bluuebunny/crossref_metadata_2025 huggingface dataset:
Body fluids should be identified before estimating the time since deposition (TsD) in microbiome-based stain analyses for forensics
Authors: Zhang Jun , Yu Daijing , Wang Tian , Gao Niu , Shi Linyu , Wang Yaya , Huo Yumei , Ji Zhimin , Li Junli , Zhang Xiaomeng , Zhang Liwei , Yan Jiangwei
Published: March 2024

Identification and the time since deposition (TsD) estimation of body fluid stains from a crime scene could provide valuable information for solving the cases and are always difficult for forensics. Microbial characteristics were considered as a promising biomarker to address the issues. However, changes in the microbiota may damage the specific characteristics of body fluids. Correspondingly, incorrect body fluid identification may result in inaccurate TsD estimation. The mutual influence is not well understood and limited the codetection. In the current study, saliva, semen, vaginal secretion, and menstrual blood samples were exposed to indoor conditions and collected at eight time points (from fresh to 30 days). High-throughput sequencing based on the 16S rRNA gene was performed to characterize the microbial communities. The results showed that a longer TsD could decrease the discrimination of different body fluid stains. However, the accuracies of identification still reached a quite high value even without knowing the TsD. Correspondingly, the mean absolute error (MAE) of TsD estimation significantly increased without distinguishing the types of body fluids. The predictive TsD of menstrual blood reached a quite low MAE (1.54 ± 0.39 d). In comparison, those of saliva (6.57 ± 1.17 d), semen (6.48 ± 1.33 d), and vaginal secretion (5.35 ± 1.11 d) needed to be further improved. The great effect of individual differences on these stains limited the TsD estimation accuracy. Overall, microbial characteristics allow for codetection of body fluid identification and TsD estimation, and body fluids should be identified before estimating TsD in microbiome-based stain analyses.

IMPORTANCE

Emerged evidences suggest microbial characteristics could be considered a promising tool for identification and time since deposition (TsD) estimation of body fluid stains. However, the two issues should be studied together due to a potential mutual influence. The current study provides the first evidence to understand the mutual influence and determines an optimal process for codetection of identification and TsD estimation for unknown stains for forensics. In addition, we involved aged stains into our study for identification of body fluid stains, rather than only using fresh stains like previous studies. This increased the predictive accuracy. We have preliminary verified that individual differences in microbiotas limited the predictive accuracy of TsD estimation for saliva, semen, and vaginal secretion. Microbial characteristics could provide an accurate TsD estimation for menstrual blood. Our study benefits the comprehensive understanding of microbiome-based stain analyses as an essential addition to previous studies.
Tectonic dismemberment and plume-ridge interaction in the Sub-Antarctic South Atlantic Ocean Basin: Confirmation from in situ geochemical and Sr isotopic compositions of minerals
Authors: Chen Shuang-Shuang , Zhang Wenjing , Dingwell Donald B. , Gao Rui , Liu Jia-Qi
Published: March 2024

The Sub-Antarctic South Atlantic Ocean has been inferred to have undergone a complex tectonic history involving dismemberment and plume-ridge interaction. Here we report new in situ major (electron probe microanalysis, EPMA), trace element (laser ablation–inductively coupled plasma–mass spectrometry, LA-ICP-MS), and Sr isotopic (laser ablation–multicollector–inductively coupled plasma–mass spectrometry, LA-MC-ICP-MS) compositions for minerals (olivine, clinopyroxene, and plagioclase) from the Northeast Georgia Rise (NGR; Sites 698 and 699), Islas Orcadas Rise (IOR; Site 701), and Meteor Rise (MR; Site 703) volcanic samples in the Sub-Antarctic South Atlantic Ocean. Plagioclases and clinopyroxenes from Sites 698, 699, and 703 are characterized by similar incompatible element patterns and Sr isotopic characteristics, suggesting that they are likely to have originated from a cogenetic mantle source. The plagioclases and clinopyroxenes exhibit an oscillatory, reverse, and normal zoning texture, and display clear evidence of Sr isotopic disequilibrium, suggesting dynamic and open fractional-crystallization processes as well as extensive mixing of compositionally distinct magmas. Rims and groundmass of plagioclase exhibit much more highly radiogenic Sr isotopes than their cores, likely indicating the involvement of both continental lithospheric and recycled oceanic crust. The in situ geochemical and isotopic compositions of these minerals exhibit the features of both the oceanic-island basalt–type Tristan-Gough mantle plume track and the normal mid-oceanic-ridge basalt–type Mid-Atlantic spreading ridge (MAR) and Agulhas spreading ridge (AR) track. We speculate that the NGR, IOR, and MR were formed from the same mantle source with volcanic flow of the Tristan-Gough mantle plume. Subsequently, tectonic movement along the MAR and AR separated the originally combined MR-IOR-NGR, resulting in the incursion of depleted asthenospheric mantle and the contamination contributions of continental and recycled oceanic crust components.
Competing effects of crustal shortening, thermal inheritance, and surface processes explain subsidence anomalies in inverted rift basins
Authors: Oravecz Éva , Balázs Attila , Gerya Taras , May Dave A. , Fodor László
Published: March 2024

