Fusion Range Research Articles

Abstract 4315: NGS-based reference materials for fusion and somatic variant detection in myeloid cancers

Abstract The large range of genetic aberrations and genes involved Myeloid malignancies, clonal diseases of hematopoietic progenitor cells which can lead to accumulation of immature blast cells in the bone marrow and peripheral blood, make Next Generation Sequencing (NGS) assays a cost effective and sensitive way to determine genetic changes. Understanding the genetic changes which lead to the clonal proliferation can aid in both determining prognosis and therapy selection. Consequently, there are an increasing number of NGS-based oncology tests available for somatic mutation detection in patients with hematological malignancies. However, reference materials that contain the relevant genetic blood cancer mutations are lacking. We designed a purified RNA reference material that contains nine RNA fusions two different ETV6-ABL1 transcripts, including BCR-ABL1, MYST3-CREBBP, RUNX1-RUNX1T1, and PML-RARα which are important in myeloid cancers. Conversely, a purified DNA reference material was designed to include 23 somatic variants included two FLT3 internal tandem duplications. The biosynthetic RNA or DNA constructs were mixed with either total RNA or purified genomic DNA from GM24385 reference human cell line. Digital PCR was used to quantify the variant sequences to determine the abundance of the fusion RNAs and the allele frequencies of the somatic mutations. NGS testing on a variety of targeted NGS assays was then performed to show compatibility. The Seraseq Myeloid RNA Mix was tested by digital PCR to confirm that each of the nine fusions in the reference samples are present at approximately 100 fusion copies per nanogram of total RNA. The FusionPlex Myeloid Kit for Illumina (ArcherDx) as well as the Oncomine Myeloid Panel (Thermo Fisher) showed positive detection for all fusions present in the reference samples. In addition, the Seraseq Myeloid DNA Mix was also tested by digital PCR to confirm the variant allele frequencies were on target at the 5%, 10% or 15% VAF. While, dPCR allele specific assays could not be obtained for CEBPA mutations, NGS testing of the reference samples by VariantPlex Core Myeloid Kit for Illumina (ArcherDx) and Oncomine Myeloid Panel (Thermo Fisher) confirmed the presence of these mutations at the expected levels, as well as all of the other variants in the DNA reference samples. In conclusion, SeraCare has developed highly multiplexed RNA and DNA-based reference materials for evaluating Myelogenous disorders by NGS. The reference materials allow monitoring of a broad range of somatic mutations and gene fusions which can aid optimization and verification of detection limits for NGS-based Myeloid disease assay testing, and provide laboratories greater assurance in their ability to correctly detect and quantify various types of genetic events in diseased patient samples. Citation Format: Farol Lovell Tomson, Praveena Kamineni, Catherine Huang, Jessica Dickens, Dan Brudzewsky, Omoshile Clement, Ram Santhanam, Bharathi Anekella. NGS-based reference materials for fusion and somatic variant detection in myeloid cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4315.

Earliest Utilization of Chicken in Upper California: The Zooarchaeology of Avian Remains from the San Diego Royal Presidio

The San Diego Presidio, established in AD 1769, was the first European settlement in Upper California. Very little is known about chicken husbandry in colonial America, which makes this study the first comprehensive analysis of chicken remains in North America. Chickens are scarcely mentioned in historical accounts describing early California, and information on their sex, age, or management is rare. The faunal assemblage from the San Diego Presidio yielded 20 avian and 14 mammalian species. Chicken remains were studied through a wide range of zooarchaeological methods, including taphonomy, biometry, medullary bone, epiphyseal fusion, butchering, and body-part representation. Taphonomic analysis indicates good preservation of the bone assemblage. The biometric study points to two breeds of chickens: a smaller (bantam) breed alongside a standard-size chicken. The percentage of juvenile chickens (23%), the rooster/hen ratio (1:8.5), and high proportion of medullary bone point to on-site chicken husbandry focusing on meat and egg production. The historical record suggests that California presidios were not self-sufficient and that they relied on food provisioned from Mexico and nearby missions. We argue that small-scale poultry production, likely managed by women and children, provided California presidios with a form of subsistence independence.

The next-generation RET inhibitor TPX-0046 is active in drug-resistant and naïve RET-driven cancer models.

