data illustrate that the collector has approximately the same transient dynamics during the collection period, while differences pronounce during the retention period. Utilizing partial vacuums is tricky and may cause to decrease in performance; however, the best retention and collection efficiencies were obtained at 16.97% and 29.33% when Ptotal = 0.7 atm was utilized. Increasing the partial vacuums to Ptotal = 0.5 atm decreases the retention efficiency significantly to nearly 3.26%. The heat gain (forward mode) coefficient was not affected significantly by partial vacuums. However, the heat loss (reverse mode) coefficient was reduced by nearly 17.63% at Ptotal = 0.7 atm compared to atmospheric pressure. The calculated heat gain and heat loss coefficients are 9.28 W/k and 19.65 W/k at Ptotal = 0.7 atm; hence, the constructed thermal diode successfully serves as a unidirectional heat transfer mechanism.

Transthyretin Binding Mode Dichotomy of Fluorescent trans-Stilbene Ligands.

The orientations of ligands bound to the transthyretin (TTR) thyroxine (T4) binding site are difficult to predict. Conflicting binding modes of resveratrol have been reported. We previously reported two resveratrol based trans-stilbene fluorescent ligands, (E)-4-(2-(naphthalen-1-yl)vinyl)benzene-1,2-diol (SB-11) and (E)-4-(2-(naphthalen-2-yl)vinyl)benzene-1,2-diol (SB-14), that bind native and misfolded protofibrillar TTR. The binding orientations of these two analogous ligands to native tetrameric TTR were predicted to be opposite. Herein we report the crystal structures of these TTR:ligand complexes. Opposite binding modes were verified but were different than predicted. The reverse binding mode (SB-14) placing the naphthalene moiety toward the opening of the binding pocket renders the fluorescent ligand pH sensitive due to changes in Lys15 amine protonation. Conversely, the forward binding mode (SB-11) placing the naphthalene inward mediates a stabilizing conformational change, allowing intersubunit H-bonding between Ser117 of different monomers across the dimer interface. Our structures of TTR complexes answer important questions in ligand design and interpretation of trans-stilbene binding modes to the TTR T4 binding site.

Bouncing dynamics of inertial self-propelled particles reveals directional asymmetry.

This study aims to examine experimental conditions in which active particles are forced by their surroundings to move forward and backward in a continuous oscillatory manner. The experimental design is based on using a vibrating self-propelled toyrobot called hexbug, which is placed inside a narrow channel closed on one end by a rigid moving wall. Using the end-wall velocity as a controlling factor, the main forward mode of the hexbug movement can be turned to mostly rearward mode. We investigate the bouncing hexbug motion on both experimental and theoretical grounds. The Brownian model of active particles with inertia is employed in the theoretical framework. The model itself uses a pulsed Langevin equationin order to simulate abrupt changes in velocity that mimic hexbug propulsion in the moments when its legs make contact with the base plate. Significant directional asymmetry is caused by the legs bending backward. We demonstrate that the simulation successfully reproduces the experimental characteristics of hexbug motion after regressing the spatial and temporal statistical characteristics, especially when directional asymmetry is under consideration.

H-Bridge Derived Topology for Dynamic On-Resistance Evaluation in Power GaN HEMTs

Gallium nitride high electron mobility transistors outperform Silicon devices due to their excellent physical properties. However, being an immature technology, it exhibits dynamic <sc xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</small> -state resistance ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$R_{\text{ds}, \text{on}}$</tex-math></inline-formula> ). This causes increased conduction loss and leads to reduced operating efficiency. To evaluate the dynamic <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$R_{\text{ds}, \text{on}}$</tex-math></inline-formula> of the device, a measurement circuit is required. In literature, a standardized double pulse test is widely used for the measurement of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$R_{\text{ds}, \text{on}}$</tex-math></inline-formula> . However, due to the uncontrolled <sc xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">off</small> -state time and inability to independently adjust, the test conditions result in restricted measurement. This article proposes a measurement circuit of the device in power electronics operations. The circuit uses an H-Bridge-derived topology with capacitive storage to enable forward and reverse conduction mode measurement of the device. In all the modes, the circuit allows measurement from the first switching cycle and independent control over the testing conditions by using a hysteresis current control. The proposed measurement circuit is validated using simulation and experimentation. Finally, analytical efficiency compared with the state-of-the-art measurement circuits is provided.