Structural inversion of rifted basins is generally associated with surface uplift and denudation of the sedimentary infill, reflecting the active contractional deformation in the crust. However, worldwide examples of inverted rifts show contrasting basin-scale subsidence and widespread sedimentation patterns during basin inversion. By conducting a series of three-dimensional coupled geodynamic and surface processes models, we investigated the dynamic controls on these subsidence anomalies during the successive stages of rifting and basin inversion, and we propose a new evolutionary model for this process. Our models show that the inherited thermo-rheological properties of the lithosphere influence the initial strain localization and subsequent migration of crustal deformation during inversion. The sense of the vertical movements (i.e., uplift or subsidence), however, is not directly linked to the underlying crustal stress patterns; rather, it reflects the balance among contraction-induced tectonic uplift, postrift thermal subsidence of the inherited lithosphere, and sediment redistribution. Based on the interplay among the competing differential vertical movements with different amplitudes and wavelengths, inversion of rifted basins may lead to the growth of intraplate orogens, or the contraction-driven localized uplift may be hindered by the thermal sag effects of the inherited shallow lithosphere-asthenosphere boundary, resulting in basin-scale subsidence. In such basins, dating the first erosional surfaces and other unconformities may not provide accurate timing for the onset of inversion.
Supplemental Material: Polymorphic transformations of titanium oxides contribute to economic uranium mineralization in sandstone
Authors: Yin Shuo , Yan Zhaobin , al. et
Published: March 2024

Methods, Figures S1–S7, and Tables S1–S3.  
Supplemental Material: Oman as a fragment of Ediacaran eastern Gondwana
Authors: Gomez-Perez Irene , al. et
Published: March 2024

Sample lists and geochronology data tables, and methodology, zircon, apatite, and rutile geochronology appendices.  
rhIL-7-hyFc and hIL-2/TCB2c combination promotes an immune-stimulatory tumor microenvironment that improves antitumor efficacy of checkpoint inhibitors
Authors: Lee Minji , Im Sun-Kyoung , Baek Seungtae , Ji Mankyu , Kim Miyoung , Lee Eun Ju , Ji Seung Taek , Ferrando-Martinez Sara , Wolfarth Alexandra , Lee Jun-Young , Kim Daeun , Choi Donghoon
Published: March 2024

Background

Recombinant human interleukin (rhIL)-7-hyFc (efineptakin alfa; NT-I7) is a potent T-cell amplifier, with two IL-7 molecules fused to IgD/IgG4 elements. rhIL-7-hyFc promotes extensive infiltration of CD8+T cells into the tumor, concurrently increasing the numbers of intratumoral PD-1+CD8+T cells. The hIL-2/TCB2 complex (SLC-3010) inhibits tumor growth by preferential activation of CD122 (IL-2Rβ)highCD8+T cells and natural killer cells, over regulatory T cells (Tregs). We investigated the underlying mechanisms of rhIL-7-hyFc and hIL-2/TCB2c antitumor activity and the potential synergistic efficacy, specifically focusing on tumor-specific CD8+cells within the tumor and the tumor-draining lymph nodes (tdLN).

Methods

MC38 and CT26 tumor-bearing mice were administered with 10 mg/kg rhIL-7-hyFc intramuscularly and 0.9 mg/kg hIL-2/TCB2c intravenously. Anti-PD-1 monoclonal antibody was administered intraperitoneally three times at 3-day intervals at a dose of 5 mg/kg. Tumor volume was measured to assess efficacy. To compare the composition of immune cells between each monotherapy and the combination therapy, we analyzed tumors and tdLNs by flow cytometry.

Results

Our data demonstrate that the combination of rhIL-7-hyFc and hIL-2/TCB2c increases efficacy and generates an immune-stimulatory tumor microenvironment (TME). The TME is characterized by an increased infiltration of tumor-specific CD8+T cells, and a decreased frequency of CD39highTIM-3+Treg cells. Most importantly, rhIL-7-hyFc increases infiltration of a CD62L+Ly108+early progenitor population of exhausted CD8+T cells (TPEX), which may retain long-term proliferation capacity and replenish functional effector CD8+T cells. hIL-2/TCB2c induces differentiation of CD62L+Ly108+TPEXrapidly into CD101+terminally differentiated subsets (terminally exhausted T cell (TEX term)). Our study also demonstrates that rhIL-7-hyFc significantly enhances the proliferation rate of TPEXin the tdLNs, positively correlating with their abundance within the tumor. Moreover, rhIL-7-hyFc and hIL-2/TCB2c can overcome the limited therapeutic effectiveness of PD-1 blockade, culminating in the complete regression of tumors.

Conclusions

rhIL-7-hyFc can expand and maintain the progenitor pool of exhausted CD8+T cells, whereas hIL-2/TCB2c promotes their differentiation into TEX term. Together, this induces an immune-stimulatory TME that improves the efficacy of checkpoint blockade.
Intrinsic compressibility of laterites and lateritic soils
Authors: Zhao Mingzhi , Gu Junjie , El Naggar M. Hesham , Liu Hongyang , Liu Gang , Wang Tengfei
Published: March 2024

Laterites and lateritic soils, prevalent in tropical and subtropical climates, have growing applications in earthwork construction. They usually present unique compression properties compared to conventional clays. Therefore, a thorough understanding of their intrinsic compressibility is crucial. This paper reports on modified oedometer tests conducted on reconstituted samples of four distinct laterites and lateritic soils with varying initial water contents. In addition, scanning electron microscopy (SEM) was utilized to identify the microstructural features to reveal the mechanisms of intrinsic compression. The results demonstrate that intrinsic compression curves of reconstituted laterites and lateritic soils align with Burland’s normalization framework. However, they exhibit a higher void ratio at an effective vertical stress of 100 kPa ( e* 100) and a lower compression index ( C* c) compared to traditional clays; therefore, existing formulas for calculating e* 100 and C* c are inapplicable to laterites and lateritic soils. The SEM analysis revealed that sesquioxide interacts with soil minerals, resulting in a porous structure and robust inter-unit cementation. This unique microstructure contributes to the observed intrinsic constants of compressibility, e* 100 and C* c. Based on the experimental observations, new empirical equations are introduced to evaluate e* 100 and C* c in laterites and lateritic soils. The experimental results elucidate the role of sesquioxide in inherent compressibility and improve our understanding of compressibility characteristics that are unique to laterites and lateritic soils.
Non-singular gravitational collapse through modified Heisenberg algebra
Authors: Barca Gabriele , Montani Giovanni
Published: March 2024

