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With the rapid development and application of the Internet, traditional storage resources have been found unable to meet the growing demand for massive data storage. An increasing number of users have attempted to upload their data to third-party cloud servers for unified storage. Efficient deduplication and secure file sharing in the cloud have emerged as critical concerns. Moreover, users have always preferred to customize their passwords for encrypting and decrypting files, only sharing encrypted files when necessary. Based on this preference, a deterministic stepwise encryption algorithm was first designed. It was such that when the keys for the two steps of encryption satisfied a certain relationship, the two steps of encryption could be equivalent to a single encryption process. A novel key-customizable encrypted deduplication scheme with access control for cloud storage was proposed, utilizing the deterministic stepwise encryption algorithm to encrypt files and a ciphertext-policy attribute-based encryption algorithm to encrypt file keys. This scheme not only offered the flexibility to customize encryption and decryption keys for different users with the same files, but also ensured secure file sharing through a dynamic access control mechanism. Moreover, the optional access control component was made compatible with the majority of existing ciphertext-policy attribute-based encryption (CP-ABE) schemes, even allowing for different CP-ABE schemes within different attribute groups. Security analysis results show that the proposed scheme achieves the highest level of security under the current encrypted deduplication paradigm. Experimental and analytical results indicate that it effectively meets the practical needs of cloud service providers and users, and also achieves acceptable efficiency.

Abstract RAG2-SCID is a primary immunodeficiency caused by mutations in Recombination-activating gene 2 (RAG2), a gene intimately involved in the process of lymphocyte maturation and function. ex-vivo manipulation of a patient’s own hematopoietic stem and progenitor cells (HSPCs) using CRISPR-Cas9/rAAV6 gene editing could provide a therapeutic alternative to the only current treatment, allogeneic hematopoietic stem cell transplantation (HSCT). Here we show an innovative RAG2 correction strategy that replaces the entire endogenous coding sequence (CDS) for the purpose of preserving the critical endogenous spatiotemporal gene regulation and locus architecture. Expression of the corrective transgene leads to successful development into CD3+TCRαβ+ and CD3+TCRγδ+ T cells and promotes the establishment of highly diverse TRB and TRG repertoires in an in-vitro T-cell differentiation platform. Thus, our proof-of-concept study holds promise for safer gene therapy techniques of tightly regulated genes.

ObjectiveTo investigate the diagnostic value of trimethylamine N-Oxide （TMAO） and serum amyloid A （SAA） levels in peripheral blood of patients with chronic cerebral hypoperfusion （CCH）. MethodsThe patients attending the Department of Neurology of Sichuan Provincial Peoples Hospital from February 2022 to June 2022 were divided into CCH group （n=55） and control group （n=42） based on the results of magnetic resonance arterial spin labeling （ASL）. The levels of TMAO and SAA were detected by ELISA and their diagnostic value for CCH were anaylzed by ROC curve. ResultsThe levels of TMAO （47.24±8.84 vs 40.81±8.33, t=3.639, P＜0.05） and SAA （14.04±2.70 vs 12.20±2.30, t=3.542, P＜0.05） in CCH group were significantly higher than those in control group. High levels of TMAO and SAA and history of primary hypertension were independent risk factors for the occurrence of CCH （P＜0.05）. The areas under ROC curve （AUC） of TMAO and SAA for diagnosing CCH were 0.701 （95%CI: 0.594-0.809） respectively and 0.675 （95%CI: 0.565-0.786）. The combined detection of TMAO and SAA achieved the highest AUC of 0.765 （95%CI: 0.667-0.863）. ConclusionBoth TMAO and SAA are related to the occurrence of CCH and can be used as auxiliary diagnostic indicators for CCH.

Severe combined immunodeficiency (SCID) is a group of disorders caused by mutations in genes involved in the process of lymphocyte maturation and function. CRISPR-Cas9 gene editing of the patient’s own hematopoietic stem and progenitor cells (HSPCs) ex vivo could provide a therapeutic alternative to allogeneic hematopoietic stem cell transplantation, the current gold standard for treatment of SCID. To eliminate the need for scarce patient samples, we engineered genotypes in healthy donor (HD)-derived CD34+ HSPCs using CRISPR-Cas9/rAAV6 gene-editing, to model both SCID and the therapeutic outcomes of gene-editing therapies for SCID via multiplexed homology-directed repair (HDR). First, we developed a SCID disease model via biallelic knockout of genes critical to the development of lymphocytes; and second, we established a knockin/knockout strategy to develop a proof-of-concept single-allelic gene correction. Based on these results, we performed gene correction of RAG2-SCID patient-derived CD34+ HSPCs that successfully developed into CD3+ T cells with diverse TCR repertoires in an in vitro T cell differentiation platform. In summary, we present a strategy to determine the optimal configuration for CRISPR-Cas9 gene correction of SCID using HD-derived CD34+ HSPCs, and the feasibility of translating this gene correction approach in patient-derived CD34+ HSPCs.

