bluuebunny/crossref_metadata_2025 huggingface dataset:
The Quality of Steam Condensate as Related to Sodium Sulphite in the Boiler Water
Authors: Alexander R. C. , Rummel J. K.
Published: July 2022

Test data and conclusions are given in this paper which relate to the effect of various concentrations of sodium sulphite on the quality of condensed steam from high-pressure central-station boilers. Increase in sodium sulphite beyond certain limits was found to lower appreciably the pH and to raise the conductivity of the condensed steam. The acid material found in the steam resembles sulphurous acid. Test data, procedures, and equipment are described.
Effect of Welding on Pressure-Vessel Steels
Authors: Scotchbrook A. F. , Eriv L. , Stout R. D. , Johnston B. G.
Published: July 2022

This paper presents the results of a study using the Lehigh slow notched-bend test to determine the effects of welding on as-received and prestrained plate. It also discusses the effects of different heat inputs in welding, the effects of plate thickness, of carbon content and deoxidation practice, and of heat-treatment after welding.
Some Factors Influencing the Economics of Reheat Installations
Authors: Hartwell R. W. , Wagner H. A.
Published: July 2022

This paper presents a discussion of some economic factors concerned with choosing between a battery boiler system as compared to a unit boiler-turbine system, and a reheat as compared to a nonreheat plant. Annual costs are compared for four power plants containing the several basic design features. Emphasis is placed upon the difference in average availability of capacity of the four plants, effect on availability of two maintenance schedules, and result of assigning capital charges based upon difference in average available capacity.
Analysis of Experimental Data Regarding Certain Design Features of Pressure Vessels
Authors: Schoessow G. J. , Brooks E. A.
Published: July 2022

This paper presents an analysis of data obtained by strain-gage experimental stress analysis on drum heads and nozzle openings in drum shells. This analysis, while referred particularly to power boilers, is also applicable to other types of pressure vessels. The data obtained are reduced to dimensionless form so that they may be applied to drums of other size and thickness but geometrically similar, and to illustrate more clearly the action of the drum in resisting pressure. The relationship between operating-stress level and the life of the vessel in service is discussed with particular reference to a drum that has given over 40 years of satisfactory service with an operating-stress range over a considerable area of the vessel of approximately the ultimate strength of the material. The effect of prestress created in the vessel by overpressuring, such as applying the 1½-times working-pressure hydrostatic test, is discussed.
The Gas-Turbine Regenerator—The Use of Compact Heat-Transfer Surfaces
Authors: London A. L. , Kays W. M.
Published: July 2022

This paper illustrates the application of high-rating compact surfaces of the plate-fin-type to the regenerator-design problem for typical gas-turbine cycles. Comparisons are made with designs employing circular tube surfaces one inch and one-quarter inch in diameter.
Influence of Compressibility on Cylindrical Pitot-Tube Measurements
Authors: Thrasher L. W. , Binder R. C.
Published: July 2022

In the cylindrical Pitot tube, an opening at the critical angle with the flow gives the static pressure. For small-diameter tubes this critical angle is 39¼ deg for incompressible fluids in a certain range of turbulent flow. Using a wind tunnel, the distribution of pressure was measured on the surface of ⅛-in. and 3/16-in-diam cylinders at Mach numbers ranging from 0.13 to 0.87. The change in the pressure distribution on the surface of the cylinders was small in the range of Mach numbers up to 0.25. In this range the critical angle was constant, and a simple cylindrical Pitot tube would be convenient for direct measurements of static pressure. At the higher Mach numbers, particularly above 0.4, the critical angle increases above that for incompressible flow. The directional accuracy of the cylindrical Pitot increases as the Mach number increases.
The Response of Thermocouples to Rapid Gas-Temperature Changes
Authors: Carbon M. W. , Kutsch H. J. , Hawkins G. A.
Published: July 2022

This paper presents practical data which were taken from the main results of a research program dealing with the response of thermocouples to changing gas temperatures. Experimental and theoretical data for the response time of thermocouples ranging in wire size from 0.01 to 0.0005 in. are presented. The experiments were performed over a range of temperatures from 70 F to 950 F, and for air velocities ranging from 0 to 125 fps. All of the experiments were carried out in such a way that the hot junction of the thermocouple was always cooled. An equation is presented for computing the response time for thermocouples fabricated from fine wires and subjected to sudden air-temperature changes. Heat transfer by conduction and radiation were negligible in the experiments performed.
Pressure Losses in Tubing, Pipe, and Fittings
Authors: Pigott R. J. S.
Published: July 2022

This paper is a continuation of the second half of the problem involved in the writer’s 1933 paper on pipe flow and Prof. Lewis F. Moody’s 1944 paper. The pipe-flow situation is shown to be in satisfactory condition; the main attention is on bends and fittings.