We study the effects of cut-off physics, in the form of a modified algebra inspired by Polymer Quantum Mechanics and by the Generalized Uncertainty Principle representation, on the collapse of a spherical dust cloud. We analyze both the Newtonian formulation, originally developed by Hunter, and the general relativistic formulation, that is the Oppenheimer–Snyder model; in both frameworks we find that the collapse is stabilized to an asymptotically static state above the horizon, and the singularity is removed. In the Newtonian case, by requiring the Newtonian approximation to be valid, we find lower bounds of the order of unity (in Planck units) for the deformation parameter of the modified algebra. We then study the behaviour of small perturbations on the non-singular collapsing backgrounds, and find that for certain range of the parameters (the polytropic index for the Newtonian case and the sound velocity in the relativistic setting) the collapse is stable to perturbations of all scales, and the non-singular super-Schwarzschild configurations have physical meaning.
Exploring plasma dynamics: Analytical and numerical insights into generalized nonlinear time fractional Harry Dym equation
Authors: Altuijri Reem , Abdel-Aty Abdel-Haleem , Nisar Kottakkaran Sooppy , Khater Mostafa M. A.
Published: March 2024

This investigation aims to examine the resolution of the generalized nonlinear time fractional Harry Dym [Formula: see text] equation through a combined application of analytical and numerical methodologies. The primary objective is to scrutinize the equation’s behavior and present proficient methodologies for its resolution. The Khater II analytical technique and numerical frameworks, specifically the Cubic-B-spline, Quantic-B-spline, and Septic-B-spline schemes, are proposed for this purpose. The outcomes of this inquiry yield substantial revelations regarding the characteristics of [Formula: see text] equation. Both the analytical approach and numerical schemes demonstrate their efficacy in yielding precise solutions. These findings carry noteworthy implications across various disciplines, encompassing physics, mathematics, and engineering. The investigated model appears in plasma physics research on soliton theory and nonlinear waves. Soliton waves, which keep their shape and velocity while propagating, are found in plasma physics and other domains. In plasma environments, the Harry Dym equation describes these solitons and their behavior. Solitons are essential for understanding plasma dynamics, including nonlinear waves and structures. They help comprehend plasma dynamics, wave interactions, and other nonlinear processes. The principal deductions drawn from this study underscore the effectiveness and viability of the proposed techniques in resolving the [Formula: see text] equation. This research introduces innovative contributions in terms of insights and methodologies pertinent to analogous nonlinear fractional equations. Its scope encompasses nonlinear dynamics, fractional calculus, and numerical analysis.
Optical properties of a tunable microcavity/microsphere polymeric composite
Authors: Scotognella Francesco
Published: March 2024

The combination of a microcavity and a microsphere has been proposed in this work to manipulate light in terms of emission wavelength and propagation direction. A microcavity with a layer of molecular photoswitch between two one-dimensional photonic crystals of polyvinyl carbazole and cellulose acetate has been designed. To tune the microcavity, the molecular photoswitch has been excited taking into account its cyclization upon irradiation at 313[Formula: see text]nm and its cycloreversion at 450[Formula: see text]nm. In this way, the emission peak of the microcavity switches from 508.5[Formula: see text]nm to 525[Formula: see text]nm. A polystyrene microsphere with a radius of 1[Formula: see text][Formula: see text]m is placed near the microcavity. With the detector at an angle of 8°, the emission at 525[Formula: see text]nm is 1.73 times higher with respect to the emission at 508.5[Formula: see text]nm, while at 10.8°, the emission at 508.5[Formula: see text]nm is 1.45 times higher with respect to the emission at 525[Formula: see text]nm. The value of these findings is that they offer the experimentalists a ready means to compare the optical data of these types of composites with theory.
Resonance-enhanced photoemission from GaInAsSb nanopillar array photocathodes
Authors: Wang Zhidong , Liu Lei , Cao Zhihao , Tian Jian , Zhangyang Xingyue
Published: March 2024

A resonance-enhanced GaInAsSb nanopillar array negative electron affinity potential photocathode based on Mie resonance excitation at infrared wavelengths can significantly enhance the absorption and quantum efficiency of nanopillar arrays. Our study indicates the different periodic structures have very little effect on the QE for the nanopillar arrays. However, the smaller the period of the array, the higher the quantum efficiency is achieved, but the probability of being collected by the anode is reduced, so a compromise should be considered in the structure design. Moreover, the incident light inclination and the external electric field can significantly affect the quantum efficiency of the nanopillar arrays. The photocathodes studied here have a quantum efficiency of over 5.7% with an angle of incidence of 30∘ and an applied electric field intensity of 1.2[Formula: see text]V/[Formula: see text]m. This work provides an important reference and theoretical basis for the design and optimization of resonance-enhanced GaInAsSb nanopillar arrays photocathode.
Edge Computing Security of Mobile Communication System Based on Computer Algorithms
Authors: Zhang Jinna
Published: March 2024

