Miracle-dz/UniFAR-FTUs huggingface dataset:
Mixed Matrix Method Provides A Reliable Metabolite Exposure Comparison for Assessment of Metabolites in Safety Testing (MIST).

BACKGROUND The regulatory guidances on metabolites in safety testing (MIST) by US Food and Drug Administration (FDA) and International Conference on Harmonisation (ICH) describe the necessity to assess exposures of major circulating metabolites in humans at steady state relative to exposures achieved in nonclinical safety studies prior to the initiation of large scale clinical trials. This comparison can be accomplished by measuring metabolite concentrations in animals and humans with validated bioanalytical methods. However, bioanalysis of metabolites in multiple species and multiple studies is resource intensive and may impact the timelines of clinical studies. METHOD A simple, reliable and accurate method has been developed for quantitative assessment of metabolite coverage in preclinical safety species by mixing equal volume of human plasma with blank plasma of animal species and vice versa followed by an analysis using LC-SRM or LC-HRMS. Here, we explored the reliability and accuracy of this method in several development projects at Genentech and compared the results to those obtained from validated bioanalytical methods. RESULTS The mixed-matrix method provided comparable accuracy (within ±20%) to those obtained from validated bioanalysis but does not require authentic standards or radiolabeled compounds, which could translate to time and resource savings in drug development. CONCLUSION Quantitative assessment of metabolite coverage in safety species can be made using mixed matrix method with similar accuracy and scientific rigor to those obtained from validated bioanalytical methods. Moving forward, we are encouraging the industry and regulators to consider accepting the mixed matrix method for assessing metabolite exposure comparisons between humans and animal species used in toxicology studies.
A Human-Centered Approach to Algorithmic Services: Considerations for Fair and Motivating Smart Community Service Management that Allocates Donations to Non-Profit Organizations

Algorithms are increasingly being incorporated into diverse services that orchestrate multiple stakeholders' needs and interests. How can we design these algorithmic services to make decisions that are not only efficient, but also fair and motivating? We take a human-centered approach to identify and address challenges in building human-centered algorithmic services. We are in the process of building an allocation algorithm for 412 Food Rescue, an organization that matches food donations with non-profit organizations. As part of this ongoing project, we conducted interviews with multiple stakeholders in the service-organization staff, donors, volunteers, recipient non-profits and their clients, and everyday citizens-in order to understand how the allocation algorithm, interfaces, and surrounding work practices should be designed. The findings suggest that we need to understand and account for varying fairness notions held by stakeholders; consider people, contexts, and interfaces for algorithms to work fairly in the real world; and preserve meaningfulness and social interaction in automation in order to build fair and motivating algorithmic services.
A distributed learning–based user association for heterogeneous networks

The coexistence of various base stations (BSs) in heterogeneous networks (HetNets) has emerged as a promising approach to meet the ever increasing network capacity. In these networks, one of the important issues is the problem of associating user equipments (UEs) to BSs. In this paper, we investigate the UE association (UEA) problem in heterogeneous networks and propose a load‐aware UEA mechanism based on the BSs' estimated load and signal‐to‐interference‐and‐noise ratio. The proposed mechanism can capture the trade‐off between UE's quality‐of‐service requirement and delay. We model this strategic UE‐BS association as a noncooperative game. To solve the game, we develop a fully distributed algorithm inspired by machine learning techniques, whereby the proposed UEA scheme corresponds to a Markov chain. In the proposed scheme, each UE senses its environment and decides which BS to select based on the satisfaction technique. Therefore, it achieves a high level of satisfaction for UEs. Furthermore, use of historical information helps UEs select BSs with better long‐term performance. Simulation results show that the proposed mechanism reduces fractional transfer time and the number of unsatisfied UEs, respectively, up to about 46% and 52.3% and improves BS throughput up to about 15.4% compared to a benchmark algorithm that is based on the received signal strength and the BS's estimated load.
WIENER-HOPF FACTORIZATION FOR LEVY PROCESSES HAVING POSITIVE JUMPS WITH RATIONAL TRANSFORMS