It has been customary in the past to rate the losses in bends and fittings as a function of velocity head. Another old method, less used, was to rate the loss in equivalent length of pipe. In the case of bends and fittings two types of loss are superposed, i.e., skin friction or pipe-loss type, and bend loss. The methods of test are less accurate than for pipe as they involve getting the difference between two much larger readings. Consequently the test data are much poorer than for pipe, for several reasons: one given above; another that the pipe fittings are not geometrically similar; and the test data are very much less than those on pipe. It seems clear that a rational formulation, however, could be attempted if we can establish some picture of the factors involved in the losses. Up to the present time bend and fitting losses have been taken from a range of factors unconnected with size, roughness, or velocity of flow. This formulation, on the basis of the tests, endeavors to show that there is a true bend loss for smooth fittings underlying the superposed losses due to roughness and Reynolds number. The final formulation involves an evaluation of the true bend loss and an evaluation of the roughness and Reynolds number effects paralleling the friction factor in pipe. The final conclusion is that the equivalent pipe length is by all means the most reliable and convenient method of tabulating losses in different kinds of fittings and bends. The final formulation is ζ=ζ1+ζ2=0.106(rd)-2.5+2000f2.5. This formulation has been checked against the test results and while it is obvious that the factors will be both plus and minus over a considerable range, the general correlation of the test data appear to be as good as our present test information will permit.
Long-Time Tension and Creep Tests of Plastics
Authors: Staff C. E. , Quackenbos H. M. , Hill J. M.
Published: July 2022

Thermosetting and thermoplastic materials have been maintained under constant load at 25 C and 75 C for periods ranging from 1000 to 14,500 hr. Creep was measured with electric strain gages and, from its course, an estimate has been made of the maximum stresses that can be sustained for 5 years by the thermosetting materials. Both creep and crazing govern the maximum stresses for the thermoplastics, and these have been estimated for 1 year. An examination has been made of the accuracy and precision of the electric strain gage in measurements of creep. It is believed that the results are not confined to use in potential structural applications but have their greatest value in many current problems.
The Mechanism of Lubrication Failure in High-Speed Ball Bearings
Authors: Jones F. C. , Wilcock D. F.
Published: July 2022

When lubrication fails, the first point of distress in a high-speed ball bearing occurs at the rolling contact between a ball and a race. Because of the curvature of the race, sliding as well as rolling must occur in the contact area. Hence the absence of an oil film results in friction and heat. The localized heating and resultant differential expansion of the parts cause preloading of the bearing owing to loss of internal clearance. This process progresses rapidly to cause spalling or pitting of the races and balls, skidding balls, broken ball separators, and a jammed bearing.
Turbulence in High-Speed Journal Bearings
Authors: Wilcock D. F.
Published: July 2022

Measurements of the operating characteristics of journal bearings up to high surface speeds have revealed abnormalities beyond a certain critical value. A rapid increase in bearing torque, power loss, and oil-film temperature occurs as speed is increased beyond the critical value, while oil flow decreases below normal. These phenomena are attributed to the onset of instability or turbulence in the bearing oil film with an accompanying increase in energy absorption within the film. The experiments were conducted in a newly designed test apparatus capable of driving large bearings at high speeds. Maximum speed attained was 14,700 rpm, or 30,800 fpm, for an 8-in-diam bearing, and 20,000 rpm, or 21,000 fpm, for a 4-in. bearing.
Closed-Cycle Gas Turbine: Escher Wyss—AK Development, 1945–1950
Authors: Keller Curt
Published: July 2022

In 1945 Ackeret and the author made the first presentation in the United States of the basic theory and results of tests on the closed-cycle gas-turbine process, which had been pioneered by the author’s company. Since then the development has progressed rapidly and larger industrial installations have been made. Compressed high-temperature air and other gases, used in closed-cycle turbines, have led to new designs of components and plant layouts. This paper describes new stationary units which will be in operation in the near future and discusses future work and possibilities.
A Pyrometer for Measuring Total Temperature in Low-Density Gas Streams
Authors: Allen Sidney , Hamm J. R.
Published: July 2022

The need for improved methods of measuring total temperature in low-density moving gas streams has been emphasized by the rapidly increasing use of gas-turbine engines for aircraft propulsion at high altitudes. Recent experience with various types of pyrometers has shown that increased errors of measurement and a reduced rate of response to temperature changes become apparent as the gas density is reduced. A design of suction pyrometer is presented in which sonic gas velocity is maintained over the thermocouple element at all operating conditions, thus insuring the maximum rate of heat transfer to the thermocouple from the gas, and enabling a simple correction for impact error to be applied to the indicated reading in order to derive the total temperature of the gas stream. The rapid rate of response to temperature change obtained with this pyrometer is a fundamental necessity in any control mechanism in which gas temperature is the operating criterion.
Thermal-Shock and Other Comparison Tests of Austenitic and Ferritic Steels for Main Steam Piping
Authors: Stewart W. C. , Schreitz W. G.
Published: July 2022

Thermal-shock tests of 6-in pipe-and-valve assemblies, representing both austenitic and ferritic steels in 80 and 160 schedules, are described. The shock-testing procedure was devised to simulate conditions resulting from carryover of boiler feedwater into main steam lines operating at 900 or 2000 psi pressure, 1050 F temperature. Other test procedures described include cyclic deflection tests of full-size mock-ups consisting of 160 schedule pipe and valves for simulating expansion bends. Results are reported for mock-ups of both austenitic and ferritic materials which were tested at 2000 psi pressure, 1050 F temperature. Each assembly was subjected to 4000 or more deflections corresponding to expansion cycles that would obtain on heating up a piping system from room temperature to 1050 F once every 2 days for approximately 20 years.
Loss Coefficients for Abrupt Changes in Flow Cross Section With Low Reynolds Number Flow in Single and Multiple-Tube Systems
Authors: Kays W. M.
Published: July 2022