To explore the correlations of B cell-activating factor (BAFF), aquaporin-4 antibody (AQP4-Ab) and brain-derived neurotrophic factor (BDNF) with the severity of neuromyelitis optica spectrum disorder (NMOSD).

Activating mutations in Interleukin-7 receptor alpha (IL7Ra) have been reported in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) but its role in leukaemogenesis is not clear. Here, the authors show that activation of IL7Ra in primary human hematopoietic progenitors initiates preleukaemia and cooperates with CDKN2A silencing to develop BCP-ALL.

BackgroundDuring the process of generating diverse T and B cell receptor (TCR and BCR, respectively) repertoires, double-strand DNA breaks are produced. Subsequently, these breaks are corrected by a complex system led by the non-homologous end-joining (NHEJ). Pathogenic variants in genes involved in this process, such as the NHEJ1 gene, cause severe combined immunodeficiency syndrome (SCID) along with neurodevelopmental disease and sensitivity to ionizing radiation.ObjectiveTo provide new clinical and immunological insights on NHEJ1 deficiency arising from a newly diagnosed patient with severe immunodeficiency.Materials and methodsA male infant, born to consanguineous parents, suspected of having primary immunodeficiency underwent immunological and genetic workup. This included a thorough assessment of T cell phenotyping and lymphocyte activation by mitogen stimulation tests, whole-exome sequencing (WES), TCR repertoire Vβ repertoire via flow cytometry analysis, and TCR and BCR repertoire analysis via next-generation sequencing (NGS).ResultsClinical findings included microcephaly, recurrent pneumonia, and failure to thrive. An immune workup revealed lymphopenia, reduced T cell function, and hypogammaglobulinemia. Skewed TCR Vβ repertoire, TCR gamma (TRG) repertoire, and BCR repertoire were determined in the patient. Genetic analysis identified a novel homozygous missense pathogenic variant in XLF/Cernunnos: c.A580Ins.T; p.M194fs. The patient underwent a successful hematopoietic stem cell transplantation (HSCT).ConclusionA novel NHEJ1 pathogenic variant is reported in a patient who presented with SCID phenotype that displayed clonally expanded T and B cells. An adjusted HSCT was safe to ensure full T cell immune reconstitution.

Patients with loss-of-function mutations in IL10 or IL10 receptor (IL10R) genes develop severe, medical-refractory, infantile-onset inflammatory bowel disease (IBD). We have previously reported significant alterations in innate and adaptive immune responses in these patients. Next generation sequencing platforms enable a comprehensive assessment of T cell receptor (TCR) and B cell receptor (BCR) repertoire patterns. We aimed to characterize TCR and BCR features in peripheral blood of patients with deleterious IL10 signaling defects. DNA was isolated from blood of seven patients with IL10R mutations and one with an IL10 mutation, along with eight controls, and subjected to next generation sequencing of TRB and IgH loci. A significant increase in clonality was observed in both TCR and BCR repertoires in circulating lymphocytes of IL10/IL10R-deficient patients, but to a much greater extent in T cells. Furthermore, short CDR3β length and altered hydrophobicity were demonstrated in T cells of patients, but not in B cells, secondary to lower rates of insertions of nucleotides, but not deletions, at the V-, D-, or J-junctions. We were unable to observe specific T or B clones that were limited only to the patients or among controls. Moreover, the expanded T cells clones were unique to each patient. In conclusion, next generation sequencing of the TCR and BCR is a powerful tool for characterizing the adaptive immune cell phenotype and function in immune-mediated disorders. The oligoclonality observed among IL10/IL10R-deficient patients may suggest specialization of unique clones that likely have a role in mediating tissue damage. Nevertheless, the lack of shared clones between patients provides another piece of evidence that the adaptive immune response in IBD is not triggered against common antigens. Additional studies are required to define the specific antigens that interact with the expanded IL10/IL10R-deficient clones.

