Static Solitons of the Sine-Gordon Equation and Equilibrium Vortex Structure in Josephson Junctions

The problem of vortex structure in a single Josephson junction in an external magnetic field, in the absence of transport currents, is reconsidered from a new mathematical point of view. In particular, we derive a complete set of exact analytical solutions representing all the stationary points (minima and saddle-points) of the relevant Gibbs free-energy functional. The type of these solutions is determined by explicit evaluation of the second variation of the Gibbs free-energy functional. The stable (physical) solutions minimizing the Gibbs free-energy functional form an infinite set and are labelled by a topological number Nv=0,1,2,... Mathematically, they can be interpreted as nontrivial ''vacuum'' (Nv=0) and static topological solitons (Nv=1,2,...) of the sine-Gordon equation for the phase difference in a finite spatial interval: solutions of this kind were not considered in previous literature. Physically, they represent the Meissner state (Nv=0) and Josephson vortices (Nv=1,2,...). Major properties of the new physical solutions are thoroughly discussed. An exact, closed-form analytical expression for the Gibbs free energy is derived and analyzed numerically. Unstable (saddle-point) solutions are also classified and discussed.Comment: 17 pages, 4 Postscript figure

Universal Crossover between Efros-Shklovskii and Mott Variable-Range-Hopping Regimes

A universal scaling function, describing the crossover between the Mott and the Efros-Shklovskii hopping regimes, is derived, using the percolation picture of transport in strongly localized systems. This function is agrees very well with experimental data. Quantitative comparison with experiment allows for the possible determination of the role played by polarons in the transport.Comment: 7 pages + 1 figure, Revte

Surgical treatment of extended spongy urethral strictures in men: minimizing the risks of narrowing in the anastomotic zones between the buccal graft and the native urethra using the dorsal inlay technique

Introduction. Currently, the most common method of treating extended urethral strictures is augmentation urethroplasty using oral mucosa grafts. Analysis of the long-term outcomes of this surgery type shows a high incidence of relapses and complications.Purpose of the study. To improve the outcomes of augmentation urethroplasty, in particular the dorsal inlay (Asopa) technique, in patients with extended spongy urethral strictures by minimizing the risk of recurrent strictures.Materials and methods. The study is based on an analysis of the surgery in 90 patients (aged 18-72 years) with extended spongy urethral strictures. Seventy patients (group I) underwent dorsal inlay augmentation urethroplasty according to the Asopa technique, and 20 patients (group II) — according to the author's modified technique. Statistical data analysis was carried out using the SPSS ver.26 software (SPSS Inc. Chicago, IL, USA).Results. A comparative analysis of the course of the early postoperative period showed a lower number of complications in group II patients compared to group I — 20.0% versus 34.3%, respectively. The recurrent strictures were registered for groups I and II in 18.8% and 5.6% of cases 6 months after surgery, respectively. The recurrent urethral narrowing was most often localized in the area of distal anastomosis between the buccal graft and the native urethra in patients from both groups.Conclusion. The modified dorsal inlay augmentation urethroplasty technique developed and implemented in clinical practice by increasing the internal urethral lumen in the areas of proximal and distal anastomosis between the buccal graft and the native spongy urethral body allows minimizing the risks of recurrent urethral narrowing after augmentation urethroplasty

Pathomorphism of buccal grafts used in surgery of extensive bulbar urethral strictures: immunohistochemical analysis