High-Gain Bidirectional LCLC Resonant Converter With Reconfigurable Capability

A reconfigurable gain circuit is proposed for an <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">LCLC</i> resonant converter with bidirectional capability considering wide varying redox flow battery source. A suitable hybrid control scheme for <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">LCLC</i> resonant converter with secondary synchronous rectifier is proposed in this work. The proposed reconfigurable circuit enables to configure secondary bridge as an active voltage doubler, full-bridge circuit during forward power transfer mode and reverse power transfer mode, respectively. The reconfigurability helps significantly to design a transformer with lower secondary turns and achieve desired high gain. The reduced transformer secondary turns result in reduced transformer parasitics. The presence of <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">LCLC</i> resonant tank helps to provide the additional gain; the hybrid control scheme ensures zero-voltage switching turn- <sc xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</small> for the primary, and secondary synchronous <sc xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">mosfets</small> throughout the operating range. The proposed converter is analysed using fundamental harmonic approximation. The proposed reconfigurable gain circuit and hybrid control scheme is verified experimentally for an 800 V/1 kW hardware prototype fed from 24 to 54 V input.

TRP channel responsible for the responses to collision, agitation, and shear in Chlamydomonas.

Swimming microorganisms show various responses to mechanical stimuli. Chlamydomonas cells temporarily swim backward on collision with an obstacle. Beat frequency of cilia increases when agitation is applied by voltexing. Cilia are detached on application of shear with a Dounce-type homogenizer. In this study, we show that a knockout mutant of TRP11, a TRP channel of Chlamydomonas, is defective in all these mechanoresponses. To mimic the mechanical stimulus on collision, we caught a single cell on a glass pipette and tapped the anterior cilia-bearing end of the cell with a micro-glass rod while recording the ciliary motility. On tapping the cell, the bending pattern of cilia changed from the forward mode to the reverse mode. The knockout mutant of TRP11 was deficient in showing this response. The response rarely occurred when the speed of the rod was slower than 100 µm/s, which roughly coincides with the swimming velocity. In addition, the bending pattern conversion hardly occurred when the rod stopped moving 1 µm or more apart from the anterior end of the cell. These findings are consistent with the localization of TRP11 in the proximal region of cilia and the idea that the avoiding reaction on collision is brought about by the activation of TRP11 through the deformation of the proximal region of cilia. TRP11 structure predicted by AlphaFold2 shows conservation of the typical TRP channel structure including pre-S1, S1-S4, S4-S5 linker, S5-pore helix-S6, and TRP helix, while bearing long but poorly resolved sequences of extracellular S1-S2 linker and intracellular C-terminal region.

Toward Ab Initio Reaction Discovery Using the Artificial Force Induced Reaction Method.

Predicting the whole process of a chemical reaction while solving kinetic equations presents an opportunity to realize an on-the-fly kinetic simulation that directly discovers chemical reactions with their product yields. Such a simulation avoids the combinatorial explosion of reaction patterns to be examined by narrowing the search space based on the kinetic analysis of the reaction path network, and would open a new paradigm beyond the conventional two-step approach, which requires a reaction path network prior to performing a kinetic simulation. The authors addressed this issue and developed a practical method by combining the artificial force induced reaction method with the rate constant matrix contraction method. Two algorithms are available for this purpose: a forward mode with reactants as the input and a backward mode with products as the input. This article first numerically verifies these modes for known reactions and then demonstrates their application to the actual reaction discovery. Finally, the challenges of this method and the prospects for ab initio reaction discovery are discussed. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 74 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Seasonal Variability in Fine Particulate Matter Water Content and Estimated pH over a Coastal Region in the Northeast Arabian Sea

