Sole Defect Research Articles

Outcomes and Complications of Sole Reconstruction Using Lateral Thoracic Free Tissue Transfer.

The complex structure of the sole of the foot makes the repair of extensive defects challenging. The present study, therefore, aimed to address a gap in current research by evaluating the potential of the lateral thoracic free flap, including perforator options and chimeric configurations, to be used as an advanced solution for comprehensive sole reconstruction. We retrospectively collected the following data from the charts of patients with sole defects, due to various causes, who underwent lateral thoracic free tissue transfers: patient demographics; etiologies; comorbidities; flap types and dimensions; pedicle length; operative time; follow-up period; complications; and management. The present study included 54 patients who underwent lateral thoracic free tissue transfer, citing infection, trauma, tumor, and posttraumatic sequelae as the major etiologies. We used the following techniques for the reconstruction of sole defects: thoracodorsal artery perforator free flap (83.3%); latissimus dorsi musculocutaneous free flap (1.9%); and various chimeric pattern flaps (14.8%). Free tissue transfer in the lateral thoracic region offers versatility for reconstruction, as well as low donor site morbidity. Complications observed in the present study included wound dehiscence (9.3%), partial necrosis (9.3%), and pressure ulcers (22.2%), although most patients healed favorably without flap loss. The lateral thoracic free flap is a viable option for the reconstruction of the sole of the foot and allows for the effective reconstruction of complex defects. It contains a sustainable skin paddle, and multiple components can be easily included as a chimeric type. Further studies should seek to identify ways to prevent pressure ulcers, which was the only known long-term complication in the present study.

Abstract A061: Grb7 is dispensible for normal development and ERBB2-driven mammary tumorigenesis, but maternal Grb7 deletion causes lactational insufficiency

Abstract Growth factor receptor-bound 7 (Grb7) is an adaptor protein implicated in signal transduction downstream of multiple receptor tyrosine kinases, including ERBB, FGFR and PDGFR pathways. Experimental studies have implicated Grb7 in regulating cell proliferation, survival, migration, and invasion through its large repertoire of protein-protein interactions. Here, we describe the generation and characterization of a Grb7 knockout (KO) mouse. These mice are viable and fertile. A lacZ knock-in reporter was used to visualize Grb7 promoter activity patterns in adult tissues, indicating widespread Grb7 expression in glandular epithelium, the central nervous system and other tissues. The sole defect observed in these animals was a failure of Grb7 KO females to successfully raise pups to weaning age, a phenotype that was independent of both paternal and pup genotypes. These data suggest a regulatory role for Grb7 in mammary lactational physiology. Grb7 is genomically adjacent to ERBB2 and commonly co-amplified with ERBB2 in human breast cancer. This adaptor protein physically interacts with ERBB2 and has been implicated in oncogenic signal propagation to intracellular pathways. We intercrossed Grb7 KO and MMTV-Neu mice to determine whether Grb7 is required for ERBB2-driven tumorigenesis. Surprisingly, there was no difference in time to tumor detection between cohorts, indicating that Grb7 is not obligately required for ERBB2-driven tumorigenesis. In conclusion, despite a considerable body of literature suggesting key roles for Grb7 in signal transduction pathways involved in both normal and malignant processes, our analysis of Grb7 KO mice demonstrates that Grb7 is largely dispensable for both development and ERBB2-driven tumorigenesis. These data raise the possibility that other Grb family members, Grb10 and Grb14, might compensate for Grb7 loss. Accordingly, a comprehensive assessment of all Grb family members may be needed to fully clarify their physiological roles. Citation Format: Kristopher A. Lofgren, Peter Feiszt, Paraic A. Kenny. Grb7 is dispensible for normal development and ERBB2-driven mammary tumorigenesis, but maternal Grb7 deletion causes lactational insufficiency [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A061.

The Value of Anterolateral Thigh Free Flap for the Reconstruction of Malignant Melanoma of the Sole of the Foot.

