Overexpression of Apolipoprotein C1 (APOC1) in Clear Cell Renal Cell Carcinoma and Its Prognostic Significance.

BACKGROUND The aims of this study included 3 aspects: 1) assessing the expression of Apolipoprotein C1 (APOC1) in clear cell renal cell carcinoma (ccRCC) and normal groups; 2) evaluating the prognostic significance of APOC1 expression in the overall survival (OS) of ccRCC patients; and 3) exploring APOC1-related signaling pathways. MATERIAL AND METHODS The APOC1 expression value and clinical data of ccRCC patients were obtained from the cBioPortal database. We then evaluated the association of APOC1 expression with clinical characteristics of ccRCC patients. We also assessed the correlation between APOC1 expression and clinical outcome using Kaplan-Meier method. Our work then verified the independent prognostic factors of ccRCC by Cox regression analysis. Finally, the potential role of genes co-expressed with APOC1 was revealed via functional enrichment analysis. RESULTS Bioinformatic data revealed that APOC1 was expressed at higher levels in ccRCC tissue than in the normal group (all P<0.05). The high expression of APOC1 was associated with unfavorable prognosis of female patients (P<0.01), but not of male patients. APOC1 high expression also shortened the survival time of ccRCC patients age ≥60 years old (P<0.05). Cox regression analysis further indicated that APOC1 expression was an independent prognostic factor for OS of ccRCC patients. Additionally, we found that APOC1 expression was significantly associated with sex, grade, clinical stage, and T stage. Finally, enrichment analysis suggested that APOC1-associated pathways were involved in tumor growth and metastasis. CONCLUSIONS The current study indicated that APOC1 was highly expressed in ccRCC and was significantly associated with key clinical features. APOC1 appears to be an independent prognostic factor in patients with ccRCC. Importantly, APOC1 might be a potential therapeutic target for ccRCC via regulating pathways involved in cell growth and metastasis.

Integrated environment-occupant-pathogen information modeling to assess and communicate room-level outbreak risks of infectious diseases.

Microbial pathogen transmission within built environments is a main public health concern. The pandemic of coronavirus disease 2019 (COVID-19) adds to the urgency of developing effective means to reduce pathogen transmission in mass-gathering public buildings such as schools, hospitals, and airports. To inform occupants and guide facility managers to prevent and respond to infectious disease outbreaks, this study proposed a framework to assess room-level outbreak risks in buildings by modeling built environment characteristics, occupancy information, and pathogen transmission. Building information modeling (BIM) is exploited to automatically retrieve building parameters and possible occupant interactions that are relevant to pathogen transmission. The extracted information is fed into an environment pathogen transmission model to derive the basic reproduction numbers for different pathogens, which serve as proxies of outbreak potentials in rooms. A web-based system is developed to provide timely information regarding outbreak risks to occupants and facility managers. The efficacy of the proposed method was demonstrated by a case study, in which building characteristics, occupancy schedules, pathogen parameters, as well as hygiene and cleaning practices are considered for outbreak risk assessment. This study contributes to the body of knowledge by computationally integrating building, occupant, and pathogen information modeling for infectious disease outbreak assessment, and communicating actionable information for built environment management.

Generalist predator dynamics under kolmogorov versus non-Kolmogorov models.

