Miracle-dz/UniFAR-FTUs huggingface dataset:
Common DNA Variants Accurately Rank an Individual of Extreme Height

Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7′6″, 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals.
An Integrative Model Accounting for the Symptom Cluster Triggered After an Acoustic Shock

Acoustic shocks and traumas sometimes result in a cluster of debilitating symptoms, including tinnitus, hyperacusis, ear fullness and tension, dizziness, and pain in and outside the ear. The mechanisms underlying this large variety of symptoms remain elusive. In this article, we elaborate on the hypothesis that the tensor tympani muscle (TTM), the trigeminal nerve (TGN), and the trigeminal cervical complex (TCC) play a central role in generating these symptoms. We argue that TTM overuse (due to the acoustic shock), TTM overload (due to muscle tension), and ultimately, TTM injury (due to hypoxia and “energy crisis”) lead to inflammation, thereby activating the TGN, TCC, and cortex. The TCC is a crossroad structure integrating sensory inputs coming from the head–neck complex (including the middle ear) and projecting back to it. The multimodal integration of the TCC may then account for referred pain outside the ear when the middle ear is inflamed and activates the TGN. We believe that our model proposes a synthetic and explanatory framework to explain the phenomena occurring postacoustic shock and potentially also after other nonauditory causes. Indeed, due to the bidirectional properties of the TCC, musculoskeletal disorders in the region of the head–neck complex, including neck injury due to whiplash or temporomandibular disorders, may impact the middle ear, thereby leading to otic symptoms. This previously unavailable model type is experimentally testable and must be taken as a starting point for identifying the mechanisms responsible for this particular subtype of tinnitus and its associated symptoms.
Exposure of Breast and Lung Cancer Cells to a Novel Estrone Analog Prior to Radiation Enhances Bcl-2-Mediated Cell Death

Following exposure of cells to gamma-radiation, a cascade of intracellular consequences may be observed in a semitemporal manner. This includes deoxyribonucleic acid (DNA) damage and reactive oxygen species (ROS) accumulation initially, with consequent signaling for DNA repair and facilitative regulation of the cell cycle. Failure to rectify the damage or ROS levels leads to induction of senescence or apoptosis. 2-Ethyl-3-O-sulfamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol), a 2-methoxyestradiole analog designed in silico for superior pharmacokinetics, was investigated for its potential to enhance apoptotic signaling and decrease the long-term survival of cells exposed to radiation. Sequential early intracellular effects within radiation-treated MCF-7 breast- and A549 lung cancer cells pre-exposed to low-dose ESE-15-ol were investigated using various flow cytometric protocols, spectrophotometry, and microscopy. Long-term cellular survival and proliferation was examined using clonogenic studies, which demonstrated a significant decrease in the presensitized cells. Combination-treated cells exhibited increased superoxide formation, and decreased Bcl-2 expression and -phosphorylation. Induction of apoptosis and elevation of the sub-G1 phase was evident in the pre-exposed MCF-7 cells, although only minimally in the A549 cells at 48-h. These results indicate that low-dose ESE-15-ol may increase tumor response to radiation. Future studies will investigate the effect of ESE-15-ol pre-exposure on radiation-induced DNA damage and repair mechanisms.
Stream Sampling Framework and Application for Frequency Cap Statistics

Unaggregated data, in a streamed or distributed form, are prevalent and come from diverse sources such as interactions of users with web services and IP traffic. Data elements have keys (cookies, users, queries), and elements with different keys interleave. Analytics on such data typically utilizes statistics expressed as a sum over keys in a specified segment of a function f applied to the frequency (the total number of occurrences) of the key. In particular, Distinct is the number of active keys in the segment, Sum is the sum of their frequencies, and both are special cases of frequency cap statistics, which cap the frequency by a parameter T. Random samples can be very effective for quick and efficient estimation of statistics at query time. Ideally, to estimate statistics for a given function f, our sample would include a key with frequency w with probability roughly proportional to f(w). The challenge is that while such “gold-standard” samples can be easily computed after aggregating the data (computing the set of key-frequency pairs), this aggregation is costly: It requires structure of size that is proportional to the number of active keys, which can be very large. We present a sampling framework for unaggregated data that uses a single pass (for streams) or two passes (for distributed data) and structure size proportional to the desired sample size. Our design unifies classic solutions for Distinct and Sum. Specifically, our ℓ-capped samples provide nonnegative unbiased estimates of any monotone non-decreasing frequency statistics and statistical guarantees on quality that are close to gold standard for cap statistics with T=Θ (ℓ). Furthermore, our multi-objective samples provide these statistical guarantees on quality for all concave sub-linear statistics (the nonnegative span of cap functions) while incurring only a logarithmic overhead on sample size.
Genetic Contribution to Initial and Progressive Alcohol Intake Among Recombinant Inbred Strains of Mice

