Type IIB Research Articles

Lumbosacral transitional vertebrae of 3096 individuals: Prevalence and morphology in a South African population and its association with population affinity

PurposeThis study sought to establish the prevalence and morphological characteristics of lumbosacral transitional vertebrae (LSTV) in the South African population and its correlation with South African's population affinities. MethodsA retrospective review was performed of 3096 consecutive thoracic-abdominal-pelvic radiographs at two large public hospitals in South Africa. Categorisation of LSTV was classified according to Castellvi et al. (1984): types II, III, and IV with unilateral (A) or bilateral (B) subtypes present. The three largest South African population groups (participant self-identified), namely Black African, Coloured and White population affinities were equally sampled, comprising 1032 radiographs for each population affinity. ResultsThe overall prevalence of LSTV was 10 % (N = 308 of 3096). Prevalence by classification/type was 67.9 %, 27.6 % and 4.5 % for II, III, and IV, respectively. The most prevalent subtype was Type IIA (41.9 %), Type IIB (26 %), Type IIIB (21.8 %), and Type IV (5.8 %), respectively. Prevalence by frequency of side was bilateral (47.7 %), left (26.6 %), right (21.1 %), while 4.5 % could not be sided (Type IV morphology). The sex distribution was 53.9 % (166/308) female and 46.1 % (142/308) male. Prevalence by population affinity was 10.5 %, 9.3 % and 9.9 % for the Black African, Coloured and White population affinities, respectively. Analyses of all groups found that the Black African and Coloured populations demonstrated two statistically significant results: greater affinity for the prevalence of sacralisation (95 % CI: 0.396–4.33, p = 0.008), and sacralisation amongst males (95 %, CI: 0.42–3.36, p = 0.010). ConclusionThis study was the first dedicated study of LSTV prevalence in a South African population. There was no significant difference in the prevalence of LSTV between the three largest population groups. Statistically, sacralisation was observed in greater proportions in the Black African and Coloured populations, particularly among males.

A novel type IIb L-asparaginase from Latilactobacillus sakei LK-145: characterization and application.

We succeeded in homogeneously expressing and purifying L-asparaginase from Latilactobacillus sakei LK-145 (Ls-Asn1) and its mutated enzymes C196S, C264S, C290S, C196S/C264S, C196S/C290S, C264S/C290S, and C196S/C264S/C290S-Ls-Asn1. Enzymological studies using purified enzymes revealed that all cysteine residues of Ls-Asn1 were found to affect the catalytic activity of Ls-Asn1 to varying degrees. The mutation of Cys196 did not affect the specific activity, but the mutation of Cys264, even a single mutation, significantly decreased the specific activity. Furthermore, C264S/C290S- and C196S/C264S/C290S-Ls-Asn1 almost completely lost their activity, suggesting that C290 cooperates with C264 to influence the catalytic activity of Ls-Asn1. The detailed enzymatic properties of three single-mutated enzymes (C196S, C264S, and C290S-Ls-Asn1) were investigated for comparison with Ls-Asn1. We found that only C196S-Ls-Asn1 has almost the same enzymatic properties as that of Ls-Asn1 except for its increased stability for thermal, pH, and the metals NaCl, KCl, CaCl2, and FeCl2. We measured the growth inhibitory effect of Ls-Asn1 and C196S-Ls-Asn1 on Jurkat cells, a human T-cell acute lymphoblastic leukemia cell line, using L-asparaginase from Escherichia coli K-12 as a reference. Only C196S-Ls-Asn1 effectively and selectively inhibited the growth of Jurkat T-cell leukemia, which suggested that it exhibited antileukemic activity. Furthermore, based on alignment, phylogenetic tree analysis, and structural modeling, we also proposed that Ls-Asn1 is a so-called "Type IIb" novel type of asparaginase that is distinct from previously reported type I or type II asparaginases. Based on the above results, Ls-Asn1 is expected to be useful as a new leukemia therapeutic agent.

