Miracle-dz/UniFAR-FTUs huggingface dataset:
Conformational and Molecular Basis for Induction of Apoptosis by a p53 C-terminal Peptide in Human Cancer Cells*

A p53-derived C-terminal peptide induced rapid apoptosis in breast cancer cell lines carrying endogenous p53 mutations or overexpressed wild-type (wt) p53 but was not toxic to nonmalignant human cell lines containing wt p53. Apoptosis occurred through a Fas/APO-1 signaling pathway involving increased extracellular levels of Fas/FasL in the absence of protein synthesis, as well as activation of a Fas/APO-1-specific protease, FLICE. The peptide activity was p53-dependent, and it had no effect in three tumor cell lines with null p53. Furthermore, the C-terminal peptide bound to p53 protein in cell extracts. Thus, p53-dependent, Fas/APO-1 mediated apoptosis can be induced in breast cancer cells with mutant p53 similar to the recently described Fas/APO-1 induced apoptosis by wt p53. However, mutant p53 without p53 peptide does not induce a Fas/APO-1 activation or apoptosis. Docking of the computed low energy conformations for the C-terminal peptide with those for a recently defined proline-rich regulatory region from the N-terminal domain of p53 suggests a unique low energy complex between the two peptide domains. The selective and rapid induction of apoptosis in cancer cells carrying p53 abnormalities may lead to a novel therapeutic modality.
Availability of Spanish Prescription Labels: A Multi-State Pharmacy Survey

Background:Patient misunderstanding of prescription drug label instructions is a leading cause of medication errors. Among Latino patients, limited English proficiency is a major barrier to comprehension of medication instructions. Objectives:To determine the availability of Spanish prescription drug label instructions. Research Design:A telephone survey was conducted in 4 states selected due to either a rapid growth in their Latino population (GA, NC) or a large, existing Latino population (CO, TX). Subjects:A list of retail pharmacies was obtained from each state board of pharmacy. A simple random sample of 10 percent of pharmacies within each state was generated (N = 764). Measures:The ability of pharmacies to print prescription instructions in Spanish and the process for translating instructions. Results:Two hundred sixty-seven (34.9%) pharmacies reported no translation services, 166 (21.7%) reported limited translation services, and 331 (43.3%) stated they were able to perform translations. In bivariate analyses, significant differences between pharmacy characteristics and the availability of Spanish labels were noted. In multivariate analysis including pharmacy type, location, percentage Latino population, and state, only metropolitan location was found to be a significant independent predictor of pharmacies offering full Spanish translation services (adjusted odds ratio: 1.72, 95% confidence interval: 1.04–2.84). Conclusions:The majority of pharmacies surveyed offered limited or no translation services. Lack of translation services is not isolated to rural areas or locations with a marginal Latino population. Spanish-speaking patients encounter barriers to acquiring instructions that support the safe and effective use of medications.
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Applications using broadband digital wireless modulation require high-resolution low-power ADC over a bandwidth of few megahertz. For a WiFi or a WiMAX standard, an ADC of ~10b resolution in 5 to 20MHz bandwidth is needed. Its sampling frequency should be in a ratio of 5× the channel bandwidth to simplify the anti-aliasing filter. In order to integrate the ADC with the digital functions in an advanced CMOS technology, compliance with the thin-oxyde voltage supply is necessary.
Indoor pedestrian navigation using miniaturized low-cost MEMS inertial measurement units

The paper presents an indoor pedestrian navigation system using miniaturized low-cost MEMS inertial measurement units (IMU). The low-cost MEMS IMU comprises of a tri-axial accelerometer, a tri-axial gyroscope, a tri-axial magnetometer, which are widely available in most smartphones, tablets, and other handheld devices. Through comparison tests of the IMU fixed on chest and foot, we found that the foot-mounted location is the proximate position, reflecting human's waking kinetic. The tri-axial accelerometer is used to measure step events and to estimate step stride. Due to magnetic disturbance indoor and gyroscope drift error, we propose a quaternion-based extended Kalman filter (EKF) for heading estimation by combining the magnetometer data and gyroscope data. Because of their complementary characteristics, a better accuracy in the heading solution is got.
Ukraine Gas Pricing Policy: Distributional Consequences of Tariff Increases