Wide excision of malignant melanoma on the foot usually results in an extensive function-destroying defect, and the reconstruction of foot defects remains challenging for reconstructive surgeons. We propose using anterolateral thigh perforator (ALT) free flaps for the reconstruction of widespread defects caused by malignant melanoma in the sole. This retrospective study included 34 patients who underwent reconstruction of sole defects caused by malignant melanoma resection with 35 ALT perforator free flaps between August 2005 and July 2021. In total, 18 male patients and 16 female patients were included (mean age at surgery, 65.4 years). The mean size of the flaps was 100.4 cm 2 . Thirty-three of the 35 flaps survived. Hematoma, seroma, and chronic ulceration were not identified in any cases. All patients achieved independent ambulation within the follow-up period, except 1 patient with gait discomfort. The 5-year overall and disease-free survival rates of patients were 64.4% and 56.6%, respectively. The ALT flap is a versatile surgical option that should be considered for reconstruction of the sole after malignant melanoma resection, considering its various surgical advantages and the functional aspects of independent ambulation, the aesthetic aspects of wearing conventional footwear, and the anatomical aspects of the sole.

Grb7 knockout mice develop normally but litters born to knockout females fail to thrive.

Growth factor receptor-bound 7 (Grb7) is an adaptor protein involved in signal transduction downstream of multiple receptor tyrosine kinases, including ERBB, FGFR, and PDGFR pathways. Experimental studies have implicated Grb7 in regulating cell proliferation, survival, migration, and invasion through its large repertoire of protein-protein interactions. Here, we describe the generation and characterization of a Grb7 knockout mouse. These mice are viable and fertile. A lacZ knock-in reporter was used to visualize Grb7 promoter activity patterns in adult tissues, indicating widespread Grb7 expression in glandular epithelium, the central nervous system, and other tissues. The sole defect observed in these animals was a failure of Grb7 knockout females to successfully raise pups to weaning age, a phenotype that was independent of both paternal and pup genotypes. These data suggest a regulatory role for Grb7 in mammary lactational physiology.

Implementasi Metode Six Sigma Untuk Menurunkan Cacat Produk Pada Ukm Onetixs

Product quality is a determining factor in customer satisfaction and trust in the products produced. Product defects can cause losses to convection convection. Therefore, this study aims to implementation of Six Sigma method to reduce product defects in Onetixs SMEs. Five stages are used to improve product quality in Onetixs convection, namely Define, Measure, Analyze, Improve, and Control (DMAIC). The results of research on Onetixs convection obtained the type of defect in Onetixs shoes based on the pareto diagram of the highest defects caused by glue stains. Another type of defect is caused by non-sticky soles, and poorly sewn seams. Of the 1040 samples observed, there were 146 defective products caused by 30% non-adhesive sole defects, 38% glue stain defects, and 32% untidy seam defects. Furthermore, the DPMO value of attribute data obtained is 46795 and is at the level of 3.18 sigma. Based on the causes of defects obtained from the fishbone diagram, the proposed improvements given to reduce defects due to glue stains are to improve the quality of work during the shoe gluing process, pay attention to the quality of the glue mixture, pay attention to the quality of the mixture of glue and tools used for gluing, improve the method of gluing, periodically check shoesKeywords: Fishbone Diagram, Pareto Diagram, Quality, Six Sigma

Medial Plantar Artery Flap for Reconstruction of Weight-bearing Sole Defect- A Series of Ten Cases

Weight-bearing areas of feet are at risk of developing ulcers due to various reasons like a neuropathic foot in diabetes mellitus, acute trauma, post-tumour excision etc., Various reconstructive options have been described in literature from split-thickness skin graft to free flap. This case series reports 10 patients with sole defects. Out of 10 patients, seven patients had heel defect and three patients had the plantar aspect of the forefoot defect. For patients with heel defect, authors used a proximally based medial plantar flap as a reconstructive tool while for forefoot sole defect distally based (reverse) Medial Plantar Artery (MPA) flap was used. The most common cause of heel defect was postdebridement defect in diabetic foot in five cases, postmelanoma excision defect in three cases, postsquamous cell carcinoma excision defect in one case and postelectric burn defect in one case. Flap size ranged from 5x5 cm to 10×7 cm. All flaps offered stable, durable, and cosmetically acceptable skin cover. No patient had a recurrent ulcer during follow-up period. Partial flap necrosis in one case was managed conservatively. The MPA flap offers excellent cover which is a sturdy, durable, cosmetically acceptable cover for medium size defect over the sole i.e., the weight-bearing part of forefoot and heel.

