Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrastructural localization of the norepinephrine transporter in superficial and deep layers of the rat prelimbic prefrontal cortex and its spatial relationship to probable dopamine terminals

The prefrontal cortex (PFC) is a likely site of action for the therapeutic efficacy of antidepressants that inhibit norepinephrine (NE) reuptake. Moreover, drugs that block the NE transporter (NET) increase extracellular levels of both NE and dopamine (DA), an interaction that may contribute to their therapeutic properties. To examine the subcellular localization of NET and to investigate the spatial relationships between presumed NE and DA axons within the rat prelimbic PFC, we combined immunogold–silver localization of NET with immunoperoxidase staining for the catecholamine synthetic enzyme tyrosine hydroxylase (TH). An additional aim was to quantify the proportion of profiles dually labeled for NET and TH to test the common observation that TH immunolabeling is relatively selective for DA axons. NET‐immunoreactive (NET‐ir) axonal profiles were typically unmyelinated and occasionally were observed to form symmetric axodendritic synapses. The majority of immunogold NET labeling was unexpectedly observed in the cytoplasm rather than on the plasma membrane. Furthermore, in tissue dually labeled for both NET and TH, only 8–10% of profiles contained both markers. Unlike observations for singly labeled profiles, gold–silver particles for NET in dually labeled axons were localized primarily to the plasmalemma. A systematic survey of terminals labeled only for TH revealed that they were typically separated by at least 1.2 μm from NET‐ir varicosities, and the two profile types were not seen to contact common targets. These results suggest that, in the rat PFC, NE axons ( 1 ) contain predominantly cytoplasmic NET, ( 2 ) infrequently contain TH immunolabeling, and ( 3 ) may interact with probable DA afferents by means of extrasynaptic mechanisms. J. Comp. Neurol. 466:478–494, 2003. © 2003 Wiley‐Liss, Inc.
Suicide by Motor Vehicle “Accident” in Queensland

Objective: Around the world, a substantial proportion of motor vehicle crash deaths are recognized as “hidden” suicides. This project sought to progress understandings of drivers who used a motor vehicle to die by suicide in Queensland, Australia, during the period 1990 to 2007. Methods: Data for this study were derived from the Queensland Suicide Register and forensic crash investigation case records. Analysis focused on life circumstances and events preceding the death, physical and mental illnesses, past suicidality, and indication of suicide intent (e.g., suicide notes or statements). Results: Compared to cases using other methods, confirmed driver suicides were more likely to be males aged between 25 and 44 years who were employed at the time of death. A large proportion of driver suicides had consumed alcohol immediately prior to the crash and experienced a number of life events, including relationship conflict, legal or criminal issues, and financial problems. Conclusion: These exploratory results indicate the need to educate crash investigators about the characteristics of those who use a motor vehicle to die. Improving the information available on the mental and physical health and background life-related factors of crash victims can help coroners and researchers determine whether these deaths were intentional. Further investigation is needed in order to formulate intervention strategies for those who may be vulnerable to driver suicide.
Using Expression Data for Quantification of Active Processes in Physiologically Based Pharmacokinetic Modeling

Active processes involved in drug metabolization and distribution mediated by enzymes, transporters, or binding partners mostly occur simultaneously in various organs. However, a quantitative description of active processes is difficult because of limited experimental accessibility of tissue-specific protein activity in vivo. In this work, we present a novel approach to estimate in vivo activity of such enzymes or transporters that have an influence on drug pharmacokinetics. Tissue-specific mRNA expression is used as a surrogate for protein abundance and activity and is integrated into physiologically based pharmacokinetic (PBPK) models that already represent detailed anatomical and physiological information. The new approach was evaluated using three publicly available databases: whole-genome expression microarrays from ArrayExpress, reverse transcription-polymerase chain reaction-derived gene expression estimates collected from the literature, and expressed sequence tags from UniGene. Expression data were preprocessed and stored in a customized database that was then used to build PBPK models for pravastatin in humans. These models represented drug uptake by organic anion-transporting polypeptide 1B1 and organic anion transporter 3, active efflux by multidrug resistance protein 2, and metabolization by sulfotransferases in liver, kidney, and/or intestine. Benchmarking of PBPK models based on gene expression data against alternative models with either a less complex model structure or randomly assigned gene expression values clearly demonstrated the superior model performance of the former. Besides accurate prediction of drug pharmacokinetics, integration of relative gene expression data in PBPK models offers the unique possibility to simultaneously investigate drug-drug interactions in all relevant organs because of the physiological representation of protein-mediated processes.
Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development

