Cone Development Software Free Download

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Endoplasmic reticulum (ER) stress and Unfolded Protein Response (UPR) signaling promote the pathology of many human diseases. Loss-of-function variants of the UPR regulator Activating Transcription Factor 6 (ATF6) cause severe congenital vision loss diseases such as achromatopsia by unclear pathomechanisms. To investigate this, we generated retinal organoids from achromatopsia patient induced pluripotent stem cells carrying ATF6 disease variants and from gene-edited ATF6 null hESCs. We found that achromatopsia patient and ATF6 null retinal organoids failed to form cone structures concomitant with loss of cone phototransduction gene expression, while rod photoreceptors developed normally. Adaptive optics retinal imaging of achromatopsia patients carrying ATF6 variants also showed absence of cone inner/outer segment structures but preserved rod structures, mirroring the defect in cone formation observed in our retinal organoids. These results establish that ATF6 is essential for human cone development. Interestingly, we find that a selective small molecule ATF6 signaling agonist restores the transcriptional activity of some ATF6 disease-causing variants and stimulates cone growth and gene expression in patient retinal organoids carrying these variants. These findings support that pharmacologic targeting of the ATF6 pathway can promote human cone development and should be further explored for blinding retinal diseases.

Cone Calculator is used to calculate Fabrication Layout Markings or Flat Pattern Layout Marking of Full Cone, Half Cone or Truncated Cone, Multi-Level concentric Cone, Eccentric Cone, Multi-Level Eccentric Cone, Tori Cone with Knuckle Radius at Large End, Tori Cone with knuckle radius at Both Ends

This calculator is useful for fabrication Industry, Process Equipment Manufacturing Industry, Pressure Vessel Manufacturing Industry, Piping Industry, Sheet Metal Industry, Heavy Equipment Fabrication Industry or any similar Industry where cone fabrication works involved.

Cone Large Diameter (D) is the Diameter of Concentric Cone or Eccentric Cone r Tori Cone at Large End. It is Denoted By D in this Calculator. If you are planning to Mark the layout on a Flat Plate Then use the Mean Diameter of the Cone that is nothing but Inside Diameter plus thickness or Outside Diameter minus thickness for higher accuracy. But if you are directly marking layout on cone then use outside diameter. Refer Standard Image for Large Diameter D. You can use any dimentional units such as Inches or MM as per your prefererance. if you are using Inches as units for your input values then please refer decimal fractional chart to enter proper input values.

Cone small Diameter (D) is the Diameter of Concentric Cone or Eccentric Cone r Tori Cone at small End. It is Denoted By d in this Calculator. If you are planning to Mark the layout on a Flat Plate Then use the Mean Diameter of the Cone that is nothing but Inside Diameter plus thickness or Outside Diameter minus thickness for higher accuracy. But if you are directly marking layout on cone then use outside diameter. You can use any dimentional units such as Inches or MM as per your prefererance. if you are using Inches as units for your input values then please refer decimal fractional chart to enter proper input values.

Cone Height is the Distance between the Large end and small end vertically. it is required for the cone fabrication layout or flat Pattern layout development. It is denoted by H. Refer Standard Image for Cone Height H. You can use any dimentional units such as Inches or MM as per your prefererance. if you are using Inches as units for your input values then please refer decimal fractional chart to enter proper input values.

No. of Levels are important dimensions while layouting Multi-Level Cones. No. of Levels nothing but no. of parts doing in Height wise. It is the process of converting the whole cone into an equal no. of parts. this types of the cone are required when the large cone is fabricated and it is not possible to layout the cone in a single part due to limitations of raw material sizes or limitations of forming process. It is denoted by N. Refer to Standard Image for Multilevel cones.

Knuckle Radius is the dimension required for flat pattern layouting of Toricone. Knuckle radius at Large end normally denoted by R and Knuckle Radius at Small end is denoted by r. Refer to Standard Image for Toricone with Knuckle radius at Large End and Knuckle radius at Both Ends. You can use any dimentional units such as Inches or MM as per your prefererance. if you are using Inches as units for your input values then please refer decimal fractional chart to enter proper input values.

