bluuebunny/crossref_metadata_2025_split huggingface dataset:
Final results on the $$0\nu \beta \beta $$ decay half-life limit of $$^{100}$$Mo from the CUPID-Mo experiment
Authors: Augier C. , Barabash A. S. , Bellini F. , Benato G. , Beretta M. , Bergé L. , Billard J. , Borovlev Yu. A. , Cardani L. , Casali N. , Cazes A. , Chapellier M. , Chiesa D. , Dafinei I. , Danevich F. A. , De Jesus M. , de Marcillac P. , Dixon T. , Dumoulin L. , Eitel K. , Ferri F. , Fujikawa B. K. , Gascon J. , Gironi L. , Giuliani A. , Grigorieva V. D. , Gros M. , Helis D. L. , Huang H. Z. , Huang R. , Imbert L. , Johnston J. , Juillard A. , Khalife H. , Kleifges M. , Kobychev V. V. , Kolomensky Yu. G. , Konovalov S. I. , Loaiza P. , Ma L. , Makarov E. P. , Mariam R. , Marini L. , Marnieros S. , Navick X.-F. , Nones C. , Norman E. B. , Olivieri E. , Ouellet J. L. , Pagnanini L. , Pattavina L. , Paul B. , Pavan M. , Peng H. , Pessina G. , Pirro S. , Poda D. V. , Polischuk O. G. , Pozzi S. , Previtali E. , Redon Th. , Rojas A. , Rozov S. , Sanglard V. , Scarpaci J. A. , Schmidt B. , Shen Y. , Shlegel V. N. , Singh V. , Tomei C. , Tretyak V. I. , Umatov V. I. , Vagneron L. , Velázquez M. , Welliver B. , Winslow L. , Xue M. , Yakushev E. , Zarytskyy M. , Zolotarova A. S. 
Published: November 2022

AbstractThe CUPID-Mo experiment to search for 0$$\nu \beta \beta $$

ν
β
β

decay in $$^{100}$$

100

Mo has been recently completed after about 1.5 years of operation at Laboratoire Souterrain de Modane (France). It served as a demonstrator for CUPID, a next generation 0$$\nu \beta \beta $$

ν
β
β

decay experiment. CUPID-Mo was comprised of 20 enriched $$\hbox {Li}_{{2}}$$

Li
2

$$^{100}$$

100

$$\hbox {MoO}_4$$

MoO
4

scintillating calorimeters, each with a mass of $$\sim 0.2$$

∼
0.2

kg, operated at $$\sim 20$$

∼
20

mK. We present here the final analysis with the full exposure of CUPID-Mo ($$^{100}$$

100

Mo exposure of 1.47 $$\hbox {kg} \times \hbox {year}$$

kg
×
year

) used to search for lepton number violation via 0$$\nu \beta \beta $$

ν
β
β

decay. We report on various analysis improvements since the previous result on a subset of data, reprocessing all data with these new techniques. We observe zero events in the region of interest and set a new limit on the $$^{100}$$

100

Mo 0$$\nu \beta \beta $$

ν
β
β

decay half-life of $$T_{1/2}^{0\nu }$$

T

1
/
2

0
ν

$$> {1.8}\times 10^{24}$$

>

1.8

×

10
24

year (stat. + syst.) at 90% CI. Under the light Majorana neutrino exchange mechanism this corresponds to an effective Majorana neutrino mass of $$\left<m_{\beta \beta }\right>$$

m

β
β

$$<~{(0.28{-}0.49)} $$

<

(
0.28
-
0.49
)

eV, dependent upon the nuclear matrix element utilized.
Qubit noise deconvolution
Authors: Mangini Stefano , Maccone Lorenzo , Macchiavello Chiara 
Published: November 2022

AbstractWe present a noise deconvolution technique to remove a wide class of noises when performing arbitrary measurements on qubit systems. In particular, we derive the inverse map of the most common single qubit noisy channels, and exploit it at the data processing step to obtain noise-free estimates of observables evaluated on a qubit system subject to known noise. We illustrate a self-consistency check to ensure that the noise characterization is accurate providing simulation results for the deconvolution of a generic Pauli channel, as well as experimental evidence of the deconvolution of decoherence noise occurring on Rigetti quantum hardware.
The sulfur solubility minimum and maximum in silicate melt
Authors: Hughes Ery C. , Saper Lee M. , Liggins Philippa , O'Neill Hugh St. C. , Stolper Edward M. 
Published: November 2022