Distinct dendritic cell (DC) subsets have been suggested to be preprogrammed to direct either T helper cell (Th) type 1 or Th2 development, although more recently different pathogen products or stimuli have been shown to render these DCs more flexible. It is still unclear how distinct mouse DC subsets cultured from bone marrow precursors, blood, or their lymphoid tissue counterparts direct Th differentiation. We show that mouse myeloid and plasmacytoid precursor DCs (pDCs) cultured from bone marrow precursors and ex vivo splenic DC subsets can induce the development of both Th1 and Th2 effector cells depending on the dose of antigen. In general, high antigen doses induced Th1 cell development whereas low antigen doses induced Th2 cell development. Both cultured and ex vivo splenic plasmacytoid-derived DCs enhanced CD4+ T cell proliferation and induced strong Th1 cell development when activated with the Toll-like receptor (TLR)9 ligand CpG, and not with the TLR4 ligand lipopolysaccharide (LPS). The responsiveness of plasmacytoid pDCs to CpG correlated with high TLR9 expression similarly to human plasmacytoid pDCs. Conversely, myeloid DCs generated with granulocyte/macrophage colony-stimulating factor enhanced Th1 cell development when stimulated with LPS as a result of their high level of TLR4 expression. Polarized Th1 responses resulting from high antigen dose were not additionally enhanced by stimulation of DCs by TLR ligands. Thus, the net effect of antigen dose, the state of maturation of the DCs together with the stimulation of DCs by pathogen-derived products, will determine whether a Th1 or Th2 response develops.
Cyclosporine A-nanoparticles enhance the therapeutic benefit of adipose tissue-derived stem cell transplantation in a swine myocardial infarction model

Treatment of myocardial infarction (MI) with adipose-derived stem cells (ASCs) has produced promising results. Cyclosporine A (CsA) inhibits apoptosis by preventing the opening of mitochondrial permeability transition pores. A CsA nanoparticle emulsion (CsA-NP) has lower toxicity and higher efficiency as compared to CsA. In this study, we hypothesized that a combination of ASCs and CsA-NP would enhance the therapeutic efficiency in a swine MI model. MI was induced in pig hearts by occlusion of the left anterior descending artery. The animals that survived MI were divided into four groups and 1 week later received intracoronary ASCs (ASCs, n=6), intracoronary culture media in combination with CsA-NP (CsA-NP, n=6), intracoronary ASCs in combination with CsA-NP (ASCs + CsA-NP, n=6), or remained untreated (control, n=4). Animals were sacrificed 8 weeks later and were evaluated for cardiac function by delayed-enhanced magnetic resonance imaging and immunohistopathology. We observed that the left ventricular ejection fraction (LVEF) was significantly increased in the ASCs + CsA-NP group, compared to the CsA-NP group (53.6%±2.4% versus 48.6%±1.5%, P<0.05), and the ASCs group (53.6%±2.4% versus 48.3%±1.8%, P<0.05). More importantly, the infarct size was significantly smaller in the ASCs + CsA-NP group as compared to the CsA-NP group (6.2±1.7 cm3 versus 9.1±3.4 cm3, P<0.05) and the ASCs group (6.2±1.7 cm3 versus 7.5±0.6 cm3, P<0.05). These findings were further confirmed by analysis of the expression of cardiomyocyte markers, myosin heavy chain (α-actinin) and troponin T. In addition, the CsA-NP + ASCs treatment promoted neovascularization (P<0.05) and inhibited cardiomyocyte apoptosis (P<0.01) compared to the control group. This study demonstrates that CsA-NP enhanced the therapeutic benefits of ASCs transplantation for MI.
A method for identifying and confirming the use of URL filtering products for censorship

