Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiotensin II blockade and low-protein diet produce additive therapeutic effects in experimental glomerulonephritis.

BACKGROUND Transforming growth factor-beta (TGF-beta) overexpression plays a key role in the accumulation of extracellular matrix in acute and chronic renal diseases. Recent studies have suggested that the degree of reduction in pathological TGF-beta overexpression can be used as a therapeutic index to evaluate the antifibrotic potential of pharmacological angiotensin II (Ang II) blockade in renal disease. Using this target, we found that treatment with the angiotensin I-converting enzyme inhibitor enalapril or the Ang II type 1 receptor antagonist losartan reduced TGF-beta overexpression more effectively at doses clearly higher than those required to control blood pressure. However, both forms of Ang II blockade were only partially effective in normalizing TGF-beta expression. This study investigated whether a greater antifibrotic, TGF-beta-reducing benefit can be achieved when Ang II blockade is combined with dietary protein restriction. METHODS Mesangioproliferative glomerulonephritis was induced in male Sprague-Dawley rats on a normal-protein diet. Treatment with a low-protein diet and/or maximally effective doses of enalapril or losartan was started one day after disease induction. On the fifth day, 24-hour urine protein excretion was measured. On the sixth day, cortical kidney tissue was taken for periodic acid-Schiff staining. Isolated glomeruli were used for mRNA extraction or were placed in culture for determination of production of TGF-beta1, the matrix protein fibronectin, and the protease inhibitor plasmin activator inhibitor type 1 (PAI-1) by enzyme-linked immunosorbent assay. RESULTS Compared with untreated nephritic animals on a normal-protein diet, a single treatment with enalapril, losartan, or low-protein diet significantly reduced glomerular TGF-beta production, albeit to a similar degree of approximately 45%. A moderate, but significant further reduction in pathological TGF-beta expression of a total of 65% for enalapril and 60% for losartan was achieved when these drugs were combined with low-protein feeding. This reduction in TGF-beta overexpression paralleled decreased proteinuria, glomerular matrix accumulation, and overproduction of fibronectin and PAI-1. CONCLUSIONS Ang II blockade and low-protein diet have additive effects on disease reduction, suggesting that disease progression in humans with chronic renal failure may be slowed more effectively when Ang II blockade and low-protein diet are combined. Since maximal pharmacological Ang II inhibition was used, it is likely that dietary protein restriction further reduces pathological TGF-beta overexpression by mechanisms different from those of enalapril or losartan.
The effect of measuring ambulatory blood pressure on nighttime sleep and daytime activity--implications for dipping.

BACKGROUND AND OBJECTIVES Ambulatory blood pressure (BP) monitoring is commonly used to assess the circadian pattern of BP. Circadian BP pattern is influenced by physical activity and sleep cycle. The effect of BP monitoring itself on the level of physical activity and sleep remains unknown. If BP monitoring affects these parameters, then monitoring itself may influence the circadian BP pattern. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS To assess the effect of ambulatory BP monitoring on sleep duration, sleep efficiency, and daytime activity, we measured physical activity using wrist actigraphy in 103 veterans with chronic kidney disease. After 6 to 7 days of continuous activity monitoring, participants underwent ambulatory BP monitoring with simultaneous actigraphy. The above experiment was repeated after 1 mo. RESULTS Among the top tertile of patients (most sleep), when wearing ambulatory BP patients spent less time in bed at night (-92 min, P < 0.0001), were less asleep during those hours (-98 min, P < 0.0001), and had reduced sleep efficiency (82% versus 77%, -5% P = 0.02). On the day of ambulatory BP monitoring, patients were more sedentary during waking hours (+27 minutes, P = 0.002). During ambulatory BP monitoring, waking after sleep onset more than median was associated with greater odds for nondipping (odds ratio 10.5, P = 0.008). CONCLUSIONS Ambulatory BP monitoring is associated with disturbed sleep and reduced physical activity, characteristics that influence dipping. Ambulatory BP monitoring may itself induce nondipping and may thus mitigate the prognostic significance of the dipping phenomenon.
An Isoform of the Neuronal Cyclin-dependent Kinase 5 (Cdk5) Activator (*)