3616 Background: RET fusions/mutations drive oncogenesis in lung and thyroid cancers, and several other malignancies. Selective RET inhibitors (selpercatinib/pralsetinib) are active in patients with these cancers; unfortunately, resistance often occurs. On-target resistance includes the acquisition of solvent front mutations (SFMs i.e. RET G810 substitutions). TPX-0046 is a structurally differentiated RET inhibitor that is potent against a range of RET fusions and mutations including SFMs. Methods: The rationally-designed, compact, macrocyclic RET/SRC inhibitor TPX-0046 was characterized in RET-driven in vitro and in vivo tumor models. Results: In enzymatic assays, TPX-0046 showed low nanomolar potency against wild-type RET and 18 RET mutations/fusions. It was potent against SRC and spared VEGFR2/KDR. TPX-0046 inhibited RET phosphorylation (IC50 < 10 nM) in tumor cell lines (LC2/ad, CCDC6-RET; TT, RET C634W) and Ba/F3 engineered RET models (WT, G810R). In cell proliferation assays, TPX-0046 inhibited KIF5B-RET Ba/F3, LC2/ad, and TT cells with IC50 values ~1 nM. Ba/F3 RET engineered cells with SFMs (e.g. G810C/R/S) were potently inhibited by TPX-0046 (mean proliferation IC50 1–17 nM). TPX-0046 demonstrated marked in vivo anti-tumor efficacy in RET-driven cell-derived and patient-derived xenograft tumor models. In a Ba/F3 KIF5B-RET xenograft model, a single dose of 5 mg/kg TPX-0046 inhibited > 80% of RET phosphorylation (corresponding mean free plasma concentration: 51 nM). At 5 mg/kg BID, tumor regression was observed in RET-dependent xenograft models, including those that harbor RET SFMs: TT, CTG-0838 PDX (NSCLC, KIF5B-RET), CR1520 PDX (CRC, NCOA4-RET), Ba/F3 KIF5B-RET, and Ba/F3 KIF5B-RET G810R. Conclusions: TPX-0046 is a unique next-generation RET inhibitor that possesses potent in vitro and in vivo activity against a diverse range of RET alterations, including SFM-mediated resistance. A phase 1/2 trial for RET inhibitor-resistant and naïve RET-driven cancers is on-going (NCT04161391).

Modular repeat protein sculpting using rigid helical junctions

The ability to precisely design large proteins with diverse shapes would enable applications ranging from the design of protein binders that wrap around their target to the positioning of multiple functional sites in specified orientations. We describe a protein backbone design method for generating a wide range of rigid fusions between helix-containing proteins and use it to design 75,000 structurally unique junctions between monomeric and homo-oligomeric de novo designed and ankyrin repeat proteins (RPs). Of the junction designs that were experimentally characterized, 82% have circular dichroism and solution small-angle X-ray scattering profiles consistent with the design models and are stable at 95 °C. Crystal structures of four designed junctions were in close agreement with the design models with rmsds ranging from 0.9 to 1.6 Å. Electron microscopic images of extended tetrameric structures and ∼10-nm-diameter "L" and "V" shapes generated using the junctions are close to the design models, demonstrating the control the rigid junctions provide for protein shape sculpting over multiple nanometer length scales.

Effect of K2O/Na2O on fusion behavior of coal ash with high silicon and aluminum level

Ash fusion temperatures (AFTs) are widely used for evaluation of fusibility of coal ash for combustion and gasification. K2O and Na2O is regarded as the effective component to enhance the ash fusibility for slag tapping. The combination of K2O and Na2O may enhance the flux efficiency. In this work, the effect of K2O/Na2O mass ratio on fusion behavior of coal ash with high silicon and alumina level was evaluated by the height variation of ash cone during heating. The results showed that AFTs and theoretical fusion range (Tliq-Tini) decreased quickly and then increased slowly as the K2O/Na2O mass ratio in the coal ash was reduced. The sub-liquidus phase changed from mullite into feldspar, which was responsible for change of AFTs. Meanwhile, most of K element occurred in leucite (KAlSi2O6) and the rest existed in nepheline (KAlSiO4), but Na almost existed in nepheline (NaAlSiO4). The competition effect between K2O and Na2O on AFTs was reflected by KAlSiO4/NaAlSiO4 in nepheline, so the SiO2-KAlSi2O6-NaAlSi2O6 ternary phase diagram was constructed, which well explained the variation of AFTs caused by K2O/Na2O mass ratio. Meanwhile, the fusion process was divided into two stages based on variation rate of ash cone height. At first stage, the amount of liquidus phase is limited and the viscosity is high, so only a low shrinkage rate of ash cone exhibits. However, at the second stage, high shrinking rate is caused by not only the rapid increase of slag content but also the sharp decrease of viscosity besides, the addition of K2O/Na2O change ash fusion process from “melting-dissolving” into “softening-melting”.

