bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF LAYERING PATTERN ON MECHANICAL AND WATER ABSORPTION PROPERTIES OF GLASS/FLAX REINFORCED EPOXY
Authors: Mat Jusoh Muhamad Shahirul , Mohd Yahya Mohd Yazid , Mustafa Zaleha , Ahmad Hariz Ahmad Israr 
Published: July 2017

In this present study, a new hybrid composite with epoxy as a resin and hybrid reinforcing glass and flax are used Â as layered mat. The composites were prepared via vacuum infusion process (VIP) comprising glass and flax fibres with the weight fraction of 57 % and 43 %, respectively. All the laminates were prepared with a total of seven plies, by varying the position of the glass and flax. The effect of stacking sequence of the laminates on the mechanical and physical was characterized by tensile, flexural and water absorption tests. The results indicated that the flexural strength and modulus were significantly dependent on the hybrid configuration in comparison to their tensile properties.Â The interplay hybrid laminates with sandwich-like sequence exhibited 10.5 % and 5.5 % higher of flexural strength and modulus, respectively as compared with intercalation. Physical property was observed based on water immersion for 14 days at different elevated temperatures of 40 Â°C and 80 Â°C. Result indicated that sandwich-like is better than intercalation sequences for water resistance at both elevated temperatures with the percentage of water intrusion about 4.4 % and 6.35 % at 40 Â°C and 80 Â°C, respectively.Â Conversely, specimens withÂ intercalation sequence exhibited 5.1 % and 7.0 % of water intrusion at 40 Â°C and 80 Â°C, respectively.
Local cohomology of Du Bois singularities and applications to families
Authors: Ma Linquan , Schwede Karl , Shimomoto Kazuma 
Published: July 2017

In this paper we study the local cohomology modules of Du Bois singularities. Let $(R,\mathfrak{m})$ be a local ring; we prove that if $R_{\text{red}}$ is Du Bois, then $H_{\mathfrak{m}}^{i}(R)\rightarrow H_{\mathfrak{m}}^{i}(R_{\text{red}})$ is surjective for every $i$. We find many applications of this result. For example, we answer a question of Kovács and Schwede [Inversion of adjunction for rational and Du Bois pairs, Algebra Number Theory 10 (2016), 969–1000; MR 3531359] on the Cohen–Macaulay property of Du Bois singularities. We obtain results on the injectivity of $\operatorname{Ext}$ that provide substantial partial answers to questions in Eisenbud et al. [Cohomology on toric varieties and local cohomology with monomial supports, J. Symbolic Comput. 29 (2000), 583–600] in characteristic $0$. These results can also be viewed as generalizations of the Kodaira vanishing theorem for Cohen–Macaulay Du Bois varieties. We prove results on the set-theoretic Cohen–Macaulayness of the defining ideal of Du Bois singularities, which are characteristic-$0$ analogs and generalizations of results of Singh–Walther and answer some of their questions in Singh and Walther [On the arithmetic rank of certain Segre products, in Commutative algebra and algebraic geometry, Contemporary Mathematics, vol. 390 (American Mathematical Society, Providence, RI, 2005), 147–155]. We extend results on the relation between Koszul cohomology and local cohomology for $F$-injective and Du Bois singularities first shown in Hochster and Roberts [The purity of the Frobenius and local cohomology, Adv. Math. 21 (1976), 117–172; MR 0417172 (54 #5230)]. We also prove that singularities of dense $F$-injective type deform.
Équivalence motivique des groupes algébriques semisimples
Authors: De Clercq Charles 
Published: July 2017

We prove that the standard motives of a semisimple algebraic group$G$with coefficients in a field of order$p$are determined by the upper motives of the group $G$. As a consequence of this result, we obtain a partial version of the motivic rigidity conjecture of special linear groups. The result is then used to construct the higher indexes which characterize the motivic equivalence of semisimple algebraic groups. The criteria of motivic equivalence derived from the expressions of these indexes produce a dictionary between motives, algebraic structures and the birational geometry of twisted flag varieties. This correspondence is then described for special linear groups and orthogonal groups (the criteria associated with other groups being obtained in De Clercq and Garibaldi [Tits$p$-indexes of semisimple algebraic groups, J. Lond. Math. Soc. (2)95(2017) 567–585]). The proofs rely on the Levi-type motivic decompositions of isotropic twisted flag varieties due to Chernousov, Gille and Merkurjev, and on the notion of pondered field extensions.
Rearing‐environment‐dependent hippocampal local field potential differences in wild‐type and inositol trisphosphate receptor type 2 knockout mice
Authors: Tanaka Mika , Wang Xiaowen , Mikoshiba Katsuhiko , Hirase Hajime , Shinohara Yoshiaki 
Published: July 2017