In testing for the flow-friction characteristics of compact heat-exchanger surfaces concurrent with heat-transfer tests, more precise data on the flow contraction- and expansion-loss coefficients are required than are presently available in the literature. This paper presents a theory for evaluating these coefficients for both single- and multiple-tube systems for various contraction and expansion geometries. The analysis takes into account the contraction and expansion area ratio and the velocity distribution. Results of experiment for the Reynolds number range 500–20,000 are presented which compare well with the analysis. This paper was originally presented at the June, 1949, meeting of the Heat Transfer and Fluid Mechanics Institute, and included only experimental data on multiple-tube systems. Since that time experiments have been performed on single-tube systems and these later results are presented here.
Sealing of High-Pressure Steam Safety Valves
Authors: Adams R. E. , Corcoran J. L.
Published: July 2022

A fundamental investigation of sealing with high-pressure steam safety valves has shown that poor sealing is a result of self-induced growth of tiny initial leaks. Expansion of the leaking steam cools local areas of the valve seat, causing contraction of the seating surfaces in a manner which increases the size of the leak. A new design of valve seat was developed, incorporating thin flexible seating surfaces. The cooling effects of the leaking steam were minimized by providing better heat transfer from the high-temperature steam. The new design resulted in considerable improvement in sealing, and service tests have shown excellent performance.
New Method for Bulk-Modulus Determinations
Authors: Kerr S. Logan , Kessler L. H. , Gamet M. B.
Published: July 2022

The bulk modulus of fluids other than water has not been reported in engineering literature to any extent, particularly in the range of pressures and temperatures ordinarily encountered in petroleum pipe-line work. In pipe-line work it is desirable to make surge investigations in advance of construction, and this requires some knowledge of the pressure wave velocity in the system for computing the magnitude of surges which may be expected in ordinary operating or in emergency conditions. While the physical characteristics of the materials and construction of the pipe line itself are known, the same is not true of the physical characteristics of the liquid. This paper relates to a method of determining the bulk-modulus values of fluids other than water to make available the missing factor in pipe-line design considerations.
Cable-Pulley Friction
Authors: Schorr W. E.
Published: July 2022

The factors contributing to the friction in cable-pulley or rope systems are analyzed, and an empirical equation for calculating this friction is derived.
Mechanism for selective binding of aromatic compounds on oxygen-rich graphene nanosheets based on molecule size/polarity matching
Authors: Fu Heyun , Wang Bingyu , Zhu Dongqiang , Zhou Zhicheng , Bao Shidong , Qu Xiaolei , Guo Yong , Ling Lan , Zheng Shourong , Duan Pu , Mao Jingdong , Schmidt-Rohr Klaus , Tao Shu , Alvarez Pedro J. J.
Published: July 2022

Selective binding of organic compounds is the cornerstone of many important industrial and pharmaceutical applications. Here, we achieved highly selective binding of aromatic compounds in aqueous solution and gas phase by oxygen-enriched graphene oxide (GO) nanosheets via a previously unknown mechanism based on size matching and polarity matching. Oxygen-containing functional groups (predominately epoxies and hydroxyls) on the nongraphitized aliphatic carbons of the basal plane of GO formed highly polar regions that encompass graphitic regions slightly larger than the benzene ring. This facilitated size match–based interactions between small apolar compounds and the isolated aromatic region of GO, resulting in high binding selectivity relative to larger apolar compounds. The interactions between the functional group(s) of polar aromatics and the epoxy/hydroxyl groups around the isolated aromatic region of GO enhanced binding selectivity relative to similar-sized apolar aromatics. These findings provide opportunities for precision separations and molecular recognition enabled by size/polarity match–based selectivity.
Longer metaphase and fewer chromosome segregation errors in modern human than Neanderthal brain development
Authors: Mora-Bermúdez Felipe , Kanis Philipp , Macak Dominik , Peters Jula , Naumann Ronald , Xing Lei , Sarov Mihail , Winkler Sylke , Oegema Christina Eugster , Haffner Christiane , Wimberger Pauline , Riesenberg Stephan , Maricic Tomislav , Huttner Wieland B. , Pääbo Svante
Published: July 2022

Since the ancestors of modern humans separated from those of Neanderthals, around 100 amino acid substitutions spread to essentially all modern humans. The biological significance of these changes is largely unknown. Here, we examine all six such amino acid substitutions in three proteins known to have key roles in kinetochore function and chromosome segregation and to be highly expressed in the stem cells of the developing neocortex. When we introduce these modern human-specific substitutions in mice, three substitutions in two of these proteins, KIF18a and KNL1, cause metaphase prolongation and fewer chromosome segregation errors in apical progenitors of the developing neocortex. Conversely, the ancestral substitutions cause shorter metaphase length and more chromosome segregation errors in human brain organoids, similar to what we find in chimpanzee organoids. These results imply that the fidelity of chromosome segregation during neocortex development improved in modern humans after their divergence from Neanderthals.
Unidirectionally excited phonon polaritons in high-symmetry orthorhombic crystals
Authors: Zhang Qing , Ou Qingdong , Si Guangyuan , Hu Guangwei , Dong Shaohua , Chen Yang , Ni Jincheng , Zhao Chen , Fuhrer Michael S. , Yang Yuanjie , Alù Andrea , Hillenbrand Rainer , Qiu Cheng-Wei
Published: July 2022