Modeling the electrical characteristic of InGaN/GaN blue-violet LED structure under electrical stress

The role of deep defects and their physical origin in InGaN/GaN LED are still widely investigated and debated, in particular their impact on the electrical and optical characteristics and on the reliability of the device. In this paper we evaluate the electrical and optical behavior of a single quantum well InGaN/GaN 420 nm LED during a medium-term accelerated ageing test. From these measurements, an increase in the sub-turn on current was observed: this process was ascribed to the stress-induced generation of defects in proximity of the active region and thus related to an increase of the correlated trap assisted tunneling. Subsequently we modelled the device electrical characteristics, evidencing the fundamental role of deep defects in determining the shape of the I-V curve in low forward bias. We reproduced with high accuracy the experimental current-voltage curves acquired during the ageing test, demonstrating that the increase in forward leakage can be entirely ascribed to the increase in concentration of a sole defect deep level located near midgap. These results provide a better understanding about the defect formation mechanism, that can be used to model and understand the behavior of the devices during ageing.

Subchondral Drilling Independent of Drill Hole Number Improves Articular Cartilage Repair and Reduces Subchondral Bone Alterations Compared With Debridement in Adult Sheep

Background: Subchondral drilling is an established marrow stimulation technique for small cartilage defects, but whether drilling is required at all and if the drill hole density affects repair remains unclear. Hypotheses: Osteochondral repair is improved when the subchondral bone is perforated by a higher number of drill holes per unit area, and drilling is superior to defect debridement alone. Study Design: Controlled laboratory study. Methods: Rectangular full-thickness chondral defects (4 × 8 mm) were created in the trochlea of adult sheep (N = 16), debrided down to the subchondral bone plate without further treatment as controls (no treatment; n = 7) or treated with either 2 or 6 (n = 7 each) subchondral drill holes (diameter, 1.0 mm; depth, 10.0 mm). Osteochondral repair was assessed at 6 months postoperatively by standardized (semi-)quantitative macroscopic, histological, immunohistochemical, biochemical, and micro–computed tomography analyses. Results: Compared with defect debridement alone, histological overall cartilaginous repair tissue quality (P = .025) and the macroscopic aspect of the adjacent cartilage (P≤ .032) were improved after both drilling densities. Only drilling with 6 holes increased type 2 collagen content in the repair tissue compared with controls (P = .038). After debridement, bone mineral density was significantly decreased in the subchondral bone plate (P≤ .015) and the subarticular spongiosa (P≤ .041) compared with both drilling groups. Debridement also significantly increased intralesional osteophyte sectional area compared with drilling (P≤ .034). No other differences in osteochondral repair existed between subchondral drilling with 6 or 2 drill holes. Conclusion: Subchondral drilling independent of drill hole density significantly improves structural cartilage repair compared with sole defect debridement of full-thickness cartilage defects in sheep after 6 months. Subchondral drilling also leads to a better reconstitution of the subchondral bone compartment below the defects. Simultaneously, drilling reduced the formation of intralesional osteophytes caused by osseous overgrowth compared with debridement. Clinical Relevance: These results have important clinical implications, as they support subchondral drilling independent of drill hole number but discourage debridement alone for the treatment of small cartilage defects. Clinical studies are warranted to further quantify the effects of subchondral drilling in similar settings.

Medial plantar artery-based perforator and island flaps: a case series of applications in sole defects.

Soft tissue defects of the plantar foot pose a challenge to the reconstructive surgeon. The plantar region of the foot has a unique skin structure, which helps in its paramount functions of weight-bearing and providing protective sensation. It is best replaced with tissue of its own kind. The medial plantar artery (MPA) flap fulfils all the requirements of an ideal replacement for small-to-medium-sized defects in the mid plantar and heel region. This study describes our experience with MPA-based flaps for small-to-medium-sized defects of the plantar foot. The study was conducted in a tertiary referral hospital between April 2017 and March 2020 on patients who presented with defects on the mid plantar region and heel. MPA perforator (MPAP) flap or island flap were applied. The donor site was covered with split-thickness skin grafts. The study included 21 patients. MPAP flap was applied in nine patients and the island flap was applied in 12 patients. The mean age of the patients was 37.95 years and the mean flap size was 36.6cm2. All flaps survived well. In two patients, venous congestion developed which resolved spontaneously, while three patients had small graft loss which also healed with conservative treatment. All patients regained protective sensation within five months of flap coverage. Based on the MPA, both perforator and island flaps can be raised due to the fairly constant position of the perforators. These flaps have the advantage of robust vascularity with the replacement of identical tissue for weight-bearing functions along with acceptable aesthetic outcomes. Since they also have the added advantage of conferring sensation, they can be used as a primary option in cases of small-to-medium-sized plantar foot defects.

