Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced sensitivity to neutralizing antibodies in a variant of equine infectious anemia virus is linked to amino acid substitutions in the surface unit envelope glycoprotein

Serial passage of the prototype (PR) cell-adapted Wyoming strain of equine infectious anemia virus (EIAV) in fetal donkey dermal (FDD) rather than fetal horse (designated fetal equine kidney [FEK]) cell cultures resulted in the generation of a variant virus strain which produced accelerated cytopathic effects in FDD cells and was 100- to 1,000-fold more sensitive to neutralizing antibodies than its parent. This neutralization-sensitive variant was designated the FDD strain. Although there were differences in glycosylation between the PR and FDD strains, passage of the FDD virus in FEK cells did not reduce its sensitivity to neutralizing antibody. Nucleotide sequencing of the region encoding the surface unit (SU) protein from the FDD strain revealed nine amino acid substitutions compared with the PR strain. Two of these substitutions resulted in changes in the polarity of charge, four caused the introduction of a charged residue, and three had no net change in charge. Nucleotide sequence analysis was extended to the region of the FDD virus genome encoding the extracellular domain of the transmembrane envelope glycoprotein (TM). Unlike the situation with the FDD virus coding region, there were minor variations in nucleotide sequence between individual molecular clones containing this region of the TM gene. Although each clone contained three nucleotide substitutions compared with the PR strain, only one of these was common to all, and this did not affect the amino acid content. Of the remaining two nucleotide substitutions, only one resulted in an amino acid change, and in each case, this change appeared to be conservative. To determine if amino acid substitutions in the SU protein of FDD cell-grown viruses were responsible for the enhanced sensitivity to neutralizing antibodies, chimeric viruses were constructed by using an infectious molecular clone of EIAV. These chimeric viruses contained all of the amino acid substitutions found in the FDD virus strain and were significantly more sensitive to neutralizing antibodies than viruses from the parental (PR) molecular clone. These results demonstrated that sensitivity to neutralizing antibodies in EIAV can be conferred by amino acid residues in the SU protein. However, such amino acid substitutions were not sufficient to enhance cytopathogenicity, as the chimeric viruses did not cause excessive degenererative effects in FDD cells, as was observed with the parental FDD virus strain.
Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma.

BACKGROUND Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. HYPOTHESIS Dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs. ANIMALS Forty-eight dogs that underwent adrenalectomy for pheochromocytoma. METHODS A retrospective medical record review for dogs that underwent adrenalectomy for pheochromocytoma at a veterinary medical teaching hospital over the period from January 1986 through December 2005. RESULTS Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly (P = .014) decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age (P = .028), lack of intraoperative arrhythmias (P = .0075), and decreased surgical time (P = .0089). CONCLUSIONS AND CLINICAL IMPORTANCE Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.
Iron: Nutritious, Noxious, and Not Readily Available

Fe(I1) and Fe(II1) are relatively small ions with a marked propensity to form six-coordinate complexes with ligands containing O, N, and S. This property, combined with the remarkable range of redox potentials covered by ironcontaining enzymes, accounts for the role of iron in such fundamental reactions as ribonucleotide and dinitrogen reduction as well as in the energy-yielding electron transfer reactions of respiration and photosynthesis. At the same time, the chemical properties of iron place limitations on the cellular accumulation of this element. First, Fe(I1) and Fe(II1) can act catalytically to generate hydroxyl radicals that are the most potent oxidizing agents known (Table I). Because of the potential of iron for wreaking cellular havoc, organisms generally regulate its uptake; as well, they store iron in the form of ferritin, a multimeric protein consisting of a 24-subunit shell that can house up to 4500 atoms of iron in its central cavity (Theil, 1987). Iron stored in this manner is nontoxic and is readily available to the cell. The second limit to iron acquisition is the fact that iron is found in nature mostly as a constituent of insoluble oxyhydroxide polymers of the general composition FeOOH (Table I). These Fe(II1) oxides (e.g. goethite, hematite) are produced by the weathering of rock. Because Fe(II1) oxides are quite stable and not very soluble at neutra1 pH, free Fe(II1) in an aerobic, aqueous environment is limited to an equilibrium concentration of approximately 10-17 M, a value far below that required for the optimal growth of plants or microbes (Table I). Thus, the problem that soil-based organisms have with iron is not one of abundance, since iron ranks fourth among a11 elements on the surface of the earth, but rather one of availability in aerobic environments at biological pH. Iron deficiency can be particularly pronounced in plants grown on calcareous soils, which cover approximately onethird of the earth's surface. Iron deficiency is usually recognized by chlorotic or yellowed interveinal areas in new leaves and, if severe, can lead to reduction in crop yields and even complete crop failure. Chemically speaking, organisms have three means at their disposal to dissolve Fe(II1) oxides: protonation, chelation, and reduction. To compete successfully for iron, organisms have thus evolved specific mechanisms to acquire iron that are based on these chemical processes. In many organisms, in-
Synthesis and Antiviral Activities of 1,2,3-triazole Functionalized Thymidines: 1,3-dipolar Cycloaddition for Efficient Regioselective Diversity Generation

