Search

Background: Care for patients with compression neuropathies (carpal tunnel syndrome, ulnar neuropathy) is often fragmented, uncoordinated, and slow. Patients go through multiple steps (neurology consultation, nerve testing, ultrasound, splints, injection, surgical opinion, surgery) with waits between each step. We used a Value-Based Health Care (VBHC) model to develop a multidisciplinary clinic with a novel care pathway. Methods: A Shared Care initiative supported the development of an Integrated Practice Unit (IPU). Key multidisciplinary team members were identified. Participants attended a curated three part VBHC workshop. Process mapping enabled identification of efficiencies. Results: 14 team members participated in the workshops. Condition specific outcome measures were identified (Boston CTS measure, 10-point touch, MRC strength and pain scale) and will be collected longitudinally. Criteria and clinical pathways were developed for mild, moderate, and severe carpal tunnel syndrome. Resource materials for patients and providers were developed. Conclusions: A VBHC framework supported development of a novel clinic for compression neuropathy. Responsibility for the full cycle of care rests with the IPU. Systematically tracking functional outcome measures enables quality improvement. By streamlining the patient journey and substantially reducing wait times between steps, the new care pathway reduces complexity and improve outcomes. Evaluation of impact if this new clinical model is ongoing.

We report, to the best of our knowledge, the first experimental observation of coexistence of scalar dark and bright solitons in a fiber laser operating in the near zero-dispersion regime. We show that because of the incoherent cross coupling, under suitable conditions a bright soliton formed in the net anomalous cavity dispersion regime could bind with a dark soliton formed in the net normal cavity dispersion regime in a fiber laser. The properties of the dark and bright solitons, as well as their bound states, are experimentally investigated. The numerical simulations based on the coupled Ginzburg–Landau equations have reproduced the experimental results well.

We report the experimental observation of coherently coupled dark-bright vector solitons in single mode fiber lasers with either normal or anomalous cavity dispersion. The properties of these vector solitons were found to agree well with theoretical predictions based on the coherently coupled nonlinear Schrödinger equations. The experimental results clearly confirmed the existence of a fundamentally new form of optical solitons in coupled nonlinear systems.

Background: Non-coding small RNAs are involved in organism development, and their aberrant regulation induces various diseases, including hepatocellular carcinoma (HCC), but their exact mechanisms have not been determined. Objective: The aim was to investigate the role of miR-142-3p on HMGB1 expression in hepatocellular carcinoma. Methods: Expression levels of miR-142-3p in HCC tissues and cultured cells were measured by RT-PCR. The invasion and metastasis abilities of HepG2 cells according to Transwell migration and invasion assays, and protein expression was measured by western blotting. Results: The present study reported that miR-142-3p promotes the invasion and migration of HCC cells. miR-142-3p levels are lower in HCC tissues than in adjacent non-cancerous tissues, suggesting a tumor suppressor role for miR-142-3p. Highmobility group box protein 1 (HMGB1) is an oncogene that promotes the metastasis of HCC. miR-142-3p or HMGB1 knockdown alone inhibits the invasion and migration of HCC cells, and HMGB1 overexpression impedes the effect of miR-142-3p. Further studies showed that HMGB1 is a direct target gene of miR-142-3p in HCC. miR-142-3p represses HMGB1 gene transcription by directly binding to the 3′ untranslated region (UTR) of HMGB1, thereby inhibiting cancer cell invasion and migration. Conclusion: This study, for the first time, reports that miR-142-3p is a novel tumor suppressor that inhibits the invasion and migration of HCC cells by directly regulating gene transcription of HMGB1. Thus, miR-142-3p may be a potential diagnostic and therapeutic biomarker for HCC patients.

