Compressed Gradient Tracking Algorithms for Distributed Nonconvex Optimization

In this paper, we study the distributed nonconvex optimization problem, which aims to minimize the average value of the local nonconvex cost functions using local information exchange. To reduce the communication overhead, we introduce three general classes of compressors, i.e., compressors with bounded relative compression error, compressors with globally bounded absolute compression error, and compressors with locally bounded absolute compression error. By integrating them with distributed gradient tracking algorithm, we then propose three compressed distributed nonconvex optimization algorithms. For each algorithm, we design a novel Lyapunov function to demonstrate its sublinear convergence to a stationary point if the local cost functions are smooth. Furthermore, when the global cost function satisfies the Polyak--{\L}ojasiewicz (P--{\L}) condition, we show that our proposed algorithms linearly converge to a global optimal point. It is worth noting that, for compressors with bounded relative compression error and globally bounded absolute compression error, our proposed algorithms' parameters do not require prior knowledge of the P--{\L} constant. The theoretical results are illustrated by numerical examples, which demonstrate the effectiveness of the proposed algorithms in significantly reducing the communication burden while maintaining the convergence performance. Moreover, simulation results show that the proposed algorithms outperform state-of-the-art compressed distributed nonconvex optimization algorithms

Spin-dependent transport for armchair-edge graphene nanoribbons between ferromagnetic leads

We theoretically investigate the spin-dependent transport for the system of an armchair-edge graphene nanoribbon (AGNR) between two ferromagnetic (FM) leads with arbitrary polarization directions at low temperatures, where a magnetic insulator is deposited on the AGNR to induce an exchange splitting between spin-up and -down carriers. By using the standard nonequilibrium Green's function (NGF) technique, it is demonstrated that, the spin-resolved transport property for the system depends sensitively on both the width of AGNR and the polarization strength of FM leads. The tunneling magnetoresistance (TMR) around zero bias voltage possesses a pronounced plateau structure for system with semiconducting 7-AGNR or metallic 8-AGNR in the absence of exchange splitting, but this plateau structure for 8-AGNR system is remarkably broader than that for 7-AGNR one. Interestingly, the increase of exchange splitting $\Delta$ suppresses the amplitude of the structure for 7-AGNR system. However, the TMR is enhanced much for 8-AGNR system under the bias amplitude comparable to splitting strength. Further, the current-induced spin transfer torque (STT) for 7-AGNR system is systematically larger than that for 8-AGNR one. The findings here suggest the design of GNR-based spintronic devices by using a metallic AGNR, but it is more favorable to fabricate a current-controlled magnetic memory element by using a semiconducting AGNR.Comment: 8 pages, 8 figure

Sex and Ethnic Differences in 47 Candidate Proteomic Markers of Cardiovascular Disease: The Mayo Clinic Proteomic Markers of Arteriosclerosis Study

Cardiovascular disease (CVD) susceptibility differs between men and women and varies with ethnicity. This variability is not entirely explained by conventional CVD risk factors. We examined differences in circulating levels of 47 novel protein markers of CVD in 2561 men and women of African-American (AA) and non-Hispanic White (NHW) ethnicity, enrolled at geographically distinct sites.Participants (1,324 AAs, mean age 63.5 y, 71% women; 1,237 NHWs, mean age 58.9 y, 57% women) belonged to sibships ascertained on the basis of hypertension. Solid-phase immunoassays and immunoturbidometric, clot-based, chromogenic, and electrophoretic assays were used to measure the 47 protein markers in plasma or serum. Marker levels were log transformed and outliers were adjusted to within 4 SD. To identify markers independently associated with sex or ethnicity, we employed multivariable regression analyses that adjusted for conventional risk factors, prior history of CVD, medication use and lifestyle factors (physical activity, alcohol consumption and education). Generalized estimating equations were used to correct for intrafamilial correlations. After adjustment for the above covariates, female sex was associated with higher levels of 29 markers and lower levels of 6 markers. Female sex was independently associated with higher levels of several inflammatory markers as well as lipoproteins, adipokines, natriuretic peptides, vasoconstrictor peptides and markers of calcification and thrombosis. AA ethnicity was associated with higher levels of 19 markers and lower levels of 6 markers, including higher levels of several inflammatory makers, higher leptin and lower adiponectin levels, lower levels of vasodilator-natriuretic peptides, higher levels of vasoconstrictor-antidiuretic peptides and markers of calcification and thrombosis.Plasma levels of several novel protein markers of CVD differ significantly in the context of sex and ethnicity. These results have implications for individualized CVD risk assessment

