Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced susceptibility to end-organ disease in the lupus-facilitating NZW mouse strain.

OBJECTIVE Although the NZW mouse strain is phenotypically normal, fulminant lupus glomerulonephritis (GN) develops when NZW mice are bred to several other strains, such as NZB, BXSB, B6.Sle1, and B6.Yaa. Based on the observation that aging NZW mice exhibit histologic evidence of GN, we sought to test our hypothesis that NZW mice may be more susceptible to immune-mediated renal damage. METHODS NZW mice, as well as C57BL/6 (B6) and BALB/c control mice, were challenged with rabbit anti-glomerular basement membrane nephrotoxic sera (NTS), to induce renal disease. The different mouse strains were monitored for the degree of clinical disease, renal pathology, chemokine profiles, and cellular infiltrates. RESULTS Although the NZW and control strains showed similar glomerular deposits of rabbit Ig and exhibited similar levels of anti-rabbit xenogeneic immune response, the NZW mice had significantly worse pathologic changes and disease. Compared with the control strains, the NTS-injected NZW mice demonstrated significantly increased proteinuria, elevated blood urea nitrogen levels, more severe histologic GN and tubulointerstitial nephritis, increased glomerular crescent formation with macrophage and neutrophil infiltrates, elevated expression of CC and CXC chemokines (monocyte chemoattractant protein 1, RANTES, KC), and significantly accelerated mortality. Importantly, these changes occurred within a few days after NTS administration. Finally, (B6 x NZW)F(1) mice were as susceptible as the NZW parents, which indicates dominant NZW contributions. CONCLUSION Collectively, these findings support the notion that a lupus-facilitating genome may contribute to disease susceptibility by modulating the degree of immune-mediated end-organ damage. The availability of B6-based congenic strains bearing individual NZW-derived lupus susceptibility loci will permit future genetic dissection of end-organ susceptibility in murine lupus.
Cardiovascular effects of prolonged delta‐9‐tetrahydrocannabinol ingestion

In contrast to the tachycardia and unchanged or increased blood pressure seen after single doses, prolonged delta‐9‐tetrahydrocannabinol (THC) ingestion produced significant heart rate slowing and blood pressure lowering in hospitalized volunteers. Impaired circulatory responses to standing, exercise, Valsalva maneuver, and cold pressor testing suggest a state of sympathetic insufficiency. Marked weight gain was observed in all subjects, which has been shown to be related to fluid retention and plasma volume expansion. Tolerance developed to orthostatic hypotension, possibly related to plasma volume expansion, but did not develop to the supine hypotensive effects. Nearly complete tolerance developed to the tachycardia and psychological effects produced by smoked marijuana while ingesting THC. Electrocardiographic changes were minimal despite the large cumulative dose of THC. The hypothesis that THC has a biphasic effect on the sympathetic nervous system in man, producing excitation with single doses and inhibition with prolonged administration, is discussed.
Early Safety Assessment Using Cellular Systems Biology Yields Insights into Mechanisms of Action

The integration of high-content screening (HCS) readers with organ-specific cell models, panels of functional biomarkers, and advanced informatics is a powerful approach to identifying the toxic liabilities of compounds early in the development process and forms the basis of “early safety assessment. ” This cellular systems biology (CSB™) approach (CellCiphr® profile) has been used to integrate rodent and human cellular hepatic models with panels of functional biomarkers measured at multiple time points to profile both the potency and specificity of the cellular toxicological response. These profiles also provide initial insights on the mechanism of the toxic response. The authors describe here mechanistic assay profiles designed to further dissect the toxic mechanisms of action and elucidate subtle effects apparent in subpopulations of cells. They measured 8 key mechanisms of toxicity with multiple biomarker feature measurements made simultaneously in populations of living primary hepatocytes and HepG2 cells. Mining the cell population response from these mechanistic profiles revealed the concentration dependence and nature of the heterogeneity of the response, as well as relationships between the functional responses. These more detailed mechanistic profiles define differences in compound activities that are not apparent in the average population response. Because cells and tissues encounter wide ranges of drug doses in space and time, these mechanistic profiles build on the CellCiphr® profile and better reflect the complexity of the response in vivo.
Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia. A pilot study.