With the progress of information technology recently, mobile communication system edge computing (EC) has been widely used in all walks of life, but the traditional mobile communication system EC mode has security problems such as privacy disclosure, malicious tampering, and virus attacks. Computer algorithms has brought new vitality to EC in mobile communication systems. This paper analyzed the application of computer algorithm in EC mode of mobile communication system, and selected 20 users as the research object. This paper adopted traditional computing mode (such as cloud computing) and computer algorithm-based mobile communication system EC security research. This text compared the effects of two modes on security performance, data transmission efficiency, energy consumption, cost savings, and user satisfaction. The experimental results in this paper showed that the average security of EC mode of mobile communication system based on computer algorithm was 84%, and the average data transmission time was 4.8[Formula: see text]s. The energy consumption was 40%, and the cost savings and user satisfaction were 432,000 yuan and 13 points, respectively. Both were superior to the traditional edge counting mode. The EC mode of mobile communication system using computer algorithms can significantly improve the security of mobile communication, data transmission speed, cost savings, user satisfaction, and reduce energy consumption. This model has important significance and value for social development.
Novel naphthalimide bridged zinc porphyrin/BODIPY nanomaterials with D-A structure for photodynamic therapy
Authors: Cui Min , Zhu Sijie , Xiong Mengmeng , Zuo Huijie , Li Xiang , Wang Kai , Jiang Jun
Published: March 2024

As a non-invasive cancer therapy method, photodynamic therapy (PDT) shows tremendous promise in clinical cancer treatment. Light-activated singlet oxygen production of photosensitizers (PSs) is the prerequisite for cancer PDT, and the use of organic photosensitizers is always limited by visible light-based activation, hydrophilicity, biocompatibility, selectivity and quantum yield of singlet oxygen. Currently, both zinc porphyrin- and BODIPY-based structures have been widely used in the development of PDT PSs. Here, we developed a novel naphthalimide bridged zinc porphyrin/BODIPY molecule (Por-BDP-1) with two poly(ethylene glycol) (PEG) chains, in which D-A structure was constructed between the naphthalimide group and porphyrin group. After self-assembly into nanoparticles, Por-BDP-1 NPs (Diameter: 122.4 nm) could quench fluorescence in 600–700 nm, bind with calf thymus-DNA, and produce singlet oxygen during light-irradiation (laser: 680 nm, 1.0 W/cm[Formula: see text]. In addition, Por-BDP-1 NPs effectively killed HeLa cells with a IC[Formula: see text] value = 44.8 μg/mL and showed a lower dark toxicity under the same conditions. All our results demonstrated that our naphthalimide bridged zinc porphyrin/BODIPY nano-photosensitizer is a promising nanoagent for PDT in the clinic.
Avoiding Breakdown in Incomplete Factorizations in Low Precision Arithmetic
Authors: Scott Jennifer , Tůma Miroslav
Published: March 2024

The emergence of low precision floating-point arithmetic in computer hardware has led to a resurgence of interest in the use of mixed precision numerical linear algebra. For linear systems of equations, there has been renewed enthusiasm for mixed precision variants of iterative refinement. We consider the iterative solution of large sparse systems using incomplete factorization preconditioners. The focus is on the robust computation of such preconditioners in half precision arithmetic and employing them to solve symmetric positive definite systems to higher precision accuracy; however, the proposed ideas can be applied more generally. Even for well-conditioned problems, incomplete factorizations can break down when small entries occur on the diagonal during the factorization. When using half precision arithmetic, overflows are an additional possible source of breakdown. We examine how breakdowns can be avoided and implement our strategies within new half precision Fortran sparse incomplete Cholesky factorization software. Results are reported for a range of problems from practical applications. These demonstrate that, even for highly ill-conditioned problems, half precision preconditioners can potentially replace double precision preconditioners, although unsurprisingly this may be at the cost of additional iterations of a Krylov solver.
Do Humans Trust Robots that Violate Moral Trust?
Authors: Rezaei Khavas Zahra , Kotturu Monish Reddy , Ahmadzadeh S. Reza , Robinette Paul
Published: March 2024

The increasing use of robots in social applications requires further research on human-robot trust. The research on human-robot trust needs to go beyond the conventional definition that mainly focuses on how human-robot relations are influenced by robot performance. The emerging field of social robotics considers optimizing a robot’s personality a critical factor in user perceptions of experienced human-robot interaction (HRI). Researchers have developed trust scales that account for different dimensions of trust in HRI. These trust scales consider one performance aspect (i.e., the trust in an agent’s competence to perform a given task and their proficiency in executing the task accurately) and one moral aspect (i.e., trust in an agent’s honesty in fulfilling their stated commitments or promises) for human-robot trust. The question that arises here is to what extent do these trust aspects affect human trust in a robot? The main goal of this study is to investigate whether a robot’s undesirable behavior due to the performance trust violation would affect human trust differently than another similar undesirable behavior due to a moral trust violation. We designed and implemented an online human-robot collaborative search task that allows distinguishing between performance and moral trust violations by a robot. We ran these experiments on Prolific and recruited 100 participants for this study. Our results showed that a moral trust violation by a robot affects human trust more severely than a performance trust violation with the same magnitude and consequences.
Review—Organic Solar Cells: Structural Variety, Effect of Layers, and Applications
Authors: Chamola Paritosh , Mittal Poornima , Kumar Brijesh
Published: March 2024

