bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of the X-Auger electron spectroscopy evolution of indium in InSb by linear and nonlinear least squares approaches
Authors: Béchu Solène , Fairley Neal
Published: January 2024

X-ray photoelectron spectroscopy is a major and valuable chemical analysis technique that can bring a wide range of information if one takes time to carefully interpret the spectra. In particular, many metrological developments deal with the modeling of photoelectron peaks while X-Auger transitions still remain hardly exploited. Here, an innovative approach examining these spectral features in a complementary way is presented and illustrated on a concrete case dealing with chemical changes of indium in the InSb semiconductor during its air aging. Indium contains an extensive range of photopeaks along the energy scale, meaning electrons emitted from different escape depths are present on the same widescan spectrum, and, thus, information from different depths is accessible. Specifically, this study focuses on indium’s X-Auger electron spectroscopy (X-AES) transitions and decomposition to track the outer surface chemistry evolution of the InSb semiconductor. To this end, we compared linear and nonlinear least-squares approaches to decompose In M4,5N4,5N4,5 X-AES transition and demonstrate oxide growth progression. For both approaches, we applied the vectorial method (also known as the informed amorphous sample model) to retrieve the different chemical environments present during air aging. Linear and nonlinear least-squares approaches were both found to yield comparable results, with a comparative error of less than 10%. Over time, a progressive growth of the oxide layer was demonstrated, ranging from 0.3 ± 0.2 to 2.9 ± 0.2 nm using the X-AES transitions. Additionally, decomposition of the In 3d and In 4d photoelectron peaks showed a lower thickness of oxide with time due to the lesser surface sensitivity of these peaks.
Pleiotropic functions of TAO kinases and their dysregulation in neurological disorders
Authors: Byeon Sujin , Yadav Smita
Published: January 2024

Thousand and one amino acid kinases (TAOKs) are relatively understudied and functionally pleiotropic protein kinases that have emerged as important regulators of neurodevelopment. Through their conserved amino-terminal catalytic domain, TAOKs mediate phosphorylation at serine/threonine residues in their substrates, but it is their divergent regulatory carboxyl-terminal domains that confer both exquisite functional specification and cellular localization. In this Review, we discuss the physiological roles of TAOKs and the intricate signaling pathways, molecular interactions, and cellular behaviors they modulate—from cell stress responses, division, and motility to tissue homeostasis, immunity, and neurodevelopment. These insights are then integrated into an analysis of the known and potential impacts of disease-associated variants of TAOKs, with a focus on neurodevelopmental disorders, pain and addiction, and neurodegenerative diseases. Translating this foundation into clinical benefits for patients will require greater structural and functional differentiation of the TAOKs afforded by their individually specialized domains.
Characterization of CD8
+
T cells in immune-privileged organs of ZIKV-infected
Ifnar1
−/−
mice
Authors: Zhang Hangjie , Xiao Wenling , Zhao Min , Zhang Yongli , Lu Dan , Lu Shuangshuang , Zhang Qingxu , Peng Weiyu , Shu Liumei , Zhang Jie , Liu Sai , Zong Kexin , Wang Pengyan , Ye Beiwei , Zhang Danni , Li Shihua , Tan Shuguang , Liu Peipei , Zhao Yingze , Zhang Fuping , Wang Huanyu , Lu Xuancheng , Gao George F. , Liu Jun
Published: January 2024

Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T cell immunity in IPOs in
Ifnar1
−/−
mice, based on an immunodominant epitope E
294-302
tetramer. The distinct kinetics and functions of virus-specific CD8
+
T cells infiltrated into different IPOs were characterized, with late elevation in the brain and spinal cord. Single epitope E
294-302
-specific T cells can account for 20-60% of the total CD8
+
T cells in the brain, spinal cord, and testicle and persist for at least 90 days in the brain and spinal cord. The E
294-302
-specific TCRαβs within the IPOs are featured with the majority of clonotypes utilizing
TRAV9N-3
paired with diverse TRBV chains, but with distinct αβ paired clonotypes in 7 and 30 days post-infection. Specific chemokine receptors,
Ccr2
and
Ccr5
, were selectively expressed in the E
294-302
-specific CD8
+
T cells within the brain and testicle, indicating an IPO-oriented migration of virus-specific CD8
+
T cells after infection. Overall, this study adds to the understanding of virus-specific CD8
+
T cell responses for controlling and clearing ZIKV infection in IPOs.

IMPORTANCE

The immune-privileged organs (IPOs), such as the central nervous system and testicles, presented pathogenicity and inflammation after Zika virus (ZIKV) infection with infiltrated CD8
+
T cells. Our data show that CD8
+
T cells keep up with virus increases and decreases in immune-privileged organs. Furthermore, our study provides the first
ex vivo
comparative analyses of the composition and diversity related to TCRα/β clonotypes across anatomical sites and ZIKV infection phases. We show that the vast majority of TCRα/β clonotypes in tissues utilize
TRAV9N-3
with conservation. Specific chemokine expression, including
Ccr2
and
Ccr5
, was found to be selectively expressed in the E
294-302
-specific CD8
+
T cells within the brain and testicle, indicating an IPO-oriented migration of the virus-specific CD8
+
T cells after the infection. Our study adds insights into the anti-viral immunological characterization and chemotaxis mechanism of virus-specific CD8
+
T cells after ZIKV infection in different IPOs.
A Rydberg atom-based amplitude-modulated receiver using the dual-tone microwave field
Authors: Yuan Jinpeng , Jin Ting , Yan Yang , Xiao Liantuan , Jia Suotang , Wang Lirong
Published: January 2024