Neuronal Cdc2-like kinase is a heterodimer of Cdk5 and a 25-kDa subunit that is derived from a 35-kDa brain- and neuron-specific protein called the neuronal Cdk5 activator (p35/p25) (Lew, J., Huang, Q.-Q., Qi, Z., Winkfein, R. J., Aebersold, R., Hunt, T., and Wang, J. H.(1994) Nature 371, 423-426; Tsai, L. H. , Delalle, I. , Caviness, V. S. , Jr., Chae, T. , and Harlow, E. (1994) Nature 371, 419-423). Upon screening of a human hippocampus library with a bovine Nck5a cDNA, we uncovered a distinct clone encoding a 39-kDa isoform of Nck5a. The isoform, designated the neuronal Cdk5 activator isoform (p39), showed a high degree of sequence similarity to p35 with 57% amino acid identity. Northern blot analysis detected its mRNA transcript in bovine and rat cerebrum and cerebellum, but not in any other rat tissues examined. In situ hybridization showed that Nck5ai was enriched in CA1 to CA3 of the hippocampus, but absent in the fimbria of hippocampal formation. Among seven cell lines in proliferating cultures, only PC12 and N2A, two cell lines capable of differentiating into neuron-like cells, were found to contain Nck5ai mRNA. A 30-kDa truncated form of Nck5ai expressed as a glutathione S-transferase fusion protein in Escherichia coli] was found to associate with Cdk5 to form an active Cdk5 kinase. Thus, the isoform shares many common characteristics with p35, including Ckd5 activating activity and brain- and neuron-specific expression. Both proteins show limited sequence homology to cyclins, suggesting that they define a new family of cyclin-dependent kinase-activating proteins.
Pharmaceutical interventions for mitigating an influenza pandemic: modeling the risks and health-economic impacts

Model-based analyses built on burden-of-disease and cost–effectiveness theory predict that pharmaceutical interventions may efficiently mitigate both the epidemiologic and economic impact of an influenza pandemic. Pharmaceutical interventions typically encompass the application of (pre)pandemic influenza vaccines, other vaccines (notably pneumococcal), antiviral treatments and other drug treatment (e.g., antibiotics to target potential complications of influenza). However, these models may be too limited to capture the full macro-economic impact of pandemic influenza. The aim of this article is to summarize current health-economic modeling approaches to recognize the strengths and weaknesses of these approaches, and to compare these with more recently proposed alternative methods. We conclude that it is useful, particularly for policy and planning purposes, to extend modeling concepts through the application of alternative approaches, including insurers’ risk theories, human capital approaches and sectoral and full macro-economic modeling. This article builds on a roundtable meeting of the Pandemic Influenza Economic Impact Group that was held in Boston, MA, USA, in December 2008.
More indirect evidence of potential neuroprotective benefits of angiotensin receptor blockers.

Angiotensin II is a potent vasoactive substance that has a variety of actions, including vasoconstriction, aldosterone release, and cell growth. Angiotensin receptor blockers (ARBs) are increasingly being used for the treatment of hypertension and in the prevention of cardiovascular events, due to their favourable efficacy profile, tolerability, and ease of use. However, there is much uncertainty over the beneficial effects of ARBs that extend beyond the control of blood pressure, for example, in the protection from ischaemic brain injury [1]. The paper by Fuentes et al. [2], therefore, adds to this controversy by demonstrating, for the first time, a specific neuroprotective effect of pretreatment with ARBs in the setting of acute ischaemic stroke in humans.
Improving the Cost-Effectiveness of Visual Devices for the Control of Riverine Tsetse Flies, the Major Vectors of Human African Trypanosomiasis

