Exploration on the potential efficacy and mechanism of methyl salicylate glycosides in the treatment of schizophrenia based on bioinformatics, molecular docking and dynamics simulation.

The etiological and therapeutic complexities of schizophrenia (SCZ) persist, prompting exploration of anti-inflammatory therapy as a potential treatment approach. Methyl salicylate glycosides (MSGs), possessing a structural parent nucleus akin to aspirin, are being investigated for their therapeutic potential in schizophrenia. Utilizing bioinformation mining, network pharmacology, molecular docking and dynamics simulation, the potential value and mechanism of MSGs (including MSTG-A, MSTG-B, and Gaultherin) in the treatment of SCZ, as well as the underlying pathogenesis of the disorder, were examined. 581 differentially expressed genes related to SCZ were identified in patients and healthy individuals, with 349 up-regulated genes and 232 down-regulated genes. 29 core targets were characterized by protein-protein interaction (PPI) network, with the top 10 core targets being BDNF, VEGFA, PVALB, KCNA1, GRIN2A, ATP2B2, KCNA2, APOE, PPARGC1A and SCN1A. The pathogenesis of SCZ primarily involves cAMP signaling, neurodegenerative diseases and other pathways, as well as regulation of ion transmembrane transport. Molecular docking analysis revealed that the three candidates exhibited binding activity with certain targets with binding affinities ranging from -4.7 to -109.2 kcal/mol. MSTG-A, MSTG-B and Gaultherin show promise for use in the treatment of SCZ, potentially through their ability to modulate the expression of multiple genes involved in synaptic structure and function, ion transport, energy metabolism. Molecular dynamics simulation revealed good binding abilities between MSTG-A, MSTG-B, Gaultherin and ATP2B2. It suggests new avenues for further investigation in this area.

In-situ evaluation the fluctuation of hypochlorous acid in acute liver injury mice models with a mitochondria-targeted NIR ratiometric fluorescent probe.

Acute liver injury (ALI) is a frequent and devastating liver disease that has been made more prevalent by the excessive use of chemicals, drugs, and alcohol in modern life. Hypochlorous acid (HClO), an important biomarker of oxidative stress originating mainly from the mitochondria, has been shown to be intimately connected to the development and course of ALI. Herein, a novel BODIPY-based NIR ratiometric fluorescent probe Mito-BS was constructed for the specific recognition of mitochondrial HClO. The probe Mito-BS can rapidly respond to HClO within 20 s with a ratiometric fluorescence response (from 680 nm to 645 nm), 24-fold fluorescence intensity ratio enhancement (I645/I680), a wide pH adaptation range (5-9) and the low detection limit (31 nM). The probe Mito-BS has been effectively applied to visualize endogenous and exogenous HClO fluctuations in living zebrafish and cells based on its low cytotoxicity and prominent mitochondria-targeting ability. Furthermore, the fluorescent probe Mito-BS makes it possible to achieve the non-invasive in-situ diagnosis of ALI through in mice, and provides a feasible strategy for early diagnosis and drug therapy of ALI and its complications.

The Application Value of Internet Health Popularization for Community Patients with Hypertension.

Objective: To explore the effect of Internet health science popularization on the use of antihypertensive drugs in patients with hypertension in the community. Methods: Ninety-six community hypertensive patients treated in our hospital from May 2021 to May 2023 were selected as the subjects of the study. According to the different intervention schemes received by the patients, they were equally divided into a control group (n = 48) and a study group (n = 48). The control group was given routine intervention, while the study group was given Internet health science popularization intervention based on the control group. The blood pressure [diastolic blood pressure (DBP), systolic blood pressure (SBP)], medication compliance, self-management behavior, disease uncertainty, mastery of hypertension-related knowledge, and quality of life were compared between the two groups. Results: After the intervention, the levels of DBP and SBP and the score of disease uncertainty in the study group were lower than those in the control group (P < .05). After the intervention, the scores of medication compliance, self-management behavior, and quality of life in the study group were higher than those in the control group (P < .05). The mastery of disease knowledge in the study group was higher than that in the control group (P < .05). Conclusion: The application of Internet health science popularization to community hypertension patients can improve their medication compliance, effectively control the level of blood pressure, improve patients' mastery of hypertension-related knowledge, enhance their self-management ability, reduce disease uncertainty, and improve patients' quality of life.