Supersymmetric AdS solitons and the interconnection of different vacua of N\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\mathcal{N} $$\\end{document} = 4 Super Yang-Mills

We find AdS soliton solutions in 5-dimensional gauged supergravity, obtained from the S5 compactification of type IIB, with a dilaton saturating the Breitenlohner-Freedman bound. The solutions depend on the value of the periodicity of an S1 cycle and the boundary values for two U(1) gauge fields, and give a scalar VEV in the dual field theory. At certain values of the gauge sources we have supersymmetric solutions, corresponding to supersymmetric flows, which are a deformation of the Coulomb Branch flow in N\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\mathcal{N} $$\\end{document} = 4 SYM. The solutions parameterize quantum phase transitions between a discrete spectrum phase, a continuous above a mass gap phase, and a continuous without a mass gap phase, in 2+1 dimensions. We analyze the phase diagram in terms of the QFT sources and we find that for every value for them, there are always two branches of supergravity solutions. We find that these two branches of solitons correspond to two possible vacua existing in the dual QFT when fermions are anti-periodic on an S1. We describe the interconnection of these states in the QFT at strong ’t Hooft coupling in the large N limit. In 10 dimensions, our solutions are related to deformations of D3-brane distributions.

On the intermediate Jacobian of M5-branes

We study Euclidean M5-branes wrapping vertical divisors in elliptic Calabi-Yau fourfold compactifications of M/F-theory that admit a Sen limit. We construct these Calabi-Yau fourfolds as elliptic fibrations over coordinate flip O3/O7 orientifolds of toric hypersurface Calabi-Yau threefolds. We devise a method to analyze the Hodge structure (and hence the dimension of the intermediate Jacobian) of vertical divisors in these fourfolds, using only the data available from a type IIB compactification on the O3/O7 Calabi-Yau orientifold. Our method utilizes simple combinatorial formulae (that we prove) for the equivariant Hodge numbers of the Calabi-Yau orientifolds and their prime toric divisors, along with a formula for the Euler characteristic of vertical divisors in the corresponding elliptic Calabi-Yau fourfold. Our formula for the Euler characteristic includes a conjectured correction term that accounts for the contributions of pointlike terminal ℤ2 singularities corresponding to perturbative O3-planes. We check our conjecture in a number of explicit examples and find perfect agreement with the results of direct computations.

D6 branes wrapped on a spindle and Yp,q manifolds

We present new solutions of 8d gauged supergravity which, upon uplift to type IIA, represent D6 branes wrapped on spindles. A further circle uplift gives 11d supergravity on a Calabi-Yau three-fold which is the cone over five-dimensional Yp,q manifolds. This highlights a connection between co-homogeneity one Sasaki-Einstein metrics in general dimension and the recently introduced spindle solutions in gauged supergravity. We find that a similar connection also exists for the small resolution of the Calabi-Yau cone over such manifolds.

Binary AdS black holes coupled to a bath in Type IIB

We construct Type IIB string theory setups which, via double holography, realize two gravitational systems in separate AdS spaces which interact with each other and with a non-gravitational bath. We employ top-down string theory solutions with concrete field theory duals in the form of 4d \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathcal{N}$$\\end{document} = 4 SYM BCFTs and a first-principles notion of double holography. The setups are used to realize pairs of ‘near’ and ‘far’ black holes from the perspective of the bath, which exchange Hawking radiation with each other and radiate into the bath. We identify three phases for the entropy in the bath characterized as no island, partial island and full island, and discuss the entropy curves. The setups differ from the black hole binaries observed in gravitational wave experiments but may capture certain aspects.

