bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonconservative unimodular gravity: a viable cosmological scenario?
Authors: Fabris Júlio C. , Alvarenga Marcelo H. , Hamani-Daouda Mahamadou , Velten Hermano 
Published: June 2022

AbstractIn this work we review the issue of imposing the conservation of the energy–momentum tensor as a necessary condition to recover the equivalence between the unimodular gravity and General Relativity (GR) equipped with a cosmological constant. This procedure is usually interpreted as an ad hoc imposition on the unimodular theory’s structure. Whereas the consequences of avoiding the conservation of the total energy–momentum tensor has been already introduced in the literature, it has been not widely explored so far. We study an expanding universe sourced by a single effective perfect fluid such that the null divergence of its energy–momentum tensor is not imposed. As we shall show, in this scheme, the unimodular theory has its own conservation equation obtained from the Bianchi identities. We explore the evolution of the homogeneous and isotropic expanding background and show that a viable cosmological scenario exists. Also, we consider scalar perturbations with particular attention given to the gauge issue. We show that contrary to the traditional unimodular theory where the synchronous and longitudinal (newtonian) gauge for cosmological perturbations are not permitted, if the conservation of the energy–momentum is relaxed the scalar perturbations in the synchronous condition survive and present a growing mode behavior. We study therefore a new cosmological scenario in which the dynamics of the universe transits from the radiative phase directly to a accelerated one but allowing thus for structure formation.
SCVS: On AI and Edge Clouds Enabled Privacy-preserved Smart-city Video Surveillance Services
Authors: Myneni Sowmya , Agrawal Garima , Deng Yuli , Chowdhary Ankur , Vadnere Neha , Huang Dijiang 
Published: June 2022

Video surveillance systems are increasingly becoming common in many private and public campuses, city buildings, and facilities. They provide many useful smart campus/city monitoring and management services based on data captured from video sensors. However, the video surveillance services may also breach personally identifiable information, especially human face images being monitored; therefore, it may potentially violate the privacy of human subjects involved. To address this privacy issue, we introduced a large-scale distributed video surveillance service model, called Smart-city Video Surveillance (SCVS). SCVS is a video surveillance data collection and processing platform to identify important events, monitor, protect, and make decisions for smart campus/city applications. In this article, the specific research focus is on how to identify and anonymize human faces in a distributed edge cloud computing infrastructure.

To preserve the privacy of data during video anonymization, SCVS utilizes a two-step approach: (i) parameter server-based distributed machine learning solution, which ensures that edge nodes can exchange parameters for machine learning-based training. Since the dataset is not located on a centralized location, the data privacy and ownership are protected and preserved. (ii) To improve the machine learning model’s accuracy, we presented an asynchronous training approach to protect data and model privacy for both data owners and data users, respectively. SCVS adopts an in-memory encryption approach, where edge computing nodes collect and process data in the memory of edge nodes in encrypted form. This approach can effectively prevent honest but curious attacks. The performance evaluation shows the presented privacy protection platform is efficient and effective compared to traditional centralized computing models as presented in Section
5
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Affective Robots Need Therapy
Authors: Bucci Paul , Marino David , Beschastnikh Ivan 
Published: June 2022

Emotion researchers have begun to converge on the theory that emotions are psychologically and socially constructed. A common assumption in affective robotics is that emotions are categorical brain-body states that can be confidently modeled. But if emotions are constructed, then they are interpretive, ambiguous, and specific to an individual’s unique experience. Constructivist views of emotion pose several challenges to affective robotics: first, it calls into question the validity of attempting to obtain objective measures of emotion through rating scales or biometrics. Second, ambiguous subjective data poses a challenge to computational systems that need structured and definite data to operate. How can a constructivist view of emotion be rectified with these challenges?
In this article, we look to psychotherapy for ontological, epistemic, and methodological guidance. These fields (1) already understand emotions to be intrinsically embodied, relative, and metaphorical and (2) have built up substantial knowledge informed by everyday practice. It is our hope that by using interpretive methods inspired by therapeutic approaches, HRI researchers will be able to focus on the practicalities of designing effective embodied emotional interactions.
Increased Heparanase Expression Is Caused by Promoter Hypomethylation and Up-Regulation of Transcriptional Factor Early Growth Response-1 in Human Prostate Cancer
Authors: Ogishima Tatsuya , Shiina Hiroaki , Breault Julia E. , Tabatabai Laura , Bassett William W. , Enokida Hideki , Li Long-Cheng , Kawakami Toshifumi , Urakami Shinji , Ribeiro-Filho Leopoldo A. , Terashima Masaharu , Fujime Makoto , Igawa Mikio , Dahiya Rajvir 
Published: June 2022

