Miracle-dz/UniFAR-FTUs huggingface dataset:
Absorption and subcellular localization of lycopene in human prostate cancer cells

Lycopene, the red pigment of the tomato, is under investigation for the chemoprevention of prostate cancer. Because dietary lycopene has been reported to concentrate in the human prostate, its uptake and subcellular localization were investigated in the controlled environment of cell culture using the human prostate cancer cell lines LNCaP, PC-3, and DU145. After 24 hours of incubation with 1.48 μmol/L lycopene, LNCaP cells accumulated 126.6 pmol lycopene/million cells, which was 2.5 times higher than PC-3 cells and 4.5 times higher than DU145 cells. Among these cell lines, only LNCaP cells express prostate-specific antigen and fully functional androgen receptor. Levels of prostate-specific antigen secreted into the incubation medium by LNCaP cells were reduced 55% as a result of lycopene treatment at 1.48 μmol/L. The binding of lycopene to the ligand-binding domain of the human androgen receptor was carried out, but lycopene was not found to be a ligand for this receptor. Next, subcellular fractionation of LNCaP cells exposed to lycopene was carried out using centrifugation and followed by liquid chromatography-tandem mass spectrometry quantitative analysis to determine the specific cellular locations of lycopene. The majority of lycopene (55%) was localized to the nuclear membranes, followed by 26% in nuclear matrix, and then 19% in microsomes. No lycopene was detected in the cytosol. These data suggest that the rapid uptake of lycopene by LNCaP cells might be facilitated by a receptor or binding protein and that lycopene is stored selectively in the nucleus of LNCaP cells. [Mol Cancer Ther 2006;5(11):2879–85]
Inhibition of Phosphodiesterase Type IV Suppresses Human Immunodeficiency Virus Type 1 Replication and Cytokine Production in Primary T Cells: Involvement of NF-κB and NFAT

ABSTRACT Rolipram, a phosphosdiesterase type IV-specific inhibitor, prevented p24 antigen release from anti-CD3-activated human immunodeficiency virus (HIV)-infected T cells and CD4+-cell depletion associated with viral replication in a dose-responsive manner but minimally inhibited T-cell proliferation. Moreover, rolipram reduced the production of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) by HIV-infected T cells. The transcriptional ability of a luciferase reporter gene under control of the HIV long terminal repeat, induced by phorbol myristic acetate plus ionomycin or by TNF-α, in primary T and Jurkat cells was also inhibited by rolipram. Rolipram inhibited NF-κB and NFAT activation induced by T-cell activation in Jurkat and primary T cells, as measured by transient transfection of reporter genes and electrophoretic mobility shift assays. Exogenous addition of TNF-α in the presence of rolipram restored NF-κB but not NFAT activation or p24 release. Addition of dibutyryl-cyclic AMP (dBcAMP) mimicked the effects of rolipram on p24 antigen release, NF-κB activation, and TNF-α secretion, but it did not affect NFAT activation or IL-10 production. The protein kinase A inhibitor KT5720 prevented the inhibition of TNF-α secretion but not that of HIV type 1 (HIV-1) replication caused by rolipram. Our data indicate that blockade of phosphodiesterase type IV could be of benefit against HIV-1 disease by modulating cytokine secretion and transcriptional regulation of HIV replication, and they suggest an important role of NFAT in HIV replication in primary T cells. Some of those activities cannot be ascribed solely to its ability to increase cAMP.
Performance of Type-I and Type-II Hybrid ARQ in Decode and Forward Relaying

Truncated Type-I and Type-II HARQ schemes are compared, in terms of throughput, when incremental decode and forward relaying is used. The comparison is based on the outage analysis of both schemes. Two different scenarios are considered: ad-hoc relaying, where all users are at ground level, and infra-structured relaying, where the relay and the destination antennas are at a higher height than the user. Moreover, we also consider the effect of rate adaptation. Results show that Type-II (incremental redundancy) only significantly outperforms Type-I schemes (selection and Chase combining) in the case of ad-hoc relaying without rate adaptation, and in the low SNR region.
Cavefish cope with environmental hypoxia by developing more erythrocytes and overexpression of hypoxia-inducible genes