Multifunctional passivation strategy based on tetraoctylammonium bromide for efficient inverted perovskite solar cells

Abstract Inverted perovskite solar cells (PSCs) have significant potential in large-scale production due to their low cost and low-temperature process-ability. Nevertheless, the efficiency of the inverted PSCs suffers from non-ideal light-harvesting, surface recombination, and charge extraction loss. Here, tetraoctylammonium bromide (TOAB) is introduced by a post-treatment strategy to address these challenges. The film properties and the corresponding device performance are systemically studied. The results show that TOAB molecules distribute throughout the perovskite films and thus effectively passivate the trap states at grain boundaries (GBs) and surface. The built-in electrical field (Vbi) of the devices and hydrophobic properties of the perovskite films are enhanced by TOAB molecular arrangement at the perovskite surface. Moreover, the light-harvesting efficiency is also improved via the redistribution of the light field in the PSCs. Benefiting from trap sates passivation, enhanced Vbi and light-harvesting, the champion power conversion efficiency (PCE) of 21.47% is achieved, which is among the reported high efficiencies for inverted PSCs. In addition, device stability has been greatly improved. The PCE of PSCs treated by TOAB can retain 81% of its initial value after 264 h in the air and can retain 94% of its initial value after 71 days in N2. This work represents a novel passivation strategy by post-treatment method without disturbing the perovskite film growth to understand the sole defect effects on the device performance of PSCs.

A comprehensive analysis about thermal conductivity of multi-layer graphene with N-doping, -CH3 group, and single vacancy

Graphene has received great attention due to its fascinating thermal properties. The inevitable defects in graphene, such as single vacancy, doping, and functional group, greatly affect the thermal conductivity. The sole effect of these defects on the thermal conductivity has been widely studied, while the mechanisms of the coupling effects are still open. We studied the combined effect of defects with N-doping, the -CH3 group, and single vacancy on the thermal conductivity of multi-layer graphene at various temperatures using equilibrium molecular dynamics with the Green-Kubo theory. The Taguchi orthogonal algorithm is used to evaluate the sensitivity of N-doping, the -CH3 group, and single vacancy. Sole factor analysis shows that the effect of single vacancy on thermal conductivity is always the strongest at 300 K, 700 K, and 1500 K. However, for the graphene with three defects, the single vacancy defect only plays a significant role in the thermal conductivity modification at 300 K and 700 K, while the -CH3 group dominates the thermal conductivity reduction at 1500 K. The phonon dispersion is calculated using a spectral energy density approach to explain such a temperature dependence. The combined effect of the three defects further decreases the thermal conductivity compared to any sole defect at both 300 K and 700 K. The weaker single vacancy effect is due to the stronger Umklapp scattering at 1500 K, at which the combined effect seriously covers almost all the energy gaps in the phonon dispersion relation, significantly reducing the phonon lifetimes. Therefore, the temperature dependence only appears on the multi-layer graphene with combined defects.