Advanced control over the excitation of ultraconfined polaritons—hybrid light and matter waves—empowers unique opportunities for many nanophotonic functionalities, e.g., on-chip circuits, quantum information processing, and controlling thermal radiation. Recent work has shown that highly asymmetric polaritons are directly governed by asymmetries in crystal structures. Here, we experimentally demonstrate extremely asymmetric and unidirectional phonon polariton (PhP) excitation via directly patterning high-symmetry orthorhombic van der Waals (vdW) crystal α-MoO
3
. This phenomenon results from symmetry breaking of momentum matching in polaritonic diffraction in vdW materials. We show that the propagation of PhPs can be versatile and robustly tailored via structural engineering, while PhPs in low-symmetry (e.g., monoclinic and triclinic) crystals are largely restricted by their naturally occurring permittivities. Our work synergizes grating diffraction phenomena with the extreme anisotropy of high-symmetry vdW materials, enabling unexpected control of infrared polaritons along different pathways and opening opportunities for applications ranging from on-chip photonics to directional heat dissipation.
Forming of Block Zeolites Using 3D Printing Technology
Authors: Bragina A. A. , Lysikov A. I. , Parkhomchuk E. V.
Published: July 2022

Zeolite blocks with 10% binder and without binder were formed using 3D printing technology. A polylactide template with the preset shape and structure of channels was printed on a 3D printer. The zeolite material was formed in the voids of this template. Finally, the template was burned out from the final block. Blocks with a binder were prepared by filling the template with a paste containing microcrystalline zeolite of MFI structural type. Blocks without binder were prepared by steam-assisted crystallization leading to the formation of zeolite nanocrystals in the H-form in the template channels. A relatively strong block consisting of MFI-type zeolite and reproducing the polymer template void volume was obtained.
Splenectomy post-splenic injury following dilatation of Roux-en-y enterostomy stomal stricture: an unexpected complication
Authors: Bennet Simon , Spiro Calista , Burlak Kateryna , Lim Hou Kiat
Published: July 2022

A 53-year-old woman presented in the early hours of the morning with generalised abdominal pain and features of hypovolaemic shock, following a dilatation of an enterostomy stricture 12 hours prior. Dilatation of this stricture was indicated by ongoing dysphagia, which had been successfully dilated twice before without incident. Standard resuscitative measures and confirmation of the endoscopically-caused splenic injury by CT scan were followed promptly by a splenectomy to control ongoing blood loss. The strictured enterostomy was revised to mitigate further need for endoscopic dilatation. The patient recovered well and was discharged shortly after on a soft diet.
University students’ understanding and opinions of eating disorders: a qualitative study
Authors: Manning Millie , Greenfield Sheila
Published: July 2022

Background

Eating disorders (EDs) affect 1.25 million people in the UK. Evidence suggests the public display stigma and poor mental health literacy (MHL) towards EDs. There is a high prevalence of EDs in university populations, so it is important to determine the MHL of this at-risk group. Qualitative research exploring the MHL of this population is incomplete.

Objective

Explore university students’ beliefs and opinions of EDs, their knowledge of symptoms, treatment and help sources and how these are influenced by biological sex.

Design

A qualitative study, using semistructured interviews analysed using inductive thematic analysis.

Setting

The University of Birmingham.

Participants

Seven female and seven male University of Birmingham students.

Results

Analysis revealed six themes, each with subthemes: ED characteristics, causes, body image, seeking help, stigma and awareness. Students displayed poor awareness towards ED signs and symptoms, causes and help sources. Students were not stigmatising towards EDs, but many perceived them as a female problem and believed society to be stigmatising. Many referenced informal sources of information such as social media and expressed a desire for ED teaching. Sex did not have a significant influence on knowledge or opinions of EDs in this study; however, there were some differences, for example, some males were more likely to see EDs as a weakness and to perceive themselves as having low levels of knowledge.

Conclusions

University students show broad awareness of EDs; however, knowledge of certain aspects of ED-MHL including help sources and symptom recognition was lacking. Although students were not stigmatising of EDs themselves, many perceived high levels of public stigma. This, alongside poor knowledge, may delay help-seeking. Campaigns educating students and the public about EDs would aid earlier diagnosis, improving long-term outcomes. Further research into awareness and knowledge in other populations would be beneficial.
Criteria to define rare diseases and orphan drugs: a systematic review protocol
Authors: Abozaid Ghada Mohammed , Kerr Katie , McKnight Amy , Al-Omar Hussain A
Published: July 2022

Introduction

Rare diseases (RDs) are often chronic and progressive life-threatening medical conditions that affect a low percentage of the population compared with other diseases. These conditions can be treated with medications known as orphan drugs (ODs). Unfortunately, there is no universal definition of RDs or ODs. This systematic review (SR) will identify the quantitative and qualitative criteria and the underlying rationale used internationally to define RDs and ODs.