Control of the Riverine (Palpalis) group of tsetse flies is normally achieved with stationary artificial devices such as traps or insecticide-treated targets. The efficiency of biconical traps (the standard control device), 1×1 m black targets and small 25×25 cm targets with flanking nets was compared using electrocuting sampling methods. The work was done on Glossina tachinoides and G. palpalis gambiensis (Burkina Faso), G. fuscipes quanzensis (Democratic Republic of Congo), G. f. martinii (Tanzania) and G. f. fuscipes (Kenya). The killing effectiveness (measured as the catch per m2 of cloth) for small targets plus flanking nets is 5.5–15X greater than for 1 m2 targets and 8.6–37.5X greater than for biconical traps. This has important implications for the costs of control of the Riverine group of tsetse vectors of sleeping sickness.
Calpain-mediated cleavage of DARPP-32 in Alzheimer’s disease

Toxicity induced by aberrant protein aggregates in Alzheimer's disease (AD) causes synaptic disconnection and concomitant progressive neurodegeneration that eventually impair cognitive function. cAMP‐response element‐binding protein (CREB) is a transcription factor involved in the molecular switch that converts short‐term to long‐term memory. Although disturbances in CREB function have been suggested to cause memory deficits in both AD and AD animal models, the mechanism of CREB dysfunction is still unclear. Here, we show that the dopamine‐ and cAMP‐regulated phosphoprotein 32 kDa (DARPP‐32), a key inhibitor of protein phosphate‐1 (PP‐1) that regulates CREB phosphorylation, is cleaved by activated calpain in both AD brains and neuronal cells treated with amyloid‐β or okadaic acid, a protein phosphatase‐2A inhibitor that induces tau hyperphosphorylation and neuronal death. We found that DARPP‐32 is mainly cleaved at Thr153 by calpain and that this cleavage of DARPP‐32 reduces CREB phosphorylation via loss of its inhibitory function on PP1. Our results suggest a novel mechanism of DARPP‐32–CREB signalling dysregulation in AD.
MIMO Linear Equalization With an$H^infty$Criterion

In this paper, we study the problem of linearly equalizing the multiple-input multiple-output (MIMO) communications channels from an$H^infty$point of view. $H^infty$estimation theory has been recently introduced as a method for designing filters that have acceptable performance in the face of model uncertainty and lack of statistical information on the exogenous signals. In this paper, we obtain a closed-form solution to the square MIMO linear$H^infty$equalization problem and parameterize all possible$H^infty$-optimal equalizers. In particular, we show that, for minimum phase channels, a scaled version of the zero-forcing equalizer is$H^infty$-optimal. The results also indicate an interesting dichotomy between minimum phase and nonminimum phase channels: for minimum phase channels the best causal equalizer performs as well as the best noncausal equalizer, whereas for nonminimum phase channels, causal equalizers cannot reduce the estimation error bounds from their a priori values. Our analysis also suggests certain remedies in the nonminimum phase case, namely, allowing for finite delay, oversampling, or using multiple sensors. For example, we show that$H^infty$equalization of nonminimum phase channels requires a time delay of at least$l$units, where$l$is the number of nonminimum phase zeros of the channel.
A correlative microscopy approach relates microtubule behaviour, local organ geometry, and cell growth at the Arabidopsis shoot apical meristem

Cortical microtubules (CMTs) are often aligned in a particular direction in individual cells or even in groups of cells and play a central role in the definition of growth anisotropy. How the CMTs themselves are aligned is not well known, but two hypotheses have been proposed. According to the first hypothesis, CMTs align perpendicular to the maximal growth direction, and, according to the second, CMTs align parallel to the maximal stress direction. Since both hypotheses were formulated on the basis of mainly qualitative assessments, the link between CMT organization, organ geometry, and cell growth is revisited using a quantitative approach. For this purpose, CMT orientation, local curvature, and growth parameters for each cell were measured in the growing shoot apical meristem (SAM) of Arabidopsis thaliana. Using this approach, it has been shown that stable CMTs tend to be perpendicular to the direction of maximal growth in cells at the SAM periphery, but parallel in the cells at the boundary domain. When examining the local curvature of the SAM surface, no strict correlation between curvature and CMT arrangement was found, which implies that SAM geometry, and presumed geometry-derived stress distribution, is not sufficient to prescribe the CMT orientation. However, a better match between stress and CMTs was found when mechanical stress derived from differential growth was also considered.
An improved sum-product estimate for general finite fields