Ecosystems often contain multiple species across two or more trophic levels, with a variety of interactions possible. In this paper we study two classes of models for generalist predators that utilize more than one food source. These models fall into two categories: predator - two prey and predator - prey - subsidy models. For the former, we consider a generalist predator which utilizes two distinct prey species, modelled via a Kolmogorov system of equations with Type II response functions. For the latter, we consider a generalist predator which exploits both a prey population and an allochthonous resource which is provided as a subsidy to the system exogenously, again with Type II response functions. This latter class of model is no longer Kolmogorov in form, due to an exogenous forcing term modelling the input of the allochthonous resource into the system. We non-dimensionalize both models, so that their respective parameter spaces may be more easily compared, and study the dynamics possible from each type of model, which will then indicate - for specific parameter regimes - which generalist predator's preferences are more favorable to survival, including the prevalence of coexistence states. We also consider the various non-equilibrium dynamics emergent from such models, and show that the non-Kolmogorov predator - prey - subsidy model of 10 admits more regular dynamics (including steady states and one type of limit cycle), whereas the predator - two prey Kolmogorov model can feature multiple types of limit cycles, as well as multistability resulting in strong sensitivity to initial conditions (with stable limit cycles and steady states both coexisting for the same model parameters). Our results highlight several interesting differences and similarities between Kolmogorov and non-Kolmogorov models for generalist predators.

SIRT1 promotes proliferation, migration, and invasion of breast cancer cell line MCF-7 by upregulating DNA polymerase delta1 (POLD1).

Sirtuin 1 (SIRT1), class III histone deacetylase, plays an important character in cell proliferation, cell cycle, apoptosis, energy metabolism and DNA repair. In recent years, researchers have attached increasing attention on the role of SIRT1 in tumorigenesis, development and drug resistance. The effect of SIRT1 on breast cancer is still controversial and its exact role remains to be elucidated. In the present study, we investigated the significant role of SIRT1 in breast cancer by exploring the effect of SIRT1 on DNA polymerase delta1 (POLD1), the gene coding for DNA polymerase δ catalytic subunit p125. Immunohistochemistry showed that the protein expression level of SIRT1 was higher in breast cancer tissues relative to adjacent normal tissues. Knockdown of SIRT1 by shRNA decreased the proliferation, migration, and invasion of human breast cancer cell line MCF-7, while the overexpression of SIRT1 promoted the proliferation, migration, and invasion of MCF-7 cells. Clinically, the immunohistochemistry results revealed that the expression of SIRT1 was positively correlated with p125. Further analysis demonstrated that silencing of SIRT1 increased the expression of p53, while the expression level of POLD1/p125 decreased, and the result by overexpressing SIRT1 was opposite. Collectively, these data suggest that SIRT1 is an oncogenic factor in breast cancer cells and can be involved in the progression of breast cancer by inhibiting p53 and activating POLD1. Our finding provides new insights into the mechanisms of breast cancer.

The same species, different nutrients: Lipidomics analysis of muscle in mud crabs (Scylla paramamosain) fed with lard oil and fish oil.

Aiming to assess the effects of lard oil (LO) and fish oil (FO) on the nutritional value of mud crabs (Scylla paramamosain), non-targeted lipidomics analysis was performed on the muscle of crabs after eight weeks of feeding trail. Compared to FO, dietary LO reduced the content of phosphatidylethanolamine (PE) and phosphatidylserine (PS) with 18:0 bound at sn-1/3 site, the content of ether phospholipids containing 20:5n-3 (EPA) and 22:6n-3 (DHA) combined at sn-2 site, and increased the content of ether PE containing 18:0 and 18:1n-9. Furthermore, the deposition of 16:0, 16:1n-7, 18:2n-6, 18:3n-3, 20:4n-6, EPA and DHA at each site of PE, PS, phosphatidylcholine and/or triacylglycerols were reduced by dietary LO, while the DHA content at the sn-2 position of PE was increased. In conclusion, the nutritional value of mud crabs was reduced by dietary LO with the manifestation of variation in FA composition and positional distribution on phospholipids.

Exploring anti-acute kidney injury mechanism of Dahuang-Gancao decoction by network pharmacology and experimental validation.

