Miracle-dz/UniFAR-FTUs huggingface dataset:
Indole-3-carbinol Inhibits the Expression of Cyclin-dependent Kinase-6 and Induces a G1 Cell Cycle Arrest of Human Breast Cancer Cells Independent of Estrogen Receptor Signaling*

Indole-3-carbinol (I3C), a naturally occurring component of Brassica vegetables such as cabbage, broccoli, and Brussels sprouts, has been shown to reduce the incidence of spontaneous and carcinogen-induced mammary tumors. Treatment of cultured human MCF7 breast cancer cells with I3C reversibly suppresses the incorporation of [3H]thymidine without affecting cell viability or estrogen receptor (ER) responsiveness. Flow cytometry of propidium iodide-stained cells revealed that I3C induces a G1 cell cycle arrest. Concurrent with the I3C-induced growth inhibition, Northern blot and Western blot analyses demonstrated that I3C selectively abolished the expression of cyclin-dependent kinase 6 (CDK6) in a dose- and time-dependent manner. Furthermore, I3C inhibited the endogenous retinoblastoma protein phosphorylation and CDK6 phosphorylation of retinoblastoma in vitro to the same extent. After the MCF7 cells reached their maximal growth arrest, the levels of the p21 and p27 CDK inhibitors increased by 50%. The antiestrogen tamoxifen also suppressed MCF7 cell DNA synthesis but had no effect on CDK6 expression, while a combination of I3C and tamoxifen inhibited MCF7 cell growth more stringently than either agent alone. The I3C-mediated cell cycle arrest and repression of CDK6 production were also observed in estrogen receptor-deficient MDA-MB-231 human breast cancer cells, which demonstrates that this indole can suppress the growth of mammary tumor cells independent of estrogen receptor signaling. Thus, our observations have uncovered a previously undefined antiproliferative pathway for I3C that implicates CDK6 as a target for cell cycle control in human breast cancer cells. Moreover, our results establish for the first time that CDK6 gene expression can be inhibited in response to an extracellular antiproliferative signal.
Linear logic and permutation stacks—the Forth shall be first

Girard's linear logic can be used to model programming languages in which each bound variable name has exactly one "occurrence"---i.e., no variable can have implicit "fan-out"; multiple uses require explicit duplication. Among other nice properties, "linear" languages need no garbage collector, yet have no dangling reference problems. We show a natural equivalence between a "linear" programming language and a stack machine in which the top items can undergo arbitrary permutations. Such permutation stack machines can be considered combinator abstractions of Moore's Forth programming language.
Differentiation‐dependent expression of hypothetical proteins in the neuroblastoma cell line N1E‐115

Several protein cascades, including signaling, cytoskeletal, chaperones, metabolic, and antioxidant proteins, have been shown to be involved in the process of neuronal differentiation (ND) of neuroblastoma cell lines. No systematic approach to detect hitherto unknown and unnamed proteins or structures that have been predicted upon nucleic acid sequences in ND has been published so far. We therefore decided to screen hypothetical protein (HP) expression by protein profiling. Two‐dimensional gel electrophoresis with subsequent matrix‐assisted laser desorption/ionization–time of flight mass spectrometry (MALDI‐TOF/TOF) identification was used for expression analysis of undifferentiated and dimethylsulfoxide‐induced neuronally differentiated N1E‐115 cells. We unambiguously identified six HPs: Q8C520, Q99LF4, Q9CXS1, Q9DAF8, Q91WT0, and Q8C5G2. A prefoldin domain in Q91WT0, a t‐SNARE domain in Q9CXS1, and a bromodomain were observed in Q8C5G2. For the three remaining proteins, no putative function using Pfam, BLOCKS, PROSITE, PRINTS, InterPro, Superfamily, CoPS, and ExPASy could be assigned. While two proteins were present in both cell lines, Q9CXS1 was switched off (i.e., undetectably low) in differentiated cells only, and Q9DAF8, Q91WT0, and Q8C5G2 were switched on in differentiated cells exclusively. Herein, using a proteomic approach suitable for screening and identification of HP, we present HP structures that have been only predicted so far based upon nucleic acid sequences. The four differentially regulated HPs may play a putative role in the process of ND. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Near-infrared spectroscopy as a tool for driving research