125 Effects of Saccharmyces yeast postbiotics on nursey pig muscle fiber cross-sectional area and oxidative capacity

Abstract This study aimed to determine effects of dietary supplementation of Saccharomyces yeast postbiotics (celluTEIN, Puretein Bioscience, LLC, Minneapolis, MN) on nursery pig muscle fiber cross-sectional area (CSA), isoform, and succinate dehydrogenase (SDH) staining intensity. Newly weaned pigs [n = 32; 16 barrows and 16 gilts; 21 d of age, body weight (BW) 6.05 ± 0.24 kg] were stratified by BW within sex, placed in individual pens, and randomly assigned to one of two dietary treatments within each two-pig strata. Dietary treatments included pigs supplemented 0 (CON; n = 16) or 175 g/ton (CT; n = 16) of celluTEIN to their standard three-phase nursery ration. Pigs were harvested at d 35 of feeding and the longissimus lumborum muscle was collected for mean SDH staining intensity and immunohistochemistry analyses. Data were analyzed as a completely randomized design with pig as the experimental unit and treatment as the fixed effect. Statistical significance was determined at P ≤ 0.05. There were no treatment effects on type I and type IIB muscle fiber CSA (P > 0.14), but CT pigs had greater type IIA and type IIX muscle fiber CSA compared with CON (P < 0.05). When not analyzed by fiber isoform, pigs fed CT had a greater (P = 0.02) average muscle fiber CSA than CON pigs. There were no treatment effects on muscle fiber type percentage or SDH intensity of all fiber types (P ≥ 0.23); however, when calculated as a muscle fiber CSA ratio, CT type IIA fibers had a smaller ratio (darker staining/µm2) than CON type IIA fibers (P = 0.05). There were no treatment effects for type I, IIX, and IIB ratios (P > 0.21). In conclusion, supplementing Saccharomyces yeast postbiotics during the nursery period increased muscle fiber hypertrophy and type IIA fiber oxidative capacity.

Current dialyzer classification in Japan and mortality risk in patients undergoing hemodialysis

Dialyzers are classified into five types based on their β2-microglobulin clearance rate and albumin sieving coefficient: Ia, Ib, IIa, and IIb. In addition, a new classification system introduced a type S dialyzer. However, limited information is available regarding the impact of dialyzer type on patient outcomes. A cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry database. Total 181,804 patients on hemodialysis (HD) were included in the study, categorized into four groups (type Ia, IIa, IIb, and S). The associations between each group and two-year all-cause mortality were assessed using Cox proportional hazard models. Furthermore, propensity score-matching analysis was performed. By the end of 2019, 34,185 patients on dialysis had died. After adjusting for all confounders, the risk for all-cause mortality was significantly lower in the type IIa, and S groups than in the type Ia group. These significant findings were consistent after propensity score matching. In conclusion, our findings suggest that super high-flux dialyzers, with a β2-microglobulin clearance of ≥ 70 mL/min, may be beneficial for patients on HD, regardless of their albumin sieving coefficient. In addition, type S dialyzers may be beneficial for elderly and malnourished patients on dialysis.Trial registration number: UMIN000018641

On the limitations of non-geometric fluxes to realize dS vacua

In this paper, we perform a systematic and analytical exploration of de Sitter conditions in type IIA compactifications with (non-)geometric fluxes along with the standard NS-NS and RR p-form fluxes. Exploiting the fact that the F-term scalar potential can be written as a bilinear form, we start by studying the most generic case. We find four conditions that the scalar fields and fluxes must satisfy to achieve de Sitter vacua. Particularizing to different configurations, we recover and extend previous results in the literature. We then impose an Ansatz in which the F-terms are proportional to the respective Kähler derivatives. In this set-up we are able to derive additional constraints and to classify the possible dS no-go scenarios in terms of eight axionic fluxes. Individually considering that any of these fluxes can be vanishing or non-vanishing leads to a total of 256 flux configurations. We find that 227 of these 256 possibilities result in a dS no-go scenario. The remaining 29 flux configurations, a priori, do not lead to dS no-go cases and would deserve further investigation.

Molecular choreography: Unveiling the dynamic landscape of type IIA DNA topoisomerases before T-segment passage through all-atom simulations

Type IIA DNA topoisomerases are molecular nanomachines responsible for controlling topological states of DNA molecules. Here, we explore the dynamic landscape of yeast topoisomerase IIA during key stages of its catalytic cycle, focusing in particular on the events preceding the passage of the T-segment. To this end, we generated six configurations of fully catalytic yeast topo IIA, strategically inserted a T-segment into the N-gate in relevant configurations, and performed all-atom simulations.The essential motion of topo IIA protein dimer was characterized by rotational gyrating-like movement together with sliding motion within the DNA-gate. Both appear to be inherent properties of the enzyme and an inbuilt feature that allows passage of the T-segment through the cleaved G-segment. Coupled dynamics of the N-gate and DNA-gate residues may be particularly important for controlled and smooth passage of the T-segment and consequently the prevention of DNA double-strand breaks. QTK loop residue Lys367, which interacts with ATP and ADP molecules, is involved in regulating the size and stability of the N-gate. The unveiled features of the simulated configurations provide insights into the catalytic cycle of type IIA topoisomerases and elucidate the molecular choreography governing their ability to modulate the topological states of DNA topology.