Dark caves lacking primary productivity can expose subterranean animals to hypoxia. We used the surface-dwelling (surface fish) and cave-dwelling (cavefish) morphs of Astyanax mexicanus as a model for understanding the mechanisms of hypoxia tolerance in the cave environment. Primitive hematopoiesis, which is restricted to the posterior lateral mesoderm in other teleosts, also occurs in the anterior lateral mesoderm in Astyanax, potentially pre-adapting surface fish for hypoxic cave colonization. Cavefish have enlarged both hematopoietic domains and develop more erythrocytes than surface fish, which are required for normal development in both morphs. Laboratory induced hypoxia suppresses growth in surface fish but not in cavefish. Both morphs respond to hypoxia by overexpressing Hypoxia-Inducible Factor (HIF) pathway genes, but some hif genes are constitutively upregulated in normoxic cavefish to similar levels as hypoxic surface fish. We conclude that cavefish cope with hypoxia by increasing erythrocyte development and constitutive HIF gene overexpression. Summary Astyanax mexicanus cavefish cope with hypoxic environments by expanding embryonic hematopoietic domains, increasing the capacity for erythrocyte development, and constitutive overexpression of hypoxia-inducible genes.
The Neck Disability Index: a study of reliability and validity.

Injuries to the cervical spine, especially those involving the soft tissues, represent a significant source of chronic disability. Methods of assessment for such disability, especially those targeted at activities of daily living which are most affected by neck pain, are few in number. A modification of the Oswestry Low Back Pain Index was conducted producing a 10-item scaled questionnaire entitled the Neck Disability Index (NDI). Face validity was ensured through peer-review and patient feedback sessions. Test-retest reliability was conducted on an initial sample of 17 consecutive "whiplash"-injured patients in an outpatient clinic, resulting in good statistical significance (Pearson's r = 0.89, p less than or equal to .05). The alpha coefficients were calculated from a pool of questionnaires completed by 52 such subjects resulting in a total index alpha of 0.80, with all items having individual alpha scores above 0.75. Concurrent validity was assessed in two ways. First, on a smaller subset of 10 patients who completed a course of conservative care, the percentage of change on NDI scores before and after treatment was compared to visual analogue scale scores of percent of perceived improvement in activity levels. These scores correlated at 0.60. Secondly, in a larger subset of 30 subjects, NDI scores were compared to scores on the McGill Pain Questionnaire, with similar moderately high correlations (0.69-0.70). While the sample size of some of the analyses is somewhat small, this study demonstrated that the NDI achieved a high degree of reliability and internal consistency. (ABSTRACT TRUNCATED AT 250 WORDS)
Popularity and Correlation-Aware Content Placement for Hierarchical Surrogates in Cloud-Based CDNs

Content placement (CP) algorithms are an integral component of Cloud-based Content Delivery Networks (CCDNs) that select a subset of content from the myriad catalogue, to be placed on surrogates to meet end-user requests with quality of service (QoS). It is challenging to conjure popularity of content, due to size of the catalogue, the heavy and long tail nature of the popularity distribution function and complexity arising from Online Social Networking (OSN) relationships. Therefore, we leverage hierarchical organization of surrogates to push and store content that is preemptively and strategically chosen, such that popular and correlated content always remains within QoS distance of each other. We design an Integer Linear Programming (ILP) model and solve it optimally and nearoptimally using CPLEX and Particle Swarm Optimization-based heuristic, respectively. We compare our model with state-of- the-art CP algorithm to show the benefits of popularity and correlation aware CP.
Intermolecular and Intramolecular Interactions Regulate Catalytic Activity of Myotonic Dystrophy Kinase-Related Cdc42-Binding Kinase α

