Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficient Synthesis of Mutants Using Genetic Crosses

The genetic cross is a fundamental, flexible, and widely-used experimental technique to create new mutant strains from existing ones. Surprisingly, the problem of how to efficiently compute a sequence of crosses that can make a desired target mutant from a set of source mutants has received scarce attention. In this paper, we make three contributions to this question. First, we formulate several natural problems related to efficient synthesis of a target mutant from source mutants. Our formulations capture experimentally-useful notions of verifiability (e.g the need to confirm that a mutant contains mutations in the desired genes) and permissibility (e.g., the requirement that no intermediate mutants in the synthesis be inviable). Second, we develop combinatorial techniques to solve these problems. We prove that checking the existence of a verifiable, permissible synthesis is NP-complete in general. We complement this result with three polynomial time or fixed-parameter tractable algorithms for optimal synthesis of a target mutant for special cases of the problem that arise in practice. Third, we apply these algorithms to simulated data and to synthetic data. We use results from simulations of a mathematical model of the cell cycle to replicate realistic experimental scenarios where a biologist may be interested in creating several mutants in order to verify model predictions. Our results show that the consideration of permissible mutants can affect the existence of a synthesis or the number of crosses in an optimal one. Our algorithms gracefully handle the restrictions that permissible mutants impose. Results on synthetic data show that our algorithms scale well with increases in the size of the input and the fixed parameters.
Structural symmetry and membrane curvature sensing.

Symmetry is closely intertwined with the function, genetics, and chemical properties of multiprotein complexes. Here, we explore the relation between structural symmetry and the ability of membrane proteins to sense and induce membrane curvature, which is a key factor for modulating the shape and organization of cell membranes. Using coarse-grained simulations and elasticity theory, we show that the potential for direction-dependent membrane curvature sensing is limited to asymmetric proteins, dimers, and tetramers, and argue that one should expect this anisotropy to be strongest for dimers. Odd and higher-order symmetries strongly suppress directional curvature sensing. This classification gives a new perspective on the structure-function relation for membrane proteins, and simplifies the task of translating between molecular sensing mechanisms and their large-scale cellular consequences.
Designing finger orientation input for mobile touchscreens

A large number of today's systems use interactive touch surfaces as the main input channel. Current devices reduce the richness of touch input to two-dimensional positions on the screen. A growing body of work develops methods that enrich touch input to provide additional degrees of freedom for touch interaction. In particular, previous work proposed to use the finger's orientation as additional input. To efficiently implement new input techniques which make use of the new input dimensions, we need to understand the limitations of the input. Therefore, we conducted a study to derive the ergonomic constraints for using finger orientation as additional input in a two-handed smartphone scenario. We show that for both hands, the comfort and the non-comfort zone depend on how the user interacts with a touch surface. For two-handed smart-phone scenarios, the range is 33.3% larger than for tabletop scenarios. We further show that the phone orientation correlates with the finger orientation. Finger orientations which are harder to perform result in phone orientations where the screen does not directly face the user.
Impacts of L1 Promoter Variation and L2 Clavulanate Susceptibility on Ticarcillin-Clavulanate Susceptibility of Stenotrophomonas maltophilia

Inducible expression of L1 and L2 β-lactamases is the principal mechanism responsible for β-lactam resistance in Stenotrophomonas maltophilia. Ticarcillin-clavulanate (TIM) is one of the few effective β-lactams for S. maltophilia treatment. ABSTRACT Inducible expression of L1 and L2 β-lactamases is the principal mechanism responsible for β-lactam resistance in Stenotrophomonas maltophilia. Ticarcillin-clavulanate (TIM) is one of the few effective β-lactams for S. maltophilia treatment. Clavulanate (CA) is a β-lactamase inhibitor that specifically targets class A, C, and D β-lactamases. In view of the presence of class B L1 β-lactamase, it is of interest to elucidate why TIM is valid for S. maltophilia treatment. The L1-L2 allelic variation and TIM susceptibilities of 22 clinical isolates were established. Based on L1 and L2 protein sequences and TIM susceptibility, three L1-based phylogenetic clusters (L1-A, L1-B, and L1-C) and three L2-based phylogenetic clusters (L2-A, L2-B1, and L2-B2) were classified. The contribution of each L1- and L2-based phylogenetic cluster to ticarcillin (TIC) and TIM susceptibility was investigated. All the L1s and L2s tested contributed to TIC resistance. The L1s tested were inert to CA; nevertheless, the sensitivities of L2s to CA were widely different. In addition, the genetic organizations upstream of the L1 gene varied greatly in these isolates. At least three different L1 promoter structures (K279a type, D457 type, and none) were found among the 22 isolates assayed. The differences in the L1 promoter structure had a great impact on TIC-induced L1 β-lactamase activities. Collectively, the L1 promoter activity in response to TIC challenge and L2 susceptibility to CA are critical factors determining TIM susceptibility in S. maltophilia.
Interaction: Beyond retrieval

