Miracle-dz/UniFAR-FTUs huggingface dataset:
Progress in Modeling of Protein Structures and Interactions Prediction versus Design Energy Function

The prediction of the structures and interactions of biological macromolecules at the atomic level and the design of new structures and interactions are critical tests of our understanding of the interatomic interactions that underlie molecular biology. Equally important, the capability to accurately predict and design macromolecular structures and interactions would streamline the interpretation of genome sequence information and allow the creation of macromolecules with new and useful functions. This review summarizes recent progress in modeling that suggests that we are entering an era in which high-resolution prediction and design will make increasingly important contributions to biology and medicine. I n 1973, Anfinsen demonstrated that the amino acid sequence of a protein completely specifies its three-dimensional structure and hence that the native structures of proteins are likely to correspond to global free-energy minima (1). Since then, the de novo structure prediction problem has been well posed—find the lowest free-energy con-formation for an amino acid sequence. Yet at the start of the structural genomics efforts in the late 1990s, computational methods remained far from achieving the high-resolution structures available from x-ray crystallography and nuclear magnetic resonance (NMR), and hence embarking on large-scale experimental structure determination with its associated high cost was well warranted. We suggest that recent progress in high-resolution modeling of biomolecules is such that, although the de novo folding problem is far from solved, computational structural biology is reaching a stage where it can contribute both to determining structures of naturally occurring biomolecules and the creation of new ones. There have been two distinct areas of development in molecular modeling methodology and software—the first aimed at simulating macromolecular dynamics, the second at prediction and design. We focus on the second area, and for the first we refer to recent reviews (2, 3). Two blind tests provide a gauge of progress in prediction of the structures of proteins and protein-protein complexes, namely CASP Ehttp://predictioncenter.org (4)^ and CAPRI ECritical Assessment of Protein Interactions ; http://capri.ebi. ac.uk/ (5, 6)^. Results obtained in the recent CASP and CAPRI experiments , together with recent design results, highlight progress in modeling. This review describes these recent results and outlines the physical basis for the new generation of computational models, the origins of improvement in modeling, and current challenges and bottlenecks. Prediction and design are inverse problems: The prediction problem is to find the lowest energy structure for a specified sequence, and the design problem, to find the …
Opposing intrinsic temporal gradients guide neural stem cell production of varied neuronal fates

Changes over time build neuronal diversity Although neural progenitors can keep generating new neurons, they can generate different neurons as the organism develops. Two different sections of the Drosophila brain, the mushroom bodies and the antennal lobes, show this characteristic, although the antennal lobes produce more different types of neurons over development than do the mushroom bodies. Liu et al. identified two RNA-binding proteins that manage this change over development in both settings. Science, this issue p. 317 Neuronal progenitors themselves change during development, even while continuing to generate new neurons. Neural stem cells show age-dependent developmental potentials, as evidenced by their production of distinct neuron types at different developmental times. Drosophila neuroblasts produce long, stereotyped lineages of neurons. We searched for factors that could regulate neural temporal fate by RNA-sequencing lineage-specific neuroblasts at various developmental times. We found that two RNA-binding proteins, IGF-II mRNA-binding protein (Imp) and Syncrip (Syp), display opposing high-to-low and low-to-high temporal gradients with lineage-specific temporal dynamics. Imp and Syp promote early and late fates, respectively, in both a slowly progressing and a rapidly changing lineage. Imp and Syp control neuronal fates in the mushroom body lineages by regulating the temporal transcription factor Chinmo translation. Together, the opposing Imp/Syp gradients encode stem cell age, specifying multiple cell fates within a lineage.
Post‐transplant outcomes of induction therapy for myeloma: Thalidomide and dexamethasone versus doxorubicin, vincristine, and dexamethasone prior to high‐dose melphalan with autologous stem cell support

High‐dose melphalan with autologous stem cell support improves survival as part of initial therapy for myeloma. Previous studies of pre‐transplant induction regimens have compared paraprotein response rates but not long‐term outcomes after transplant. We reviewed the records of all patients with multiple myeloma who received an autologous stem cell transplant at the University of Pennsylvania Medical Center. We compared outcomes for 69 patients who received high‐dose melphalan conditioning after January 1, 2003 as part of initial therapy for myeloma, including 41 patients who received anthracycline‐based induction (VAD or DVD) and 28 patients who received thalidomide and dexamethasone induction. Baseline characteristics in these two groups were not different, though potentially clinically important differences were apparent in assignment to post‐transplant consolidation and maintenance therapy. Despite similar response rates during induction therapy, thalidomide and dexamethasone induction was associated with better progression‐free survival (hazard ratio 0.18, P = 0.011) after transplant. This effect persisted in multivariable regression models including baseline characteristics and post‐transplant treatment. Overall survival was not different between the two groups. These results suggest that the use of thalidomide during induction therapy may lead to improved long‐term outcomes after transplant. Future trials comparing induction therapies should examine progression‐free and overall survival after transplant to confirm this benefit. Am. J. Hematol. , 2007. © 2007 Wiley‐Liss, Inc.
Estudi microsintàctic del verb «caldre» en el català antic i en l'actual