We show that the positive Wiener-Hopf factor of a Levy process with positive jumps having a rational Fourier transform is a rational function itself, expressed in terms of the parameters of the jump distribution and the roots of an associated equation. Based on this, we give the closed form of the ruin probability for a Levy process, with completely arbitrary negatively distributed jumps, and finite intensity positive jumps with a distribution characterized by a rational Fourier transform. We also obtain results for the ladder process and its Laplace exponent. A key role is played by the analytic properties of the characteristic exponent of the process and by a Baxter-Donsker-type formula for the positive factor that we derive.
Evidence that increased 12‐lipoxygenase activity induces apoptosis in fibroblasts

The 12‐lipoxygenase (LO) enzyme has been implicated in playing a role in pancreatic beta cell inflammatory damage and atherosclerosis. 12‐LO reacts with fatty acids to form hydroperoxides which may alter cellular growth. In this study we investigated the direct effect of mouse leukocyte type 12‐LO cDNA overexpression on apoptosis in Chinese hamster ovary fibroblast cells that also stably overexpress the angiotensin II type 1a receptor. CHO‐AT1a cells expressing background levels of 12‐LO exhibited clear increases in growth in response to angiotensin II. In contrast, the new 12‐LO transfected cells (CHO‐AT1a/ML12‐LO cells) displayed reduced basal and angiotensin Il‐induced growth compared to CHO‐AT1a cells. Furthermore, serum‐deprivation resulted in a significantly greater number of non‐viable cells in clones having the greatest magnitude of 12‐LO overexpression. These results suggested that reduction of the proliferation rate of CHO‐AT1a/ML12‐LO cells was due to an increasing rate of cell death. To determine whether the increase in cell death was due to apoptosis, we evaluated nuclear DNA fragmentation, cell morphologic changes, and activation of caspase‐3. Cells overexpressing 12‐LO cDNA displayed all these changes characteristic of apoptosis. In addition the 12‐LO product, 12‐hydroperoxyeicosatetraenoic acid (12‐HPETE), directly induced apoptosis in CHO‐AT1a cells. These results demonstrate for the first time that 12‐LO activation can lead to apoptosis in fibroblasts, suggesting a role of 12‐LO in leading to inflammatory mediated cellular damage. J. Cell. Physiol. 186:357–365, 2001. © 2001 Wiley‐Liss, Inc.
Capacity enhancement in SDMA scheme with orthogonal code

We introduce a novel merger of SDMA and CDMA systems. In order to examine the potentialities of this merger, the performance of the conventional SDMA is investigated. A new scheme called dynamic space code (DSC) signature that can enhance the system capacity is presented and analyzed in various scenarios. This scheme is form by inserting an orthogonal code which origin from CDMA system into each SDMA user to create more transparent signature scheme to distinguish each mobile user. The properties of linkair communications' large area synchronous (LAS) or smart codes, which are claimed to be fully orthogonal code and are used to combat major interferences, are studied. Finally, all system performance in term of carrier to interference ratio (C/I) is presented.
Detection of wide linear structures by fusion of width and gray

Lines provide important information in images and line detection is crucial in many applications. Many line features can be used to detect line position while line width (i.e., thickness) is a more structured, higher-level feature compared to edge or other line features. Every point of the wide line structure has its own width in spite of the structure's asymmetry. In this paper, we use the parallel edges to get the line orientation and width. We do not need to know the actual width of the line, but rather recover it to get the region of interest (ROI). Then use a modified OTSU obtaining proper region threshold T to segment the wide line structures. By fusing feature of width and gray, a sequence of tests has been conducted on a variety of image samples obtained from simple natural scene and our experimental results demonstrate the practical and robust of the proposed method.
The Paradox of Openness: How Product and Patenting Experience Affect R&D Sourcing in China?