Ukraine's gas pricing policy subsidizes gas and heating for all households. As the cost of imported gas rises, this policy increasingly weighs on government finances, sustains energy over-consumption, dampens investment in delivery systems, and undermines incentives for domestic production. However, gas price hikes have been deferred to the medium-term as they are politically unpopular. Through estimation of household demand functions by income quintiles to evaluate the distributional consequences of tarrif reform, this paper finds that tariff reforms combined with targeted social support can address the economic inefficiencies of the current pricing policy without large welfare costs to the lower income segments of the population.
Virtuous and vicious cycles on the road towards international supply chain management

An increasing number of companies claim to pursue international supply chain management (ISCM), but the empirical evidence of successful implementation programs is still scarce. This paper aims to contribute to theory‐building in this area by presenting an exploratory causal model of goals, barriers, and enablers on the road towards effective ISCM. The model was established in a workshop with a panel of content matter experts. The results point at a disturbingly gloomy picture of vicious cycles frustrating the implementation of effective ISCM strategies. Fortunately, it appears that it is possible to apply the same generic mechanisms to create a virtuous cycle, for instance by promoting cross‐functional careers and by actively responding to demanding customer needs. The challenge ahead is to test the model’s content and validity.
Conditional Predictions of Bond Prices and Returns

MODERN THEORIES of the term structure of interest rates posit that the values of default-free discount bonds of all maturities may be expressed as deterministic functions of a small number of state variables, which follow a continuous diffusion process. Arbitrage arguments of the type familiar in the options pricing literature may then be employed to derive a single partial differential equation which must be satisfied by the values of all such bonds. This differential equation typically involves as many unknown parameters as there are stochastic state variables, each of these parameters representing the market price of the risk associated with one of the stochastic state variables. The power of such arbitrage theories depends upon the number of relevant stochastic state variables being manageably small. ' Models with a single state variable have been studied by Brennan and Schwartz [1977], Cox, Ingersoll and Ross [1978], Dothan [1978], and Vasicek [1977], all of these authors taking the instantaneously riskless interest rate as the relevant state variable. Two state variable models, in which the second state variable is the exogenously determined stochastic rate of inflation or the price level, have been developed by Cox, Ingersoll and Ross [1978], and Richard [1978]. The Cox, Ingersoll and Ross model of the term structure is distinguished from all of the other work in this area by being derived within a general equilibrium framework. Cox, Ingersoll and Ross have pointed out that yields on bonds of different maturities are deterministic functions of the underlying state variables, so that if it is possible to invert this system and thereby express the state variables as twice differentiable functions of a vector of interest rates, then the vector of interest rates may be used as instruments for the state variables. Brennan and Schwartz [1979] have taken this approach in expressing the whole term structure of yields as a deterministic function of the instantaneous riskless interest rate, r, and the consol yield, 1. While this leaves the issue of the identity of the underlying state variables unresolved, it has the advantage for empirical purposes of eliminating from the partial differential equation one of the utility dependent market price of risk parameters.2 In Brennan and Schwartz [1979] preliminary evidence was presented of the ability of such a two-factor model to price a sample of Government of Canada bonds conditional on r and 1. In this paper the results of a more detailed empirical analysis of the model are presented: the intertemporal stability and predictive
Costameric proteins in human skeletal muscle during muscular inactivity