STUDY OBJECTIVE To evaluate inhaled or reduced-dose intravenous pentamidine for the treatment of patients with mild Pneumocystis carinii pneumonia. DESIGN Open, nonrandomized pilot study; measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS Of 22 men with mild P. carinii pneumonia (PO2 greater than or equal to 55 mm Hg), 15 (9 in the inhaled group and 6 in the intravenous group) received treatment for their first episode and 7 for a repeat episode. INTERVENTIONS Pentamidine isethionate, 4 mg/kg body weight by inhalation, or 3 mg/kg intravenously, was given once daily, as long as clinically indicated. MEASUREMENTS AND MAIN RESULTS Of the 13 patients in the inhaled group, 9 has a satisfactory response; and of the 10 in the reduced-dose intravenous group, 9 had a satisfactory response. Major adverse reactions occurred in two patients in each group. Three patients in the inhaled group appeared to have had early relapses. Bronchoalveolar lavage fluid concentrations of pentamidine ranged between 16.8 +/- 7.3 ng/mL and 149.7 +/- 38.2 ng/mL in the inhaled group and 3.4 +/- 0.2 ng/mL and 10.9 ng/mL in the intravenous group. CONCLUSIONS Inhaled or reduced-dose intravenous pentamidine may be an effective and less toxic therapy for mild P. carinii pneumonia. These regimens are not recommended for general use until larger controlled trials are conducted.
Expression of leukocyte integrins and tissue factor in mononuclear phagocytes.

Coagulation is intimately involved in the pathology of inflammation. The leukocyte beta2-integrins have several functions, including serving as receptors for coagulation factor X and fibrinogen. Tissue factor (TF) is a receptor for factor VII and a very potent trigger of coagulation. The intention of this study was to examine a possible coexpression of beta2-integrins (CD11b/CD18 and CD11c/CD18) and the procoagulant TF in alveolar macrophages (AM) and blood monocytes, i.e. cells of the same differentiation lineage. The expression of beta2-integrins in human AM isolated by bronchoalveolar lavage and in blood monocytes was analysed by flow cytometry, whereas TF activity was analysed in a one-stage clotting assay. In monocytes, TF activity, CD11b and CD11c expression were highly inducible by lipopolysaccharide (LPS), with a 13-, 19- and four-fold increase, respectively. In AM, TF and beta2-integrins were all constitutively expressed, but the expression could not be further enhanced by LPS stimulation. CD11b and CD11c expression varied inversely with the cell size of AM, in contrast to TF activity which is known to be proportional to AM cell size. In vitro expression of beta2-integrins and tissue factor in lipopolysaccharide-stimulated blood monocytes seems to be intimately coregulated, whereas the expression of these receptors in alveolar macrophages seems to be unresponsive to lipopolysaccharide. These results indicate that blood monocytes and alveolar macrophages have different roles and use different mechanisms in cell-induced fibrin formation.
Ask not what philosophy can do for critical management studies

In seeking to re-evaluate praxis and contribute to the current Critical Management Studies (CMS) debate, this paper pursues a number of inter-related strands of scholarship. We begin by examining the nature of the ‘things’ we ostensibly do with words and invoke A.S Byatt’s novel, The Biographer’s Tale, as a vehicle for exploring academic disaffection with exclusively wordy pursuits. This leads into a discussion of the political quietism characteristic of contemporary academic life and question how this state of affairs has arisen. We discover that, among other conditions, the opposition of philosophy and action has a legacy that stretches back many centuries. Using the work of the French classicist Pierre Hadot (1995), we trace a genealogy that reveals how modern ‘philosophy’ has been systematically emptied of both the ‘love’ and the ‘wisdom’ that lie at its semantic core. Political inaction is one consequence of the rejection of philosophy as a way of life in favour of philosophical discourse. Austin’s work is pivotal to our argument, for it allows us to examine Derrida’s deconstructive reading of How To Do Things With Words and thus to ponder the kinds of (re)solutions of the praxis debate provided by this particular form of post-structural analysis. For all its penetrative subtlety and mind-altering insight, however, Derrida’s reading of Austin – and through it the broader project of deconstructionism – turns out still to be burdened by the problem of ‘modern philosophy’ as we have framed it. Is there any way back from this seeming impasse? We think so, but find ourselves looking toward the premodern and non-modern philosophies of antiquity for resolution, in particular those of Stoicism and Buddhism.
Cloning and Functional Expression of a Voltage-gated Calcium Channel α1 Subunit from Jellyfish*

Voltage-gated Ca2+channels in vertebrates comprise at least seven molecular subtypes, each of which produces a current with distinct kinetics and pharmacology. Although several invertebrate Ca2+ channel α1 subunits have also been cloned, their functional characteristics remain unclear, as heterologous expression of a full-length invertebrate channel has not previously been reported. We have cloned a cDNA encoding the α1 subunit of a voltage-gated Ca2+ channel from the scyphozoan jellyfishCyanea capillata, one of the earliest existing organisms to possess neural and muscle tissue. The deduced amino acid sequence of this subunit, named CyCaα1, is more similar to vertebrateL-type channels (α1S, α1C, and α1D) than to non-L-type channels (α1A, α1B, and α1E) or low voltage-activated channels (α1G). Expression of CyCaα1 in Xenopus oocytes produces a high voltage-activated Ca2+ current that, unlike vertebrateL-type currents, is only weakly sensitive to 1,4-dihydropyridine or phenylalkylamine Ca2+ channel blockers and is not potentiated by the agonist S(−)-BayK 8644. In addition, the channel is less permeable to Ba2+than to Ca2+ and is more permeable to Sr2+. CyCaα1 thus represents an ancestral L-type α1 subunit with significant functional differences from mammalian L-type channels.
Subungual Exostosis: A Simple Technique of Excision