The alpha subunit of IL-7 receptor (IL7R7α) is critical for the differentiation of T cells, specifically for the development and maintenance of γδT cells. Mutations in IL7RA are associated with Severe Combined Immunodeficiency (SCID). Infants with IL7RA deficiency can be identified through newborn screening program. We aimed at defining the immunological and genetic parameters that are directly affected by the IL7RA mutation on the immune system of five unrelated patients which were identified by our newborn screening program for SCID. The patients were found to have a novel identical homozygote mutation in IL7RA (n.c.120 C>G; p.F40L). Both surface expression of IL7Rα and functionality of IL-7 signaling were impaired in patients compared to controls. Structural modeling demonstrated instability of the protein structure due to the mutation. Lastly the TRG immune repertoire of the patients showed reduced diversity, increased clonality and differential CDR3 characteristics. Interestingly, the patients displayed significant different clinical outcome with two displaying severe clinical picture of immunodeficiency and three had spontaneous recovery. Our data supports that the presented IL7RA mutation affects the IL-7 signaling and shaping of the TRG repertoire, reinforcing the role of IL7RA in the immune system, while non-genetic factors may exist that attribute to the ultimate clinical presentation and disease progression.

The CO2 moving average window(MAW) method is used to process RDE (real drive emissions) emissions data in China 6 light duty vehicle emissions regulations, while the Euro 6 light duty vehicle emission regulations allow to use both of MAW and power binning(PB) method to deal with RDE emission data. In order to study the difference between the two data processing methods and analyze the differences in the emission results, 10 different types of light duty vehicles are conducted RDE test with PEMS (portable emissions measurement system), and the test data are processed by the two methods separately. The results show that there is a little difference between MAW and PB, while both of them can satisfy the vehicle emission assessment. The PB method calculates the emission factors higher than the MAW method. After removing the cold start and idle condition data, the results of PB is similar to MAW. Besides, reducing the average speed limit of urban working conditions in PB has a greater impact on the urban driving condition emission factor, but less on the whole cycle emission factor.

The corrosion behavior of X65 carbon steel under different deposits in CO2 saturated formation water was studied by weight loss measurements, electrochemical measurements, wire beam electrode and microscopic analysis. The results show that the corrosion rate of the steel slightly decreases by being covered with sand, clay or ferrous carbonate. However, covered with ferrous sulfide, elemental sulfur or mixture, the corrosion rate obviously accelerates, especially in the specimen covered with elemental sulfur. The corrosion rate of the specimen covered with mixture deposits also significantly increases, in which elemental sulfur plays a dominant role. The significant increase in corrosion rate of the specimen covered with elemental sulfur is attributed to the self-catalytic action of elemental sulfur on the cathodic reaction of steel corrosion. The current and potential distributions of wire beam electrodes indicate that the potentials of the electrodes covered with mixture deposits are more positive than those without deposits. During the corrosion, severe localized corrosion occurs on the electrodes under mixture deposits. The current and potential maps of wire beam electrodes can effectively reflect the localized corrosion behavior of the steel under deposits due to the change of local environment.

In this paper, cooperative predator–prey system with impulsive effects and Beddington–DeAngelis functional response is studied. By using comparison theorem and some analysis techniques as well as the coincidence degree theory, sufficient conditions are obtained for the permanence, extinction and the existence of positive periodic solution.

The Wiskott Aldrich syndrome (WAS) is due to mutations of the WAS gene encoding for the cytoskeletal WAS protein (WASp), leading to abnormal downstream signaling from the T cell and B cell antigen receptors (TCR, BCR). We hypothesized that the impaired signaling through the TCR and BCR in WAS would subsequently lead to aberrations in the immune repertoire of WAS patients. Using next generation sequencing, the T cell receptor beta (TRB) and B cell immunoglobulin heavy chain (IGH) repertoires of 8 patients with WAS and 6 controls were sequenced. Clonal expansions were identified within memory CD4+ cells, as well as in total, naïve and memory CD8+ cells from WAS patients. In the B cell compartment, WAS patient IGH repertoires were also clonally expanded and showed skewed usage of IGHV and IGHJ genes, and increased usage of IGHG constant genes, compared with controls. To our knowledge, this is the first study that demonstrates significant abnormalities of the immune repertoire in WAS patients using next generation sequencing.

A novel analysis model for computing the load of wireless ad hoc network that uses multipath routing was proposed. This model took the number of paths, the way of route selecting and the density of the network nodes into account and could analyse or compute the load in different network conditions. The result of the simulation fits the theory perfectly and give the conclusion that using multipath routing alone in wireless ad hoc network can not balance the load of network effectively. This is not the same as we always accept （using multipath routing in wireless ad hoc network can balance the load of network and increase throughput just as in the normal network）.