This review is focused on the current development in domain of organic photovoltaic cells (OPVs). Solar cells play a vital role for electricity production by converting sunlight to electric current. This paper presents an exhaustive literature review on advancements in field of OPVs. The solar cells, as a substitute for fossil fuels are, at the forefront in a wide range of research applications. The organic solar cells efficiency and operational lifespan made outstanding advancement by refining materials of the photoactive layer and presenting new inter-layers. The functioning of organic solar cells is centered on photoinduced electron transfer. Organic solar cell technology has immense potential owing to lower production cost and flexible characteristics. The latest advancement in the material engineering and sophisticated device structure have significantly improved the solar cells commercial feasibility. Further, we highlight the research and advancements of organic bioelectronics in powering numerous bio-medical electronic devices. The important challenges, engineering result, and forthcoming prospects driving the progress of OSCs are explored.
A Multifactor Combination Optimization Design Based on Orthogonality for a Two‐Degree‐of‐Freedom Floating Machine Gun Vibration System
Authors: Wang Yang , Xu Cheng , He Long , Cao Yanfeng
Published: March 2024

This paper introduces a novel type of floating machine gun that can be simplified as a self‐balancing two‐degree‐of‐freedom mechanical system with distinct vibration characteristics. The model accounts for intricate motion patterns and encompasses numerous potential influencing factors. Multifactor combination optimization of the system represents a pressing engineering challenge. After establishing a simulation model for the machine gun and validating it experimentally, seven factors were chosen as optimization variables. The maximum recoil displacement of the inner receiver (MRD) and the firing rate were chosen to be indicators. Orthogonal combinations and variance analyses were used, and the effects of multiple factors were analyzed using SPSS software; these processes led to a determination of the optimal combination. The results indicated that the piston cylinder pressure, the bi‐directional buffer spring energy storage, and the inner receiver mass significantly affected the MRD. Furthermore, the automaton mass and the reset spring energy storage were found to substantially affect the firing rate. Careful analysis of the variance results facilitated the determination of the optimal combination of parameter values. Remarkably, the optimal combination chosen resulted in an MRD reduction of approximately 20.2% and a firing rate increase of approximately 26.6%.
Design of a Microwave Quadrature Hybrid Coupler with Harmonic Suppression Using Artificial Neural Networks
Authors: Roshani Saeed , Yahya Salah I. , Assaad Maher , Chaudhary Muhammad Akmal , Hazzazi Fawwaz , Yasin Ghadi Yazeed , Mostafaei Saeed , Roshani Sobhan
Published: March 2024

In this paper, a compact and simple structure of an elliptic microstrip lowpass filter (LPF) is designed for harmonic suppression in microwave quadrature hybrid coupler (QHC) applications. A radial resonator and a rectangular resonator are used to produce an elliptic LPF. The proposed LPF is used on the outer sides of the branch line coupler, which has improved the coupler harmonic suppression. Furthermore, artificial neural networks (ANNs) are incorporated to improve the LPF design process. The LPF best structure is obtained using the proposed ANN model. The proposed LPF has a compact size, which only occupies 16.4 mm × 7.3 mm equals to 0.164 λg × 0.073 λg, has a cut frequency of 2.2 GHz, and shows a sharp transmission band with a roll-off rate of 158.3 dB/GHz. Finally, the deigned QHC operates correctly at 1 GHz, which shows high harmonic suppression ability. The proposed QHC provides wide suppression band from 2.25 GHz up to more than 14 GHz, which can effectively suppress 3rd, to 14th harmonics. The proposed coupler features desirable parameters of S11, S21, S31, and S41, with magnitude of −21 dB, −3.4 dB, −3.3 dB, and −22.5 dB, at the operating frequency. The proposed approach mitigates the complexity of the circuit fabrication, compared with the previous methods while achieved desirable performances for the proposed QHC.
Data from Suppression of Epidermal Growth Factor Receptor Signaling by Protein Kinase C-α Activation Requires CD82, Caveolin-1, and Ganglioside
Authors: Wang Xiao-qi , Yan Qiu , Sun Ping , Liu Ji-Wei , Go Linda , McDaniel Shauntae M. , Paller Amy S.
Published: March 2024

Abstract
Activation of protein kinase C (PKC)-α decreases normal and neoplastic cell proliferation by inhibiting epidermal growth factor receptor (EGFR)-related signaling. The molecular interactions upstream to PKC-α that influence its suppression of EGFR, however, are poorly understood. We have found that caveolin-1, tetraspanin CD82, and ganglioside GM3 enable the association of EGFR with PKC-α, ultimately leading to inhibition of EGFR signaling. GM3- and CD82-induced inhibition of EGFR signaling requires PKC-α translocation and serine/threonine phosphorylation, which eventually triggers EGFR Thr654 phosphorylation and receptor internalization. Within this ordered complex of signaling molecules, the ability of CD82 to associate with PKC-α requires the presence of caveolin-1, whereas the interaction of caveolin-1 or PKC-α with EGFR requires the presence of CD82 and ganglioside GM3. Disruption of the membrane with methyl-β-cyclodextrin dissociates the EGFR/GM3/caveolin-1/CD82/PKC-α complex and prevents the inhibitory effect of PKC-α on EGFR phosphorylation, suggesting that caveolin-1, CD82, and ganglioside interact with EGFR and PKC-α within intact cholesterol-enriched membrane microdomains. Given the role of these membrane molecules in suppressing EGFR signaling, up-regulation of GM3, caveolin-1, and CD82 function may be an effective adjunctive therapy for treating epithelial cell malignancies. [Cancer Res 2007;67(20):9986–95]
Data from Isogenic Normal Basal and Luminal Mammary Epithelial Isolated by a Novel Method Show a Differential Response to Ionizing Radiation
Authors: Huper Gudrun , Marks Jeffrey R.
Published: March 2024