Efficient regioselective synthesis of nucleoside conjugates was achieved by cycloaddition reaction of azides and alkynes using sodium ascorbate/CuSO4 system as a catalyst. These 16 novel thymidine analogues were obtained in excellent yields (75–100%), employing mild reaction conditions with a broad scope of structural modification. For the compounds tested, no specific antiviral effects could be witnessed against a broad range of viruses.
Retina The Retinal Clock Drives the Expression of Kcnv 2 , a Channel Essential for Visual Function and Cone Survival

PURPOSE. The gene Kcnv2 codes for the voltage-gated potassium channel subunit Kv8.2, which can coassemble with Kv2.1 subfamily members to constitute functional voltagegated potassium channels. Mutations in the Kcnv2 gene result in a retinal disorder designated ‘‘cone dystrophy with supernormal rod response (CDSRR),’’ revealing that Kcnv2 is essential for visual processing and cone survival. The aim of this study was to determine whether expression of Kcnv2 and Kv2.1 is under circadian regulation and may thus contribute to the clock-driven adjustment of photoreceptor function.
A generalised natural balance model and balance booster filter design for three level neutral point clamped converters

Three level Neutral Point Clamped (NPC) inverters exhibit a natural balancing property that can self-regulate the intermediate Neutral Point (NP) voltage to half the overall DC link voltage. However, the underlying mechanisms of this process are not well understood, its performance under various load conditions has not been properly explored, and the requirements and benefits of (RLC) balance booster filters to enhance the natural balancing response are not clear. This paper presents a generalised model of the NPC natural balancing process that allows these issues to be explored for various load structures and balance booster configurations (i.e. isolated wye, wye with a grounded star point, etc.). The model accurately predicts the dominant balancing time constant, identifies the harmonics that drive the balancing process, and can quantify the steady state balance booster losses for a designed target natural balance response. Extensive simulation and experimental tests have been performed to validate the theoretical model.
The cell cycle and related concepts in cell proliferation

A L R E A D Y in the nineteenth century Virchow, " the father of pathology " had concluded that a proper understanding of human pathology must depend upon the study of cells, their innate behaviour, and reactions to each other or to insults from the external world. In many instances pathological conditions result from, or in, changes in the proliferative behaviour of cells. Of these proliferative disorders perhaps the most serious and intractable are the malignant neoplasias, but benign neoplasias, hyperplasias and aplasias can all involve considerable distress, and present serious cause for concern. The study of cell proliferation is, therefore, both necessary and urgently to be pursued on practical grounds. It presents, at the same time, one of the most fascinating and fundamental challenges to the academic cell biologist. In this review I propose to discuss some of the more basic aspects of cell proliferation in mammals as currently understood. It has to be admitted that as yet the practical fruits of such studies remain somewhat sparse and the most I can do in this respect is to identify some of the more serious difficulties still standing in the way of ambitions to devise rational approaches to the control of cell proliferation in pathological states.
Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and -8, but not tumor necrosis factor, responses of the baboon to LD100 Escherichia coli.

Antitissue factor antibody attenuated the coagulopathic and lethal responses to LD100 Escherichia coli, whereas active site inhibited factor Xa inhibited only the coagulopathic response. In this study, we wished to determine: (1) whether active site inhibited factor VIIa blocks the coagulopathic and/or attenuates the lethal effects of LD100 E coli and (2) whether these effects are accompanied by attenuation of the inflammatory cytokine response to LD100 E coli. Eight baboons infused for 2 hours with LD100 E coli also were given five bolus infusions of DEGR VIIa of 280 microg/kg at T = -10 minutes, +2, 4, 6, and 8 hours and observed for changes in vital signs, and the concentrations of hemostatic components (fibrinogen, platelets, fibrin degradation products) and inflammatory mediators (tumor necrosis factor [TNF], interleukin-6 [IL-6], IL-8) at T = 0, 1, 2, 4, 6, and 8 hours. Eight control baboons were also infused with LD100 E coli alone and followed as described above. Four of the eight baboons treated with DEGR VIIa were permanent 7-day survivors versus none in the control group. The mean survival times for the treated and control groups were 116 +/- 22 and 26 +/- 8 hours, respectively. These values differed significantly from each other, (P = .0008). The decrease in platelet and fibrinogen concentrations and the increase in fibrin degradation products observed in the control group were significantly attenuated in the treated group, as was thrombosis of renal glomerular capillaries. Treatment with DEGR VIIa showed no effect on the peak TNF response to LD100 E coli at T = 2 hours (170 +/- 32 v 120 +/- 35 ng/mL). DEGR VIIa, however, did attenuate the IL-6 and IL-8 responses at T = 8 hours (ie, the IL-6 concentrations were 81 +/- 10 for treated and 1,256 +/- 236 for the control groups and the IL-8 concentrations were 28 +/- 3.9 for the treated and 60 +/- 8.2 for the control group). These values for IL-6 and IL-8 differed significantly from each other between the treated and control groups (P = .0001 and .0074, respectively). It should be noted that the initial responses of IL-6 and IL-8 up to T = 4 hours were not attenuated. We concluded that DEGR VIIa treatment attenuates inflammatory, as well as hemostatic system responses to LD100 E coli. We hypothesize that this occurs through interference with the assembly and/or interactions of tissue factor/VIIa complexes.
A Novel Intravertebral Tumor Model in Rabbits