The article offers a microsyntactic study about the clitics position in the sentences with impersonal existential verbs belonging to the class of caldre ‘to be necessary’. We contrast the behavior of this deontic verb in Old Catalan and in two present dialects: Ribagorcan Catalan and Central Catalan. It is shown that Ribagorcan dialect is parallel to Old Catalan: clitics related to the infinitive subordinated verb appear adjoined to caldre, in the main clause. This is the case of the clitic u (= «ho») in Old Catalan example «No u cal dir ara» (Roig, Spill, 7048) and its Ribagorcan equivalent: «No ho cal dir ara». However, in Central Catalan, there is not clitic climbing. Clitic objects of the infinitive verb have to remain in the subordinate clause: No cal dir-ho. This type of microcomparative analysis reveal itself as a proper way to establish a solid base for future studies on comparative syntax.
Secure Outsourcing Mechanism for Linear Programming in Cloud Computing

Cloud Computing is a subscription based service where you can obtain the networked storage space and computer resources. In cloud computing model, the customers plug into the cloud to access IT resources which are priced and provided on demand services. This cloud computing model composed of five essential characteristics, three service models and four deployment models. Users can store their data in the cloud and there is a lot of personal information and potentially secure data that people store on their computers, and this information is now being transferred to the cloud. Here we must ensure the security of user's data, which is in stored in the cloud. This paper presents the secure outsourcing mechanism for linear programming in the cloud computing environment. Linear programming is an algorithmic and computational tool which captures the first order effects of various system parameters that should be optimized, and is essential to the engineering optimization. It has been widely used in various engineering disciplines that analyze and optimize real world systems, such as - packet routing, flow control, power management of data centers, etc.
Knowledge-based Subtractive Integration of mRNA and miRNA Expression Profiles to Differentiate Myelodysplastic Syndrome

The goal of our work is to integrate conventional mRNA expression profiles with miRNA expressions using the knowledge of their validated or predicted interactions in order to improve class prediction in genetically determined diseases. The raw mRNA and miRNA expression features become enriched or replaced by new aggregated features that model the mRNA-miRNA interaction. The proposed subtractive integration method is directly motivated by the inhibition/degradation models of gene expression regulation. The method aggregates mRNA and miRNA expressions by subtracting a proportion of miRNA expression values from their respective target mRNAs. The method is used to model the outcome or development of myelodysplastic syndrome, a blood cell production disease often progressing to leukemia. The reached results demonstrate that the integration improves classification performance when dealing with mRNA and miRNA profiles of comparable predictive power.
The influence of cognitive tasks on mentoring provided: Investigating the moderating influence of professionally educated staffs

Purpose – The main purpose of this article is to study the influence of cognitive tasks on mentoring provided and the moderating influence of professional teacher education. Design/methodology/approach – This cross-sectional survey was based on a questionnaire that was sent to a total of 435 employees from 29 pre-schools in Norway. A total of 284 responses were returned, a response rate of 65.3 per cent. Two research hypotheses were formulated. Confirmatory factor analysis (CFA) was used to develop three measurement models and structural equation modelling (SEM) based on multi-group analysis was used to test the hypotheses. Findings – The results revealed that cognitive tasks increase the occurrence of mentoring provided at work and professional teacher education moderates this relationship. Research limitations/implications – The use of convenience sampling and self-reports are discussed, especially related to representativeness and reporting biases. Practical implications – The findings implicate a need.
Autoimmune hemophilia at rescue

Acquired hemophilia is much more clinically severe than congenital hemophilia, and is more difficult to diagnose, also because cases are seen in an array of clinical settings that are not usually equipped to tackle them. In this perspective article Drs. Mannucci and Peyvandi examine the management of this condition. See related article on page 566.
Estimating the Effect of Human Base Excision Repair Protein Variants on the Repair of Oxidative DNA Base Damage

