DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_2818776

Curator: @scibot

SciCrunch record: RRID:AB_2818776

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (R and D Systems Cat# AB-108-C, RRID:AB_354267)

Curator: @scibot

SciCrunch record: RRID:AB_354267

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_10638319

Curator: @scibot

SciCrunch record: RRID:AB_10638319

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Proteintech Cat# 19563-1-AP, RRID:AB_10643379)

Curator: @scibot

SciCrunch record: RRID:AB_10643379

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_3662631

Curator: @scibot

SciCrunch record: RRID:AB_3662631

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Abcam Cat# ab23345, RRID:AB_778267)

Curator: @scibot

SciCrunch record: RRID:AB_778267

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BD Biosciences Cat# 555473, RRID:AB_395865)

Curator: @scibot

SciCrunch record: RRID:AB_395865

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_2936254

Curator: @scibot

SciCrunch record: RRID:AB_2936254

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BD Biosciences Cat# 559777, RRID:AB_398671)

Curator: @scibot

SciCrunch record: RRID:AB_398671

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Abcam Cat# ab206406, RRID:AB_2936253)

Curator: @scibot

SciCrunch record: RRID:AB_2936253

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BD Biosciences Cat# 555472, RRID:AB_395864)

Curator: @scibot

SciCrunch record: RRID:AB_395864

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 105812, RRID:AB_313221)

Curator: @scibot

SciCrunch record: RRID:AB_313221

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_2880966

Curator: @scibot

SciCrunch record: RRID:AB_2880966

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# 47-5921-82, RRID:AB_1548786)

Curator: @scibot

SciCrunch record: RRID:AB_1548786

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# 25-5931-82, RRID:AB_469663)

Curator: @scibot

SciCrunch record: RRID:AB_469663

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 116222, RRID:AB_2281408)

Curator: @scibot

SciCrunch record: RRID:AB_2281408

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# 47-0452-82, RRID:AB_1518810)

Curator: @scibot

SciCrunch record: RRID:AB_1518810

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 100204, RRID:AB_312661)

Curator: @scibot

SciCrunch record: RRID:AB_312661

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# 47-0112-82, RRID:AB_1603193)

Curator: @scibot

SciCrunch record: RRID:AB_1603193

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 103222, RRID:AB_313005)

Curator: @scibot

SciCrunch record: RRID:AB_313005

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# 47-5931-82, RRID:AB_1518804)

Curator: @scibot

SciCrunch record: RRID:AB_1518804

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_2564604

Curator: @scibot

SciCrunch record: RRID:AB_2564604

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 100220, RRID:AB_1732057)

Curator: @scibot

SciCrunch record: RRID:AB_1732057

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_2564293

Curator: @scibot

SciCrunch record: RRID:AB_2564293

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 104317, RRID:AB_2687360)

Curator: @scibot

SciCrunch record: RRID:AB_2687360

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 148506, RRID:AB_2564602)

Curator: @scibot

SciCrunch record: RRID:AB_2564602

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Emfret Cat# X488, RRID:AB_2890921)

Curator: @scibot

SciCrunch record: RRID:AB_2890921

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 133928, RRID:AB_2572132)

Curator: @scibot

SciCrunch record: RRID:AB_2572132

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 101216, RRID:AB_312799)

Curator: @scibot

SciCrunch record: RRID:AB_312799

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# 47-0031-82, RRID:AB_11149861)

Curator: @scibot

SciCrunch record: RRID:AB_11149861

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_2750526

Curator: @scibot

SciCrunch record: RRID:AB_2750526

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 133906, RRID:AB_2129745)

Curator: @scibot

SciCrunch record: RRID:AB_2129745

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BD Biosciences Cat# 553848, RRID:AB_395085)

Curator: @scibot

SciCrunch record: RRID:AB_395085

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (BioLegend Cat# 133914, RRID:AB_11125581)

Curator: @scibot

SciCrunch record: RRID:AB_11125581

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Solarbio Cat# SE134, RRID:AB_2797593)

Curator: @scibot

SciCrunch record: RRID:AB_2797593

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Proteintech Cat# 11224-1-AP, RRID:AB_2210206)

Curator: @scibot

SciCrunch record: RRID:AB_2210206

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_10678802

Curator: @scibot

SciCrunch record: RRID:AB_10678802

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# A-11012, RRID:AB_2534079)

Curator: @scibot

SciCrunch record: RRID:AB_2534079

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (IMSR Cat# JAX_018397,RRID:IMSR_JAX:018397)

Curator: @scibot

SciCrunch record: RRID:IMSR_JAX:018397

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# A-11007, RRID:AB_10561522)

Curator: @scibot

SciCrunch record: RRID:AB_10561522

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Molecular Probes Cat# A-21207, RRID:AB_141637)

Curator: @scibot

SciCrunch record: RRID:AB_141637

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Molecular Probes Cat# A-21206 (also A21206), RRID:AB_2535792)

Curator: @scibot

SciCrunch record: RRID:AB_2535792

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# A-21070, RRID:AB_2535731)

Curator: @scibot

SciCrunch record: RRID:AB_2535731

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:IMSR_GPT:T011044

Curator: @scibot

SciCrunch record: RRID:IMSR_GPT:T011044

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (IMSR Cat# JAX_009669,RRID:IMSR_JAX:009669)

Curator: @scibot

SciCrunch record: RRID:IMSR_JAX:009669

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: RRID:AB_3718041

Curator: @scibot

SciCrunch record: RRID:AB_3718041

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Abcam Cat# ab78078, RRID:AB_2256751)

Curator: @scibot

SciCrunch record: RRID:AB_2256751

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Santa Cruz Biotechnology Cat# sc-53941, RRID:AB_2100038)

Curator: @scibot

SciCrunch record: RRID:AB_2100038

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Abcam Cat# ab32454, RRID:AB_776174)

Curator: @scibot

SciCrunch record: RRID:AB_776174

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Abcam Cat# ab203912, RRID:AB_2801537)

Curator: @scibot

SciCrunch record: RRID:AB_2801537

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Abcam Cat# ab177487, RRID:AB_2532109)

Curator: @scibot

SciCrunch record: RRID:AB_2532109

What is this?

DOI: 10.1016/j.devcel.2026.04.005

Resource: (Thermo Fisher Scientific Cat# A-11055, RRID:AB_2534102)

Curator: @scibot

SciCrunch record: RRID:AB_2534102

What is this?

DOI: 10.1016/j.crmeth.2026.101454

Resource: FlowJo (RRID:SCR_008520)

Curator: @scibot

SciCrunch record: RRID:SCR_008520

What is this?

DOI: 10.1016/j.crmeth.2026.101454

Resource: R Project for Statistical Computing (RRID:SCR_001905)

Curator: @scibot

SciCrunch record: RRID:SCR_001905

What is this?

DOI: 10.1016/j.crmeth.2026.101454

Resource: CytExpert Software (RRID:SCR_017217)

Curator: @scibot

SciCrunch record: RRID:SCR_017217

What is this?

DOI: 10.1016/j.crmeth.2026.101454

Resource: GraphPad Prism (RRID:SCR_002798)

Curator: @scibot

SciCrunch record: RRID:SCR_002798

What is this?

DOI: 10.1016/j.crmeth.2026.101454

Resource: (Thermo Fisher Scientific Cat# A-21235, RRID:AB_2535804)

Curator: @scibot

SciCrunch record: RRID:AB_2535804

What is this?

DOI: 10.1016/j.crmeth.2026.101454

Resource: (Hypoxyprobe Cat# HP MAb-1, RRID:AB_2801307)

Curator: @scibot

SciCrunch record: RRID:AB_2801307

What is this?

DOI: 10.1016/j.chom.2026.04.011

Resource: (Abcam Cat# ab97057, RRID:AB_10680316)

Curator: @scibot

SciCrunch record: RRID:AB_10680316

What is this?

DOI: 10.1016/j.bcp.2026.118037

Resource: (CLS Cat# 300278/p514_MDA-MB-436, RRID:CVCL_0623)

Curator: @scibot

SciCrunch record: RRID:CVCL_0623

What is this?

DOI: 10.1016/j.bbrc.2026.153874

Resource: RRID:Addgene_36046

Curator: @scibot

SciCrunch record: RRID:Addgene_36046

What is this?

DOI: 10.1016/j.bbi.2026.106795

Resource: Diabetic Complications Consortium (RRID:SCR_001415)

Curator: @scibot

SciCrunch record: RRID:SCR_001415

What is this?

DOI: 10.1016/j.agrcom.2026.100145

Resource: (BCRC Cat# 60057, RRID:CVCL_2160)

Curator: @scibot

SciCrunch record: RRID:CVCL_2160

What is this?

DOI: 10.1016/j.agrcom.2026.100145

Resource: (CCLV Cat# CCLV-RIE 0103, RRID:CVCL_4528)

Curator: @scibot

SciCrunch record: RRID:CVCL_4528

What is this?

DOI: 10.1016/j.agrcom.2026.100145

Resource: (RRID:CVCL_1926)

Curator: @scibot

SciCrunch record: RRID:CVCL_1926

What is this?

DOI: 10.1002/mrc.70110

Resource: RRID:SCR_027247

Curator: @scibot

SciCrunch record: RRID:SCR_027247

What is this?

DOI: 10.1002/mdc3.70664

Resource: Parkinson's Progression Markers Initiative (RRID:SCR_006431)

Curator: @scibot

SciCrunch record: RRID:SCR_006431

What is this?

DOI: 10.1002/mdb2.70037

Resource: (Proteintech Cat# 66009-1-Ig, RRID:AB_2687938)

Curator: @scibot

SciCrunch record: RRID:AB_2687938

What is this?

DOI: 10.1002/mdb2.70037

Resource: RRID:AB_2764979

Curator: @scibot

SciCrunch record: RRID:AB_2764979

What is this?

DOI: 10.1002/jev2.70289

Resource: RRID:Addgene_183045

Curator: @scibot

SciCrunch record: RRID:Addgene_183045

What is this?

DOI: 10.1002/jcp.70187

Resource: (CLS Cat# 602280/p823_MDCK_(NBL-2), RRID:CVCL_0422)

Curator: @scibot

SciCrunch record: RRID:CVCL_0422

What is this?

DOI: 10.1002/jcp.70185

Resource: (Thermo Fisher Scientific Cat# A-11008, RRID:AB_143165)

Curator: @scibot

SciCrunch record: RRID:AB_143165

What is this?

DOI: 10.1002/jcp.70185

Resource: (BioLegend Cat# 801201, RRID:AB_2313773)

Curator: @scibot

SciCrunch record: RRID:AB_2313773

What is this?

DOI: 10.1002/jcp.70185

Resource: (Thermo Fisher Scientific Cat# MA1-110, RRID:AB_2536821)

Curator: @scibot

SciCrunch record: RRID:AB_2536821

What is this?

DOI: 10.1002/jcp.70185

Resource: (Molecular Probes Cat# A-11003, RRID:AB_141370)

Curator: @scibot

SciCrunch record: RRID:AB_141370

What is this?

DOI: 10.1002/jcp.70185

Resource: (Millipore Cat# MAB1580, RRID:AB_11213204)

Curator: @scibot

SciCrunch record: RRID:AB_11213204

What is this?

DOI: 10.1002/jcp.70185

Resource: (Cell Signaling Technology Cat# 3512, RRID:AB_2294590)

Curator: @scibot

SciCrunch record: RRID:AB_2294590

What is this?

DOI: 10.1002/jcp.70185

Resource: (Sigma-Aldrich Cat# C6219, RRID:AB_476857)

Curator: @scibot

SciCrunch record: RRID:AB_476857

What is this?

DOI: 10.1002/jcp.70185

Resource: (Santa Cruz Biotechnology Cat# sc-47778, RRID:AB_626632)

Curator: @scibot

SciCrunch record: RRID:AB_626632

What is this?

DOI: 10.1002/jcp.70185

Resource: (Thermo Fisher Scientific Cat# 37-4600, RRID:AB_2533320)

Curator: @scibot

SciCrunch record: RRID:AB_2533320

What is this?

DOI: 10.1002/jcp.70185

Resource: (Cell Signaling Technology Cat# 4058, RRID:AB_331168)

Curator: @scibot

SciCrunch record: RRID:AB_331168

What is this?

DOI: 10.1002/jcp.70185

Resource: RRID:AB_2533972

Curator: @scibot

SciCrunch record: RRID:AB_2533972

What is this?

DOI: 10.1002/jcp.70185

Resource: (Cell Signaling Technology Cat# 9272, RRID:AB_329827)

Curator: @scibot

SciCrunch record: RRID:AB_329827

What is this?

DOI: 10.1002/jcp.70185

Resource: (Thermo Fisher Scientific Cat# 31430, RRID:AB_228307)

Curator: @scibot

SciCrunch record: RRID:AB_228307

What is this?

DOI: 10.1002/jcp.70185

Resource: (Thermo Fisher Scientific Cat# 31460, RRID:AB_228341)

Curator: @scibot

SciCrunch record: RRID:AB_228341

What is this?

DOI: 10.1002/jcp.70185

Resource: (Abcam Cat# ab97959, RRID:AB_2341193)

Curator: @scibot

SciCrunch record: RRID:AB_2341193

What is this?

DOI: 10.1002/jcp.70185

Resource: (Abcam Cat# ab14715, RRID:AB_301433)

Curator: @scibot

SciCrunch record: RRID:AB_301433

What is this?

DOI: 10.1002/jcp.70185

Resource: RRID:AB_2533479

Curator: @scibot

SciCrunch record: RRID:AB_2533479

What is this?

DOI: 10.1002/jcp.70185

Resource: RRID:AB_1140895

Curator: @scibot

SciCrunch record: RRID:AB_1140895

What is this?

DOI: 10.1002/ijc.70526

Resource: (ECACC Cat# 90011609, RRID:CVCL_2659)

Curator: @scibot

SciCrunch record: RRID:CVCL_2659

What is this?

DOI: 10.1002/ijc.70526

Resource: (RRID:CVCL_6298)

Curator: @scibot

SciCrunch record: RRID:CVCL_6298

What is this?

DOI: 10.1002/ijc.70526

Resource: (DSMZ Cat# ACC-510, RRID:CVCL_2218)

Curator: @scibot

SciCrunch record: RRID:CVCL_2218

What is this?

DOI: 10.1002/ijc.70517

Resource: SHapley Additive ExPlanations (RRID:SCR_021362)

Curator: @scibot

SciCrunch record: RRID:SCR_021362

What is this?

DOI: 10.1002/ijc.70517

Resource: XGBoost (RRID:SCR_021361)

Curator: @scibot

SciCrunch record: RRID:SCR_021361

What is this?

DOI: 10.1002/ijc.70517

Resource: R Project for Statistical Computing (RRID:SCR_001905)

Curator: @scibot

SciCrunch record: RRID:SCR_001905

What is this?

DOI: 10.1002/ijc.70517

Resource: UK Biobank (RRID:SCR_012815)

Curator: @scibot

SciCrunch record: RRID:SCR_012815

What is this?

DOI: 10.1002/dvg.70053

Resource: RRID:BDSC_7629

Curator: @scibot

SciCrunch record: RRID:BDSC_7629

What is this?

DOI: 10.1002/dvg.70053

Resource: RRID:BDSC_5137

Curator: @scibot

SciCrunch record: RRID:BDSC_5137

What is this?

DOI: 10.1002/dvg.70053

Resource: RRID:BDSC_6175

Curator: @scibot

SciCrunch record: RRID:BDSC_6175

What is this?

DOI: 10.1002/dvg.70053

Resource: RRID:BDSC_37933

Curator: @scibot

SciCrunch record: RRID:BDSC_37933

What is this?

DOI: 10.1002/dvg.70053

Resource: (Jackson ImmunoResearch Labs Cat# 703-545-155, RRID:AB_2340375)

Curator: @scibot

SciCrunch record: RRID:AB_2340375

What is this?

DOI: 10.1002/dvg.70053

Resource: Affinity Designer (RRID:SCR_016952)

Curator: @scibot

SciCrunch record: RRID:SCR_016952

What is this?

DOI: 10.1002/dvg.70053

Resource: Fiji (RRID:SCR_002285)

Curator: @scibot

SciCrunch record: RRID:SCR_002285

What is this?

DOI: 10.1002/dvg.70053

Resource: RRID:BDSC_13502

Curator: @scibot

SciCrunch record: RRID:BDSC_13502

What is this?

DOI: 10.1002/dvg.70053

Resource: (Jackson ImmunoResearch Labs Cat# 115-165-003, RRID:AB_2338680)

Curator: @scibot

SciCrunch record: RRID:AB_2338680

What is this?

DOI: 10.1002/dvdy.70144

Resource: (Thermo Fisher Scientific Cat# A-11001, RRID:AB_2534069)

Curator: @scibot

SciCrunch record: RRID:AB_2534069

What is this?

DOI: 10.1002/dvdy.70144

Resource: (Thermo Fisher Scientific Cat# A-11012, RRID:AB_2534079)

Curator: @scibot

SciCrunch record: RRID:AB_2534079

What is this?

DOI: 10.1002/dvdy.70144

Resource: (Thermo Fisher Scientific Cat# 14-5923-82, RRID:AB_2572892)

Curator: @scibot

SciCrunch record: RRID:AB_2572892

What is this?

DOI: 10.1002/dvdy.70144

Resource: RRID:CVCL_D5A6

Curator: @scibot

SciCrunch record: RRID:CVCL_D5A6

What is this?

DOI: 10.1002/dvdy.70144

Resource: RRID:CVCL_D5A7

Curator: @scibot

SciCrunch record: RRID:CVCL_D5A7

What is this?

DOI: 10.1002/dvdy.70144

Resource: RRID:AB_10856008

Curator: @scibot

SciCrunch record: RRID:AB_10856008

What is this?

DOI: 10.1002/cbdv.71312

Resource: (RRID:CVCL_0291)

Curator: @scibot

SciCrunch record: RRID:CVCL_0291

What is this?

DOI: 10.1002/cbdv.71312

Resource: (RRID:CVCL_0062)

Curator: @scibot

SciCrunch record: RRID:CVCL_0062

What is this?

DOI: 10.1002/cbdv.71312

Resource: (BCRJ Cat# 0278, RRID:CVCL_0132)

Curator: @scibot

SciCrunch record: RRID:CVCL_0132

What is this?

DOI: 10.1002/cbdv.71312

Resource: (JCRB Cat# JCRB9041, RRID:CVCL_0556)

Curator: @scibot

SciCrunch record: RRID:CVCL_0556

What is this?

DOI: 10.1002/cbdv.71299

Resource: (BCRJ Cat# 0278, RRID:CVCL_0132)

Curator: @scibot

SciCrunch record: RRID:CVCL_0132

What is this?

DOI: 10.1002/cbdv.71279

Resource: (KCB Cat# KCB 200770YJ, RRID:CVCL_0182)

Curator: @scibot

SciCrunch record: RRID:CVCL_0182

What is this?

DOI: 10.1002/cbdv.71265

Resource: (ATCC Cat# TIB-71, RRID:CVCL_0493)

Curator: @scibot

SciCrunch record: RRID:CVCL_0493

What is this?

DOI: 10.1002/cbdv.202503695

Resource: RRID:CVCL_A9J4

Curator: @scibot

SciCrunch record: RRID:CVCL_A9J4

What is this?

DOI: 10.1002/cbdv.202503695

Resource: RRID:CVCL_3241

Curator: @scibot

SciCrunch record: RRID:CVCL_3241

What is this?

DOI: 10.1002/cbdv.202503695

Resource: (KCB Cat# KCB 200970YJ, RRID:CVCL_0336)

Curator: @scibot

SciCrunch record: RRID:CVCL_0336

What is this?

DOI: 10.1002/cbdv.202503695

Resource: RRID:CVCL_6990

Curator: @scibot

SciCrunch record: RRID:CVCL_6990

What is this?

DOI: 10.1002/cbdv.202503506

Resource: (ATCC Cat# SCRC-1041, RRID:CVCL_3285)

Curator: @scibot

SciCrunch record: RRID:CVCL_3285

What is this?

DOI: 10.1002/cbdv.202503421

Resource: (CCLV Cat# CCLV-RIE 1035, RRID:CVCL_0023)

Curator: @scibot

SciCrunch record: RRID:CVCL_0023

What is this?

DOI: 10.1002/cbdv.202502045

Resource: (ATCC Cat# CRL-2254, RRID:CVCL_0140)

Curator: @scibot

SciCrunch record: RRID:CVCL_0140

What is this?

DOI: 10.1002/cbdv.202502045

Resource: (KCLB Cat# 10119, RRID:CVCL_0207)

Curator: @scibot

SciCrunch record: RRID:CVCL_0207

What is this?

DOI: 10.1002/btm2.70148

Resource: (RRID:CVCL_0062)

Curator: @scibot

SciCrunch record: RRID:CVCL_0062

What is this?

DOI: 10.1002/ana.78252

Resource: Parkinson's Progression Markers Initiative (RRID:SCR_006431)

Curator: @scibot

SciCrunch record: RRID:SCR_006431

What is this?

DOI: 10.1002/ana.78250

Resource: Parkinson's Progression Markers Initiative (RRID:SCR_006431)

Curator: @scibot

SciCrunch record: RRID:SCR_006431

What is this?

DOI: 10.1002/ana.78249

Resource: Parkinson's Progression Markers Initiative (RRID:SCR_006431)

Curator: @scibot

SciCrunch record: RRID:SCR_006431

What is this?

DOI: 10.1002/ana.78242

Resource: Parkinson's Progression Markers Initiative (RRID:SCR_006431)

Curator: @scibot

SciCrunch record: RRID:SCR_006431

What is this?

DOI: 10.1002/advs.202523574

Resource: (CLS Cat# 300342/p657_SK-OV-3, RRID:CVCL_0532)

Curator: @scibot

SciCrunch record: RRID:CVCL_0532

What is this?

DOI: 10.1002/advs.202523574

Resource: RRID:CVCL_0063

Curator: @areedewitt04

SciCrunch record: RRID:CVCL_0063

What is this?

DOI: 10.1002/advs.202523374

Resource: (CLS Cat# 300342/p657_SK-OV-3, RRID:CVCL_0532)

Curator: @scibot

SciCrunch record: RRID:CVCL_0532

What is this?

DOI: 10.1002/advs.202523374

Resource: (NCI-DTP Cat# OVCAR-8, RRID:CVCL_1629)

Curator: @scibot

SciCrunch record: RRID:CVCL_1629

What is this?

DOI: 10.1002/advs.202523374

Resource: (RRID:CVCL_0297)

Curator: @scibot

SciCrunch record: RRID:CVCL_0297

What is this?

DOI: 10.1002/advs.202521188

Resource: (BCRJ Cat# 0331, RRID:CVCL_B260)

Curator: @scibot

SciCrunch record: RRID:CVCL_B260

What is this?

DOI: 10.1002/advs.202521188

Resource: (CCLV Cat# CCLV-RIE 1035, RRID:CVCL_0023)

Curator: @scibot

SciCrunch record: RRID:CVCL_0023

What is this?

DOI: 10.1002/advs.202521188

Resource: (BCRC Cat# 60414, RRID:CVCL_2142)

Curator: @scibot

SciCrunch record: RRID:CVCL_2142

What is this?

DOI: 10.1002/advs.202519344

Resource: (RCB Cat# RCB0988, RRID:CVCL_0025)

Curator: @scibot

SciCrunch record: RRID:CVCL_0025

What is this?

DOI: 10.1002/advs.202519344

Resource: (ATCC Cat# CRL-1446, RRID:CVCL_0286)

Curator: @scibot

SciCrunch record: RRID:CVCL_0286

What is this?

DOI: 10.1002/adfm.75716

Resource: Massachusetts Institute of Technology Swanson Biotechnology Center Nanotechnology Materials Core Facility (RRID:SCR_018674)

Curator: @scibot

SciCrunch record: RRID:SCR_018674

What is this?

DOI: 10.1002/1878-0261.70266

Resource: ImageJ (RRID:SCR_003070)

Curator: @scibot

SciCrunch record: RRID:SCR_003070

What is this?

DOI: 10.1002/1878-0261.70266

Resource: RRID:Addgene_48138

Curator: @scibot

SciCrunch record: RRID:Addgene_48138

What is this?

DOI: 10.1002/1878-0261.70266

Resource: (Cell Signaling Technology Cat# 3024, RRID:AB_331253)

Curator: @scibot

SciCrunch record: RRID:AB_331253

What is this?

DOI: 10.1002/1878-0261.70266

Resource: GraphPad Prism (RRID:SCR_002798)

Curator: @scibot

SciCrunch record: RRID:SCR_002798

What is this?

DOI: 10.1002/1878-0261.70266

Resource: (Cell Signaling Technology Cat# 3027, RRID:AB_2122378)

Curator: @scibot

SciCrunch record: RRID:AB_2122378

What is this?

DOI: 10.1002/1878-0261.70266

Resource: (RRID:CVCL_4Y35)

Curator: @scibot

SciCrunch record: RRID:CVCL_4Y35

What is this?

DOI: 10.1002/1878-0261.70266

Resource: (CLS Cat# 300168/p708_DU-145, RRID:CVCL_0105)

Curator: @scibot

SciCrunch record: RRID:CVCL_0105

What is this?

DOI: 10.1002/1878-0261.70266

Resource: (RRID:CVCL_3422)

Curator: @scibot

SciCrunch record: RRID:CVCL_3422

What is this?

DOI: 10.1113/JP290832

Resource: RRID:AB_2799176

Curator: @areedewitt04

SciCrunch record: RRID:AB_2799176

What is this?

DOI: 10.1016/j.stem.2026.04.013

Resource: RRID:IMSR_JAX:008610

Curator: @nmaralla

SciCrunch record: RRID:IMSR_JAX:008610

What is this?

Le "coup libriste" : subvertir depuis les marges, pour redonner du pouvoir d'action → c'est plus ou moins l'idée du libre, mais avec un soin particulier aux individus qui n'ont pas les compétences nécessaires pour appréhender ces problématiques.

UK Travel Photography Blog Next Steps

You can find more UK travel photography in the NHC Search Engine. Or see the original source.

Read the UK Travel Photography Blog for interesting locations and beautiful photos. Personalised with occasional gaming stories.

UK Travel Photography Blog Introduction

When The Sassy Owl isn't showing you great photos from the UK, they may be entertaining you with gaming stories. Such as Kubb Lawn Game.

2026-05-12T10:09:05+00:00

uk travel photography blog

UK Travel Photography Blog

2026-05-12T10:08:05+00:00

Do you love reading about Science, Technology, Engineering, and Mathematics? Then cyprianj's STEM Blog is just right for you. Browse the STEM Blog now for interesting facts, experience and opinions.

cyprianj's STEM Blog

Science, Technology, Engineering, and Mathematics are fascinating. Get great insight from this STEM Blog now.

stem blog

eLife Assessment

This study provides a useful demonstration that, at least for the systems examined, aspects of the entropic contribution to protein-ligand binding can be inferred directly from crystallographic data. In doing so, it strengthens a view of crystal structures as heterogeneous ensembles that are amenable to statistical-mechanical analysis rather than purely static models. The analytical approaches are carefully developed and transparently discussed, with thoughtful consideration of both successful and less effective methods, lending solid support to the central conclusions. However, because the analysis is based on a relatively small and narrowly sampled set of protein-ligand complexes, the generality of these findings remains speculative and will require broader validation.

Reviewer #1 (Public review):

Summary:

The authors show that if they generate a weighted multi-conformer ensemble of structural models to fit crystallographic electron density data, the application of statistical mechanical methodologies to that ensemble can provide reasonable estimates of configurational entropy terms related to protein-ligand binding.

Strengths:

A fair range of proteins (12) and ligands (70) is included in the study. The analytical methodologies are well described. Both successful and less successful analytical approaches are discussed, and the latter are frequently as insightful as the former.

Weaknesses:

Compared to the universe of protein-ligand complexes, this dataset is inevitably very limited, so the generality of the observations made here remains speculative. Though a fair range of proteins is studied, the dynamic range in the binding affinity data is limited. The practical utility of the approach is never really commented on.

Reviewer #2 (Public review):

The manuscript by Miller and Wankowicz (M&W) develops a crystallographic approach to predict the contribution of protein conformational entropy to the total binding entropy using multi-conformer ensemble models. The approach loosely follows the path developed by Wand using NMR relaxation methods. Their approach is to generate local crystallographic order parameters (analogous to NMR order parameters) to estimate protein conformational entropy and then combine this with statements about water entropy. The static view of the ensemble is perhaps easier to grasp, with respect to entropy, than the NMR-based dynamical view. This approach is potentially ground-breaking and of great importance given the ease, relative to NMR, with which the source data can be obtained. However, the approach has several deficiencies, only some of which are noted by the authors.

Like the initial Wand approach (Frederick et al Nature, 2007), M&W develop a simple counting relationship between members of the ensemble and a statement about conformational entropy. For reasons that are not clear, M&W utilize "per residue" scaling, which was initially introduced by Wand but later discarded for the more physically meaningful "per torsion angle" scaling. As noted in the Nature 2007 paper, this assumes uncorrelated occupancy. The current Wand approach (Caro et al PNAS, 2017) subsumes correlated occupancy and potentially incomplete sampling of the ensemble into an empirically determined scaling parameter (sd). This is likely a major contributor to the mysterious 1/4 scaling factor that is introduced. It is not clear to me how discrete conformational states are counted from the qFit models. Using the B-factor, as opposed to a thermal factor, to account for motion in a rotamer well seems suspect. With some irony, M&W only look at chi-1 rotamers in distinct contrast to the NMR approach, which looks at the end of the side chain, which captures the entire disorder. On the other hand, the crystallographic approach "sees" all side chains, whereas the NMR approach, as currently rendered, looks only at methyl-bearing side chains and requires coupling to neighbors to report on all side chains (see Kasinath JACS 2013 and Wand & Sharp ARB 2018).

Nevertheless, as noted by Nature 2007, the fact that a linear relationship is seen between the apparent conformational entropy and total binding entropy suggests that the former is a major component of the latter. It also reinforces the idea that dSrt is constant for higher affinity complexes, i.e., residual rigid-body motion of protein relative to ligand is limited (a conclusion reached in PNAS 2017) but not mentioned. This is an important result.

The classic hydrophobic effect is potentially a significant component of total binding entropy. Here, the manuscript falls flat by focusing on crystallographically resolved waters. As shown in site-resolved detail (Nucci et al, NSMB 2011 and others), hydration water has a range of residual motion (entropy) that will modulate contributions to water entropy upon displacement from an interface. A very clear example of the potential for large contributions was demonstrated in the wet interface of a barnase-DNA complex (PNAS 2017). The fact that the classic dASA treatment failed, I think, points to problems elsewhere in the approach.

I note that the range of ligand types explored by M&W is quite limited as compared to PNAS 2017, making generalization somewhat difficult (see Wand Cur. Opin. Struct. Biol, 2013 for why this is important). Finally, it is disappointing that the authors chose not to examine systems common to PNAS 2017, making direct comparison to the NMR method impossible.

In summary, this manuscript sets the field in a new direction. It is a first serious look at conformational entropy using crystallographic approaches. If fully validated, this approach would permit an explosion of insight since the crystallography is now straightforward, very fast and capable of approaching larger systems, relative to the NMR approach. However, there are missing quantitative elements represented by a formal relationship that is fitted by the data. I do not think this is a fatal flaw for this manuscript, however. If the supplementary material is improved for clarity and completeness (e.g, include tables of thermodynamic data; conformer analysis; B-factors) such that all figures could be independently reproduced and therefore analyzed in different ways, and the comments made above are addressed, if not resolved, then I think this manuscript could become a keystone for this new direction.

eLife Assessment

This study provides valuable insights into how cells maintain sphingolipid homeostasis through transcriptional control and regulated protein degradation in response to changes in sphingolipid levels. The evidence supporting the conclusions is convincing overall, with solid genetic and biochemical approaches, while some mechanistic aspects remain to be clarified. This work will be of interest to researchers studying lipid metabolism and membrane biology.