Abstract Background The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. Methods We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. Results HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001). Conclusion Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA typing has been performed in order to try to establish an association with malignancy.

Using a laser light source in imaging devices provides a wide color gamut, high brightness, resolution, and efficiency. At the same time, it creates a speckle pattern that deteriorates the image quality. This paper is related to the application of the moving binary code diffractive optical element (DOE) for speckle suppression in a laser display. Analytical optimization of DOE parameters is made in this paper. The optimal DOE pitch is found analytically. Limitation of the DOE code length is shown, and the highest possible code length is estimated. Application of the compound Barker code for the DOE design is suggested. As an alternative, the M-sequence and minimum peak side-lobe codes are considered. The expected residual speckle contrast ratio after application of those codes is estimated for the number of codes. A comparison of the different codes is done, and recommendations for speckle suppression DOE design are provided.

Hybrid structures of silicon with organic-inorganic perovskites are proposed for optically controllable switching of terahertz (THz) waves over a broad spectral range from 0.2 to 2THz. A 532-nm external laser was utilized to generate photoexcited free carriers at the devices and consequentially to control the terahertz amplitude modulation, obtaining a depth of up to 68% at a laser irradiance of 1.5 W/cm 2 . In addition, we compared the performances from three types of perovskite devices fabricated via different solution processing methods and suggested a stable and highly efficient THz switch based on a one-step processing. By this we demonstrated the possibility of perovskites as THz wave switching devices in addition to photovoltaics.

Aligned silver nanorod (AgNR) array films were fabricated by oblique thermal evaporation. The substrate temperature during evaporation was varied from 10 to 100 °C using a home-built water cooling system. Deposition angle and substrate temperature were found to be the most important parameters for the morphology of fabricated films. Especially, it was found that there exists a critical temperature at ~90 °C for the formation of the AgNR array. The highest enhancement factor of the surface-enhanced Raman scattering (SERS), observed in the Ag films coated with benzenethiol monolayer, was ~6 × 10(7). Hot spots, excited in narrow gaps between nanorods, were attributed to the huge enhancement factor by our finite-difference time-domain (FDTD) simulation reflecting the real morphology.

The limit of sensing resolution of water temperature by remote Raman spectroscopy was investigated experimentally. A remote Raman spectrometer, which employed a telescope of 20 cm in pupil size and the second harmonic generation (SHG) of a Q-switched Nd:YAG laser, was used for the measurement. By analyzing the broad O-H stretching Raman band located near 3500  cm⁻¹, a parameter which is in second-order polynomial relation with water temperature from 13°C to 50°C could be obtained. The resolution of our remote Raman temperature sensor was better than ±0.2°C with measurement time shorter than 10 s. The influence of the Raman signal's signal-to-noise ratio on the resolution and salinity effect on the accuracy of temperature sensing were also investigated.

To extract optical constants of nontransmitted samples in the terahertz (THz) spectral region, we employ a THz emitter-sample hybrid structure where THz pulses are generated at the emitter surface and multiply reflected at the interface between the THz emitter and the sample. Since each THz electric field profile appears well separated in a time domain, we could obtain the amplitude and phase spectra for each pulse from the Fourier transform, and determine the optical constants of the sample numerically based on the Fresnel equations. We applied this technique for doped semiconductors, and found that obtained optical constants are in good agreement with the values determined by using other conventional THz techniques.

Nonlinear absorption - such as green-induced infrared absorption (GRIIRA) - increases the risk of the catastrophic damage during high peak- power wavelength conversion. We propose a novel concept to suppress parasitic green second-harmonic generation (SHG) in optical parametric oscillation (OPO) using specially engineered quasi-phase-matched (QPM) structures. This selective suppression was achieved by relative π-phase shift in only SHG not OPO. Compared with a periodic device, a parasitic-light-suppressed (PLS) QPM device produced smaller normalized conversion efficiency in green and maintained singly resonant OPO performance.

A broadband green light source was demonstrated using a tandem-poled lithium niobate (TPLN) crystal. The measured wavelength and temperature bandwidth were 6.5 nm and 100 °C, respectively, spectral bandwidth was 36 times broader than the periodically poled case. Although the conversion efficiency was smaller than in the periodic case, the TPLN device had a good figure of merit owing to the extremely large bandwidth for wavelength and temperature. The developed broadband green light source exhibited speckle noise approximately one-seventh of that in the conventional approach for a laser projection display.