We profiled individual differences in alcohol consumption upon initial exposure and during 5 weeks of voluntary alcohol intake in female mice from 39 BXD recombinant inbred strains and parents using the drinking in the dark (DID) method. In this paradigm, a single bottle of 20% (v/v) alcohol was presented as the sole liquid source for 2 or 4 h starting 3 h into the dark cycle. For 3 consecutive days mice had access to alcohol for 2 h followed by a 4th day of 4 h access and 3 intervening days where alcohol was not offered. We followed this regime for 5 weeks. For most strains, 2 or 4 h alcohol intake increased over the 5-week period, with some strains demonstrating greatly increased intake. There was considerable and heritable genetic variation in alcohol consumption upon initial early and sustained weekly exposure. Two different mapping algorithms were used to identify QTLs associated with alcohol intake and only QTLs detected by both methods were considered further. Multiple suggestive QTLs for alcohol intake on chromosomes (Chrs) 2, 6, and 12 were identified for the first 4 h exposure. Suggestive QTLs for sustained intake during later weeks were identified on Chrs 4 and 8. Thirty high priority candidate genes, including Entpd2, Per3, and Fto were nominated for early and sustained alcohol intake QTLs. In addition, a suggestive QTL on Chr 15 was detected for change in 2 h alcohol intake over the duration of the study and Adcy8 was identified as a strong candidate gene. Bioinformatic analyses revealed that early and sustained alcohol intake is likely driven by genes and pathways involved in signaling, and/or immune and metabolic function, while a combination of epigenetic factors related to alcohol experience and genetic factors likely drives progressive alcohol intake.
Musicians' initial encounters with a smart guitar

This paper presents a case study of a fully working prototype of the Sensus smart guitar. Eleven professional guitar players were interviewed after a prototype test session. The smartness of the guitar was perceived as enabling the integration of a range of equipment into a single device, and the proactive exploration of novel expressions. The results draw attention to the musicians' sense-making of the smart qualities, and to the perceived impact on their artistic practices. The themes highlight how smartness was experienced in relation to the guitar's agency and the skills it requires, the tension between explicit (e.g. playing a string) and implicit (e.g. keeping rhythm) body movements, and to performing and producing music. Understanding this felt sense of smartness is relevant to how contemporary HCI research conceptualizes mundane artefacts enhanced with smart technologies, and to how such discourse can inform related design issues.
Functional connectivity with cortical depth assessed by resting state fMRI of subregions of S1 in squirrel monkeys

Whereas resting state blood oxygenation‐level dependent (BOLD) functional MRI has been widely used to assess functional connectivity between cortical regions, the laminar specificity of such measures is poorly understood. This study aims to determine: (a) whether the resting state functional connectivity (rsFC) between two functionally related cortical regions varies with cortical depth, (b) the relationship between layer‐resolved tactile stimulus‐evoked activation pattern and interlayer rsFC pattern between two functionally distinct but related somatosensory areas 3b and 1, and (c) the effects of spatial resolution on rsFC measures. We examined the interlayer rsFC between areas 3b and 1 of squirrel monkeys under anesthesia using tactile stimulus‐driven and resting state BOLD acquisitions at submillimeter resolution. Consistent with previous observations in the areas 3b and 1, we detected robust stimulus‐evoked BOLD activations with foci were confined mainly to the upper layers (centered at 21% of the cortical depth). By carefully placing seeds in upper, middle, and lower layers of areas 3b and 1, we observed strong rsFC between upper and middle layers of these two areas. The layer‐resolved activation patterns in areas 3b and 1 agree with their interlayer rsFC patterns, and are consistent with the known anatomical connections between layers. In summary, using BOLD rsFC pattern, we identified an interlayer interareal microcircuit that shows strong intrinsic functional connections between upper and middle layer areas 3b and 1. RsFC can be used as a robust invasive tool to probe interlayer corticocortical microcircuits.
Estimating the cost and cost-effectiveness for obstetric fistula repair in hospitals in Uganda: a low income country