We propose a Rydberg atom-based receiver for amplitude-modulation (AM) reception utilizing a dual-tone microwave field. The pseudo-random binary sequence (PRBS) signal is encoded in the basic microwave field (B-MW) at the frequency of 14.23 GHz. The signal can be decoded by the atomic receiver itself but more obvious with the introduction of an auxiliary microwave (A-MW) field. The receiver’s amplitude variations corresponding to microwave field are simulated by solving density matrices to give this mechanism theoretical support. An appropriate AM frequency is obtained by optimizing the signal-to-noise ratio, guaranteeing both large data transfer capacity (DTC) and high fidelity of the receiver. The power of two MW fields, along with the B-MW field frequency, is studied to acquire larger DTC and wider operating bandwidth. Finally, the readout of PRBS signals is performed by both the proposed and conventional mechanisms, and the comparison proves the obvious increment of DTC with the proposed scheme. This proof-of-principle demonstration exhibits the potential of the dual-tone scheme and offers a novel pathway for Rydberg atom-based microwave communication, which is beneficial for long-distance communication and weak signal perception outside the laboratory.
Quantum torque on a non-reciprocal body out of thermal equilibrium and induced by a magnetic field of arbitrary strength
Authors: Kennedy Gerard
Published: January 2024

A stationary body that is out of thermal equilibrium with its environment, and for which the electric susceptibility is non-reciprocal, experiences a quantum torque. This arises from the spatially non-symmetric electrical response of the body to its interaction with the non-equilibrium thermal fluctuations of the electromagnetic field: the non-equilibrium nature of the thermal field fluctuations results in a net energy flow through the body, and the spatially non-symmetric nature of the electrical response of the body to its interaction with these field fluctuations causes that energy flow to be transformed into a rotational motion. We establish an exact, closed-form, analytical expression for this torque in the case that the environment is the vacuum and the material of the body is described by a damped oscillator model, where the non-reciprocal nature of the electric susceptibility is induced by an external magnetic field, as for magneto-optical media. We also generalise this expression to the context in which the body is slowly rotating. By exploring the high-temperature expansion of the torque, we are able to identify the separate contributions from the continuous spectral distribution of the non-reciprocal electric susceptibility, and from the resonance modes. In particular, we find that the torque persists in the limiting case of zero damping parameter, due to the contribution of the resonance modes. We also consider the low-temperature expansion of the torque. This work extends our previous consideration of this model to an external magnetic field of arbitrary strength, thereby including non-linear magnetic field effects.
Evaluating the Impact of Using Multiple-Metal Layers on the Layout Area of Switch Blocks for Tile-Based FPGAs in FinFET 7nm
Authors: Rostami Sani Sajjad , Ye Andy
Published: January 2024

A new area model for estimating the layout area of switch blocks is introduced in this work. The model is based on a realistic layout strategy. As a result, it not only takes into consideration the active area that is needed to construct a switch block but also the number of metal layers available and the actual dimensions of these metals. The model assigns metal layers to the routing tracks in a way that reduces the number of vias that are needed to connect different routing tracks together while maintaining the tile-based structure of FPGAs. It also takes into account the wiring area required for buffer insertion for long wire segments. The model is evaluated based on the layouts constructed in the ASAP7 FinFET 7nm Predictive Design Kit. We found that the new model, while specific to the layout strategy that it employs, improves upon the traditional active-based area estimation models by considering the growth of the metal area independently from the growth of the active area. As a result, the new model is able to more accurately estimate the layout area by predicting when the metal area will overtake the active area as the number of routing tracks is increased. This ability allows the more accurate estimation of the true layout cost of FPGA fabrics at the early floor planning and architectural exploration stage; and this increase in accuracy can encourage a wider use of custom FPGA fabrics that target specific sets of benchmarks in future SOC designs. Furthermore, our data indicate that the conclusions drawn from several significant prior architectural studies remain to be correct under FinFET geometries and wiring area considerations despite their exclusive use of active-only area models. This correctness is due to the small channel widths, around 30–60 tracks per channel, of the architectures that these studies investigate. For architectures that approach the channel width of modern commercial FPGAs with more than 100–200 tracks per channel, our data show that wiring area models justified by detailed layout considerations are an essential addition to active area models in the correct prediction of the implementation area of FPGAs.
Utility-aware Privacy Perturbation for Training Data
Authors: Li Xinjiao , Wu Guowei , Yao Lin , Zheng Zhaolong , Geng Shisong
Published: January 2024

Data perturbation under differential privacy constraint is an important approach of protecting data privacy. However, as the data dimensions increase, the privacy budget allocated to each dimension decreases and thus the amount of noise added increases, which eventually leads to lower data utility in training tasks. To protect the privacy of training data while enhancing data utility, we propose a Utility-aware training data Privacy Perturbation scheme based on attribute Partition and budget Allocation (UPPPA). UPPPA includes three procedures: the quantification of attribute privacy and attribute importance, attribute partition, and budget allocation. The quantification of attribute privacy and attribute importance based on information entropy and attribute correlation provide an arithmetic basis for attribute partition and budget allocation. During the attribute partition, all attributes of training data are classified into high and low classes to achieve privacy amplification and utility enhancement. During the budget allocation, a γ-privacy model is proposed to balance data privacy and data utility so as to provide privacy constraint and guide budget allocation. Three comprehensive sets of real-world data are applied to evaluate the performance of UPPPA. Experiments and privacy analysis show that our scheme can achieve the tradeoff between privacy and utility.
Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues
Authors: Chan Deva D. , Guilak Farshid , Sah Robert L. , Calve Sarah
Published: January 2024