This study aimed to investigate the effects of SOST and the Wnt/β-catenin signaling pathway on the proliferation, migration, invasion, and apoptosis of human retinoblastoma cells. Fifty-five retinoblastoma and 21 normal retinal tissue samples were collected as the case group and control group, respectively. HXO-RB44 and SO-RB50 cells were selected and assigned into blank, negative control (NC), siRNA 1, siRNA 2, siRNA 3, IWR-1-endo 1, IWR-1-endo 2 and IWR-1-endo 3 groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of SOST, Wnt-1, and β-catenin in the collected tissue samples. MTT assay, flow cytometry, transwell assay and the starch test were employed to determine the cell proliferation, cell cycle, apoptosis, invasion and migration after transfection. The qRT-PCR and western blotting were also used to detect the mRNA and protein expressions of SOST, Wnt-1, β-catenin, C-myc, Cyclin D1, MMP-2 and MMP-9. The tumor formation in nude mice was conducted to evaluate the effects of SOST on the growth of a transplanted tumor. Compared with normal retinal tissues, the retinoblastoma tissues exhibited a downregulation of SOST but an upregulation of Wnt-1 and β-catenin. The proliferation, invasion and migration of HXO-RB44 and SO-RB50 cells in the SOST-siRNA group were significantly higher than the cells in the blank and NC groups. The expressions of Wnt-1, β-catenin, C-myc, Cyclin D1, MMP-2 and MMP-9 in the three SOST-siRNA groups were elevated, but the SOST decreased when compared with the blank and NC groups. SOST silencing promoted the growth of transplanted tumors in nude mice. These findings indicate that SOST silencing promotes the proliferation, invasion and migration, and decreases the apoptosis of human retinoblastoma cells by activating the Wnt/β-catenin signaling pathway.

The frequency of the Robertonian (ROB) translocation in newborn babies is approximately one in 1000. Robertsonian translocation is an unusual type of chromosome rearrangement caused by two particular chromosomes joining together. The aim of the study was to analyze the segregation of the ROB translocations in 13 male carriers, and to verify a possible inter-chromosomal effect (ICE) of the ROB translocation on chromosomes 18, X, and Y. Thirteen male patients were included in the study. Multicolor fluorescent in situhybridization (FISH) was used to analyze chromosomes 13, 14, 15, 21, 22, 18, X and Y in sperm. Among the heterozygous ROB translocation carriers, the frequency of normal/balanced spermatozoa resulting from alternate segregation varied between 70.4 and 85.2%. The frequency of unbalanced spermatozoa resulting from adjacent segregation varied between 14.8 and 29.6%. Increased frequencies of aneuploidy for a sex chromosome were found in 10 ROB translocation carriers (P2-P8, P10-P12). Increased frequencies of aneuploidy for chromosome 18 were found in10 ROB translocation carriers (P3-P9, P11-P13). In addition, increased frequencies of diploid were found in 11 ROB translocation carriers (P2-P9, P11-P13). Among the homozygous ROB translocation carriers, the rate of balanced spermatozoa was 99.7% and the frequency of unbalanced spermatozoa was 0.3%. However, the frequencies of aneuploidy for a sex chromosome and chromosome 18 were normal. Despite the high number of normal/balanced frequencies, there remained many unbalanced spermatozoa resulting from alternate segregation. The ROB translocation carriers may be at an increased risk for ICE. Robertsonian translocation homozygosity could be seen as a potential speciation in humans with 44 chromosomes.