Abstract Driving a motor vehicle requires various cognitive functions to process surrounding information, to guide appropriate actions, and especially to respond to or integrate with numerous contextual and perceptual hindrances or risks. It is, thus, imperative to examine driving performance and road safety from a perspective of cognitive neuroscience, which considers both the behaviour and the functioning of the brain. However, because of technical limitations of current brain imaging approaches, studies have primarily adopted driving games or simulators to present participants with simulated driving environments that may have less ecological validity. Near-infrared spectroscopy (NIRS) is a relatively new, non-invasive brain-imaging technique allowing measurement of brain activations in more realistic settings, even within real motor vehicles. This study reviews current NIRS driving research and explores NIRS’ potential as a new tool to examine driving behaviour, along with various risk factors in natural situations, promoting our understanding about neural mechanisms of driving safety. Practitioner Summary: Driving a vehicle is dependent on a range of neurocognitive processing abilities. Near-infrared spectroscopy (NIRS) is a non-invasive brain-imaging technique allowing measurement of brain activation even in on-road studies within real motor vehicles. This study reviews current NIRS driving research and explores the potential of NIRS as a new tool to examine driving behaviour.
The Number of Metastatic Lymph Nodes in Extrahepatic Bile Duct Carcinoma as a Prognostic Factor

The number of lymph nodes with metastases is known to be an important prognostic factor in carcinomas of many organs. The insufficient sampling of lymph nodes has also been associated with worse outcome in several types of carcinoma. However, the prognostic significance of lymph node dissection is not well characterized in extrahepatic bile duct (EBD) carcinomas. For 209 patients with EBD carcinoma, the total number of retrieved lymph nodes and the number of metastatic lymph nodes were evaluated, and other clinicopathologic variables were correlated with patient survival. The number of retrieved lymph nodes was not significantly correlated with survival in this study. The presence of metastasis to lymph nodes significantly decreased survival of patients with EBD carcinoma. The patients with 5 or more metastatic lymph nodes had significantly worse survival than those with 4 or less metastatic lymph nodes. To evaluate the prognosis of the patients with EBD carcinomas more precisely, the number of metastatic lymph nodes as well as the status of metastasis to lymph nodes should be examined and reported. Based on the present data, we propose that nodal classification should be divided into N1 (metastasis in 1 to 4 regional lymph nodes) and N2 (metastasis in 5 or more regional lymph nodes).
The Syk protein tyrosine kinase can function independently of CD45 or Lck in T cell antigen receptor signaling.

The protein tyrosine phosphatase CD45 is a critical component of the T cell antigen receptor (TCR) signaling pathway, acting as a positive regulator of Src family protein tyrosine kinases (PTKs) such as Lck. Most CD45‐deficient human and murine T cell lines are unable to signal through their TCRs. However, there is a CD45‐deficient cell line that can signal through its TCR. We have studied this cell line to identify a TCR signaling pathway that is independent of CD45 regulation. In the course of these experiments, we found that the Syk PTK, but not the ZAP‐70 PTK, is able to mediate TCR signaling independently of CD45 and of Lck. For this function, Syk requires functional kinase and SH2 domains, as well as intact phosphorylation sites in the regulatory loop of its kinase domain. Thus, differential expression of Syk is likely to explain the paradoxical phenotypes of different CD45‐deficient T cells. Finally, these results suggest differences in activation requirements between two closely related PTK family members, Syk and ZAP‐70. The differential activities of these two kinases suggest that they may play distinct, rather than completely redundant, roles in lymphocyte signaling.
Determination of Oxidized Low‐Density Lipoproteins (ox‐LDL) versus ox‐LDL/β2GPI Complexes for the Assessment of Autoimmune‐Mediated Atherosclerosis