The acidity of atmospheric particles can promote specific chemical processes that result in the production of extra condensed phases from lesser volatile species (secondary fine particulate matter), change the optical and water absorption characteristics of particles, and enhance trace metal solubility that can function as essential nutrients in nutrient-limited environments. In this study, we present an estimated pH of fine particulate matter (FPM) through a thermodynamic model and assess its temporal variability over a coastal location in the northeast Arabian Sea. Here, we have used the chemical composition of FPM (PM2.5) collected during the period between 2017–2019. Chemical composition data showed large variability in water-soluble ionic concentrations (WSIC; range: 2.3–39.9 μg m−3) with higher and lower average values during the winter and summer months, respectively. SO42− ions were predominant among anions, while NH4+ was a major contributor among cations throughout the season. The estimated pH of FPM from the forward and reverse modes exhibits a moderate correlation for winter and summer samples. The estimated pH of FPM is largely regulated by SO42− content and strongly depends on the relative ambient humidity, particularly in the forward mode. Major sources of FPM assessed based on Positive matrix factorization (PMF) and air-mass back trajectory analyses demonstrate the dominance of natural sources (sea salt and dust) during summer months, anthropogenic sources in winter months and mixed sources during the post-monsoon season.

Automatic parameter tuning for plug-and-play algorithms using generalized cross validation and Stein's unbiased risk estimation for linear inverse problems in computational imaging

We propose two automatic parameter tuning methods for Plug-and-Play (PnP) algorithms that use CNN denoisers. We focus on linear inverse problems and propose an iterative algorithm to calculate generalized cross-validation (GCV) and Stein&#xE2;&#x20AC;&#x2122;s unbiased risk estimator (SURE) functions for a half-quadratic splitting-based PnP (PnP-HQS) algorithm that uses a state-of- the-art CNN denoiser. The proposed methods leverage forward mode automatic differentiation to calculate the GCV and SURE functions and tune the parameters of a PnP-HQS algorithm automatically by minimizing the GCV and SURE functions using grid search. Because linear inverse problems appear frequently in computational imaging, the proposed methods can be applied in various domains. Furthermore, because the proposed methods rely on GCV and SURE functions, they do not require access to the ground truth image and do not require collecting an additional training dataset, which is highly desirable for imaging applications for which acquiring data is costly and time-consuming. We evaluate the performance of the proposed methods on deblurring and MRI experiments and show that the GCV-based proposed method achieves comparable performance to that of the oracle tuning method that adjusts the parameters by maximizing the structural similarity index between the ground truth image and the output of the PnP algorithm. We also show that the SURE-based proposed method often leads to worse performance compared to the GCV-based proposed method.

Probability inequalities for direct and inverse dynamical outputs in driven fluctuating systems.

When a fluctuating system is subjected to a time-dependent drive or nonconservative forces, the direct-inverse symmetry of the dynamics can be broken so inducing an average bias. Here we start from the fluctuation theorem, a cornerstone of stochastic thermodynamics, for inspecting the unbalancing between direct and inverse dynamical outputs, here called "events," in a bidirectional forward-backward setup. The occurrence of an event might correspond to the realization of a quantitative output, or to the realization of a sequence of acts that compose a complex "narrative." The focus is on mutual bounds between the probabilities of occurrence of direct and inverse events in the forward and backward mode. The inspection is made for systems in contact with a thermal bath, and by assuming Markov dynamics on the uncontrolled degrees of freedom. The approach comprises both the case of systems under a time-dependent drive and time-independent external forces. The general formulation is then used to derive (or re-derive) specialized results valid for finite-time processes, and for systems taken into steady conditions (either periodic steady states or steady states) starting from equilibrium. Among the results, we find already known forms of "generalized" thermodynamic uncertainty relations, and derive useful constraints concerning the work distribution function for systems in steady conditions.

Validation of carbon isotopologue distribution measurements by GC-MS and application to 13C-metabolic flux analysis of the tricarboxylic acid cycle in Brassica napus leaves.