The behaviour of sulfur in magmas is complex because it dissolves as both sulfide (S
2−
) and sulfate (S
6+
) in silicate melt. Interesting aspects of the behaviour of sulfur are the solubility minimum (SS
min
) and maxima (SS
max
) observed with varying oxygen fugacity (

f

O

2

). We use a simple ternary model (silicate–S
2
–O
2
) to explore the varying

f

O

2

paths where these phenomena occur. Both SS
min
and SS
max
occur when S
2−
and S
6+
are present in the silicate melt in similar quantities owing to the differing solubility mechanisms of melt species containing these oxidation states of sulfur. At constant
T
, a minimum in dissolved total S content in vapour-saturated silicate melt (

w

S

T

m

) occurs along paths of increasing

f

O

2

and either constant

f

S

2

or constant
P
. For paths on which

w

S

T

m

is held constant with increasing

f

O

2

, the SS
min
is expressed as a maximum in
P
. The SS
min
occurs when the fraction of S
6+
in the melt ([S
6+
/S
T
]

m

) is 0.25 for constant

f

S

2

and [S
6+
/S
T
]

m

≈

0.75 for constant

w

S

T

m

and
P
. A minimum in

w

S

T

m

is not encountered during closed- or open-system depressurization in the simple system we modelled. However, the SS
min
marks a change from reduction to oxidation during degassing. Various SS
max
occur when the silicate melt is multiply saturated with at least two phases: vapour, sulfide melt, and/or anhydrite. The SS
min
and SS
max
are potentially important features of magmatic process involving S, such as mantle melting, magma mixing, and degassing. These concepts influence calculations of the pressures of vapour-saturation,

f

O

2

, and SO
2
emissions using melt inclusions.

Supplementary material:
Additional information and data used to create the figures are available at
https://doi.org/10.6084/m9.figshare.c.6274527

Thematic collection:
This article is part of the Sulfur in the Earth system collection available at:
https://www.lyellcollection.org/topic/collections/sulfur-in-the-earth-system
Running to Outcompete Metastasis
Authors: Zerhouni Marwa , Piskounova Elena 
Published: November 2022

The role of exercise in cancer progression is an emerging field of research, with intriguing evidence for physical activity playing an inhibitory role in cancer onset. In their recent publication, Sheinboim and colleagues demonstrate the impact of physical exercise on melanoma primary tumor growth and metastasis. They establish that physical exercise decreases metastatic spread, using both human epidemiologic data and in vivo models of melanoma metastasis. Systemic metabolic reprogramming of organs, induced by exercise, leads to a decrease in melanoma growth and progression as healthy organs are able to outcompete melanoma cells for nutrients. Exercise led to systemic metabolic changes in carbohydrate metabolism, glycolysis, and oxidative phosphorylation as well as mitochondrial biogenesis. Interestingly, the “metabolic shield” created by exercise could be reversed using the mTOR inhibitor rapamycin. This study highlights the importance of metabolic plasticity in metastasis and uncovers a direct link between systemic metabolic reprogramming and mTOR signaling. Overall, the study by Sheinboim and colleagues provides a more detailed understanding of the metastatic requirements in the context of energy and nutrient availability and the impact of exercise on cancer progression, highlighting novel opportunities for therapeutic intervention.See related article by Sheinboim et al., p. 4164
Abstract B014: TLR signaling coordinates SAA-dependent liver metastasis in pancreatic cancer
Authors: Lee Jesse , Stone Meredith L. , Choi Hana , Beatty Gregory L. 
Published: November 2022

Abstract
Metastasis remains the primary cause of mortality in cancer. This is especially true in pancreatic ductal adenocarcinoma (PDAC) - where the liver is the most common site of metastasis and the 5-year overall survival rate for these patients has remained &lt;3% for the past 20 years. Accumulating evidence shows a critical role for a niche microenvironment in the liver, termed the pro-metastatic niche, that supports metastatic seeding and outgrowth. Our previous work demonstrated that hepatocytes orchestrate the formation of this pro-metastatic niche during early tumorigenesis through the release of Serum Amyloid A1 and 2 (SAA). However, the mechanisms by which SAA directs formation of a pro-metastatic niche in the liver, and the impact of this niche on the fate of disseminating tumor cells (DTCs) seeding the liver, remain ill-defined. To begin to identify the cellular determinants of niche formation, we first analyzed the expression of SAA receptors within the normal liver and found predominant expression of receptors on the resident F4/80+ macrophages. This is in line with current published work as SAA is well characterized to control liver biology through toll-like receptors (TLRs) expressed by liver resident immune cells and hepatic stellate cells. Consistent with this, we also found that SAA is a specific, potent agonist of TLR2 in vitro. In tumor bearing mice we then found increased expression of TLR2 transcripts as well as an accumulation of TLR2+ inflammatory monocytes within the niche. Together, these findings suggested that SAA might form a pro-metastatic niche in the liver withough a TLR2-dependent mechanism. To test this, we next examined the livers of TLR2-/- tumor bearing mice and found a decrease in the expression of surrogate markers of the pro-metastatic niche. We also sought to determine a role for TLR2 in metastatic outgrowth. Using TLR2-/- mice in a model of PDAC with direct metastasis to the liver, we found significantly decreased metastatic burden and outgrowth in the liver. Analysis of micro-metastatic lesions in TLR2-/- tumor bearing mice also revealed that DTCs demonstrated molecular markers of cellular dormancy. Altogether, our findings suggest the evolution of an inflammatory mechanism within the niche wherein SAA may continue to signal through TLR2+ inflammatory monocytes, which then act to coordinate metastatic outgrowth. Future work aims to further elucidate the role of TLR2+ resident macrophages and monocytes in the formation of a pro-metastatic niche in the liver and in regulating metastatic outgrowth.
Citation Format: Jesse Lee, Meredith L. Stone, Hana Choi, Gregory L. Beatty. TLR signaling coordinates SAA-dependent liver metastasis in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B014.
Abstract B020: Retinoic acid produced by hepatic stellate cells facilitates Netrin-1 mediated pancreatic cancer metastasis
Authors: Dudgeon Crissy , Casabianca Anthony , Harris Chris , Astsaturov Igor , Ogier Charline , Su Xiaoyang , Pitarresi Jason , Narrow Wade , Soliman Fady , Withers Tracy , Mehlen Patrick , Carpizo Darren 
Published: November 2022

Abstract
A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its proclivity for metastasis as evidenced by the fact that 85% are stage IV at diagnosis. This highlights the need to better understand the biology of metastatic PDAC and identify novel therapies for this patient population. Axon guidance genes have been shown to be involved in PDAC progression, but their role is unclear. We have investigated the role of the axon guidance molecule Netrin-1 and its receptors Unc5b and DCC in PDAC. We found that in both murine and human samples that NTN1 expression is increased in metastatic PDAC and the quasi-mesenchymal subtype. Murine and TCGA data indicate that Unc5b is the dominant NTN1 receptor and genetic knock-down (KD) or knock-out (KO) of either Netrin-1 or Unc5b decreases migration, invasion, and cell survival in vitro and hepatic metastatic growth in vivo. The mechanism of Netrin-1 upregulation in metastatic PDAC is unknown. We found that hepatic stellate cell (HSC) secreted retinoic acid upregulates NTN1 through both an RXR/RAR and Elf mediated mechanism. To determine if NTN1 is involved in the process of HSC activation we found that recombinant NTN1 added to HSCs in vitro induced activation. We examined the livers of mice harboring orthotopic PDAC tumors using murine pancreatic cancer lines that were either NTN1 wild type (WT) or KO, and found that the NTN-expressing lines increased HSC activation providing evidence that NTN1 is important for long distance intercellular communication between primary pancreatic tumors and the pre-metastatic liver. We detected NTN1 within extracellular vesicles, and mice pre-conditioned with EVs from NTN1 KO cells demonstrated a decreased metastatic burden as compared mice preconditioned with NTN1 WT cells. Treatment of several murine PDAC models (autochthonous and metastatic) with a monoclonal antibody to NTN1 led to decreased metastases and increased survival. These studies reveal that NTN1 is upregulated in metastatic PDAC mediated by a novel mechanism that involves EVs, HSC activation and RXR/RAR signaling. These studies provide pre-clinical evidence to support a human clinical trial of anti-NTN1 therapy in PDAC.
Citation Format: Crissy Dudgeon, Anthony Casabianca, Chris Harris, Igor Astsaturov, Charline Ogier, Xiaoyang Su, Jason Pitarresi, Wade Narrow, Fady Soliman, Tracy Withers, Patrick Mehlen, Darren Carpizo. Retinoic acid produced by hepatic stellate cells facilitates Netrin-1 mediated pancreatic cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B020.
Abstract B065: Polymerase theta inhibition activates the cGAS-STING signaling pathway and elicits an immune response in homologous recombination-deficient pancreatic adenocarcinoma
Authors: Oh Grace , Wang Annie , Wang Lidong , Li Jiufeng , Werba Gregor , Weissinger Daniel , Zhao Ende , Dhara Surajit , Hernandez Rosmel , Ackermann Amanda , Kalfakakou Despoina , Kawaler Emily A. , Golan Talia , Welling Theodore H. , Sfeir Agnel , Simeone Diane M. 
Published: November 2022