Isotope engineering for spin defects in van der Waals materials

Spin defects in van der Waals materials offer a promising platform for advancing quantum technologies. Here, we propose and demonstrate a powerful technique based on isotope engineering of host materials to significantly enhance the coherence properties of embedded spin defects. Focusing on the recently-discovered negatively charged boron vacancy center ($\mathrm{V}_{\mathrm{B}}^-$) in hexagonal boron nitride (hBN), we grow isotopically purified $\mathrm{h}{}^{10}\mathrm{B}{}^{15}\mathrm{N}$ crystals for the first time. Compared to $\mathrm{V}_{\mathrm{B}}^-$ in hBN with the natural distribution of isotopes, we observe substantially narrower and less crowded $\mathrm{V}_{\mathrm{B}}^-$ spin transitions as well as extended coherence time $T_2$ and relaxation time $T_1$. For quantum sensing, $\mathrm{V}_{\mathrm{B}}^-$ centers in our $\mathrm{h}{}^{10}\mathrm{B}{}^{15}\mathrm{N}$ samples exhibit a factor of $4$ ($2$) enhancement in DC (AC) magnetic field sensitivity. For quantum registers, the individual addressability of the $\mathrm{V}_{\mathrm{B}}^-$ hyperfine levels enables the dynamical polarization and coherent control of the three nearest-neighbor ${}^{15}\mathrm{N}$ nuclear spins. Our results demonstrate the power of isotope engineering for enhancing the properties of quantum spin defects in hBN, and can be readily extended to improving spin qubits in a broad family of van der Waals materials.Comment: 8+4+8 pages, 4+4+6 figure

In vitro and in vivo evaluation of a single chain antibody fragment generated in planta with potent rabies neutralisation activity.

Rabies causes more than 60,000 human deaths annually in areas where the virus is endemic. Importantly, rabies is one of the few pathogens for which there is no treatment following the onset of clinical disease with the outcome of infection being death in almost 100% of cases. Whilst vaccination, and the combination of vaccine and rabies immunoglobulin treatment for post-exposure administration are available, no tools have been identified that can reduce or prevent rabies virus replication once clinical disease has initiated. The search for effective antiviral molecules to treat those that have already developed clinical disease associated with rabies virus infection is considered one of the most important goals in rabies research. The current study assesses a single chain antibody molecule (ScFv) based on a monoclonal antibody that potently neutralises rabies in vitro as a potential therapeutic candidate. The recombinant ScFv was generated in Nicotiana benthamiana by transient expression, and was chemically conjugated (ScFv/RVG) to a 29 amino acid peptide, specific for nicotinic acetylcholine receptor (nAchR) binding in the CNS. This conjugated molecule was able to bind nAchR in vitro and enter neuronal cells more efficiently than ScFv. The ability of the ScFv/RVG to neutralise virus in vivo was assessed using a staggered administration where the molecule was inoculated either four hours before, two days after or four days after infection. The ScFv/RVG conjugate was evaluated in direct comparison with HRIG and a potential antiviral molecule, Favipiravir (also known as T-705) to indicate whether there was greater bioavailability of the ScFv in the brains of treated mice. The study indicated that the approach taken with the ScFv/RVG conjugate may have utility in the design and implementation of novel tools targetting rabies virus infection in the brain

A Novel Solid-Phase Site-Specific PEGylation Enhances the In Vitro and In Vivo Biostabilty of Recombinant Human Keratinocyte Growth Factor 1