Abstract: The immunolocalization of oxidized low‐density lipoproteins (ox‐LDL), β2‐glycoprotein I (β2GPI), CD4+/CD8+ immunoreactive lymphocytes, and immunoglobulins in atherosclerotic lesions strongly suggested an active participation of the immune system in atherogenesis. Oxidative stress leading to ox‐LDL production is thought to play a central role in both the initiation and progression of atherosclerosis. ox‐LDL is highly proinflammatory and chemotactic for macrophage/monocyte and immune cells. Enzyme‐linked immunosorbent assays (ELISAs) to measure circulating ox‐LDL have been developed and are being currently used to assess oxidative stress as risk factor or marker of atherosclerotic disease. ox‐LDL interacts with β2GPI and circulating ox‐LDL/β2GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It has been postulated that β2GPI binds ox‐LDL to neutralize its proinflammatory and proatherosclerotic effects. Because β2GPI is ubiquitous in plasma, its interaction with ox‐LDL may mask oxidized epitopes recognized by capture antibodies potentially interfering with immunoassays results. The measurement of ox‐LDL/β2GPI complexes may circumvent this interference representing a more physiological and accurate way of measuring ox‐LDL.
The Performance of Uniaxially Strained Phosphorene Tunneling Field- Effect Transistors

The performance of uniaxially strained phosphorene tunneling field-effect transistors (TFETs) is assessed by first-principles-based quantum mechanical simulations in this letter. Due to the highly anisotropic band structure, the devices without strain along the armchair direction (AD) show superior performance to those without strain along the zigzag direction (ZD), and the same tendency is maintained with increasing compressive strain. However, tensile strain induces band switching between the first and second conduction subbands, where the heavy effective mass of electrons along the ZD becomes light, while the opposite is observed along the AD. Furthermore, a point on the $\Gamma$ to X path starts to contribute dominantly to band-to-band tunneling and improves the ON-state current of ZD TFETs, which becomes comparable to that of AD TFETs. These results demonstrate that, through strain engineering, the performance gap between AD and ZD TFETs can be significantly narrowed, lessening the orientation dependence of phosphorene.
Src Homology 3-interacting Domain of Rv1917c of Mycobacterium tuberculosis Induces Selective Maturation of Human Dendritic Cells by Regulating PI3K-MAPK-NF-κB Signaling and Drives Th2 Immune Responses*

Mycobacterium tuberculosis, an etiological agent of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Pathogenic mycobacteria survive in the host by subverting host innate immunity. Dendritic cells (DCs) are professional antigen-presenting cells that are vital for eliciting immune responses to infectious agents, including pathogenic mycobacteria. DCs orchestrate distinct Th responses based on the signals they receive. In this perspective, deciphering the interactions of the proline-glutamic acid/proline-proline-glutamic acid (PE/PPE) family of proteins of M. tuberculosis with DCs assumes significant pathophysiological attributes. In this study, we demonstrate that Rv1917c (PPE34), a representative member of the proline-proline-glutamic-major polymorphic tandem repeat family, interacts with TLR2 and triggers functional maturation of human DCs. Signaling perturbations implicated a critical role for integrated cross-talk among PI3K-MAPK and NF-κB signaling cascades in Rv1917c-induced maturation of DCs. However, this maturation of DCs was associated with a secretion of high amounts of anti-inflammatory cytokine IL-10, whereas Th1-polarizing cytokine IL-12 was not induced. Consistent with these results, Rv1917c-matured DCs favored secretion of IL-4, IL-5, and IL-10 from CD4+ T cells and contributed to Th2-skewed cytokine balance ex vivo in healthy individuals and in patients with pulmonary tuberculosis. Interestingly, the Rv1917c-skewed Th2 immune response involved induced expression of cyclooxygenase-2 (COX-2) in DCs. Taken together, these results indicate that Rv1917c facilitates a shift in the ensuing immunity toward the Th2 phenotype and could aid in immune evasion by mycobacteria.
A Fog-Based Emergency System for Smart Enhanced Living Environments

Ubiquitous computing paradigms, empowered by the fifth-generation networking and emerging smart ambient intelligence environments, could play a crucial role in creating better living environments for activity-challenged individuals, such as disabled or elderly people requiring constant care. Cloud computing has been an empowering force for this endeavor, although it raises several ethical, security, and user experience issues. This article presents a virtualized fog-based infrastructure for harvesting and managing distributed IT resources, shifting the entire cloud functionality to the network edge, and utilizing the cloud in an assistive manner to ensure system robustness. The infrastructure facilitates an ambient assisted-living emergency system that alerts nearby authorities when the target user leaves the identified home boundaries. It uses an outdoor positioning mechanism and emergency and Internet of Things communication protocols.
Impact analysis of electric vehicles on distribution systems considering uncertainties