Population pharmacokinetic analysis and dosing regimen optimization of teicoplanin in critically ill patients with sepsis.

Objectives: Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens. Methods: A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients' clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic/pharmacodynamic parameters, including trough concentration (Cmin), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC0-24/MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA. Results: A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03 L/h, 20.1 L, 3.12 L/h and 101 L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12/15 mg/kg every 12 h followed by a maintenance dose of 12/15 mg/kg every 24 h-72 h for patients with different renal functions were required to achieve a target Cmin of 15 mg/L and a target AUC0-24/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC0-24/MIC than reducing the unit dose for renal insufficient patients. Conclusion: A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic Cmin and AUC, and a single dose of at least 12 mg/kg may be needed. AUC0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin Cmin on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended.

Miniature Fourier Transform Spectrometer Based on Thin-Film Lithium Niobate.

A miniature Fourier transform spectrometer is proposed using a thin-film lithium niobate electro-optical modulator instead of the conventional modulator made by titanium diffusion in lithium niobate. The modulator was fabricated by a contact lithography process, and its voltage-length and optical waveguide loss were 2.26 V·cm and 1.01 dB/cm, respectively. Based on the wavelength dispersion of the half-wave voltage of the fabricated modulator, the emission spectrum of the input signal was retrieved by Fourier transform processing of the interferogram, and the analysis of the experimental data of monochromatic light shows that the proposed miniaturized FTS can effectively identify the input signal wavelength.

Low-loss, ultracompact n-adjustable waveguide bends for photonic integrated circuits.

Countless waveguides have been designed based on four basic bends: circular bend, sine/cosine bend, Euler bend (developed in 1744) and Bezier bend (developed in 1962). This paper proposes an n-adjustable (NA) bend, which has superior properties compared to other basic bends. Simulations and experiments indicate that the NA bends can show lower losses than other basic bends by adjusting n values. The circular bend and Euler bend are special cases of the proposed NA bend as n equals 0 and 1, respectively. The proposed bend are promising candidates for low-loss compact photonic integrated circuits.

Comparative efficacy and safety of disease-modifying therapies in patients with relapsing multiple sclerosis: A systematic review and network meta-analysis.

BACKGROUND: Currently, 19 disease-modifying therapies (DMTs) have been approved for the treatment of patients with relapsing forms of multiple sclerosis (RMS). OBJECTIVE: The objective of this study was to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of DMTs in adults with RMS. METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the Food and Drug Administration, and European Medicines Agency websites for randomized controlled trials (RCTs) (from inception to July 2021). Eligible RCTs evaluated approved treatments for RMS as monotherapy and reported at least one of the primary outcome measures of interest. The primary outcome was efficacy (annualized relapse rate and 12-week confirmed disability progression) and safety (serious adverse events [AEs] and discontinuation due to AEs). We assessed the risk of bias (RoB) of included studies using the Cochrane RoB tool version 2.0 (https://www.bmj.com/content/343/bmj.d5928) for RCTs. Surface under the cumulative ranking (SUCRA) was used to rank therapies and to assess quality of general evidence, respectively. The Grading of Recommendations Assessment, Development and Evaluation framework was used to rank therapies and to assess quality of general evidence. RESULTS: A total of 43 records represent 45 RCTs selected for network meta-analysis. In total, 30,720 participants (median of 732; interquartile range: 248-931) were included, of which 67% were female. By SUCRA analysis, alemtuzumab (94.3%) presented the highest probability of being the best alternative for annualized relapse rate, whereas ofatumumab (93.5%) presented the highest probability of being the best alternative for 12-week confirmed disability progression. Interferon beta-1b subcutaneous (87.0%) presented the highest probability of the best safety among all DMTs for serious AEs, whereas alemtuzumab (92.4%) presented the highest probability of the best safety among all DMTs for discontinuation due to AEs. CONCLUSION: Network meta-analysis shows that alemtuzumab and ofatumumab present the highest efficacy among DMTs. Because there is little difference between these probabilities for many treatments, health professionals should use clinical shared decision making when formulating treatment plans with patients.