Finsler geometry of topological singularities for multi‐valued fields: Applications to continuum theory of defects

Topological singularity in a continuum theory of defects and a quantum field theory is studied from a viewpoint of differential geometry. The integrability conditions of singularity (Clairaut‐Schwarz‐Young theorem) are expressed by a torsion tensor and a curvature tensor when a Finslerian intrinsic parallelism holds for the multi‐valued function. In the context of the quantum field theory, the singularity called an extended object is expressed by the torsion when the intrinsic parallelism is related to the spontaneous breakdown of symmetry. In the continuum theory of defects, the path‐dependency of point and line defects within a crystal is interpreted by the non‐vanishing condition of torsion tensor in a non‐Riemannian space osculated from the Finsler space, and the domain is not simply connected. On the other hand, for the rotational singularity, an energy integral (J‐integral) around a disclination field is path‐independent when a nonlinear connection is single‐valued. This means that the topological expression for the sole defect (Gauss‐Bonnet theorem with genus ) is understood by the integrability of nonlinear connection.image

Control of GVHD by regulatory T cells depends on TNF produced by T cells and TNFR2 expressed by regulatory T cells

AbstractTherapeutic CD4+Foxp3+ natural regulatory T cells (Tregs) can control experimental graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HCT) by suppressing conventional T cells (Tconvs). Treg-based therapies are currently tested in clinical trials with promising preliminary results in allo-HCT. Here, we hypothesized that as Tregs are capable of modulating Tconv response, it is likely that the inflammatory environment and particularly donor T cells are also capable of influencing Treg function. Indeed, previous findings in autoimmune diabetes revealed a feedback mechanism that renders Tconvs able to stimulate Tregs by a mechanism that was partially dependent on tumor necrosis factor (TNF). We tested this phenomenon during alloimmune response in our previously described model of GVHD protection using antigen specific Tregs. Using different experimental approaches, we observed that control of GVHD by Tregs was fully abolished by blocking TNF receptor type 2 (TNFR2) or by using TNF-deficient donor T cells or TNFR2-deficient Tregs. Thus, our results show that Tconvs exert a powerful modulatory activity on therapeutic Tregs and clearly demonstrate that the sole defect of TNF production by donor T cells was sufficient to completely abolish the Treg suppressive effect in GVHD. Importantly, our findings expand the understanding of one of the central components of Treg action, the inflammatory context, and support that targeting TNF/TNFR2 interaction represents an opportunity to efficiently modulate alloreactivity in allo-HCT to either exacerbate it for a powerful antileukemic effect or reduce it to control GVHD.

Cockayne syndrome group B (CSB) protein: At the crossroads of transcriptional networks

Cockayne syndrome (CS) is a rare genetic disorder characterized by a variety of growth and developmental defects, photosensitivity, cachectic dwarfism, hearing loss, skeletal abnormalities, progressive neurological degeneration, and premature aging. CS arises due to mutations in the CSA and CSB genes. Both gene products are required for the transcription-coupled (TC) branch of the nucleotide excision repair (NER) pathway, however, the severe phenotype of CS patients is hard to reconcile with a sole defect in TC-NER. Studies using cells from patients and mouse models have shown that the CSB protein is involved in a variety of cellular pathways and plays a major role in the cellular response to stress. CSB has been shown to regulate processes such as the transcriptional recovery after DNA damage, the p53 transcriptional response, the response to hypoxia, the response to insulin-like growth factor-1 (IGF-1), transactivation of nuclear receptors, transcription of housekeeping genes and the transcription of rDNA. Some of these processes are also affected in combined XP/CS patients. These new advances in the function(s) of CSB shed light onto the etiology of the clinical features observed in CS patients and could potentially open therapeutic avenues for these patients in the future. Moreover, the study of CS could further our knowledge of the aging process.

Effect of Compound of Gelatin Hydrogel Microsphere Incorporated with Platelet-Rich-Plasma and Alginate on Sole Defect in Cattle

Platelet-rich plasma (PRP) was administered to cattle with hoof defects (10-mm drill hole) to promote sole defect healing. Two types of gels were prepared. One was a mixed gel [compound of gelatin microspheres (GM) incorporated with PRP and alginate] and was used for the test group, while the other was an alginate gel used for the control group. Each hole was filled with one of these gels. The drill hole depth, pressure pain, and hardness of the regenerated tissue were measured for 3 weeks after treatment. These measurements improved significantly in the test group than in the control group. The results suggest that a compound of GM incorporated with PRP and alginate had a hoof-regenerating effect in cattle.