Methods and analysis

This protocol follows the conventions for the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (2015 guidelines). A SR will be conducted, including a search of the following databases: PubMed, MEDLINE, EMBASE, Scopus, Web of Science, GreyLit and OpenGrey. Eligible publications will be selected based on predetermined inclusion criteria. Extracted data will be analysed using thematic and content analyses of qualitative descriptors, whereas quantitative data will be analysed descriptively and reported in the form of frequencies and percentages.

Ethics and dissemination

No ethical approval is required since this SR focuses on the secondary analysis of data retrieved from the scientific literature. The outcomes of this SR will be published as part of a PhD thesis, presented at conferences, and published in peer-reviewed journals.

PROSPERO registration number

CRD42021252701.
Associations between night-time sleep duration and fasting glucose and ratio of triglyceride to high-density lipoprotein cholesterol among adults free of type 2 diabetes or without diagnosed type 2 diabetes: a multicentre, cross-sectional study in China
Authors: He Jiangshan , Hong Chenglin , Zhang Li , Li chunjun , Wang Yuxue , Fan Yaqi , Guo Pei , Zhang Binbin , Qi Xin , Chen Shuo , Niu Yu-jie , Liu Feng , Zhang Rong , Li Qiang , Ma Shitao , Zhang Mianzhi , Zhang Minying
Published: July 2022

Objectives

We aimed to assess the associations between night-time sleep duration and fasting glucose (FG), triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio and body mass index (BMI) among adults free of type 2 diabetes (T2D) or without diagnosed T2D.

Design

Cross-sectional study.

Setting

Medical examination centres at six hospitals in Beijing-Tianjin-Hebei region, China.

Participants

Participants were recruited via multistage, stratified cluster sampling. We included adults free of T2D or without diagnosed T2D who attended for physical examination and completed the validated questionnaire. 32 497 participants were included in the study, of whom 52.50% were men.

Primary and secondary outcome measures

FG, TG, HDL-C, height and weight were measured.

Results

Overall, 12.80% and 9.67% reported night sleep duration <7 hours and ≥9 hours, respectively; 6.91% had elevated FG and 3.57% had undiagnosed T2D. Sleep duration had an independent, U-shaped associated with FG (β1(linear term)=−0.111, p=0.047; β2(quadratic term)=0.008, p=0.026) with 6.9 hours of sleep associated with the lowest FG and a negative association with BMI (β=−0.154, p<0.001). BMI mediated a U-shaped association of sleep duration with TG/HDL-C (β1=−0.040, p=0.017; β2=0.003, p=0.023).

Conclusions

Both short and long night-time sleep was associated with elevated FG, and short sleep duration was associated with increased BMI. BMI mediated a U-shaped association between sleep duration and TG/HDL-C.
Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome
Authors: Hart Thomas C , Hart P Suzanne , Bowden Donald W , Michalec Michael D , Callison Scott A , Walker Steve J , Zhang Yingze , Firatli Erhan
Published: July 2022

Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar hyperkeratosis and severe early onset periodontitis that results in the premature loss of the primary and secondary dentitions. A major gene locus for PLS has been mapped to a 2.8 cM interval on chromosome 11q14. Correlation of physical and genetic maps of this interval indicate it includes at least 40 ESTs and six known genes including the lysosomal protease cathepsin C gene (CTSC). The CTSCmessage is expressed at high levels in a variety of immune cells including polymorphonuclear leucocytes, macrophages, and their precursors. By RT-PCR, we found CTSC is also expressed in epithelial regions commonly affected by PLS, including the palms, soles, knees, and oral keratinised gingiva. The 4.7 kbCTSC gene consists of two exons. Sequence analysis of CTSC from subjects affected with PLS from five consanguineous Turkish families identified four different mutations. An exon 1 nonsense mutation (856C→T) introduces a premature stop codon at amino acid 286. Three exon 2 mutations were identified, including a single nucleotide deletion (2692delA) of codon 349 introducing a frameshift and premature termination codon, a 2 bp deletion (2673-2674delCT) that results in introduction of a stop codon at amino acid 343, and a G→A substitution in codon 429 (2931G→A) introducing a premature termination codon. All PLS patients were homozygous for cathepsin C mutations inherited from a common ancestor. Parents and sibs heterozygous for cathepsin C mutations do not show either the palmoplantar hyperkeratosis or severe early onset periodontitis characteristic of PLS. A more complete understanding of the functional physiology of cathepsin C carries significant implications for understanding normal and abnormal skin development and periodontal disease susceptibility.
Incomplete masculinisation of XX subjects carrying the SRY gene on an inactive X chromosome
Authors: Kusz Kamila , Kotecki Maciej , Wojda Alina , Szarras-Czapnik Maria , Latos-Bielenska Anna , Warenik-Szymankiewicz Alina , Ruszczynska-Wolska Anna , Jaruzelska Jadwiga
Published: July 2022