Costameres are regions that are associated with the sarcolemma of skeletal muscle fibres and comprise proteins of the dystrophin–glycoprotein complex and vinculin–talin–integrin system. Costameres play both a mechanical and a signalling role, transmitting force from the contractile apparatus to the extracellular matrix in order to stabilize skeletal muscle fibres during contraction and relaxation. Recently, it was shown that bidirectional signalling occurs between sarcoglycans and integrins, with muscle agrin potentially interacting with both types of protein to enable signal transmission. Although numerous studies have been carried out on skeletal muscle diseases, such as Duchenne muscular dystrophy, recessive autosomal muscular dystrophies and other skeletal myopathies, insufficient data exist on the relationship between costameres and the pathology of the second motor nerve and between costameric proteins and muscle agrin in other conditions in which skeletal muscle atrophy occurs. Previously, we carried out a preliminary study on skeletal muscle from patients with sensitive‐motor polyneuropathy, in which we analysed the distribution of sarcoglycans, integrins and agrin by immunostaining only. In the present study, we have examined the skeletal muscle fibres of ten patients with sensitive‐motor polyneuropathy. We used immunofluorescence and reverse transcriptase PCR to examine the distribution of vinculin, talin and dystrophin, in addition to that of those proteins previously studied. Our aim was to characterize in greater detail the distribution and expression of costameric proteins and muscle agrin during this disease. In addition, we used transmission electron microscopy to evaluate the structural damage of the muscle fibres. The results showed that immunostaining of α7B‐integrin, β1D‐integrin and muscle agrin appeared to be severely reduced, or almost absent, in the muscle fibres of the diseased patients, whereas staining of α7A‐integrin appeared normal, or slightly increased, compared with that in normal skeletal muscle fibres. We also observed a lower level of α7B‐ and β1D‐integrin mRNA and a normal, or slightly higher than normal, level of α7A‐integrin mRNA in the skeletal muscle fibres of the patients with sensitive‐motor polyneuropathy, compared with those in the skeletal muscle of normal patients. Additionally, transmission electron microscopy of transverse sections of skeletal muscle fibres indicated that the normal muscle fibre architecture was disrupted, with no myosin present inside the actin hexagons. Based on our results, we hypothesize that skeletal muscle inactivity, such as that found after denervation, could result in a reorganization of the costameres, with α7B‐integrin being replaced by α7A‐integrin. In this way, the viability of the skeletal muscle fibre is maintained. It will be interesting to clarify, by future experimentation, the mechanisms that lead to the down‐regulation of integrins and agrin in muscular dystrophies.
Inhibitory Effect of Interleukin-8 on the Secretion of Platelet-Activating Factor Acetylhydrolase by Human Decidual Macrophages

Objective: To determine whether interleukin-8 (IL-8) regulates platelet-activating factor acetylhydrolase (PAF-AH) secretion by decidual cells in vitro. Methods: Decidual macrophages were obtained from human term decidual tissue by enzymic digestion and Ficoll-Paque centrifugation. The effect of IL-8 and phorbol esters on the secretion of PAF-acetylhydrolase by these cells was examined. Results: IL-8 inhibited PAF-AH secretion by decidual macrophages in a dose-dependent manner. The inhibition was reversed partially by antibodies against tumor necrosis factor-α and IL-1β. IL-8-induced inhibition was blocked partially by the protein kinase C (PKC) inhibitors, sphingosine, and H-7 1-(5-isoquinoline sulfonyl)-2-methylpiperazine. A PKC activator, 12-O-tetradecanoyl phorbol 13-acetate, decreased PAF-AH secretion. Conclusion: IL-8 may increase the PAF concentration in the decidua via its inhibitory effect on PAF-AH secretion by decidual macrophages. IL-8-induced inhibition of enzyme secretion may have been mediated in part by PKC-dependent signal transduction.
Herbivore species richness and feeding complementarity affect community structure and function on a coral reef

Consumer effects on prey are well known for cascading through food webs and producing dramatic top-down effects on community structure and ecosystem function. Bottom-up effects of prey (primary producer) biodiversity are also well known. However, the role of consumer diversity in affecting community structure or ecosystem function is not well understood. Here, we show that herbivore species richness can be critical for maintaining the structure and function of coral reefs. In two experiments over 2 years, we constructed large cages enclosing single herbivore species, equal densities of mixed species of herbivores, or excluding herbivores and assessed effects on both seaweeds and corals. When compared with single-herbivore treatments, mixed-herbivore treatments lowered macroalgal abundance by 54–76%, enhanced cover of crustose coralline algae (preferred recruitment sites for corals) by 52–64%, increased coral cover by 22%, and prevented coral mortality. Complementary feeding by herbivorous fishes drove the herbivore richness effects, because macroalgae were unable to effectively deter fishes with different feeding strategies. Maintaining herbivore species richness appears critical for preserving coral reefs, because complementary feeding by diverse herbivores produces positive, but indirect, effects on corals, the foundation species for the ecosystem.
An Introduction to the Green Paradox: The Unintended Consequences of Climate Policies