The objective of this study was to evaluate the effect of residual feed intake (RFI) on rumen function in finishing lambs. A total of 60 male Hu lambs (average initial BW = 25.2 ± 2.5kg) were used and were offered a pelleted high-concentrate diet, of which the forage to concentrate ratio was 25:75. Individual feed intake was recorded over a period of 42 d, then 10 lambs with the lowest RFI and the highest RFI were selected, respectively. The rumen fluid used for fermentation variables and relative abundance of bacteria measurement was obtained on d 10 and 20 after RFI measurement. At the end of this experiment, the selected lambs were slaughtered and rumen epithelium and liver tissues were collected for RNA extraction. Low-RFI lambs had lower (P< 0.01) DMI and greater (P< 0.05) G:F than the high-RFI ones, while the RFI groups did not differ in ADG and BW (P> 0.05). Additionally, RFI was positively (r= 0.57; P< 0.01) correlated with DMI and negatively (r= −0.53; P< 0.05) correlated with G:F. Total VFA and individual VFA decreased (P< 0.05) over time. The concentrations of total VFA, acetate, valerate, isobutyrate, isovalerate, and rumen pH (P> 0.05) were not affected by RFI classification. Nonetheless, low-RFI group lambs had a greater (P< 0.05) concentration of propionate, a lower (P< 0.05) concentration of butyrate, and a lower (P< 0.05) acetate to propionate ratio compared with the high-RFI group. There was a significant (P< 0.05) effect of RFI on the relative abundance of Butyrivibrio fibrisolvensand Escherichia coli. The relative abundance of Ruminococcus albus, Ruminococcus flavefaciens, and Prevotella bryantiidecreased (P< 0.05) over time in high-RFI group. And the relative abundance of B. fibrisolvensin high-RFI group was greater (P< 0.05) than its low-RFI counterpart. Furthermore, RFI had no effect (P> 0.05) on gene expression associated with intracellular pH regulation (PAT1, AE2, DRA, NHE2, NHE3, MCT1, MCT4, and ATPase) in rumen epithelium and β-hydroxybutyrate metabolism (HMGCS2) in both rumen epithelium and liver tissues. In conclusion, even though low-RFI lambs had lower DMI, however, the number of B. fibrisolvenswas lower. Additionally, there was no difference in gene expressions level associated with intracellular pH regulation in rumen epithelium between RFI groups.

Zeolite imidazole frameworks (ZIF-8) are a group of metal–organic frameworks (MOFs) that harbor application potential due to their unique high porosity and other physicochemical properties. However, the small cavities, unstable dispersion, and the lack of surface functional groups hinder the practical application of ZIF-8. In this study, we aimed to develop a ZIF-8-based multifaceted platform with hollow structure and abundant functional groups via a simple one-pot method. We synthesized the ZIF-8 with thiol functionalization (ZSH), while 2-mercaptoimidazole was served as both etching agent and functional counterpart. The hollow morphology and the thiol-groups modification were validated by scanning electron microscopy, transmission electron microscopy with energy-disperse X-ray mapping and X-ray photoelectron spectroscopy. The interparticle structure was estimated by Brunauer–Emmmett–Teller and ultraviolet–visible spectroscopy. The hollow architecture, colloidal stable, and thiol-abundant surface endow ZSHs exploiting the antioxidant and anti-inflammatory ability than pristine ZIF-8 toward a broad scale of morphological change with high functionalization degree. Moreover, ZSHs can specifically encapsulate gold nanoparticles in large quantities for further applications. Finally, ZSHs possess good biocompatibility in human cells and in vivozebrafish model and could potentially protect human cells against oxidative stress. This concept valuably elucidated the new era for functionalized ZIF-8 to apply as the next generation of multifunctional biomaterials.

Advanced prostate adenocarcinomas enriched in stem-cell features, as well as variant androgen receptor (AR)-negative neuroendocrine (NE)/small-cell prostate cancers are difficult to treat, and account for up to 30% of prostate cancer-related deaths every year. While existing therapies for prostate cancer such as androgen deprivation therapy (ADT), destroy the bulk of the AR-positive cells within the tumor, eradicating this population eventually leads to castration-resistance, owing to the continued survival of AR-/lostem-like cells. In this study, we identified a critical nexus between p38MAPK signaling, and the transcription factor Forkhead Box Protein C2 (FOXC2) known to promote cancer stem-cells and metastasis. We demonstrate that prostate cancer cells that are insensitive to ADT, as well as high-grade/NE prostate tumors, are characterized by elevated FOXC2, and that targeting FOXC2 using a well-tolerated p38 inhibitor restores epithelial attributes and ADT-sensitivity, and reduces the shedding of circulating tumor cells in vivo with significant shrinkage in the tumor mass. This study thus specifies a tangible mechanism to target the AR-/lopopulation of prostate cancer cells with stem-cell properties.

