Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterizing User Behavior in Mobile Internet

Smart devices bring us the ubiquitous mobile accessing to Internet, making mobile Internet grow rapidly. Using the mobile traffic data collected at core metropolitan 2G and 3G networks of China over a week, this paper studies the mobile user behavior from three aspects: 1) data usage; 2) mobility pattern; and 3) application usage. We classify mobile users into different groups to study the resource consumption in mobile Internet. We observe that traffic heavy users and high mobility users tend to consume massive data and radio resources simultaneously. Both the data usage and the mobility pattern are closely related to the application access behavior of the users. Users can be clustered through their application usage behavior, and application categories can be identified by the ways to attract the users. Our analysis provides an comprehensive understanding of user behavior in mobile Internet, which may be used by network operators to design appropriate mechanisms in resource provision and mobility management for resource consumers based on different categories of applications.
Validation and Optimization of Novel High-Throughput Assays for Human Epithelial Sodium Channels

The epithelial sodium channel (ENaC) plays a crucial role in salt and water homeostasis and is primarily involved in sodium reabsorption in the kidney and lung. Modulators of ENaC function, particularly within lung epithelia, could offer potential treatments for a number of diseases. As a constitutively active sodium channel, ENaC expression at the cell membrane is highly regulated through rapid turnover. This short half-life of the channel at the membrane and cytotoxicity from overexpression pose a problem for reagent generation and assay development in drug discovery. We have generated an HEK293 stable cell line expressing ENaC β and γ subunits containing the PY motif trafficking mutations found in Liddle’s syndrome to overcome rapid channel turnover at the membrane. A BacMam virus was used to transiently express the ENaC α subunit to reconstitute channel function to reduce the toxicity associated with long-term overexpression. We have configured a 384-well FLIPR membrane potential antagonist assay for high-throughput screening and an IonWorks Quattro electrophysiology antagonist assay that is predictive of potency values derived from primary lung epithelial cell short-circuit measurements. The triage strategy for compound screening and profiling against this target using these assays has resulted in the discovery of novel chemotypes.
High-Throughput Screening of Formulations to Optimize the Thermal Stability of a Therapeutic Monoclonal Antibody

Monoclonal antibodies (mAbs) are an important class of biotherapeutics. Successful development of a mAb depends not only on its biological activity but also on its physicochemical properties, such as homogeneity and stability. mAb stability is affected by its formulation. Among the many techniques used to study the stability of mAbs, differential scanning fluorimetry (DSF) offers both excellent throughput and minimal material consumption. DSF measures the temperature of the protein unfolding transition (Tm) based on the change in fluorescence intensity of the environmentally sensitive dye SYPRO Orange. With DSF adapted to a 96-well plate format, we have shown that low-pH or high-salt concentrations decrease the thermal stability of mAb1, whereas some excipients, such as sucrose, polysorbate 80, and sodium phosphate, increase its stability. The basal fluorescence of SYPRO Orange was enhanced by the presence of detergents, limiting the use of this approach to diluted detergent solutions. Throughput of DSF can be increased further with the use of a 384-well plate. DSF thermograms are in good agreement with the melting profiles obtained by differential scanning calorimetry (DSC). The Tms determined by DSF and DSC were well correlated, with the former being on average lower by 3 °C.
On the performance of multiple-objective genetic local search on the 0/1 knapsack problem - a comparative experiment

Multiple-objective metaheuristics, e.g., multiple-objective evolutionary algorithms, constitute one of the most active fields of multiple-objective optimization. Since 1985, a significant number of different methods have been proposed. However, only few comparative studies of the methods were performed on large-scale problems. We continue two comparative experiments on the multiple-objective 0/1 knapsack problem reported in the literature. We compare the performance of two multiple-objective genetic local search (MOGLS) algorithms to the best performers in the previous experiments using the same test instances. The results of our experiment indicate that our MOGLS algorithm generates better approximations to the nondominated set in the same number of functions evaluations than the other algorithms.
An evolutionary approach to automatic synthesis of high-performance analog integrated circuits

This paper presents an analog integrated circuit synthesis system based on an evolutionary approach. The system contains several novel features. One of these is the high-performance optimization algorithm, which is a combination of evolutionary strategies and simulated annealing. Modeling of dc parameters is done via a fast dc simulator developed for this purpose whereas modeling of ac parameters can be done either with user-defined equations or with neural-fuzzy performance models trained from SPICE simulations. Another novel feature of the system is the incorporation of matching properties of devices. This way, the optimized circuit becomes tolerant to process variations. The synthesis system has been tested on several independent examples and synthesized circuits have been verified functionally with SPICE simulations. Finally, a prototype chip composed of the three examples has been manufactured. The measurement results have demonstrated the validity of the synthesis system on silicon.
A faster algorithm for calculating hypervolume