Thermal behavior of a sodium acetate trihydrate-based PCM: T-history and full-scale tests

Latent heat thermal energy storage (LHTES) has been receiving increasing attention from researchers and engineers. A practical LHTES installation requires a deep understanding of phase change material’s (PCM’s) thermal behavior under thermal property testing and realistic operating conditions. To enrich this understanding, an experimental study on a commercial sodium acetate trihydrate-based PCM (Climsel C58) is presented in this article. C58 was characterized with two test methods: T-history tests and full-scale LHTES tests. The results are presented and discussed to exhibit the thermal behavior of C58 with these two test methods and the variations between them. With T-history tests, the thermal properties of C58 such as melting/solidification temperature range (57–61 °C/55–50 °C) and latent heat of fusion (216 kJ/kg) were determined. In full-scale LHTES tests, a parametric study was conducted to investigate the effects of heat transfer fluid flowrate and operating temperature range on the thermal performance of a 0.38 m3 storage prototype containing cylindrically macro-encapsulated C58. Moreover, longitudinal and radial PCM temperature distributions in full-scale tests were analyzed, suggesting the presence of phase separation. In general, C58 behaved differently between the two test methods regarding phase separation (negligible in T-history tests), supercooling effects (within 3 K in full-scale but up to 10 K in T-history tests), and thermal energy storage capacity (10% lower in full-scale tests). When using C58 or other salt hydrate-based PCMs for large-scale heat storage, these thermal behavior differences between the property-measurement and the application-oriented environments should be properly addressed in the design stage to ensure performance.

Enhancement of droplet ejection from molten and liquid plasma-facing surfaces by the electric field of the sheath**Substantial portions of this paper are adapted from section 4.1 of the first author’s recent PhD thesis.

Maintaining the stability of a liquid surface in contact with a plasma is of crucial importance in a range of industrial and fusion applications. The most fundamental feature of a plasma-surface interaction, the formation of a highly-charged sheath region, has been neglected from the majority of previous studies of plasma-liquid interactions. This paper considers the effect of the electric field of the sheath on the ejection of micron-scale droplets from bubbles bursting at the liquid surface. A numerical simulation method, based on the ideal electrohydrodynamic model, is introduced and validated against the well-known Taylor cone theory. This model is then used to include the electrical effects of the sheath in simulations of bubble bursting events at a plasma-liquid interface. The results show a significant enhancement in droplet ejection at modest electric fields of between 10% and 20% of the critical field strength required for a solely electrohydrodynamic instability. This finding is in good qualitative agreement with experimental observations and its importance in a wide range of fusion and atmospheric-pressure plasma-liquid interactions is discussed. The inclusion of sheath physics in future studies of plasma-liquid interactions is strongly advocated.

Testing NTRK testing: Wet-lab and in silico comparison of RNA-based targeted sequencing assays.

NTRK fusions involving three neurotrophic tyrosine receptor kinase genes NTRK1, NTRK2, and NTRK3 and a variety of fusion partners were identified as oncogenic drivers across many cancer types. Drugs that target the chimeric protein product require the identification of the underlying gene fusion. This advocates the diagnostic use of molecular assays ranging from fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR)/Sanger approaches to targeted next-generation sequencing (NGS). Immunohistochemistry may be used as a screening tool and adjunct diagnostic assay in this context. Although FISH and RT-PCR/Sanger approaches are widely adopted in routine diagnostics, current experience with targeted RNA-based NGS is limited. Here, we report on the analysis of major assays (TruSight TST170 and TruSight RNA Fusion [Illumina]; Archer FusionPlex Solid Tumor, Archer FusionPlex Lung, and Archer FusionPlex Oncology [Archer]; Oncomine Comprehensive Assay v3 RNA and Oncomine Focus RNA [Thermo Fisher Scientific]) that are commercially available. The data set includes performance results of a multicentric comparative wet-lab study as well as an in silico analysis on the ability to detect the broad range of NTRK fusions reported until now. A test algorithm that reflects assay methodology is provided. This data will support implementation of targeted RNA sequencing in routine diagnostics and inform screening and testing strategies that have been brought forward.

