Channel Loss Research Articles

Hydraulic Performance and Energy Dissipation Mechanism Analysis of the Tesla-Shaped Emitter

In this paper, a tesla-shaped emitter is proposed based on the structure of the “tesla valve” as the source of inspiration, so that the water flow in the channel would produce a variety of energy dissipation phenomena, such as diversion, hedging, and mixing, to explore the hydraulic performance and energy dissipation mechanism of the tesla-shaped emitter. The channel structure parameters were taken as factors, and 16 groups of orthogonal tests were arranged. Based on CFD technology, the pressure–flow relationship curve slope, flow ratio between the main channel and secondary channel, flow field, and head loss of the emitter were calculated and analyzed for different combinations of structural parameters. Based on a significance level α = 0.05 test, the main channel inlet section length (L3) had a significant impact on the curve slope, and the secondary channel length (L1) and main channel inlet section length (L3) had a significant impact on the flow. The multiple linear regression mathematical models between the channel structure parameters and the curve slope and the flow were constructed. The larger the ratio between the main channel and the secondary channel flow, the better the hydraulic performance of the emitter. The channel unit loss coefficient increased linearly with the increase of the emitter inlet pressure, and its value ranged from 4.5769 to 8.1716, with an excellent energy dissipation effect. The hedge mixing of the water flow was the core of the energy dissipation of the tesla-shaped emitter. By appropriately increasing the inlet size of the main channel and other elements to increase the main channel flow and optimize the flow ratio between the main channel and the secondary channel, the mixing was improved, which consequently improved the hydraulic performance of the emitter.

Non-Gaussian approach: Withstanding loss and noise of multi-scattering underwater channel for continuous-variable quantum teleportation

Underwater quantum communication plays a crucial role in ensuring secure data transmission and extensible quantum networks in underwater environments. However, the implementation of such applications encounters challenges due to the light attenuation caused by the complicated natural seawater. This paper focuses on employing a model based on seawater chlorophyll-a concentration to characterize the absorption and scattering of light through quantum channels. We propose a multi-scattering random channel model, which demonstrates characteristics of the excess noise in different propagation directions of communication links. Furthermore, we consider the fidelity of a continuous-variable quantum teleportation through seawater channel. To enhance transmission performance, non-Gaussian operations have been conducted. Numerical simulations show that incorporating non-Gaussian operations enables the protocol to achieve higher fidelity transmission or lower fidelity fading rates over longer transmission distances.

5G millimeter wave wideband MIMO antenna arrays with high isolation

In this paper, a compact two-port MIMO antenna array system is described. The antenna array spans the range from 27 to 40 GHz, whereas the impedance of the antenna element is matched at 50 Ω. The gain of the antenna element is between 5.5 and 8.5 dBi, and its radiation efficiency is between 65 and 90%. With high impedance matching for 5G MMW (Millimeter Wave), particularly at 28 GHz and 38 GHz, the 2-port antenna array operates in the frequency range of 27–40 GHz. The suggested MIMO array operates effectively with a gain of approximately 10 dBi and a radiation efficiency of approximately 95%. The antenna array's overall dimensions are a length of 55.27 mm, a width of 27.635 mm, and a depth of 1.6 mm with partial ground. A FR-4 substrate is used in the antenna's fabrication, greatly reducing the cost. In the antenna array, a decoupling surface is used between the antennas, with orthogonality being maintained between the ports to reduce mutual coupling. The results of the modelling show a reduction in the measured mutual coupling between array ports of less than − 35 dB. An envelope correlation coefficient (ECC) of less than 1 × 10–4 is preferable. Additionally, the channel loss capacity is less than 0.3 bits/s/Hz, the mean effective gain is approximately − 6 dB, and the total active reflection coefficient is upgraded to be less than − 30 dB. Moreover, a diversity gain of approximately 10 dB is achieved. The proposed construction was created using CST Microwave Studio 2019. When the antennas are constructed and tested, the experimental outcomes surpass those of the simulation. Each antenna element is 27.635 mm long, 27.635 mm wide, and 1.6 mm thick. Slots in the radiating circular patch antenna element could be used to improve the radiation characteristics across the intended bands. The parametric study specifies that the distance between the antenna elements should be 0.5 λ, where λ is the operational wavelength.

The effect of leakage on pressure loss of rotary regenerative heat exchangers

The pressure loss of the rotary exchanger is an important parameter that affects the energy consumption. Based on the literature review, the available correlations for calculating the pressure loss of rotary regenerative heat exchangers are presented in the article. The article presents extensive experimental research of rotary regenerative exchangers with different wheel geometries. A total of nine exchangers with eight different heat wheel geometries were investigated. The experiment was divided into two tasks concerning the pressure loss of the wheel channel and the total pressure loss of the built-in exchanger. The results of both approaches show differences that are caused by the leakage of rotary exchangers, which is their natural property. Based on the results of the experiment, correlations were proposed for determining the coefficient of friction in a channel in the shape of a sinusoid and a correlation for calculating the total pressure loss of the built-in rotary exchanger. The presented correlations have been experimentally verified and can be applied with a sufficient accuracy of ±5%. The new correlations were compared with the published results. The article discusses the effect of leakage of exchangers equipped with a labyrinth seal. Based on the experimental investigation, it was found that the leakage of the examined exchangers varies in a wide range of 1 to 4% and depends on the quality of the exchanger construction.

Loss of the large conductance calcium-activated potassium channel causes an increase in mitochondrial reactive oxygen species in glioblastoma cells.

Mitochondrial potassium (mitoK) channels play an important role in cellular physiology. These channels are expressed in healthy tissues and cancer cells. Activation of mitoK channels can protect neurons and cardiac tissue against injury induced by ischemia-reperfusion. In cancer cells, inhibition of mitoK channels leads to an increase in mitochondrial reactive oxygen species, which leads to cell death. In glioma cell activity of the mitochondrial, large conductance calcium-activated potassium (mitoBKCa) channel is regulated by the mitochondrial respiratory chain. In our project, we used CRISPR/Cas9 technology in human glioblastoma U-87 MG cells to generate knockout cell lines lacking the α-subunit of the BKCa channel encoded by the KCNMA1 gene, which also encodes cardiac mitoBKCa. Mitochondrial patch-clamp experiments showed the absence of an active mitoBKCa channel in knockout cells. Additionally, the absence of this channel resulted in increased levels of mitochondrial reactive oxygen species. However, analysis of the mitochondrial respiration rate did not show significant changes in oxygen consumption in the cell lines lacking BKCa channels compared to the wild-type U-87 MG cell line. These observations were reflected in the expression levels of selected mitochondrial genes, organization of the respiratory chain, and mitochondrial morphology, which did not show significant differences between the analyzed cell lines. In conclusion, we show that in U-87 MG cells, the pore-forming subunit of the mitoBKCa channel is encoded by the KCNMA1 gene. Additionally, the presence of this channel is important for the regulation of reactive oxygen species levels in mitochondria.

A Deep Echo State Network-Based Novel Signal Processing Approach for Underwater Wireless Optical Communication System with PAM and OFDM Signals

Underwater wireless optical communication (UWOC) plays key role in the underwater wireless sensor networks (UWSNs), which have been widely employed for both scientific and commercial applications. UWOC offers high transmission data rates, high security, and low latency communication between nodes in UWSNs. However, significant absorption and scattering loss in underwater channels, due to ocean water conditions, can introduce highly non-linear distortion in the received signals, which can severely deteriorate communication quality. Consequently, addressing the challenge of processing UWOC signals with low optical signal-to-noise ratios (OSNRs) is critical for UWOC systems. Increasing the transmitting optical power and investigating more advanced signal processing technologies to recover transmitted symbols are two primary approaches to improve system tolerance in noisy UWOC signal channels. In this paper, we propose and demonstrate the application of deep echo state networks (DeepESNs) for channel equalization in high-speed UWOC systems to enhance system performance with both PAM and QPSK-OFDM modulations. Our experimental results demonstrate the effectiveness of DeepESNs in UWOC systems, achieving error-free underwater transmission over 40.5 m with data rates up to 167 Mbps. Moreover, we compare the performance of DeepESNs to conventional echo state networks and provide suggestions on the configuration of a DeepESN for UWOC signals.