Growth modes of single-walled carbon nanotubes on catalysts.

Understanding the growth mechanism of single-walled carbon nanotubes (SWCNTs) and achieving selective growth requires insights into the catalyst structure-function relationship. Using an in situ aberration-corrected environmental transmission electron microscope, we reveal the effects of the state and structure of catalysts on the growth modes of SWCNTs. SWCNTs grown from molten catalysts via a vapor-liquid-solid process generally present similar diameters to those of the catalysts, indicating a size correlation between nanotubes and catalysts. However, SWCNTs grown from solid catalysts via a vapor-solid-solid process always have smaller diameters than the catalysts, namely, an independent relationship between their sizes. The diameter distribution of SWCNTs grown from crystalline Co7W6, which has a unique atomic arrangement, is discrete. In contrast, nanotubes obtained from crystalline Co are randomly dispersed. The different growth modes are linked to the distinct chiral selectivity of SWCNTs grown on intermetallic and monometallic catalysts. These findings will enable rational design of catalysts for chirality-controlled SWCNTs growth.

Simultaneous frequency up/down converting interface based on a single hardware incorporating two phase-correlated photonic mixers.

A novel photonic frequency up/down-converting interface (FCI) with the capability of up-converting an intermediate frequency (IF) signal to a radio frequency (RF) signal and simultaneously down-converting a RF signal to a low IF signal is proposed, and a new application scenario, where both up and down frequency conversion stages of a deramp-on-receive linearly frequency modulated (LFM) continuous wave (CW) radar system are replaced by the FCI, is demonstrated. The five-port photonic FCI can be seen as two ultra-wideband phase-correlated photonic RF mixers incorporated in a single hardware, and the working frequency range of the FCI is up to Ka-band. The FCI is tested by an LFM waveform with 1GHz bandwidth in a deramp-on-receive LFM CW imaging radar system. In the test, the LFM signal can be transmitted and received correctly, and deramp output signals are able to coherently combine among multiple pulses, which generates a clear image of two point-targets with a 3dB range resolution of 15cm.

Effect of different initial rituximab regimens on B cell depletion in children with autoimmune neurological diseases.

BACKGROUND: Rituximab (RTX) is a promising B-cell-depleting monoclonal antibody used to treat several autoimmune neurological diseases in children. The RTX administration regimen relies on the reconstitution of B cells in the peripheral blood. OBJECTIVE: The objective of this study was to investigate the effect of different initial RTX regimens on B cell depletion. METHODS: This single-center retrospective analysis included children with autoimmune neurological diseases who received RTX; Group 1 received two infusions of 375 mg/m2 RTX, while Group 2 received four infusions of the same dose. We examined the evolution of B cells at regular intervals in patients. The time required for B cell reconstitution, risk factors, and the effect on immunoglobulin (Ig) and T cells were studied. RESULTS: A total of 113 patients with the first course of rituximab were included. Median time required for B cell reconstitution was 147.7 [130.1-165.2] and 181.9 [165.2-198.6] days in Group 1 and 2 respectively (p = 0.008). Ig production was affected by RTX, which reduced IgG, IgA and IgM serum concentrations, yet within the normal level. There was significant difference in the decline of IgG between the two groups. Absolute cell counts for T cells did not change over time after treatment, and the variation trend was similar in the two groups. CONCLUSION: The initial regimen of RTX impacts time required for B cell reconstitution. There was an increased time to B cell reconstitution with four standard infusions of RTX when compared with two standard infusions. Furthermore, as the prolonged B cell depletion leads to decreased antibody production, regular measurements of serum Ig concentrations after RTX treatment and follow-up should be performed regularly.

