Adaptive Second-Order Sliding Mode Control Design for a Class of Nonlinear Systems with Unknown Input

An adaptive second-order sliding mode controller is proposed for a class of nonlinear systems with unknown input. The proposed controller continuously drives the sliding variable and its time derivative to zero in the presence of disturbances with unknown boundaries. A Lyapunov approach is used to show finite time stability for the system in the presence of a class of uncertainty. An illustrative simulation example is presented to demonstrate the performance and robustness of the proposed controller

Structural, Stability, Dynamic and Binding Properties of the ALS-Causing T46I Mutant of the hVAPB MSP Domain as Revealed by NMR and MD Simulations

T46I is the second mutation on the hVAPB MSP domain which was recently identified from non-Brazilian kindred to cause a familial amyotrophic lateral sclerosis (ALS). Here using CD, NMR and molecular dynamics (MD) simulations, we characterized the structure, stability, dynamics and binding capacity of the T46I-MSP domain. The results reveal: 1) unlike P56S which we previously showed to completely eliminate the native MSP structure, T46I leads to no significant disruption of the native secondary and tertiary structures, as evidenced from its far-UV CD spectrum, as well as Cα and Cβ NMR chemical shifts. 2) Nevertheless, T46I does result in a reduced thermodynamic stability and loss of the cooperative urea-unfolding transition. As such, the T46I-MSP domain is more prone to aggregation than WT at high protein concentrations and temperatures in vitro, which may become more severe in the crowded cellular environments. 3) T46I only causes a 3-fold affinity reduction to the Nir2 peptide, but a significant elimination of its binding to EphA4. 4) EphA4 and Nir2 peptide appear to have overlapped binding interfaces on the MSP domain, which strongly implies that two signaling networks may have a functional interplay in vivo. 5) As explored by both H/D exchange and MD simulations, the MSP domain is very dynamic, with most loop residues and many residues on secondary structures highly fluctuated or/and exposed to bulk solvent. Although T46I does not alter overall dynamics, it does trigger increased dynamics of several local regions of the MSP domain which are implicated in binding to EphA4 and Nir2 peptide. Our study provides the structural and dynamic understanding of the T46I-causing ALS; and strongly highlights the possibility that the interplay of two signaling networks mediated by the FFAT-containing proteins and Eph receptors may play a key role in ALS pathogenesis

Novel Sulfated Polysaccharides Disrupt Cathelicidins, Inhibit RAGE and Reduce Cutaneous Inflammation in a Mouse Model of Rosacea

Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37.We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs) on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN) proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE) with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w) SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37.Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases

Unique Structure and Dynamics of the EphA5 Ligand Binding Domain Mediate Its Binding Specificity as Revealed by X-ray Crystallography, NMR and MD Simulations

10.1371/journal.pone.0074040PLoS ONE89-POLN

Shaping tourists' green behavior: the hosts' efforts at rural Chinese B&Bs

Tourists' green behavior has recently attracted much academic interest. The majority of the existing studies use quantitative research methods and explore how tourists' cognitive and emotional factors influence their environmental actions. This study assesses tourists' green behavior from a unique perspective, that is, how hosts at rural Chinese B&Bs interact with tourists and shape their sustainable actions. The research team analyzed why the rural hosts are motivated to promote tourists' green behavior, and identified the strategies they pursue to convince the tourists to be more sustainable. Guzhu Village, well known for its rural tourism and popular with senior tourists in the Yangtze River Delta, was the site for the study. Auto-ethnography was used as the key research method. It was found that both tangible and intangible environmental benefits motivate the hosts to guide tourists' sustainable behavior. Hosts specifically structure some leisure activities and use compelling signage to both promote positive environmental actions and simultaneously enhance tourists' satisfaction. This is the first study to emphasize the active roles of the hosts in shaping tourists' green behavior through dynamic social interaction. The findings highlight the processes, such as humor and social approval, which have broad international applicability. Further, it was noted that the hosts employ 'face', a distinctive Chinese concept, to limit tourists' less-desirable behaviors. Practical implications are also offered for sustainable destination management

Identification of a Novel Nonstructural Protein, VP9, from White Spot Syndrome Virus: Its Structure Reveals a Ferredoxin Fold with Specific Metal Binding Sites