Investigation of energy dissipation mechanism and the influence of vortical structures in a high-power double-suction centrifugal pump

The extensive applications of double-suction centrifugal pumps consume a considerable amount of energy. It is urgent to reveal the detailed energy dissipation generation and find the critical factor for pump performance enhancement. In this investigation, the internal flow field of a double-suction centrifugal pump was obtained by solving the Reynolds averaged Navier–Stokes equations. The entropy production method was utilized to calculate and visualize irreversible energy dissipation. The Omega vortex method was utilized to identify vortical structures and determine the temporal and spatial relationship between entropy production and vortices. The results indicate that the entropy production in the main flow regions was critical in hydraulic loss, accounting for 54%–71% of the loss, and turbulent dissipation in the main flow regions of the impeller and volute casing dominated the variation of pump efficiency. The near-wall entropy production in the impeller positively correlated with the flow rate, but the impact was insignificant in volute casing. Although the suction chamber contributed minimally to the hydraulic loss, the backflows at the impeller inlet were relieved near the ribs, and the dissipation at the impeller inlet was reduced when the blade leading edges passed the ribs. By adopting Omega vortex identification, wake vortices, separation vortices, and their interactions were determined to correlate strongly with hydraulic loss in volute channels and near cutwaters. Furthermore, these vortices were influenced by the back flows from the impeller sidewall gaps. Additionally, this study can also provide the foundational principles for the optimal design of this type of pump.

PERFORMANCE ANALYSIS AND DEVELOPMENT OF PATH LOSS MODEL FOR TELEVISION SIGNALS IN IMO STATE, NIGERIA

It is impossible to overstate the importance of propagation models in wireless network planning, frequency assignment, and television parameter evaluation. The fact that no two locations are identical in terms of climatic conditions, building patterns, terrain, etc. makes using path loss predicting models for any area extremely challenging. Therefore, it is impossible to develop a single path loss model that applies to all environmental settings. The main aim of this study is to develop a path loss model for NTA channel 12 Owerri and evaluate its performance based on received signal strength values along five selected routes in Imo State, Nigeria.A suitable path loss model was developed by critically analyzing the measured path loss values of each base station, which were retrieved from the signal strength data received. The values of the developed path loss model were compared to those of other empirical path loss models developed by other researchers as well as the measured path loss values. The results show that the proposed path loss model is well suited for predicting the path loss of NTA channel 12 Owerri signals in the study environment, while the other conventional empirical models taken into consideration in this study overestimated the path loss of NTA channel 12 Owerri signals with Root Mean Square Error and Mean Error of 63.65 and above. Additionally, the findings indicate that NTA Owerri performs poorly at a distance of 18 kilometers from the base transmitting station. The overall findings are helpful for designing prospective television network channels in the study location and other similar environments.

A PAM4 transceiver design scheme with threshold adaptive and tap adaptive

To meet the demand of low bit error rate and high bandwidth for high-speed links, a reliable 112 Gb/s four-level pulse amplitude modulation (PAM4) transceiver design scheme with adaptive threshold voltage and adaptive decision feedback equalizer is proposed in this paper. In this scheme, three continuous time linear equalizers (CTLEs) at the front end of receiver are used to compensate the high-frequency, mid-frequency and low-frequency signals, respectively, and the variable gain amplifier (VGA) and saturation amplifier (SatAmp) are used to scale the signal amplitude. In addition to the three data samplers, four auxiliary samplers are also used for threshold adaptation. The sign-sign least mean squares algorithm uses the offset between the data sampler and the auxiliary sampler at the receiver side to drive the auxiliary reference voltage to converge to the signal constellation level, thus ensuring that the eye diagram of the PAM4 received signal has equal spacing and a constant signal–noise ratio for the three eyes in the vertical direction. In addition, the adaptive DFE for PAM4 signaling allows the transceiver to better adapt to the channel and thus achieve better equalizer performance. The simulation results show that the PAM4 transceiver design can compensate up to 25 dB of channel loss with an average eye height of 59.6 mv and an average eye width of 0.27 UI at a bit error rate of 10−12 under the condition of 3-tap feedforward equalizer (FFE) transmitter.

Memoryless Quantum Repeaters Based on Cavity‐QED and Coherent States

AbstractA quantum repeater scheme based on cavity‐quantum electrodynamics (QED) and quantum error correction of channel loss via rotation‐symmetric bosonic codes (RSBCs) is proposed to distribute atomic entangled states over long distances without memories and at high clock rates. In this scheme, controlled rotation gates, i.e., phase shifts of the propagating light modes conditioned upon the state of an atom placed in a cavity, provide a mechanism both for the entangled‐state preparations and for the error syndrome identifications. In order to assess the performance of this repeater protocol, an explicit instance of RSBCs—multicomponent cat codes—are studied quantitatively. It is found that the total fidelity and the success probability for quantum communication over a long distance (such as 1000 km) both can almost approach unity provided a small enough elementary distance between stations (smaller than 0.1 or 0.01 km) and rather low local losses (up to 0.1%) are considered. In a quantum key distribution application, secret key rates can become correspondingly high, both per channel use, beating the repeaterless bound, and per second thanks to the relatively high clock rates of the memoryless scheme. Based upon the cavity‐QED setting, this scheme can be realized at room temperature and at optical frequencies.

A Fast Sand Dust Image Enhancement Algorithm and Number Plate Detection

Abstract: The color variation and limited visibility of images taken in sand-dust conditions have a significant negative impact on computer vision systems. We suggest a quick and efficient approach to improve photographs taken in sand-dust weather in order to address the aforementioned issues. First, we make amends for the blue channel's loss value. The color of the image that has been damaged by sand dust is then corrected using white balance technology. In order to improve the image contrast and edge accuracy, guided image filtering is utilized, and an adaptive approach is used to determine the detail layer's magnification factor in order to improve the image detail information. We also added an additional feature of number plate detection of the sandy images.The aim of this task is to develop an automated system that can accurately and efficiently detect and recognize number plates from sandy images captured by a camera. This technology has various applications, such as traffic control, toll collection, parking management, and law enforcement. The experimental results demonstrate that the approach can successfully restore the fading characteristics of a large number of sand-dust-damaged photos. The proposed method may considerably improve the photos acquired during sand-dust weather conditions, and the results are better than those of existing methods, according to experimental results via qualitative and quantitative assessments

Breaking universal limitations on quantum conference key agreement without quantum memory

Quantum conference key agreement is an important cryptographic primitive for future quantum network. Realizing this primitive requires high-brightness and robust multiphoton entanglement sources, which is challenging in experiment and unpractical in application because of limited transmission distance caused by channel loss. Here we report a measurement-device-independent quantum conference key agreement protocol with enhanced transmission efficiency over lossy channel. With spatial multiplexing nature and adaptive operation, our protocol can break key rate bounds on quantum communication over quantum network without quantum memory. Compared with previous work, our protocol shows superiority in key rate and transmission distance within the state-of-the-art technology. Furthermore, we analyse the security of our protocol in the composable framework and evaluate its performance in the finite-size regime to show practicality. Based on our results, we anticipate that our protocol will play an important role in constructing multipartite quantum network.

Thermal-Fluid-Solid coupling mechanism of a novel friction reduction cooling structure for gas turbine

To supply the higher safety design demands of the new generation of gas turbines, it is urgent to solve the difficulties in mid-chord region of high-temperature turbine blades, including excessive friction loss of traditional two-pass channel, lack of experimental data, lack of stress-strain characteristics in the solid domain and so on. Therefore, this research aims to propose an integrated method of the high-efficiency and low-friction cooling design and Thermo-Fluid-Solid (TFS) coupling analysis. Firstly, a turbine blade rotating cooling experimental system is designed and built independently. Then, a novel friction reduction method with cross bridge structure is proposed. The friction reduction mechanism and the effect mechanism of the cooling performance on the solid strain are revealed through experimental test and TFS coupling numerical study. The results show that the cross brige has an excellent friction reduction effect on the channel. The influence of ‘peak cutting and valley filling’ effectively enhances the heat transfer uniformity as well as successfully reduces the overall strain. The average Nu/Nu0 of the leading edge surface decreases by 14.7% (stationary condition) and 16.4% (rotating condition), respectively. And the Nu/Nu0 of the trailing edge surface achieves a maximum improvement effect of 3.3%. The f/f0 of each channel decreases initially and followed by an increase as Ro increasing. Among them, the channel with two and three cross bridges can achieve friction reduction effects of 24.7–37.3% and 32.2–40.9%, respectively. The strain is related to the Nu/Nu0 of each region, and the value of the rotating trailing edge surface is generally higher than that of the rotating leading edge surface.

