Miracle-dz/UniFAR-FTUs huggingface dataset:
EVOLVING USE OF OKT3 MONOCLONAL ANTIBODY FOR TREATMENT OF RENAL ALLOGRAFT REJECTION

OKT3, a monoclonal antibody reactive with a surface glycoprotein present on all postthymic T cells, was used to treat the initial acute episode of rejection in 30 recipients of cadaveric donor renal allografts. The first 16 patients received 1–5 mg daily for a period of 10–21 days during which the azathioprine and prednisone dosages were sharply reduced. Circulating T cells were eliminated within minutes after the first OKT3 infusion. T cells reactive with OKT3 remained depressed throughout the period of treatment, although a significant number of cells reactive with other T cell subset reagents became detectable after several days of OKT3 treatment. In all instances, the established rejection episode was reversed in 2–8 days without the addition of other immunosuppressive measures. Recurrent rejection occurred in 12 of 16 patients, but with further conventional immunosuppression, 50% of the renal allografts remain functional 20–44 months after transplantation. Fever, chills, and, in some instances, dyspnea following the first dose of OKT3 were the only side-effects observed. Most patients developed antiidiotypic or antimouse immunoglobulin antibodies without apparent clinical sequelae. In the subsequent 14 patients, modifications in the protocol included a steroid bolus prior to the first OKT3 infusion, limitation of therapy to 10 days, resumption of maintenance levels of azathioprine and prednisone prior to discontinuing OKT3, and addition of 3 i.v. doses of cyclophosphamide at the termination of treatment. Respiratory symptoms after the first infusion of the reagent have been eliminated. Antibody responses to OKT3 have been reduced, occurring in 38% as compared with 73% of patients treated previously. Recurrent rejection episodes observed in 8 of 14 patients have been reversible in all but one case. Allograft survival is 86% at 6–17 months posttransplantation. In the entire series of 30 OKT3-treated patients, only 4 grafts (13%) have been lost because of recurrent episodes of rejection.
CD4-independent infection by human immunodeficiency virus type 2 strain ROD/B: the role of the N-terminal domain of CXCR-4 in fusion and entry

The human immunodeficiency virus type 2 (HIV-2) strain ROD/B can efficiently use the 7tm chemokine receptor CXCR-4 as a primary receptor to enter CD4-negative cells. We have stably expressed CXCR-4 on mink lung Mv-1-lu and feline kidney CCC cells (normally restrictive to HIV entry) and have shown efficient fusion, entry, and replication of ROD/B. Mutation of the two N-linked glycosylation sites on CXCR-4 (N11-->I, and N176-->Q) or pretreatment of CCC or Mv-1-lu cells expressing wild-type CXCR-4 with the glycosylation inhibitor tunicamycin increased fusion and entry by ROD/B. Deletion of portions of the N terminus of CXCR-4 resulted in a 3- to 10-fold decrease in cell-free infection by ROD/B and complete inhibition of cell-cell fusion by both ROD/B and another HIV-2 strain, CBL23. These data suggest that the N-terminal domain of CXCR-4 is involved in but is not essential for the efficient fusion of ROD/B with CD4-negative cells. Deletion of the C-terminal (intracellular) domain of CXCR-4 did not significantly affect entry by ROD/B, indicating that intracellular signalling through this domain does not play a significant role in entry by HIV-2.
Lifetime of the 23S1 state of heliumlike xenon (Xe52+).

A precision measurement has been made of the lifetime of the ${2}^{3}$${S}_{1}$ state of ${\mathrm{Xe}}^{52+}$ by beam-foil time-of-flight spectroscopy. The result is \ensuremath{\tau}${(2}^{3}$${S}_{1}$)=2.554(76)\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}12}$ sec, in agreement with theortical calculations. This measurement provides the most precise test of the theory of relativistic M1 decay and is sensitive for the first time to corrections of O(Z\ensuremath{\alpha}${)}^{2}$ to the leading term.
Flow-volume characteristics in the pulmonary circulation.