46,XX subjects carrying the testis determining SRY gene usually have a completely male phenotype. In this study, five very rare cases of SRY carrying subjects (two XX males and three XX true hermaphrodites) with various degrees of incomplete masculinisation were analysed in order to elucidate the cause of sexual ambiguity despite the presence of the SRY gene. PCR amplification of 20 Y chromosome specific sequences showed the Yp fragment to be much longer in XX males than in true hermaphrodites. FISH analysis combined with RBG banding of metaphase chromosomes of four patients showed that in all three true hermaphrodites and in one XX male the Yp fragment was translocated onto a late replicating inactive X chromosome in over 90% of their blood lymphocytes. However, in a control classical XX male with no ambiguous features, the Yp fragment (significantly shorter than in the XX male with sexual ambiguity and only slightly longer than in XX hermaphrodites) was translocated onto the active X chromosome in over 90% of cells.

These studies strongly indicate that inactivation on the X chromosome spreading into a translocated Yp fragment could be the major mechanism causing a sexually ambiguous phenotype in XX (SRY+) subjects.
A new simple enzyme assay for pre- and postnatal diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) and its variants
Authors: Voznyi Y V , Keulemans J L M , Mancini G M S , Catsman-Berrevoets C E , Young E , Winchester B , Kleijer W J , van Diggelen O P
Published: July 2022

Palmitoyl-protein thioesterase (PPT) deficiency was recently shown to be the primary defect in infantile neuronal ceroid lipofuscinosis (INCL). The available enzyme assay is complicated and impractical for diagnostic use and is, in practice, unavailable. We have developed a new fluorimetric assay for PPT based on the sensitive fluorochrome 4-methylumbelliferone. This PPT assay is simple, sensitive, and robust and will facilitate the definition of the full clinical spectrum associated with a deficiency of PPT. PPT activity was readily detectable in fibroblasts, leucocytes, lymphoblasts, amniotic fluid cells, and chorionic villi, but was profoundly deficient in these tissues from INCL patients. Similarly, a deficiency of PPT was shown in patients with the variant juvenile NCL with GROD. These results show that rapid pre- and postnatal diagnosis can be performed with this new enzyme assay for PPT.
Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation
Authors: Lam Wayne W K , Hatada Izuho , Ohishi Sachiko , Mukai Tsunehiro , Joyce Johanna A , Cole Trevor R P , Donnai Dian , Reik Wolf , Schofield Paul N , Maher Eamonn R
Published: July 2022

Beckwith-Wiedemann syndrome (BWS) is a human imprinting disorder with a variable phenotype. The major features are anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumours. BWS is genetically heterogeneous and epigenetic changes in the IGF2/H19 genes resulting in overexpression of IGF2 have been implicated in many cases. Recently germline mutations in the cyclin dependent kinase inhibitor gene CDKN1C (p57KIP2) have been reported in a variable minority of BWS patients. We have investigated a large series of familial and sporadic BWS patients for evidence of CDKN1C mutations by direct gene sequencing. A total of 70 patients with classical BWS were investigated; 54 were sporadic with no evidence of UPD and 16 were familial from seven kindreds. Novel germline CDKN1C mutations were identified in five probands, 3/7 (43%) familial cases and 2/54 (4%) sporadic cases. There was no association between germline CDKN1C mutations and IGF2 or H19 epigenotype abnormalities. The clinical phenotype of 13 BWS patients with germline CDKN1C mutations was compared to that of BWS patients with other defined types of molecular pathology. This showed a significantly higher frequency of exomphalos in the CDKN1C mutation cases (11/13) than in patients with an imprinting centre defect (associated with biallelic IGF2 expression and H19 silencing) (0/5, p<0.005) or patients with uniparental disomy (0/9, p<0.005). However, there was no association between germline CDKN1C mutations and risk of embryonal tumours. No CDKN1C mutations were identified in six non-BWS patients with overgrowth and Wilms tumour. These findings (1) show that germline CDKN1C mutations are a frequent cause of familial but not sporadic BWS, (2) suggest that CDKN1C mutations probably cause BWS independently of changes in IGF2/H19 imprinting, (3) provide evidence that aspects of the BWS phenotype may be correlated with the involvement of specific imprinted genes, and (4) link genotype-phenotype relationships in BWS and the results of murine experimental models of BWS.
Angelman syndrome resulting from UBE3A mutations in 14 patients from eight families: clinical manifestations and genetic counselling
Authors: Moncla Anne , Malzac Perrine , Livet Marie-Odile , Voelckel Marie-Antoinette , Mancini Josette , Delaroziere Jean Christophe , Philip Nicole , Mattei Jean-François
Published: July 2022