This study aimed to investigate the pharmacological effects and molecular mechanisms of Dahuang-Gancao Decoction (DHGC) on acute kidney injury (AKI). Network pharmacology was utilized to analyze the key targets of DHGC against AKI. These targets were used to construct a protein-protein interaction (PPI) network, which was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to predict the mechanism of action. Based on the network pharmacological analysis, Sirtuin 3 (SIRT3) was identified as a key target, and apoptosis was suggested as a mechanism of DHGC for AKI treatment. Subsequently, an AKI mouse model was induced using lipopolysaccharide (LPS), and the study demonstrated that DHGC gradient intervention significantly reduced plasma urea and creatinine levels in AKI mice, ameliorated renal pathological changes, reduced apoptosis, and lowered serum inflammatory factors. The mechanism of DHGC's anti-AKI effect may lie in the activation of the SIRT3/NRF2/HO-1 signaling pathway, which plays an antiapoptotic role in renal cells. In summary, DHGC improved LPS-induced AKI in mice by activating the SIRT3/NRF2/HO-1 signaling pathway. These findings shed light on the potential clinical application of DHGC for the treatment of nephropathy.

NF-κB activation enhances STING signaling by altering microtubule-mediated STING trafficking.

It is widely known that stimulator of interferon genes (STING) can trigger nuclear factor κB (NF-κB) signaling. However, whether and how the NF-κB pathway affects STING signaling remains largely unclear. Here, we report that Toll-like receptor (TLR)-, interleukin-1 receptor (IL-1R)-, tumor necrosis factor receptor (TNFR)-, growth factor receptor (GF-R)-, and protein kinase C (PKC)-mediated NF-κB signaling activation dramatically enhances STING-mediated immune responses. Mechanistically, we find that STING interacts with microtubules, which plays a crucial role in STING intracellular trafficking. We further uncover that activation of the canonical NF-κB pathway induces microtubule depolymerization, which inhibits STING trafficking to lysosomes for degradation. This leads to increased levels of activated STING that persist for a longer period of time. The synergy between NF-κB and STING triggers a cascade-amplified interferon response and robust host antiviral defense. In addition, we observe that several gain-of-function mutations of STING abolish the microtubule-STING interaction and cause abnormal STING trafficking and ligand-independent STING autoactivation. Collectively, our data demonstrate that NF-κB activation enhances STING signaling by regulating microtubule-mediated STING trafficking.

Discovery of Podofilox as a Potent cGAMP-STING Signaling Enhancer with Antitumor Activity.

Cyclic GMP-AMP (cGAMP) is a second messenger that activates the stimulator of interferon genes (STING) innate immune pathway to induce the expression of type I IFNs and other cytokines. Pharmacologic activation of STING is considered a potent therapeutic strategy in cancer. In this study, we used a cell-based phenotypic screen and identified podophyllotoxin (podofilox), a microtubule destabilizer, as a robust enhancer of the cGAMP-STING signaling pathway. We found that podofilox enhanced the cGAMP-mediated immune response by increasing STING-containing membrane puncta and the extent of STING oligomerization. Furthermore, podofilox changed the trafficking pattern of STING and delayed trafficking-mediated STING degradation. Importantly, the combination of cGAMP and podofilox had profound antitumor effects on mice by activating the immune response through host STING signaling. Together, these data provide insights into the regulation of cGAMP-STING pathway activation and demonstrate what we believe to be a novel approach for modulating this pathway and thereby promoting antitumor immunity.

Deep quantum neural networks on a superconducting processor.

Deep learning and quantum computing have achieved dramatic progresses in recent years. The interplay between these two fast-growing fields gives rise to a new research frontier of quantum machine learning. In this work, we report an experimental demonstration of training deep quantum neural networks via the backpropagation algorithm with a six-qubit programmable superconducting processor. We experimentally perform the forward process of the backpropagation algorithm and classically simulate the backward process. In particular, we show that three-layer deep quantum neural networks can be trained efficiently to learn two-qubit quantum channels with a mean fidelity up to 96.0% and the ground state energy of molecular hydrogen with an accuracy up to 93.3% compared to the theoretical value. In addition, six-layer deep quantum neural networks can be trained in a similar fashion to achieve a mean fidelity up to 94.8% for learning single-qubit quantum channels. Our experimental results indicate that the number of coherent qubits required to maintain does not scale with the depth of the deep quantum neural network, thus providing a valuable guide for quantum machine learning applications with both near-term and future quantum devices.