An improved sum-product estimate for subsets of a finite field whose order is not prime is provided. It is shown, under certain conditions, that max{|A+A|,|A·A|}≫|A|12/11(log2|A|)5/11. This new estimate matches, up to a logarithmic factor, the current best known bound obtained over prime fields by Rudnev.
The heat shock factor family from Triticum aestivum in response to heat and other major abiotic stresses and their role in regulation of heat shock protein genes

Heat shock factors (Hsfs) play a central regulatory role in acquired thermotolerance. To understand the role of the major molecular players in wheat adaptation to heat stress, the Hsf family was investigated in Triticum aestivum. Bioinformatic and phylogenetic analyses identified 56 TaHsf members, which are classified into A, B, and C classes. Many TaHsfs were constitutively expressed. Subclass A6 members were predominantly expressed in the endosperm under non-stress conditions. Upon heat stress, the transcript levels of A2 and A6 members became the dominant Hsfs, suggesting an important regulatory role during heat stress. Many TaHsfA members as well as B1, C1, and C2 members were also up-regulated during drought and salt stresses. The heat-induced expression profiles of many heat shock protein (Hsp) genes were paralleled by those of A2 and A6 members. Transactivation analysis revealed that in addition to TaHsfA members (A2b and A4e), overexpression of TaHsfC2a activated expression of TaHsp promoter-driven reporter genes under non-stress conditions, while TaHsfB1b and TaHsfC1b did not. Functional heat shock elements (HSEs) interacting with TaHsfA2b were identified in four TaHsp promoters. Promoter mutagenesis analysis demonstrated that an atypical HSE (GAACATTTTGGAA) in the TaHsp17 promoter is functional for heat-inducible expression and transactivation by Hsf proteins. The transactivation of Hsp promoter-driven reporter genes by TaHsfC2a also relied on the presence of HSE. An activation motif in the C-terminal domain of TaHsfC2a was identified by amino residue substitution analysis. These data demonstrate the role of HsfA and HsfC2 in regulation of Hsp genes in wheat.
Syntactic Proofs of Compositional Compiler Correctness

Semantic preservation by compilers for higher-order languages can be verified using simple syntactic methods. At the heart of classic techniques are relations between source-level and target-level values. Unfortunately, these relations are specific to particular compilers, leading to correctness theorems that have nothing to say about linking programs with functions compiled by other compilers or written by hand in the target language. Theorems based on logical relations manage to avoid this problem, but at a cost: standard logical relations do not apply directly to programs with non-termination or impurity, and extensions to handle those features are relatively complicated, compared to the classical compiler verification literature. In this paper, we present a new approach to “open” compiler correctness theorems that is “syntactic” in the sense that the core relations do not refer to semantics. Though the technique is much more elementary than previous proposals, it scales up nicely to realistic languages. In particular, untyped and impure programs may be handled simply, while previous work has addressed neither in this context. Our approach is based on the observation that it is an unnecessary handicap to consider proofs as black boxes. We identify some theorem-specific proof skeletons, such that we can define an algebra of nondeterministic compilations and their proofs, and we can compose any two compilations to produce a correct-by-construction result. We have prototyped these ideas with a Coq implementation of multiple CPS translations for an untyped Mini-ML source language with recursive functions, sums, products, mutable references, and exceptions.
New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4(a) receptor splice variant: roles in receptor targeting