How important is the Green Paradox? We address this question in three ways. First, we present a simple model explaining how announcing a future climate policy may increase carbon emissions today – the Green Paradox effect. This effect is a result of fossil fuel producers increasing their extraction today as a response to a reduction in future resource rents. Second, we examine the theoretical and empirical literature to assess whether green paradoxes are likely to occur, and if they are, whether they are big enough to be of concern for policy makers. We consider several factors that affect the existence of the green paradox, including long-term extraction costs, short-term extraction capacities, the mix of policy instruments, and potential spatial carbon leakage to countries that have no climate policy. We find that these and other factors can sometimes strengthen, but mostly weaken, the case for concern about the green paradox. Third, we identify the lessons the literature offers for policy makers. We argue that in designing climate policy, policy makers need to consider the supply side of the fossil fuel market.
Vaccination with Dukoral® against travelers’ diarrhea (ETEC) and cholera

There is currently only one vaccine available that provides protection against diarrhea caused by Vibrio cholerae and, to a lesser degree, enterotoxigenic Escherichia coli (ETEC). Adverse events of this oral whole-cell/recombinant B-subunit vaccine have been negligible. Protective efficacy against cholera is 85%, while protection against the heat-labile toxin of ETEC reaches 67%. There is still a need for data on protection of Western travelers against travelers’ diarrhea in general by Dukoral® vaccination. However, current studies show a protective effect of up to 43%. Although the vaccine is only licensed for vaccination against cholera in most Western countries, there is mounting evidence that the oral cholera vaccine is a valuable option to those traveling to high-risk endemic areas. Vaccination against cholera and ETEC should be recommended for at-risk travelers, in particular those with high exposure at their travel destination or high personal risks through fluid loss.
Influence of minor groove substituents on the structure of DNA Holliday junctions.

The inosine-containing sequence d(CCIGTACm(5)CGG) is shown to crystallize as a four-stranded DNA junction. This structure is nearly identical to the antiparallel junction formed by the parent d(CCGGTACm(5)()CGG) sequence [Vargason, J. M. , and Ho, P. S. (2002) J. Biol. Chem. 277, 21041-21049] in terms of its conformational geometry, and inter- and intramolecular interactions within the DNA and between the DNA and solvent, even though the 2-amino group in the minor groove of the important G(3). m(5)C(8) base pair of the junction core trinucleotide (italicized) has been removed. In contrast, the analogous 2,6-diaminopurine sequence d(CCDGTACTGG) crystallizes as resolved duplex DNAs, just like its parent sequence d(CCAGTACTGG) [Hays, F. A. , Vargason, J. M. , and Ho, P. S. (2003) Biochemistry 42, 9586-9597]. These results demonstrate that it is not the presence or absence of the 2-amino group in the minor groove of the R(3). Y(8) base pair that specifies whether a sequence forms a junction, but the positions of the extracyclic amino and keto groups in the major groove. Finally, the study shows that the arms of the junction can accommodate perturbations to the B-DNA conformation of the stacked duplex arms associated with the loss of the 2-amino substituent, and that two hydrogen bonding interactions from the C(7) and Y(8) pyrimidine nucleotides to phosphate oxygens of the junction crossover specify the geometry of the Holliday junction.
Differential CD40/CD40L Expression Results in Counteracting Antitumor Immune Responses1