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis.

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity.

Cyclic 2',3'-GMP-AMP (cGAMP) binds to and activates stimulator of interferon genes (STING), which then induces interferons to drive immune responses against tumors and pathogens. Exogenous cGAMP produced by infected and malignant cells and synthetic cGAMP used in immunotherapy must traverse the cell membrane to activate STING in target cells. However, as an anionic hydrophilic molecule, cGAMP is not inherently membrane permeable. Here, we show that LL-37, a human host defense peptide, can function as a transporter of cGAMP. LL-37 specifically binds cGAMP and efficiently delivers cGAMP into target cells. cGAMP transferred by LL-37 activates robust interferon responses and host antiviral immunity in a STING-dependent manner. Furthermore, we report that LL-37 inducers vitamin D3 and sodium butyrate promote host immunity by enhancing endogenous LL-37 expression and its mediated cGAMP immune response. Collectively, our data uncover an essential role of LL-37 in innate immune activation and suggest new strategies for immunotherapy.

Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials.

Background: Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE. Methods: Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/). Results: A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%). Conclusions: Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

Airborne infection risks of SARS-CoV-2 in U.S. schools and impacts of different intervention strategies.

The potential airborne transmission of SARS-CoV-2 has triggered concerns as schools continue to reopen and resume in-person instruction during the current COVID-19 pandemic. It is critical to understand the risks of airborne SARS-CoV-2 transmission under different epidemiological scenarios and operation strategies for schools to make informed decisions to mitigate infection risk. Through scenario-based analysis, this study estimates the airborne infection risk of SARS-CoV-2 in 111,485 U.S. public and private schools and evaluates the impacts of different intervention strategies, including increased ventilation, air filtration, and hybrid learning. Schools in more than 90% of counties exhibit infection risk of higher than 1%, indicating the significance of implementing intervention strategies. Among the considered strategies, air filtration is found to be most effective: the school average infection risk when applying MERV 13 is over 30% less than the risk levels correlating with the use of increased ventilation and hybrid learning strategies, respectively. For most schools, it is necessary to adopt combined intervention strategies to ensure the infection risk below 1%. The results provide insights into airborne infection risk in schools under various scenarios and may guide schools and policymakers in developing effective operations strategies to maintain environmental health.

Cross-talk between stem cells and the dysfunctional brain is facilitated by manipulating the niche: evidence from an adhesion molecule.

In the injured brain, the behavior of neural stem/progenitor cells (NSCs) is regulated by multiple converging factors encountered in the niche, which is composed of several neural and non-neural cell types. Signals emanating from the host influence the migration, survival, distribution, and fate of transplanted NSCs, which in turn can create host microenvironments that favor a return to homeostasis. We tested the hypothesis that overexpression of key facilitatory molecules that define the injury niche might enhance this bidirectional stem cell-host interaction to therapeutic advantage. As proof of concept, we investigated whether conditioning the niche with the neural cell adhesion molecule L1 might enhance recovery in a prototypical neurodegenerative milieu-the MPTP-induced model of Parkinson's disease in aged mice-where cross-talk between NSCs and imperiled host dopaminergic neurons is known to be pivotal in rescuing the function and connectivity of the latter. In lesioned mice (and in unlesioned controls), we overexpressed L1 in the NSCs to be transplanted into the ventral mesencephalon. Several pairwise experimental combinations were tested based on variations of engrafting L1 overexpressing versus nonoverexpressing NSCs into wild-type (WT) versus L1-overexpressing transgenic mice (specifically L1 transcribed from the GFAP promoter and, hence, overexpressed in host astrocytes). Enrichment for L1-particularly when expressed simultaneously in both donor NSCs and host brain-led to rapid and extensive distribution of exogenous NSCs, which in turn rescued (with an efficacy greater than in nonengineered controls) dysfunctional host dopaminergic nigral neurons, even when grafting was delayed by a month. L1 overexpression by NSCs also enhanced their own differentiation into tyrosine hydroxylase-expressing neurons in both WT and transgenic hosts. Graft-host interactions were thus favored by progressively increasing levels of L1. More broadly, this study supports the view that manipulating components of the niche (such as an adhesion molecule) that facilitate cross-talk between stem cells and the dysfunctional brain may offer new strategies for more efficacious neurotransplantation, particularly when treatment is delayed as in chronic lesions or advanced stages of a neurodegenerative disease.

