Miracle-dz/UniFAR-FTUs huggingface dataset:
The Additional Value of SPECT/CT in Lymphatic Mapping in Breast Cancer and Melanoma

The recently introduced SPECT/CT integrates the physiologic data of SPECT with the anatomic data of CT into a single image. The purpose of this pilot study was to explore the additional value of SPECT/CT in breast cancer patients and melanoma patients with inconclusive planar image findings. Methods: Thirty-one patients had planar lymphoscintigrams showing unexpected lymphatic drainage, 6 had lymphoscintigrams that were difficult to interpret, and 3 showed no drainage on planar imaging. SPECT/CT was performed immediately after delayed planar imaging. Results: In 4 patients, SPECT/CT showed 6 additional sentinel nodes, of which 2 were tumor-positive and led to upstaging and tailored management in 5% of patients. SPECT/CT depicted sentinel nodes in 3 patients whose delayed planar imaging had shown no drainage. Conclusion: SPECT/CT was of additional value in finding the exact anatomic location of sentinel nodes in patients with inconclusive planar image findings. SPECT/CT also detected sentinel nodes in addition to those found on planar images, and SPECT/CT detected sentinel nodes in patients whose planar images had shown none.
The ERK1/2 Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina

This study was conducted to determine the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in a time-dependent manner and the effect of extracellular-signal-regulated kinases-1/2 (ERK1/2) inhibition on the expressions of MMP-9, TIMP-1, and inflammatory biomarkers in the retinas of diabetic rats. The expression of MMP-9 was quantified by zymography, and the mRNA level of MMP-9 and TIMP-1 was quantified by RT-PCR. The expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was examined by Western blot analysis. MMP-9 expression was significantly higher in diabetic rat retinas compared to controls at all time points.TIMP-1 expression was nonsignificantly upregulated at 1week of diabetes and was significantly downregulated at 4 and 12 weeks of diabetes. Intravitreal administration of the ERK1/2 inhibitor U0126 prior to induction of diabetes decreased ERK1/2 activation, attenuated diabetes-induced upregulation of MMP-9, iNOS, IL-6, and TNF-α and upregulated TIMP-1 expression. In MMP-9 knockout mice, diabetes had no effect on retinal iNOS expression and its level remained unchanged. These data provide evidence that ERK1/2 signaling pathway is involved in MMP-9, iNOS, IL-6, and TNF-α induction in diabetic retinas and suggest that ERK1/2 can be a novel therapeutic target in diabetic retinopathy.
Distinct proteolytic processes generate the C and N termini of MHC class I-binding peptides.

Most of the MHC class I peptides presented to the immune system are generated during the course of protein breakdown by the proteasome. However, the precise role of the proteasome, e.g., whether this particle or some other protease generates the carboxyl (C) and amino (N) termini of the presented 8- to 10-residue peptides, is not clear. Here, we show that presentation on Db of ASNENMETM, a peptide from influenza nucleoprotein, and on Kb of FAPGNYPAL, a peptide from Sendai virus nucleoprotein, was blocked by the proteasome inhibitor, lactacystin. Using plasmid minigene constructs encoding oligopeptides of various lengths, we found that presentation of ASNENMETM from C-terminally extended peptides that contain this antigenic peptide plus three or five additional amino acids and presentation of FAPGNYPAL from a peptide containing FAPGNYPAL plus one additional C-terminal residue required the proteasome. In contrast, the proteasome inhibitor did not reduce presentation of cytosolically expressed ASNENMETM or FAPGNYPAL or N-terminally extended versions of these peptides, suggesting involvement of aminopeptidase(s) in trimming these N-extended variants. Accordingly, when the N termini of these 3N-extended peptides were blocked by acetylation, they were resistant to hydrolysis by cellular aminopeptidases and pure leucine aminopeptidase. Moreover, if introduced into the cytosol, Ag presentation of these peptides occurred to a much lesser extent than from their nonacetylated counterparts. Thus, the proteasome is essential for the generation of ASNENMETM and FAPGNYPAL peptides from the full-length nucleoproteins. Although it generates the C termini of these presented peptides, distinct aminopeptidase(s) can trim the N termini of these presented peptides to their proper size.
Comparison of birth weight between school health records and medical birth records in Denmark: determinants of discrepancies