OBJECTIVE:Although the majority of human epidural spinal metastases originate in the vertebral body, current animal models of spinal epidural tumors are limited to extraosseous tumor placement. We investigated the onset of paraparesis, radiographic changes (magnetic resonance imaging [MRI] and computed tomographic [CT] scans), and histopathological findings after intraosseous injection of VX2 carcinoma cells into the lower thoracic vertebrae of rabbits. METHODS:New Zealand white rabbits (n = 23) were injected with a 15-&mgr;l suspension containing 300,000 VX2 carcinoma cells in the lowest thoracic vertebral body. Lower extremity motor function was assessed daily. For the first 3 animals, MRI scans (T2-weighted and T1-weighted ± gadolinium) were acquired at postoperative day (POD) 14 and at the onset of paraparesis. Noncontrast CT scans were obtained on POD 7 and at the time of paraparesis. At the onset of paraparesis, the animals ware killed and the spines were dissected. After demineralization, hematoxylin and eosin cross sections were obtained. RESULTS:Before the onset of paraparesis, the CT and MRI scans revealed no gross tumor. At the onset of paraparesis, CT scans demonstrated an osteolytic tumor centered at the junction of the left pedicle and vertebral body, and MRI scans demonstrated epidural tumor arising from the body and compressing the spinal cord. Histopathological examination confirmed carcinoma arising from the body and extending into the canal, with widespread osteolytic activity. By POD 28, 72% of the animals had become paraparetic, and by the termination of the experiment on POD 120, 89% had become paraparetic. CONCLUSION:We established a novel intraosseous intravertebral tumor model in rabbits and characterized it with respect to onset of paraparesis, imaging features, and histopathological findings.
Non-destructive testing of machines to reduce maintenance time and cost

This paper presents time domain methods for early fault detection and severity analysis in non-destructive testing (NDT) of electromechanical rotating machines. An adaptive band pass filtering technique has been used to detect faulty pulses present in the signal emanating from a gearbox. A pulse position analysis method is used to calculate rotational speed of faulty components in the gearbox. Faulty pulse shape is further analyzed visually to estimate fault severity. Visual inspection of the gearbox is also performed to verify the results obtained through proposed methods. The proposed method is a useful input to manage maintenance personnel in an effective way and reduce maintenance costs.
The Procedural Egalitarian Solution

In this paper we introduce and analyze the procedural egalitarian solution for transferable utility games. This new concept is based on the result of a coalitional bargaining procedure in which egalitarian considerations play a central role. The procedural egalitarian solution is the first single-valued solution which coincides with the constrained egalitarian solution of Dutta and Ray (1989) on the class of convex games and which exists for any TU-game.
Kalman Filter-Based Disturbance Observer and its Applications to Sensorless Force Control

Force estimation plays a very important role in many application areas. The disturbance observer is significantly becoming the preferred approach since it offers distinct advantages of improving the robustness of force control and the accuracy of force estimation. However, one of the main disadvantages is the limitation from white Gaussian noise. This paper proposes an improved design methodology for the disturbance observer. The main contribution of the work described in this paper is the design of disturbance observers combined with a Kalman filter with a multisensor system. From the experimental results, white Gaussian noise was reduced and fast response in contact motion was achieved. The effectiveness of the proposed disturbance observer has been confirmed through comparisons with conventional methods in 1-d.o. f. linear motor systems.
Visitor Perceptions of Appropriate Management Actions Across the Recreation Opportunity Spectrum