Connection of discontinuous segments in early functional recovery from thoracic ossification of the posterior longitudinal ligament treated with posterior instrumented surgery.

The objective of this study was to investigate the relationship between morphological changes in thoracic ossification of the posterior longitudinal ligament (T-OPLL) and postoperative neurological recovery after thoracic posterior fusion surgery. Changes of OPLL morphology and postoperative recovery in cases with T-OPLL have not been examined. In this prospective study, the authors evaluated data from 44 patients (23 male and 21 female) who underwent posterior decompression and fusion surgery with instrumentation for the treatment of T-OPLL at our hospital. The patients' mean age at surgery was 50.7 years (range 38-68 years). The minimum duration of follow-up was 2 years. The location of thoracic ossification of the ligamentum flavum (T-OLF), T-OLF at the OPLL level, OPLL morphology, fusion range, estimated blood loss, operative time, pre- and postoperative Japanese Orthopaedic Association (JOA) scores, and JOA recovery rate were investigated. Reconstructed sagittal multislice CT images were obtained before and at 3 and 6 months and 1 and 2 years after surgery. The basic fusion area was 3 vertebrae above and below the OPLL lesion. All parameters were compared between patients with and without continuity across the disc space at the OPLL at 3 and 6 months after surgery. The preoperative morphology of OPLL was discontinuous across the disc space between the rostral and caudal ossification regions on sagittal CT images in all but one of the patients. Postoperatively, these segments became continuous in 42 patients (97.7%; occurring by 6.6 months on average) without progression of OPLL thickness. Patients with continuity at 3 months had significantly lower rates of diabetes mellitus (p < 0.05) and motor palsy in the lower extremities (p < 0.01). The group with continuity also had significantly higher mean postoperative JOA scores at 3 (p < 0.01) and 6 (p < 0.05) months and mean JOA recovery rates at 3 and 6 months (both p < 0.01) after surgery. Preoperatively, discontinuity of rostral and caudal ossified lesions was found on CT in all patients but one of this group of 44 patients who needed surgery for T-OPLL. Rigid fixation with instrumentation may have allowed these segments to connect at the OPLL. Such OPLL continuity at an early stage after surgery may accelerate spinal cord recovery.

Prognosis of Hardware-Related Problems in Anterior Cervical Discectomy and Fusion with Cage and Plate Constructs

To analyze hardware-related problems and their prognoses after anterior cervical discectomy and fusion (ACDF) using cages and plates for degenerative and traumatic cervical disc diseases. The study included 808 patients who underwent anterior cervical discectomy and fusion for degenerative and traumatic disc diseases with >1 year of follow-up. We investigated time of onset and progression of problems associated with instrumentation and cage usage. The mean follow-up time was 3.4 years. Type of plate, range and level of fusion, patient factors (age, sex, body mass index, and bone mineral density), and local kyphosis were evaluated. Complications were found in 132 cases (16.5%), including subsidence in 69 cases, plate loosening in 8 cases, screw loosening in 8 cases, screw breakage in 1 case, and multiple complications in 36 cases. In 3 cases, additional posterior cervical surgery was performed. One case needed hardware revision. There were no esophageal, tracheal, or neurovascular structural injuries secondary to metal failure. There were no significant differences in type of plate, level of surgery, or patient factors. The greater the number of fusion segments, the greater the incidence of complications (P= 0.001). The clinical outcomes improved regardless of the complications (P= 0.083). Most hardware-related complications are not symptomatic and can be treated conservatively. Only a few cases need revision surgery. Precise surgical techniques are needed in multilevel anterior cervical discectomy and fusion (>3 levels) because of the increased complication rate.