The coherent control of optical images has garnered attention because all information embedded in optical images is expected to be controlled in a parallel way. One of the most important control processes is switch for information delivery. We experimentally demonstrated phase-controlled optical image switching in a double-Λ system where the transmission of the image through a medium was switched. Two independent laser sources were adopted for a double-Λ system such that images inscribed in two weak probe light beams were incoherent with each other. Arbitrary phase was added to the optical images to show that switching could be accomplished just with the relative phase difference between the probe pixels.

Ferromagnetic Mn-doped In(0.05)Ga(0.95)As and GaAs(0.95)Sb(0.05) nanowires were synthesized by chemical vapor transport and their Mn concentration was about 2%. The Mn doped homogeneously into both the single-crystalline zinc blende InGaAs and GaAsSb without the formation of metal clusters. X-ray magnetic circular dichroism and magnetic moment measurements revealed their distinctive room-temperature ferromagnetic behaviors. While the incorporation of In enhances the ferromagnetism, that of Sb reduces it, which can be ascribed to the increase or decrease of the dopant-acceptor hybridization. These GaAs-based NWs exhibit an efficient terahertz emission at room temperature, due to a strong local field enhancement by coherent surface plasmons. The Mn doping significantly enhances the intensity and bandwidth of the terahertz emission, with an excellent correlation with their magnetization.

We described the principle and the fabrication of a Nd:YVO(4)/KTP microchip for the linearly-polarized green laser and verified its availability by manufacturing and characterizing the green laser using the microchip. Under the driving condition having the modulation frequency of 60 Hz and the duty ratio of 25%, the laser showed the stable linear polarization, the maximum average power of 37 mW, yielding the high electrical-to-optical efficiency of 10.9%.

We have demonstrated the bandwidth control of a Ti-diffused periodically poled LiNbO(3) (Ti:PPLN) Solc filter by a temperature-gradient-control technique. Up to 2.8 nm of filtering bandwidth was achieved with a simple temperature-gradient-control technique in a 78-mm-long of Ti:PPLN waveguide, which has a 0.2 nm filtering bandwidth at an uniform temperature. We have also analyzed the experimental results with the theoretical calculation which is derived from the codirectional coupled mode equations.

We have analyzed the Solc filtering characteristics in a periodically poled Ti:LiNbO3 (Ti:PPLN) multimode waveguide. The single- and dual-wavelength filtering were achieved under the optimized guiding condition for the TEM(00)-like mode and two mode (TEM(00)- and TEM(01)-like mode), respectively. The full width at half-maximum of the filter was about 0.21 nm at both guiding conditions. We found that the origin of two peaks of the dual-wavelength Solc filter in the two-mode guiding condition is the different effective refractive index between the TEM(00)- and TEM(01)-like modes. The wavelength difference of two peaks is about 0.8 nm at room temperature.

We demonstrate optical parametric chirped pulse amplification (OPCPA) at 1-kHz repetition rate in periodically poled stoichiometric LiTaO3 (PPSLT) with 1 mol % MgO doping. Diode pumping was used both for the fiber laser generating the femtosecond seed pulses and the nanosecond laser/amplifier employed as a pump source. The high gain ( approximately 63 dB) and large bandwidth (20 nm) obtained for single-stage nondegenerate OPCPA operation provide a compact and efficient solution for amplification of ultrashort pulses near 1.57 microm. Stretched femtosecond pulses could be amplified up to 39.5 microJ in a 7-mm long, 2-mm thick sample of PPSLT. The pulse duration of the amplified signal pulses (FWHM) after recompression amounted to 315 fs.

Large nonlinear phase shifts were generated with femtosecond pulses at 1560 nm through cascaded quadratic interactions in periodically poled MgO-doped LiNbO3. The off-diagonal component of the nonlinear coefficient was utilized for simultaneous quasi phase matching and group-velocity matching. The effective nonlinear refractive index was varied from -2.9 x 10(-14) to +3.3 x 10(-14) cm2/W by tuning the phase-mismatch conditions.

A novel scheme for broadband second-harmonic generation was developed with type I quasi phase matching by use of an off-digital nonlinear optical coefficient d(31) . This was achieved by matching of the group velocities of the second harmonic and the fundamental, while the phase velocities were quasi phase matched. The desired group-velocity dispersion could be obtained with LiNbO(3) doped with 5 mol. % of MgO. Efficient second-harmonic generation with a bandwidth of 52 nm was obtained for the fundamental wavelength centered at 1566 nm in MgO-doped periodically poled LiNbO(3) , compared with a bandwidth of 1.3 nm for the conventional scheme using d(33) . Efficient frequency doubling of an ultrafast pulse is expected without group-velocity walk-off or pulse distortion.