Experimental Twin-Field Quantum Key Distribution over 1000km Fiber Distance.

Quantum key distribution (QKD) aims to generate secure private keys shared by two remote parties. With its security being protected by principles of quantum mechanics, some technology challenges remain towards practical application of QKD. The major one is the distance limit, which is caused by the fact that a quantum signal cannot be amplified while the channel loss is exponential with the distance for photon transmission in optical fiber. Here using the 3-intensity sending-or-not-sending protocol with the actively-odd-parity-pairing method, we demonstrate a fiber-based twin-field QKD over 1002km. In our experiment, we developed a dual-band phase estimation and ultra-low noise superconducting nanowire single-photon detectors to suppress the system noise to around 0.02Hz. The secure key rate is 9.53×10^{-12} per pulse through 1002km fiber in the asymptotic regime, and 8.75×10^{-12} per pulse at 952km considering the finite size effect. Our work constitutes a critical step towards the future large-scale quantum network.

Noncryogenic Quantum Repeaters with hot Hybrid Alkali-Noble Gases

We propose a quantum repeater architecture that can operate without cryogenics. Each node in our architecture builds on a cell of hot alkali atoms and noble-gas spins that offer an hours-long storage time. Such a cell of hybrid gases is placed in a ring cavity, which allows us to suppress the detrimental four-wave-mixing noise in the system. We investigate the protocol based on a single-photon source made of an ensemble of the same hot alkali atoms. A single photon emitted from the source is either stored in the memory or transmitted to the central station to be detected. We quantify the fidelity and success probability of generating entanglement between two remote ensembles of noble-gas spins by taking into account finite memory efficiency, channel loss, and dark counts in detectors. We describe how the entanglement can be extended to long distances via entanglement swapping operations by retrieving the stored signal. Moreover, we quantify the performance of this proposed repeater architecture in terms of repeater rates and overall entanglement fidelities and compare it to another recently proposed noncryogenic quantum repeater architecture based on nitrogen-vacancy (N-V) centers and optomechanical spin-photon interfaces. As the system requires a relatively simple setup, it is easier to perform multiplexing, which enables achieving rates comparable to the rates of repeaters with N-V centers and optomechanics, while the overall entanglement fidelities of the present scheme are higher than the fidelities of the previous scheme. Our work shows that a scalable long-distance quantum network made of hot hybrid atomic gases is within reach of current technological capabilities.

Performance Bounds of ADC-Based Receivers Due to Clock Jitter

The maximum tolerable clock jitter for high-speed ADCs is pessimistically predicted by Nyquist-rate input sinusoidal tests. We prove that the jitter can be greatly relaxed in the presence of lossy channels in wireline systems. We derive compact expressions that allow PLL designers to decide how much jitter can be tolerated for a given channel loss and symbol rate.

Antiaging hormone Klotho derived from renal distal-convolution regulates calcium but not phosphate homeostasis

Soluble-Klotho (sKl) is the shed ectodomain of the transmembrane protein-Klotho (mKl) that exhibits pleiotropic actions, including lifespan extension, mineral metabolism, slowing-down kidney diseases and cardioprotection. The sKl is derived from the kidneys, but what type/s of renal cells secrete it is unknown. Secondly the respective roles of mKl versus sKl in regulating mineral metabolism is unclear due to the lack of appropriate in vivo models. Here, using scRNA-seq of renal distal-convolution (DC) cells, we found an unexpected pattern revealing that Klotho transcripts ( Kl) are moderately expressed in overall distal convoluted tubule (DCT), but highly enriched in the end of DCT and in connecting tubule (CNT). Immunohistochemistry further confirmed this pattern for mKl protein as well. Next, Kl was knocked-out only in renal DC to check if it affects sKl production. Interestingly, deleting Kl in the DCT and late-DCT+CNT in mice showed ~20% and ~80% reduction in sKl levels, respectively. Expectedly, knocking-out Kl along the entire DC in mice (Kl-KO DC ) abolished sKl levels. Furthermore, we found that compared to control mice, Kl-KO DC mice exhibited reduced renal TRPV5-Ca 2+ channel expression, profound calciuria, and loss of bone mineral density. The RNA-seq of automated-sorted DC cells from Kl-KO DC mice revealed enhanced caveolae-mediated endocytosis of TRPV5. On the other hand, Kl-KO DC mice had normal phosphate metabolism as confirmed by unchanged serum FGF23, serum phosphate, urinary phosphate excretion, and renal NaPi-IIa expression. Our findings reveal that a small population of renal DC cells accounts for the sKl levels. The lack of sKl may leads to disturbed Ca 2+ homeostasis and bone loss without affecting phosphate balance in mice. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ultrabright polarization-entangled photon pair source for frequency-multiplexed quantum communication in free-space.