White spot syndrome virus (WSSV) is a major pathogen in shrimp aquaculture. VP9, a full-length protein of WSSV, encoded by open reading frame wsv230, was identified for the first time in the infected Penaeus monodon shrimp tissues, gill, and stomach as a novel, nonstructural protein by Western blotting, mass spectrometry, and immunoelectron microscopy. Real-time reverse transcription-PCR demonstrated that the transcription of VP9 started from the early to the late stage of WSSV infection as a major mRNA species. The structure of full-length VP9 was determined by both X-ray and nuclear magnetic resonance (NMR) techniques. It is the first structure to be reported for WSSV proteins. The crystal structure of VP9 revealed a ferredoxin fold with divalent metal ion binding sites. Cadmium sulfate was found to be essential for crystallization. The Cd(2+) ions were bound between the monomer interfaces of the homodimer. Various divalent metal ions have been titrated against VP9, and their interactions were analyzed using NMR spectroscopy. The titration data indicated that VP9 binds with both Zn(2+) and Cd(2+). VP9 adopts a similar fold as the DNA binding domain of the papillomavirus E2 protein. Based on our present investigations, we hypothesize that VP9 might be involved in the transcriptional regulation of WSSV, a function similar to that of the E2 protein during papillomavirus infection of the host cells

Ultrasound-Guided Renal Access and Tract Dilation

Introduction: Ultrasound guidance is a unique alternative to fluoroscopy for percutaneous renal access. Besides being free of ionizing radiation exposure to the patient and intraoperative personnel, it offers several advantages including easier identification of the posterior renal calix and surrounding visceral structures. In this video, we demonstrate how ultrasound can be used to guide percutaneous nephrolithotomy (PCNL) in a step-by-step manner. Materials and Methods: From March to June 2016, 16 consecutive patients of age 18 and more with kidney or proximal ureteral stones underwent completely X-ray-free ultrasound-guided PCNL. No patients were excluded during the study period. Under general anesthesia, we place an externalized ureteral catheter through a flexible cystoscope with the patient in a frog-leg position. Retrograde saline injection is used to distend the collecting system only when needed. Then the patient is placed in a prone position. An ultrasound machine with a 3.5-MHz convex abdominal probe (Hitachi Aloka Medical America) is used to guide all steps of PCNL. For renal access, a longitudinal approach for needle insertion is usually chosen.1 An 18-gauge Echotip needle (Cook Medical) is slowly advanced through the skin either in front of or behind the probe. On the ultrasound screen, the entire needle should be fully seen from skin to kidney and into the targeted calix. Entry into the collecting system is confirmed with either aspiration of urine or efflux of urine through the puncture needle. Then, the needle stylet is removed and a J-tip coaxial guidewire (Bard Medical) is inserted into the renal pelvis or down the proximal ureter under ultrasound monitoring. Gently moving the wire back and forth will help identify the location of the wire tip relative to the collecting system. Subsequently, the needle is withdrawn, a 1-cm skin incision is made surrounding the wire, and a 10F fascial dilator and a safety wire introducer are then passed over the wire. Although the wire appears with a bright echogenic signal, the dilator and the safety wire introducer are not echogenic. Their advancement over the wire can be observed ultrasonographically as they obscure the echogenic appearance of the wire. A second wire is subsequently advanced into the collecting system through the safety wire introducer. A high-pressure balloon dilator (BARD X-Force, Bard Medical) is then advanced into the collecting system over one of the wires. Because the deflated balloon tip can be difficult to identify on the ultrasound screen, the wire should be moved back and forth while passing the balloon and the operative surgeon should look for a change in the wire contour to judge where the balloon tip is relative to the wire. The placement of the tip of this balloon dilator is crucial, as ideally, it should be just within the collecting system of the target calix.2 A working tract is then dilated and the access sheath is carefully advanced until the back end of the balloon is seen. Then the balloon is withdrawn, an offset rigid nephroscope is inserted, and the stone is treated. Results: The mean age of patients was 48.8 ± 19.9 years. Forty-four percent of patients were male with a mean body mass index of 29.9 ± 7.9 kg/m2 and a mean stone size of 33.7 ± 15.0 mm. All procedures were effectively performed with ultrasound guidance with a mean operative time of 101.3 ± 32.2 minutes. Patients and intraoperative personnel were not exposed to any ionizing radiation during the surgery. No patients experienced any significant immediate postoperative complication. All patients were stone free (no visible stone fragments) based on intraoperative visual inspection using a flexible nephroscope and a renal ultrasound and KUB at 30 days after surgery, and no secondary procedures were required. Conclusions: Ultrasound guidance for renal access and tract dilation in prone PCNL is feasible and efficient. Although some situations such as obese patients or nondilated collecting system may present a challenge, the benefits of adopting this technique-namely eliminating ionizing radiation exposure and live imaging of anatomy surrounding the collecting system-provide value during PCNL. Acknowledgments: This study was supported by the NIH R21-DK-109433 (TC) and the NIH NIDDK K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC). No competing financial interests exist. Runtime of video: 5 mins 12 secs