Chronic Exposure to Sulfide Causes Accelerated Degradation of Cytochrome c Oxidase in Ethylmalonic Encephalopathy

Ethylmalonic encephalopathy (EE) is an autosomal recessive, invariably fatal disorder associated with mutations in ETHE1, a gene encoding a mitochondrial sulfur dioxygenase (SDO). The main consequence of the absence of Ethe1-SDO is the accumulation of sulfide (H(2)S) in critical tissues, including colonic mucosa, liver, muscle, and brain. To make progress in the elucidation of the biochemical mechanisms leading to cytochrome c oxidase (COX) deficiency, we (i) generated tissue-specific conditional Ethe1 knockout mice to clarify the different contributions of endogenous and exogenous H(2)S production, and (ii) studied the development of H(2)S-driven COX deficiency in Ethe1(-/-) mouse tissues and human cells. Ethe1(-/-) conditional animals displayed COX deficiency limited to the specific targeted tissue. The accumulation of H(2)S over time causes progressive COX deficiency in animal tissues and human cells, which is associated with reduced amount of COX holoenzyme, and of several COX subunits, including mitochondrially encoded cytochrome c oxidase 1 (MTCO1), MTCO2, COX4, and COX5A. This reduction is not paralleled by consistent downregulation in expression of the corresponding mRNAs. Tissue-specific ablation of Ethe1 causes COX deficiency in targeted organs, suggesting that failure in neutralizing endogenous, tissue-specific production of H(2)S is sufficient to cause the biochemical defect but neither to determine a clinical impact nor to induce the biomarker profile typical of EE. The mechanism by which H(2)S causes COX deficiency consists of rapid heme a inhibition and accelerated long-term degradation of COX subunits. However, the pleiotropic devastating effects of H(2)S accumulation in EE cannot be fully explained by the sole defect of COX in critical tissues, but are likely consequent to several toxic actions on a number of enzymatic activities in different tissues, including endothelial lining of the small vessels, leading to multiorgan failure.

Clonal Hematopoiesis in Philadelphia Chromosome-Negative Bone Marrow Cells of Chronic Myeloid Leukemia Patients Receiving Tyrosine Kinase Inhibitors

Patients with chronic myeloid leukemia (CML) are experiencing prolonged survival due to successful therapy with tyrosine kinase inhibitors. However, some CML patients who have achieved longstanding remissions with these agents harbor clonal cytogenetic abnormalities in their Philadelphia chromosome negative (Ph-) bone marrow cells. Because CML patients in remission often have peripheral blood count abnormalities, including cytopenias, we investigated whether these patients may have developed myelodysplastic syndrome (MDS) within the Ph- cell population. Bone marrow samples from 26 CML patients who had achieved a major cytogenetic remission (MCyR) with tyrosine kinase inhibitor therapy between 2 and 15 years after diagnosis were evaluated; 6 patients had advanced disease prior to their last therapy, 20 were in chronic phase. At the time of evaluation, 2 of the patients were receiving imatinib, 23 dasatinib, and 1 PHA739358. At least one peripheral blood lineage was abnormal in 21 patients, of whom 7 had pancytopenia. Routine metaphase cytogenetics (MC) revealed a persistent clonal chromosomal abnormality in 10% of the Ph- metaphases in 5 patients (+8 in 2, −7 in 2, and 20q- in 1). We hypothesized that clonal hematopoiesis might exist in additional patients and applied single nucleotide array (SNP-A) based karyotyping and X-linked human androgen receptor (HUMARA) clonality assay to further delineate the nature of the hematopoietic defect in these patients. HUMARA was performed on bone marrow samples and germ-line DNA from peripheral blood T lymphocytes of the female patients. Clonality, as assessed by skewing of X-chromosome inactivation in bone marrow cells compared to germline control cells, could not be demonstrated in the12 female patients. SNP-A karyptyping using 250K Affymetrix SNP array confirmed the known cytogenetic abnormalities. Several microdeletions were found, but comparison with purified T lymphocytes demonstrated that these “lesions” represented germ line-encoded copy number variants. However, SNP-A karyotyping revealed the presence of uniparental disomy (UPD) involving chromosome 17(p12-pter) in bone marrow, but not germ line cells, from one male patient with normal karyotype by routine MC. In the context of secondary AML, del17p or UPD17 have been observed always in the presence of del7/q and 5q and were associated with poor prognosis. However, in our patient UPD17 occurred as a sole defect. Because in our studies in AML, UPD of chromosome 17p was found in association with p53 mutations, genomic sequencing of this gene was performed. A 5 bp deletion destroying the splice acceptor region of exon 6 was identified in bone marrow cells from this patient. Alternative splicing leading to loss of exon 6 was predicted to result in a frame shift and premature introduction of a stop codon. These methods revealed clonal hematopoiesis in the Ph- bone marrow cells of 6/26 patients with longstanding CML in remission from tyrosine kinase inhibitors and persistent peripheral blood abnormalities. The approaches used here probably underestimate the frequency of this condition, as oligoclonal populations may be present in numbers below the limit of assay sensitivity. The Ph- clonal bone marrow populations have cytogenetic and molecular features in common with MDS. After a median follow up of two years, one patient with monosomy 7 developed acute myeloid leukemia, but longer follow up will be required to determine the natural history of the Ph- clonal disorders.