Key points
Mice reared in an enriched environment are demonstrated to have larger hippocampal gamma oscillations than those reared in isolation, thereby confirming previous observations in rats.
To test whether astrocytic Ca2+ surges are involved in this experience‐dependent LFP pattern modulation, we used inositol trisphosphate receptor type 2 (IP3R2)‐knockout (KO) mice, in which IP3/Ca2+ signalling in astrocytes is largely diminished.
We found that this experience‐dependent gamma power alteration persists in the KO mice.
Interestingly, hippocampal ripple events, the synchronized events critical for memory consolidation, are reduced in magnitude and frequency by both isolated rearing and IP3R2 deficiency.
AbstractRearing in an enriched environment (ENR) is known to enhance cognitive and memory abilities in rodents, whereas social isolation (ISO) induces depression‐like behaviour. The hippocampus has been documented to undergo morphological and functional changes depending on these rearing environments. For example, rearing condition during juvenility alters CA1 stratum radiatum gamma oscillation power in rats. In the present study, hippocampal CA1 local field potentials (LFP) were recorded from bilateral CA1 in urethane‐anaesthetized mice that were reared in either an ENR or ISO condition. Similar to previous findings in rats, gamma oscillation power during theta states was higher in the ENR group. Ripple events that occur during non‐theta periods in the CA1 stratum pyramidale also had longer intervals in ISO mice. Because astrocytic Ca2+ elevations play a key role in synaptic plasticity, we next tested whether these changes in LFP are also expressed in inositol trisphosphate receptor type 2 (IP3R2)‐knockout (KO) mice, in which astrocytic Ca2+ elevations are largely diminished. We found that the gamma power was also higher in IP3R2‐KO‐ENR mice compared to IP3R2‐KO‐ISO mice, suggesting that the rearing‐environment‐dependent gamma power alteration does not necessarily require the astrocytic IP3/Ca2+ pathway. By contrast, ripple events showed genotype‐dependent changes, as well as rearing condition‐dependent changes: ISO housing and IP3R2 deficiency both lead to longer inter‐ripple intervals. Moreover, we found that ripple magnitude in the right CA1 tended to be smaller in IP3R2‐KO. Because IP3R2‐KO mice have been reported to have depression phenotypes, our results suggest that ripple events and the mood of animals may be broadly correlated.
Abstract 100: Pancreatic cancer cells rely on the NADPH producing enzyme, IDH1, for adaptive survival against acute metabolic stress
Authors: Vaziri-Gohar Ali , Zarei Mahsa , Brody Jonathan R. , Winter Jordan M. 
Published: July 2017