Introduction. The adverse effects of urine on unadapted tissues are known. This is also entirely relevant for buccal grafts used in augmentation urethroplasty, where these effects have not been thoroughly studied so far.Objective. To assess the ongoing pathomorphosis in buccal grafts used for urethral augmentation of extensive strictures in the bulbous region and to evaluate how much urine influences their histological transformation following surgery.Materials & methods. The study included 15 patients with extensive strictures of the bulbous urethra, who underwent a two-stage augmentation urethroplasty with buccal grafts. The grafts pathomorphosis was studied 6 months after the first surgery stage where urethrotomy had been performed with graft augmentation of the dorsal semicircle and the formation of distal and proximal neomeatuses. Natural urination through the latter was restored on days 14 – 20 following the surgery. During the second stage, six months later, urethral tubularisation was performed with two preliminary biopsies of the proximal and distal segments of the grafts implanted in the areas of the neomeatuses formed earlier. The distal area of the graft had no contact with urine, while this contact has occurred in the proximal segment since restoration of natural urination. In biopsy specimens, pathomorphosis of the grafts was studied using immunohistochemical markers: vimentin, clone SRL33; CD34, clone QBEnd/10; MSA HHF-35; СD3, clone LN10; Bcl-2, clone bcl-2\100\D5; CK-HMW 34BE-12.Results. It was found that inflammation was minimal in areas of grafts implanted that had no contact with urine, while in areas where such contact occurred it was verified to be pronounced even 6 months after the operation. On the submucosal level, this was manifested by an uneven arrangement of collagen fibers, a dysplastically developed vascular network, uneven proliferation of the endothelium with swelling and loss of cellular connectivity, in contrast to areas where there was no contact with urine. In such areas, the graft submucosa had a dense collagen framework with organized microvasculature and uniform epithelial surface.Conclusion. The impact of urine on buccal grafts used in augmentation urethroplasty is characterised by the disorganisation of its collagen framework, with a pronounced inflammatory component and the “reactivity” of the epithelial lining to the “toxic agent” that persists even 6 months after surgery. This may underlie the risk of a stenosis relapse in the proximal anastomosis area

Precise measurement of RudsR_{\text{uds}} and RR between 1.84 and 3.72 GeV at the KEDR detector

The present work continues a series of the KEDR measurements of the $R$ value that started in 2010 at the VEPP-4M $e^+e^-$ collider. By combining new data with our previous results in this energy range we measured the values of $R_{\text{uds}}$ and $R$ at nine center-of-mass energies between 3.08 and 3.72 GeV. The total accuracy is about or better than $2.6\%$ at most of energy points with a systematic uncertainty of about $1.9\%$. Together with the previous precise $R$ measurement at KEDR in the energy range 1.84-3.05 GeV, it constitutes the most detailed high-precision $R$ measurement near the charmonium production threshold.Comment: arXiv admin note: text overlap with arXiv:1610.02827 and substantial text overlap with arXiv:1510.0266

Clinico-immunological compensatory reactions in reproductive age women with acute salpingitis

Aim of the study: investigation of clinico-immunological peculiarities of compensatory and adaptive reactions in reproductive age women with acute salpingitis. Patients and methods. Opened comparative cohort study was performed in general gynecology department of City Hospital №7 and Clinical-Diagnotics Center (Ekaterinburg). Overall 70 women were enrolled in the present study. 36 patients with acute bilateral salpingitis urgently hospitalized to the gynecology department (median age 23 years, interquartile range 20-28 years) were included in the study group. Control group consisted of 34 women without somatic and gynecological disorders (median age 26 years, interquartile range 25-29 years). Results. Neutrophilic phagocytes number increase (p=0,012) as well as decrease of CD19+, CD20+, CD3+, CD4+, CD8+-lymphocytes absolute count (p<0.001, p<0.001, p=0.014, p=0.031 and p=0.012 respectively) and IgG (p=0.012) were observed as the general adaptive reaction. In acute salpingitis during immune response development Th1 -response predominates over humoral immunity. Immunological parameters as well as clinical signs could indicate severity of the disease. Thus compensatory reaction in women with acute salpingitis consisted of circulating immune complexes formation, neutrophilic phagocytosis increase and Th1-response prevalence was identified.Цель работы состоит в изучении клинико-иммуннологических особенностей компенсаторных и адаптивных реакций при остром сальпингите у женщин репродуктивного возраста. Материал и методы. Проведено открытое, сравнительное, когортное исследование на базе отделения общей гинекологии МУ ЦГБ № 7 и МУ «Клинико-диагностический центр», г.Екатеринбург. Всего в исследуемые группы было включено 70 женщин. 1-ая (основная, п=36) группа - пациентки с диагнозом острый двусторонний сальпингит, поступившие в отделения общей гинекологии МУ ЦГБ № 7 в неотложном порядке - средний возраст ME 23 (р2520 - р7528). 2-ую группу (контрольную, п=34) составили женщины, не имевшие соматических и гинекологических заболеваний - средний возраст ME 26 (р2525 - р7529). Общей адаптивной реакцией при остром сальпингите является повышение численности фагоцитарных нейтрофилов (где р=0,012), снижение содержания иммуноглобулина G (р=0,012) и CD19+, CD20+ В-лимфоцитов (р=0,0001), и уменьшение численности CD3+, CD4+, CD8+ -лимфоцитов (р=0,014, р=0,031, р=0,012 соответственно). При формировании иммунного ответа при остром сальпингите преобладает Th-1 клеточный иммунитет над гуморальным. Иммунологические показатели наряду с общеклиническими могут указывать на тяжесть заболевания. Установлена компенсаторная реакция при остром сальпингите: образование ЦИК, повышение нейтрофильного фагоцитоза, преобладание Th-1 порядка