Abstract
Epithelial cells within the normal breast duct seem to be the primary target for neoplastic transformation events that eventually produce breast cancer. Normal epithelial cells are easily isolated and propagated using standard techniques. However, these techniques almost invariably result in populations of cells that are largely basal in character. Because only ∼20% of human breast cancers exhibit a basal phenotype, our understanding of the disease may be skewed by using these cells as the primary comparator to cancer. Further, because germ line mutations in BRCA1 yield breast cancers that are most often of the basal type, a comparison of normal basal and luminal cells could yield insight into the tissue and cell type specificity of this hereditary cancer susceptibility gene. In this report, we describe a simplified and efficient method for isolating basal and luminal cells from normal human breast tissue. These isogenic cells can be independently propagated and maintain phenotypic markers consistent with their respective lineages. Using these cultured cells, we show that basal and luminal cells exhibit distinct responses to ionizing radiation. Basal cells undergo a rapid but labile cell cycle arrest, whereas luminal cells show a much more durable arrest, primarily at the G2-M boundary. Molecular markers, including p53 protein accumulation, p53-activated genes, and BRCA1 nuclear focus formation all correlate with the respective cell cycle responses. Further, we show that short-term cultures of human breast tissue fragments treated with ionizing radiation show a similar phenomenon as indicated by the biphasic accumulation of p53 protein in the basal versus luminal layer. Together, these results indicate that normal basal cells have a transitory cell cycle arrest after DNA damage that may underlie their increased susceptibility to transformation after the loss of functional BRCA1. [Cancer Res 2007;67(7):2990–3001]
Data from Control of Androgen Receptor Signaling in Prostate Cancer by the Cochaperone Small Glutamine–Rich Tetratricopeptide Repeat Containing Protein α
Authors: Buchanan Grant , Ricciardelli Carmela , Harris Jonathan M. , Prescott Jennifer , Yu Zoe Chiao-Li , Jia Li , Butler Lisa M. , Marshall Villis R. , Scher Howard I. , Gerald William L. , Coetzee Gerhard A. , Tilley Wayne D.
Published: March 2024

Abstract
Although the androgen receptor (AR) is accepted as the major determinant of prostate cancer cell survival throughout disease progression, it is currently unclear how the receptor sustains genomic signaling under conditions of systemic androgen ablation. Here, we show that the evolutionarily conserved Hsp70/Hsp90 cochaperone, small glutamine–rich tetratricopeptide repeat containing protein α (αSGT), interacts with the hinge region of the human AR in yeast and mammalian cells. Overexpression and RNA interference revealed that αSGT acts to (a) promote cytoplasmic compartmentalization of the AR, thereby silencing the receptors basal/ligand-independent transcriptional activity, (b) regulate the sensitivity of receptor signaling by androgens, and (c) limit the capacity of noncanonical ligands to induce AR agonist activity. Immunofluorescence, coactivator, and chromatin immunoprecipitation analyses strongly suggest that these effects of αSGT on AR function are mediated by interaction in the cytoplasm and are distinct from the receptors response to classic coregulators. Quantitative immunohistochemical analysis of αSGT and AR levels in a cohort of 32 primary and 64 metastatic human prostate cancers revealed dysregulation in the level of both proteins during disease progression. The significantly higher AR/αSGT ratio in metastatic samples is consistent with the sensitization of prostate tumor cells to androgen signaling with disease progression, particularly in a low-hormone environment. These findings implicate αSGT as a molecular rheostat of in vivo signaling competence by the AR, and provide new insight into the determinants of androgen sensitivity during prostate cancer progression. [Cancer Res 2007;67(20):10087–96]
Data from Different S/M Checkpoint Responses of Tumor and Non–Tumor Cell Lines to DNA Replication Inhibition
Authors: Rodríguez-Bravo Verónica , Guaita-Esteruelas Sandra , Salvador Noelia , Bachs Oriol , Agell Neus
Published: March 2024

Abstract
Cell cycle checkpoint abrogation, especially the inhibition of Chk1 in combination with DNA-damaging treatments, has been proposed as a promising way of sensitizing cancer cells. However, less is known about the possibility to selectively affect tumor cells when they are treated with agents that block DNA synthesis in combination with replication checkpoint inhibitors. Here, we present clear insights in the different responses of tumor and non-transformed cells to the inhibition of DNA replication with hydroxyurea in combination with checkpoint abrogation via inhibition of Ataxia telangiectasia–mutated– (ATM) and Rad3-related/ATM (ATR/ATM) and Chk1 kinases. Interestingly, we find that non-transformed cell lines activate ATR/ATM- and Chk1-independent pathways in response to replication inhibition to prevent mitotic entry with unreplicated DNA. In contrast, tumor cell lines such as HCT116 and HeLa cells rely entirely on Chk1 activity for a proper response to replication inhibitors. Our results show that p38 is activated in response to hydroxyurea treatment and collaborates with Chk1 to prevent mitotic entry in non-transformed cell lines by maintaining cyclin B1/Cdk1 complexes inactive. Furthermore, DNA replication arrest down-regulates cyclin B1 promoter activity in non-transformed cells, but not in tumor cells in a Chk1- and p38-independent way. Thus, our data show that non-transformed cells present a more robust DNA replication checkpoint response compared with tumor cells that involves activation of the p38 pathway. We show that some of these responses to replication block can be lost in tumor cells, causing a defective checkpoint and providing a rationale for tumor-selective effects of combined therapies. [Cancer Res 2007;67(24):11648–56]
Data from Detection of Early Prostate Cancer Using a Hepsin-Targeted Imaging Agent
Authors: Kelly Kimberly A. , Setlur Sunita R. , Ross Robert , Anbazhagan Rajesh , Waterman Peter , Rubin Mark A. , Weissleder Ralph
Published: March 2024