Dramatic Rebrightening of the Type-changing Stripped-envelope Supernova SN 2023aew

Multipeaked supernovae with precursors, dramatic light-curve rebrightenings, and spectral transformation are rare, but are being discovered in increasing numbers by modern night-sky transient surveys like the Zwicky Transient Facility. Here, we present the observations and analysis of SN 2023aew, which showed a dramatic increase in brightness following an initial luminous (−17.4 mag) and long (∼100 days) unusual first peak (possibly precursor). SN 2023aew was classified as a Type IIb supernova during the first peak but changed its type to resemble a stripped-envelope supernova (SESN) after the marked rebrightening. We present comparisons of SN 2023aew’s spectral evolution with SESN subtypes and argue that it is similar to SNe Ibc during its main peak. P-Cygni Balmer lines are present during the first peak, but vanish during the second peak’s photospheric phase, before Hα resurfaces again during the nebular phase. The nebular lines ([O i], [Ca ii], Mg i], Hα) exhibit a double-peaked structure that hints toward a clumpy or nonspherical ejecta. We analyze the second peak in the light curve of SN 2023aew and find it to be broader than that of normal SESNe as well as requiring a very high 56Ni mass to power the peak luminosity. We discuss the possible origins of SN 2023aew including an eruption scenario where a part of the envelope is ejected during the first peak and also powers the second peak of the light curve through interaction of the SN with the circumstellar medium.

The effect of Ding’s screws and tension band wiring for treatment of olecranon fractures: a biomechanical study

Although tension band wiring (TBW) is popular and recommended by the AO group, the high rate of complications such as skin irritation and migration of the K-wires cannot be ignored. Ding’s screw tension band wiring (DSTBW) is a new TBW technique that has shown positive results in the treatment of other fracture types. The objective of this study was to evaluate the stability of DSTBW in the treatment of olecranon fractures by biomechanical testing. We conducted a Synbone biomechanical model by using three fixation methods: DSTBW, intramedullary screw and tension band wiring (IM-TBW), and K-wire TBW, were simulated to fix the olecranon fractures. We compared the mechanical stability of DSTBW, IM-TBW, and TBW in the Mayo Type IIA olecranon fracture Synbone model using a single cycle loading to failure protocol or pullout force. During biomechanical testing, the average fracture gap measurements were recorded at varying flexion angles in three different groups: TBW, IM-TBW, and DSTBW. The TBW group exhibited measurements of 0.982 mm, 0.380 mm, 0.613 mm, and 1.285 mm at flexion angles of 0°, 30°, 60°, and 90° respectively. The IM-TBW group displayed average fracture gap measurements of 0.953 mm, 0.366 mm, 0.588 mm, and 1.240 mm at each of the corresponding flexion angles. The DSTBW group showed average fracture gap measurements of 0.933 mm, 0.358 mm, 0.543 mm, and 1.106 mm at the same flexion angles. No specimen failed in each group during the cyclic loading phase. Compared with the IM-TBW and TBW groups, the DSTBW group showed significant differences in 60° and 90° flexion angles. The mean maximum failure load was 1229.1 ± 110.0 N in the DSTBW group, 990.3 ± 40.7 N in the IM-TBW group, and 833.1 ± 68.7 N in the TBW group. There was significant difference between each groups (p < 0.001).The average maximum pullout strength for TBW was measured at 57.6 ± 5.1 N, 480.3 ± 39.5 N for IM-TBW, and 1324.0 ± 43.8 N for DSTBW. The difference between maximum pullout strength of both methods was significant to p < 0.0001. DSTBW fixation provides more stability than IM-TBW and TBW fixation models for olecranon fractures.