ABSTRACT Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) is a Cdc42-binding serine/threonine kinase with multiple functional domains. We had previously shown MRCKα to be implicated in Cdc42-mediated peripheral actin formation and neurite outgrowth in HeLa and PC12 cells, respectively. Here we demonstrate that native MRCK exists in high-molecular-weight complexes. We further show that the three independent coiled-coil (CC) domains and the N-terminal region preceding the kinase domain are responsible for intermolecular interactions leading to MRCKα multimerization. N terminus-mediated dimerization and consequent transautophosphorylation are critical processes regulating MRCKα catalytic activities. A region containing the two distal CC domains (CC2 and CC3; residues 658 to 930) was found to interact intramolecularly with the kinase domain and negatively regulates its activity. Its deletion also resulted in an active kinase, confirming a negative autoregulatory role. We provide evidence that the N terminus-mediated dimerization and activation of MRCK and the negative autoregulatory kinase–distal CC interaction are two mutually exclusive events that tightly regulate the catalytic state of the kinase. Disruption of this interaction by a mutant kinase domain resulted in increased kinase activity. MRCK kinase activity was also elevated when cells were treated with phorbol ester, which can interact directly with a cysteine-rich domain next to the distal CC domain. We therefore suggest that binding of phorbol ester to MRCK releases its autoinhibition, allowing N-terminal dimerization and subsequent kinase activation.
21.3 A 2GHz 130mW direct-digital frequency synthesizer with a nonlinear DAC in 55nm CMOS

Direct-digital frequency synthesizers (DDFSs) have been employed in many frequency-agile communication systems because of their wide bandwidth, fine frequency resolution, and fast frequency-hopping characteristics. Recent developments in DDFSs are towards enhancing performances through reduction of both complexity and power consumption [1-3]. The segmented nonlinear DAC (NLDAC) structures in [1,2] require additional coarse phase information for fine amplitude decoding with a complex decoder. Moreover, the quarter-sine-wave technique incorporated into the segmented NLDACs in [1,2] degrades spectral purity due to the need of the MSB shift DAC that introduces additional offset. Another scheme in [3] reduces complexity and power consumption by replacing the digital-based phase-to-amplitude converter with an analog-based converter, resulting in limited spectral purity. Unlike previous schemes, this work presents comprehensive enhancements in all key areas of a DDFS, the pipelined phase accumulator (PACC), digital decoder, and NLDAC as shown in Fig. 21.3. 1. First, the low-power PACC with multi-level momentarily activated bias (M2AB) is presented to reduce power dissipation. Second, the coarse phase-based consecutive fine-amplitude grouping (C2FAG) scheme reduces the hardware complexity and the power consumption in digital decoder circuits. Third, the mixed-wave conversion topology (MCT) in the NLDAC improves the output spectral purity.
T98G: An anchorage‐independent human tumor cell line that exhibits stationary phase G1 arrest in vitro

T98 and T98G are two related cell lines that were derived from a human glioblastoma multiforma tumor. T98G has almost twice as many chromosomes as T98, suggesting that it is a polyploid variant of T98. Three aspects of control of cellular proliferation were studied in T98 and T98G cells in comparison to WI‐38 normal human diploid cells. WI‐38 cells have the following properties: (1) they can undergo only a limited number of population doublings in vitro; (2) they cannot proliferate without anchorage; and (3) they become arrested in G1 phase under stationary phase conditions. T98 cells differ from normal cells in all three of these properties, as do many other transformed cell lines. However, the derivative of T98, namely T98G, expresses an unique combination of normal and transformed aspects of the control of cellular proliferation. T98G cells are like normal cells in that they become arrested in G1 phase under stationary phase conditions, yet they also exhibit the transformed characteristics of anchorage independence and immortality. Thus, T98G cells demonstrate that transformation to immortality and anchorage independence can exist without concomitant loss of the normal mechanism for G1 arrest in response to stationary phase conditions. This result supports the hypothesis that each of these three aspects of control of cellular proliferation can be altered independently. Partially transformed cell lines, such as T98G, should be useful for sorting out the biochemical changes associated with transformation in each of these aspects.
Incidence of Conversion to Active Waitlist Status Among Temporarily Inactive Obese Renal Transplant Candidates