The 5-hydroxytryptamine type 4 receptor (5-HT4R) is involved in learning, feeding, respiratory control and gastrointestinal transit. This receptor is one of the G-protein-coupled receptors for which alternative mRNA splicing generates the most variants that differ in their C-terminal extremities. Some 5-HT4R variants (a, e and f) express canonical PDZ ligands at their C-termini. Here, we have examined whether some mouse 5-HT4R variants associate with specific sets of proteins, using a proteomic approach based on peptide-affinity chromatography, two-dimensional electrophoresis and mass spectrometry. We have identified ten proteins that interact specifically with the 5-HT4(a)R and three that only associate with the 5-HT4(e)R. Most of them are PDZ proteins. Among the proteins that associated specifically with the 5-HT4(a)R variant, NHERF greatly modified its subcellular localization. Moreover, NHERF recruited the 5-HT4(a)R to microvilli, where it localized with activated ezrin, consistent with the role of 5-HT4(a)R in cytoskeleton remodelling. The 5-HT4(a)R also interacted with both the constitutive and inducible (upon methamphetamine treatment) forms of the recently cloned sorting nexin 27 (SNX27a and b, respectively). We found that SNX27a redirected part of 5-HT4(a)R to early endosomes. The interaction of the 5-HT4R splice variants with distinct sets of PDZ proteins might specify their cellular localization as well as their signal transduction properties.
A Reverse Auction for Toxic Assets

The proposed 2008 TARP auction was intended to facilitate rapid purchases by the U.S. department of Treasury of a wide array of mortgage-backed securities in order to remove these “toxic assets” from the portfolios of financially stressed banks. The Treasury had selected a Reference Price design whereby bids to sell different securities would be normalized or “scored” by reference prices that reflect estimates of relative values. Although the auction was suspended just prior to the 2008 Presidential election, we continued with a series of laboratory experiments aimed at evaluating the performance of Reference Price auctions relative to several benchmark conditions. The experimental results indicate that a simple Reference Price auction can be an effective mechanism for avoiding serious effects of adverse selection and strategic bid manipulation, even when reference prices are not set accurately. An econometric analysis of bidding patterns and auction outcomes reveals how underlying behavior produces efficiency differences in this common-value framework.
ELF‐magnetic flux densities measured in a city environment in summer and winter

Epidemiological studies have indicated a connection between extremely low frequency magnetic flux densities above 0.4 µT (time weighted average) and childhood leukemia risks. This conclusion is based mainly on indoor exposure measurements. We therefore regarded it important to map outdoor magnetic flux densities in public areas in Trondheim, Norway. Because of seasonal power consumption variations, the fields were measured during both summer and winter. Magnetic flux density was mapped 1.0 m above the ground along 17 km of pavements in downtown Trondheim. The spectrum was measured at some spots and the magnetic flux density emanated mainly from the power frequency of 50 Hz. In summer less than 4% of the streets showed values exceeding 0.4 µT, increasing to 29% and 34% on cold and on snowy winter days, respectively. The average levels were 0.13 µT (summer), 0.85 µT (winter, cold), and 0.90 µT (winter, snow), with the highest recorded value of 37 µT. High spot measurements were usually encountered above underground transformer substations. In winter electric heating of pavements also gave rise to relatively high flux densities. There was no indication that the ICNIRP basic restriction was exceeded. It would be of interest to map the flux density situation in other cities and towns with a cold climate. Bioelectromagnetics 29:20–28, 2008. © 2007 Wiley‐Liss, Inc.
Match and manage: the use of knowledge matching and project management to integrate knowledge in collaborative inbound open innovation

Despite mounting evidence on the potential benefits of inbound open innovation, little is known about how firms purposefully manage inflows of knowledge. We investigate the use of two knowledge governance procedures—project management and knowledge matching—in collaborative inbound open innovation. Our findings suggest that, in addition to “knowledge-precursors,” which the literature on open innovation and absorptive capacity has shown to be important for the integration of external knowledge, the firm’s choice of knowledge governance matters for innovation performance.
Evaluating approaches for solving the area restriction model in harvest scheduling.

We survey three integer-programming approaches for solving the area restriction model (ARM) for harvest scheduling. We describe and analyze each of these approaches in detail, comparing them both from a modeling and computational point of view. In our analysis of these formulations as modeling tools we show how each can be extended to incorporate additional harvest scheduling concerns. In our computational analysis we illustrate the strengths and weaknesses of each formulation as a practical optimization tool by studying harvest scheduling in four North American forests.