In Africa, about 33 000 cases of obstetric fistula occur each year. Women with fistula experience debilitating incontinence of urine and/or faeces and are often socially ostracized. Worldwide, Uganda ranks third among countries with the highest burden of obstetric fistula. Obstetric fistula repair competes for scarce resources with other healthcare interventions in resource-limited settings, even though it is surgically efficacious. There is limited documentation of its cost-effectiveness in the most affected settings. We therefore sought to assess the cost-effectiveness of surgical intervention for obstetric fistula in Uganda so as to provide appropriate data for policy-makers to prioritize fistula repair and reduce women's suffering in similarly burdened countries. We built a decision-analytic model from the perspective of Uganda's National Health System to estimate the cost-effectiveness of vesico-vaginal and recto-vaginal fistula surgery vs a competing strategy of no surgery for Ugandan women with fistula. Long-term disability outcomes were assessed based on a lifetime Markov state-transition cohort and effectiveness of surgery. Surgical costs were estimated by micro-costing local Ugandan health resources. Disability weights associated with vesico-vaginal, recto-vaginal fistula and mortality rates among the general population in Uganda were based on published sources. The cost of providing fistula repair surgery in Uganda was estimated at $378 per procedure. For a hypothetical 20-year-old woman, surgery was estimated to decrease the lifetime disability burden from 8.53 DALYs to 1.51 DALYs, yielding a cost per DALY averted of $54. The results were robust to variations in model inputs in one-way and probabilistic sensitivity analyses. Surgery for obstetric fistula appears highly cost-effective in Uganda. In similar low-income countries, governments and non-governmental organizations need to prioritize training and strengthening surgical capacity to increase access to fistula surgical care, which would be an important step towards achieving universal health coverage.
Corrosion Behavior of the As-Cast and As-Solid Solution Mg-Al-Ge Alloy

The corrosion behavior of Mg-3Al-xGe (x = 1, 3, 5) alloy in as-cast and as-solid was investigated by virtue of microstructure, corrosion morphology observation, and electrochemical measurement. Among the as-cast alloys, the corrosion rate of Mg-3Al-1Ge with a discontinuous bar-morphology was the highest, which was 101.7 mm·a−1; the corrosion rate of Mg-3Al-3Ge with a continuous network distribution was the lowest, which was 23.1 mm·a−1; and the corrosion rate of Mg-3Al-5Ge of Ge-enriched phase with sporadic distribution was in-between, which was 63.9 mm·a−1. It is suggested that the morphology of the Mg2Ge phase changes with a change in Ge content, which affects the corrosion performance of the alloy. After solid solution treatment, the corrosion rate of the corresponding solid solution alloy increased—Mg-3Al-1Ge to 140.5 mm·a−1, Mg-3Al-3Ge to 52.9 mm·a−1, and Mg-3Al-5Ge to 87.3 mm·a−1, respectively. After investigation of the microstructure, it can be suggested that solid solution treatment dissolves the Mg17Al12 phase, which changes the phase composition of the alloy and also affects its microstructure, thus affecting its corrosion performance.
High-Performance Stateful Stream Processing on Solid-State Drives

Stream processing has been widely used in big data analytics because it provides real-time information on continuously incoming data streams with low latency. As the volume of data increases and the processing logic becomes more complicated, the size of internal states in stream processing applications also increases. To deal with large states efficiently, modern stream processing systems support storing internal states on solid state drives (SSDs) by utilizing persistent key-value (KV) stores optimized for SSDs. For example, Apache Flink and Apache Samza store internal states on RocksDB. However, delegating state management to persistent KV stores degrades the performance, because the KV stores cannot optimize their state management strategies according to stream query semantics as they are not aware of the query semantics. In this paper, we investigate the performance limitations of current state management approaches on SSDs and show that query-aware optimizations can significantly improve the performance of stateful query processing on SSDs. Based on our observation, we propose a new stream processing system design with static and runtime query-aware optimizations. We also discuss additional research directions on integrating emerging storage technologies with stateful stream processing.
Crosstalk between p53 modifiers at PML bodies

ABSTRACT Tumor protein p53 (TP53, best known as p53), the most frequently mutated tumor suppressor in cancer, plays a central role in cell fate decisions induced by DNA damage. Regulation of p53 activity by post-translational modifications has been linked to promyelocytic leukemia nuclear bodies (PML-NBs), where p53 encounters many of its regulators. Recent evidence implies that crosstalk between p53 regulators at the PML-NB shapes post-translational modifications and function of p53.
Differential Relationship between Intermuscular Adipose Depots with Indices of Cardiometabolic Health