Abstract
Purpose: Heparanase degrades heparan sulfate and has been implicated in tumor invasion and metastasis. The transcription factor, early growth response 1 (EGR1), is associated with the inducible transcription of the heparanase gene. We hypothesize that CpG hypomethylation in the heparanase promoter coupled with up-regulation of EGR1 levels may induce heparanase expression in human prostate cancer.
Experimental Design: Cultured prostate cancer cell lines (Du145, DuPro, LNCaP, and PC-3) with and without 5′-aza-2-deoxycytidine treatment, 177 prostate cancer samples, and 69 benign prostatic hyperplasia (BPH) samples were used. The frequency and level of heparanase promoter methylation were analyzed by methylation-specific primers which covered the core binding motif of EGR1 (GGCG) or SP1 (GGGCGG) or both.
Results: In cultured Du145, DuPro, LNCaP, and PC-3 cell lines, mRNA transcripts of heparanase were significantly increased after 5′-aza-2-deoxycytidine treatment, suggesting that promoter methylation was involved in the regulation of heparanase mRNA transcript. Significantly higher methylation was found in BPH samples than in prostate cancer samples (P &lt; 0.0001), whereas mRNA transcripts of the heparanase gene were inversely lower in BPH samples than in prostate cancer samples (P &lt; 0.01). EGR1 expression in prostate cancer tissues was significantly higher than in BPH tissues (P &lt; 0.001) and correlated with heparanase expression (P &lt; 0.0001). Moreover, multiple regression analysis revealed that up-regulation of EGR1 contributed significantly more to heparanase expression than did promoter CpG hypomethylation in prostate cancer samples (P &lt; 0.0001).
Conclusions: To our knowledge this is the first comprehensive study demonstrating that increased heparanase expression in prostate cancer tissues is due to promoter hypomethylation and up-regulation of transcription factor EGR1.
Patterns of Cyclin E, Retinoblastoma Protein, and p21Cip1/WAF1 Immunostaining in the Oncogenesis of Papillary Thyroid Carcinoma
Authors: Brzeziński Jan , Migodziński Adam , Toczek Aleksandra , Tazbir Józef , Dedecjus Marek 
Published: June 2022

Abstract
Purpose: Uncontrolled cell proliferation, a hallmark of cancer, may result from an increased expression of cell cycle up-regulators, and/or from a reduced expression of cell cycle down-regulators. In the present study, we analyzed, by immunohistochemistry, the expression of a panel of three proteins: cyclin E and two cell cycle inhibitors, p21Cip1/WAF1 and retinoblastoma protein (pRb) product, in different stages of papillary thyroid carcinomas (PTC).
Experimental Design: We investigated immunostaining patterns of the proteins in question in 51 resected PTC in pathologic stages, ranging from pT1a to pT4, taking into consideration their relation to clinicohistopathologic factors.
Results: We observed a significant, progressive loss of expression of p21Cip1/WAF1 with advancing tumor grade. The differences reached values of significance between pT1a [papillary thyroid microcarcinomas (PMC)] and pT2 and between PMC and pT4 stages of PTC. pRb presented a similar immunostaining pattern to that of p21Cip1/WAF1 and the differences reached values of significance between pT1a and pT2, and between PMC and pT4 stages of PTC. The results of cyclin E immunostaining corresponded to our recently published result, and a negative correlation was observed between the immunostaining index of cyclin E and pRb.
Conclusions: The results of the present study suggest that cyclin E expression and suppression of pRb and p21Cip1/WAF1 may be characteristic patterns of immunostaining for PTC with a tendency to early metastasizing. If our results are confirmed in a larger study, the diagnostic panel, constructed of the antibodies against these proteins, may become a valuable tool in predicting the metastatic potential in PTC.
Macrophage Migration Inhibitory Factor Promotes Tumor Invasion and Metastasis via the Rho-Dependent Pathway
Authors: Sun Bailong , Nishihira Jun , Yoshiki Takashi , Kondo Masao , Sato Yuji , Sasaki Fumiaki , Todo Satoru 
Published: June 2022