Subungual or Dupuytren's exostosis is a benign lesion of the distal phalanx that is prone to recurrence if incompletely excised. We report on a series of five patients treated with our simple excision technique. Despite sacrifice of a portion of the nail bed, the cosmetic appearance of the nail was excellent in four patients and good in one patient. There were no recurrences.
Plasma circulating tumor DNA as an alternative to metastatic biopsies for mutational analysis in breast cancer.

BACKGROUND Molecular screening programs use next-generation sequencing (NGS) of cancer gene panels to analyze metastatic biopsies. We interrogated whether plasma could be used as an alternative to metastatic biopsies. PATIENTS AND METHODS The Ion AmpliSeq™ Cancer Hotspot Panel v2 (Ion Torrent), covering 2800 COSMIC mutations from 50 cancer genes was used to analyze 69 tumor (primary/metastases) and 31 plasma samples from 17 metastatic breast cancer patients. The targeted coverage for tumor DNA was ×1000 and for plasma cell-free DNA ×25 000. Whole blood normal DNA was used to exclude germline variants. The Illumina technology was used to confirm observed mutations. RESULTS Evaluable NGS results were obtained for 60 tumor and 31 plasma samples from 17 patients. When tumor samples were analyzed, 12 of 17 (71%, 95% confidence interval (CI) 44% to 90%) patients had ≥1 mutation (median 1 mutation per patient, range 0-2 mutations) in either p53, PIK3CA, PTEN, AKT1 or IDH2 gene. When plasma samples were analyzed, 12 of 17 (71%, 95% CI: 44-90%) patients had ≥1 mutation (median 1 mutation per patient, range 0-2 mutations) in either p53, PIK3CA, PTEN, AKT1, IDH2 and SMAD4. All mutations were confirmed. When we focused on tumor and plasma samples collected at the same time-point, we observed that, in four patients, no mutation was identified in either tumor or plasma; in nine patients, the same mutations was identified in tumor and plasma; in two patients, a mutation was identified in tumor but not in plasma; in two patients, a mutation was identified in plasma but not in tumor. Thus, in 13 of 17 (76%, 95% CI 50% to 93%) patients, tumor and plasma provided concordant results whereas in 4 of 17 (24%, 95% CI 7% to 50%) patients, the results were discordant, providing complementary information. CONCLUSION Plasma can be prospectively tested as an alternative to metastatic biopsies in molecular screening programs.
The relationship between depressive symptom levels and subsequent increases in substance use among youth with severe emotional disturbance.

OBJECTIVE This study examined the relationship between levels of depressive symptoms and subsequent increases in substance use among 784 youth with severe emotional disturbance enrolled in Medicaid-funded behavioral health care plans. METHOD Youth at five sites nationwide were interviewed about their emotional and behavior problems, as well as their use of cigarettes, alcohol, and drugs--at both baseline and follow-up. RESULTS (1) Levels of depressive symptoms were significantly associated with concurrent substance use at baseline. (2) Baseline levels of depressive symptoms predicted subsequent changes in substance use, especially use of illicit drugs and multiple drugs. (3) These findings remained significant, even after controlling for sociodemographic, family, and individual characteristics. CONCLUSIONS These results indicate that depressive symptoms early in life may signal a risk for increasing involvement in substance use among severe emotional disturbed youth. This finding has important clinical implications for the prevention of substance misuse in this population.
Statistically Bounding Detection Latency in Low-Duty-Cycled Sensor Networks

Detecting abnormal events represents an important family of applications for wireless sensor networks. To achieve high performance of event detection, a sensor network should stay active most of the time, which is energy inefficient for battery driven sensor networks. This paper studies the fundamental problem of bounding detection delays when the sensor network is low duty cycled. We propose a novel approach for statistically bounding detection latency for event detection in sensor networks. The key issue is the wakeup scheduling of sensor nodes and minimization of wakeup activity. We propose a lightweight distributed algorithm for coordinating the wakeup scheduling of the sensor nodes. A distinctive feature of this algorithm is that it ensures that the detection delay of any event occurring anywhere in the sensing field is statistically bounded. In addition, the algorithm exposes a convenient interface for users to define the requirement on detection latency, thereby tuning the intrinsic tradeoff between energy efficiency and event detection performance. Extensive simulations have been conducted and results demonstrate that this algorithm can successfully meet delay bound and significantly reduce energy consumption.
Cross-layer CQI feedback window adaptation for OFDMA systems under feedback budget constraint