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that harbors mutations in homologous recombination (HR) repair genes in up to 25% of cases. Defects in HR impart to tumor cells a specific vulnerability to poly-ADP ribose polymerase inhibitors and platinum-based chemotherapy. However, not all patients respond, and some who initially respond develop resistance and progress. Thus, new therapies that are effective against HR-deficient PDAC are needed. Here, we show that inactivation of the HR pathway in PDAC is associated with overexpression of polymerase theta (Polθ, or POLQ), a key enzyme that regulates the alternative non-homologous end-joining (alt-NHEJ) pathway of double-strand break (DSB) DNA repair. Using both human and murine HR-deficient PDAC models, we find that POLQ knockdown is synthetically lethal with mutations in HR genes (BRCA1, BRCA2, and PALB2) as well as the DNA damage repair gene ATM. Further, we present the first findings that POLQ knockdown enhances cytosolic micronucleus formation and activates cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling. In an in vivo murine model, POLQ inhibition also leads to STING-dependent recruitment of immune cells and enhanced CD8+ T cell infiltration in the BRCA2-deficient tumor microenvironment (TME). Through its role in the alt-NHEJ pathway, we thus find that POLQ is critical for DSB repair in HR-deficient PDAC, and its inhibition presents a novel synthetic lethal approach to suppress tumor growth while simultaneously stimulating an immune response in the PDAC TME.
Citation Format: Grace Oh, Annie Wang, Lidong Wang, Jiufeng Li, Gregor Werba, Daniel Weissinger, Ende Zhao, Surajit Dhara, Rosmel Hernandez, Amanda Ackermann, Despoina Kalfakakou, Emily A. Kawaler, Talia Golan, Theodore H. Welling, Agnel Sfeir, Diane M. Simeone. Polymerase theta inhibition activates the cGAS-STING signaling pathway and elicits an immune response in homologous recombination-deficient pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B065.
Abstract B069: Inhibiting pancreatic cancer growth by dual targeting of ERK and PI3K signaling
Authors: Nair Gauthami G. , Reindl Katie , Quadir Mohiuddin 
Published: November 2022