Abstract
We recently demonstrated that pancreatic cancer cells adapt to low nutrient conditions and chemotherapeutic stress through an adaptive response where HuR (ELAVL1) protects cells from oxidative damage induced by metabolic stress. RNA sequencing data and a series of protein-RNA interaction assays proved that HuR stabilizes transcript levels of the NADPH producing enzyme, isocitrate dehydrogenase 1 (IDH1). HuR-knockout cells had near-complete loss of IDH1 expression (manuscript under review). In light of the fact that IDH1-null mice are particularly sensitive to oxidative damage, we hypothesize that this enzyme plays a critical role in PDA survival of acute stress. We examined the expression levels of all eight well-characterized NADPH-generating enzymes in pancreatic cancer cells in vitro, and demonstrate that only IDH1 and phosphogluconate dehydrogenase (PGD) are upregulated by &gt;2-fold after incubation in low glucose (5 mM) for 48 hours. IDH1-knockout MiaPaCa2 cells were generated through CRISPR gene editing, such that mRNA expression was detected at &lt;5% of control levels. ROS levels detected by DCFDA measurements were increased by 55% in IDH1-knockout cells compared to isogenic controls under normal culture conditions, with even higher levels under low glucose and chemotherapy stress for 48 hours. Additionally, IDH1-knockout cells were more sensitive to chemotherapy under both high and low glucose conditions, compared to IDH1-proficient control cells. Taken together these results suggest that IDH1 expression is important for acute antioxidant defense in pancreatic cancer cells in the face of metabolic stress, and represents a potential therapeutic target.
Citation Format: Ali Vaziri-Gohar, Mahsa Zarei, Jonathan R. Brody, Jordan M. Winter. Pancreatic cancer cells rely on the NADPH producing enzyme, IDH1, for adaptive survival against acute metabolic stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 100. doi:10.1158/1538-7445.AM2017-100
Abstract 1000: Estrogen receptor coactivator MED1 in breast tumorigenesis and therapeutic resistance
Authors: Zhang Xiaoting 
Published: July 2017

Abstract
Recent studies have established Mediator Subunit 1 (MED1) as a key ER transcriptional coactivator for in both normal mammary gland development and breast cancer. Significantly, the MED1 gene is located at the chromosome 17q12 region, also known as the HER2 amplicon, and co-amplifies with HER2 in almost all instances. Importantly, we found that MED1 serves as a key crosstalk point for the HER2 and ER pathways in anti-estrogen resistance of breast cancer. Significantly, MED1 expression highly correlates with poor disease-free survival of breast cancer patients; and most recent studies have discovered increased frequency of MED1 mutations in circulating tumor cells of human patients following anti-estrogen and anti-HER2 treatments. To determine the role of MED1 in HER2-driven tumorigenesis, we have crossed the MMTV-HER2 mammary tumor model with our established MED1 mutant knockin and newly generated MED1 mammary specific overexpression mouse models. Collectively, our studies revealed critical roles for MED1 in tumor progression, metastasis, cancer stem cell formation and therapeutic resistance in HER2-mediated mammary tumorigenesis. These studies not only for the first time reported key roles for a HER2 amplicon co-amplified gene in HER2-driven tumorigenesis but also support MED1 as a potential therapeutic target. To test that, we have assembled highly innovative RNA nanotechnology-based pRNA-HER2apt-siMED1 nanoparticles. We found these RNA nanoparticles have a very high Tm value, and is ultra-stable under RNase A, 8 M urea, serum and PBS conditions. Importantly, pRNA-HER2apt-siMED1 nanoparticles could specifically target HER2+ human breast cancer, efficiently deplete the expression of MED1 and decrease ER-mediated gene transcription both in vitro and in vivo. Most significantly, pRNA-HER2apt-siMED1 nanoparticles not only greatly reduce the growth, metastasis and cancer stem cell formation of HER2+ breast cancer, but are also able to overcome their therapeutic resistance. (This work is supported by Susan G. Komen for the Cure Foundation Career Catalyst Grant, American Cancer Society Research Scholar Grant and NIH/NCI Grant Number R01CA197865).
Citation Format: Xiaoting Zhang. Estrogen receptor coactivator MED1 in breast tumorigenesis and therapeutic resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1000. doi:10.1158/1538-7445.AM2017-1000
Abstract 1015: Directionality of T-cell-mediated cross-protection against the same tumor in lungs versus skin
Authors: O'Konek Jessica J. , Ambrosino Elena , Bloom Anja , Izhak Liat , Berzofsky Jay A. , Terabe Masaki 
Published: July 2017