Ultrasound-Guided Renal Access and Tract Dilation

Introduction: Ultrasound guidance is a unique alternative to fluoroscopy for percutaneous renal access. Besides being free of ionizing radiation exposure to the patient and intraoperative personnel, it offers several advantages including easier identification of the posterior renal calix and surrounding visceral structures. In this video, we demonstrate how ultrasound can be used to guide percutaneous nephrolithotomy (PCNL) in a step-by-step manner. Materials and Methods: From March to June 2016, 16 consecutive patients of age 18 and more with kidney or proximal ureteral stones underwent completely X-ray-free ultrasound-guided PCNL. No patients were excluded during the study period. Under general anesthesia, we place an externalized ureteral catheter through a flexible cystoscope with the patient in a frog-leg position. Retrograde saline injection is used to distend the collecting system only when needed. Then the patient is placed in a prone position. An ultrasound machine with a 3.5-MHz convex abdominal probe (Hitachi Aloka Medical America) is used to guide all steps of PCNL. For renal access, a longitudinal approach for needle insertion is usually chosen.1 An 18-gauge Echotip needle (Cook Medical) is slowly advanced through the skin either in front of or behind the probe. On the ultrasound screen, the entire needle should be fully seen from skin to kidney and into the targeted calix. Entry into the collecting system is confirmed with either aspiration of urine or efflux of urine through the puncture needle. Then, the needle stylet is removed and a J-tip coaxial guidewire (Bard Medical) is inserted into the renal pelvis or down the proximal ureter under ultrasound monitoring. Gently moving the wire back and forth will help identify the location of the wire tip relative to the collecting system. Subsequently, the needle is withdrawn, a 1-cm skin incision is made surrounding the wire, and a 10F fascial dilator and a safety wire introducer are then passed over the wire. Although the wire appears with a bright echogenic signal, the dilator and the safety wire introducer are not echogenic. Their advancement over the wire can be observed ultrasonographically as they obscure the echogenic appearance of the wire. A second wire is subsequently advanced into the collecting system through the safety wire introducer. A high-pressure balloon dilator (BARD X-Force, Bard Medical) is then advanced into the collecting system over one of the wires. Because the deflated balloon tip can be difficult to identify on the ultrasound screen, the wire should be moved back and forth while passing the balloon and the operative surgeon should look for a change in the wire contour to judge where the balloon tip is relative to the wire. The placement of the tip of this balloon dilator is crucial, as ideally, it should be just within the collecting system of the target calix.2 A working tract is then dilated and the access sheath is carefully advanced until the back end of the balloon is seen. Then the balloon is withdrawn, an offset rigid nephroscope is inserted, and the stone is treated. Results: The mean age of patients was 48.8 ± 19.9 years. Forty-four percent of patients were male with a mean body mass index of 29.9 ± 7.9 kg/m2 and a mean stone size of 33.7 ± 15.0 mm. All procedures were effectively performed with ultrasound guidance with a mean operative time of 101.3 ± 32.2 minutes. Patients and intraoperative personnel were not exposed to any ionizing radiation during the surgery. No patients experienced any significant immediate postoperative complication. All patients were stone free (no visible stone fragments) based on intraoperative visual inspection using a flexible nephroscope and a renal ultrasound and KUB at 30 days after surgery, and no secondary procedures were required. Conclusions: Ultrasound guidance for renal access and tract dilation in prone PCNL is feasible and efficient. Although some situations such as obese patients or nondilated collecting system may present a challenge, the benefits of adopting this technique-namely eliminating ionizing radiation exposure and live imaging of anatomy surrounding the collecting system-provide value during PCNL. Acknowledgments: This study was supported by the NIH R21-DK-109433 (TC) and the NIH NIDDK K12-DK-07-006: Multidisciplinary K12 Urologic Research Career Development Program (TC). No competing financial interests exist. Runtime of video: 5 mins 12 secs