Abstract
Purpose: Macrophage migration inhibitory factor (MIF) plays an important role not only in the immune system but also in tumorigenesis. In this study, we investigated the potential role of MIF in association with tumor invasion and metastasis.
Methods: To assess the function of MIF, we knocked down the MIF mRNA using small interfering RNA (siRNA). Twenty-one base siRNA specific for the mRNA sequence of mouse MIF was introduced to a murine colon cancer cell line, colon 26. Tumor cell invasion was evaluated using a transwell method (8-μm pores) coated with Matrigel on the upperside membrane and with fibronectin on the underside membrane. Moreover, we investigated the signal transduction of lysophosphatidic acid (LPA) relevant to the Rho-dependent pathway and further examined the effect of MIF siRNA on this signal transduction system. In vivo, the tumor cells were pretreated with MIF siRNA and injected into the portal vein, and the effects on metastasis to the liver were evaluated.
Results: We found that MIF siRNA markedly reduced the invasion of the cells from the upperside to lowerside membranes. We revealed that the Rho-dependent pathway activated by LPA was suppressed by MIF siRNA. Next, we found that the tyrosine-phosphorylation of focal adhesion kinase and LPA-induced expressions of integrin β1 were significantly suppressed by MIF siRNA. In vivo, metastasis to the liver was significantly inhibited by pretreatment of the cells with MIF siRNA.
Conclusion: Taken together, these results suggest that MIF promotes tumor invasion and metastasis via the Rho-dependent pathway.
Polymorphisms in ER-α Gene Interact with Estrogen Receptor Status in Breast Cancer Survival
Authors: Boyapati Sonia M. , Shu Xiao Ou , Ruan Zhi Xian , Cai Qiuyin , Smith Jeffrey R. , Wen Wanqing , Gao Yu-Tang , Zheng Wei 
Published: June 2022

Abstract
Purpose: The effects of estrogens are mediated primarily through estrogen receptor (ER) in breast tissue, and polymorphisms in the ER genes may alter the functions of these receptors. Polymorphisms in the ER-α gene have been reported to be associated with breast cancer risk. However, to our knowledge, no study has been published on the relation between ER-α gene polymorphisms and breast cancer survival.
Experimental Design: To determine whether three common polymorphisms in the ER-α gene, PvuII, XbaI, and GT dinucleotide repeats are associated with breast cancer survival, we evaluated data from a cohort of 1,069 breast cancer patients who participated in the Shanghai Breast Cancer Study between 1996 and 1998. The median follow-up time for this cohort of women was 5.2 years.
Results: No overall association was observed between ER gene polymorphisms and breast cancer survival. The genotype associations, however, were modified by ER status in breast cancer tissues. Comparing those with the PP genotype to the pp genotype of the PvuII polymorphism, the hazard ratios (HR) of dying were 3.30 [95% confidence interval (95% CI), 1.42-7.69] and 0.54 (95% CI, 0.24-1.23), respectively, for participants with ER-negative breast cancer and ER-positive breast cancer. Similarly, compared with those with no (GT)23 alleles, carrying one or two (GT)23 alleles of the GT repeat polymorphism was related to a HR of 1.48 (95% CI, 0.77-2.87) for ER-negative breast cancer and a HR of 0.25 (95% CI, 0.09-0.69) for ER-positive cancer. The effect of ER on breast cancer survival was also modified by genotypes of ER-α gene. Tests for multiplicative interaction were highly significant.
Conclusions: These data suggest that the ER-α gene polymorphisms and ER status may have an interactive effect on breast cancer survival.
Plasma Protein Profiling for Diagnosis of Pancreatic Cancer Reveals the Presence of Host Response Proteins
Authors: Koomen John M. , Shih Lichen Nancy , Coombes Kevin R. , Li Donghui , Xiao Lian-chun , Fidler Isaiah J. , Abbruzzese James L. , Kobayashi Ryuji 
Published: June 2022

Abstract
Plasma protein profiling using separations coupled to matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) has great potential in translational research; it can be used for biomarker discovery and contribute to disease diagnosis and therapy. Previously reported biomarker searches have been done solely by MS protein profiling followed by bioinformatics analysis of the data. To add to current methods, we tested an alternative strategy for plasma protein profiling using pancreatic cancer as the model. First, offline solid-phase extraction is done with 96-well plates to fractionate and partially purify the proteins. Then, multiple profiling and identification experiments can be conducted on the same protein fractions because only 5% of the fractions are used for MALDI MS profiling. After MALDI MS analysis, the mass spectra are normalized and subjected to a peak detection algorithm. Over three sets of mass spectra acquired using different instrument variables, ∼400 unique ion signals were detected. Classification schemes employing as many as eight individual peaks were developed using a training set with 123 members (82 cancer patients) and a blinded validation set with 125 members (57 cancer patients). The sensitivity of the study was 88%, but the specificity was significantly lower, 75%. The reason for the low specificity becomes apparent upon protein identification of the ion signals used for the classification. The identifications reveal only common serum proteins and components of the acute phase response, including serum amyloid A, α-1-antitrypsin, α-1-antichymotrypsin, and inter-α-trypsin inhibitor.
The Expression of Hypoxia-Inducible Factor 1α Is a Favorable Independent Prognostic Factor in Renal Cell Carcinoma
Authors: Lidgren Anders , Hedberg Ylva , Grankvist Kjell , Rasmuson Torgny , Vasko Janos , Ljungberg Börje 
Published: June 2022

Abstract
Purpose: Renal cell carcinoma (RCC) is the most common malignancy of the kidney composed of specific tumor types. The sporadic conventional RCCs are, in contrast to the other RCC types, characterized by a high rate of von Hippel-Lindau (VHL) mutations and hypermethylation. The majority of these tumors lack functional VHL protein (pVHL) that leads to increased hypoxia-inducible factor 1α (HIF-1α) expression. The pVHL is the physiologic regulator of the activity of HIF-1α by targeting it to the proteasome for degradation under normoxia. Both pVHL and HIF-1α target other genes that are important for cancer survival and proliferation. Expression of HIF-1α has been linked to poor prognosis in different malignancies, although few studies have been done on the relation between HIF-1α and clinical variables in RCC.
Experimental Design: HIF-1α protein expression was analyzed in tumor tissue from 92 patients with RCC. HIF-1α was quantified by Western blot relative to a positive control.
Results: The HIF-1α protein was expressed as two bands which strongly correlated (r = 0.906, P &lt; 0.001); therefore, they were added and the sum evaluated against clinicopathologic variables. There was no association between HIF-1α and gender, stage, grade, tumor size, or vein invasion. Conventional RCCs had significantly higher HIF-1α expression compared with papillary and chromophobe RCCs and kidney cortex. In conventional RCC, HIF-1α was an independent prognostic factor.
Conclusion: HIF-1α levels varied significantly between the different RCC types. In conventional RCC, HIF-1α was an independent prognostic factor. These data indicate that HIF-1α is involved in tumorogenesis and progression of RCC. Evaluation of other HIF target gene products and correlation to angiogenesis seems warranted.
Preclinical Evaluation of New and Highly Potent Analogues of Octreotide for Predictive Imaging and Targeted Radiotherapy
Authors: Ginj Mihaela , Chen Jianhua , Walter Martin A. , Eltschinger Veronique , Reubi Jean Claude , Maecke Helmut R. 
Published: June 2022

Abstract
Purpose: Molecular imaging and targeted radiotherapy are emerging fields in nuclear oncology. Five human somatostatin receptors (hsstr1-hsstr5) are known to be overexpressed to some degree on various tumors, sstr2 being the most important one. Clinically used somatostatin based radiopeptides target exclusively sstr2. The aim of this study was to develop novel analogues with a broader sstr profile for diagnostic (positron emission tomography and single-photon emission computed tomography) and radiotherapeutic applications.
Experimental Design: The following promising structures emerged from a parallel synthetic approach: [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA0),1-Nal3,Thr8]-octreotide (1, DOTA-NOC-ATE) and [DOTA0,BzThi3,Thr8]-octreotide (2, DOTA-BOC-ATE). The conjugates were labeled with cold and radioactive 111In. Pharmacologic properties were compared with [111In-DOTA,Tyr3]-octreotide ([111In-DOTA]-TOC).
Results: The receptor affinity profile showed high affinity of both peptides to hsstr2, hsstr3, and hsstr5 and some intermediate affinity to hsstr4, whereas [111In-DOTA]-TOC shows affinity only to sstr2. The internalization is fast in sstr2 expressing AR4-2J and in transfected sstr3 expressing human embryonic kidney 293 cells. Both radiopeptides internalize much more efficiently than [111In-DOTA]-TOC. Animal biodistribution studies showed very high and specific uptake of [111In]-1 and [111In]-2 in s.c. implanted AR4-2J tumors (Lewis rats) and in somatostatin receptor expressing normal tissues. The uptake was at least 2-fold higher in these tissues and in the tumor compared with [111In-DOTA]-TOC. In addition, the kidney uptake was significantly lower for both radiopeptides.
Conclusions: These data suggest that the novel radiopeptides are superior to [111In/90Y-DOTA]-TOC and show great promise for the clinical application in the imaging of somatostatin receptor–positive tumors and their targeted radiotherapy.
Transcriptional Profiles in Peripheral Blood Mononuclear Cells Prognostic of Clinical Outcomes in Patients with Advanced Renal Cell Carcinoma
Authors: Burczynski Michael E. , Twine Natalie C. , Dukart Gary , Marshall Bonnie , Hidalgo Manuel , Stadler Walter M. , Logan Theodore , Dutcher Janice , Hudes Gary , Trepicchio William L. , Strahs Andrew , Immermann Fred , Slonim Donna K. , Dorner Andrew J. 
Published: June 2022