Isolated ferret and canine lungs were used to validate a method for assessing determinants of vascular volume in the pulmonary circulation. With left atrial pressure (Pla) constant at 5 mmHg, flow (Q) was raised in steps over a physiological range. Changes in vascular volume (delta V) with each increment in Q were determined as the opposite of changes in perfusion system reservoir weight or from the increase in lung weight. At each level of Q, the pulmonary arterial and left atrial cannulas were simultaneously occluded, allowing all vascular pressures to equilibrate at the same static pressure (Ps), which was equal to the compliance-weighted average pressure in the circulation before occlusion. Hypoxia (inspired PO2 25 Torr) in ferret lungs, which causes intense constriction in arterial extra-alveolar vessels, had no effect on the slope of the Ps-Q relationship, interpreted to represent the resistance downstream from compliance (control 0.025 +/- 0.006 mmHg.ml-1.min, hypoxia 0.030 +/- 0.013). The Ps-axis intercept increased from 8.94 +/- 0.50 to 13.43 +/- 1.52 mmHg, indicating a modest increase in the effective back-pressure to flow downstream from compliant regions. The compliance of the circulation, obtained from the slope of the relationship between delta V and Ps, was unaffected by hypoxia (control 0.52 +/- 0.08 ml/mmHg, hypoxia 0.56 +/- 0.08). In contrast, histamine in canine lungs, which causes constriction in veins, caused the slope of the Ps-Q relationship to increase from 0.013 +/- 0.007 to 0.032 +/- 0.006 mmHg.ml-1.min (P less than 0.05) and the compliance to decrease from 3.51 +/- 0.56 to 1.68 +/- 0.37 ml/mmHg (P less than 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)
Acute responses to exercise training and relationship with exercise adherence in moderate chronic obstructive pulmonary disease

The objectives of our study were to (i) compare, in chronic obstructive pulmonary disease (COPD) patients, acute responses to continuous training at high intensity (CTHI), continuous training at ventilatory threshold (CTVT) and interval training (IT); (ii) examine associations between acute responses and 12-week adherence; and (iii) investigate whether the relationship between acute responses and adherence is mediated/moderated by affect/vigour. Thirty-five COPD patients (forced expiratory volume in 1 second = 60.2 ± 15.8% predicted), underwent baseline assessments, were randomly assigned to CTHI, CTVT or IT, were monitored throughout about before training, and underwent 12 weeks of exercise training during which adherence was tracked. Compared with CTHI, CTVT was associated with lower respiratory exchange ratio, heart rate and respiratory rate (RR), while IT induced higher V ̇ E , V ̇ E / maximal voluntary ventilation, RR and lower pulse oxygen saturation. From pre- to post-exercise, positive affect increased (F = 9.74, p < 0.001) and negative affect decreased (F = 6.43, p = 0.005) across groups. CTVT reported greater end-exercise vigour compared to CTHI (p = 0.01) and IT (p = 0.02). IT exhibited lowest post-exercise vigour (p = 0.04 versus CTHI, p = 0.02 versus CTVT) and adherence rate (F = 6.69, p = 0.004). Mean V ̇ O 2 (r = −0.466, p = 0.007) and end-exercise vigour (r = 0.420, p = 0.017) were most strongly correlated with adherence. End-exercise vigour moderated the relationship between V ̇ O 2 and adherence (β = 2.74, t(32) = 2.32, p = 0.03). In summary, CTHI, CTVT and IT improved affective valence from rest to post-exercise and induced a significant 12-week exercise training effect. However, they elicited different acute physiological responses, which in turn were associated with differences in 12-week adherence to the target training intensity. This association was moderated by acute end-exercise vigour.
A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD.