External R&D sourcing may help firms compete in an environment characterized by rapid technological changes. Yet, prior studies have produced conflicting findings on how a firm's technological experience affects the extent to which the firm engages in external R&D sourcing. Although many highlight that firms with extensive technological experience are equipped with more technological knowledge, collaborative skills, and absorptive capacity, encouraging greater levels of external R&D, others suggest the opposite due to potential exchange hazards and partnership conflicts. Adopting an external partner's perspective, the current study reconsiders this “paradox of openness” by analyzing how a focal firm's product experience and patenting experience affect an external partner's tendency to provide external R&D services to the focal firm. Specifically, this study explore how a focal firm's knowledge protectiveness and tacitness embedded in its product and patenting experience influences the external partners' motivation for knowledge transfer. This study predicts that a firm's product experience increases the focal firm's external R&D sourcing because it provides high levels of knowledge tacitness and external openness and can encourage external partners to share and exchange knowledge with the focal firm. In contrast, a firm's patenting experience decreases the focal firm's external R&D sourcing because it denotes knowledge explicitness and protectiveness and may discourage external partners to share and exchange knowledge with the focal firm. This study further predicts that patenting experience has a negative moderating effect on the relationship between product experience and external R&D sourcing. Using a data set of 575 high-tech firms in China, this study finds support for our predictions. Our findings contribute to the growing literature on the knowledge-based view and technology entrepreneurship in emerging markets.
Identification and Characterization of a Re-Citrate Synthase in Dehalococcoides Strain CBDB1

ABSTRACT The genome annotations of all sequenced Dehalococcoides strains lack a citrate synthase, although physiological experiments have indicated that such an activity should be encoded. We here report that a Re face-specific citrate synthase is synthesized by Dehalococcoides strain CBDB1 and that this function is encoded by the gene cbdbA1708 (NCBI accession number CAI83711), previously annotated as encoding homocitrate synthase. Gene cbdbA1708 was heterologously expressed in Escherichia coli, and the recombinant enzyme was purified. The enzyme catalyzed the condensation of oxaloacetate and acetyl coenzyme A (acetyl-CoA) to citrate. The protein did not have homocitrate synthase activity and was inhibited by citrate, and Mn2+ was needed for full activity. The stereospecificity of the heterologously expressed citrate synthase was determined by electrospray ionization liquid chromatography-mass spectrometry (ESI LC/MS). Citrate was synthesized from [2-13C]acetyl-CoA and oxaloacetate by the Dehalococcoides recombinant citrate synthase and then converted to acetate and malate by commercial citrate lyase plus malate dehydrogenase. The formation of unlabeled acetate and 13C-labeled malate proved the Re face-specific activity of the enzyme. Shotgun proteome analyses of cell extracts of strain CBDB1 demonstrated that cbdbA1708 is expressed in strain CBDB1.
Adipose Stromal/Stem Cells: Basic and Translational Advances: The IFATS Collection

In October 2007, the International Federation of Adipose Therapeutics and Science (IFATS), the world’s only multidisciplinary society focused on the biology of multipotent stromal/ stem cells derived from adipose tissue, as well as applications of these cells for repair and regeneration of tissue injury, met in Indianapolis, Indiana for its fifth Annual Scientific Meeting. This meeting was the occasion for a call for submissions to STEM CELLS of original manuscripts related to these cells. In this issue, STEM CELLS, in collaboration with IFATS, presents a special IFATS Collection, peer-reviewed and selected from among those submissions. This issue comprises nine papers; part two of this collection will be forthcoming in another issue of STEM CELLS in the near future.
Modulation of gait coordination by subthalamic stimulation improves freezing of gait