Effects of steady background noise on binaural pitch fusion

Binaural pitch fusion is the fusion of dichotic stimuli across the two ears. The current study was designed to investigate how steady background noise can influence binaural fusion. The binaural fusion ranges, the frequency ranges over which binaural fusion occurred, were measured with various levels (30—70 dB/ERBN) of the threshold-equalizing noise (Moore et al., 2004) and compared with those measured in quiet. Two interleaved adaptive procedures were used to estimate the fusion ranges at the reference frequencies of 2 and 3 kHz: Single-Interval Adjustment Matrix (SIAM; Kaernbach, 1990) and Maximum-Likelihood (ML; Green, 1992). The results show that the TEN decreases the fusion ranges to about 1.5 to 2 times narrower than those in the quiet condition. Even soft noise levels (i.e., the 30 dB/ERBN) significantly decreased fusion ranges. For some subjects, the fusion range asymptoted with a soft level and did not increase with increased noise level; for other subjects, the fusion range minimized only at the specific noise level. Both SIAM and ML procedures showed similar performance in fusion range estimation. The findings suggest that the importance of steady background noise, specifically TEN, in binaural fusion may vary across subjects. This may provide potential rehabilitation approaches to reduce broad fusion in hearing impaired listeners.Binaural pitch fusion is the fusion of dichotic stimuli across the two ears. The current study was designed to investigate how steady background noise can influence binaural fusion. The binaural fusion ranges, the frequency ranges over which binaural fusion occurred, were measured with various levels (30—70 dB/ERBN) of the threshold-equalizing noise (Moore et al., 2004) and compared with those measured in quiet. Two interleaved adaptive procedures were used to estimate the fusion ranges at the reference frequencies of 2 and 3 kHz: Single-Interval Adjustment Matrix (SIAM; Kaernbach, 1990) and Maximum-Likelihood (ML; Green, 1992). The results show that the TEN decreases the fusion ranges to about 1.5 to 2 times narrower than those in the quiet condition. Even soft noise levels (i.e., the 30 dB/ERBN) significantly decreased fusion ranges. For some subjects, the fusion range asymptoted with a soft level and did not increase with increased noise level; for other subjects, the fusion range minimized only at the...

Effects of additives blended in corn straw to control agglomeration and slagging in combustion

Four additives including two specimens of kaolin clay, limestone, and a byproduct of a sugar mill (BSM) (mainly CaCO3) were utilized to increase ash fusion temperature (AFT) of corn straw. The results showed that the ash softening temperature (ST) was increased by 250 to 380 °C and agglomeration or slagging could be avoided during combustion with each additive. Meanwhile, the slagging/fouling tendency of all ash samples fell within the “low” range according to alkali index. Lime was shown to have the best effect, which indicated that calcium oxide was the best compound to increase the AFT of corn straw densification (CSDF). Both kaolin specimens made the fusion range very narrow. BSM had the least effect on ST among the four. All the additives diluted the concentration of chlorine by more than 50%. No agglomeration or slagging phenomenon appeared in real boilers burning CSDF with lime blended as additive.

Clinical measurements of normative subjective cyclotorsion and cyclofusion in a healthy adult population.

To investigate normative subjective cyclotorsion values and cyclofusion ranges in a healthy adult population. A cross-sectional investigation was performed in 120 healthy, non-strabismic adults, 60 men and 60 women in the age range of 18-69years. All subjects were assessed for cyclotorsion using the synoptophore and the single Maddox rod (SMR) methods. Cyclofusion was investigated with the synoptophore in 60 of the subjects. All age groups showed low values of subjective torsion, mainly excyclotorsion with mean values of -1 degree for both methods. Reference ranges of cyclotorsion were between -0.7 and -1.5 degrees for the SMR method and between -0.7 and -1.4 degrees using the synoptophore method. There were no significant differences between gender (p=0.48), but the effect of age was significant for both methods (p=0.026) demonstrating a slight increase in excyclotorsion with age. Cyclofusion showed a total mean amplitude of 16 degrees, the fusion range was +7 degrees of incyclotorsion to -9 degrees of excyclotorsion. Subjective reference ranges for cyclotorsion and cyclofusion reveal that low values of torsion are to be expected upon clinical investigation in non-strabismic adult individuals. Values outside of the reference range may be indicators of possible binocular abnormalities or physiological variations. The cyclotorsional measurements and prevalence in this adult population group can be regarded as normative data in clinical settings.