Objective To compare reported birth weight (BW) information in school health records with BW from medical birth records, and to investigate if maternal and offspring characteristics were associated with any discrepancies. Design Register-based cohort study. Setting Denmark, 1973–1991. Participants The study was based on BW recorded in the Copenhagen School Health Records Register (CSHRR) and in The Medical Birth Register (MBR). The registers were linked via the Danish personal identification number. Primary and secondary outcome measures Statistical comparisons of BW in the registers were performed using t tests, Pearson's correlation coefficients, Bland-Altman plots and κ coefficients. Odds of BW discrepancies >100 g were examined by logistic regressions. Results The study population included 47 534 children. From 1973 to 1979 when BW was grouped in 500 g intervals in the MBR, mean BW differed significantly between the registers. During 1979–1991 when BW was recorded in 10 and 1 g intervals, mean BW did not significantly differ between the two registers. BW from both registers was highly correlated (0.93–0.97). Odds of a BW discrepancy significantly increased with parity, the child's age at recall and by marital status (children of married women had the highest odds). Conclusions Overall, BW information in school health records agreed very well with BW from medical birth records, suggesting that reports of BWs in school health records in Copenhagen, Denmark generally are valid.
Control of scrapie in the UK sheep population

SUMMARY Scrapie is a fatal transmissible spongiform encephalopathy (TSE) of sheep, endemic in the UK for centuries. Interest in the disease has been heightened over the last decade by the possibility of the related BSE being transmissible to and between sheep and a range of control interventions has been proposed and implemented. In this paper, we examined the effect of these policies and their components on observed case rate, susceptible allele frequency and R0 within the framework of a large simulation model of the British sheep population and its breeding and trading structure. We compared interventions with the natural fade-out of scrapie in the population through loss of susceptible genotypes in the absence of control. We compare the results of interventions with the natural course of the scrapie epidemic. Our model suggested that scrapie will persist in the national flock for 300–400 years with the impact on gene frequencies confined largely to high case-rate breeds, such as Shetland and Swaledale. We found the National Scrapie Plan (NSP) to be the most effective in terms of the removal of both susceptible genotypes and scrapie from the population. Complete eradication of scrapie can be achieved within 32 years (95% CI 23–43 years). The Compulsory Scrapie Flock Scheme (CSFS) is as effective as the NSP in reducing the observed case rate but has a limited impact on the frequencies of susceptible genotypes in the population overall. In combination with the NSP, eradication of scrapie is achieved >10 years faster. Of the components of the CSFS, the breeding and culling aspects are each almost as effective as the full policy, with trading restrictions contributing little. We have speculated on the impact of control measures on the possibility BSE infection within the national flock by examining their effect on flock R0 for BSE across different breeds.
Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction

The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology.
Exploiting Replicated Cache Blocks to Reduce L2 Cache Leakage in CMPs

Modern chip multiprocessors (CMPs) employ large L2 caches to reduce the performance gap between processors and off-chip memory. However, as the size of an L2 cache increases, its leakage power consumption also becomes a major contributor to the total power dissipation. Managing the leakage power of L2 caches, therefore, is an important issue in realizing low-power CMPs. In CMPs with private L2 caches, each processor makes a copy of the data in its local cache in order to access the data faster, which is called replication. In this paper, we propose a novel leakage management technique that dynamically turns off replications in private L2 caches for leakage power reduction by exploiting two key observations: 1) the cost of an extra cache miss due to the turned-off replication is small because the same cache block exists in another on-chip cache and 2) turning off the replication incurs no extra cache miss if it is invalidated by other processors in order to maintain cache coherence. Since blindly turning off the frequently accessed replications can degrade performance, the proposed technique dynamically controls the number of turned-off replications. The proposed technique can be implemented by slightly modifying the MESI protocol with a new turned-off shared (TOS) coherence state. The TOS state indicates that the corresponding block is shared by other caches but turned off. Experiments on a four-processor CMP with private L2 caches show that the proposed technique reduces the energy consumption of the L2 caches and the main memory by 19.4% on average, with less than 1% performance loss over the existing cache leakage management technique.
Performance targets, models and innovation in interactive system design

This paper presents an approach to designing interactive systems that enables critical performance parameters to be identified and models of performance to be constructed. The methods described are intended to enable designers to improve the performance of systems, and the provision of performance targets is expected to encourage innovation in design. An example is quoted in which digital camera technology was applied to the support of authors using paper source documents, to enable them to capture source text more rapidly and thus increase their productivity, measured in terms of words per hour. A model of the capture task was constructed, and was used to set a target time for capturing short text segments. This target was presented to a design team, who responded with an innovative interface incorporating auto-completion. A prototype auto-completion tool demonstrated that the performance target could be met.
Proof linking: a modular verification architecture for mobile code systems