Background Candidates may be active or temporarily inactive (status 7) on the kidney transplant waiting list. One reason candidates may be inactive is for a “weight currently inappropriate for transplantation. ” We hypothesized that many of these candidates would not achieve active status. Methods Using OPTN/UNOS data from 2006 to 2012, we used competing risks methods to determine the cumulative incidence of conversion to active status (activation), death, and delisting before conversion among 1679 obese adult kidney candidates designated as status 7 because of a weight inappropriate for transplantation. Fine and Gray competing risks regression was performed to characterize factors associated with conversion to active status in the overall study population and of transplantation among a subgroup of activated candidates. Results At 6 years, the cumulative incidence of activation was 49%, of death before conversion was 15%, and of delisting was 21%. Higher body mass index (BMI) was strongly associated with a decreased subhazard of activation (BMI ≥45 versus 30–34.9, sHR: 0.22; 95% CI, 0.16–0.33). Female sex, diabetic end-stage renal disease, history of a previous transplant, panel reactive antibodies less than 80%, dialysis dependence at listing, and UNOS region 5 were negatively associated with activation. Among activated candidates, the cumulative incidence of transplantation at 6 years after initial waitlisting was 61%. Conclusion Our findings indicate that half of obese status 7 candidates with a weight inappropriate for transplantation will not achieve active waitlist status. BMI at listing had a strong association with conversion to active status; comorbid factors and regional variation also impact activation.
5‐aminolaevulinic acid photodynamic therapy in a transgenic mouse model of skin melanoma

Abstract: Photodynamic therapy (PDT) is widely used to treat preneoplastic skin lesions and non‐melanoma skin tumours. Studies analyzing the effects of PDT on malignant melanoma have yielded conflicting results. On the one hand, melanoma cell lines in culture as well as cell lines transplanted into experimental animals were sensitive to PDT. On the other hand, spontaneous melanomas of human patients responded poorly to most PDT regimens tested so far. Here, we analyzed effects of 5‐aminolaevulinic acid (5‐ALA)‐based PDT on melanoma cell lines and on experimental melanomas. To mimic the clinical situation as closely as possible, metallothionein‐I/ret (MT‐ret) mice, a transgenic model of skin melanoma development, were used. Optimal doses of 5‐ALA as well as energy doses and power densities were determined in vitro using a cell line (Mel25) established by us from a melanoma of an MT‐ret transgenic mouse as well as commercially available human and mouse melanoma cell lines. Treatment with light irradiation alone had no effect. In combination with 5‐ALA, however, this illumination readily induced the death of all mouse and human melanoma cell lines examined. Still, 5‐ALA PDT caused only minor focal regressive changes including haemorrhages and fibrosis of MT‐ret melanomas in vivo and did not significantly delay tumour growth. These results show that, even though MT‐ret melanoma cells are vulnerable to 5‐ALA PDT in vitro, malignant MT‐ret melanomas in vivo are quite resistant to this type of therapy at doses which are highly effective in vitro.
Current prospects for the treatment of clinical sepsis.

OBJECTIVES To review the role of antimediator therapy in the inflammatory cascade associated with sepsis, and to review the status of animal and clinical studies being conducted on novel therapies for septic shock. DATA SOURCES Information presented at the 22nd Educational and Scientific Meeting of the Society of Critical Care Medicine on June 9-13, 1993 in New York City was reviewed, along with supportive documentation from the English language literature. STUDY SELECTION Controlled animal studies that provide evidence for the effectiveness of antiendotoxin and anticytokine therapies. The preliminary results of selected clinical trials are also presented. DATA EXTRACTION This review focuses on data describing the potential role of mediator antagonists in the treatment of septic shock. DATA SYNTHESIS Information concerning the effectiveness and tolerability of these therapies has been integrated into a description of emerging therapies for septic shock. CONCLUSIONS Clinical trials of antiendotoxin antibodies have not shown them to have therapeutic benefit. New agents that neutralize or antagonize the cellular effects of endotoxin may provide an alternative means to inhibit endotoxin effects during severe Gram-negative infections. Anti-interleukin-1 and antitumor necrosis factor-alpha therapies have demonstrated efficacy in animal models, but the results have been inconsistent in human trials. Preliminary results from clinical trials of cytokine antagonists suggest that these therapies may be effective in the most severely ill patients. Further clinical trials will be required to determine the therapeutic role of these agents in septic shock.
How Proteolysis Drives the Cell Cycle