The effect of subthalamic deep brain stimulation on gait coordination and freezing of gait in patients with Parkinson's disease is incompletely understood. The purpose of this study was to investigate the extent to which modulation of symmetry and coordination between legs by subthalamic deep brain stimulation alters the frequency and duration of freezing of gait in patients with Parkinson's disease. We recruited 13 post‐subthalamic deep brain stimulation patients with Parkinson's disease with off freezing of gait and evaluated them in the following 4 conditions: subthalamic deep brain stimulation on (ON) and stimulation off (OFF), 50% reduction of stimulation voltage for the leg with shorter step length (worse side reduction) and for the leg with longer step length (better side reduction). Gait analysis was performed on a treadmill and recorded by an optoelectronic analysis system. We measured frequency and duration of freezing of gait episodes. Bilateral coordination of gait was assessed by the Phase Coordination Index, quantifying the ability to generate antiphase stepping. From the OFF to the ON state, freezing of gait improved in frequency (2.0 ± 0.4 to 1.4 ± 0.5 episodes) and duration (12.2 ± 2.6 to 2.6 ± 0.8 seconds; P = .005). Compared with the ON state, only better side reduction further reduced freezing of gait frequency (0.2 ± 0.2) and duration of episodes (0.2 ± 0.2 seconds; P = .03); worse side reduction did not change frequency (1.3 ± 0.4) but increased freezing of gait duration (5.2 ± 2.1 seconds). The better side reduction–associated improvements were accompanied by normalization of gait coordination, as measured by phase coordination index (16.5% ± 6.0%), which was significantly lower than in the other 3 conditions. Reduction of stimulation voltage in the side contralateral to the leg with longer step length improves frequency and duration of freezing of gait through normalization of gait symmetry and coordination in subthalamic deep brain stimulation patients with Parkinson's disease. This identifies poor leg coordination as a risk factor for causing freezing of gait. © 2011 Movement Disorder Society
Investigating the Impact of Corporate Social Responsibility on Firm’s Short- and Long-Term Performance with Online Text Analytics

Despite expectations of short- or long-term positive effects of corporate social responsibility (CSR) on firm performance, the results of existing research into this relationship are inconsistent partly due to lack of clarity about subordinate CSR concepts. In this study, keywords related to CSR concepts are extracted from atypical sources, such as newspapers, using text mining techniques to examine the relationship between CSR and firm performance. The analysis is based on data from the New York Times, a major news publication, and Google Scholar. We used text analytics to process unstructured data collected from open online documents to explore the effects of CSR on short- and long-term firm performance. The results suggest that the CSR index computed using the proposed text - online media - analytics predicts long-term performance very well compared to short-term performance in the absence of any internal firm reports or CSR institute reports. Our study demonstrates the text analytics are useful for evaluating CSR performance with respect to convenience and cost effectiveness.
Simulation-Based Approaches for Verification of Embedded Control Systems: An Overview of Traditional and Advanced Modeling, Testing, and Verification Techniques

Designers of industrial embedded control systems, such as automotive, aerospace, and medical-device control systems, use verification and testing activities to increase their confidence that performance requirements and safety standards are met. Since testing and verification tasks account for a significant portion of the development effort, increasing the efficiency of testing and verification will have a significant impact on the total development cost. Existing and emerging simulation-based approaches offer improved means of testing and, in some cases, verifying the correctness of control system designs.
Stability and Performance of Haptic Interfaces with Active/Passive Actuators—Theory and Experiments

This paper addresses both theoretical and experimental studies of the stability and performance of haptic interfaces containing active/passive actuators. Three different realizations of haptic interfaces are introduced to investigate their stability and performance: an active system equipped with a motor; a passive system equipped with a brake; and a hybrid system equipped with both brake and motor. The first objective is to demonstrate that a hybrid system is superior in its stability and performance to an active system via passivity theorem and Z-width. The second objective of this paper is to show that the conditions for the asymptotic stability of haptic interfaces during the static friction display are investigated via the absolute stability theory. Theoretical and experimental results are compared. An alternative haptic interface is proposed that provides its highly stable haptic interaction with high performance.
ARE RATING AGENCIES STILL CREDIBLE AFTER THE SUBPRIME CRISIS

Reputational concerns should discipline credit rating agencies (CRAs), eliminate any conflicts of interest, and motivate them to provide unbiased ratings. However, the recent financial crisis confirms models of CRAs’ behavior that predict inflated ratings for complex products and during booms. We test whether CRAs suffered a reputational damage for this behavior. We find strong support in the data for our hypothesis. The stock price reaction to rating revisions is significantly lower after the financial crisis, particularly in the financial sector. In multivariate tests, we find that the stock price reaction is lower, on average, in the post-crisis period by 2.3%.
Orientational order in bipolar nematic microdroplets close to the phase transition.