We present an algorithm for calculating hypervolume exactly, the Hypervolume by Slicing Objectives (HSO) algorithm, that is faster than any that has previously been published. HSO processes objectives instead of points, an idea that has been considered before but that has never been properly evaluated in the literature. We show that both previously studied exact hypervolume algorithms are exponential in at least the number of objectives and that although HSO is also exponential in the number of objectives in the worst case, it runs in significantly less time, i.e., two to three orders of magnitude less for randomly generated and benchmark data in three to eight objectives. Thus, HSO increases the utility of hypervolume, both as a metric for general optimization algorithms and as a diversity mechanism for evolutionary algorithms.
MHC Class I–Associated Phosphopeptides Are the Targets of Memory-like Immunity in Leukemia

Immunity against phosphopeptide antigens lacking in leukemia patients can be restored with stem cell transplantation. Adding to the Toolkit for Cancer Therapy The immune system is increasingly being used as a tool for cancer therapy. Researchers have harnessed the body’s own defense system to specifically target tumors. However, one limitation of immune-targeting strategies is the relative lack of targets. Because cancer cells are derived from normal human tissue, ideal antigens would be specifically or differentially expressed by tumor cells and healthy tissues. Now, Cobbold et al. find that phosphoproteins may broaden the pool of tumor antigens that can be targeted with immunotherapy. One difference between cancer and normal cells is the way in which they are regulated. Indeed, signal transduction pathways are frequently dysregulated in cancer cells. The authors now use a hallmark of signal transduction—protein phosphorylation—to identify and characterize new phosphoantigens that stimulate immune cells. They identified 95 phosphopeptides presented on the surface of leukemic cells and demonstrated that they could be recognized and killed by phosphopeptide-specific cytotoxic T lymphocytes. Somewhat surprisingly, healthy individuals had high levels of responses to phosphopeptides, but these responses were muted in leukemia patients with poor prognosis. What’s more, allogeneic stem cell transplant could restore phosphoprotein immune response in patients. These data suggest that phosphopeptides could be developed as new targets for cancer immunotherapy. Deregulation of signaling pathways is a hallmark of malignant transformation. Signaling-associated phosphoproteins can be degraded to generate cancer-specific phosphopeptides that are presented by major histocompatibility complex (MHC) class I and II molecules and recognized by T cells; however, the contribution of these phosphoprotein-specific T cells to immune surveillance is unclear. We identified 95 phosphopeptides presented on the surface of primary hematological tumors and normal tissues, including 61 that were tumor-specific. Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8+ T cell lines specific for these phosphopeptides recognized and killed both leukemia cell lines and human leukocyte antigen–matched primary leukemia cells ex vivo. Notably, healthy individuals showed robust CD8+ T cell responses against many of these phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some leukemia patients. This reduction correlated with clinical outcome; however, immunity was restored after allogeneic stem cell transplantation. These results suggest that phosphopeptides may be targets of cancer immune surveillance in humans, and point to their importance for development of vaccine-based and T cell adoptive transfer immunotherapies.
Simultaneous High-Throughput Conformational and Colloidal Stability Screening Using a Fluorescent Molecular Rotor Dye, 4-(4-(Dimethylamino)styryl)-N-Methylpyridinium Iodide (DASPMI)

Technologies to improve the throughput for screening protein formulations are continuously evolving. The purpose of this article is to highlight novel applications of a molecular rotor dye, 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (DASPMI) in screening for the conformational stability, colloidal stability, and subtle pretransition dynamics of protein structures during early formulation development. The measurement of the apparent unfolding temperature (Tm) for a monoclonal antibody in the presence of Tween 80 was conducted and data were compared to the results of differential scanning calorimetry (DSC) measurements. Additionally, measuring the fluorescence intensity of DASPMI as a function of protein concentration shows consistent correlation to the diffusion interaction parameter (kD) for two distinct monoclonal antibody formulations measured by DLS. Lastly, due to the sensitivity of the molecular rotor dye to changes in microviscosity (ηmicro), subtle pretransition dynamics were discernable for two monoclonal antibody formulations that correlate with findings by red-edge excitation shift (REES) experiments. This novel application of molecular rotor dyes offers a valuable and promising approach for streamlining the early formulation development process due to low material consumption and rapid analysis time in a 96-well plate format.
SURGERY OF EXPERIMENTAL LESION OF SPINAL CORD EQUIVALENT TO CRUSH INJURY OF FRACTURE DISLOCATION OF SPINAL COLUMN: A PRELIMINARY REPORT