Hyaluronan (HA) plays well-recognized mechanical and biological roles in articular cartilage and synovial fluid, where it contributes to tissue structure and lubrication. An understanding of how HA contributes to the structure of other musculoskeletal tissues, including muscle, bone, tendon, and intervertebral discs, is growing. In addition, the use of HA-based therapies to restore damaged tissue is becoming more prevalent. Nevertheless, the relationship between biomechanical stimuli and HA synthesis, degradation, and signaling in musculoskeletal tissues remains understudied, limiting the utility of HA in regenerative medicine. In this review, we discuss the various roles and significance of endogenous HA in musculoskeletal tissues. We use what is known and unknown to motivate new lines of inquiry into HA biology within musculoskeletal tissues and in the mechanobiology governing HA metabolism by suggesting questions that remain regarding the relationship and interaction between biological and mechanical roles of HA in musculoskeletal health and disease.
Mitochondrial Dynamics at Different Levels: From Cristae Dynamics to Interorganellar Cross Talk
Authors: Kondadi Arun Kumar , Reichert Andreas S.
Published: January 2024

Mitochondria are essential organelles performing important cellular functions ranging from bioenergetics and metabolism to apoptotic signaling and immune responses. They are highly dynamic at different structural and functional levels. Mitochondria have been shown to constantly undergo fusion and fission processes and dynamically interact with other organelles such as the endoplasmic reticulum, peroxisomes, and lipid droplets. The field of mitochondrial dynamics has evolved hand in hand with technological achievements including advanced fluorescence super-resolution nanoscopy. Dynamic remodeling of the cristae membrane within individual mitochondria, discovered very recently, opens up a further exciting layer of mitochondrial dynamics. In this review, we discuss mitochondrial dynamics at the following levels: (a) within an individual mitochondrion, (b) among mitochondria, and (c) between mitochondria and other organelles. Although the three tiers of mitochondrial dynamics have in the past been classified in a hierarchical manner, they are functionally connected and must act in a coordinated manner to maintain cellular functions and thus prevent various human diseases.
Warning Labels as a Public Health Intervention: Effects and Challenges for Tobacco, Cannabis, and Opioid Medications
Authors: Popova Lucy , Massey Zachary B. , Giordano Nicholas A.
Published: January 2024

Warning labels help consumers understand product risks, enabling informed decisions. Since the 1966 introduction of cigarette warning labels in the United States, research has determined the most effective message content (health effects information) and format (brand-free packaging with pictures). However, new challenges have emerged. This article reviews the current state of tobacco warning labels in the United States, where legal battles have stalled pictorial cigarette warnings and new products such as electronic cigarettes and synthetic nicotine products pose unknown health risks. This article describes the emerging research on cannabis warnings; as more places legalize recreational cannabis, they are adopting lessons from tobacco warnings. However, its uncertain legal status and widespread underestimation of harms impede strict warning standards. The article also reviews opioid medication warning labels, suggesting that lessons from tobacco could help in the development of effective and culturally appropriate FDA-compliant opioid warning labels that promote safe medication use and increased co-dispensing of naloxone.
Multi-Instance Contingent Fusion for the Verification of Infant Fingerprints
Authors: Odu Tiwalade O. , Olaniyan Moses O. , Ogunfunmi Tokunbo , Samuel Isaac A. , Badejo Joke A. , Atayero Aderemi A.
Published: January 2024

It is imperative to establish an automated system for the identification of neonates (1–28 days old) and infants (29 days–12 months old) through the utilisation of the readily accessible 500 ppi fingerprint reader. This measure is crucial in addressing the issue of newborn swapping, facilitating the identification of missing children, monitoring immunisation records, maintaining comprehensive medical history, and other related purposes. The objective of this study is to demonstrate the potential for future identification of infants using fingerprints obtained from a 500 ppi fingerprint reader by employing a fusion technique that combines multiple instances of fingerprints, specifically the left thumb and right index fingers. The fingerprints were acquired from babies who were between the ages of one day and six months at the enrolment session. The sum-score fusion algorithm was implemented. The approach mentioned above yielded verification accuracies of 73.8%, 69.05%, and 57.14% for time intervals of 1 month, 3 months, and 6 months, respectively, between the enrolment and query fingerprints.
Different Degrees of Sulfated Laminaria Polysaccharides Recovered Damaged HK-2 Cells and Inhibited Adhesion of Nano-COM and Nano-COD Crystals
Authors: Xu Qiu-Shi , Wu Zhi-Jian , Sun Jian-Ming , Liu Jing-Hong , Huang Wei-Bo , Ouyang Jian-Ming
Published: January 2024

Purpose. The crystal adhesion caused by the damage of renal tubular epithelial cells (HK-2) is the key to the formation of kidney stones. However, no effective preventive drug has been found. This study aims to explore the recovery effects of four Laminaria polysaccharides (SLPs) with different sulfate (–OSO3–) contents on damaged HK-2 cells and the difference in the adhesion of damaged cells to nanometer calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) before and after recovery. Methods. Sodium oxalate (2.6 mmol/L) was used to damage HK-2 cells to establish a damaged model. SLPs (LP0, SLP1, SLP2, and SLP3) with –OSO3– contents of 0.73%, 15.1%, 22.8%, and 31.3%, respectively, were used to restore the damaged cells, and the effects of SLPs on the adhesion of COM and COD, with a size of about 100 nm before and after recovery, were measured. Results. The following results were observed after SLPs recovered the damaged HK-2 cells: increased cell viability, restored cell morphology, decreased reactive oxygen levels, increased mitochondrial membrane potential, decreased phosphatidylserine eversion ratio, increased cell migration ability, reduced expression of annexin A1, transmembrane protein, and heat shock protein 90 on the cell surface, and reduced adhesion amount of cells to COM and COD. Under the same conditions, the adhesion ability of cells to COD crystals was weaker than that to COM crystals. Conclusions. As the sulfate content in SLPs increases, the ability of SLPs to recover damaged HK-2 cells and inhibit crystal adhesion increases. SLP3 with high –OSO3– content may be a potential drug to prevent kidney stones.
Supplementary Table 9 from SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma
Authors: Akashi Hidehiko , Yachida Nozomi , Ueda Haruka , Yamaguchi Manako , Yamawaki Kaoru , Tamura Ryo , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Nagase Yoshikazu , Ueda Yutaka , Ueda Masashi , Abiko Kaoru , Kagabu Masahiro , Baba Tsukasa , Nakaoka Hirofumi , Enomoto Takayuki , Murai Junko , Yoshihara Kosuke
Published: January 2024