Keystone flap: Suitable option for coverage of soft tissue defect over Tendo Achilles following open repair

Introduction: Wound complications are not uncommon following operative Tendo Achilles repair. Patients presented in Plastic surgery department with soft tissue defect on Tendo achilles region with exposed Tendon. The paucity of tissue and poor blood circulation are main challenges for the reconstructive surgeon. The study aimed to evaluate the Keystone flap for soft tissue coverage of defects following Tendo achilles repair. Methods: This prospective study was conducted on January 2021 to December 2022 in Plastic surgery department of Rajshahi Medical College Hospital and all 12 cases were done by single surgeon. All patients had history of repair for ruptured Tendo Achilles and were presented with defect over Tendo achilles near or at its insertion, where the defect length was larger than width. Keystone flap type IIA was done for each defect. Results: Mean age of the study patients was 43.42 ±9.79 years. The highest dimension of wound was 36.80 (8 X 4.6) cm2 and flap was 66 (10 X 6.6) cm2. The range of advancement of flap was 3- 4.6 cm (mean: 3.43 ±0.54 cm) in transverse axis of leg. Mean duration of operative time was 53.58± 10.06 minutes. Follow up period was 3 months to measure outcome the flap. Conclusion: The keystone flap has high survivability rate with low complications rate providing with good functional outcome of joint. So, keystone flap is a suitable option for coverage of soft tissue defects following operative Tendo Achilles repair. J Bangladesh Coll Phys Surg 2024; 42: 155-160

Experimental investigation of tension-reducing effectiveness of keystone perforator island flap.

Nowadays, the reconstruction of large and complex defects with keystone perforator island flaps (KPIF) has gained popularity in plastic and reconstructive surgery. The keystone perforator island flap was described as a curvilinear shaped trapezoidal design flap, with two V-Y advancement flaps end-to-side. It is a multiperforator advancement flap, based on multiple fasciocutaneous or musculocutaneous perforators, described by Behan in 2003. These flaps have a simple harvest technique, an easy-to-implement design, and they are time and cost-saving. Their blood supply lends a versatile and robust character, with less complications. Nonetheless, their biomechanical properties and effectiveness are unclear, the wound-closure tension-reducing effect is not well documented in existing literature. The present study aims to investigate the wound closure tension-reducing effect of type I, type IIA, type Sidney Melanoma Unit I (SMU) and type SMU II KPIFs. The main purpose of this study was to clarify the tension-reducing effect of the KPIF technique, which can contribute to the understanding of the biomechanical benefits of the KPIF. This is an experimental, in vivo study, based on twelve white race porcine models (PIC-FII-377), as their anatomy and wound healing process is very similar to that of humans. In this study, 42 wounds that could not be closed by primary wound closure, known as 'unclosable' elliptical defects, were created in six different anatomical regions. The criteria used for not achieving primary wound closure were the breaking of 0 nylon suture or the edges of the wound. Each defect was closed with different types of keystone perforator island flap: type I, type IIA, type Sydney Melanoma Unit I and type Sydney Melanoma Unit II. Keystone perforator island flaps were used in 42 cases. Intraoperative tissue tension was measured by an AXIS FB50, 50 N force gauge tensiometer. In all cases a wide elliptical excision was performed for the primary defect. Before reconstruction, tissue tension was measured across the widest point of the elliptical primary defect. Skin incision was performed for the first flap, without division of deep fascia. After preparing first flap, tension was measured at the widest point of the wound. Furthermore, deep fascia for the second flap was divided, tissue tension across the widest point of the primary defect was measured. Finally, tension was measurement across the widest point of the donor-site after closure of the defect-side flap and V-Y closure of either end of keystone perforator island flap. In this study were included 12 porcine model (PIC-FII-377). A number of 42 keystone perforator island flaps were performed in this study, in six different anatomical regions, ranging between 3.3 x 12 cm and 16 x 30 cm. All elliptical defects were unclosable, with varying sizes ranging between 2 x 4 cm and 8 x 20 cm. The mean tension that was required to close all wounds with primary closure initially was 24.51 N 10.73 N. After using a type I KPIF a tension decrease of -7.04 N ± 4.93 N was seen, in the case of type IIA KPIF the tension decreased to -12.43 N± 5.63 N. Furthermore, after reconstruction with type SMU I KPIF the tension decreased to -7.38N ± 5.21N. After using a type SMU II KPIF a tension decrease of -10.52 N± 5.74 N was seen. The main purpose of this study was to clarify the tension-reducing effect of the KPIF technique, which can contribute to the understanding of the biomechanical benefits of the KPIF. The outcomes of the present study suggest that type I, type IIA, type SMU I, and SMU II of keystone perforator island flaps have a significant tension-reducing effects, especially the technique that involves the division of the deep fascia. The results of this experimental research thoroughly explain the benefits of these flaps. The effectiveness of the flap and doubts on biomechanical properties have not been answered so far. It will encourage more plastic surgeons to use the flap, especially given its proven benefits.