This paper proposes a stochastic modeling and simulation technique for analyzing the impacts of electric vehicles (EV) charging on distribution network. Different from the deterministic models used in the previous studies, the models for feeder daily load profile, EV start charging time, and battery state of charge (SOC) during charging are derived based on actual measurements or survey data, and represented as stochastic parameters using Roulette wheel selection concept. Voltage and congestion impact indicators are defined and comparison of deterministic and stochastic analytical approaches in providing information required in distribution system planning for accommodating EV charging needs is conducted. Comparative results show the capability of stochastic models in reflecting system loss and security impacts due to EV integrations. Information about security risks such as over-current and under-voltage can be considered for optimal network reinforcement planning. A mitigation scheme with a controlled charging algorithm that can be used to relieve operation problems is also presented.
Integrating Proteomic and Functional Genomic Technologies in Discovery-driven Translational Breast Cancer Research*

The application of state-of-the-art proteomics and functional genomics technologies to the study of cancer is rapidly shifting toward the analysis of clinically relevant samples derived from patients, as the ultimate aim of translational research is to bring basic discoveries closer to the bedside. Here we describe the essence of a long-term initiative undertaken by The Danish Centre for Translational Breast Cancer Research and currently underway for cancer biomarker discovery using fresh tissue biopsies and bio-fluids. The Centre is a virtual hub that brings together scientists working in various areas of basic cancer research such as cell cycle control, invasion and micro-environmental alterations, apoptosis, cell signaling, and immunology, with clinicians (oncologists, surgeons), pathologists, and epidemiologists, with the aim of understanding the molecular mechanisms underlying breast cancer progression and ultimately of improving patient survival and quality of life. The unifying concept behind our approach is the use of various experimental paradigms for the prospective analysis of clinically relevant samples obtained from the same patient, along with the systematic integration of the biological and clinical data.
The Sex-Determining Mechanism of Drosophila Miranda.

SERIES of recent papers (DOBZHANSKY 1935; DOBZHANSKY and A TAN 1936; DOBZHANSKY 1937)) has described the unusual and interesting features which characterize the breeding behavior of Drosophila miranda and especially its method of sex determination. These papers have also reported the results of hybridization of miranda with the closely related and better known species, Drosophila pseudoobscura, and have given a detailed description, based on the study of the salivary gland chromosomes of the hybrids, of the similarities and differences in gene arrangement in these two species. In spite of these studies, there remained much that was obscure about the operation of the sex-chromosome mechanism, and particularly about the manner in which such an organization of the sex-determining material could have been derived from the more familiar sort'found in D . pseudoobscura and, indeed, throughout the genus Drosophila. Because of the need for more information on these interesting points, PROF. DOBZHANSKY suggested that I attempt to review and extend his observations. For this, for his kindness in furnishing me with stocks used in the investigation, and for much helpful criticism, I wish to express my gratitude to PROF. DOBZHANSKY. Helpful suggestions for the revision of the manuscript have been kindly given by PROF. F. R. IMMER and PROF. C. R. BURNHAM. To PROF. A. H. STURTEVANT, under whose direction this work was performed, I am deeply indebted for advice and encouragement. The studies here reported have been sufficient to render more understandable the operation of the sex-determining mechanism of Drosophila miranda, and to indicate the manner in which it has been derived from the type present in the common ancestor of pseudoobscura and miranda.
Fundamental study of direct current resistance effect on transmission line characteristics

High-speed transmission line characteristics have been analyzed from the point view of many parameter's effects in huge amount of papers. As far as maintaining geometric (dimensional) similarity of transmission line configurations, i.e., shrink or expansion of cross-sectional dimension, characteristics of transmission lines are not affected by their configurations based on electromagnetism from Maxwell's equations. However, direct current resistance (DCR) and skin depth surface/bulk ratio (SBR) of metal conductor in constant transmission length are changed even if geometric similarity is maintained. There have been seen no previous studies performed from this stand point. Therefore, as a fundamental study we examined on characteristics of transmission lines with geometric similarity by focusing on the effect of DCR and SBR. Time domain reflectometry (TDR) profiles, clock pulse rise/fall times (tr/tf), and eye-patterns were measured on the transmission line samples with different dimensions (line width and thickness) while maintaining geometric similarity. Experimental results suggest that the surface electron behavior would be related with DCR and SBR on the characteristics of transmission lines despite experimental accuracy is still not enough. These phenomena should more care for recent printed circuit boards over 10 Gbps/pin preferably toward 20 Gbps/pin.
Optimal sampling intervals to assess long-term glycemic control using continuous glucose monitoring.