Products used for managing network traffic and restricting access to Web content represent a dual-use technology. While they were designed to improve performance and protect users from inappropriate content, these products are also used to censor the Web by authoritarian regimes around the globe. This dual use has not gone unnoticed, with Western governments placing restrictions on their export. Our contribution is to present methods for identifying installations of URL filtering products and confirming their use for censorship. We first present a methodology for identifying externally visible installations of URL filtering products in ISPs around the globe. Further, we leverage the fact that many of these products accept user-submitted sites for blocking to confirm that a specific URL filtering product is being used for censorship. Using this method, we are able to confirm the use of McAfee SmartFilter in Saudi Arabia and the United Arab Emirates (UAE) and Netsweeper in Qatar, the UAE, and Yemen. Our results show that these products are being used to block a range of content, including oppositional political speech, religious discussion and gay and lesbian material, speech generally protected by international human rights norms.
Fleas (Siphonaptera) Collected from Small Mammals in Southern Viet Nam in 1997–1998

Abstract We report on fleas collected from small mammals in two forests, a lowland semideciduous dipterocarp forest and a highland evergreen forest, in southern Viet Nam. In the lowland forest, only one species of flea (Xenopsylla vexabilis Jordan) infested a single species of rodent [Berylmys berdmorei (Blyth)]. In the highland forest, seven species of fleas were collected from eight species of small mammals. Three species of fleas, Lentistivalius insolli (Traub), Lentistivalius occidentayunnanus Li, Xie & Gong, and Gryphopsylla jacobsoni (Jordan & Rothschild), collected from mammals in the highland forest represent new records for Viet Nam.
Novel Multidimensional Models of Opinion Dynamics in Social Networks

Unlike many complex networks studied in the literature, social networks rarely exhibit unanimous behavior, or consensus. This requires a development of mathematical models that are sufficiently simple to be examined and capture, at the same time, the complex behavior of real social groups, where opinions and actions related to them may form clusters of different size. One such model, proposed by Friedkin and Johnsen, extends the idea of conventional consensus algorithm (also referred to as the iterative opinion pooling) to take into account the actors’ prejudices, caused by some exogenous factors and leading to disagreement in the final opinions. In this paper, we offer a novel multidimensional extension, describing the evolution of the agents’ opinions on several topics. Unlike the existing models, these topics are interdependent, and hence the opinions being formed on these topics are also mutually dependent. We rigorously examine stability properties of the proposed model, in particular, convergence of the agents’ opinions. Although our model assumes synchronous communication among the agents, we show that the same final opinions may be reached “on average” via asynchronous gossip-based protocols.
Asian breast cancer survival in the US: a comparison between Asian immigrants, US-born Asian Americans and Caucasians.

BACKGROUND This study examines whether acculturation of Asian American women, assessed by place of birth, is associated with survival after diagnosis of breast cancer. We hypothesized that environmental factors associated with acculturation, such as a high-fat diet, would result in a pattern of better survival for first-generation Asians compared with subsequent-generation Asian Americans. METHODS Analyses compare survival among women of four ethnic groups (Chinese [n = 1842], Japanese [n = 3319], Filipino [n = 1598] and a random sample of Caucasians [n = 10,000]) who were diagnosed with primary invasive breast carcinoma in three Surveillance, Epidemiology, and End Results Program (SEER) regions (San Francisco/Oakland, Hawaii, Seattle/Puget Sound) between 1973 and 1994. Analyses by birthplace compare first-generation Asian immigrants with subsequent-generation Asian Americans of the same ethnicity. Analyses were based on the Cox proportional hazards model and adjusted for age at diagnosis, stage of disease, year of diagnosis, type of treatment, marital status, and SEER region. RESULTS Japanese women had significantly better survival than all other races, but there were no significant differences in survival between Chinese, Filipino, and Caucasian women. There were no significant differences in survival by place of birth within each Asian ethnic group, after adjustment for demographic characteristics, stage of disease, and treatment. CONCLUSION The findings do not support the hypothesis that acculturation of Asian American women is associated with decreased breast cancer survival.
Whole-genome prokaryotic phylogeny