Accelerated sarcopenia precedes learning and memory impairments in the P301S mouse model of tauopathies and Alzheimer's disease.

Alzheimer's disease (AD) impairs cognitive functions and peripheral systems, including skeletal muscles. The PS19 mouse, expressing the human tau P301S mutation, shows cognitive and muscular pathologies, reflecting the central and peripheral atrophy seen in AD. We analysed skeletal muscle morphology and neuromuscular junction (NMJ) through immunohistochemistry and advanced image quantification. A factorial Analysis of Variance assessed muscle weight, NCAM expression, NMJ, myofibre type distribution, cross-sectional areas, expression of single or multiple myosin heavy-chain isoforms, and myofibre grouping in PS19 and wild type (WT) mice over their lifespan (1-12months). Significant weight differences in extensor digitorum longus (EDL) and soleus muscles between WT and PS19 mice were noted by 7-8months. For EDL muscle in females, WT weighed 0.0113±0.0005 compared with PS19's 0.0071±0.0008 (P<0.05), and in males, WT was 0.0137±0.0001 versus PS19's 0.0069±0.0006 (P<0.005). Similarly, soleus muscle showed significant differences; females (WT: 0.0084±0.0004; PS19: 0.0057±0.0005, P<0.005) and males (WT: 0.0088±0.0003; PS19: 0.0047±0.0004, P<0.0001). Analysis of the NMJ in PS19 mice revealed a marked reduction in myofibre innervation at 5months, with further decline by 10months. NMJ pre-terminals in PS19 mice became shorter and simpler by 5months, showing a steep decline by 10months. Genotype and age strongly influenced muscle NCAM immunoreactivity, denoting denervation as early as 5-6months in EDL muscle Type II fibres, with earlier effects in soleus muscle Type I and II fibres at 3-4months. Muscle denervation and subsequent myofibre atrophy were linked to a reduction in Type IIB fibres in the EDL muscle and Type IIA fibres in the soleus muscle, accompanied by an increase in hybrid fibres. The EDL muscle showed Type IIB fibre atrophy with WT females at 1505±110μm2 versus PS19's 1208±94μm2, and WT males at 1731±185μm2 versus PS19's 1227±116μm2. Similarly, the soleus muscle demonstrated Type IIA fibre atrophy from 5 to 6months, with WT females at 1194±52μm2 versus PS19's 858±62μm2, and WT males at 1257±43μm2 versus PS19's 1030±55μm2. Atrophy also affected Type IIX, I+IIA, and IIA+IIX fibres in both muscles. The timeline for both myofibre and overall muscle atrophy in PS19 mice was consistent, indicating a simultaneous decline. Progressive and accelerated neurogenic sarcopenia may precede and potentially predict cognitive deficits observed in AD.

Differentially co-expressed myofibre transcripts associated with abnormal myofibre proportion in chronic obstructive pulmonary disease.

Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD. Forty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype. Abnormal myofibre proportion was defined in males with COPD (n=29) as <18% type I and/or >22% type IIx/IIax fibres and in females with COPD (n=17) as <36% type I and/or >12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0kg, P=0.022), 6-min walk distance (300 vs. 353m, P=0.039) and forced expiratory volume in 1s-to-forced vital capacity ratio (0.42 vs. 0.48, P=0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density. Our findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

Hampshire Sheep as a Large-Animal Model for Cochlear Implantation.