Angelman syndrome (AS) is a neurological disorder with a heterogeneous genetic aetiology. It most frequently results from a de novo interstitial deletion in the 15q11-q13 region, but in a few cases it is caused by paternal uniparental disomy (UPD) or an imprinting mutation. The remaining 20 to 30% of AS patients exhibit biparental inheritance and a normal pattern of allelic methylation in the 15q11-q13 region. In this latter group, mutations in the UBE3A gene have recently been shown to be a cause of AS. Here we describe the phenotypic expression in 14 AS cases involving eight UBE3A mutations. These comprise 11 familial cases from five families and three sporadic cases. Subtle differences from the typical phenotype of AS were found. Consistent manifestations were psychomotor delay, a happy disposition, a hyperexcitable personality, EEG abnormalities, and mental retardation with severe speech impairment. The other main manifestations of AS, ataxia, epilepsy, and microcephaly, were either milder or absent in various combinations among the patients. In addition, myoclonus of cortical origin was frequently observed with severe fits inducing myoclonic seizures. The majority of the patients were overweight. This study showed that ataxia, myoclonus, EEG abnormalities, speech impairment, characteristic behavioural phenotype, and abnormal head circumference are attributable to a deficiency in the maternally inherited UBE3A allele. Furthermore, analysis of mutation transmission showed an unexpectedly high rate of somatic mosaicism in normal carriers. These data have important consequences for genetic counselling.
Genetic analysis of the guanylate cyclase activator 1B (GUCA1B) gene in patients with autosomal dominant retinal dystrophies: Table 1
Authors: Payne Annette M , Downes Susan M , Bessant David A R , Plant Catherine , Moore Tony , Bird Alan C , Bhattacharya Shomi S
Published: July 2022

The guanylate cyclase activator proteins (GCAP1 and GCAP2) are calcium binding proteins which by activating Ret-GC1 play a key role in the recovery phase of phototransduction. Recently a mutation in theGUCA1A gene (coding for GCAP1) mapping to the 6p21.1 region was described as causing cone dystrophy in a British family. In addition mutations in Ret-GC1have been shown to cause Leber congenital amaurosis and cone-rod dystrophy. To determine whether GCAP2 is involved in dominant retinal degenerative diseases, the GCAP2 gene was screened in 400 unrelated subjects with autosomal dominant central and peripheral retinal dystrophies.

A number of changes involving the intronic as well as the coding sequence were observed. In exon 1 a T to C nucleotide change was observed leaving the tyrosine residue 57 unchanged. In exon 3 a 1 bp intronic insertion, a single nucleotide substitution G to A in the intron 3′ of this exon, and a GAG to GAT change at codon 155 were observed. This latter change results in a conservative change of glutamic acid to aspartic acid. In exon 4 a 7 bp intronic insertion, a single nucleotide A to G substitution in the intron 5′ of this exon, and a single base pair change C to G in the intron 3′ of exon 4 were seen. None of these changes would be expected to affect correct splicing of this gene. All these changes were observed in controls. The results of this study do not show any evidence so far that GCAP2 is involved in the pathogenesis of autosomal dominant retinal degeneration in this group of patients. All the changes detected were found to be sequence variations or polymorphisms and not disease causing.
Mapping access to endovascular stroke care in the USA and implications for transport models
Authors: Aldstadt Jared , Waqas Muhammad , Yasumiishi Misa , Mokin Maxim , Tutino Vincent M , Rai Hamid H , Chin Felix , Levy Bennett R , Rai Ansaar T , Mocco J , Snyder Kenneth V , Davies Jason M , Levy Elad I , Siddiqui Adnan H
Published: July 2022

Background

The purpose of this cross-sectional study was to determine the percentage of the US population with 60 min ground or air access to accredited or state-designated endovascular-capable stroke centers (ECCs) and non-endovascular capable stroke centers (NECCs) and the percentage of NECCs with an ECC within a 30 min drive.

Methods

Stroke centers were identified and classified broadly as ECCs or NECCs. Geographic mapping of stroke centers was performed. The population was divided into census blocks, and their centroids were calculated. Fastest air and ground travel times from centroid to nearest ECC and NECC were estimated.

Results

Overall, 49.6% of US residents had 60 min ground access to ECCs. Approximately 37.7% (113 million) lack 60 min ground or air access to ECCs. Approximately 84.4% have 60 min access to NECCs. Ground-only access was available to 77.9%. Approximately 738 NECCs (45.4%) had an ECC within a 30 min drive.

Conclusion

Nearly one-third of the US population lacks 60 min access to endovascular stroke care, but this is highly variable. Transport models and planning of additional centers should be tailored to each state depending on location and proximity of existing facilities.
Fast and slow progressors of infarct growth in basilar artery occlusion strokes
Authors: Desai Shashvat M , Tonetti Daniel A , Jovin Tudor G , Jadhav Ashutosh P
Published: July 2022

Background

Heterogeneity in the infarct growth rate among anterior circulation large vessel occlusion (LVO) strokes has triage and treatment implications. Such data are lacking for basilar artery occlusion (BAO) strokes. We aim to describe the variability in brainstem infarct volume at presentation and compute the distribution of the infarct growth rate (IGR) and rate of loss of neurons during BAO strokes.

Methods

A retrospective review of consecutive patients with BAO stroke with pretreatment MRI was performed. Ischemic core volume was manually calculated (product of slice thickness and sum of area of region of interests) for the brainstem lesion. The distribution of various brainstem infarct volume groups was analyzed and the IGR (including rate of loss of neurons) was computed.