Abstract
Immunotherapy is a new pillar of cancer therapy. One theoretical advantage of immunotherapy of cancer is that effector cells induced at one site should be able to kill metastatic cancer cells in other sites or tissues. On the other hand, it has been recognized that each tissue has unique immune components that play critical roles in protection against pathogens. However, very little is known whether effector T cells induced against tumors in one tissue can work against the same tumors in other tissues. To address this question, we compared the effect of effector cells induced against the same tumor cells growing in either the skin or the lung by using CT26 murine tumor models. Rejection of s.c. CT26 tumors was achieved by pretreatment with anti-CD25, which blocks the function of Treg cells. Both CD4 and CD8 T cells were necessary for the protection. When anti-CD25-pretreated mice challenged with s.c. CT26 were simultaneously inoculated i.v. with CT26, they also rejected tumors in the lung, while anti-CD25-pretreated mice without s.c. CT26 did not. This observation suggested that T cell mediated anti-tumor protective immunity induced against s.c. tumors can also protect against lung metastases of the same tumors. In contrast to Treg depletion which allowed for the induction of protective immunity in the s.c. tumor model, NKT cell-deficiency in CD1d KO mice induced significant CD8 T cell-mediated protection against lung metastasis of CT26 but had no effect on the growth of s.c. CT26 tumors. When CD1d KO mice rejecting i.v. CT26 were simultaneously challenged with s.c. CT26, the development of s.c. tumors was not affected, indicating that tumor rejection induced against the CT26 in the lung did not confer protection for the same tumor cells in the skin. Since the protection against CT26 in the lung in CD1d KO mice is mediated by CD8 T cells, we transferred T cells from CD1d KO mice inoculated i.v. with CT26 into RAG1 KO recipients, and challenged the recipient mice with the CT26 tumor cells. The recipient RAG1 KO mice were highly resistant to CT26 inoculated i.v. but not s.c. confirming that the CD8 T cells protective in the lung are not protective in the skin. These data
indicate the effector cells against the same tumor do not work in all tissues, and the induction site of the effector T cells is critical to control metastasis.
Citation Format: Jessica J. O'Konek, Elena Ambrosino, Anja Bloom, Liat Izhak, Jay A. Berzofsky, Masaki Terabe. Directionality of T-cell-mediated cross-protection against the same tumor in lungs versus skin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1015. doi:10.1158/1538-7445.AM2017-1015
Abstract 1025: Controlled and endogenous depletion of a synthetic lethal target in human cancer cell lines via SMASh degron engineering
Authors: Rago Florencia , Dimare Matthew T. , Bushold Geoffrey , Kapoor Avnish , Bhang Hyo-eun C. , Jagani Zainab 
Published: July 2017

Abstract
The SWI/SNF multi-subunit complexes play an important role in regulating processes such as gene transcription through ATP-dependent remodeling of chromatin. The importance of this role is highlighted by the prevalence of mutations in various SWI/SNF subunits across approximately 20% of cancers encompassing various lineages and subtypes. Functional genomics screening via pooled shRNAs has led to the discovery of distinct vulnerabilities of SWI/SNF mutant cancers to loss of mutually exclusive subunits. In particular, cancer cells with BRG1 loss become exquisitely dependent on the remaining BRG1 counterpart, BRM. To further understand the synthetic lethal relationship between BRM and BRG1, we have adapted a recently described degron, the small molecule assisted shutoff (SMASh) tag, showing for the first time the ability to apply this system to control endogenous levels of target protein, in this case BRM. We used the SMASh tag to target the endogenous BRM locus in both a BRG1 wild-type and mutant cancer cell line. Using these engineered cell lines, we were able to show that we can achieve tunable protein levels by varying the concentration of the effector molecule. The ability to tune BRM depletion allowed us to investigate the nature of the BRG1/BRM synthetic lethal relationship. Our data interestingly suggests that while modest depletion of BRM is sufficient to observe changes in the expression of a target gene regulated by SWI/SNF in a dose-dependent manner, a higher level of BRM depletion is required to elicit a growth arrest phenotype in the BRG1-mutant non-small cell lung cancer line. Together these results uncover a novel relationship between the catalytic SWI/SNF subunit and gene expression, where we find that the latter responds in a dose dependent manner to BRM levels. Additionally, we elucidate the level of BRM depletion required to observe the synthetic lethal phenotype, providing insight and informing on strategies for therapeutic targeting whether by protein degradation approaches, such as PROTAC, or other small molecule approaches. Finally, having provided a proof-of-concept, such tools can be readily adapted for application to endogenous degradation of other target proteins in different systems.
Citation Format: Florencia Rago, Matthew T. Dimare, Geoffrey Bushold, Avnish Kapoor, Hyo-eun C. Bhang, Zainab Jagani. Controlled and endogenous depletion of a synthetic lethal target in human cancer cell lines via SMASh degron engineering [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1025. doi:10.1158/1538-7445.AM2017-1025
Abstract 1027: Development of orthotopically grafted organoid models to study pancreatic cancer progression
Authors: Hwang Chang-Il , Lee Eunjung , Silva Brandon Da , Wright Kevin , Park Youngkyu , Tuveson David A. 
Published: July 2017