The estimation of metabolic fluxes in photosynthetic organisms represents an important challenge that has gained interest over the last decade with the development of 13C-Metabolic Flux Analysis at isotopically non-stationary steady-state. This approach requires a high level of accuracy for the measurement of Carbon Isotopologue Distribution in plant metabolites. But this accuracy has still not been evaluated at the isotopologue level for GC-MS, leading to uncertainties for the metabolic fluxes calculated based on these fragments. Here, we developed a workflow to validate the measurements of CIDs from plant metabolites with GC-MS by producing tailor-made E. coli standard extracts harboring a predictable binomial CID for some organic and amino acids. Overall, most of our TMS-derivatives mass fragments were validated with these standards and at natural isotope abundance in plant matrices. Then, we applied this validated MS method to investigate the light/dark regulation of plant TCA cycle by incorporating U-13C-pyruvate to Brassica napus leaf discs. We took advantage of pathway-specific isotopologues/isotopomers observed between two and six hours of labeling to show that the TCA cycle can operate in a cyclic manner under both light and dark conditions. Interestingly, this forward cyclic flux mode has a nearly four-fold higher contribution for pyruvate-to-citrate and pyruvate-to-malate fluxes than the phosphoenolpyruvate carboxylase (PEPc) flux reassimilating carbon derived from some mitochondrial enzymes. The contribution of stored citrate to the mitochondrial TCA cycle activity was also questioned based on dynamics of 13C-enrichment in citrate, glutamate and succinate and variations of citrate total amounts under light and dark conditions. Interestingly, there was a light-dependent 13C-incorporation into glycine and serine showing that decarboxylations from pyruvate dehydrogenase complex and TCA cycle enzymes were actively reassimilated and could represent up to 5% to net photosynthesis.

Diferencijabilno programiranje u mašinskom učenju

This paper explains automatic differentiation, discussing two primary modes - forward and backward - and their respective implementation methods. In the context of issues encountered in machine learning and deep learning, the forward mode is deemed more suitable as it efficiently differentiates functions with numerous inputs compared to outputs. Given Python's pivotal role in the ML landscape, the paper elaborates on two widely used deep learning libraries-PyTorch and TensorFlow. While both these libraries support automatic differentiation, they adopt distinct approaches, each carrying its unique strengths and weaknesses.

An Algorithm Based on Hodgkin-Huxley Model and Latin Square for Image Encryption

Image transmission is happening more frequently in this era of technologically sophisticated digital information. Additionally, more individuals are becoming aware of its importance. In order to secure images, many academics are participating in research, which is advantageous for guaranteeing data security. In order to strengthen the security of images during transmission, we have investigated new encryption algorithms to guarantee this. First, a current representing the Lorenz chaotic system is introduced into the neuron model. The neuron model generates sequences after receiving the current signal. The next move is made as the current shifts based on whether the sequence that results is chaotic or not. If so, the subsequent operation is carried out; otherwise, the current is altered until chaotic sequences are produced. Second, a global scrambling with de-duplication technique is used to scramble the image using the resulting chaotic sequence. To complete the dislocation effect, the Latin square is used to dislocate the image after the initial dislocation. Fourth, the image that has been scrambled is subjected to two rounds of additive mode diffusion. They are diffusion in the forward additive mode and diffusion in the inverse additive mode. Lastly, to improve the diffusion effect, the image is diffused in the finite domain. Eventually, the encrypted image is obtained. After evaluation tests and comparison with related literature, it can be found that the algorithm of this study has certain advantages. Also, the resistance to attack is good. It can protect the security of the image.

A Quasi-Square-Wave Modular Multilevel Resonant DC/DC Converter With ZCS and Current-Shaping Capacity for High Step-Ratio Application

High step-ratio dc/dc converter is one of the key equipments for dc grids to satisfy the requirement of interconnecting low voltage dc and medium voltage dc buses. This article proposes a high step-ratio modular multilevel resonant dc/dc converter, where two full bridges are connected in parallel at LV side, and two submodules (SMs) strings are connected in series at MV side. Due to the series connection of two SM strings, the number of SMs and the size of the passive filter at MV terminal can be significantly reduced. Moreover, with the quasi-square-wave (QSW) modulation, the proposed converter can achieve flexible current-shaping capability. On this basis, through an internal phase-shifted angle of QSW modulation, the output voltage can be regulated with a fixed switching frequency, simplifying the design procedure of magnetic components. And zero current switching turn- <sc xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">off</small> of full-bridge switches at LV side can be realized in forward and backward mode. In addition, based on the analysis of the operation principle with the time-domain method, the basic control strategy and parameter design procedure are introduced in detail. Finally, the feasibility of the proposed converter is validated by a 100 V/1 kV/4 kW prototype.