An assumption of the Recreation Opportunity Spectrum is that direct or regulatory management strategies are more appropriate in modern or developed settings, but less appropriate in primitive settings, where indirect visitor management techniques are considered more appropriate. During the summer of 2003, 410 visitors to eight recreation settings (representing urban through primitive) in the American River watershed of California participated in a survey about their perceptions of 25 direct and indirect visitor management techniques. From four generic ROS settings described in both text and photos, participants chose the type of setting in which they most frequently recreated. For that chosen setting type, participants then rated the appropriateness of each of the 25 management actions. What we found suggests that the assumed linear relationship of direct and indirect management actions to the ROS is not fully supported. Instead, management actions are perceived differently in different types of recreation settings, and certain types of actions may be more accepted in certain ROS settings. Respondents who recreate most often in primitive settings were the most supportive (of the four groups) of direct or regulatory management actions, while respondents who recreate most often in semi-primitive motorized settings were the least supportive of direct or regulatory actions. The primitive setting respondents were less supportive of what we called engineering-type management actions. We found more differences among the ROS settings for direct management actions than we did for indirect actions, and our results suggest that management actions may play a smaller role in defining primitive settings, a moderate role in defining rural and urban settings, and a major role in defining semi-primitive motorized settings.
Reducing frequency reuse distance in cellular communications using trellis coded modulation

Cochannel interference is of great concern when planning modern cellular communication systems. The commonly used seven-cell frequency reuse pattern is based on the fact that the carrier to interference ratio (C/I) should be higher than 18 dB, which is based on subjective tests. A scheme based on trellis coded modulation (TCM) is proposed which enables the system to perform satisfactorily even at reduced levels of C/I. The proposed scheme gives the flexibility to use four or three cell repeat patterns, thus substantially increasing the spectral efficiency of the system. The scheme proposes the use of different TCMs in the different co-channel cells. Simulation results have shown that for a four-cell repeat pattern, the proposed scheme resulted in a bit error rate of 10/sup -5/ or better, with an outage probability of 0.86%.
Interleukin-7 in T-cell acute lymphoblastic leukemia: An extrinsic factor supporting leukemogenesis?

The malignant transformation and expansion of tumor cells involve both cell-autonomous mechanisms and microenvironment signals that regulate viability, nutrient utilization, metabolic activity and cell growth. In T-cell acute lymphoblastic leukemia (T-ALL), the co-culture of leukemic cells with stroma or the addition of particular cytokines prevents ex vivo spontaneous apoptosis. Interleukin-7 (IL-7), a cytokine produced by thymic and bone marrow stroma, increases the viability and proliferation of T-ALL cells. IL-7 induces the activation of Jak/STAT, MEK/Erk and PI3K/Akt signaling pathways in T-ALL cells. PI3K/Akt is the dominant pathway that mediates the effects of IL-7 on T-ALL. PI3K signaling is required for the induction of Bcl-2, the down-regulation of p27(kip1) and cell cycle progression. PI3K signaling is also required for the expression of the glucose transporter Glut1, uptake of glucose, activation of the metabolic machinery, increase in cell size, and maintenance of mitochondrial integrity. These observations suggest that substrates of molecular pathways activated by microenvironmental factors represent attractive molecular targets for the regulation of the viability and proliferation of T-ALL cells and provide the means for the development of novel treatment strategies.
Opioids in chronic noncancer pain: more faces from the crowd.

BACKGROUND The use of opioids for chronic noncancer pain (CNCP) remains very controversial. There are several randomized controlled trials, mostly in neuropathic pain, reporting efficacy and safety in the short term, but more long-term data are needed. Randomized controlled trials may be limited in providing data about the patients who benefit from often high-dose opioids over the long term. The present article provides details of these patients and adds to a previous case series. METHODS The present article contains 17 case reports of 11 CNCP conditions (followed to 2011) selected to illustrate specific issues from a survey of 84 patients with intractable CNCP treated with opioids and followed every three months for a median of 11 years. The previous published survey of this group reported outcomes of pain severity, adverse effects, pain relief, satisfaction, mood, problematic opioid use, tolerance, physical dependency, functional status, health-related quality of life (HRQL), immune status and sexual function. The outcome measures for that study included a numerical rating scale for pain, the Hospital Anxiety and Depression Scale, the Brief Pain Inventory Interference Scale, the Pain Disability Index and, for HRQL, the Short-Form Health Survey 12 version 2. Most patients in the total sample reported 50% or greater relief and a moderate improvement in disability. Scores for functional status and HRQL were not severely affected. Problematic use, tolerance and serious adverse effects, including constipation, were not major issues. These selected patient reports were chosen, not to illustrate optimal results, but rather important aspects of the diagnoses, opioids and doses, the paucity of intolerable adverse effects, particular issues (concurrent addiction history, bipolar disorder and combination therapy), disease-specific and other outcomes and duration of follow-up with complex pain problems. RESULTS Opioids were found to be safe and useful in the long term for these particular patients, as well as in the larger group from which they originated. INTERPRETATION These 17 reports of patients with intractable CNCP treated with opioids with some success over many years puts a face on more of the participants in the larger survey of 84 subjects, suggesting that this approach is effective and safe for some patients over many years.