Keratinocyte growth factor 1 (KGF-1) has proven useful in the treatment of pathologies associated with dermal adnexae, liver, lung, and the gastrointestinal tract diseases. However, poor stability and short plasma half-life of the protein have restricted its therapeutic applications. While it is possible to improve the stability and extend the circulating half-life of recombinant human KGF-1 (rhKGF-1) using solution-phase PEGylation, such preparations have heterogeneous structures and often low specific activities due to multiple and/or uncontrolled PEGylation. In the present study, a novel solid-phase PEGylation strategy was employed to produce homogenous mono-PEGylated rhKGF-1. RhKGF-1 protein was immobilized on a Heparin-Sepharose column and then a site-selective PEGylation reaction was carried out by a reductive alkylation at the N-terminal amino acid of the protein. The mono-PEGylated rhKGF-1, which accounted for over 40% of the total rhKGF-1 used in the PEGylation reaction, was purified to homogeneity by SP Sepharose ion-exchange chromatography. Our biophysical and biochemical studies demonstrated that the solid-phase PEGylation significantly enhanced the in vitro and in vivo biostability without affecting the over all structure of the protein. Furthermore, pharmacokinetic analysis showed that modified rhKGF-1 had considerably longer plasma half-life than its intact counterpart. Our cell-based analysis showed that, similar to rhKGF-1, PEGylated rhKGF-1 induced proliferation in NIH 3T3 cells through the activation of MAPK/Erk pathway. Notably, PEGylated rhKGF-1 exhibited a greater hepatoprotection against CCl4-induced injury in rats compared to rhKGF-1

A Better Anti-Diabetic Recombinant Human Fibroblast Growth Factor 21 (rhFGF21) Modified with Polyethylene Glycol

As one of fibroblast growth factor (FGF) family members, FGF21 has been extensively investigated for its potential as a drug candidate to combat metabolic diseases. In the present study, recombinant human FGF21 (rhFGF21) was modified with polyethylene glycol (PEGylation) in order to increase its in vivo biostabilities and therapeutic potency. At N-terminal residue rhFGF21 was site-selectively PEGylated with mPEG20 kDa-butyraldehyde. The PEGylated rhFGF21 was purified to near homogeneity by Q Sepharose anion-exchange chromatography. The general structural and biochemical features as well as anti-diabetic effects of PEGylated rhFGF21 in a type 2 diabetic rat model were evaluated. By N-terminal sequencing and MALDI-TOF mass spectrometry, we confirmed that PEG molecule was conjugated only to the N-terminus of rhFGF21. The mono-PEGylated rhFGF21 retained the secondary structure, consistent with the native rhFGF21, but its biostabilities, including the resistance to physiological temperature and trypsinization, were significantly enhanced. The in vivo immunogenicity of PEGylated rhFGF21 was significantly decreased, and in vivo half-life time was significantly elongated. Compared to the native form, the PEGylated rhFGF21 had a similar capacity of stimulating glucose uptake in 3T3-L1 cells in vitro, but afforded a significantly long effect on reducing blood glucose and triglyceride levels in the type 2 diabetic animals. These results suggest that the PEGylated rhFGF21 is a better and more effective anti-diabetic drug candidate than the native rhFGF21 currently available. Therefore, the PEGylated rhFGF21 may be potentially applied in clinics to improve the metabolic syndrome for type 2 diabetic patients

Can body mass index, waist circumference, waist-hip ratio and waist-height ratio predict the presence of multiple metabolic risk factors in Chinese subjects?

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with metabolic risk factors. Body mass index (BMI), waist circumference, waist-hip ratio (WHR) and waist-height ratio (WHtR) are used to predict the risk of obesity related diseases. However, it has not been examined whether these four indicators can detect the clustering of metabolic risk factors in Chinese subjects.</p> <p>Methods</p> <p>There are 772 Chinese subjects in the present study. Metabolic risk factors including high blood pressure, dyslipidemia, and glucose intolerance were identified according to the criteria from WHO. All statistical analyses were performed separately according to sex by using the SPSS 12.0.</p> <p>Results</p> <p>BMI, waist circumference and WHtR values were all significantly associated with blood pressure, glucose, triglyceride and also with the number of metabolic risk factors in both male and female subjects (all of P < 0.05). According to receiver operating characteristic (ROC) analysis, the area under curve values of BMI, waist circumference and WHtR did not differ in male (0.682 vs. 0.661 vs. 0.651) and female (0.702 vs. 0.671 vs. 0.674) subjects, indicating that the three values could be useful in detecting the occurrence of multiple metabolic risk factors. The appropriate cut-off values of BMI, waist circumference and WHtR to predict the presence of multiple metabolic risk factors were 22.85 and 23.30 kg/m2 in males and females, respectively. Those of waist circumference and WHtR were 91.3cm and 87.1cm, 0.51 and 0.53 in males and females, respectively.</p> <p>Conclusion</p> <p>The BMI, waist circumference and WHtR values can similarly predict the presence of multiple metabolic risk factors in Chinese subjects.</p