5-HT2A Receptor and 5-HT Degradation Play a Crucial Role in Atherosclerosis by Modulating Macrophage Foam Cell Formation, Vascular Endothelial Cell Inflammation, and Hepatic Steatosis.

AIM: Previously, we found that diabetes-related liver dysfunction is due to activation of the 5-HT2A receptor (5-HT2AR) and increased synthesis and degradation of 5-HT. Here, we investigated the role of 5-HT in the development of atherosclerosis. METHODS: The study was conducted using high-fat diet-fed male ApoE-/- mice, THP-1 cell-derived macrophages, and HUVECs. Protein expression and biochemical indexes were determined by Western blotting and quantitative analysis kit, respectively. The following staining methods were used: oil red O staining (showing atherosclerotic plaques and intracellular lipid droplets), immunohistochemistry (showing the expression of 5-HT2AR, 5-HT synthase, and CD68 in the aortic wall), and fluorescent probe staining (showing intracellular ROS). RESULTS: In addition to improving hepatic steatosis, insulin resistance, and dyslipidemia, co-treatment with a 5-HT synthesis inhibitor and a 5-HT2AR antagonist significantly suppressed the formation of atherosclerotic plaques and macrophage infiltration in the aorta of ApoE-/- mice in a synergistic manner. Macrophages and HUVECs exposed to oxLDL or palmitic acid in vitro showed that activated 5-HT2AR regulated TG synthesis and oxLDL uptake by activating PKCε, resulting in formation of lipid droplets and even foam cells; ROS production was due to the increase of both intracellular 5-HT synthesis and mitochondrial MAO-A-catalyzed 5-HT degradation, which leads to the activation of NF-κB and the release of the inflammatory cytokines TNF-α and IL-1ß from macrophages and HUVECs as well as MCP-1 release from HUVECs. CONCLUSION: Similar to hepatic steatosis, the pathogenesis of lipid-induced atherosclerosis is associated with activation of intracellular 5-HT2AR, 5-HT synthesis, and 5-HT degradation.

Host-Guest Molecular Interaction Enabled Separation of Large-Diameter Semiconducting Single-Walled Carbon Nanotubes.

Semiconducting single-walled carbon nanotubes (s-SWCNTs) with a diameter of around 1.0-1.5 nm, which present bandgaps comparable to silicon, are highly desired for electronic applications. Therefore, the preparation of s-SWCNTs of such diameters has been attracting great attention. The inner surface of SWCNTs has a suitable curvature and large contacting area, which is attractive in host-guest chemistry triggered by electron transfer. Here we reported a strategy of host-guest molecular interaction between SWCNTs and inner clusters with designed size, thus selectively separating s-SWCNTs of expected diameters. When polyoxometalate clusters of ∼1 nm in size were filled in the inner cavities of SWCNTs, s-SWCNTs with diameters concentrated at ∼1.3-1.4 nm were selectively extracted with the purity of ∼98% by a commercially available polyfluorene derivative. The field-effect transistors built from the sorted s-SWCNTs showed a typical behavior of semiconductors. The sorting mechanisms associated with size-dependent electron transfer from nanotubes to inner polyoxometalate were revealed by the spectroscopic and in situ electron microscopic evidence as well as the theoretical calculation. The polyoxometalates with designable size and redox property enable the flexible regulation of interaction between the nanotubes and the clusters, thus tuning the diameter of sorted s-SWCNTs. The present sorting strategy is simple and should be generally feasible in other SWCNT sorting techniques, bringing both great easiness in dispersant design and improved selectivity.