PREFATORY REMARKS In two former papers I have dwelt at length on the mechanical considerations of injury to the spinal cord in cases of fracture dislocation of the spinal column. 1, 2 In this communication, therefore, I shall limit myself to the discussion of the experimental work in which I have been engaged for the past year in the laboratories of the University of Pennsylvania. I would accentuate the fact that this is a preliminary report and that I am fully aware of the amount of control experimentation necessary before an ex cathedra statement can be made as to applicability of this work in the human subject. MEASUREMENT OF IMPACT ON SPINAL CORD IN SPINAL FRACTURE DISLOCATION In order to arrive at an adequate concept as to the amount of impact a spinal cord could receive and yet recover its function, I designed an instrument whereby a given weight could
High-Throughput Screens to Discover Small-Molecule Modulators of Ryanodine Receptor Calcium Release Channels

Using time-resolved fluorescence resonance energy transfer (FRET), we have developed and validated the first high-throughput screening (HTS) method to discover compounds that modulate an intracellular Ca2+ channel, the ryanodine receptor (RyR), for therapeutic applications. Intracellular Ca2+ regulation is critical for striated muscle function, and RyR is a central player. At resting [Ca2+], an increased propensity of channel opening due to RyR dysregulation is associated with severe cardiac and skeletal myopathies, diabetes, and neurological disorders. This leaky state of the RyR is an attractive target for pharmacological agents to treat such pathologies. Our FRET-based HTS detects RyR binding of accessory proteins calmodulin (CaM) or FKBP12.6. Under conditions that mimic a pathological state, we carried out a screen of the 727-compound NIH Clinical Collection, which yielded six compounds that reproducibly changed FRET by >3 SD. Dose–response of FRET and [3H]ryanodine binding readouts reveal that five hits reproducibly alter RyR1 structure and activity. One compound increased FRET and inhibited RyR1, which was only significant at nM [Ca2+], and accentuated without CaM present. These properties characterize a compound that could mitigate RyR1 leak. An excellent Z′ factor and the tight correlation between structural and functional readouts validate this first HTS method to identify RyR modulators.
A Pareto Corner Search Evolutionary Algorithm and Dimensionality Reduction in Many-Objective Optimization Problems

Many-objective optimization refers to the optimization problems containing large number of objectives, typically more than four. Non-dominance is an inadequate strategy for convergence to the Pareto front for such problems, as almost all solutions in the population become non-dominated, resulting in loss of convergence pressure. However, for some problems, it may be possible to generate the Pareto front using only a few of the objectives, rendering the rest of the objectives redundant. Such problems may be reducible to a manageable number of relevant objectives, which can be optimized using conventional multiobjective evolutionary algorithms (MOEAs). For dimensionality reduction, most proposals in the paper rely on analysis of a representative set of solutions obtained by running a conventional MOEA for a large number of generations, which is computationally overbearing. A novel algorithm, Pareto corner search evolutionary algorithm (PCSEA), is introduced in this paper, which searches for the corners of the Pareto front instead of searching for the complete Pareto front. The solutions obtained using PCSEA are then used for dimensionality reduction to identify the relevant objectives. The potential of the proposed approach is demonstrated by studying its performance on a set of benchmark test problems and two engineering examples. While the preliminary results obtained using PCSEA are promising, there are a number of areas that need further investigation. This paper provides a number of useful insights into dimensionality reduction and, in particular, highlights some of the roadblocks that need to be cleared for future development of algorithms attempting to use few selected solutions for identifying relevant objectives.
Two Decades of Terror Management Theory: A Meta-Analysis of Mortality Salience Research

A meta-analysis was conducted on empirical trials investigating the mortality salience (MS) hypothesis of terror management theory (TMT). TMT postulates that investment in cultural worldviews and self-esteem serves to buffer the potential for death anxiety; the MS hypothesis states that, as a consequence, accessibility of death-related thought (MS) should instigate increased worldview and self-esteem defense and striving. Overall, 164 articles with 277 experiments were included. MS yielded moderate effects (r = .35) on a range of worldview- and self-esteem-related dependent variables (DVs), with effects increased for experiments using (a) American participants, (b) college students, (c) a longer delay between MS and the DV, and (d) people-related attitudes as the DV. Gender and self-esteem may moderate MS effects differently than previously thought. Results are compared to other reviews and examined with regard to alternative explanations of TMT. Finally, suggestions for future research are offered.
QRP06-4: A Server Reassignment Algorithm for DHT Load Balance and the Effect of Heterogeneity

Application layer peer to peer (P2P) networks are considered to be the most important development for next generation Internet infra-structure. For these systems to be effective, load balancing among the peers is critical. Early structured P2P systems rely on the randomness of object ID generated with a consistent hash function to avoid the load imbalance issue, and has been known to result in an imbalance factor in the number of items stored at a node, even in the case of a homogeneous system where all nodes have the same capacity. We propose to address the problem systematically using an optimization based approach, and show that the problem of rearranging loads among the peers can be cast in the framework of a generalized assignment problem. The dual space local search (DSLS) heuristic algorithm is proposed, which minimizes the load movement involved in an efficient manner. We demonstrate the superior performance of our proposal in general, and its advantages over previous strategies. We also explore other important issues vital to the performance for the virtual server framework, such as the performance ramification of peer registration strategies. Significantly, we characterize systematically the effect of heterogeneity on load balancing algorithm performance, and the conditions in which heterogeneity may be easy or hard to deal with.
Homosexuality and Pro-Gay Ideology as Pathogens? Implications of a Disease-Spread Lay Model for Understanding Anti-Gay Behaviors