Abstract
Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult human malignancies to treat. The 5-year survival rate of PDA patients is 7% and PDA is predicted to become the second leading cancer-related cause of death in the USA. A subset of potential tumor suppressor genes was identified by genome-wide analysis of human PDA and insertional mutagenesis in genetically engineered mouse models (GEMMs). Since the functional validation of these genes in GEMMs is time-consuming and labor-intensive, we have developed a rapid and efficient ‘orthotopically grafted organoid’ (OGO) models in conjunction with RNAi and CRISPR/Cas9 technology to study PDA progression. Previously, we showed that OGO model represents the full spectrum of PDA progression in vivo upon orthotopic engraftment. Here, as a proof-of-concept experiment, we demonstrate that ablation of Trp53 by viral introduction of shRNA or gRNA in PanIN-derived organoids accelerates PDA progression upon transplantation. In addition, we engineered tetracyclin-inducible shRNA against Trp53 in ColA1 locus by Flpe recombinase-mediated cassette exchange in organoids derived from Kras +/G12D ; Rosa26-rtTA ; ColA1-homing cassette mouse. Orthotopic transplantation followed by doxycycline administration resulted in rapid PDA progression with metastases. Isolated tumor organoids were re-transplanted to evaluate the effect of p53 restoration in PDA progression. Restoration of p53 by doxycycline withdrawal led to reduced liver metastases, although there was no difference in survival and primary tumor growth. This will provide a new insight how p53 regulates PDA metastasis. Therefore, OGO models should provide an excellent platform to study the functional role of genes in PDA progression in vivo.
Citation Format: Chang-Il Hwang, Eunjung Lee, Brandon Da Silva, Kevin Wright, Youngkyu Park, David A. Tuveson. Development of orthotopically grafted organoid models to study pancreatic cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1027. doi:10.1158/1538-7445.AM2017-1027
Abstract 1028: Genetic disruption of Kras sensitizes lung cancer cells to Fas-mediated apoptosis
Authors: Mou Haiwei , Moore Jill , Malonia Sunil , Li Yingxiang , Ozata Deniz , Hough Soren , Song Chunqing , Smith Jordan , Yin Has , Fisher Andrew , Anderson Daniel , Weng Shipping , Green Michael , Xue Wen 
Published: July 2017

Abstract
Genetic lesions that activate KRAS account for ~30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras. Here we show that tumor cells can survive CRISPR-mediated knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment. Kras-independent cancer cells exhibit decreased colony formation in vitro but retain the ability to form tumors in mice. Comparing the transcriptomes of oncogenic Kras cells and Kras knockout cells, we identified 603 genes that were specifically upregulated in Kras knockout cells, including the Fas gene, which encodes a cell surface death receptor involved in physiological regulation of apoptosis. Antibodies recognizing Fas-receptor efficiently induced apoptosis of Kras knockout cells but not oncogenic Kras expressing cells. Increased Fas expression in Kras knockout cells was attributed to decreased association of repressive epigenetic marks at the Fas promoter. Concordant with this observation, treating oncogenic Kras cells with histone-deacetylase inhibitor and Fas-activating antibody efficiently induced apoptosis, thus bypassing the need to inhibit Kras. Our results suggest that activation of Fas could be exploited as an Achilles’ heel in tumors initiated by oncogenic Kras.
Citation Format: Haiwei Mou, Jill Moore, Sunil Malonia, Yingxiang Li, Deniz Ozata, Soren Hough, Chunqing Song, Jordan Smith, Has Yin, Andrew Fisher, Daniel Anderson, Shipping Weng, Michael Green, Wen Xue. Genetic disruption of Kras sensitizes lung cancer cells to Fas-mediated apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1028. doi:10.1158/1538-7445.AM2017-1028