In this paper, we propose an adaptive feedback reduction scheme FWA (Feedback Window Adaptation) for OFDMA systems with limited feedback budget. The FWA algorithm adapts channel quality indicator (CQI) feedback rate for each mobile station (MS) exploiting the signaling of MAC layer automatic repeat request (ARQ) protocol and users application profile. We applied this FWA algorithm in two feedback mechanisms namely prediction and interval based feedback (PBF and IBF) schemes. We also developed a mathematical model to derive performance metric of both integrated schemes in terms of probability of adapting feedback window. Simulation results compare the performance of FWA combined to IBF and PBF schemes with non-FWA schemes which demonstrates the performance improvement in downlink throughput and MAC frame loss rate.
The impact of caregiver‐mediated JASPER on child restricted and repetitive behaviors and caregiver responses

Restricted and repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD). Compared to the social‐communication impairments, we know considerably less about why children engage in RRBs and if and how to intervene with these behaviors. As a result, early intervention has typically focused on social‐communication. In this study, we were interested in understanding how child RRBs changed following an intervention targeting social‐communication behaviors and if caregiver training changed how they responded to their child's RRBs. Eighty‐six toddlers with ASD and their caregivers received one of two interventions: caregivers were either actively coached while playing with their child (JASPER) or attended information sessions about ASD. On three different occasions (when they entered the study, following 10 weeks of intervention and 6‐months after) caregivers were filmed playing with their child. From these recordings, we coded child RRBs and caregiver responses to these behaviors. Child RRBs remained relatively stable following intervention in both groups, but increased when the children returned at 6‐months. Caregivers who received one‐on‐one coaching (JASPER) responded to a greater number of their child's RRBs and their responses were rated as more successful. Our study showed that a short‐term social‐communication intervention delivered through caregivers had “spillover effects” on how they also responded to their child's RRBs. Interventions targeting social‐communication behaviors should also examine how these treatments affect child RRBs and how caregiver responses to these behaviors may change following training. Autism Res 2017, 10: 983–992. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Bystander signaling via oxidative metabolism

The radiation-induced bystander effect (RIBE) is the initiation of biological end points in cells (bystander cells) that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS) act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to pursue this field of science.
Granulosa Cell Tumors: A Clinical Review of 61 Cases

Sixty-one patients with granulosa cell tumors of the ovary were treated in the A.M. Evans Clinic of the British Columbia Cancer Control Agency between 1944 and 1974. Their treatment and follow-up are reviewed, and while the 5-year survival rate was 78%, the 15-year rate fell to 50%. The material suggests that the trend to total hysterectomy and bilateral salpingo-oophorectomy has improved the prognosis, but other explanations are, of course, possible as this is a historical comparison.
Primary role of the liver in thrombopoietin production shown by tissue-specific knockout.

To the Editor: Maintenance of an appropriate number of circulating platelets is required for hemostasis and blood coagulation. The control of platelet production is mediated by thrombopoietin (Tpo) through its effect on the proliferation of megakaryocyte progenitors and on megakaryocyte ploidy. [1][
Development of sodium channels during differentiation of chick skeletal muscle in culture. I. Binding studies

[125I]Scorpion toxin and [3H]saxitoxin, two neurotoxins that bind specifically to different sites on sodium channels, were used to monitor the development of sodium channels during synchronous differentiation of chick skeletal muscle in culture. [3H]Saxitoxin- binding sites are not detectable in myoblasts. They appear only after myoblasts fuse to form myotubes and increase gradually to reach a maximal value of 58 fmol/mg of protein by 8 days in culture. In contrast, [125I]scorpion toxin-binding sites are first detected during the period of cell fusion and increase after fusion to reach a maximum by 4 days in culture, well before either the maximal value of the [3H]saxitoxin binding or the appearance of fully developed sodium action potentials. Neither [3H]saxitoxin binding nor [125I] scorpion toxin binding affinity changes during development; they have values of 1.4 and 62 nM, respectively. These data, and data described in the companion paper (Baumgold, J., J. B. Parent, and I. Spector (1983) J. Neurosci. 3: 1004–1013), suggest that sodium channel development involves two sequential steps: incorporation into the cell membrane of an immature form of the sodium channel capable of binding scorpion toxin alone, followed by the acquisition of the ability to bind saxitoxin and thus to become a mature and functional channel.