Size Increase in Panum's Fusional Range Is Driven by Eccentricity and Not Separation.

Previous research has demonstrated that Panum’s fusional range increases in the periphery, and this increase is usually attributed to eccentricity. However, it is unclear whether the increase in the periphery is driven by eccentricity or separation between the stimulus and the central fixation marker. In Experiment 1, we independently measured the effects of eccentricity and stimulus separation on Panum’s fusional range for horizontal disparities. We observed significant increases in Panum’s range as eccentricity increased independently of stimulus separation. Experiment 2 revealed that the extent of Panum’s fusional range for vertical disparities increased with eccentricity independently of stimulus separation. Taken together, these results strongly support previously held conclusions that Panum’s fusional range for both horizontal and vertical disparities increases with increasing eccentricity and is little impacted by stimulus separation.

Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion

AbstractBackground: The anterior cervical discectomy for cervical disc prolapse has been the work horse for ages and it works fine but the mechanical problems that follows is actually problematic hence the evolution of total disc replacement.Aim of Study: The aim was to compare the efficacy and safety of arthroplasty using the artificial cervical disc with the standard Anterior Cervical Discectomy and Fusion (ACDF) for the management of cervical disc prolapse at single level.Patients and Methods: Sixty patients were included and randomized to one of two groups: Investigational patients (30) underwent arthroplasty using a disc prosthesis, and a control group (30 patients) underwent ACDF with a cervical cage. Patients were assessed pre-operatively, immediate post-operative period and at six weeks, three months, six, twelve, eighteen and-twenty-four months postoperatively. Efficacy and safety outcomes were measured according to the Neck Disability Index (NDI), visual analogue score, gait disturbance, disc height, range of motion (arthroplasty group) or bony fusion (control group), complications, rate of second surgery, and neurological outcome. Overall outcome was considered successful according to four pivot criteria: (1): Improvement of post-operative NDI score more than fifteen points over the preoperative score, (2): Improved neurological presenting symptoms, (3): No serious complications caused by the prosthesis or by the surgical procedure, and (4): No resurgery needed (superimposed fixation, revision, or non-elective implant removal).Results: The one year rate of overall outcome were ninety five percent for the arthroplasty group and eighty six percent for the control group, the arthroplasty group was better than the control group for the NDI score improvement. The per-centage of patients experiencing any adverse effects was six percent in the arthroplasty group and eight percent in the control group, which were not statistically different. Radio-graphic success was achieved in 9 ninety five percent of the arthroplasty group (maintenance of range of motion without bony fusion) and one hundred percent of control patients (fusion).Conclusions: Arthroplasty is as efficient and successful as ACDF for the management of cervical disc pathology.

Improved prediction of critical-viscosity temperature by fusion behavior of coal ash

Coal ash slag viscosity is critical for slag tapping in entrained-flow coal gasifiers, so the accurate prediction of slag viscosity and the critical temperature of viscosity (Tcv) will help the coal selection, flux addition and gasifier operation. Many empirical correlation models based on ash fusion temperature have been proposed to calculate Tcv. In order to correlate the viscosity with the fusion behavior and then improve the prediction of Tcv, we measured the viscosity of several synthetic coal ash slags with a high-temperature rotary viscometer and studied their ash fusion behavior through thermomechanical analysis. X-ray diffraction was used to compare the mineral transformation before and after Tcv combined with the FactSage calculation. The viscosity measurement shows that the viscosity above Tcv of glassy slags is higher than that of the crystalline type. The mineral transformation from FactSage also demonstrates that the precipitation rate of solid phase is lower for glassy slags. The fusion behavior for the glassy and the crystalline slag is also distinctly different.The fusion range from deformation temperature (DT) to flow temperature (FT) of the ash for the glassy slag was larger than that of the crystalline one, and the shrinkage above FT in TMA trace slopes gently. The correlation between the fusion behavior and viscosity-temperature behavior for the glassy slag is reasonable, because the large temperature range from DT to FT and the low shrinking rate of the stage III indicate the high viscosity of the liquid phase formed and the slow melting of the remained solid phase respectively, which are also the correlative condition prefer for the formation of glass as mentioned above. For the crystalline slag, the small fusion range from DT to FT means the rapid melting of the solid phase and the high flowability of the liquid phase which are indicative for the rapid precipitation during cooling. The slow rate of the stage III indicates the slow melting of the remained solid which can be the crystal nucleus. When the viscosity of the liquid phase is low, it also benefit for the formation of crystalline slags. The characteristic in fusion behavior for different type of slag also suggested that the predicting Tcv by applying one method to all the crystalline slags and non-crystalline slags is not appropriate.