Abstract
Purpose: Given their accessibility, surrogate tissues, such as peripheral blood mononuclear cells (PBMC), may provide potential predictive biomarkers in clinical pharmacogenomic studies. In leukemias and lymphomas, the prognostic value of peripheral blast expression profiles is clear; however, it is unclear whether circulating mononuclear cells of patients with solid tumors might yield profiles with similar prognostic associations.
Experimental Design: In this study, we evaluated the association of expression profiles in PBMCs with clinical outcomes in patients with advanced renal cell cancer. Transcriptional patterns in PBMCs of 45 renal cell cancer patients were compared with clinical outcome data at the conclusion of a phase II study of the mTOR kinase inhibitor CCI-779 to determine whether pretreatment transcriptional patterns in PBMCs were correlated with eventual patient outcomes.
Results: Unsupervised hierarchical clustering of the PBMC profiles using all expressed genes identified clusters of patients with significant differences in survival. Cox proportional hazards modeling showed that the expression levels of many PBMC transcripts were predictors for the patient outcomes of time to progression and overall survival (time to death). Supervised class prediction approaches identified multivariate expression patterns in PBMCs capable of assigning favorable outcomes of time to death and time to progression in a test set of renal cancer patients, with overall performance accuracies of 72% and 85%, respectively.
Conclusions: The present study provides the first example of gene expression profiling in peripheral blood, a clinically accessible surrogate tissue, for identifying patterns of gene expression associated with higher likelihoods of positive outcome in patients with a solid tumor.
Identification of Epigenetic Aberrant Promoter Methylation in Serum DNA Is Useful for Early Detection of Lung Cancer
Authors: Fujiwara Keiichi , Fujimoto Nobukazu , Tabata Masahiro , Nishii Kenji , Matsuo Keitaro , Hotta Katsuyuki , Kozuki Toshiyuki , Aoe Motoi , Kiura Katsuyuki , Ueoka Hiroshi , Tanimoto Mitsune 
Published: June 2022

Abstract
Purpose: The purpose of this study is to evaluate the usefulness of serum DNA methylation of five tumor suppressor genes for early detection of lung cancer.
Experimental Design: Methylation status in serum DNA from 200 patients undergoing bronchofiberscopic examination for abnormal findings on chest radiograph detected by lung cancer screening or surveillance was examined using methylation-specific PCR.
Results: Ninety-one patients were given a pathologic diagnosis of lung cancer, 9 other malignant diseases, and 100 nonmalignant pulmonary diseases. In patients with lung cancer, methylation was detected in 18.7% for MGMT, 15.4% for p16INK4a, 12.1% for RASSF1A, 11.0% for DAPK, and 6.6% for RAR-β, which was higher compared with that in patients with nonmalignant diseases. Age and smoking status seemed to associate with methylation status. Sensitivity, specificity, and predictive value of methylation in at least one gene for diagnosis of lung cancer were 49.5%, 85.0%, and 75.0%, respectively. Adjusted odds ratio (95% confidence interval) for having lung cancer was 5.28 (2.39-11.7) for patients with methylation in one gene and 5.89 (1.53-22.7) for those with methylation in two or more genes. It is of note that methylation was identified in 50.9% of stage I lung cancer patients, whereas serum protein tumor markers were positive in 11.3% of them.
Conclusions: These results suggest that identification of promoter methylation of tumor suppressor genes in serum DNA could be useful for early detection of lung cancer.