Background: Resistin-like molecule-α (RELMα) has diverse regulatory functions in inflammation, but its role in severe acute pancreatitis (SAP) and acute pancreatitis associated lung injury (APALI) remains unclear. Methods: SAP was induced in rats. RELM protein expression was detected in lung tissue of rats to determine the relationship between APALI and RELM. To investigate the effect of RELM overexpression or knockdown on APALI, rats were given an intravenous injection of adenovirus vector before SAP induction. Lung and pancreatic samples were harvested 16 h after induction. After detection of RELM protein levels, the severity of pancreatic and pulmonary injury was scored histologically, and serum and tissue levels of inflammatory mediators were measured. TUNEL assay and immunofluorescence were used to estimate pulmonary apoptosis and endothelial barrier integrity in lung tissue of SAP rats with RELM knockdown. Results: RELM expression was significantly up-regulated in APALI and was related to the lung injury index. RELM overexpression aggravated the release of inflammatory cytokines including interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-, and serum C-reaction protein; the expression of inflammatory mediators phosphorylated (p)-AKT, p-P65, p-P38 mitogen activated protein kinase, p-extracellular regulated kinase, and intracellular adhesion molecule-1; and lung injury. RELM knockdown had opposite effects. In addition, RELM knockdown improved expression of proliferative cellular nuclear antigen, Bcl-2, zonal occluding-1 and Claudin-1 in lung tissue of SAP rats. Conclusion: RELMα is associated with lung injury severity in SAP. RELM augments inflammatory activity by increasing inflammatory cytokine release.

Optical sampling based on ultrafast optical nonlinearities is a useful technique to monitor the waveforms of ultrashort optical pulses. In this paper, we present a new implementation of optical waveform sampling systems by employing our newly constructed free–running mode–locked fibre laser with a tunable repetition rate and a low timing jitter, an all–optical waveform sampler with a highly nonlinear fibre (HNLF), and our developed computer algorithm for optical waveform display and measurement, respectively. Using a femtosecond fibre laser to generate the highly stable optical sampling pulses and exploiting the four–wave mixing effect in a 100m–long HNLF, we successfully demonstrate the all–optical waveform sampling of a 10GHz optical clock pulse sequence with a pulse width of 1.8 ps and a 80Gbit/s optical data signal, respectively. The experimental results show that waveforms of the tested optical pulse signals are accurately reproduced with a pulse width of 2.0 ps. This corresponds to a temporal resolution of 0.87 ps for optical waveform measurement. Moreover, the optical eye diagram of a 10Gbit/s optical data signal with a 1.8 ps pulse width is also accurately measured by employing our developed optical sampling system.

PurposeTo estimate the prevalence of myopia among primary and middle school-aged students in Guangzhou and to explore the potentially contributing factors to myopia.MethodsThis cross-sectional study was based on a sample of students in grades 1–6 and grades 7–9. Data were collected from refractive error measurements and a structured questionnaire.ResultsA total of 3055 participants were involved in this analysis, and the overall prevalence of myopia was 47.4% (95% confidence interval (CI)= 45.6–49.2%). The prevalence of myopia in students increased along with the growth of grade level; the prevalence of myopia in students in grade 1 was only 0.2%, as it increased to 38.8% in students in grade 3, and the rate was the highest (68.4%) in students in grade 9. Girls were at a higher risk of myopia than boys (adjusted odds ratio=1.22, 95% CI=1.04–1.44). Both male and female students whose distance of reading was longer than 25 cm were less likely to have myopia and who have one or two myopic parents were at a higher risk of myopia. In addition, reading for pleasure more than 2 h per day (adjusted odds ratio=1.84, 95% CI=1.09–3.12) was only positively associated with myopia in boys and spending time watching television per week was only positively associated with myopia in girls.ConclusionMyopia in students is a significant public health problem in Guangzhou. Female gender, higher grade, longer time spent for near work, shorter distance of near work, and parental myopia were shown to be associated with the increasing risk of myopia in children.