Establishment of host-protective memory T cells against tumors is the objective of an antitumor immunoprophylactic strategy such as reinforcing T cell costimulation via CD40-CD40L interaction. Previous CD40-targeted strategies assumed that T cell costimulation is an all-or-none phenomenon. It was unknown whether different levels of CD40L expression induce quantitatively and qualitatively different effector T cell responses. Using mice expressing different levels of CD40L, we demonstrated that the greater the T cell CD40L expression the less tumor growth occurred; the antitumor T cell response was host-protective. Lower levels of CD40L expression on T cells induced IL-10-mediated suppression of tumor-regressing effector CD8+ T cells and higher productions of IL-4 and IL-10. Using mice expressing different levels of CD40 or by administering different doses of anti-CD40 Ab, similar observations were recorded implying that the induction of protumor or antitumor T cell responses was a function of the extent of CD40 cross-linking. IL-10 neutralization during priming with tumor Ags resulted in a stronger tumor-regressing effector T cell response. Using IL-10−/− DC for priming of mice expressing different levels of CD40L and subsequent transfer of the T cells from the primed mice to nu/nu mice, we demonstrated the protumor role of IL-10 in the induction of tumor-promoting T cells. Our results demonstrate that a dose-dependent cross-linking of a costimulatory molecule dictates the functional phenotype of the elicited effector T cell response. The T cell costimulation is a continuum of a function that induces not only graded T cell responses but also two counteracting responses at two extremes.
Governing the new metropolis

The expansion of globalising cities into global city-regions poses fundamental questions about how best to govern the new metropolis. Partly because of the relentless pace of change, these newly emerging metropolitan spaces are often reliant on inadequate urban-economic infrastructure and fragmented urban-regional planning and governance arrangements. Moreover, as the demand for more ‘appropriate’, widely understood to mean more flexible, networked and smart, forms of planning and governance increases, new expressions of territorial cooperation and conflict are emerging around issues of increased competitiveness, infrastructure development, the collective provision of services, and further governmentalised remapping(s) of state space. We identify four central tenets of the metropolitan region/governance debate and discuss their relevance for future research on city-regions: (1) periodisation and trajectories, (2) democracy and accountability, (3) form and function, and (4) fragility and mobilisation. These, we argue, pose key challenges for rethinking city-region governance within the emerging new metropolitan paradigm.
Inference based on Fuzzy Deformable Prototypes for information filtering in dynamic web repositories

In this paper, a novel document filtering model in dynamic web repositories based on fuzzy deformable prototypes is presented. This model is based on fuzzy hierarchical categorization of documents. It defines an easy process to deal with the incoming documents and an efficient method to update their structure. The process is performed comparing the fuzzy prototypes of document cluster with the available information about documents contents. It exploits conceptual-based filtering criteria and category-based filtering techniques to deliver to the user an intelligent structure of the documents. Since filtering is a dynamic process, the knowledge base can update the hierarchy of existing documents. The clusters hierarchy can be easily and efficiently updated when new documents income on the repository by means of an inference method which is based on fuzzy deformable prototypes.
Ferulates, amurenlactone A and amurenamide A from traditional Chinese medicine cortex Phellodendri Amurensis

Two new ferulate compounds, amurenlactone A (1) and amurenamide A (2), along with 11 known compounds have been isolated from the cortex of Phellodendron amurense. The structures of the new compounds were established based on 1D, 2D NMR and mass spectral analyzes. The known compounds were identified by comparison with authentic samples.
Automated Underwriting and the Profitability of Mortgage Securitization

This paper develops a game-theoretic model of mortgage securitization, which is then used to examine a potential effect of automated underwriting. The paper's primary supposition is that automated underwriting lowers the costs to competitive mortgage originators and a monopolist securitizer of identifying mortgage applicants who are good credit risks. Faced with lower underwriting costs, originators will screen a larger number of mortgage applicants in the hopes of holding more good risks in their portfolios and passing through more bad risks to the securitizer. This mounting adverse-selection problem causes the securitizer's expected revenues to decline; this effect can outweigh the cost-saving benefit of automated underwriting, causing the securitizer's return on equity to fall. Copyright American Real Estate and Urban Economics Association.