The outcome of intervertebral surgery in the treatment of lumbar tuberculosis in children: A case series and long-term follow-up.

During the operation of treating lumbar tuberculosis in children, a long-segment or short-segment fixation, and fusion method were usually applied, which would adversely affect the function of normal motion unit. And so, we have been focusing on how we can shorten the range of fixation and fusion using intervertebral surgery. The objective of this retrospective study is to investigate the clinical outcome of intervertebral surgery, in the treatment of lumbar tuberculosis in children.From June 2003 to June 2013, 18 children with lumbar tuberculosis underwent intervertebral surgery, using a combined posterior and anterior approach, in our hospital. The surgical treatments included posterior pedicle screw fixation of affected vertebrae and posterolateral bone grafting, anterior debridement, compression, and strut bone grafting. Indicators such as preoperative and postoperative erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, neurological function, visual analog scale (VAS) score, kyphotic Cobb angle, complications, healing of lesions, bone graft healing, and recurrence were statistically analyzed.The mean follow-up time was 86.5 months (range, 62–120 months). Three months after the operation, all patients’ ESR and CRP levels decreased to normal, and both the American Spinal Injury Association neurological function scores and VAS scores improved. Successful bone graft healing was achieved, with lesions completely healed at 6 months after surgery, and no recurrence occurred. The preoperative kyphotic was 24.00° ± 13.15° (range −10°–39°), which decreased to −4.61° ± 7.31° (range −19°–10°) postoperative (Z = −4.34, P < .01); the mean deformity correction angle was 28.61° ± 8.43° (range 9°–43°). There was no significant difference between the kyphotic angle measured immediately after surgery at (−4.61° ± 7.31°) and the kyphotic angle measured at 5-year follow-up at (−3.11° ± 7.56°). The mean loss of correction was 1.50° ± 0.90°.Intervertebral surgery using a combined posterior and anterior approach is an effective and safe method for the treatment of lumbar tuberculosis in children. It can also preserve the function of normal motor segments to the maximum extent.

A central hydrophobic E1 region controls the pH range of hepatitis C virus membrane fusion and susceptibility to fusion inhibitors

Hepatitis C virus (HCV) infection causes chronic liver disease. Antivirals have been developed and cure infection. However, resistance can emerge and salvage therapies with alternative modes of action could be useful. Several licensed drugs have emerged as HCV entry inhibitors and are thus candidates for drug repurposing. We aimed to dissect their mode of action, identify improved derivatives and determine their viral targets. HCV entry inhibition was tested for a panel of structurally related compounds, using chimeric viruses representing diverse genotypes, in addition to viruses containing previously determined resistance mutations. Chemical modeling and synthesis identified improved derivatives, while generation of susceptible and non-susceptible chimeric viruses pinpointed E1 determinants of compound sensitivity. Molecules of the diphenylpiperazine, diphenylpiperidine, phenothiazine, thioxanthene, and cycloheptenepiperidine chemotypes inhibit HCV infection by interfering with membrane fusion. These molecules and a novel p-methoxy-flunarizine derivative with improved efficacy preferentially inhibit genotype 2 viral strains. Viral residues within a central hydrophobic region of E1 (residues 290-312) control susceptibility. At the same time, viral features in this region also govern pH-dependence of viral membrane fusion. Small molecules from different chemotypes related to flunarizine preferentially inhibit HCV genotype 2 membrane fusion. A hydrophobic region proximal to the putative fusion loop controls sensitivity to these drugs and the pH range of membrane fusion. An algorithm considering viral features in this region predicts viral sensitivity to membrane fusion inhibitors. Resistance to flunarizine correlates with more relaxed pH requirements for fusion. This study describes diverse compounds that act as HCV membrane fusion inhibitors. It defines viral properties that determine sensitivity to these molecules and thus provides information to identify patients that may benefit from treatment with membrane fusion inhibitors.