End-Tagging of Ultra-Short Antimicrobial Peptides by W/F Stretches to Facilitate Bacterial Killing

BACKGROUND: Due to increasing resistance development among bacteria, antimicrobial peptides (AMPs), are receiving increased attention. Ideally, AMP should display high bactericidal potency, but low toxicity against (human) eukaryotic cells. Additionally, short and proteolytically stable AMPs are desired to maximize bioavailability and therapeutic versatility. METHODOLOGY AND PRINCIPAL FINDINGS: A facile approach is demonstrated for reaching high potency of ultra-short antimicrobal peptides through end-tagging with W and F stretches. Focusing on a peptide derived from kininogen, KNKGKKNGKH (KNK10) and truncations thereof, end-tagging resulted in enhanced bactericidal effect against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Through end-tagging, potency and salt resistance could be maintained down to 4-7 amino acids in the hydrophilic template peptide. Although tagging resulted in increased eukaryotic cell permeabilization at low ionic strength, the latter was insignificant at physiological ionic strength and in the presence of serum. Quantitatively, the most potent peptides investigated displayed bactericidal effects comparable to, or in excess of, that of the benchmark antimicrobial peptide LL-37. The higher bactericidal potency of the tagged peptides correlated to a higher degree of binding to bacteria, and resulting bacterial wall rupture. Analogously, tagging enhanced peptide-induced rupture of liposomes, particularly anionic ones. Additionally, end-tagging facilitated binding to bacterial lipopolysaccharide, both effects probably contributing to the selectivity displayed by these peptides between bacteria and eukaryotic cells. Importantly, W-tagging resulted in peptides with maintained stability against proteolytic degradation by human leukocyte elastase, as well as staphylococcal aureolysin and V8 proteinase. The biological relevance of these findings was demonstrated ex vivo for pig skin infected by S. aureus and E. coli. CONCLUSIONS/SIGNIFICANCE: End-tagging by hydrophobic amino acid stretches may be employed to enhance bactericidal potency also of ultra-short AMPs at maintained limited toxicity. The approach is of general applicability, and facilitates straightforward synthesis of hydrophobically modified AMPs without the need for post-peptide synthesis modifications

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

BACKGROUND: Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. METHODS: The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. RESULTS: The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. CONCLUSION: The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients

Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?

Transverse (t)-tubules are invaginations of the plasma membrane that form a complex network of ducts, 200–400 nm in diameter depending on the animal species, that penetrates deep within the cardiac myocyte, where they facilitate a fast and synchronous contraction across the entire cell volume. There is now a large body of evidence in animal models and humans demonstrating that pathological distortion of the t-tubule structure has a causative role in the loss of myocyte contractility that underpins many forms of heart failure. Investigations into the molecular mechanisms of pathological t-tubule remodelling to date have focused on proteins residing in the intracellular aspect of t-tubule membrane that form linkages between the membrane and myocyte cytoskeleton. In this review, we shed light on the mechanisms of t-tubule remodelling which are not limited to the intracellular side. Our recent data have demonstrated that collagen is an integral part of the t-tubule network and that it increases within the tubules in heart failure, suggesting that a fibrotic mechanism could drive cardiac junctional remodelling. We examine the evidence that the linkages between the extracellular matrix, t-tubule membrane and cellular cytoskeleton should be considered as a whole when investigating the mechanisms of t-tubule pathology in the failing heart