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a dismal 5-year survival rate of only 11%. Due to its late-stage detection and metastasis, surgery is not an option in most cases, and chemotherapy has become the sought-after strategy to combat PDAC. Current treatment strategies involve combining chemotherapeutic agents; however, these drugs show limited response in some patients and frequently result in acquired drug resistance. There is a need for new treatment approaches to more specifically target molecules involved in PDAC growth. The KRAS gene is mutated in almost 95% of the pancreatic cancers resulting in hyperactivated K-ras protein, which activates downstream growth-promoting signaling pathways such as extracellular receptor kinase (ERK) and phosphatidylinositol 3 kinase (PI3K). Thus, we hypothesized that the combination of ERK and PI3K inhibitors would lead to enhanced PDAC growth inhibition compared to either drug alone. To test our hypothesis, we used SCH772984 (an ERK1/2 inhibitor) and pictilisib (a class I PI3K inhibitor) to perform a cell viability assay using human PDAC cell lines, MIA PaCa-2 and PANC-1, for both 2-D cells and 3-D spheroids. Our results indicated that the cancer cells treated with both drugs showed reduced cell proliferation compared to either of the drugs administered individually. Our next steps will involve evaluation of this combination in animal models as well as testing these drugs against clinical PDAC samples. This research may lead to a novel combination of pictilisib and SCH772984 to enhance treatment for PDAC patients.
Citation Format: Gauthami G. Nair, Katie Reindl, Mohiuddin Quadir. Inhibiting pancreatic cancer growth by dual targeting of ERK and PI3K signaling [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B069.
Abstract C018: Co-activation of myeloid signaling pathways for pancreatic cancer immunotherapy
Authors: Wattenberg Max M. , Coho Heather , Herrera Veronica M. , Graham Kathleen , Stone Meredith L. , Xue Yuqing , Chang Renee B. , Cassella Christopher , Liu Mingen , Choi-Bose Shaanti , Thomas Stacy K. , Choi Hana , Li Yan , Melendez Lauren , Giannone Michael , Bose Nandita , Beatty Gregory L. 
Published: November 2022

Abstract
Pancreatic ductal adenocarcinoma (PDA) is characterized by a robust myeloid cell infiltrate. Although myeloid cells in PDA most commonly associate with immunosuppression, they also show plasticity and possess the capacity to engage productive anti-tumor immunity, thereby providing a potential therapeutic vulnerability. Here, we show that distinct myeloid cell subsets infiltrating human PDA express non-redundant activating receptors. Among the most highly expressed receptors was the pattern recognition receptor CLEC7A, which was expressed by macrophages, monocytes, and immature myeloid cells. In contrast, the TNF superfamily member CD40, was expressed by dendritic cells (DC) and SPP1+ macrophages. We hypothesized that combinatory targeting of myeloid activating receptors might be needed to restore productive immunosurveillance in PDA. In immune checkpoint blockade-resistant mouse models of PDA, pharmacologic activation of CLEC7A, using beta glucan (BG) therapy was associated with upregulation of the CXCL2/3-CXCR2 axis and triggered increases in intra-tumoral macrophages and granulocytes. Conversely, CD40 agonist therapy induced activity of the CXCL9-CXCR3 axis and drove conventional DC type 1-dependent infiltration of CD4+ and CD8+ T cells into tumors. Neither myeloid agonist alone, though, was sufficient to trigger durable anti-tumor immunity. By contrast, induction of both myeloid and lymphoid immunosurveillance by co-activation of CLEC7A/CD40 pathways caused tumor eradication, durable tumor control and T cell dependent immunological memory. Depletion of CSF1R+ myeloid cells or T cells significantly reduced the anti-tumor activity of treatment thereby highlighting the cooperativity of innate and adaptive immunity for anti-tumor activity. Moreover, the efficacy of CLEC7A and CD40 co-activation was independent of immune checkpoint blockade. Thus, beyond inhibitory checkpoint molecules on T cells, combinatory activation of non-redundant myeloid signaling pathways can be leveraged to trigger durable anti-tumor immunity, suggesting a new immunotherapy paradigm. A clinical trial of CLEC7A and CD40 agonist therapy for the treatment of patients with PDA is under development.
Citation Format: Max M. Wattenberg, Heather Coho, Veronica M. Herrera, Kathleen Graham, Meredith L. Stone, Yuqing Xue, Renee B. Chang, Christopher Cassella, Mingen Liu, Shaanti Choi-Bose, Stacy K. Thomas, Hana Choi, Yan Li, Lauren Melendez, Michael Giannone, Nandita Bose, Gregory L. Beatty. Co-activation of myeloid signaling pathways for pancreatic cancer immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C018.