Background:: Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Methods:: Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I–III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Results:: Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27–0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15–10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40–6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09–3.35). Conclusions:: In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing—suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Ferroptosis is a recently recognized form of regulated cell death. It is characterized morphologically by the presence of smaller than normal mitochondria with condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, and outer mitochondrial membrane rupture. It can be induced by experimental compounds (e.g., erastin, Ras-selective lethal small molecule 3, and buthionine sulfoximine) or clinical drugs (e.g., sulfasalazine, sorafenib, and artesunate) in cancer cells and certain normal cells (e.g., kidney tubule cells, neurons, fibroblasts, and T cells). Activation of mitochondrial voltage-dependent anion channels and mitogen-activated protein kinases, upregulation of endoplasmic reticulum stress, and inhibition of cystine/glutamate antiporter is involved in the induction of ferroptosis. This process is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism and can be pharmacologically inhibited by iron chelators (e.g., deferoxamine and desferrioxamine mesylate) and lipid peroxidation inhibitors (e.g., ferrostatin, liproxstatin, and zileuton). Glutathione peroxidase 4, heat shock protein beta-1, and nuclear factor erythroid 2-related factor 2 function as negative regulators of ferroptosis by limiting ROS production and reducing cellular iron uptake, respectively. In contrast, NADPH oxidase and p53 (especially acetylation-defective mutant p53) act as positive regulators of ferroptosis by promotion of ROS production and inhibition of expression of SLC7A11 (a specific light-chain subunit of the cystine/glutamate antiporter), respectively. Misregulated ferroptosis has been implicated in multiple physiological and pathological processes, including cancer cell death, neurotoxicity, neurodegenerative diseases, acute renal failure, drug-induced hepatotoxicity, hepatic and heart ischemia/reperfusion injury, and T-cell immunity. In this review, we summarize the regulation mechanisms and signaling pathways of ferroptosis and discuss the role of ferroptosis in disease.

Despite a paucity of data regarding both the incidence of ocular candidiasis and the utility of ophthalmic examination in critically ill patients, routine ophthalmic examination is recommended for critically ill patients with candidaemia. The objectives were to estimate the incidence of ocular candidiasis and evaluate whether ophthalmic examination influenced subsequent management of these patients. We conducted a ten-year retrospective observational study. Data were extracted for all ICU patients who were blood culture positive for fungal infection. Risk factors for candidaemia and eye involvement were quantified and details regarding ophthalmic examination were reviewed. Candidaspecies were cultured in 93 patients. Risk factors for ocular candidiasis were present in 57% of patients. Forty-one percent of patients died prior to ophthalmology examination and 2% of patients were discharged before candidaemia was identified. During examination, signs of ocular candidiasis were only present in one (2.9%) patient, who had a risk factor for ocular candidiasis. Based on these findings, the duration of antifungal treatment for this patient was increased. Ocular candidiasis occurs rarely in critically ill patients with candidaemia, but because treatment regimens may be altered when diagnosed, routine ophthalmic examination is still indicated.

The effect of the time taken to add the alloy and the gas injection mode are significant factors for fast decarburisation. Industrial experiments and thermodynamic calculations are adopted to show the transition of the main factors and reaction sites with time. The results indicate that adding steel scrap and alloy are not recommended in the first 7 min in order to keep good thermodynamic and dynamic conditions. The gas injection mode is more critical for reducing the chamber pressure to 67 Pa in 8.5 min and the gas volume should be less than 10 m3in the first 4 min after the reaction begins. This method is effective in improving the decarburisation rate and decreasing the carbon content at the end of decarburisation. For 69 of the site tests the final carbon content was kept to about 10 ppm within 15 min.

The effect of the time taken to add the alloy and the gas injection mode are significant factors for fast decarburisation. Industrial experiments and thermodynamic calculations are adopted to show the transition of the main factors and reaction sites with time. The results indicate that adding steel scrap and alloy are not recommended in the first 7 min in order to keep good thermodynamic and dynamic conditions. The gas injection mode is more critical for reducing the chamber pressure to 67 Pa in 8.5 min and the gas volume should be less than 10 m3in the first 4 min after the reaction begins. This method is effective in improving the decarburisation rate and decreasing the carbon content at the end of decarburisation. For 69% of the site tests the final carbon content was kept to about 10 ppm within 15 min.