Abstract
Early detection and diagnosis of prostate cancer is key to designing effective treatment strategies. Microarrays have resulted in the discovery of hepsin (HPN) as a biomarker for detection of prostate cancer. In this study, we explore the development of HPN imaging probes for detection of prostate cancer. We used phage display to isolate HPN binding peptides with 190 + 2.2 nmol/L affinity in monomeric form and high specificity. The identified peptides were able to detect human prostate cancer on tissue microarrays and in cell-based assays. HPN-targeted imaging agents were synthesized by conjugating multiple peptides to fluorescent nanoparticles to further improve avidity through multivalency and to improve pharmacokinetics. When injected into mouse xenograft models, HPN-targeted nanoparticles bound specifically to HPN-expressing LNCaP xenografts compared with non–HPN-expressing PC3 xenografts. HPN imaging may provide a new method for detection of prostate cancer. [Cancer Res 2008;68(7):2286–91]
Data from The Human let-7a-3 Locus Contains an Epigenetically Regulated MicroRNA Gene with Oncogenic Function
Authors: Brueckner Bodo , Stresemann Carlo , Kuner Ruprecht , Mund Cora , Musch Tanja , Meister Michael , Sültmann Holger , Lyko Frank
Published: March 2024

Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that repress their target mRNAs by complementary base pairing and induction of the RNA interference pathway. It has been shown that miRNA expression can be regulated by DNA methylation and it has been suggested that altered miRNA gene methylation might contribute to human tumorigenesis. In this study, we show that the human let-7a-3 gene on chromosome 22q13.31 is associated with a CpG island. Let-7a-3 belongs to the archetypal let-7 miRNA gene family and was found to be methylated by the DNA methyltransferases DNMT1 and DNMT3B. The gene was heavily methylated in normal human tissues but hypomethylated in some lung adenocarcinomas. Let-7a-3 hypomethylation facilitated epigenetic reactivation of the gene and elevated expression of let-7a-3 in a human lung cancer cell line resulted in enhanced tumor phenotypes and oncogenic changes in transcription profiles. Our results thus identify let-7a-3 as an epigenetically regulated miRNA gene with oncogenic function and suggest that aberrant miRNA gene methylation might contribute to the human cancer epigenome. [Cancer Res 2007;67(4):1419–23]
Data from MUC1 Oncoprotein Regulates Bcr-Abl Stability and Pathogenesis in Chronic Myelogenous Leukemia Cells
Authors: Kawano Takeshi , Ito Masaki , Raina Deepak , Wu Zekui , Rosenblatt Jacalyn , Avigan David , Stone Richard , Kufe Donald
Published: March 2024

Abstract
Chronic myelogenous leukemia (CML) results from expression of the Bcr-Abl fusion protein in hematopoietic stem cells. The MUC1 heterodimeric protein is aberrantly overexpressed in diverse human carcinomas. The present studies show that MUC1 is expressed in the human K562 and KU812 CML cell lines. The results show that MUC1 associates with Bcr-Abl through a direct interaction between the Bcr N-terminal region and the MUC1 cytoplasmic domain. Stable silencing of MUC1 decreased cytoplasmic Bcr-Abl levels by promoting Bcr-Abl degradation. Silencing MUC1 was also associated with decreases in K562 and KU812 cell self-renewal capacity and with a more differentiated erythroid phenotype. The results further show that silencing MUC1 increases sensitivity of CML cells to imatinib-induced apoptosis. Analysis of primary CML blasts confirmed that, as found with the CML cell lines, MUC1 blocks differentiation and the apoptotic response to imatinib treatment. These findings indicate that MUC1 stabilizes Bcr-Abl and contributes to the pathogenesis of CML cells by promoting self renewal and inhibiting differentiation and apoptosis. [Cancer Res 2007;67(24):11576–84]
Data from Transcription Factor Stat5 Synergizes with Androgen Receptor in Prostate Cancer Cells
Authors: Tan Shyh-Han , Dagvadorj Ayush , Shen Feng , Gu Lei , Liao Zhiyong , Abdulghani Junaid , Zhang Ying , Gelmann Edward P. , Zellweger Tobias , Culig Zoran , Visakorpi Tapio , Bubendorf Lukas , Kirken Robert A. , Karras James , Nevalainen Marja T.
Published: March 2024