Supplementary Table 9
Supplementary Table 8 from SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma
Authors: Akashi Hidehiko , Yachida Nozomi , Ueda Haruka , Yamaguchi Manako , Yamawaki Kaoru , Tamura Ryo , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Nagase Yoshikazu , Ueda Yutaka , Ueda Masashi , Abiko Kaoru , Kagabu Masahiro , Baba Tsukasa , Nakaoka Hirofumi , Enomoto Takayuki , Murai Junko , Yoshihara Kosuke
Published: January 2024

Supplementary Table 8
Supplementary Table 6 from SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma
Authors: Akashi Hidehiko , Yachida Nozomi , Ueda Haruka , Yamaguchi Manako , Yamawaki Kaoru , Tamura Ryo , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Nagase Yoshikazu , Ueda Yutaka , Ueda Masashi , Abiko Kaoru , Kagabu Masahiro , Baba Tsukasa , Nakaoka Hirofumi , Enomoto Takayuki , Murai Junko , Yoshihara Kosuke
Published: January 2024

Supplementary Table 6
Supplementary Table 10 from SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma
Authors: Akashi Hidehiko , Yachida Nozomi , Ueda Haruka , Yamaguchi Manako , Yamawaki Kaoru , Tamura Ryo , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Nagase Yoshikazu , Ueda Yutaka , Ueda Masashi , Abiko Kaoru , Kagabu Masahiro , Baba Tsukasa , Nakaoka Hirofumi , Enomoto Takayuki , Murai Junko , Yoshihara Kosuke
Published: January 2024

Supplementary Table 10
Figure S4 from Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity
Authors: Heiser Ryan A. , Cao Anthony T. , Zeng Weiping , Ulrich Michelle , Younan Patrick , Anderson Martha E. , Trueblood Esther S. , Jonas Mechthild , Thurman Robert , Law Che-Leung , Gardai Shyra J.
Published: January 2024

Supplementary Figure S4. pIRE, pJNK, and CHOP upregulation in lymphoma lines treated with brentuximab vedotin or MMAE
Supplementary Table S3 from Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer
Authors: Mulkearns-Hubert Erin E. , Esakov Rhoades Emily , Ben-Salem Salma , Bharti Rashmi , Hajdari Nicole , Johnson Sadie , Myers Alex , Smith Iris Nira , Bandyopadhyay Smarajit , Eng Charis , Downs Erinn , Lathia Justin D. , Reizes Ofer
Published: January 2024

Estimates for tumorsphere formation efficiency and p-values from Fig. 3C-F.
Supplementary Table S2 from Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer
Authors: Mulkearns-Hubert Erin E. , Esakov Rhoades Emily , Ben-Salem Salma , Bharti Rashmi , Hajdari Nicole , Johnson Sadie , Myers Alex , Smith Iris Nira , Bandyopadhyay Smarajit , Eng Charis , Downs Erinn , Lathia Justin D. , Reizes Ofer
Published: January 2024

Dissociation constants derived from SPR showing that FAK and NANOG specifically bind to amino acids 216-220 of the Cx26 cytosolic tail.
Supplementary Figure S4 from Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer
Authors: Mulkearns-Hubert Erin E. , Esakov Rhoades Emily , Ben-Salem Salma , Bharti Rashmi , Hajdari Nicole , Johnson Sadie , Myers Alex , Smith Iris Nira , Bandyopadhyay Smarajit , Eng Charis , Downs Erinn , Lathia Justin D. , Reizes Ofer
Published: January 2024

Representative images from the tumorsphere formation assays shown in Fig. 3C (MDA-MB-231). Scale bar, 400 µm.
Supplementary Figure S3 from Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer
Authors: Mulkearns-Hubert Erin E. , Esakov Rhoades Emily , Ben-Salem Salma , Bharti Rashmi , Hajdari Nicole , Johnson Sadie , Myers Alex , Smith Iris Nira , Bandyopadhyay Smarajit , Eng Charis , Downs Erinn , Lathia Justin D. , Reizes Ofer
Published: January 2024

SPR sensograms demonstrating no binding of Cx26 extracellular loop peptides to FAK or NANOG proteins.
Supplementary Table S6 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

The complete list of identified phosphopeptides after global (pS/T/Y) phosphopeptide enrichment in crizotinib vs DMSO treated CUTO28 cells with fold changes and p-value calculation.
Figure S8 from Delivery versus Potency in Treating Brain Tumors: BI-907828, a MDM2-p53 Antagonist with Limited BBB Penetration but Significant In Vivo Efficacy in Glioblastoma
Authors: Zhang Wenjuan , Vaubel Rachael A. , Oh Ju-Hee , Mladek Ann C. , Talele Surabhi , Zhang Wenqiu , Waller Katie L. , Burgenske Danielle M. , Sarkaria Jann N. , Elmquist William F.
Published: January 2024