Results

Fifty-nine patients were included. Mean age was 64±13 and 34% were men. Mean National Institutes of Health Stroke Scale score was 20±11 and time to MRI was 9±5 hours. Mean brainstem ischemic core volume was 4.5±4.6 mL. According to predefined thresholds, 13% and 6% of patients with BAO stroke in the 0–6 hour time window were fast (5–10 mL) and ultra-fast progressors (>10 mL), respectively, and 14% of patients in the 6–24 hour time window were slow progressors (<1 mL). Median and mean rate of loss of neurons was 146 300 neurons/min and 261 300 (±400 000) neurons/min, respectively, and ranged from <19 400 to >2.12 million.

Conclusion

Approximately 14% of BAO strokes are slow progressors and 19% are fast/ultra-fast progressors, with the rate of loss of neurons ranging from <19 000 to >2.1 million/min. Large heterogeneity exists in brainstem infarct volume at presentation and IGR among patients with BAO stroke.
Multiple Mechanistic Models Reveal the Neuroprotective Effects of Diterpene Ginkgolides against Astrocyte-Mediated Demyelination via the PAF-PAFR Pathway
Authors: Wang Tuan-Jie , Wu Zi-Yin , Yang Chun-Hua , Cao Liang , Wang Zhen-Zhong , Cao Ze-Yu , Yu Ming-Yang , Zhao Meng-Ru , Zhang Chen-Feng , Liu Wen-Jun , Zhao Bin-Jiang , Shang Xue-Qi , Feng Yu , Wang Hui , Deng Li-Li , Xiao Bao-Guo , Guo Hong-Yan , Xiao Wei
Published: July 2022

Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.
Nonlinear dynamical analysis to explore the N-soliton solutions of time-fractional coupled Burger’s model
Authors: Usman Muhammad , Alhowaity Awatif , Hamid Muhammad , Hamam Haneen , Khan Nawab
Published: July 2022

The modeling of nonlinear dynamical models and their solutions have imperative values, whereas the soliton mathematical methods are favorable tools for analyzing such highly nonlinear practical problems. Herein, time-fractional coupled Burger’s model is analyzed. Some solitary wave solutions, containing one-soliton, two-soliton, three-soliton and [Formula: see text]-soliton, have been fetched using a modified sort of the well-known exp-function approach. Dominant effects of the fractional parameters have been illustrated and it is noted that the higher values of the fractional number cause a significant impact on the wave propagation. The one wave pattern for the [Formula: see text]-component is quite identical, while an increase in the fractional parameter is producing an increment in the wave structure while a similar but opposite pattern is noted for the [Formula: see text]-component. An increment in the wave structure is noted for higher values of the time-fractional parameter for both [Formula: see text]- and [Formula: see text]-components in the case of a two-wave solution. The benefits of the proposed computational code of the exp-function scheme are consistent, a general form of exact solutions, reduced computational complexity and stable and efficiently useful. The obtained solitary waves solutions will be a useful extension to the preceding results and greatly assist in clarifying the features of nonlinear waves in viscous flow.
A mathematical model that describes the relation of low-density lipoprotein and oxygen concentrations in a stenosed artery
Authors: Narayan S. Shankar , Anuradha B. , Sunanda S. , Puneeth V. , Khan M. Ijaz , Abdullah A. , Guedri Kamel , Jameel Mohammed
Published: July 2022

The cellular activities of the endothelium layer between lumen and intima are significantly linked to the origin of the disease atherosclerosis. Three stages of atherosclerosis were investigated in this study (40%-mild, 50%-modest, and 60%-acute) concerning the coronary arterial segment. The essence of the hemodynamic factors like flow velocity, pressure, and wall shear stress has been investigated, as well as the interrelationships between them. At all degrees of stenosis, the biophysical relationship between convection-diffusion of low-density lipoproteins (LDL) and convection-diffusion of oxygen in the bloodstream is investigated. The Finite Element Methods (FEM) are used to solve the modeled partial differential equation systems. The method adopted is numerical in nature providing accurate graphical solutions to the framed systems. The physical effects of the deposition of LDL on the arterial wall, like a decrease in the diameter of the lumen, and toughening of the walls, are analyzed through the evaluation of the physical parameters. The study revealed that the deposition of LDL molecules in the post stenotic region leads to the depletion of oxygen in the region leading to the rapid dysfunctioning of the endothelial layer of the lumen-intima boundary.
Immune–Pathogen Dynamics
Authors: Shinbrot Troy
Published: July 2022

Motivated by curiosities of disease progression seen in the coronavirus pandemic, we analyze a minimalist predator–prey model for the immune system (predator), competing against a pathogen (prey). We find that the mathematical model alone accounts for numerous paradoxical behaviors observed in this and other infections. These include why an exponentially growing pathogen requires an exposure threshold to take hold, how chronic and recurrent infections can arise, and what can allow very sick patients to recover, while healthier patients succumb. We also examine the distinct dynamical roles that nonspecific, “innate,” and specific, “adaptive,” immunity play, and we describe mathematical effects of infection history on prognosis. Finally, we briefly discuss predictions for some of the effects of timing and strengths of antibiotics or immunomodulatory agents.