BACKGROUND AST-120 (Kremezin; Kureha Chemical Industry Co Ltd, Tokyo, Japan) is an orally administered adsorbent showing adsorption ability superior to activated charcoal for certain organic compounds known to be precursors of substances that accumulate in patients with chronic kidney disease (CKD) and that are believed to accelerate the decline in kidney function. AST-120 is approved in Japan for prolonging time to hemodialysis therapy and improving uremic symptoms in patients with CKD. METHODS A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study was designed to examine the nephroprotective effects of 3 doses of AST-120 versus placebo in adult patients with moderate to severe CKD and elevated serum indoxyl sulfate levels while following an adequate protein-intake diet. Eligible patients were randomly assigned to 1 of 3 doses of AST-120 (0.9, 2.1, or 3.0 g) or placebo 3 times daily for 12 weeks. RESULTS AST-120 decreased serum indoxyl sulfate levels in a dose-dependent fashion. During the 12-week treatment period, AST-120 did not affect serum creatinine levels or 24-hour urine creatinine appearance. Significant improvements in malaise were observed in a dose-dependent fashion. All doses of AST-120 were well tolerated and did not adversely affect the general health status of patients. CONCLUSION Results suggest that the dose of 3 g 3 times daily is an optimal dose for the US population, and it may be useful in the treatment of patients with CKD. Because AST-120 did not directly affect serum creatinine levels or 24-hour urine creatinine appearance, the composite end point of doubling of serum creatinine level, transplantation, and dialysis therapy would be appropriate for a confirmatory phase III therapeutic outcome study.
Emerging treatments for pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by a progressive pulmonary vasculopathy with ensuing right heart failure if left untreated. In the 1980s, prior to the current treatment era, idiopathic PAH carried a very poor prognosis, with a median survival of 2.8 years from the time of diagnosis. Since then, continuous intravenous epoprostenol has been used for the treatment of severe PAH with tremendous success, improving haemodynamics, quality of life, exercise capacity, functional class and even survival. In addition, in the past 5 years there have been several new advances in the treatment of PAH; however, there is still no cure. A better understanding of how the currently available agents work together is essential to optimise the long-term care of patients with PAH. Ultimately, additional agents that target the underlying pulmonary vasculopathy and endothelial abnormalities are necessary to cure this fatal disease. This comprehensive review of the currently available and emerging novel therapies provides insight into future management of PAH patients.
Allosteric Regulation of Hsp70 Chaperones Involves a Conserved Interdomain Linker*

The 70-kDa heat shock proteins (Hsp70) are essential members of the cellular chaperone machinery that assists protein-folding processes. To perform their functions Hsp70 chaperones toggle between two nucleotide-controlled conformational states. ATP binding to the ATPase domain triggers the transition to the low affinity state of the substrate-binding domain, while substrate binding to the substrate-binding domain in synergism with the action of a J-domain-containing cochaperone stimulates ATP hydrolysis and thereby transition to the high affinity state. Thus, ATPase and substrate-binding domains mutually affect each other through an allosteric control mechanism, the basis of which is largely unknown. In this study we identified two positively charged, surface-exposed residues in the ATPase domain and a negatively charged residue in the linker connecting both domains that are important for interdomain communication. Furthermore, we demonstrate that the linker alone is sufficient to stimulate the ATPase activity, an ability that is lost upon amino acid replacement. The linker therefore is most likely the lever that is wielded by the substrate-binding domain and the cochaperone onto the ATPase domain to induce a conformation favorable for ATP hydrolysis. Based on our results we propose a mechanism of interdomain communication.
Energy and Communication Efficient Partitioning for Large-scale Finite Element Computations

Load balancing and partitioning are critical when it comes to parallel computations. Generally partitioning involves equally dividing the work and data among the processors, reducing processor idle time and communication costs. As we march towards exascale machines , the cost of data movement and load-imbalances therein are a major bottleneck for achieving scalability. Space Filling Curves (SFC) are commonly used for partitioning meshes for large-scale PDE systems. They are particularly common while dealing with adaptive meshes, such as those based on quadtrees and octrees. We propose an alternative SFC-based partitioning scheme where we allow some (user-specified) flexibility (tolerance or slack) in the work assignment, so as to minimize the data-dependencies across partitions. Effectively, we allow the flexibility in minimizing the communication-imbalance and overall energy consumption at the cost of a marginal increase in work load-imbalance. The traditional SFC-based partitioning can be recovered by setting the flexibility to zero. One of the main advantage of SFC based partitioning is the preservation of geometric locality of objects between processors. Depending on the SFC (i.e. Morton, Moore, Hilbert) that used for partitioning, the amount of locality preserved differs [1]. In this work we evaluate how the commonly used SFC’s, HILBERT and MORTON based partitioning behave with the proposed user specified flexibility in terms of reducing communication costs and overall energy consumption.
Impact on the quality of management of asthmatic children by monitoring of inflammation