Distribution of BI-907828 in mice with intracranial GBM108 tumors. Tissue-to-plasma unbound concentration ratio.
*P < 0.05, **P < 0.01, ***P < 0.001, comparison between brain and tumor in each group by paired t-test.
##P < 0.01, ####P < 0.0001, comparison between 6 hr and 24 hr in the same dose group by unpaired t-test.
Data represent mean ± S.D. (n=5).
Figure S7 from Delivery versus Potency in Treating Brain Tumors: BI-907828, a MDM2-p53 Antagonist with Limited BBB Penetration but Significant In Vivo Efficacy in Glioblastoma
Authors: Zhang Wenjuan , Vaubel Rachael A. , Oh Ju-Hee , Mladek Ann C. , Talele Surabhi , Zhang Wenqiu , Waller Katie L. , Burgenske Danielle M. , Sarkaria Jann N. , Elmquist William F.
Published: January 2024

In vivo efficacy of BI-907828 in intracranial GBM10 and GBM14 tumor models under two dose levels after orally dosing weekly until moribund.
Supplementary Table S12 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

EGFR to MIG6 ratios in relation with crizotinib IC50s in cell lines.
Supplementary Table S11 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

Result of RNA-seq differential expression analysis for CUTO37-ER vs CUTO37.
Supplementary Table S10 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

Result of RNA-seq differential expression analysis for H3122-CR vs H3122.
Supplementary Table S1 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

Patient-derived CUTO cell line details.
Figure S2 from Delivery versus Potency in Treating Brain Tumors: BI-907828, a MDM2-p53 Antagonist with Limited BBB Penetration but Significant In Vivo Efficacy in Glioblastoma
Authors: Zhang Wenjuan , Vaubel Rachael A. , Oh Ju-Hee , Mladek Ann C. , Talele Surabhi , Zhang Wenqiu , Waller Katie L. , Burgenske Danielle M. , Sarkaria Jann N. , Elmquist William F.
Published: January 2024

Chemical structure of BI-907828 (15).
Figure S1 from Delivery versus Potency in Treating Brain Tumors: BI-907828, a MDM2-p53 Antagonist with Limited BBB Penetration but Significant In Vivo Efficacy in Glioblastoma
Authors: Zhang Wenjuan , Vaubel Rachael A. , Oh Ju-Hee , Mladek Ann C. , Talele Surabhi , Zhang Wenqiu , Waller Katie L. , Burgenske Danielle M. , Sarkaria Jann N. , Elmquist William F.
Published: January 2024

Schematic of BI-907828 inhibiting p53-MDM2 interaction and activating the p53 pathway (created with BioRender).
Supplemental Tables from Targeting DNA Repair and Survival Signaling in Diffuse Intrinsic Pontine Gliomas to Prevent Tumor Recurrence
Authors: Sharma Monika , Barravecchia Ivana , Teis Robert , Cruz Jeanette , Mumby Rachel , Ziemke Elizabeth K. , Espinoza Carlos E. , Krishnamoorthy Varunkumar , Magnuson Brian , Ljungman Mats , Koschmann Carl , Chandra Joya , Whitehead Christopher E. , Sebolt-Leopold Judith S. , Galban Stefanie
Published: January 2024

Supplemental Tables 1, 2, 3
Supplemental Material from Targeting DNA Repair and Survival Signaling in Diffuse Intrinsic Pontine Gliomas to Prevent Tumor Recurrence
Authors: Sharma Monika , Barravecchia Ivana , Teis Robert , Cruz Jeanette , Mumby Rachel , Ziemke Elizabeth K. , Espinoza Carlos E. , Krishnamoorthy Varunkumar , Magnuson Brian , Ljungman Mats , Koschmann Carl , Chandra Joya , Whitehead Christopher E. , Sebolt-Leopold Judith S. , Galban Stefanie
Published: January 2024

Supplemental Methods, Synthesis
Supplemental Figures from Targeting DNA Repair and Survival Signaling in Diffuse Intrinsic Pontine Gliomas to Prevent Tumor Recurrence
Authors: Sharma Monika , Barravecchia Ivana , Teis Robert , Cruz Jeanette , Mumby Rachel , Ziemke Elizabeth K. , Espinoza Carlos E. , Krishnamoorthy Varunkumar , Magnuson Brian , Ljungman Mats , Koschmann Carl , Chandra Joya , Whitehead Christopher E. , Sebolt-Leopold Judith S. , Galban Stefanie
Published: January 2024

Supplemental Figures 1, 2
Table S4 from Site-Specific Dolasynthen Antibody–Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios
Authors: Clardy Susan M. , Uttard Alex , Du Bingfan , Catcott Kalli C. , Lancaster Kelly L. , Ditty Elizabeth , Sadowsky Jack , Zurita Jeffrey , Malli Naniye , Qin LiuLiang , Bradley Stephen P. , Avocetien Kenneth , Carter Tyler , Kim Dokyong , Nazzaro Mark , Xu Ling , Pillow Thomas H. , Zacharias Neelie T. , Lewis Gail D. , Rowntree Rebecca K. , Iyengar Radha , Lee David H. , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: January 2024

Table S4 compares the nominal DAR to the calculated DAR values from measured Cmax values for each ADC
Supplemental Data File 1 from Site-Specific Dolasynthen Antibody–Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios
Authors: Clardy Susan M. , Uttard Alex , Du Bingfan , Catcott Kalli C. , Lancaster Kelly L. , Ditty Elizabeth , Sadowsky Jack , Zurita Jeffrey , Malli Naniye , Qin LiuLiang , Bradley Stephen P. , Avocetien Kenneth , Carter Tyler , Kim Dokyong , Nazzaro Mark , Xu Ling , Pillow Thomas H. , Zacharias Neelie T. , Lewis Gail D. , Rowntree Rebecca K. , Iyengar Radha , Lee David H. , Damelin Marc , Toader Dorin , Lowinger Timothy B.
Published: January 2024