Abstract
The molecular mechanisms underlying progression of prostate cancer to the hormone-independent state are poorly understood. Signal transducer and activator of transcription 5a and 5b (Stat5a/b) is critical for the viability of human prostate cancer cells. We have previously shown that Stat5a/b is constitutively active in high-grade human prostate cancer, but not in normal prostate epithelium. Furthermore, activation of Stat5a/b in primary human prostate cancer predicted early disease recurrence. We show here that transcription factor Stat5a/b is active in 95% of clinical hormone-refractory human prostate cancers. We show for the first time that Stat5a/b synergizes with androgen receptor (AR) in prostate cancer cells. Specifically, active Stat5a/b increases transcriptional activity of AR, and AR, in turn, increases transcriptional activity of Stat5a/b. Liganded AR and active Stat5a/b physically interact in prostate cancer cells and, importantly, enhance nuclear localization of each other. The work presented here provides the first evidence of synergy between AR and the prolactin signaling protein Stat5a/b in human prostate cancer cells. [Cancer Res 2008;68(1):236–48]
Data from Cyclin-Dependent Kinase 2/Cyclin E Complex Is Involved in p120 Catenin (p120ctn)–Dependent Cell Growth Control: A New Role for p120ctn in Cancer
Authors: Chartier Nicolas T. , Oddou Christiane I. , Lainé Michèle G. , Ducarouge Benjamin , Marie Christiane A. , Block Marc R. , Jacquier-Sarlin Muriel R.
Published: March 2024

Abstract
Depending on its cellular localization, p120 catenin (p120ctn) can participate in various processes, such as cadherin-dependent cell-cell adhesion, actin cytoskeleton remodeling, and intracellular trafficking. Recent studies also indicate that p120ctn could regulate cell proliferation and contact inhibition. This report describes a new function of p120ctn in the regulation of cell cycle progression. Overexpression of the p120ctn isoform 3A in human colon adenocarcinoma cells (HT-29) results in cytoplasmic accumulation of the protein, as observed in many tumors. This cytoplasmic increase is correlated with a reduction in proliferation and inhibition of DNA synthesis. Under these conditions, experiments on synchronized cells revealed a prolonged S phase associated with cyclin E stabilization. Both confocal microscopy and biochemical analysis showed that cyclin E and cyclin-dependent kinase 2 colocalized with p120ctn in centrosomes during mitosis. These proteins are associated in a functional complex evidenced by coimmunoprecipitation experiments and the emergence of Thr199-phosphorylated nucleophosmin/B23. Such post-translational modification of this centrosomal target has been shown to trigger the initiation of centrosome duplication. Therefore, p120ctn-mediated accumulation of cyclin E in centrosomes may participate in abnormal amplification of centrosomes and the inhibition of DNA replication, thus leading to aberrant mitosis and polyploidy. Because these modifications are often observed in cancer, p120ctn may represent a new therapeutic target for future therapy. [Cancer Res 2007;67(20):9781–90]
Data from Fms-like Tyrosine Kinase 3 Ligand Stimulation Induces MLL-Rearranged Leukemia Cells into Quiescence Resistant to Antileukemic Agents
Authors: Furuichi Yoshiyuki , Goi Kumiko , Inukai Takeshi , Sato Hiroki , Nemoto Atsushi , Takahashi Kazuya , Akahane Koshi , Hirose Kinuko , Honna Hiroko , Kuroda Itaru , Zhang Xiaochun , Kagami Keiko , Hayashi Yasuhide , Harigaya Kenichi , Nakazawa Shinpei , Sugita Kanji
Published: March 2024

Abstract
Fms-like tyrosine kinase 3 (FLT3) is highly expressed in acute lymphoblastic leukemia with the mixed-lineage leukemia (MLL) gene rearrangement refractory to chemotherapy. We examined the biological effect of FLT3-ligand (FL) on 18 B-precursor leukemic cell lines with variable karyotypic abnormalities, and found that nine of nine MLL-rearranged cell lines with wild-type FLT3, in contrast to other leukemic cell lines, are significantly inhibited in their proliferation in a dose-dependent manner by FL. This inhibition was due to induction of the G0-G1 arrest. A marked up-regulation of p27 by suppression of its protein degradation and an abrogation of constitutive signal transducers and activators of transcription 5 phosphorylation were revealed in arrested leukemia cells after FL stimulation. Importantly, FL treatment rendered not only cell lines but also primary leukemia cells with MLL rearrangement resistant to chemotherapeutic agents. MLL-rearranged leukemia cells adhering to the bone marrow stromal cell line, which expresses FL as the membrane-bound form, were induced to quiescent state resistant to chemotherapeutic agents, but their chemosensitivity was significantly restored in the presence of neutralizing anti-FL antibody. The FL/FLT3 interaction between leukemia cells and bone marrow stromal cells expressing FL at high levels should contribute, at least in part, to persistent minimal-residual disease of MLL-rearranged leukemia in bone marrow. [Cancer Res 2007;67(20):9852–61]
Data from Genome-Scale MicroRNA and Small Interfering RNA Screens Identify Small RNA Modulators of TRAIL-Induced Apoptosis Pathway
Authors: Ovcharenko Dmitriy , Kelnar Kevin , Johnson Charles , Leng Nan , Brown David
Published: March 2024

Abstract
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) binds to death receptors 4/5 and selectively induces caspase-dependent apoptosis. The RNA interference screening approach has led to the discovery and characterization of several TRAIL pathway components in human cells. Here, libraries of synthetic small interfering RNA (siRNA) and microRNAs (miRNA) were used to probe the TRAIL pathway. In addition to known genes, siRNAs targeting CDK4, PTGS1, ALG2, CLCN3, IRAK4, and MAP3K8 altered TRAIL-induced caspase-3 activation responses. Introduction of the miRNAs let-7c, mir-10a, mir-144, mir-150, mir-155, and mir-193 also affected the activation of the caspase cascade. Putative targets of these endogenous miRNAs included genes encoding death receptors, caspases, and other apoptosis-related genes. Among the novel genes revealed in the screen, CDK4 was selected for further characterization. CDK4 was the only member of the cyclin-dependent kinase gene family that bore a unique function in apoptotic signal transduction. [Cancer Res 2007;67(22):10782–8]