Despite what appear to have been dramatic improvements in the understanding and management of established asthma, both prevalence and severity of disease has increased dramatically in the last 15-20 years both in the UK ( 5 ) and in other industrialised countries in the world (4). Furthermore, the condition remains incurable with no therapy to date having any effect on the natural history of the condition following established therapeutic protocols (20). It is clear that inflammatory mechanisms are important in the disease process and thus the focus of treatment has been directed away from symptom relief with bronchodilators towards the use of so-called disease modifying agents which affect inflammation (8). Only sodium cromoglycate and inhaled corticosteroids have a clear role in this respect. Neither normalise lung function, bronchial hyperreactivity or histology even with energetic use over long periods in patients with chronic established disease. There is, however, some suggestion that the use of very high dose inhaled and oral steroids for long periods of time does appreciably improve the situation and may, even in patients with milder disease, truly switch off inflammatory processes (12). The potential side effects of such an approach, particularly in childhood, are such that this would be at the expense of growth retardation and possibly other serious side effects (23). Under such circumstances, it is imperative that we should identify markers which will reliably predict the development of more chronic severe disease which might allow effective early intervention with both environmental and therapeutic measures. This may in the long-term be the only way of truly altering the natural history ofchildhood asthma.
iDMAa 2006: CODE Track Nine: Game Code Video Games as Learning Tools for Project Management

In this paper, we begin by discussing some of the statistics that reveal electronic gaming’s place as a major force in today’s economy. We next discuss two of the major problems involved with the usage of video games as a tool for teaching and learning in digital media: the issues of inconsistency and complexity. Gee’s pioneering work (2004) is used to establish some principles of gaming that transcend these problems and present a unique medium with which to examine the nature of digital media and its principles and tools. We expand upon Gee’s work to suggest specific ways that video games can be used to teach digital media students about a particular subset of digital media – in this case, that of project management, and speculate as to how this might be done in several genres of gaming. We conclude with a brief case study of our experiences in working with digital media students to build a video game that was used to teach fourth graders about African-American history and the Underground Railroad.
A Novel Cytotoxin from Clostridium difficileSerogroup F Is a Functional Hybrid between Two Other Large Clostridial Cytotoxins*

The large clostridial cytotoxins (LCTs) constitute a group of high molecular weight clostridial cytotoxins that inactivate cellular small GTP-binding proteins. We demonstrate that a novel LCT (TcdB-1470) from Clostridium difficile strain 1470 is a functional hybrid between “reference” TcdB-10463 andClostridium sordellii TcsL-1522. It bound to the same specific receptor as TcdB-10463 but glucosylated the same GTP-binding proteins as TcsL-1522. All three toxins had equal enzymatic potencies but were equally cytotoxic only when microinjected. When applied extracellularly TcdB-1470 and TcdB-10463 were considerably more potent cytotoxins than TcsL-1522. The small GTP-binding protein R-Ras was identified as a target for TcdB-1470 and also for TcsL-1522 but not for TcdB-10463. R-Ras is known to control integrin-extracellular matrix interactions from inside the cell. Its glucosylation may be a major determinant for the cell rounding and detachment induced by the two R-Ras-attacking toxins. In contrast, fibroblasts treated with TcdB-10463 were arborized and remained attached, with phosphotyrosine containing structures located at the cell-to-cell contacts and β3-integrin remaining at the tips of cellular protrusions. These components were absent from cells treated with the R-Ras-inactivating toxins. The novel hybrid toxin will broaden the utility of the LCTs for clarifying the functions of several small GTPases, now including also R-Ras.
An intuitive system for 3D avatar with high-quality