Sheep have been proposed as a large-animal model for studying cochlear implantation. However, prior sheep studies report that the facial nerve (FN) obscures the round window membrane (RWM), requiring FN sacrifice or a retrofacial opening to access the middle-ear cavity posterior to the FN for cochlear implantation. We investigated surgical access to the RWM in Hampshire sheep compared to Suffolk-Dorset sheep and the feasibility of Hampshire sheep for cochlear implantation via a facial recess approach. Sixteen temporal bones from cadaveric sheep heads (ten Hampshire and six Suffolk-Dorset) were dissected to gain surgical access to the RWM via an extended facial recess approach. RWM visibility was graded using St. Thomas' Hospital (STH) classification. Cochlear implant (CI) electrode array insertion was performed in two Hampshire specimens. Micro-CT scans were obtained for each temporal bone, with confirmation of appropriate electrode array placement and segmentation of the inner ear structures. Visibility of the RWM on average was 83% in Hampshire specimens and 59% in Suffolk-Dorset specimens (p = 0.0262). Hampshire RWM visibility was Type I (100% visibility) for three specimens and Type IIa (> 50% visibility) for seven specimens. Suffolk-Dorset RWM visibility was Type IIa for four specimens and Type IIb (< 50% visibility) for two specimens. FN appeared to course more anterolaterally in Suffolk-Dorset specimens. Micro-CT confirmed appropriate CI electrode array placement in the scala tympani without apparent basilar membrane rupture. Hampshire sheep appear to be a suitable large-animal model for CI electrode insertion via an extended facial recess approach without sacrificing the FN. In this small sample, Hampshire specimens had improved RWM visibility compared to Suffolk-Dorset. Thus, Hampshire sheep may be superior to other breeds for ease of cochlear implantation, with FN and facial recess anatomy more similar to humans.

Supersymmetric Wormholes in String Theory.

We construct a large family of Euclidean supersymmetric wormhole solutions of type IIB supergravity which are asymptotically AdS_{5}×S^{5}. The solutions are constructed using consistent truncation to maximally gauged supergravity in five dimensions which is further truncated to a four scalar model. Within this model we perform a full analytic classification of supersymmetric domain wall solutions with flat Euclidean domain wall slices. On each side of the wormhole, the solution asymptotes to AdS_{5} dual to N=4 supersymmetric Yang-Mills deformed by a supersymmetric mass term.

Structural basis of DNA crossover capture by Escherichia coli DNA gyrase.

DNA supercoiling must be precisely regulated by topoisomerases to prevent DNA entanglement. The interaction of type IIA DNA topoisomerases with two DNA molecules, enabling the transport of one duplex through the transient double-stranded break of the other, remains elusive owing to structures derived solely from single linear duplex DNAs lacking topological constraints. Using cryo-electron microscopy, we solved the structure of Escherichia coli DNA gyrase bound to a negatively supercoiled minicircle DNA. We show how DNA gyrase captures a DNA crossover, revealing both conserved molecular grooves that accommodate the DNA helices. Together with molecular tweezer experiments, the structure shows that the DNA crossover is of positive chirality, reconciling the binding step of gyrase-mediated DNA relaxation and supercoiling in a single structure.

Revisiting a Realistic Intersecting D6-Brane with Modified Soft SUSY Terms

Because there are a few typos in the supersymmetry-breaking sfermion masses and trilinear soft term, regarding the current Large Hadron Collider (LHC) and dark matter searches, we revisit a three-family Pati–Salam model based on intersecting D6-branes in Type IIA string theory on a T6/(Z2×Z2) orientifold with a realistic phenomenology. We study the viable parameter space and discuss the spectrum consistent with the current LHC Supersymmetry searches and the dark matter relic density bounds from the Planck 2018 data. For the gluinos and first two generations of sfermions, we observe that the gluino mass is in the range [2, 14] TeV, the squarks mass range is [2, 13] TeV and the sleptons mass is in the range [1, 5] TeV. We achieve the cold dark matter relic density consistent with 5σ Planck 2018 bounds via A-funnel and coannihilation channels such as stop–neutralino, stau–neutralino, and chargino–neutralino. Except for a few chargino–neutralino coannihilation solutions, these solutions satisfy current nucleon-neutralino spin-independent and spin-dependent scattering cross-sections and may be probed by future dark matter searches.