No. of Development lines are a very important input field in this calculator. It is the no. of equal division lines for flat pattern layout marking. It is required to give this input while layouting Eccentric Cone. No. of development lines play a very important role in the accuracy of the layout so optimum no of development lines are needed to select. We always recommend users give this value in multiples of four such as 12, 24, 36, 48, 72, 96, etc.

Development Radius has calculated this calculator and Denoted By R1 and R2 for Inner and Outer Radius respectively. This development Radius is used to layout cone fabrication layout markings or Flat Pattern Markings. Refer to Standard Image for understanding these dimensions at Output sections

Development Angle has calculated by this calculator and Denoted By θ. This development Angle is used to layout cone fabrication layout markings or Flat Pattern Markings. Refer to Standard Image for understanding these dimensions at Output sections.

Development Cord Length has calculated by this calculator and Denoted By X1 and X2. This development Angle is used to layout cone fabrication layout markings or Flat Pattern Markings. Refer to Standard Image for understanding these dimensions at Output sections.

Cone Calculator is useful for fabrication Industry, Process Equipment Manufacturing Industry, Pressure Vessel Manufacturing Industry, Piping Industry, Sheet Metal Industry, Heavy Equipment Fabrication Industry or any similar Industry

Cone Calculator helps to Fabrication Engineer, Fabrication Fitter, Production Engineer, Quality Engineer, Design Engineer, Costing and Estimating Engineer, Fabrication Contractor, Workshop Supervisor, Fabrication shop, Piping Engineer, Process Equipment manufacturers, Pressure Vessels Fabricators, Heat Ex-changer Manufacturers, Storage tank Manufacturers.

We have the lower base radius, radius of the upper base (in case of a truncated cone), and cone height. We need to find the length of the lateral side (or slant height), the lower arc radius, the radius of the upper arc (again, in case of a truncated cone), and the common central angle.

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Photoreceptor loss is a leading cause of blindness, but mechanisms underlying photoreceptor degeneration are not well understood. Treatment strategies would benefit from improved understanding of gene-expression patterns directing photoreceptor development, as many genes are implicated in both development and degeneration. Neural retina leucine zipper (NRL) is critical for rod photoreceptor genesis and degeneration, with NRL mutations known to cause enhanced S-cone syndrome and retinitis pigmentosa. While murine Nrl loss has been characterized, studies of human NRL can identify important insights for human retinal development and disease. We utilized iPSC organoid models of retinal development to molecularly define developmental alterations in a human model of NRL loss. Consistent with the function of NRL in rod fate specification, human retinal organoids lacking NRL develop S-opsin dominant photoreceptor populations. We report generation of two distinct S-opsin expressing populations in NRL null retinal organoids and identify MEF2C as a candidate regulator of cone development.

Normal visual function requires light detection by photoreceptors followed by signal transduction through the neural retina to the brain. Mammalian retinas contain rod and cone photoreceptors, with rods responsible for dim-light and peripheral vision and cones for color, high acuity, and central vision. Rods and cones arise from a common precursor, and photoreceptor cell fate is dictated by key transcription factors1. Neural retina leucine zipper (NRL) is required for rod development, and it activates Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3), which suppresses expression of cone-specific genes, promoting the rod developmental program2. Previous murine studies have shown that Nrl loss leads to development of cone dominant retinas; specifically, an increase in S-cones3.

Like the murine phenotype, loss of NRL in humans can cause enhanced S-cone syndrome, a rare retinal disease characterized by supranormal blue cone function due to an increased proportion of S-cones and night blindness due to the absence of rods4,5. However, the range of clinical phenotypes caused by NRL mutations is broad, with dominant missense mutations leading to a clinical picture more akin to retinitis pigmentosa4,5,6. Similarly, enhanced S-cone syndrome can result from mutations in genes other than NRL, usually NR2E3. Using an induced pluripotent stem cell (iPSC) line derived from a patient carrying a homozygous NRL mutation, we sought to characterize the developmental and molecular effects of NRL loss in human stem cell-derived retinal organoids. Retinal organoids, which closely mirror in vivo retinal development, provide a human model for studying retinal development and degeneration7,8,9,10,11,12,13,14,15,16,17,18,19,20. Organoids closely mimic retinal structure and apical-basal polarity, with an outer layer of photoreceptors capable of ribbon synapse formation and inner layers of retinal ganglion, amacrine, horizontal, and bipolar cells.

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