Regulation of miR-375 and Sonic hedgehog on vascular endothelial growth factor in preeclampsia rats and its effect on trophoblast cells.

PURPOSE: To study the mechanism of vascular endothelial growth factor (VEGF) regulated by miR-375 and Sonic hedgehog (SHH) signaling pathways on the characteristics of trophoblast cells (TCs) in preeclampsia (PE) rats. METHODS: Female (100) Wistar rats in rut were mated with males (50) at a ratio of 2:1, and 60 pregnant rats were assigned to a normal group (Nor, n=10) and a model group (Mod, n=50) in a random manner. Rat TCs of placental villus were isolated and were divided into 8 groups. The related indicators in each group were detected, respectively. RESULTS: In contrast to the NC group, miR-375 expression greatly elevated in the miR-375 mimic group (mimic group); in the mimic and cyclopamine groups, VEGF, proliferating cell nuclear antigen（PCNA, N- cadherin and Bcl-2 expression, cell proliferation, S phase cells, and migration and invasion ability were significantly decreased and E-cadherin and Bax expression, G1 phase cells and apoptosis rate were increased significantly, but in Over expressing-VEGF（ov-VEGF） group, the above indicators presented contrary results (all P< 0.05). In contrast to the mimic group, the expression of SHH, VEGF, PCNA, N- cadherin and Bcl-2, cell proliferation, S phase cells and the invasion and migration activity in the miR-375 mimic + oe-VEGF group were evidently increased. CONCLUSIONS: Over-expressing miR-375 can inhibit the expression of VEGF, thus slow down the invasion and proliferation of TCS in PE rats, which is realized by regulating SHH signal pathway.

Gastrointestinal stromal tumors (GISTs) with remarkable cystic change: a specific subtype of GISTs with relatively indolent behaviors and favorable prognoses.

PURPOSE: Gastrointestinal stromal tumors (GISTs) are typically solid neoplasms with small cystic change detected occasionally but in rare instances may present predominantly as cystic lesions. The histopathologic features and prognoses of cystic GISTs (cGISTs) are poorly understood. METHODS: We herein reviewed 20 cGISTs resected or consulted in our institution from January 1, 2003 to December 31, 2014. RESULTS: Of the 20 patients included, the mean age was 61 years and the male-to-female ratio was 9:11. The original locations were the stomach (n = 10, 50%), the small intestine (n = 9, 45%) and the omentum (n = 1, 5%). Indistinct diagnosis or misdiagnosis was established in 15 cases based only on preoperative radiology. Grossly, the cystic component made up the bulk of masses and was filled by dark bloody fluid and necrotic debris in 18 cases. Microscopically, cyst wall was composed of neoplastic spindle (n = 14, 70%)/epithelioid cells (n = 6, 30%) and collagenous fiber, with necrotic debris and granulation tissue lining on the inner surface. cGISTs resembled their solid counterparts in terms of morphology and immunohistology but demonstrated fewer malignant parameters. c-kit or PDGFRα mutations were detected in eleven cases with the remaining being wild type for these two mutations. Although classified as intermediate or high (3 and 17, respectively) risk of recurrence according to modified National Institute of Health criterion, most patients with cGISTs experienced long-term recurrence-free survival without adjuvant imatinib. CONCLUSIONS: Cystic GISTs is a relatively indolent subset of GISTs with favorable prognoses and adjuvant imatinib should be a prudent consideration.

Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population.

PURPOSE: To determine whether the main mitochondrial DNA (mtDNA) haplogroups of the Han people have an impact on long-term clinical outcome. METHODS: We prospectively studied 181 individuals who were sequentially admitted to the intensive care unit. Demographic and clinical data were recorded along with clinical outcome over 180 days. Follow-up was completed for all study participants. We then determined the mtDNA haplogroups of the patients and 570 healthy, age-matched Han people from Zhejiang province, Southeast China, by analyzing sequences of hypervariable mtDNA segments and testing diagnostic polymorphisms in the mtDNA coding region with DNA probes. RESULT: The frequency of the main subhaplogroups of the Han population in the study cohort did not differ significantly from the control group. mtDNA haplogroup R, one of the three main mtDNA haplogroups of the Han people, was a strong independent predictor for the outcome of severe sepsis, conferring a 4.68-fold (95% CI 1.903-10.844, P = 0.001) increased chance of survival at 180 days compared with those without the haplogroup R. CONCLUSION: In the Han population, mtDNA haplogroup R was a strong independent predictor for the outcome of severe sepsis, conferring an increased chance of long-term survival compared with individuals without the R haplogroup.

Predictions of psychophysical measurements for sinusoidal amplitude modulated (SAM) pulse-train stimuli from a stochastic model.

Two approaches have been proposed to reduce the synchrony of the neural response to electrical stimuli in cochlear implants. One approach involves adding noise to the pulse-train stimulus, and the other is based on using a high-rate pulse-train carrier. Hypotheses regarding the efficacy of the two approaches can be tested using computational models of neural responsiveness prior to time-intensive psychophysical studies. In our previous work, we have used such models to examine the effects of noise on several psychophysical measures important to speech recognition. However, to date there has been no parallel analytic solution investigating the neural response to the high-rate pulse-train stimuli and their effect on psychophysical measures. This work investigates the properties of the neural response to high-rate pulse-train stimuli with amplitude modulated envelopes using a stochastic auditory nerve model. The statistics governing the neural response to each pulse are derived using a recursive method. The agreement between the theoretical predictions and model simulations is demonstrated for sinusoidal amplitude modulated (SAM) high rate pulse-train stimuli. With our approach, predicting the neural response in modern implant devices becomes tractable. Psychophysical measurements are also predicted using the stochastic auditory nerve model for SAM high-rate pulse-train stimuli. Changes in dynamic range (DR) and intensity discrimination are compared with that observed for noise-modulated pulse-train stimuli. Modulation frequency discrimination is also studied as a function of stimulus level and pulse rate. Results suggest that high rate carriers may positively impact such psychophysical measures.

Predicting dynamic range and intensity discrimination for electrical pulse-train stimuli using a stochastic auditory nerve model: the effects of stimulus noise.

This work investigates dynamic range and intensity discrimination for electrical pulse-train stimuli that are modulated by noise using a stochastic auditory nerve model. Based on a hypothesized monotonic relationship between loudness and the number of spikes elicited by a stimulus, theoretical prediction of the uncomfortable level has previously been determined by comparing spike counts to a fixed threshold, Nucl. However, no specific rule for determining Nucl has been suggested. Our work determines the uncomfortable level based on the excitation pattern of the neural response in a normal ear. The number of fibers corresponding to the portion of the basilar membrane driven by a stimulus at an uncomfortable level in a normal ear is related to Nucl at an uncomfortable level of the electrical stimulus. Intensity discrimination limens are predicted using signal detection theory via the probability mass function of the neural response and via experimental simulations. The results show that the uncomfortable level for pulse-train stimuli increases slightly as noise level increases. Combining this with our previous threshold predictions, we hypothesize that the dynamic range for noise-modulated pulse-train stimuli should increase with additive noise. However, since our predictions indicate that intensity discrimination under noise degrades, overall intensity coding performance may not improve significantly.