Dalfampridine in the treatment of multiple sclerosis: a meta-analysis of randomised controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a chronic illness involving the central nervous system (CNS) that is characterised by inflammation, demyelination, and degenerative changes. Dalfampridine is one of the available treatments for MS symptoms and comorbidities. This meta-analysis aimed to assess the safety and benefits of dalfampridine versus placebo in MS by summarising data deriving from previously published clinical randomised controlled studies (RCTs). RESULTS: A total of 9 RCTs were included in this meta-analysis, involving 1691 participants. There were significant differences between dalfampridine and placebo in terms of decreased 12-item Multiple Sclerosis Walking Scale score (weighted mean difference [WMD] = - 3.68, 95% confidence interval [CI] [- 5.55, - 1.80], p = 0.0001), improved response to the timed 25-foot walk test (relative risk [RR] = 2.57, 95% CI [1.04, 6.33], p = 0.04), increased 6-min walk test (WMD = 18.40, 95% CI [1.30, 35.51], p = 0.03), increased 9-Hole Peg Test score (WMD = 1.33, 95% CI [0.60, 2.05], p = 0.0004), and increased Symbol Digit Modalities Test score (WMD = 4.47, 95% CI [3.91, 5.02], p < 0.00001). Significant differences in the incidence of side effects were also observed (RR = 1.12, 95% CI [1.04, 1.21], p = 0.002). CONCLUSION: Dalfampridine exerts positive effects on walking ability, finger dexterity, and cognitive function. Treatment should be administered under the guidance of a physician or pharmacist given the higher incidence of adverse events.

Denosumab Versus Zoledronic Acid in the Prevention of Skeletal-related Events in Vulnerable Cancer Patients: A Meta-analysis of Randomized, Controlled Trials.

PURPOSE: Bone metastases from solid tumors and multiple myeloma (MM) represent an important source of morbidity. The present meta-analysis was performed with the purpose of comparing the efficacy and tolerability of denosumab versus zoledronic acid (ZA) in the prevention of skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors or bone lesions in multiple myeloma. METHODS: We searched PubMed, PubMed Central, EMBASE, the Cochrane Library, and ClinicalTrials.gov for relevant studies published until April 23, 2020. We included randomized, controlled trials that investigated the efficacy and tolerability of denosumab 120 mg SC versus ZA 4 mg IV, given every 4 weeks, in patients with bone lesions in multiple myeloma or bone metastases secondary to advanced solid tumors. Two reviewers independently identified studies, assessed the risk for bias, and extracted the data. Times to event outcomes were analyzed using hazard ratios (HRs) and 95% CIs. We analyzed tolerability outcomes using risk ratios (RRs) and 95% CIs, with a fixed-effects model. FINDINGS: Four randomized, controlled trials (7379 patients) were identified as suitable for analysis. The pooled data indicated that denosumab was more favorable than ZA in delaying the time to first on-study SRE (HR = 0.86; 95% CI, 0.80-0.93; P = 0.0001) as well as the time to first and subsequent on-study SREs (HR = 0.83; 95% CI, 0.76-0.90; P < 0.0001); however, the results on overall survival and disease progression were similar between the 2 drugs. Additionally, denosumab was associated with lower risks for bone pain (risk ratio [RR] = 0.88; 95% CI, 0.80-0.97; P = 0.01), osteonecrosis of the jaw (RR = 0.75; 95% CI, 0.61-0.93; P = 0.007), and acute-phase reactions (RR = 0.47; 95% CI, 0.40-0.56; P < 0.00001). IMPLICATIONS: Compared with ZA, denosumab demonstrated efficacy in significantly delaying on-study SREs. Furthermore, it showed a better tolerability profile, despite being associated with potential yet manageable adverse events. This study was registered with PROSPERO (identifier: CRD42019126390).

Channelized photonic-assisted deramp receiver with an extended detection distance along the range direction for LFM-CW radars.