The ordering in bipolar liquid-crystal droplets close to the nematic-paranematic phase translation is studied. Here, ``paranematic'' refers to the phase above the nematic-isotropic transition temperature. The structure of spherical droplets is obtained after the minimization of the Landau\char21{}de Gennes-type free energy assuming a constant value of the surface order parameter and strong anchoring of the molecules parallel to the surface. Disordered defect regions caused by elastic deformations are found close to the poles. The defect regions grow into the droplet as the coexistence temperature between the paranematic and nematic phases is approached from below. The temperature-radius phase diagram shows the first-order coexistence curve terminating in the critical point and a pronounced decrease of the coexistence temperature on approaching the critical radius.
Classification of Urban Point Clouds: A Robust Supervised Approach With Automatically Generating Training Data

To reduce the cost of manually annotating training data for parsing outdoor scenes, we propose a supervised approach with automatically generating training data for classifying 3-D point clouds of large-scale urban scenes. In this approach, the input point cloud is aggregated into point clusters, and the disjoint set union issue is combined with geometric attributes of each point cluster to obtain object segments. The prior knowledge among different classes is used to label the segments by using the decision-tree model. Then, the initialized training samples are generated automatically. The confidence estimation for the labeling is employed to filter the mislabeled training samples. With the generated training data, we train a random forest classifier to create the initial classification of the 3-D scene on the set of descriptors for each 3-D point. The classification results are further optimized by multilabel conditional Random Fields. Experimental results on five urban point clouds captured by different types of scanners (i.e., terrestrial laser scanning, vehicle laser scanning, and airborne laser scanning datasets) demonstrate that the proposed approach achieves a competitive classification performance.
N‐Acetylation of L‐Aspartate in the Nervous System: Differential Distribution of a Specific Enzyme

Abstract: L‐Aspartate N‐acetyltransferase, a nervous system enzyme that mediates the synthesis of N‐acetyl‐L‐aspartic acid, has been characterized. In the presence of acetyl‐CoA, L‐aspartate was acetylated 10‐fold more efficiently than L‐glutamate, and the acetylation of aspartylglutamate was not detectable. Within the nervous system, a 10‐fold variation in the enzyme activity was observed, with the brainstem and spinal cord exhibiting the highest activity (10–15 pmol/min/mg tissue) and retina the lowest detectable activity (1–1.5 pmol/min/mg). No enzyme activity was detected in pituitary, heart, liver, or kidney. The enzyme activity was found to be membrane‐associated and was solubilized by treatment with Triton X‐100.
Bilateral Laparoscopic Stone Surgery for Renal Stones- A Case Series.

PURPOSE To present our experience with synchronous or metachronous laparoscopic pyelolithotomy and ureterolithotomy for patients with bilateral urolithiasis. MATERIALS AND METHODS The data of all patients who underwent laparoscopic pyelolithotomy (± ureterolithotomy) for bilateral renal and/or ureteral stones from November 2009 to July 2014 were included. Laparoscopic operations were performed through a transperitoneal approach. RESULTS 10 patients underwent laparoscopic operations for renal stones (19 kidney stones) and ureteral stones (1 ureteral stone). 4 patients underwent synchronous operations and 6 patients underwent metachronous operations. The mean ± SD of operation duration were 212 ± 51 minutes for synchronous operations and 166 ± 41 minutes for metachronous operations. Residual stone was observed 5 patients. No patient developed urinary leakage. CONCLUSION Laparoscopic pyelolithotomy and/or ureterolithotomy for bilateral stones is a feasible option in centers with experience in laparoscopy.