We show both theoretically and experimentally the temporal cavity soliton formation in a fiber ring laser. The cavity-induced modulation instability can automatically destabilize the CW operation of a fiber ring laser, transferring the CW laser beam into a periodic pulse train. Under strong laser emission, and particularly under the action of the effective gain bandwidth limitation, each pulse of the periodic pulse train could be further shaped into a dissipative soliton. The features of the temporal cavity solitons thus formed are experimentally studied and their similarity and difference to those of the mode-locked fiber lasers are discussed.

We report on an ultrahigh repetition rate dark soliton fiber laser. We show both numerically and experimentally that by taking advantage of the cavity self-induced modulation instability and the dark soliton formation in a net normal dispersion cavity fiber laser, stable ultrahigh repetition rate dark soliton trains can be formed in a dispersion-managed cavity fiber laser. Stable dark soliton trains with a repetition rate as high as ∼280  GHz have been generated in our experiment. Numerical simulations have shown that the effective gain bandwidth limitation plays an important role on the stabilization of the formed dark solitons in the laser.

PTEN (Phosphatase and Tensin homologue deleted on chromosome 10, 10q23.3) is the dominant phosphatase responsible for the dephosphorylation of the 3-position phosphate from the inositol ring of phosphatidylinositol 3,4,5 triphosphate (PIP3), and thereby directly antagonizes the actions mediated by Phosphatidylinositol-3 Kinase (PI3K). PI3K functions in numerous pathways and cellular processes, including tumourigenesis. Therefore, mechanisms regulating PTEN function, either positively or negatively are of great interest not only to oncogenesis but also to other aspects of human health. Since its discovery in 1997, PTEN has been one of the most-heavily studied tumour suppressors and has been the subject of numerous reviews. Most investigations and reviews center on PTEN’s function and its regulation. While the regulation of PTEN function via genetic and/or epigenetic mechanisms has been extensively studied, the impact of protein-protein interaction on PTEN function remains less clear. Recent research has revealed that PTEN can be specifically inhibited by its interaction with other proteins, which are collectively termed PTEN-negative regulators (PTENNRs). This review will summarize our current understanding on the protein network that influences PTEN function with a specific focus on PTEN-NRs.

Diabetic nephropathy (DN) is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD). Approximately, one third of diabetic patients develop diabetic nephropathy. As diabetes and its associated metabolic diseases are becoming epidemic, DN is emerging as a major health threat to humans. Currently, there are no effective therapeutic treatments for the disease. As a result, most DN cases progress to ESRD; patients with ESRD will need to undergo renal replacement through either dialysis or kidney transplantation. Therefore, developing new and effective means to control DN has been a major focus in the diabetes research. DN is a complex disease with pathological changes occurred in the glomerulus and renal tubules. It is, nonetheless, widely believed that the primary defects lie in the glomeruli, which lead to disrupting the integrity of the glomerular filtration barrier. While a variety of factors contribute to the impairment of glomerular filtration function, a large body of evidence demonstrates that damage in podocytes is the leading cause. Renal fibrosis plays critical roles in promoting DN progression. The primary mechanism responsible for renal fibrosis is abnormal activation of the transforming growth factor (TGF)- pathway. Based on this understanding of DN pathogenesis, one strategy to control DN is to specifically protect podocytes from diabetes-induced injuries and to inhibit TGF- signaling using gene therapy methodology. In this review, we will discuss the current research effort in developing gene therapy for DN.