AIMS AND HYPOTHESIS The optimal duration and frequency of short-term continuous glucose monitoring (CGM) to reflect long-term glycemia have not been determined. The Juvenile Diabetes Research Foundation CGM randomized trials provided a large dataset of longitudinal CGM data for this type of analysis. METHODS The analysis included 185 subjects who had 334 3-month intervals of CGM data meeting specific criteria. For various glucose indices, correlations (r²) were computed for the entire 3-month interval versus selected sampling periods ranging from 3 to 15 days. Other computed agreement measures included median relative absolute difference, values within ± 10% and ± 20% of full value, and median absolute difference. RESULTS As would be expected, the more days of glucose data that were sampled, the higher the correlation with the full 3 months of data. For 3 days of sampling, the r² value ranged from 0.32 to 0.47, evaluating mean glucose, percentage of values 71-180 mg/dL, percentage of values > 180 mg/dL, percentage of values ≤ 70 mg/dL, and coefficient of variation; in contrast, for 15 days of sampling, the r² values ranged from 0.66 to 0.75. The results were similar when the analysis intervals were stratified by age group (8-14, 15-24, and ≥ 25 years), by baseline hemoglobin A1c level (< 7.0% and ≥ 7.0%), and by CGM device type. CONCLUSIONS AND INTERPRETATION Our data suggest that a 12-15-day period of monitoring every 3 months may be needed to optimally assess overall glucose control. Shorter periods of sampling can be useful, but the correlation with 3-month measures of glycemic control is lower.
A pilot pharmacokinetic and immunoscintigraphic study with the technetium‐99m‐labeled monoclonal antibody BC‐1 directed against oncofetal fibronectin in patients with brain tumors

Preliminary experiments in an animal model have shown the favorable tumor targeting potential in vivo of radiolabeled BC‐1, an immunoglobulin (Ig)G1 monoclonal antibody (MoAb) that recognizes the human fibronectin isoform (B+) containing the ED‐B oncofetal domain. This antigen has extremely restricted distribution in normal adult tissues. Instead, it is highly expressed in fetal and tumor tissues, especially in high grade astrocytomas and malignant gliomas of the brain, in which the process of neoangiogenesis linked to tumor growth is particularly important.
Prospective Assessment of Postoperative Pain After Craniotomy

Pain after craniotomy may be underdiagnosed, despite the fact that it can increase postoperative complications for example arterial hypertension and postoperative hemorrhage. This study investigates the incidence and intensity of pain after craniotomy and characterizes the influencing parameters. During a 1-year period 256 patients undergoing elective craniotomy were prospectively included in the study. Intensity of pain was evaluated 1, 4, and 24 hours after extubation using a verbal numerical rating scale (NRS) ranging from 0 (no pain) to 10 (maximal pain). Routine perioperative pain management was not influenced by the investigators. Parameters including patient-related factors, drug administration, and surgical factors were correlated with incidence and intensity of postcraniotomy pain. Statistical analysis: logistic regression and χ2 using SPSS program (Windows, version 12.0). During the first 24 hours 87% of the patients experienced pain (NRS 1 to 3: 32%, NRS 4 to 7: 44%, NRS 8 to 10: 11%). For postoperative analgesia, the opioid piritramide (a μ-receptor agonist) was administered to 70% and nonopiod analgesics to 73% of the patients. The probability of experiencing postcraniotomy pain was reduced by 3% for each year of life. Maintenance of anesthesia with sevoflurane increased the probability of suffering from postcraniotomy pain by 147% and the absence of corticosteroids by 119%. Other investigated parameters did not influence pain after craniotomy. This study shows that pain is experienced by the majority of patients after craniotomy, despite conventional pain management, emphasizing the necessity for improved and individualized pain management in this special group of patients.