According to advancements in computer technology, there are lots of needs for customized contents, which show up a user as a main character. These needs are implemented in computer games for the first time. In these games, a user can easily create a game character which resembles him/her and is called avatar. But for the limit of game itself, the game supports the avatar with low quality. When the user wants realistic his/her avatar and uses conventional computer graphics, the user might be amazed at the high level avatar as well as the production costs and periods. In this paper, we suggest an intuitive system to generate the 3D avatar easily from the user's picture and user's minimum interaction. The result 3D avatar has high quality and resembles the user. Our system will be helpful at 3D UCC.
Site-specific Phosphorylation of the p65 Protein Subunit Mediates Selective Gene Expression by Differential NF-κB and RNA Polymerase II Promoter Recruitment*

Background: Phosphorylation of nuclear factor-κB (NF-κB) subunits is critical for NF-κB activity. Results: Mutation of phospho-acceptor sites within the p65 Rel homology domain influences NF-κB activity in a gene-dependent manner by altering p65 and RNA polymerase II promoter recruitment. Conclusion: Differential p65 phosphorylation serves as a code to target NF-κB transcriptional activity to distinct gene subsets. Significance: Our data provide insight into how NF-κB transcriptional specificity is achieved. Phosphorylation of NF-κB plays an important role in modulating transcriptional activity of NF-κB independently of inhibitor of κB (IκB) proteins. For the p65 subunit, multiple phosphorylation sites have been mapped in and adjacent to both the N-terminal Rel homology domain and the C-terminal transactivation domain. Their impact on NF-κB-dependent transcription, however, has never been assessed at a broader level. In this study, we evaluate the importance of differential p65 phosphorylation on four serine acceptor sites in the Rel homology domain for the expression of an array of NF-κB-dependent genes in endothelial cells. We find that inhibition of p65 phosphorylation on these serine residues targets NF-κB activity to distinctive gene subsets in a κB enhancer element-specific context. We show that the phosphorylation-dependent alterations in gene and protein expression are reflective of the amount of p65 and phosphorylated RNA polymerase II (p-RNAP II) bound to respective gene promoter regions. Depending on the gene subset, impaired gene expression was either a result of decreased p65 promoter recruitment or of a failure of bound p65 to recruit p-RNAP II. In conclusion, our findings demonstrate that site-specific p65 phosphorylation targets NF-κB activity to particular gene subsets on a global level by influencing p65 and p-RNAP II promoter recruitment.
Color-histogram-based tracking at 2000 fps

A high-speed vision system can be applied to color-histogram-based tracking at 2000 fps by hardware-implementing an improved CamShift algorithm. In the improved CamShift algorithm, the size, position, and orientation of a color-patterned object to be tracked in an image can be simultaneously extracted using only the hardware implementation of a color-histogram circuit module for calculating moment features of binary images quantized by 16 hue-based color bins. By hardware-implementing color-histogram circuit modules on a high-speed vision platform, IDP Express, the improved CamShift algorithm enables color-histogram-based tracking at 2000 fps for 512×511 pixel images in real-time. By installing our tracking system on a two-axis mechanical active vision system, we demonstrate the effectiveness of 2000 fps color-histogram-based tracking by performing several experiments of color-patterned objects, which are always tracked in the camera views even when they move rapidly under complicated backgrounds.
MVDR spectral estimation by spectral peak dichotomous search

Canonical correlation analysis (CCA) and minimum variance distortionless response (MVDR) are typical nonparametric spectral estimation methods based on matched filterbank theory. To avoid the common signal mismatch problem, an algorithm combining CCA and MVDR is proposed for peak frequency modification. It consists of two stages: a coarse-peak search in CCA spectrum, and followed with a fine-peak search using dichotomous search strategy in MVDR spectrum. Furthermore the new algorithm is extended to the magnitude squared coherence (MSC) spectral estimation. Simulations show that the peak frequency estimation accuracy is improved simply and efficiently, with only slight computation increased.