The recovery efficiency of aquifer storage systems with radial flow fields are studied for heterogeneous aquifers. Macrodispersion, arising from spatially heterogeneous hydraulic conductivity, is modeled as a scale‐dependent mechanical dispersion process. Approximate solutions for the recovery efficiency as a function of local dispersion and macrodispersion parameters, the injection‐extraction rate Q$Q$and duration T$T$, and storage cycle count, are derived and validated against numerical simulations. If macrodispersion dominates and the macrodispersion coefficient scales linearly with distance, the recovery efficiency is independent of both Q,T$Q,T$. For sublinear and superlinear scalings, recovery increases and decreases respectively if Q,T$Q,T$increases. However, if local dispersion dominates, increasing Q,T$Q,T$always increases recovery. As macrodispersion becomes increasingly dominant with scale, the recovery efficiency may be a nonmonotonic function of Q,T$Q,T$, with a maximum. In homogeneous aquifers, nonmonotonicity does not occur for 1D and 2D radial flow, but occurs for 3D radial flow fields only as a function of T$T$, not Q$Q$. These methods may also be used for fitting local dispersion and macrodispersion parameters with push‐pull tests using recovery data, with advantages in scope of applicability and ease of data acquisition and interpretation, compared to existing push‐pull test methods, which fit to breakthrough curves and do not consider macrodispersion. Furthermore, characterizing macrodispersion with push‐pull tests may be advantageous over methods that use observation wells, as observation well placement may be challenging in highly heterogeneous aquifers. The results show that the macrodispersion parameters are not innate aquifer hydraulic properties, as their values vary with flow field geometry. New methods for evaluating heat (ATES) and freshwater (ASR) storage systems, and interpreting push‐pull tests, in heterogeneous aquifersApproximate solutions for recovery efficiency, where macrodispersion is modeled as a scale‐dependent dispersion processDepending on the scale‐dependence function, recovery may vary non‐monotonically with stored volume under planar and cylindrical flow New methods for evaluating heat (ATES) and freshwater (ASR) storage systems, and interpreting push‐pull tests, in heterogeneous aquifers Approximate solutions for recovery efficiency, where macrodispersion is modeled as a scale‐dependent dispersion process Depending on the scale‐dependence function, recovery may vary non‐monotonically with stored volume under planar and cylindrical flow

The Raf-MEK-ERK pathway is commonly activated in human cancers, largely attributable to the extracellular signal-regulated kinases (ERKs) being a common downstream target of growth factor receptors, Ras, and Raf. Elevation of these up-stream signals occurs frequently in a variety of malignancies and ERK kinases play critical roles in promoting cell proliferation. Therefore, inhibition of MEKmediated ERK activation is very appealing in cancer therapy. Consequently, numerous MEK inhibitors have been developed over the years. However, clinical trials have yet to produce overwhelming support for using MEK inhibitors in cancer therapy. Although complex reasons may have contributed to this outcome, an alternative possibility is that the MEK-ERK pathway may not solely provide proliferation signals to malignancies, the central scientific rationale in developing MEK inhibitors for cancer therapy. Recent developments may support this alternative possibility. Accumulating evidence now demonstrated that the MEK-ERK pathway contributes to the proper execution of cellular DNA damage response (DDR), a major pathway of tumor suppression. During DDR, the MEK-ERK pathway is commonly activated, which facilitates the proper activation of DDR checkpoints to prevent cell division. Inhibition of MEK-mediated ERK activation, therefore, compromises checkpoint activation. As a result, cells may continue to proliferate in the presence of DNA lesions, leading to the accumulation of mutations and thereby promoting tumorigenesis. Alternatively, reduction in checkpoint activation may prevent efficient repair of DNA damages, which may cause apoptosis or cell catastrophe, thereby enhancing chemotherapys efficacy. This review summarizes our current understanding of the participation of the ERK kinases in DDR.

We demonstrate experimentally that few atomic layer graphene possesses ultrafast, super broadband saturable absorption, which can be exploited to passive mode lock fiber lasers of different operation wavelengths. Passive mode locking performance of an erbium-doped fiber laser operating at the 1.55m and an ytterbium-doped fiber laser operating at the 1.06m with a graphene saturable absorber mirror has been experimentally demonstrated, and wavelength tuneable solitons, vector solitons, as well as the bound state of solitons have been observed.

The thermal contact conductance (TCC) is one of the principal parameter in heat transfer mechanism of tube—fin heat exchangers. Because of the difficulties in experimental measurements, the tube—fin TCC has not been focused deeply. This article presents a novel method in evaluating the TCC of tube—fin heatexchanger. First, the tube—fin contact status is investigated with a finite-element model of tube expansion process. Distribution of contact pressure along the tube—fin interface is obtained from the simulation results. Then, experiments are carried out for the relationship between the contact pressure and the TCC. Combining the experiment result with the contact pressure distribution, the tube—fin TCC can be evaluated. Based on the method, effect of processing factors of the expansion forming process, such as expanding ratio and die geometry, are examined.