Complete synthetic route for Monomeric Dolasynthen linker-scaffold-payload
Figure S3 from A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models
Authors: Hillen Hanne , Candi Aurélie , Vanderhoydonck Bart , Kowalczyk Weronika , Sansores-Garcia Leticia , Kesikiadou Elena C. , Van Huffel Leen , Spiessens Lore , Nijs Marnik , Soons Erik , Haeck Wanda , Klaassen Hugo , Smets Wim , Spieser Stéphane A. , Marchand Arnaud , Chaltin Patrick , Ciesielski Fabrice , Debaene Francois , Chen Lei , Kamal Adeela , Gwaltney Stephen L. , Versele Matthias , Halder Georg A.
Published: January 2024

Figure S3 shows Heatmap of differential pathway analysis comparing the tumors of vehicle and SWTX-143-treated mice.
Figure S2 from A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models
Authors: Hillen Hanne , Candi Aurélie , Vanderhoydonck Bart , Kowalczyk Weronika , Sansores-Garcia Leticia , Kesikiadou Elena C. , Van Huffel Leen , Spiessens Lore , Nijs Marnik , Soons Erik , Haeck Wanda , Klaassen Hugo , Smets Wim , Spieser Stéphane A. , Marchand Arnaud , Chaltin Patrick , Ciesielski Fabrice , Debaene Francois , Chen Lei , Kamal Adeela , Gwaltney Stephen L. , Versele Matthias , Halder Georg A.
Published: January 2024

Figure S2 shows A) Heatmap showing YAP signature genes in vehicle and SWTX-143-treated kidney cancer cell line. B) Gene Set Enrichment Analysis of the YAP signature.
Figure S2 from Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy
Authors: Pham Andrew C. , Holstein Sarah A. , Borgstahl Gloria E.O.
Published: January 2024

AlphaFold model of an hGGDPS monomer (hGGDPSAF) and sequence alignment of hGGDPS with yGGDPS. A. Regions are colored based on the per-residue confidence scores (pLDDT) ranging from 0 – 100 with higher scores reflecting well-defined parts of the structure. Residues which show a “very high” confidence score have been determined with supporting crystal structures. These residues include those at the active site. Disordered loops that have not been structurally established are shown to have “confident” scores (His194-Phe204, Leu22-Thr29). The N-terminal (Met1-Lys3) and C-terminal ends (Glu297-Glu300) are very disordered and are shown to have “low” and “very low” confidence scores. B. A sequence alignment of the conservation of residues between yGGDPS and hGGDPS. Conserved residues are colored in a dark blue while unconserved residues are colored a light blue. A pairwise alignment calculation found yGGDPS and hGGDPS to be 39.2% similar. Asterisks represent binding sites for the respective ligands as indicated in the legend. Allignment was performed with the Jalview software of Saccharomyces cerevisiae GGDPS (yGGDPS Uniprot: Q12051, top) and Homo sapiens GGDPS (hGGDPS Uniprot: O95749, bottom). C. Sequence alignment highlighting the conservation of residue properties. Helices are shown as red cylinders and are numbered sequentially. Residues contributing to IPP, FDP, and GGDP binding are shown as colored asterisks.
Data from Targeting NANOG and FAK via Cx26-derived Cell-penetrating Peptides in Triple-negative Breast Cancer
Authors: Mulkearns-Hubert Erin E. , Esakov Rhoades Emily , Ben-Salem Salma , Bharti Rashmi , Hajdari Nicole , Johnson Sadie , Myers Alex , Smith Iris Nira , Bandyopadhyay Smarajit , Eng Charis , Downs Erinn , Lathia Justin D. , Reizes Ofer
Published: January 2024

Abstract
Triple-negative breast cancer (TNBC) represents the most lethal and treatment-resistant breast cancer subtype with limited treatment options. We previously identified a protein complex unique to TNBC composed of the gap junction protein connexin 26 (Cx26), the pluripotency transcription factor NANOG, and focal adhesion kinase (FAK). We sought to determine whether a peptide mimetic of the interaction region of Cx26 attenuated tumor growth in preclinical models. We designed peptides based on Cx26 juxtamembrane domains and performed binding experiments with NANOG and FAK using surface plasmon resonance. Binding studies revealed that the Cx26 C-terminal tail and intracellular loop bound to NANOG and FAK with submicromolar-to-micromolar affinity and that a 5-amino acid sequence in the C-terminal tail of Cx26 (RYCSG) was sufficient for binding. Peptides with high affinity were engineered with a cell-penetrating antennapedia sequence and assessed in functional assays including cell proliferation, tumorsphere formation, and in vivo tumor growth, and downstream signaling changes were measured. The cell-penetrating Cx26 peptide (aCx26-pep) disrupted self-renewal while reducing nuclear FAK and NANOG and inhibiting NANOG target gene expression in TNBC cells but not luminal mammary epithelial cells. In vivo, aCx26-pep reduced tumor growth and proliferation and induced cell death. Here, we provide proof-of-concept that a Cx26 peptide–based strategy inhibits growth and alters NANOG activity specifically in TNBC, indicating the therapeutic potential of this targeting approach.
Data from Bruton's Tyrosine Kinase Inhibitors with Distinct Binding Modes Reveal Differential Functional Impact on B-Cell Receptor Signaling
Authors: Li Wei , Sano Renata , Apatira Mutiah , DeAnda Felix , Gururaja Tarikere , Yang Muhua , Lundgaard Greta , Pan Chin , Liu Jing , Zhai Yongjiao , Yoon Woo Hyun , Wang Longcheng , Tse Chris , Souers Andrew J. , Lee Chih-Hung
Published: January 2024