Epidemiologic studies have revealed a complex association between human genetic variance and cancer risk. Quantitative biological modeling based on experimental data can play a critical role in interpreting the effect of genetic variation on biochemical pathways relevant to cancer development and progression. Defects in human DNA base excision repair (BER) proteins can reduce cellular tolerance to oxidative DNA base damage caused by endogenous and exogenous sources, such as exposure to toxins and ionizing radiation. If not repaired, DNA base damage leads to cell dysfunction and mutagenesis, consequently leading to cancer, disease, and aging. Population screens have identified numerous single-nucleotide polymorphism variants in many BER proteins and some have been purified and found to exhibit mild kinetic defects. Epidemiologic studies have led to conflicting conclusions on the association between single-nucleotide polymorphism variants in BER proteins and cancer risk. Using experimental data for cellular concentration and the kinetics of normal and variant BER proteins, we apply a previously developed and tested human BER pathway model to (i) estimate the effect of mild variants on BER of abasic sites and 8-oxoguanine, a prominent oxidative DNA base modification, (ii) identify ranges of variation associated with substantial BER capacity loss, and (iii) reveal nonintuitive consequences of multiple simultaneous variants. Our findings support previous work suggesting that mild BER variants have a minimal effect on pathway capacity whereas more severe defects and simultaneous variation in several BER proteins can lead to inefficient repair and potentially deleterious consequences of cellular damage. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1000–8)
Image-guided thermochemical ablation: Theoretical and practical considerations

Purpose: To test thermochemical ablation for potential as a new method to coagulate tissue and create a prototype device for administration. Materials and Methods: Reactions of either HCl or acetic acid and either NH4OH or NaOH were run in triplicate in a gel phantom as a simple calorimeter. Data were recorded over a period of 5 minutes using concentrations from 1-12M in the case of HCl and NH4OH. Comparison reactions were run at 11M using each acid reacted with each base. Two early device prototypes were devised using readily available components. Results: Maximum temperature rise was nearly instantaneous and was observed to peak with the 12M solutions at 106ºC. The maximum temperatures in the 11M comparisons were seen with the strong acid HCl paired with the strong base NaOH. The lowest temperatures were seen with the weak acid acetic acid paired with the weak base NH4OH. Conclusion: Thermochemical ablation reactions can release adequate amounts of heat energy to cause tissue ablation.
A New Hybrid Model for Associative Reinforcement Learning

In this paper, a new model, addressing the Associative Reinforcement Learning (ARL) problem, based on learning automata and self organizing map is proposed. The model consists of two layers. The First layer comprised of a SOM which is utilized to quantize the state (context) space and the second layer contains of a team of learning automata which is used to select an optimal action in each state of the environment. First layer is mapped to the second layer via an associative function. In other words, each learning automaton is in correspondence with only one neuron of the self organizing map. In order to show the performance of the proposed method, it has been applied successfully to classification applications on Iris, Ecoli, and Yeast data sets, as examples of ARL task. The results of experiments show that the proposed method is reached the accuracy near to or even higher than the highest reported accuracy. The results obtained for Ecoli and Yeast data sets indicate that the method is able to classify in relatively high dimensional context space and high number of classes.
Generative leadership : Nurturing innovation in complex systems

This paper contributes a theoretical framework for generative leadership, a form of leadership that creates a context to stimulate innovation in complex systems. Our framework links theories of leadership with perspectives on innovation and complex systems to suggest that generative leadership involves balancing connectivity and interaction among individuals and groups in complex systems by managing complexity and institutionalizing innovation. By focusing on how generative leaders create conditions that nurture innovation rather than individual traits or creativity, our framework provides new directions for leadership research and policy implications for managers.
In vitro cellular responses in the RTG‐2 cell line to complex mixtures of dioxins and dioxin‐like PCDDs, PCDFs and PCBs

High‐resolution gas chromatography/mass spectrometry (HRGC/MS) is the standard method for analysing dioxin, furan and polybrominated retardants in hazardous waste. Determination of dioxin‐like compounds using in vitro bioassays such as ethoxyresorufin‐O‐deethylase (EROD) is an important tool to evaluate their Ah receptor‐mediated toxic effects, because it detects all arylhydrocarbon receptor ligands in a variety of sample matrices. In the present work, we compared RTG‐2 cell line EROD bioassay with HRGC/MS for assessing waste samples (liquid and solid) contaminated with polychlorinated dibenzo‐p‐dioxins and dibenzofurans, polychlorinated biphenyls (dioxin‐like PCBs) and other xenobiotics. For liquid samples, HRGC/MS‐toxic equivalent (HRGC/MS‐TEQ) values ranged from 273.26 to 5.84 ng TEQ l−1 and correlated well (correlation coefficient 0.99) with values obtained by EROD‐TEQ, which ranged from 128 to 2.5 ng TEQ l−1. For solid samples, HRGC/MS‐TEQ values ranged from 3.44 to 0.49 ng TEQ g−1 and correlated less well than liquid samples (correlation coefficient 0.64) with values obtained by EROD‐TEQ ranging from 2.27 to 0.93 ng TEQ g−1. The overestimation of RTG‐2 EROD‐TEQ (1.2 ± 0.92 of values established by HRGC/MS) and the absence of false‐negative results may limit analytical costs by eliminating the need for follow‐up GC/MS analysis on the negative samples. We suggest that RTG‐2 EROD bioassay is an inexpensive means for preliminary dioxin and furan positive screenings of waste samples. Copyright © 2010 John Wiley & Sons, Ltd.
Influence of Interferon-Alpha Combined with Chemo (Radio) Therapy on Immunological Parameters in Pancreatic Adenocarcinoma

Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combination of chemo (radio) therapies with interferon-2α. Low doses of interferon-2α led to a decrease in total leukocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2α therapy on the dendritic cells and NK (natural killer) cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-γ and IL-10 in the serum following the interferon-2α therapy. These data clearly demonstrate that pancreatic carcinoma patients also show an immunomodulatory response to interferon-2α therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumors of the mice treated with interferon-2α and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of immunosuppressive mechanisms induced by combined chemo-immunotherapy.
Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF‐κB‐independent, FoxO1‐dependent mechanism

Myostatin, a transforming growth factor‐beta (TGF‐β) super‐family member, has been well characterized as a negative regulator of muscle growth and development. Myostatin has been implicated in several forms of muscle wasting including the severe cachexia observed as a result of conditions such as AIDS and liver cirrhosis. Here we show that Myostatin induces cachexia by a mechanism independent of NF‐κB. Myostatin treatment resulted in a reduction in both myotube number and size in vitro, as well as a loss in body mass in vivo. Furthermore, the expression of the myogenic genes myoD and pax3 was reduced, while NF‐κB (the p65 subunit) localization and expression remained unchanged. In addition, promoter analysis has confirmed Myostatin inhibition of myoD and pax3. An increase in the expression of genes involved in ubiquitin‐mediated proteolysis is observed during many forms of muscle wasting. Hence we analyzed the effect of Myostatin treatment on proteolytic gene expression. The ubiquitin associated genes atrogin‐1, MuRF‐1, and E214k were upregulated following Myostatin treatment. We analyzed how Myostatin may be signaling to induce cachexia. Myostatin signaling reversed the IGF‐1/PI3K/AKT hypertrophy pathway by inhibiting AKT phosphorylation thereby increasing the levels of active FoxO1, allowing for increased expression of atrophy‐related genes. Therefore, our results suggest that Myostatin induces cachexia through an NF‐κB‐independent mechanism. Furthermore, increased Myostatin levels appear to antagonize hypertrophy signaling through regulation of the AKT‐FoxO1 pathway. J. Cell. Physiol. 209: 501–514, 2006. © 2006 Wiley‐Liss, Inc.
Resummation and NLO matching of event shapes with effective field theory

The resummed differential thrust rate in e{sup +}e{sup -} annihilation is calculated using soft-collinear effective theory (SCET). The resulting distribution in the two-jet region (T{approx}1) is found to agree with the corresponding expression derived by the standard approach. A matching procedure to account for finite corrections at T<1 is then described. There are two important advantages of the SCET approach. First, SCET manifests a dynamical seesaw scale q=p{sup 2}/Q in addition to the center-of-mass energy Q and the jet mass scale p{approx}Q{radical}((1-T)). Thus, the resummation of logs of p/q can be cleanly distinguished from the resummation of logs of Q/p. Second, finite parts of loop amplitudes appear in specific places in the perturbative distribution: in the matching to the hard function, at the scale Q, in matching to the jet function, at the scale p, and in matching to the soft function, at the scale q. This allows for a consistent merger of fixed order corrections and resummation. In particular, the total NLO e{sup +}e{sup -} cross section is reproduced from these finite parts without having to perform additional infrared regulation.
Compact Model for Inversion Charge in III–V Bulk MOSFET Including Non-Parabolicity

In this paper, Poisson-Schrödinger simulations of bulk MOSFETs with an InGaAs channel, including traps and nonparabolicity, are compared against experimental data. These simulations are later used to validate a compact model for the inversion charge in the channel as a function of the gate voltage. Finally, an expression for the long-channel drain current is derived from this inversion charge model, and confirmed with experimental data. This current model, adapted for alternative channel devices, is suitable for the evaluation of III-V MOSFET performance.
Frameworks : Why They Are Important and How to Apply Them Effectively

In today’s competitive, fast-paced computing industry, successful software must increasingly be (1) extensible to support successions of quick updates and additions to address new requirements and take advantage of emerging markets, (2) flexible to support a growing range of multimedia data types, traffic flows, and end-to-end quality of service (QoS) requirements, (3)portable to reduce the effort required to support applications on heterogeneous OS platforms and compilers, (4) reliable to ensure that applications are robust and tolerant to faults, (5)scalableto enable applications to handle larger numbers of clients simultaneously, and (6) affordable to ensure that the total ownership costs of software acquisition and evolution are not prohibitively high. It is hard to achieve these qualities, however, when: