Miracle-dz/UniFAR-FTUs huggingface dataset:
Reaction phenotyping in drug discovery: moving forward with confidence?

For the pharmaceutical industry, one of the challenges in evaluating the risk of future compound attrition at the discovery stage is the successful prediction of the major routes of clearance in humans. For compounds cleared by metabolism, such information will help to avoid the development of compounds that will exhibit large interpatient differences in pharmacokinetics via 1). routes of metabolism catalyzed by functionally polymorphic enzymes and/or 2). clinically significant metabolic drug-drug interactions, in the later stages of development. The degree of intersubject variability that is acceptable for a drug candidate is uncertain in the discovery stage where knowledge of other important factors is limited or unavailable (i.e. therapeutic index, pharmacodynamic variability, etc). Reaction phenotyping is the semi-quantitative in vitro estimation of the relative contributions of specific drug-metabolizing enzymes to the metabolism of a test compound. However, reaction phenotyping in the discovery stage of drug development is complicated by the absence of radiolabelled parent compound or metabolite bioanalytical standards relative to later stages of development. In this commentary, some of the approaches, based on published data, which can be taken to overcome these challenges are discussed. In addition, knowledge of the molecular structure (i.e. specific chemical substituents), physicochemical properties, and routes of clearance in animals can all help in making a successful prediction for the routes of clearance in humans. In combination, the objective of these studies should be to reduce to a minimum the risk of finding significant inter-patient differences in pharmacokinetics at a later stage in development due to significant metabolism by polymorphic enzymes or drug-drug interactions. Consequently, this data should be used to avoid costly late stage attrition.
QualitySpy: a framework for monitoring software development processes

The growing popularity of highly iterative, agile processes creates increasing need for au- tomated monitoring of the quality of software artifacts, which would be focused on short terms (in the case of eXtreme Programming process iteration can be limited to one week). This paper presents a framework that calculates software metrics and cooperates with de- velopment tools (e.g. source version control system and issue tracking system) to describe current state of a software project with regard to its quality. The framework is designed to support high level of automation of data collection and to be useful for researchers as well as for industry. The framework is currently being developed hence the paper reports al- ready implemented features as well as future plans. The first release is scheduled for July.
Thermofluid Properties of Ti-6Al-4V Melt Pool in Powder-Bed Electron Beam Additive Manufacturing

Electron beam additive manufacturing (EBAM) is a powder-bed fusion additive manufacturing (AM) technology that can make full density metallic components using a layer-by-layer fabrication method. To build each layer, the EBAM process includes powder spreading, preheating, melting, and solidification. The quality of the build part, process reliability, and energy efficiency depends typically on the thermal behavior, material properties, and heat source parameters involved in the EBAM process. Therefore, characterizing those properties and understanding the correlations among the process parameters are essential to evaluate the performance of the EBAM process. In this study, a three-dimensional computational fluid dynamics (CFD) model with Ti-6Al-4V powder was developed incorporating the temperature-dependent thermal properties and a moving conical volumetric heat source with Gaussian distribution to conduct the simulations of the EBAM process. The melt pool dynamics and its thermal behavior were investigated numerically, and results for temperature profile, melt pool geometry, cooling rate and variation in density, thermal conductivity, specific heat capacity, and enthalpy were obtained for several sets of electron beam specifications. Validation of the model was performed by comparing the simulation results with the experimental results for the size of the melt pool.
Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer

Targeting nonviral antigens in viral-driven cancer Adoptive cell transfer harnesses a patient's own T cells to destroy cancer. The strategy can successfully treat epithelial tumors driven by human papillomavirus (HPV), but it remains unclear why only some patients respond. Stevanović et al. examined the antitumor T cell response associated with HPV+ cervical cancers that underwent complete regression. Unexpectedly, reactive T cells were not directed against virally associated antigens, but rather against cancer germline antigens or neoantigens not previously recognized by the immune system. These findings counter the widely held belief that T cell responses against viral antigens are responsible for therapeutic effects in HPV-driven cancers. Science, this issue p. 200 Reactive T cells directed against nonviral antigens lead to regression of human papilloma virus–positive cervical cancer. Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus–associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens. T cells targeting viral tumor antigens did not display preferential in vivo expansion. Both viral and nonviral tumor antigen–specific T cells resided predominantly in the programmed cell death 1 (PD-1)–expressing T cell compartment, which suggests that PD-1 blockade may unleash diverse antitumor T cell reactivities. These findings suggest a new paradigm of targeting nonviral antigens in immunotherapy of virally associated cancers.
Relativity in the Perception of Emotion in Facial Expressions

SUMMARY The same facial expression will be seen as expressing different types and degrees of emotion, depending on what other faces are seen. A relatively neutral face seems sad when presented alongside a happier face, happy alongside a sadder face. A relatively unhappy face seems sad when presented alongside an angrier face, angry alongside a sadder face. The specific emotion seen in a face can be predicted by combining the idea that human judgment is relative with a model of the scale implicit in the judgment of emotion. In that model, categories and dimensions descriptive of feelings are interrelated in a systematic fashion: Categorical descriptors such as happy, sad, calm, and angry are at specific locations around the periphery of an emotion judgment space defined by degree of pleasure and degree of arousal. Viewing one facial expression (an anchor) shifts the entire scale of judgment, displacing the emotion seen in a subsequent expression (the target) in the opposite direction. Specifically, (a) magnitude of shift in perception of the target is proportional to the distance of the anchor from the center of the emotion space, (b) the angle of shift differs by 180° from the angle from the center to the anchor, and (c) the quantitative pleasure-arousal shift in the target corresponds to predictable shifts in the applicability of categorical descriptors. The geometric formulation of these ideas, although perhaps exaggerating our ability to quantify the message seen in a facial expression, did suggest specific hypotheses, some of which were tested here in six experiments. Supportive results were found with successive and with simultaneous presentation of anchor and target, with various target expressions including expressions of neutral, surprised, and angry feelings, with both posed and spontaneous target expressions, with target expressions posed by the same actor seen in the anchor and by a different actor, with different groups of observers, and with different
REACH 2 -Mote: A Range Extending Passive Wake-up Wireless Sensor Node

A wireless sensor network that employs passive radio wake-up of the sensor nodes can reduce the energy cost for unnecessary idle listening and communication overhead, extending the network lifetime. A passive wake-up radio is powered by the electromagnetic waves transmitted by a wake-up transmitter rather than a battery on the sensor node. However, this method of powering the wake-up radio results in a short wake-up range, which limits the performance of a passive wake-up radio sensor network. In this paper, we describe our design of a passive wake-up radio sensor node, called REACH 2 -Mote, using a high efﬁciency energy harvesting module and a very low power wake-up circuit to achieve an extended wake-up range. We implemented REACH 2 -Mote in hardware and performed ﬁeld tests to characterize its performance. The experimental results show that the REACH 2 -Mote can achieve a wake-up range of 44 ft. We also modeled the REACH 2 -Mote and evaluated its performance through simulations, comparing its performance with that of another passive wake-up radio approach, an active wake-up radio approach, and a conventional duty cycling approach. The simulation results show that the REACH 2 -Mote can signiﬁcantly extend the network lifetime, while achieving high packet delivery rate and low latency.
Pmr, a Histone-Like Protein H1 (H-NS) Family Protein Encoded by the IncP-7 Plasmid pCAR1, Is a Key Global Regulator That Alters Host Function

ABSTRACT Histone-like protein H1 (H-NS) family proteins are nucleoid-associated proteins (NAPs) conserved among many bacterial species. The IncP-7 plasmid pCAR1 is transmissible among various Pseudomonas strains and carries a gene encoding the H-NS family protein, Pmr. Pseudomonas putida KT2440 is a host of pCAR1, which harbors five genes encoding the H-NS family proteins PP_1366 (TurA), PP_3765 (TurB), PP_0017 (TurC), PP_3693 (TurD), and PP_2947 (TurE). Quantitative reverse transcription-PCR (qRT-PCR) demonstrated that the presence of pCAR1 does not affect the transcription of these five genes and that only pmr, turA, and turB were primarily transcribed in KT2440(pCAR1). In vitro pull-down assays revealed that Pmr strongly interacted with itself and with TurA, TurB, and TurE. Transcriptome comparisons of the pmr disruptant, KT2440, and KT2440(pCAR1) strains indicated that pmr disruption had greater effects on the host transcriptome than did pCAR1 carriage. The transcriptional levels of some genes that increased with pCAR1 carriage, such as the mexEF-oprN efflux pump genes and parI, reverted with pmr disruption to levels in pCAR1-free KT2440. Transcriptional levels of putative horizontally acquired host genes were not altered by pCAR1 carriage but were altered by pmr disruption. Identification of genome-wide Pmr binding sites by ChAP-chip (chromatin affinity purification coupled with high-density tiling chip) analysis demonstrated that Pmr preferentially binds to horizontally acquired DNA regions. The Pmr binding sites overlapped well with the location of the genes differentially transcribed following pmr disruption on both the plasmid and the chromosome. Our findings indicate that Pmr is a key factor in optimizing gene transcription on pCAR1 and the host chromosome.
Classification of normal and pathological infant cries using bispectrum features

In this paper, bispectrum-based feature extraction method is proposed for classification of normal vs. pathological infant cries. Bispectrum is computed for all segments of normal as well as pathological cries. Bispectrum is a two-dimensional (2-D) feature. A tensor is formed using these bispectrum features and then for feature reduction, higher order singular value decomposition theorem (HOSVD) is applied. Our experimental results show 70.56 % average accuracy of classification with support vector machine (SVM) classifier, whereas baseline features, viz., MFCC, LPC and PLP gave classification accuracy of 52.41 %, 61.27 % and 57.41 %, respectively. For showing the effectiveness of the proposed feature extraction method, a comparison with other feature extraction methods which uses diagonal slice and peaks and their locations as feature vectors is given as well.
The Influences of Acculturation, Marianismo and Ethnic Identity on Sexual Activity Among Latina Adolescents

THE INFLUENCES OF ACCULTURATION, MARIANISMO AND ETHNIC IDENTITY ON SEXUAL ACTIVITY AMONG LATINA ADOLESCENTS Keyona M. Jarrett, M.A. Marquette University, 2011 This mixed methods study examined the influences of acculturation (e.g., assimilation and enculturation), marianismo, and ethnic identity on the sexual behaviors and attitudes of Latina adolescents. In the quantitative portion of the study, 204 Latina adolescents completed measures regarding acculturation, gender roles, ethnic identity, and sexual behaviors. In the qualitative portion of the study, three focus groups were conducted (with a total of 10 participants) in which Latina youth were asked questions regarding their ethnic group membership and its influence on their attitudes about sex. The results of the quantitative portion of the study revealed that ethnic affirmation was negatively associated with the variable “ever had sex. ” Ethnic affirmation was positively associated with contraception use at first sexual intercourse and ethnic identity achievement was positively associated with age of first sexual intercourse. Additionally, there was a significant interaction between ethnic affirmation and assimilation for age at first sexual intercourse, such that participants who reported high levels of assimilation and low levels of ethnic affirmation reported a younger age of first sexual intercourse than those who reported a high level of assimilation and a high level of ethnic affirmation. The qualitative results revealed that the participants live in a cultural context characterized by ethnic pride and biculturalism. Experiences of discrimination, awareness of negative stereotypes, and bicultural difficulties are also important aspects of the cultural context of the Latina youth. The cultural context of these adolescents helped to shape their sexual attitudes. The core sexual attitude expressed by the majority of the Latina youth was that marriage is a necessary condition for them to engage in sexual activity. The qualitative results also revealed how gender roles, cultural differences, family values, personal knowledge, peer pressure, and stressors/abuse shape the core sexual attitude of the Latina adolescents. Specifically gender roles, cultural differences, family values, and personal knowledge discouraged them from engaging in sexual activity, while peer pressure and stressors/abuse encouraged them to engage in sexual activity. Convergence and divergence between the qualitative and quantitative data are identified and explained. Limitations and implications of the current study and future directions are also discussed.
Effect of molecular crowding on self‐association of phosphorylase kinase and its interaction with phosphorylase b and glycogen

Self‐association of phosphorylase kinase (PhK) and its interaction with glycogen (M=5500 kDa) and phosphorylase b (Phb) has been studied using analytical ultracentrifugation and turbidimetry under the conditions of molecular crowding arising from the presence of high concentrations of osmolytes. In accordance with the predictions of the molecular crowding theory, trimethylamine N‐oxide (TMAO) and betaine greatly favor self‐association of PhK induced by Mg2+ and Ca2+ and PhK interaction with glycogen. In contrast, proline suppresses these processes, probably, due to its specific interaction with PhK. All osmolytes tested prevented the complex formation between PhK and its physiological substrate, Phb. The specific interactions of PhK and Phb with glycogen, in the living cell, presumably is a factor allowing the negative effect of crowding on the recognition of Phb by PhK to be overcome. Copyright © 2004 John Wiley & Sons, Ltd.
Replication Protein A-Directed Unloading of PCNA by the Ctf18 Cohesion Establishment Complex

ABSTRACT The replication clamp PCNA is loaded around DNA by replication factor C (RFC) and functions in DNA replication and repair. Regulated unloading of PCNA during the progression and termination of DNA replication may require additional factors. Here we show that a Saccharomyces cerevisiae complex required for the establishment of sister chromatid cohesion functions as an efficient unloader of PCNA. Unloading requires ATP hydrolysis. This seven-subunit Ctf18-RFC complex consists of the four small subunits of RFC, together with Ctf18, Dcc1, and Ctf8. Ctf18-RFC was also a weak loader of PCNA onto naked template-primer DNA. However, when the single-stranded DNA template was coated by the yeast single-stranded DNA binding protein replication protein A (RPA) but not by a mutant form of RPA or a heterologous single-stranded DNA binding protein, both binding of Ctf18-RFC to substrate DNA and loading of PCNA were strongly inhibited, and unloading predominated. Neither yeast RFC itself nor two other related clamp loaders, containing either Rad24 or Elg1, catalyzed significant unloading of PCNA. The Dcc1 and Ctf8 subunits of Ctf18-RFC, while required for establishing sister chromatid cohesion in vivo, did not function specifically in PCNA unloading in vitro, thereby separating the functionality of the Ctf18-RFC complex into two distinct paths.
OPTICAL EMISSION LINE PROFILES OF THE LV KNOTS (PROPLYDS) IN ORION

Compact emission line “LV knots” discovered by Laques and Vidal (1979) in the Orion Nebula (M 42) are found to spatially coincide with some of the “proplyds” discovered by O’Dell, Wen and Hu (1993) in their HST images. We therefore attempt to reproduce the line profiles observed for the LV knots with the photoevaporated disk/wind interaction model that has been developed by Henney et al. (1996) for modelling the proplyds. In particular, we present high resolution [O iii] 5007Å line profiles of the knots LV 1 (OW 168–326E), LV 2 (OW 167–317), LV 3 (OW 163–317) and LV 5 (OW 158–323), and also of another faint emission line knot (OW 171–334) in the vicinity of θ1 Ori C. Good agreement between the theoretical predictions and the observed line profiles is found for three of the knots, in which most of the main features of the line profiles are reproduced by the model. A partial, qualitative agreement is also found for the other knots. From these results we conclude that the model of a photoevaporated disk wind interacting with the wind from θ1 Ori C at least partially succeeds in reproducing the line profiles of the proplyds associated with the LV knots.
Statistics and ethics in medical research: III How large a sample?

Whatw~r type of statistical design is used for a study, the problem of sample size must be faced. This aspect, which causes considerable difficulty for researchers, is perhaps the most common reason for consulting a statistician. There are also, however, many who give little thought to sample size, choosing the most convenient number (20, 50, 100, etc) or time period (one month, one year, etc) for their study. They, and those who approve such studies, should realise that there are important statistical and ethical implications in the choice of sample size for a study. A study with an overlarge sample may be deemed unethical through the unnecessary involvement of extra subjects and the correspondingly increased costs. Such studies are probably rare. On the other hand, a study with a sample that is too small will be unable to detect clinically important effects. Such a study may thus be scientifically useless, and hence unethical in its use of subjects and other resources. Studies that are too small
Epidemic-style Monitoring in Large-Scale Sensor Networks

As wireless sensor nodes become more powerful, affordable and compact, the possibility of deploying massive numbers of networked nodes for various purposes becomes more and more attractive. Large-scale networks of wireless sensor nodes constructed “on the fly” could easily monitor environment variables over large geographical areas if a scalable and efficient communication layer were in place. However, the unpredictable nature of ad hoc networks seems to be at odds with the deterministic characteristics of most routing protocols, making them unsuitable for large-scale deployment. In this paper, we explore epidemic techniques for disseminating information in ad hoc environments. By taking a gossip-based approach instead of purposefully routing data to a destination we aim to sidestep the scalability constraints faced by other more sophisticated routing protocols. We present a framework under which three protocols are built. Through various simulations, we explore how the subtle differences between them affect their characteristics for large-scale data dissemination. Formal analysis of our protocols gives insight into the mechanics that make epidemic protocols a reliable and scalable solution for ad hoc networks.
Quantum mechanics versus macroscopic realism: Is the flux there when nobody looks?

It is shown that, in the context of an idealized ``macroscopic quantum coherence'' experiment, the predictions of quantum mechanics are incompatible with the conjunction of two general assumptions which are designated ``macroscopic realism'' and ``noninvasive measurability at the macroscopic level. '' The conditions under which quantum mechanics can be tested against these assumptions in a realistic experiment are discussed.
Dynamically Controlled Resource Allocation in SMT Processors

SMT processors increase performance by executing instructions from several threads simultaneously. These threads use the resources of the processor better by sharing them but, at the same time, threads are competing for these resources. The way critical resources are distributed among threads determines the final performance. Currently, processor resources are distributed among threads as determined by the fetch policy that decides which threads enter the processor to compete for resources. However, current fetch policies only use indirect indicators of resource usage in their decision, which can lead to resource monopolization by a single thread or to resource waste when no thread can use them. Both situations can harm performance and happen, for example, after an L2 cache miss. In this paper, we introduce the concept of dynamic resource control in SMT processors. Using this concept, we propose a novel resource allocation policy for SMT processors. This policy directly monitors the usage of resources by each thread and guarantees that all threads get their fair share of the critical shared resources, avoiding monopolization. We also define a mechanism to allow a thread to borrow resources from another thread if that thread does not require them, thereby reducing resource under-use. Simulation results show that our dynamic resource allocation policy outperforms a static resource allocation policy by 8%, on average. It also improves the best dynamic resource-conscious fetch policies like FLUSH++ by 4%, on average, using the harmonic mean as a metric. This indicates that our policy does not obtain the ILP boost by unfairly running high ILP threads over slow memory-bounded threads. Instead, it achieves a better throughput-fairness balance.