Abstract
Small molecule inhibitors of Bruton's tyrosine kinase (BTK) have been approved for the treatment of multiple B-cell malignancies and are being evaluated for autoimmune and inflammatory diseases. Various BTK inhibitors (BTKi) have distinct potencies, selectivity profiles, and binding modes within the ATP-binding site. On the basis of the latter feature, BTKis can be classified into those that occupy the back-pocket, H3 pocket, and the hinge region only. Hypothesizing that differing binding modes may have differential impact on the B-cell receptor (BCR) signaling pathway, we evaluated the activities of multiple BTKis in B-cell lymphoma models in vitro and in vivo. We demonstrated that, although all three types of BTKis potently inhibited BTK-Y223 autophosphorylation and phospholipase C gamma 2 (PLCγ2)-Y1217 transphosphorylation, hinge-only binders were defective in inhibiting BTK-mediated calcium mobilization upon BCR activation. In addition, PLCγ2 activation was effectively blocked by back-pocket and H3 pocket binders but not by hinge-only binders. Further investigation using TMD8 cells deficient in Rac family small GTPase 2 (RAC2) revealed that RAC2 functioned as a bypass mechanism, allowing for residual BCR signaling and PLCγ2 activation when BTK kinase activity was fully inhibited by the hinge-only binders. These data reveal a kinase activity–independent function of BTK, involving RAC2 in transducing BCR signaling events, and provide mechanistic rationale for the selection of clinical candidates for B-cell lymphoma indications.
Data from Delivery versus Potency in Treating Brain Tumors: BI-907828, a MDM2-p53 Antagonist with Limited BBB Penetration but Significant In Vivo Efficacy in Glioblastoma
Authors: Zhang Wenjuan , Vaubel Rachael A. , Oh Ju-Hee , Mladek Ann C. , Talele Surabhi , Zhang Wenqiu , Waller Katie L. , Burgenske Danielle M. , Sarkaria Jann N. , Elmquist William F.
Published: January 2024

Abstract
MDM2–p53 inhibition may be effective in glioblastoma (GBM). This study evaluates the pharmacokinetics/pharmacodynamics of BI-907828, a potent antagonist of MDM2, in GBM, and demonstrates a translational paradigm with a focus on a unified “Delivery – Potency – Efficacy” relationship in drug development for central nervous system(CNS) tumors. BI-907828 was tested for cytotoxicity and MDM2–p53 pathway inhibition. Systemic pharmacokinetics and transport mechanisms controlling CNS distribution were evaluated in mice. BI-907828 free fractions in cell media, mouse and human specimens were measured to determine “active” unbound concentrations. Efficacy measures, including overall survival and target expression were assessed in mouse orthotopic GBM xenografts. BI-907828 exhibited potent inhibition of MDM2–p53 pathway and promoted cell death in GBM TP53 wild-type cells. MDM2-amplified cells are highly sensitive to BI-907828, with an effective unbound concentration of 0.1 nmol/L. The CNS distribution of BI-907828 is limited by blood–brain barrier (BBB) efflux mediated by P-gp, resulting in a Kp,uu_brain of 0.002. Despite this seemingly “poor” BBB penetration, weekly administration of 10 mg/kg BI-907828 extended median survival of orthotopic GBM108 xenografts from 28 to 218 days (P < 0.0001). This excellent efficacy can be attributed to high potency, resulting in a limited, yet effective, exposure in the CNS. These studies show that efficacy of BI-907828 in orthotopic models is related to high potency even though its CNS distribution is limited by BBB efflux. Therefore, a comprehensive understanding of all aspects of the “Delivery – Potency – Efficacy” relationship is warranted in drug discovery and development, especially for treatment of CNS tumors.
Data from A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models
Authors: Hillen Hanne , Candi Aurélie , Vanderhoydonck Bart , Kowalczyk Weronika , Sansores-Garcia Leticia , Kesikiadou Elena C. , Van Huffel Leen , Spiessens Lore , Nijs Marnik , Soons Erik , Haeck Wanda , Klaassen Hugo , Smets Wim , Spieser Stéphane A. , Marchand Arnaud , Chaltin Patrick , Ciesielski Fabrice , Debaene Francois , Chen Lei , Kamal Adeela , Gwaltney Stephen L. , Versele Matthias , Halder Georg A.
Published: January 2024

Abstract
The Hippo pathway and its downstream effectors, the YAP and TAZ transcriptional coactivators, are deregulated in multiple different types of human cancer and are required for cancer cell phenotypes in vitro and in vivo, while largely dispensable for tissue homeostasis in adult mice. YAP/TAZ and their main partner transcription factors, the TEAD1–4 factors, are therefore promising anticancer targets. Because of frequent YAP/TAZ hyperactivation caused by mutations in the Hippo pathway components NF2 and LATS2, mesothelioma is one of the prime cancer types predicted to be responsive to YAP/TAZ-TEAD inhibitor treatment. Mesothelioma is a devastating disease for which currently no effective treatment options exist. Here, we describe a novel covalent YAP/TAZ-TEAD inhibitor, SWTX-143, that binds to the palmitoylation pocket of all four TEAD isoforms. SWTX-143 caused irreversible and specific inhibition of the transcriptional activity of YAP/TAZ-TEAD in Hippo-mutant tumor cell lines. More importantly, YAP/TAZ-TEAD inhibitor treatment caused strong mesothelioma regression in subcutaneous xenograft models with human cells and in an orthotopic mesothelioma mouse model. Finally, SWTX-143 also selectively impaired the growth of NF2-mutant kidney cancer cell lines, suggesting that the sensitivity of mesothelioma models to these YAP/TAZ-TEAD inhibitors can be extended to other tumor types with aberrations in Hippo signaling. In brief, we describe a novel and specific YAP/TAZ-TEAD inhibitor that has potential to treat multiple Hippo-mutant solid tumor types.
Supplementary Table.4 from The Tautomerase Activity of Tumor Exosomal MIF Promotes Pancreatic Cancer Progression by Modulating MDSC Differentiation
Authors: Jia Xuebing , Xi Jianbei , Tian Binle , Zhang Yuanyuan , Wang Zhilong , Wang Fan , Li Zheng , Long Jiang , Wang JianFei , Fan Guo-Huang , Li Qi
Published: January 2024