Qualification of the inverse problem of defect reconstruction using optimized mesh database

PurposeTo propose a novel method for defect reconstruction in electromagnetic non‐destructive testing (NDT).Design/methodology/approachThe inversion method is based on an optimized database that contains the measured signals for some predefined defect prototypes. The database is supported by an anisotropic simplex mesh, which has been generated adaptively in the abstract n‐dimensional space, spanned by the model parameters of the defect type. The actual reconstruction reduces to a mesh search and interpolation. The described theory is demonstrated in the paper by a solved NDT test problem.FindingsWe have realized that in addition to sole defect reconstruction, the database provides meta‐information about the quality of the inversion, the suitability of the chosen defect model parameters, as well as the capabilities of the testing experiment.Research limitations/implicationsDefect models having several parameters require a sophisticated mesh generation algorithm, which works in higher dimensions.Originality/valueIn the authors' opinion the mesh database approach offers a totally new point of view of a given inverse problem, and may help in the better understanding of its nature.

Variable phenotype related to a novel PAX 6 mutation (IVS4+5G>C) in a family presenting congenital nystagmus and foveal hypoplasia

Several ocular defects have been identified as a consequence of the PAX6 gene mutations. With regard to the implication of this gene in unusual phenotypes, we report a family presenting with congenital nystagmus, foveal hypoplasia, and iris hypoplasia or atypical coloboma. Observational case report. The entire transcribed region of the PAX6 gene was submitted to mutation search at the DNA and mRNA levels in five affected members of a French family in test with 82 normal subjects. A novel heterozygous PAX6 gene splice mutation (IVS4 + 5G>C) was identified. The mutation is located in IVS4 within the consensus donor splice site. A mutant mRNA lacking exon 4 as the sole defect was evidenced. The resultant protein was predicted to contain a cryptic ATG initiation codon in exon 3 and a slightly altered paired-domain in an open reading frame extended by 13 amino acids. The association of anterior segment anomalies and foveal hypoplasia with one of the slightest alterations of the PAX6 protein described to date confirms the association of variant phenotypes with hypomorphic alleles. Mutation screening of the PAX6 gene could be useful in elucidating the origin of complex ocular malformations.

Tissue-specific gene expression identifies a gene in the lysogenic phage Gifsy-1 that affects Salmonella enterica serovar typhimurium survival in Peyer's patches.

In vivo expression technology was used to identify Salmonella enterica serovar Typhimurium genes that are transcriptionally induced when the bacteria colonize the small intestines of mice. These genes were subsequently screened for those that are transcriptionally inactive during the systemic stages of disease. This procedure identified gipA, a gene that is specifically induced in the small intestine of the animal. The gipA gene is carried on the lambdoid phage Gifsy-1. Consistent with the expression profile, the sole defect conferred by a gipA null mutation is in growth or survival in a Peyer's patch. The gipA strain is wild type in its ability to initially colonize the small intestine and invade the intestinal epithelium. The mutant also survives and propagates at wild-type levels during the systemic stages of disease. The gipA open reading frame is homologous to a family of putative insertion sequence elements, although our evidence shows that transposition is not required for gipA function in the Peyer's patch. These results suggest that the bacteria sense and respond to the particular environment of the Peyer's patch, a critical site for the replication of Salmonella serovar Typhimurium.