Background Globally, accumulation of intermuscular adipose tissue (IMAT) is positively associated with insulin resistance. Whether this association is observed consistently in different skeletal muscles and encompasses other markers of cardiometabolic health is not well known. Objectives The purpose of this secondary analysis study was to investigate associations among thigh or calf IMAT stores and indices of cardiometabolic health in adults who are overweight and obese participating in dietary interventions. A subset of calf data was analyzed to assess relations between IMAT in the gastrocnemius (type II fiber predominance) and soleus (type I fiber predominance) with markers of cardiometabolic health. Materials and Methods Thigh and calf compositions were assessed via magnetic resonance imaging in 113 subjects (mean ± SD, age: 50 ± 16 y (range: 21–77 y), BMI: 31 ± 3 kg/m2), 103 of which completed dietary interventions with or without energy restriction-induced weight loss. A subset of data (n = 37) was analyzed for relations between muscle compartments (gastrocnemius and soleus) and cardiometabolic health. IMAT was regressed separately against fasting serum glucose concentrations, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), and lipids and lipoproteins. Results In general, total thigh IMAT was predictive of markers of glucose control, while total calf IMAT was not. Specifically, baseline thigh IMAT was positively associated with fasting glucose, insulin, and HOMA-IR. IMAT content changes in any depot did not predict improvement in cardiometabolic health. Conclusions The strength of the relationship between IMAT and glucose control-related indices of cardiometabolic health is dependent on IMAT location. Specifically, greater IMAT in the thigh is a better predictor of cardiometabolic risk than greater IMAT in the calf in adults who are overweight and obese.
The Role of Ethnography in Agile Requirements Analysis

The integration of ethnography analysis with agile methods is a new topic of the research of software engineering. In agile development, ethnography is particularly effective at discovering two types of requirements: the functions requested from customers and the functions observed from the ethnographic analyst. The proposed model depends on the role of ethnographic analyst in understanding how people operate actually and discover requirements that support software functionality. This help to predicts implicit system requirements that not defined by the organization. The proposed ethnographic model requires that the ethnographic analyst remain in the organization and observe the actual ways in which people work, rather than only the formal requirements documented by the organization.
Proteases Shape the Chlamydomonas Secretome: Comparison to Classical Neuropeptide Processing Machinery

The recent identification of catalytically active peptidylglycine α-amidating monooxygenase (PAM) in Chlamydomonas reinhardtii, a unicellular green alga, suggested the presence of a PAM-like gene and peptidergic signaling in the last eukaryotic common ancestor (LECA). We identified prototypical neuropeptide precursors and essential peptide processing enzymes (subtilisin-like prohormone convertases and carboxypeptidase B-like enzymes) in the C. reinhardtii genome. Reasoning that sexual reproduction by C. reinhardtii requires extensive communication between cells, we used mass spectrometry to identify proteins recovered from the soluble secretome of mating gametes, and searched for evidence that the putative peptidergic processing enzymes were functional. After fractionation by SDS-PAGE, signal peptide-containing proteins that remained intact, and those that had been subjected to cleavage, were identified. The C. reinhardtii mating secretome contained multiple matrix metalloproteinases, cysteine endopeptidases, and serine carboxypeptidases, along with one subtilisin-like proteinase. Published transcriptomic studies support a role for these proteases in sexual reproduction. Multiple extracellular matrix proteins (ECM) were identified in the secretome. Several pherophorins, ECM glycoproteins homologous to the Volvox sex-inducing pheromone, were present; most contained typical peptide processing sites, and many had been cleaved, generating stable N- or C-terminal fragments. Our data suggest that subtilisin endoproteases and matrix metalloproteinases similar to those important in vertebrate peptidergic and growth factor signaling play an important role in stage transitions during the life cycle of C. reinhardtii.
A Machine Learning-Based Topic Extraction and Categorization of State Universities and Colleges (SUC) Customer Feedbacks

Academic institutions collect an increasing amount of data through surveys. Aside from the usual numeric ratings obtained from the survey, the hierarchical concerns and sentiments can also be identified through the text-based customer feedbacks. These feedbacks contain text about customer experiences with the products offered and services delivered by an institution. A challenge in analyzing unstructured customer feedback is in making sense of the topics that are expressed in words used to describe these experiences. This study develops a model for text analysis of the customer feedbacks that exploits machine learning algorithms such as topic modeling. This further described the text mining process steps undergone in extracting useful information from the customer survey feedbacks of one of the SUCs in the Philippines, the Bicol State College of Applied Sciences and Technology (BISCAST). Moreover, the Latent Dirichlet Allocation (LDA), a topic modeling method, was used for automatic text summarization and topic extraction from these text-based data. The topmost concerns extracted from the feedbacks were identified. This information provides useful insights for management analysis as well as inputs for policy making.
DARA: assisting drivers to reflect on how they hold the steering wheel

This paper presents DARA, the Driving Awareness and Reflection Assistant that makes drivers aware of potentially dangerous practices on how they hold the steering wheel, and helps them reflect. DARA utilizes a hand recognition component and a feedback one. The first recognizes how drivers hold the steering wheel and classifies their actions through a Leap Motion controller and machine learning. The second is comprised by a mobile application that provides drivers with feedback during and after their drive. DARA was evaluated with three studies for its accuracy, relevance and utility. Our findings show that DARA was successful both in making holding patterns present-at-hand for the drivers and in assisting them to reflect. We conclude our paper with a discussion on the broader implication of our findings on in-car hand recognition and feedback systems.