This dissertation presents a critical rethinking of the Java bytecode verification architecture from the perspective of a software engineer. In existing commercial implementations of the Java Virtual Machine, there is a tight coupling between the dynamic linking process and the bytecode verifier. This leads to delocalized and interleaving program plans, making the verifier difficult to maintain and comprehend. A modular mobile code verification architecture, called Proof Linking, is proposed. By establishing explicit verification interfaces in the form of proof obligations and commitments, and by careful scheduling of linking events, Proof Linking supports the construction of bytecode verifier as a separate engineering component, fully decoupled from Java's dynamic linking process. This turns out to have two additional benefits: (1) Modularization enables distributed verification protocols, in which part of the verification burden can be safely offloaded to remote sites; (2) Alternative static analyses can now be integrated into Java's dynamic linking process with ease, thereby making it convenient to extend the protection mechanism of Java. These benefits make Proof Linking a competitive verification architecture for mobile code systems. A prototype of the Proof Linking Architecture has been implemented in an open source Java Virtual Machine, the Aegis VM (http://aegisvm.sourceforge.net). On the theoretical side, the soundness of Proof Linking was captured in three correctness conditions: Safety, Monotonicity and Completion. Java instantiations of Proof Linking with increasing complexity have been shown to satisfy all the three correctness conditions. The correctness proof had been formally verified by the PVS proof checker.
Bandwidth Selection in an EM-Like Algorithm for Nonparametric Multivariate Mixtures

In this paper we describe a method to select the bandwidth used in the nonparametric EM (npEM) algorithm of Benaglia et al. (2008). This method is a generalization of the Silverman’s rule of thumb used to select a bandwidth in kernel density estimation, and it results in one bandwidth for each mixture component and each block of conditionally independent and identically distributed repeated measures.
Throwing Good Money after Bad? Political and Institutional Influences on Sequential Decision Making in the Venture Capital Industry

This study focuses on the political and institutional influences that lead organizational decision makers to avoid terminating unsuccessful investments, even when there is competition and they have the experience and incentives to maximize profits. I examine multilevel influences on sequential investment decisions in the U.S. venture capital industry through a qualitative study of the investment process and a quantitative examination of venture capital investments between 1989 and 2004. Results show that venture capital firms become less likely to terminate investments as they participate in more rounds of financing, despite evidence that expected returns are declining over rounds. Intraorganizational politics, as well as coercive and normative pressures from co-investors and limited partners, may influence the decisions to continue or terminate investments, regardless of the expected returns. The findings suggest that organizational safeguards designed to mitigate individual biases may give rise to political and institutional influences, which may in turn undermine the effectiveness of the decision process.
Premedication and Infusion Reactions With Infliximab: Results From a Pediatric Inflammatory Bowel Disease Consortium

Background: Infusion reactions (IRs) are the most common adverse events associated with the use of infliximab for inflammatory bowel disease (IBD). Antipyretics, antihistamines, and corticosteroids have been used to prevent the development of IRs, but their efficacy is not known. We studied the proportion of pediatric patients receiving infliximab for IBD that developed IRs and the potential effects of premedication on IR. Methods: Uniformly collected data from a cohort of pediatric patients with IBD enrolled between January 2000 and May 2003 at 6 pediatric centers were analyzed. Data were retrospectively reviewed and analyzed. Results: A total of 1652 infusions given to 243 patients in 6 centers was analyzed. Overall, 60 IRs were recorded in 40 patients (3.6% of infusions, 16.5% of patients). Thirty‐three of 243 patients received premedication before the first IR (group 1). Two hundred ten patients did not receive premedication until the development of IRs, if at all (group 2). IRs were more common among patients in group 1 than in group 2 (12/33 versus 28/210, P < 0.01). Of the 28 patients in group 2 with IRs, 10 began receiving premedication with each subsequent infusion, 12 continued without premedications, and 6 had no further infusions recorded. Two of 10 who began receiving premedication had a subsequent IR versus 6 of 12 who did not receive premedication (P = 0.15). Conclusions: IRs occur in a small proportion of infusions among pediatric patients receiving infliximab for IBD. Premedication does not seem to prevent the development of IRs; however, once an IR has occurred, premedication may be indicated to prevent subsequent IRs.
Testing Tasks Management in Testing Cloud Environment