The distribution of entanglement via satellite links will drastically extend the reach of quantum networks. Highly efficient entangled photon sources are an essential requirement towards overcoming high channel loss and achieving practical transmission rates in long-distance satellite downlinks. Here we report on an ultrabright entangled photon source that is optimized for long-distance free-space transmission. It operates in a wavelength range that is efficiently detected with space-ready single photon avalanche diodes (Si-SPADs), and readily provides pair emission rates that exceed the detector bandwidth (i.e., the temporal resolution). To overcome this limitation, we demultiplex the photon flux into wavelength channels that can be handled by current single photon detector technology. This is achieved efficiently by using the spectral correlations due to hyper-entanglement in polarization and frequency as an auxiliary resource. Combined with recent demonstrations of space-proof source prototypes, these results pave the way to a broadband long-distance entanglement distribution network based on satellites.

Experimental quantum secret sharing based on phase encoding of coherent states

Quantum secret sharing (QSS) is one of the basic communication primitives in future quantum networks which addresses part of the basic cryptographic tasks of multiparty communication and computation. Nevertheless, it is a challenge to provide a practical QSS protocol with security against general attacks. A QSS protocol that balances security and practicality is still lacking. Here, we propose a QSS protocol with simple phase encoding of coherent states among three parties. Removing the requirement of impractical entangled resources and the need for phase randomization, our protocol can be implemented with accessible technology. We provide the finite-key analysis against coherent attacks and implement a proof-of-principle experiment to demonstrate our scheme's feasibility. Our scheme achieves a key rate of 85.3 bps under a 35 dB channel loss. Combined with security against general attacks and accessible technology, our protocol is a promising candidate for practical multiparty quantum communication networks.

Simulations of active zone structure and function at mammalian NMJs predict that loss of calcium channels alone is not sufficient to replicate LEMS effects.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disease thought to be caused by autoantibodies against P/Q-type voltage-gated calcium channels (VGCCs), which attack and reduce the number of VGCCs within transmitter release sites (active zones; AZs) at the neuromuscular junction (NMJ), resulting in neuromuscular weakness. However, patients with LEMS also have antibodies to other neuronal proteins, and about 15% of patients with LEMS are seronegative for antibodies against VGCCs. We hypothesized that a reduction in the number of P/Q-type VGCCs alone is not sufficient to explain LEMS effects on transmitter release. Here, we used a computational model to study a variety of LEMS-mediated effects on AZ organization and transmitter release constrained by electron microscopic, pharmacological, immunohistochemical, voltage imaging, and electrophysiological observations. We show that models of healthy AZs can be modified to predict the transmitter release and short-term facilitation characteristics of LEMS and that in addition to a decrease in the number of AZ VGCCs, disruption in the organization of AZ proteins, a reduction in AZ number, a reduction in the amount of synaptotagmin, and the compensatory expression of L-type channels outside the remaining AZs are important contributors to LEMS-mediated effects on transmitter release. Furthermore, our models predict that antibody-mediated removal of synaptotagmin in combination with disruption in AZ organization alone could mimic LEMS effects without the removal of VGCCs (a seronegative model). Overall, our results suggest that LEMS pathophysiology may be caused by a collection of pathological alterations to AZs at the NMJ, rather than by a simple loss of VGCCs.NEW & NOTEWORTHY We used a computational model of the active zone (AZ) in the mammalian neuromuscular junction to investigate Lambert-Eaton myasthenic syndrome (LEMS) pathophysiology. This model suggests that disruptions in presynaptic active zone organization and protein content (particularly synaptotagmin), beyond the simple removal of presynaptic calcium channels, play an important role in LEMS pathophysiology.