Effect of CaO/Fe2O3 on fusion behaviors of coal ash at high temperatures

The ash fusibility, usually investigated and evaluated by the ash chemical composition, is widely used for guiding the coal utilization in boiler and gasifier. The ratio of basic and acidic oxides (B/A) in coal ash is the most important parameter for ash fusibility evaluation. While the coal ash has the identical B/A ratio, SiO2/Al2O3 and CaO/Fe2O3 ratio also show significant influence on the ash fusibility. However, the researches on CaO/Fe2O3 on ash fusibility are rare. In order to quantify the influence of CaO/Fe2O3 on the ash fusibility, thermal mechanical analyzer (TMA) is applied to investigate the ash fusion behavior of coal ash with various CaO/Fe2O3 ratios. XRD, FactSage and DSC are combined to explore the ash fusion characteristics and mechanisms. The results showed that AFTs increased with the increasing of CaO/Fe2O3 ratio, which was attributed to variation of Fe2O3 content and iron valence. However, the ash with low CaO/Fe2O3 ratio trended to form mullite, increasing AFTs. Hence, the optimal CaO/Fe2O3 ratio for fluxing effect existed to balance the mineral component and iron valence. The different shrinkage curves were attributed to the different fusion events and different mechanism. The fusion process of ash (CaO/Fe2O3 = 0.25) exhibited as the behavior of a pure substance, which has the narrow fusion range. And the fusion range was dominated by the low temperature eutectics including spinel, quartz, corundum, and anorthite, which were beneficial for preventing ash sintering. Meanwhile, the fusion process of ash sample (CaO/Fe2O3 = 4) occurred step by step, and it had a wide fusion range. The low-melting point minerals such as wollastonite, clinopyroxene, calcium silicate induced and manipulated the fusion process. These ash samples with the wide fusion range were favored for slagging process. Besides, the shrinkage rate of ash was mainly determined by the slag formation rate when viscosity was low, but it was dependent on slag formation rate as well as viscosity for the high viscosity slag. Two correlated relations between shrinkage rate and ratio of liquid phase formation rate and viscosity for ash with CaO/Fe2O3 < 1 and CaO/Fe2O3 ≥ 1 were established to prevent ash sintering at high temperatures.

Motility Changes and Diplopia After Baerveldt Glaucoma Drainage Device Implantation or After Trabeculectomy.

PurposeThe purpose of this study was to quantify any diplopia and motility changes after the implantation of a Baerveldt glaucoma implant (BGI) or after trabeculectomy (TE).MethodsWe analyzed 51 patients with a BGI and 52 patients with a TE from a prospective cohort study. To quantify any diplopia, we asked patients about the presence of diplopia at 1 year after surgery. To quantify any ocular motility changes, we measured ductions in eight gaze directions, the patients' ocular alignment and their fusion range before and 1 year after surgery.ResultsIn the BGI group, 14 patients (28%) experienced diplopia compared with one patient (2%) in the TE group (P < 0.001). Duction changes were more commonly observed in the BGI group (35%) than in the TE group (19%). In the BGI group, ductions were mostly restricted in elevation (13%; P < 0.001), in abduction (13%), in elevation in 25° adduction (13%; P = 0.044), and in elevation in 25° abduction (25%; P < 0.001). In 32% of the patients, their near horizontal ocular alignment shifted, notably in exodirection (P = 0.04). The fusion range decreased significantly in the horizontal direction (−12.6° ± 10.3°, mean ± standard deviation; P = 0.01).ConclusionsBGI surgery was significantly associated with postoperative diplopia and impaired eye motility (reduced ductions), mostly present in abduction, elevation, elevation in 25° adduction, and elevation in 25° abduction. Even without impaired ductions, diplopia could come about.Translational RelevanceBy studying diplopia across glaucoma patients prospectively with diplopia questionnaires and extensive orthoptic measurements, we gain better insight into its occurrence.