Design and Implementation of an Isolated Bidirectional Phase-Shift Full-Bridge Converter With High Transformation Ratio

In this paper, a bidirectional full-bridge phase-shift converter with high transformation ratio scheme is proposed. The main architecture of this converter is dual active full-bridge circuit. By using phase-shift modulation, the energy can be transmitted between high-voltage-side and low-voltage-side, and also can make the power switches have the function of soft-switching. This converter is designed with the transmission power of 1kW and the digital signal processor TMS320F28335 is utilized as the main system controller core. Finally, it realizes the bidirectional power conversion mechanism between battery 50 Vdc and DC grid 400 Vdc. The experimental results show that the maximum conversion efficiency of this converter when operating in the forward charging mode (G2V mode) is up to 92.25 %, and in the reverse discharging mode (V2G mode), the maximum conversion efficiency is up to 93.02 %. In comparison with the related studies for dual active full-bridge converters, the conventional transformation ratio is lower or equal to 4. This study with high transformation ratio can reach 8 for practical high-low voltage bidirectional applications. After the validation for both modes, the proposed concept is practical in the high transformation scenarios.

Astrocytes Reduce Store-Operated Ca2+ Entry in Microglia under the Conditions of an Inflammatory Stimulus and Muscarinic Receptor Blockade.

Inflammation and loss of cholinergic transmission are involved in neurodegenerative diseases, but possible interactions between them within neurons, astrocytes, and microglia have not yet been investigated. We aimed to compare store-operated Ca2+ entry (SOCE) in neurons, astrocytes, and microglia following cholinergic dysfunction in combination with (or without) an inflammatory stimulus and to investigate the effects of linalyl acetate (LA) on this process. We used the SH-SY5Y, U373, and BV2 cell lines related to neurons, astrocytes, and microglia, respectively. Scopolamine or lipopolysaccharide (LPS) was used to antagonize the muscarinic receptors or induce inflammatory responses, respectively. The concentration of intracellular Ca2+ was measured using Fura-2 AM. Treatment with scopolamine and LPS significantly increased SOCE in the neuron-like cells and microglia but not in the scopolamine-pretreated astrocytes. LA significantly reduced SOCE in the scopolamine-pretreated neuron-like cells and microglia exposed to LPS, which was partially inhibited by the Na+-K+ ATPase inhibitor ouabain and the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Notably, SOCE was significantly reduced in the LPS plus scopolamine-pretreated cells mixed with astrocytes and microglia, with a two-fold increase in the applied number of astrocytes. LA may be useful in protecting neurons and microglia by reducing elevated SOCE that is induced by inflammatory responses and inhibiting the muscarinic receptors via Na+-K+ ATPase and the forward mode of NCX. Astrocytes may protect microglia by reducing increased SOCE under the conditions of inflammation and a muscarinic receptor blockade.

Chlorinated Naringenin Analogues as Potential Inhibitors of Transthyretin Amyloidogenesis.

Misfolding and aggregation of transthyretin are implicated in the fatal systemic disease known as transthyretin amyloidosis. Here, we report the development of a naringenin derivative bearing two chlorine atoms that will be efficacious for preventing aggregation of transthyretin in the eye. The amyloid inhibitory activity of the naringenin derivative was as strong as that of tafamidis, which is the first therapeutic agent targeting transthyretin in the plasma. X-ray crystal structures of the compounds in complex with transthyretin demonstrated that the naringenin derivative with one chlorine bound to the thyroxine-binding site of transthyretin in the forward mode and that the derivative with two chlorines bound to it in the reverse mode. An ex vivo competitive binding assay showed that naringenin derivatives exhibited more potent binding than tafamidis in the plasma. Furthermore, an in vivo pharmacokinetic study demonstrated that the dichlorinated derivative was significantly delivered to the eye.