Current understanding of the phylogeny of prokaryotes is based on the comparison of the highly conserved small ssu-rRNA subunit and similar regions. Although such molecules have proved to be very useful phylogenetic markers, mutational saturation is a problem, due to their restricted lengths. Now, a growing number of complete prokaryotic genomes are available. This paper addresses the problem of determining a prokaryotic phylogeny utilizing the comparison of complete genomes. We introduce a new strategy, GBDP, 'genome blast distance phylogeny', and show that different variants of this approach robustly produce phylogenies that are biologically sound, when applied to 91 prokaryotic genomes. In this approach, first Blast is used to compare genomes, then a distance matrix is computed, and finally a tree- or network-reconstruction method such as UPGMA, Neighbor-Joining, BioNJ or Neighbor-Net is applied.
Relevance of Endocavitary Structures in Ablation Procedures for Ventricular Tachycardia

Endocavitary Structures and Ventricular Tachycardia Ablation. Background: Radiofrequency (RF) ablation for ventricular tachycardia (VT) has high failure rates. Whether endocavitary structures (ECS) such as the papillary muscles (PMs), moderator bands (MBs), or false tendons (FTs) impact VT ablation is unknown.
Mineral balance of finishing pigs fed copper sulfate or a copper-lysine complex at growth-stimulating levels.

Twenty-four crossbred barrows (average BW, 70.8 kg) were used to compare the digestibility of dry matter and the mineral absorption and retention by pigs fed two Cu sources. Dietary treatments were 1) basal (B) (16% CP corn-soybean meal-based diet, 36 mg/kg of Cu), 2) B + 200 mg/kg of Cu from CuSO4.5 H2O (CuSO4), and 3) B + 200 mg/kg of Cu from a copper lysine complex (CuLys). All diets contained equal lysine content and . 05% chromic oxide for indirect determination of absorption. Two 7-d total collection periods were conducted. Pigs were fed 8% of metabolic BW (BW.75) divided into two equal feedings. Average daily gain tended to be higher for pigs fed CuLys than for pigs fed CuSO4 (P < .02). Dry matter digestibilities were similar (P > .10) among treatments. The absolute amount of Cu absorbed and retained was greater for pigs fed both Cu sources (P < .001) than for pigs fed the control diet. Iron and Zn intake and excretion and the percentage of Fe absorbed and retained were similar (P > .10) among treatment groups. Chromium intake and excretion in feces were not different (P > .10), with an average recovery of 93.8%. Indirect DM digestibility was similar to total collection values; however, mineral values were similar only after correction for Cr recovery. Pigs fed elevated Cu absorbed more Cu, with no difference between the two sources. Zinc and Fe absorption and retention were generally not affected (P > .10) by Cu addition or sources. The absorption and retention of Cu was similar for pigs fed growth-stimulative levels of Cu from CuSO4 or copper lysine complex.
Some reflection on research ‘Schools’ and geographies

Reflecting on real and perceived differences between European and North American research cultures, I challenge views that ‘European’ research is under appreciated or discriminated against, and caution against isolationist European positions. Instead, I argue that although no distinctive and coherent European tradition or culture really exists, there may be elements of the prevalent research culture that can be turned into an advantage for Europe-based and/or European-trained researchers in helping to influence and improve one, global research conversation. Of course, a range of sub-communities and sub-conversations will and should exist, but there is no reason for these to be based on geography.
Productive infection of dendritic cells by HIV-1 and their ability to capture virus are mediated through separate pathways.