In testing Cloud environment testing tasks requested by different tenants have many uncertainties. The arriving time, deadline and the number of tasks are unknown in advance. Especially, the relationships between testing tasks and testing environments are very complex. How to efficiently manage these tasks is really a challenging problem. This paper studies the special features of testing tasks and presents a task management framework. We analyze the dependencies and conflicts associated with testing tasks and their related runtime environments, using rule matching mechanism to derive the relationships supported by domain knowledge. Based on these analyses, improved algorithms are introduced to cluster and dynamically schedule testing tasks to minimize the make-span or meet deadlines with the consideration of testing task resource requirements and Cloud resource utilization balance at the same time. A fault tolerance mechanism is built to cope with testing errors, whose results are studied to ameliorate clustering and scheduling algorithms. A suite of experiments compares the effectiveness of the proposed approach with other algorithms.
A Mixed Methods Exploration of Family Involvement in Medical Care for Older Adults with Serious Mental Illness

Objective: Many older persons with serious mental illness (SMI) suffer from high rates of comorbid medical conditions. Although families play a critical role in psychiatric illness management among adults with SMI, their contributions to improving health outcomes in this population has received little attention. This study explored family involvement in medical care for older adults with SMI. Methods: This mixed methods study involved analysis of quantitative data collected from older adults with SMI and cardiovascular risk (n = 28) participating in a pilot study of an intervention designed to improve patient-centered primary care augmented by qualitative interviews with their relatives (n = 13) to explore family involvement in medical care. Results: Approximately 89% of older adults with SMI reported family involvement in at least one aspect of their medical care (e.g., medication reminders, medical decision making). However, many family members reported that they were rarely involved in their relative's medical visits, and most did not perceive a need to be involved during routine care. Family members identified obesity as their relative's primary health concern and many wanted guidance from providers on effective strategies for supporting weight loss. Conclusions: Although many family members did not perceive a need to be involved in their relative's routine medical visits, they expressed interest in talking with providers about how to help their relative change unhealthy behaviors. Educating patients, families, and providers about the potential benefits of family involvement in medical care, including routine medical visits for persons with SMI and cardiovascular health risk may promote patient- and family-centered collaboration in this high-risk population.
Major urinary protein 5, a scent communication protein, is regulated by dietary restriction and subsequent re-feeding in mice

Major urinary proteins (Mups) are important for rodent scent communication and sexual behaviour. Recent evidence suggests that Mup1 may be regulated by fasting and re-feeding (RF). However, other Mup isoforms are poorly investigated, and data on the impact of long-term dietary restriction (DR) and ad libitum RF on Mup expression are missing. We investigated the effects of long-term 25 per cent DR and subsequent RF on Mup expression in male C57BL6 mice. DR significantly decreased Mup gene expression, hepatic and urinary protein levels compared with ad libitum (AL) fed control mice, with the greatest downregulation found for Mup5 expression. The decline in Mup expression was inverted by six months of RF. Because of inhibitory glucocorticoid response elements in the genomic sequence of the Mup5 gene, the observed inverse correlation of nuclear glucocorticoid receptor levels with Mup expression in response to DR and subsequent RF is a possible regulatory mechanism. Additionally, gene-expression-inhibiting histone deacetylation (H3K9) occurred in the region of the Mup5 gene in response to DR. We assume that Mup may act as a molecular switch linking nutritional status to sexual behaviour of mice, and thereby regulating male fertility and reproduction in response to food supply.
The interaction of C60 and its derivatives with a lipid bilayer via molecular dynamics simulations

Coarse-grained molecular dynamics simulations have been used to explore the interactions of C60 and its derivatives with lipid bilayers. Pristine C60 partitions into the bilayer core, whilst C60(OH)20 experiences a central energetic barrier to permeation across the bilayer. For intermediate levels of derivatization, e.g. C60(OH)10, this central barrier is smaller and there is an energetic well at the bilayer/water interface, thus promoting entry into cells via bilayer permeation whilst maintaining solubility in water.
Two-stage algorithm for extended target tracking by multistatic UWB radar

A two-stage extended target tracking algorithm for multistatic UWB radar is proposed. The first-stage tracking rejects clutter and multipath significantly and reduces the number of possible ghost targets in positioning and partially improves the data association performance for tracking in Cartesian coordinates. At the second stage, the Taylor series positioning algorithm is applied firstly to utilise the target states from all the 1D trackers to provide 2D Cartesian coordinates of targets. After that, the 2D tracker employs the nearest neighbour based Kalman filter to track targets. The algorithm performance has been compared with that of a conventional one-stage approach both on simulated and experimental data.