Reviewer #1 (Public review):

Matsumoto et al. identify Com2, a C2H2-type zinc finger transcription factor not previously linked to sphingolipid metabolism, as a regulator of this pathway in budding yeast. They show that depletion of sphingolipids by myriocin, an inhibitor of serine palmitoyl transferase, increases Com2 expression. This, in turn, promotes the expression of the protein kinase Ypk1 and enhances TORC2-dependent phosphorylation of Ypk1. The authors identify a Com2-binding site in the YPK1 promoter and provide evidence that Com2 functions upstream of Ypk1 to regulate its<br /> expression. They further report that Com2 abundance is controlled by the ubiquitin-proteasome system: degradation of Com2 is inhibited by myriocin treatment and enhanced by phytosphingosine. Mutational analyses of putative phosphorylation and ubiquitination sites support a role for these modifications in regulating Com2 stability. Based on these findings, the authors propose that Com2 acts as a transcriptional regulator of sphingolipid metabolism that responds to sphingolipid levels and promotes Ypk1 expression.

Strengths:

This study provides a valuable finding on the regulation of sphingolipid synthesis by the transcription factor Com2 in budding yeast. The evidence supporting the authors' claims is solid, although additional evidence clarifying the mechanisms and biological significance of ubiquitin-proteasome-mediated degradation of Com2 would strengthen the work. This work will be of interest to microbiologists studying budding yeast.

Weaknesses:

The biological significance of Com2 degradation is not sufficiently clear, which represents an important limitation of the study. It would also be important to determine whether Com2 is actively degraded under normal growth conditions, such as during logarithmic growth in the absence of drug treatment.

Reviewer #2 (Public review):

Summary:

In this study, Matsumoto and co-workers use budding yeast as a model organism to identify and characterize transcriptional mechanisms that homeostatically regulate sphingolipid metabolism. Through a genetic suppressor screen and a series of genetic, molecular, and biochemical analyses, they identify the transcription factor Com2 as a key regulator that responds to sphingolipid levels and regulates the expression of genes such as YPK1, which in turn controls the activity of several enzymes in the yeast sphingolipid biosynthetic pathway.

Com2 itself is further regulated by the ubiquitin proteasome system in response to sphingolipid levels. High sphingolipid levels promote proteasomal degradation of Com2, whereas low sphingolipid levels stabilize Com2. These findings suggest that Com2 is a central component of a feedback system that helps maintain sphingolipid homeostasis.

Strengths:

The identification of Com2 as an upstream regulator of the TORC2-Ypk1 pathway is supported by multiple orthogonal lines of evidence. The authors also provide mechanistic insight into how Com2 protein levels are dynamically controlled through phosphorylation and ubiquitin-mediated degradation. Stabilization of Com2 in response to sphingolipid depletion appears to be required for the transcriptional upregulation of YPK1 expression.

Weaknesses:

Although several important questions remain unresolved, such as which kinases function upstream of Com2 and which ubiquitin ligase(s) target Com2, this work is nevertheless likely to have a meaningful impact on the field of sphingolipid metabolism. The identification of a regulated transcription factor that responds to sphingolipid levels may also be of broader interest to researchers studying membrane homeostasis.

Reviewer #3 (Public review):

This paper extends the authors' 2022 studies of how the synthesis of membrane sphingolipids is regulated in budding yeast. Here, they hypothesized that overexpression of a protein involved in sphingolipid (SL) biosynthesis would confer resistance of lip1-1 cells, which are Dox-inducibly defective in expression of a ceramide synthase regulatory subunit, to myriocin (Myr), a serine palmitoyltransferase inhibitor that inhibits SL synthesis. To test this idea, they transformed lip1-1 cells with a multi-copy genomic library, selecting for Myr resistance. Apart from LIP1 itself and YPK1, a protein kinase downstream of TORC2, COM2, which encodes the Com2 C2H2-type zinc finger transcription factor, was the most frequent hit in the screen. They went on to show that com2Δ cells exhibited Myr sensitivity, and that Com2 protein expression was induced under conditions that reduced complex sphingolipid synthesis, such as Myr-treatment. Using ypk1-as ypk2Δ cells and the 3-MB-PP1 Ypk1as a selective Ypk1as kinase inhibitor, they showed that Com2 phosphorylation was independent of Ypk1 activity, suggesting that Ypk1 lies downstream of Com2. Consistently, Myr treatment, which reduces SL synthesis, resulted in an increase in both Com2 and Ypk1 proteins. By generating a Ptet-off-GFP-COM2 strain they showed that when Dox was removed to induce GFP-Com2 overexpression, Myr resistance was increased. They went on to show that Com2 binds to a Com2 response element in the YPK1 promoter and drives expression of Ypk1. This was confirmed by showing that expression of a YPK1-driven lacZ reporter gene was also elevated when GFP-Com2 overexpression was induced. CRISPR deletion of the putative Com2-binding site (CBS) from the endogenous YPK1 promoter was used to generate PYPK1-ΔCBS cells, which showed a significant reduction in Ypk1 expression and exhibited intermediate Myr sensitivity, suggesting that Com2 is important for but not the only regulator of Ypk1 expression. Analysis of SL levels showed that they largely paralleled the levels of Ypk1 protein and active pT662 Ypk1. Using deletion analysis of the COM2 gene, they showed that residues 2-190 and the C-terminal DNA binding domain of Com2 were essential for Com2 function in the SL synthesis pathway. Deletion of {greater than or equal to}40 amino acids from the N-terminus increased expression of Com2 protein irrespective of Myr treatment, suggesting that Com2 protein levels are regulated by protein stability. Consistently, they found the high level of Com2 protein induced by Myr was rapidly reversed by treatment with phytosphingosine (PHS), a ceramide precursor that bypasses the Myr-blocked step and restores SL synthesis. The reduction in Com2 protein plus PHS was prevented by MG132 proteasome inhibitor treatment and led to the accumulation of polyUb-Com2 species, consistent with Com2 being negatively regulated by SL-induced UPS-mediated degradation. Based on the use of selective inhibitors of different steps in SL synthesis, they showed that SL biosynthesis up to the level of MIPC (mannnosyldiinositol phosphorylceramide) is required for the SL-mediated degradation response. Based on individual and combined K to R mutagenesis of the three Lys in Com2 1-49, they showed that K23, K35 and K51 in combination are needed for PHS-induced Com2 degradation, and therefore are likely to be the main Com2 Ub sites. Finally, they observed that PHS induced an increase in K3R Com2 phosphorylation, finding that an S/T10A mutant was only weakly phosphorylated and was resistant to PHS-induced degradation, suggesting that phosphorylation of Com2 is required for PHS-dependent degradation.