There is substantial evidence that dendritic cells (DC) residing within epithelial surfaces (e.g., Langerhans cells) are the initial cells infected with HIV after mucosal exposure to virus. To study DC-HIV interactions in detail, we propagated Langerhans cell-like DC from cord blood CD34(+) cells and from adult blood plastic-adherent PBMC in the presence of cytokines (GM-CSF, IL-4, and/or TNF-alpha). DC pulsed overnight with HIVBaL or HIVIIIB were infected productively with both viral subtypes (as assessed by PCR, supernatant p24 protein levels, electron microscopy, and antibody staining). Productive infection could be blocked by anti-CD4 mAbs, RANTES (regulated upon activation, normal T cell expressed and secreted) (for HIVBaL), stromal cell-derived factor-1 (for HIVIIIB), or azidothymidine added during the HIV pulse, as well as by blocking DC proliferation. However, pulsing DC with HIV under these blocking conditions had no effect on the ability of DC to capture virus and transmit infection to cocultured antigen-stimulated CD4(+) T cells. Thus, we show by several criteria that (a) productive infection of DC and (b) the ability of DC to capture virus are mediated through separate pathways. We suggest that strategies designed to block mucosal transmission of HIV should consider interfering with both virus infection and virus capture by DC.
NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcinoma cells

The osmosensitive transcription factor nuclear factor of activated T-cells (NFAT) 5, also known as tonicity enhancer binding protein (TonEBP), has been associated with the development of a variety of tumor entities, among them breast cancer, colon carcinoma, and melanoma. The aim of the present study was to determine whether NFAT5 is also involved in the development of renal cell carcinoma (RCC). The most common type of RCC, the clear cell RCC, originates from the proximal convoluted tubule. We tested our hypothesis in the clear cell RCC cell line CaKi-1 and the non-cancerous proximal tubule cell line HK-2, as control. Basal expression of NFAT5 and NFAT5 activity in CaKi-1 cells was several times higher than in HK-2 cells. Osmotic stress induced an increased NFAT5 activity in both CaKi-1 and HK-2 cells, again with significantly higher activities in CaKi-1 cells. Analysis of NFAT5-regulating signaling pathways in CaKi-1 cells revealed that inhibition of the MAP kinases p38, c-Jun-terminal kinase (JNK) and extracellular regulated kinase (ERK) and of the focal adhesion kinase (FAK) partially blunted NFAT5 activity. FAK and ERK were both constitutively active, even under isotonic conditions, which may contribute to the high basal expression and activity of NFAT5 in CaKi-1 cells. In contrast, the MAP kinases p38 and JNK were inactive under isotonic conditions and became activated under osmotic stress conditions, indicating that p38 and JNK mediate upregulation of NFAT5 activity under these conditions. siRNA-mediated knockdown of NFAT5 in CaKi-1 cells reduced the expression of S100A4, a member of the S100 family of proteins, which promotes metastasis. Knockdown of NFAT5 was accompanied by a significant decrease in proliferation and migration activity. Taken together, our results indicate that NFAT5 induces S100A4 expression in CaKi-1 cells, thereby playing an important role in RCC proliferation and migration.
A 50 nm depleted-substrate CMOS transistor (DST)

In this paper we show a Depleted-Substrate Transistor (DST) technology which demonstrates significant performance gain over bulk Si transistors without the floating body effect (FBE). We have fabricated depleted-substrate CMOS transistors on thin silicon body (/spl les/30 nm) with physical gate lengths down to 50 nm which show much steeper subthreshold slopes (/spl les/75 mV/decade) and improved DIBL (/spl les/50 mV/V) over both partially-depleted (P-D) SOI and bulk Si, for both PMOS and NMOS transistors. The salicide formation and high parasitic resistance problems associated with the use of thin Si body can be overcome by using raised source/drain. Depleted-substrate PMOS transistors with 50 nm physical gate length and raised source/drain were fabricated and achieved I/sub on/=0.65 mA/um and I/sub off/=9 nA/um at V/sub cc/=1.3 V. This PMOS drive current is the highest ever reported, and is about 30% higher than any previously published PMOS I/sub on/ value for both PD-SOI and bulk Si at a given I/sub off/. The use of raised source/drain improved the I/sub on/ of the depleted-substrate NMOS transistors by /spl sim/20%. Depleted-substrate NMOS transistors with 65 nm physical gate length and raised source/drain achieved DIBL=45 mV/V, subthreshold slope=75 mV/decade, I/sub on/=1.18 mA/um and I/sub off/ =60 nA/um at V/sub cc/=1.3 V, as well as significant improvement in Id-Vd characteristics due to a 60% reduction in DIBL and >25% improvement in subthreshold slope over the bulk Si.