A novel photonic-assisted deramp receiver extends detection distance along range direction of linearly-frequency-modulated continuous wave (LFM-CW) radars is proposed. A dual-polarization quadrature phase shift keying (DP-QPSK) modulator is used to modulate an optical frequency-comb (OFC) to generate orthogonally polarized optical signals. Then the orthogonally polarized optical signals are coherently detected with an optical local oscillator (OLO), which is generated by modulating the other OFC with the RF-reference signal on a null-biased Mach-Zehnder modulator (MZM). At the output of each detection unit, beating results can be recovered using a digital signal processing algorithm. By stitching the beating results of several paralleled detection units, the deramp signal corresponded to an extended range distance can be recovered. The proposed technique is experimentally evaluated through both simulated echoes and real echoes of two static trihedral corner reflectors (TCRs) distributed along range direction.

Wide-band RF receiver based on dual-OFC-based photonic channelization and spectrum stitching technique.

A novel wide-band RF receiver based on a dual-OFC-based channelization and spectrum stitching technique is proposed and demonstrated experimentally. In the scheme, a dual-OFC-based channelizer is utilized as the front-end to slice the RF signals into multiple channels. In the back-end, through the channel estimation and spectrum stitching, the received signals can be well reconstructed in the digital domain. A proof-of-concept experiment is performed, in which signals with 3 GHz bandwidths are sliced and reconstructed using the proposed receiver with a normalized mean squared error (NMSE) of 7.9×10-3. The performances of the reconstructed signals on pulse compression are also demonstrated to evaluate the potential of the proposed technique in practical applications.

Study of lung toxicity in rats exposed to silica powder with different hard metal constituents.

The objective of this study was to assess the lung toxicity induced by the inhalation of different hard metal constituents and silica powder and screen for potential toxicity biomarkers. Rats were randomly divided into saline, cobalt, tungsten carbide, silica, and hard metal (HM) groups and were administered a single 10-mg dose of the respective treatments. After 8 weeks, the lung tissue structure in the HM group was deformed, numerous nucleated giant and epithelial-like cells appeared in the stroma, and the computed tomography scanning images appeared abnormal. Krebs von den Lungen-6 (KL-6), transforming growth factor (TGF)-ß1, and TGF-ß2 expression in bronchoalveolar lavage fluid (BALF) significantly differed between the groups ( p < 0.05). Serum KL-6 and TGF-ß1, but not TGF-ß2, levels significantly differed between some groups ( p < 0.05). We observed multinucleated giant cells in the rat lung tissue. While the serum and BALF levels of KL-6 and TGF-ß2 are not highly specific, TGF-ß1 may be a valuable reference diagnostic marker in HM lung disease.

Demonstration of a microwave photonic synthetic aperture radar based on photonic-assisted signal generation and stretch processing.

A microwave photonic synthetic aperture radar (MWP SAR) is developed and experimentally demonstrated. In the transmitter, microwave photonic frequency doubling is used to generate a linearly-frequency-modulated (LFM) radar signal; while in the receiver, photonic stretch processing is employed to receive the reflection signal. The presented MWP SAR operates in Ku band with a bandwidth of 600MHz, and is evaluated through a series of inverse SAR imaging tests both in a microwave anechoic chamber and in a field trial. Its imaging performance verifies that the proposed MWP SAR works perfect and shows the potential of overcoming the conventional radar bandwidth bottleneck.

Frequency tunable optoelectronic oscillator based on a directly modulated DFB semiconductor laser under optical injection.

A frequency tunable optoelectronic oscillator based on a directly modulated distributed-feedback (DFB) semiconductor laser under optical injection is proposed and experimentally demonstrated. Through optical injection, the relaxation oscillation frequency of the DFB laser is enhanced and its high modulation efficiency can enable the loop oscillation with a RF threshold gain of less than 20 dB. The DFB laser is a commercial semiconductor laser with a package of 10 GHz, and its packaging limitation can be overcome by optical injection. In our scheme, neither a high-speed external modulator nor an electrical bandpass filter is required, making the system simple and low-cost. Microwave signals with a frequency tuning range from 5.98 to 15.22 GHz are generated by adjusting the injection ratio and frequency detuning between the master and slave lasers. The phase noise of the generated 9.75 GHz microwave signal is measured to be -104.8 dBc/Hz @ 10 kHz frequency offset.