Oscillations in the activity of cyclin-dependent kinases (CDKs) promote progression through the eukaryotic cell cycle. This review examines how proteolysis regulates CDK activity—by degrading CDK activators or inhibitors—and also how proteolysis may directly trigger the transition from metaphase to anaphase. Proteolysis during the cell cycle is mediated by two distinct ubiquitin-conjugation pathways. One pathway, requiring CDC34, initiates DNA replication by degrading a CDK inhibitor. The second pathway, involving a large protein complex called the anaphase-promoting complex or cyclosome, initiates chromosome segregation and exit from mitosis by degrading anaphase inhibitors and mitotic cyclins. Proteolysis therefore drives cell cycle progression not only by regulating CDK activity, but by directly influencing chromosome and spindle dynamics.
Neuronal effects of nicotine during auditory selective attention in schizophrenia

Although nicotine has been shown to improve attention deficits in schizophrenia, the neurobiological mechanisms underlying this effect are poorly understood. We hypothesized that nicotine would modulate attention‐associated neuronal response in schizophrenia patients in the ventral parietal cortex (VPC), hippocampus, and anterior cingulate based on previous findings in control subjects. To test this hypothesis, the present study examined response in these regions in a cohort of nonsmoking patients and healthy control subjects using an auditory selective attention task with environmental noise distractors during placebo and nicotine administration. In agreement with our hypothesis, significant diagnosis (Control vs. Patient) X drug (Placebo vs. Nicotine) interactions were observed in the VPC and hippocampus. The interaction was driven by task‐associated hyperactivity in patients (relative to healthy controls) during placebo administration, and decreased hyperactivity in patients after nicotine administration (relative to placebo). No significant interaction was observed in the anterior cingulate. Task‐associated hyperactivity of the VPC predicted poor task performance in patients during placebo. Poor task performance also predicted symptoms in patients as measured by the Brief Psychiatric Rating Scale. These results are the first to suggest that nicotine may modulate brain activity in a selective attention‐dependent manner in schizophrenia. Hum Brain Mapp 37:410–421, 2016. © 2015 Wiley Periodicals, Inc.
Shepard's Universal Law Supported by Honeybees in Spatial Generalization

An animal that is rewarded for a response in one situation (the S+) is likely to respond to similar but recognizably different stimuli, the ubiquitous phenomenon of stimulus generalization. On the basis of functional analyses of the probabilistic structure of the world, Shepard formulated a universal law of generalization, claiming that generalization gradients, as a function of the appropriately scaled distance of a stimulus from S+, should be exponential in shape. This law was tested in spatial generalization in honeybees. Based on theoretically derived scales, generalization along both the dimensions of the distance from a landmark and the direction to a landmark followed Shepard's law. Support in an invertebrate animal increases the scope of the law, and suggests that the ecological structure of the world may have driven the evolution of cognitive structures in diverse animals.
Structural Modifications of Methanococcus Jannaschii Flagellin Proteins Revealed by Proteome Analysis

Methanococcus jannaschii is an autotrophic archaeon originally isolated from an oceanic thermal vent. The primary metabolic pathway for energy production in this hyperthermophilic microbe is methanogenesis from H2 and CO2. As an autotroph, M. jannaschii requires only CO2 as a carbon source for synthesizing all necessary biomolecules. Changes in the environmental availability of these molecules can be expected to activate regulatory mechanisms manifested as the up and down regulation of specific genes and the concomitant increase and decrease in abundance of the corresponding proteins. In our analysis of the proteome of M. jannaschii, we have observed significant changes in the abundance of a common subset of predominant proteins in response to reduced H2 concentration, limited ammonium availability and the stage of cell growth (exponential compared with stationary). The masses of tryptic peptides from these proteins match those predicted by M. jannaschii genome open reading frames annotated as flagellin B1 (MJ0891) and flagellin B2 (MJ0892). Multiple proteins with different isoelectric points and molecular weights match each of these proteins and the abundance of these protein variants changes with growth conditions. These data indicate that structural modifications altering both the isoelectric point and size of the M. jannaschii flagellin B1 and B2 proteins occur in response to growth conditions and growth stage of M. jannaschii and further suggest the regulation of M. jannaschii motility through structural modifications of the building blocks of the flagella.