Negative behaviors targeting gay men and lesbians range from violent physical assault to casting a vote against gay marriage, with very different implications for those targeted. Existing accounts of such actions, however, are unable to differentially predict specific anti-gay behaviors, leaving a large theoretical hole in the literature and hindering the design of effective interventions. We propose (a) that many sexually prejudiced laypersons conceptualize homosexuality and pro-gay ideology as “contaminants” analogous to infectious pathogens and (b) that anti-gay behaviors can thus be viewed as strategic attempts to prevent, contain, treat, or eradicate the “pathogens” of homosexuality and pro-gay ideology. By considering analogues to disease-spread processes (e.g., susceptibility of specific subpopulations, inoculation procedures, prevalence in the local environment, interconnections among community members), we derive novel predictions regarding the incidence and nature of anti-gay behaviors and provide leverage for creating more tailored interventions to reduce such discrimination.
SPC04-4: Distribution of "Bad Urban" Uplink Multipaths' Arrival Delay & Azimuth-Elevation Arrival Angles, with Scatterers Distributed Cylindrically Above the Mobile

This paper presents a new trivariate joint and bivariate distributions of a landmobile cellular wireless communication system's uplink multipaths' time-of-arrival (TOA) and two-dimensional (2D) azimuth-elevation direction-of-arrival (DOA). These distributions are rigorously derived via thorough mathematics, based on a "geometrical" model of the three-dimensional (3D) spatial relationships among the mobile-station (MS), the scatterers, and the base-station (BS). Unlike earlier "geometric models" that assume the scatterers to have only a 2D spatial density (for example, uniform density within a disc around the mobile), this present "geometric model" have the scatterer spatial density as uniform within a 3D vertical above ground cylinder whose flat bottom circular base centers at the mobile.
Functional Network Pipeline Reveals Genetic Determinants Associated with in Situ Lymphocyte Proliferation and Survival of Cancer Patients

Genomic alterations result in changes of immune cell densities within the tumor. There Goes the Neighborhood Just as a new homeowner will remodel when moving into a house, a tumor also alters the local microenvironment. One of the least tumor-friendly things in the tumor microenvironment is the immune response. Mlecnik et al. now examine the network of changes to cytokines that contribute to shaping the intratumoral immune response in colorectal tumors. The authors found changes in local expression of 13 cytokines. Deletion of one cytokine, interleukin 15, was associated with tumor recurrence and reduced patient survival, potentially by affecting the local proliferation of B and T cells. Their results show that chromosome instability contributes to the regulation of cytokines and downstream tumor immune response. The tumor microenvironment is host to a complex network of cytokines that contribute to shaping the intratumoral immune reaction. Chromosomal gains and losses, coupled with expression analysis, of 59 cytokines and receptors and their functional networks were investigated in colorectal cancers. Changes in local expression for 13 cytokines were shown. Metastatic patients exhibited an increased frequency of deletions of cytokines from chromosome 4. Interleukin 15 (IL15) deletion corresponded with decreased IL15 expression, a higher risk of tumor recurrence, and reduced patient survival. Decreased IL15 expression affected the local proliferation of B and T lymphocytes. Patients with proliferating B and T cells at the invasive margin and within the tumor center had significantly prolonged disease-free survival. These results delineate chromosomal instability as a mechanism of modulating local cytokine expression in human tumors and underline the major role of IL15. Our data provide further mechanisms resulting in changes of specific immune cell densities within the tumor, and the importance of local active lymphocyte proliferation for patient survival.
Awareness of Formal and Informal Sources of Help for Victims of Elder Abuse Among Korean American and Caucasian Elders in Los Angeles

ABSTRACT This study examines and compares the awareness of formal and informal sources of help for victims of elder abuse and the factors that might influence this awareness among Korean American and Caucasian elders. The study sample consisted of 95 Korean American and 90 Caucasian elders age 60 or older living in Los Angeles County, California in 1997. It shows that overall, Korean American respondents were significantly less aware of the four general and specific sources of help measured-general formal and informal sources, the Elder Abuse Hotline, and the Adult Protective Services (APS). Findings further suggest that most respondents in both groups have little or no knowledge of the two elder abuse-specific sources of formal help, the Hotline and APS. Logistic regression analysis on 12 independent variables reveal ethnicity and income as significant predictors of respondents' awareness of available help. The implications of the study results for strategies for early intervention and prevention of elder abuse are also discussed.