The effect of IPG1576 in SD rats.
Supplementary Figures and Legends from T cell–Dependent Bispecific Therapy Enhances Innate Immune Activation and Antibody-Mediated Killing
Authors: Besla Rickvinder , Penuel Elicia , Del Rosario Geoff , Cosino Ely , Myrta Szymon , Dillon Mike , Lazar Greg A. , Nickles Dorothee , Spiess Christoph , Yu Shang-Fan , Polson Andrew G.
Published: January 2024

Supplementary Figures and Legends
Supplementary Table.2 from The Tautomerase Activity of Tumor Exosomal MIF Promotes Pancreatic Cancer Progression by Modulating MDSC Differentiation
Authors: Jia Xuebing , Xi Jianbei , Tian Binle , Zhang Yuanyuan , Wang Zhilong , Wang Fan , Li Zheng , Long Jiang , Wang JianFei , Fan Guo-Huang , Li Qi
Published: January 2024

Primer sequences for quantitative real-time PCR
Supplementary Figure.5 from The Tautomerase Activity of Tumor Exosomal MIF Promotes Pancreatic Cancer Progression by Modulating MDSC Differentiation
Authors: Jia Xuebing , Xi Jianbei , Tian Binle , Zhang Yuanyuan , Wang Zhilong , Wang Fan , Li Zheng , Long Jiang , Wang JianFei , Fan Guo-Huang , Li Qi
Published: January 2024

Effects of IPG1576 on the appearance of the spleen and the splenic immune cells.
Supplementary Figure.4 from The Tautomerase Activity of Tumor Exosomal MIF Promotes Pancreatic Cancer Progression by Modulating MDSC Differentiation
Authors: Jia Xuebing , Xi Jianbei , Tian Binle , Zhang Yuanyuan , Wang Zhilong , Wang Fan , Li Zheng , Long Jiang , Wang JianFei , Fan Guo-Huang , Li Qi
Published: January 2024

A 32-day repeated dose toxicity study of IPG1576 in SD rats.
Supplementary Figure.2 from The Tautomerase Activity of Tumor Exosomal MIF Promotes Pancreatic Cancer Progression by Modulating MDSC Differentiation
Authors: Jia Xuebing , Xi Jianbei , Tian Binle , Zhang Yuanyuan , Wang Zhilong , Wang Fan , Li Zheng , Long Jiang , Wang JianFei , Fan Guo-Huang , Li Qi
Published: January 2024

MDSCs were significantly increased in pancreatic cancer mice and suppressed the proliferation of CD8+ T cells.
Table S2 from Notch Signaling Regulates Immunosuppressive Tumor-Associated Macrophage Function in Pancreatic Cancer
Authors: Yan Wei , Menjivar Rosa E. , Bonilla Monica E. , Steele Nina G. , Kemp Samantha B. , Du Wenting , Donahue Katelyn L. , Brown Kristee L. , Carpenter Eileen S. , Avritt Faith R. , Irizarry-Negron Valerie M. , Yang Sion , Burns William R. , Zhang Yaqing , Pasca di Magliano Marina , Bednar Filip
Published: January 2024

Primer sequences for quantitative RT-PCR
Figure S5 from Notch Signaling Regulates Immunosuppressive Tumor-Associated Macrophage Function in Pancreatic Cancer
Authors: Yan Wei , Menjivar Rosa E. , Bonilla Monica E. , Steele Nina G. , Kemp Samantha B. , Du Wenting , Donahue Katelyn L. , Brown Kristee L. , Carpenter Eileen S. , Avritt Faith R. , Irizarry-Negron Valerie M. , Yang Sion , Burns William R. , Zhang Yaqing , Pasca di Magliano Marina , Bednar Filip
Published: January 2024

γ-secretase inhibitor treatment reduces expression of HES1 in vivo.
Figure S1 from Notch Signaling Regulates Immunosuppressive Tumor-Associated Macrophage Function in Pancreatic Cancer
Authors: Yan Wei , Menjivar Rosa E. , Bonilla Monica E. , Steele Nina G. , Kemp Samantha B. , Du Wenting , Donahue Katelyn L. , Brown Kristee L. , Carpenter Eileen S. , Avritt Faith R. , Irizarry-Negron Valerie M. , Yang Sion , Burns William R. , Zhang Yaqing , Pasca di Magliano Marina , Bednar Filip
Published: January 2024

Notch activation in the tumor microenvironment of human PDA.
Figure S1 from Tyrosine Kinase Inhibition Activates Intratumoral γδ T Cells in Gastrointestinal Stromal Tumor
Authors: Etherington Mark S. , Hanna Andrew N. , Medina Benjamin D. , Liu Mengyuan , Tieniber Andrew D. , Kwak Hyunjee V. , Tardy Katherine J. , Levin Lillian , Do Kevin J. , Rossi Ferdinando , Zeng Shan , DeMatteo Ronald P.
Published: January 2024

Supplemental Figure S1. (A) Alternate gating strategy for identifying γδ T cells in KitV558Δ/+ tumors by flow cytometry (B) Prevalence of γδ T cells as a percentage of T cells in KitV558Δ/+ mice across multiple anatomic compartments. (C) Percent of cells positive for IFNγ in KitV558Δ/+ tumor by flow cytometry after intracellular cytokine stimulation. (D) Histograms of flow cytometry staining for the transcription factors T-bet and EOMES in T cells from KitV558Δ/+ tumors. (E) Vγ2 expression in tumor and spleen γδ T cells from KitV558Δ/+ mice. Representative of 4 mice. Data represent mean ± SEM; p values were calculated using a two-sided Student’s t test; *, P < 0.05.