The paper is clearly written, and the data in Figures 1-6 show convincingly that the Com2 zinc finger protein, by inducing the expression of a set of genes, including YPK1 and LCB1, plays an important role in sphingolipid (SL) homeostasis in yeast under conditions when sphingolipid levels are low. However, the data in Figures 7 and 8, where the authors provide evidence that the Com2 protein was rapidly degraded in a proteasome-dependent manner in response to phytosphingosine (PHS) treatment, dependent on the N-terminal 40 residues of Com2 and a combination of three Lys residues in this region, are intriguing but incomplete. There are a number of issues, including the identity of the Com2 ubiquitylation sites. They showed that the K23/35/51R Com2 mutant was stabilized, but did they provide direct evidence that these three Lys are in fact ubiquitylated (e.g. GG-K peptide enrichment based MS analysis of Ub-Com2 from PHS-treated, MG132-treated cells). They showed that PHS treatment increased Myc13-tagged Com2 ubiquitylation in the presence of MG132, but did not show that the K3R Com2 mutant (or the S/T10A phosphorylation site Com2 mutant) failed to be ubiquitylated. They also found that the WT Com2 and particularly the K3R Com2 mutant protein exhibited hyperphosphorylation in response to PHS treatment, and that mutation of 10 potential pSer sites to Ala abolished this effect, and stabilized the Com2 protein. However, it is unclear whether the K3R mutation led to increased Com2 hyperphosphorylation per se following PHS treatment, or whether this is because there is more K3R protein, as they suggest might be the case. It is also not clear what protein kinase is responsible or how it might be activated when SL levels are high. In addition, the E3 Ub ligase needed for Com2 degradation was not identified, and it is not clear whether Com2 phosphorylation is directly involved in its recognition by a phosphodependent E3 Ub ligase, as they propose in the model shown in Figure 9. Finally, and perhaps most importantly. It is unclear how elevated levels of phytosphingosine or any sphingolipid are sensed by the Com2 pathway in order to switch on the degradation response as a negative feedback event. The model depicted in Figure 9 exposes all of these unknowns. The paper would be significantly strengthened by additional experiments defining how complex SL levels are sensed, how Com2 is phosphorylated in response to SL sensor signals, and how (phospho)Com1 is recognized for ubiquitylation and degradation.

In summary, the finding that the Com2 zinc finger transcription factor is an upstream regulator of the sphingolipid biosynthesis pathway in budding yeast, acting as part of an SL sensor system to maintain sphingolipid homeostasis, is new and potentially important. However, more mechanistic work needs to be done to address the unanswered questions raised by the data in Figures 7 and 8.

eLife Assessment

This study presents important findings on the molecular mechanisms governing how the natural killer cell receptor KIR2DL4 interacts with HLA-G and undergoes internalization. The authors provide solid evidence for an allosteric disulfide-bond switch that regulates receptor activity, using a multifaceted approach that includes mutagenesis, mass spectrometry, and imaging. The work would be further strengthened by validating these mechanisms in primary immune cells and providing direct structural evidence for the proposed ligand-binding interface.

Reviewer #1 (Public review):

Summary:

This paper asks how the NK cell receptor KIR2DL4 binds HLA-G and undergoes endocytosis. The authors propose that an allosteric disulfide-bond switch controls whether the receptor is in a ligand-binding or non-binding state, and they support this model using mutagenesis, imaging, mass spectrometry, and structural prediction.

Strengths:

A major strength is the use of diverse, complementary approaches to validate the central claim. The authors combined unbiased random mutagenesis to identify key residues, confocal microscopy to track cellular localization , and mass spectrometry to quantify the redox states of specific disulfide bonds. These methods consistently support a single model: an allosteric disulfide switch. The transition between a Cys10-Cys28 bond and a Cys28-Cys74 bond serves as a functional switch that controls whether the receptor resides at the plasma membrane to bind ligand or remains inactive in endosomes.

Weaknesses:

The core model is interesting, but some of the strongest mechanistic claims still rely heavily on structure prediction rather than direct structural evidence, especially the proposed HLA-G contact surface in Figure 6.

The paper supports an effect of the disulfide state on trafficking and uptake, but the case for direct KIR2DL4-HLA-G binding still feels somewhat indirect. The manuscript itself notes that direct binding had not been previously shown, and the current explanation partly depends on inference about which disulfide state is present.

Most of the main experiments are done in transfected 293T cells, so it is still not fully clear how strongly this mechanism carries over to the more relevant NK-cell setting discussed in the paper.

The cellular evidence for the PDI story is not specific, since it depends a lot on inhibitor and blocking experiments that could affect the broader extracellular redox environment.

Reviewer #2 (Public review):

Summary:

Rajagopalan et al show how extracellular domain features regulate KIR2DL4 internalization. The trafficking phenotypes of cysteine mutants are logically organized, and well-summarized in a Table. The disulfide mapping and differential alkylation strategy are appropriate and provide strong support for alternative disulfide configurations in D0. The higher accessibility or more selective reduction of Cys10-Cys28 as compared to Cys28-Cys74 by PDI is a key mechanistic anchor.

Strengths:

The identification of a conformational switch in KIR2DL4 is conceptually novel. Experimental elegance, detailed and well-written.

Weaknesses:

Most of the mechanistic work was shown in HEK293. The authors should exhibit relevance using primary NK cells (using primary NK)

Horizontal carousels may make navigation harder - Potential accessibility issue

This horizontal carousel may create accessibility challenges. Some content is partially hidden off-screen, and users need to scroll sideways or use small arrow controls to view everything. This could make navigation less intuitive for keyboard users, screen reader users, or people with motor impairments. From the Operable principle, content should be easy to navigate without requiring precise or difficult interactions.

Large visual product carousel — Potential accessibility issue

This large visual product carousel may be less accessible for some users. Because the section relies heavily on images and horizontal navigation, users with visual impairments, motor impairments, or those using keyboard navigation may find it more difficult to browse all of the content. This connects to the Operable principle, which emphasizes that web interfaces should be easy to navigate without requiring overly precise or complex interaction.

Clear category structure

Clear category labels, such as “Kitchen & appliances” and “Outdoor products,” make the page easier to understand and navigate. This supports the Understandable principle of accessibility because users can quickly identify where different types of content are located. A clear category structure is also helpful for users who rely on screen readers or who may feel overwhelmed by a visually busy shopping page.

“28% off, save $70"

This is a positive accessibility feature because the sale is communicated through both colour and text, rather than colour alone. The red price helps draw attention visually, but the written discount information, such as “28% off, save $70.00,” ensures that users who are colourblind or using assistive technologies can still understand the meaning. This supports the Perceivable principle.

Clear section headings - “Inspiration for every room”

This is a good example of the Understandable principle of web accessibility. Clear section headings help users quickly understand how the page is organized and what kind of content appears in each area. They also support screen reader navigation, since users can move through a page by headings instead of reading every item in order.

1. 内联（Inline）：打破物理边界的利器与代价 既然 HLS 把子函数当黑盒，这就带来一个问题：它无法做全局优化。 比如，如果在小黑盒的末尾有一个乘法，在大黑盒里拿到结果后马上跟了一个加法。因为有函数边界的阻挡，HLS 可能会强行在这两个操作中间插入寄存器（断开操作链接）。

这时候，inline（内联指令） 就派上用场了。 如图 2.11 所示，一旦你在子函数上加了 inline：

HLS 会直接抹除函数的物理边界。

所有的子逻辑全部暴露给顶层，融合成一坨巨大的组合逻辑。

好处： HLS 获得了“上帝视角”，它可以跨界进行资源共享和操作链接（Operation Chaining），从而缩短延迟（Latency），省下一些边界上的寄存器。

坏处与警告： 就像之前提到的“循环完全展开”一样，如果你的顶层逻辑极度复杂，你还把所有子模块都 inline 进来，这会生成一个无比庞大的数据流图。Vivado HLS 会被这海量的约束关系搞得内存溢出、耗费几个小时都综合不出来，甚至导致布线失败。

一句话总结： 层次化结构（不内联）是帮 EDA 工具减负，让代码结构模块化，但可能损失一点点跨界优化的性能；内联（Inline）是帮硬件提速，让逻辑融会贯通，但极容易让综合工具崩溃。合理的架构设计，就是在两者之间找平衡。

static 意味着这是必须保存状态的物理寄存器（D触发器）。你需要 4 个独立的滤波器同时运行，就必须在芯片上分配 4 套完全不同的物理寄存器。写 4 个不同的函数名，就是强迫 HLS 去生成 4 个独立的物理黑盒子。（注：在现代 HLS C++ 开发中，我们通常用面向对象的 Class/Template 或 HLS Allocation 指令来优雅地解决这个问题，而不需要傻傻地复制 4 遍代码）。

它是一个由 Xilinx 提供、专为硬件综合定制的 C++ 第三方类库。如果你试图脱离 Vivado HLS 环境，用纯 GCC 或 Clang 编译器去编译这段代码且不指定 Xilinx 头文件的路径，编译器是会报错找不到 ap_int 定义的。

虽然它是 Vivado HLS 专有的，但它完全符合 C++ 的语法规范。 实际上，ap_int 和 ap_uint 是 Xilinx 工程师用 C++ 写好的 模板类（Template Classes）。

当你 #include "ap_int.h" 时，你实际上引入了一大堆 C++ 的类定义。

这些类内部使用了 C++ 运算符重载（Operator Overloading） 技术，重载了 +、-、*、>>、== 等所有常用运算符。

这就使得你在写代码时，操作 ap_uint<12> a; 感觉就像在操作一个普通的 int 一样自然，但底层其实是在调用 Xilinx 写好的类方法进行位运算。

在第 44 个时钟周期结束那一瞬间，最终的累加结果 acc 已经被成功写入了寄存器。至于第 45 个周期硬件还在那里傻傻地检查退出条件、清理状态机，这些动作对下游接收数据的模块来说毫无意义。 因为在第 44 拍末尾，结果已经有效（Valid）了。所以，HLS 的报告会减去最后那个无效等待周期，告诉你：“下游模块在第 44 个周期就能拿走数据了”。

对于微小循环（Micro-loops），尽情使用“完全展开”来榨干延迟；但对于大循环（Macro-loops），必须老老实实使用带有特定因子的“部分展开（Partial Unroll）”再配合“流水线（Pipeline）”，这才是寻找最佳性价比硬件架构的核心能力。

硬件上会表现为全1（-1的补码），读出来的数可能全是XXX

操作链接（Operation Chaining）是指在硬件电路中，将多个“组合逻辑（Combinational Logic）”首尾相连，中间不插入任何寄存器（Register/FF），从而让这些串联的计算在“同一个时钟周期内”一口气完成的综合技术。

Never thought about it this way. Guess that's part of why it's called compsci.

Como conclusión, me deja reflexionando sobre el futuro de la democracia en la región, porque la forma democrática que conocemos (votar), es realmente insuficiente sin la esencia o contenido democrático (participación real de la ciudadanía).

América Latina tiene que construir una democracia sustantiva, que termine con el Estado Burocrático Autoritario.

Sin duda, hay una crisis de representación, porque la democracia actualmente ha generado una ciudadanía apática, que ya no confía en sus servidores públicos, ni en los procesos de gobierno, así que no existe una democracia real.

Este modelo termina con la idea de la soberanía popular, porque la democracia se reduce a un grupo electoral donde los ciudadanos somos consumidores de partidos políticos, y el gobierno se ejerce por élites que se consideran las únicas capaces de manejar el Edo.

Yo entiendo que nos habla de una democracia que se rige por el poder económico, en la cual la distribución de riqueza queda fuera de la negociación, limitando la democracia a lo procedimental solamente, y no a un tema de fondo.

Pienso que la soberanía nacional se ve comprometida en este modelo, porque el Estado ya no le hace caso a la sociedad, a su electorado, sino a los requerimientos de organismos internacionales y flujos de capital extranjero.

Estos 3 puntos considero que implican una reforma constitucional, ya que el Edo pierde un poco su responsabilidad social para convertirse en un garante de la estabilidad macroeconómica, subordinando los derechos sociales a los intereses del mercado.

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