What is the role of interaction in the next generation of information systems? In classical information retrieval systems, interaction enables and facilitates the search for relevant documents. Typically, the interface is based on a three-pronged interaction paradigm: formulating keyword queries, scanning results lists, and browsing hypertext structures. This paradigm has been enormously successful. It is the basis for almost every modern, mainstream, large-scale information system, from digital libraries to web search engines and corporate intranets. But is this retrieval-centric approach to interaction a suitable foundation for the next generation of information systems? Is it a satisfactory basis for supporting the full cycle of knowledge discovery, creation, and use?
Design guidelines for hands-free speech interaction

As research on speech interfaces continues to grow in the field of HCI, there is a need to develop design guidelines that help solve usability and learnability issues that exist in hands-free speech interfaces. While several sets of established guidelines for GUIs exist, an equivalent set of principles for speech interfaces does not exist. This is critical as speech interfaces are so widely used in a mobile context, which in itself evolved with respect to design guidelines as the field matured. We explore design guidelines for GUIs and analyze how these are applicable to speech interfaces. For this we identified 21 papers that reflect on the challenges of designing (predominantly mobile) voice interfaces. We present an investigation of how GUI design principles apply to such hands-free interfaces. We discuss how this can serve as the foundation for a taxonomy of design guidelines for hands-free speech interfaces.
Patterns of Compartment Involvement in End‐stage Knee Osteoarthritis in a Chinese Orthopedic Center: Implications for Implant Choice

Knee osteoarthritis (OA) is a prevalent disease in the elderly, causing pain and contributing to poor quality of life. Surgical intervention, such as knee arthroplasty, can be used in those with end‐stage knee OA. Total knee arthroplasty (TKA) is one of the most common surgical procedures for end‐stage knee OA, with promising clinical outcomes. However, a large proportion of patients with isolated compartment OA can be treated with unicompartmental knee arthroplasty (UKA) instead. UKA has shown better patient‐reported functional outcomes, and lower mortality and major complication rates than TKA. The percentage of UKA in knee arthroplasty varied in different orthopedic centers, and we believed that the requirement for UKA was underestimated in many centers. A retrospective study was carried out on our Chinese patient population presenting for knee arthroplasty; it aimed to identify the proportion of patients that might be suitable for UKA.
BubbleFlick: investigating effective interface for Japanese text entry on smartwatches

We propose BubbleFlick, an effective interface for Japanese text entry on smartwatches. While various ideas have been proposed to provide easy and fast text entry for the Latin alphabet, Japanese text entry has additional challenges such as having more than fifty syllabary characters, or kana, to enter and the subsequent kana-kanji conversion, which translates a sequence of the syllabary characters into a standard expression with a mixture of kanji and kana characters. This paper focuses on interfaces for entry of kana syllabary characters. We designed and prototyped three interfaces: 1) Japanese kana syllabary keyboard, 2) Dial&Flick interface, and 3) DualBelts interface. Through a comparative pilot study of the prototypes, we refined the most promising Dial&Flick interface into BubbleFlick. BubbleFlick provides the widest possible area for easy flick operations while also leaving an area for editing text. We conducted a 30-day consecutive user study on BubbleFlick in comparison with Google's latest Japanese text-entry method based on a numeric keypad. After thirty days, BubbleFlick showed a text-entry speed of over 35 characters per minute, which was comparable to Google's numeric-keypad-based method for novice participants. Through the user study, BubbleFlick showed a lower error rate and gave us informative hints for further improvement.
Chitosan–Carboxymethylcellulose-Based Polyelectrolyte Complexation and Microcapsule Shell Formulation

Chitosan (CH)–carboxymethyl cellulose sodium salt (NaCMC) microcapsules containing paraffin oil were synthesized by complex formation, and crosslinked with glutaraldehyde (GTA). The electrostatic deposition of NaCMC onto the CH-coated paraffin oil emulsion droplets was demonstrated by zeta potential and optical microscopy. The optimal process conditions were identified in terms of pH of the aqueous solution (5.5) and CH/NaCMC mass ratio (1:1). Encapsulation of paraffin oil and microcapsule morphology were analyzed by ATR-FTIR and SEM, respectively. The effect of GTA crosslinking on paraffin oil latent heat was investigated by DSC and combined with the values of encapsulation efficiency and core content, supporting the compact shell formation.
Liquid Biopsy Biomarkers in Bladder Cancer: A Current Need for Patient Diagnosis and Monitoring

Bladder Cancer (BC) represents a clinical and social challenge due to its high incidence and recurrence rates, as well as the limited advances in effective disease management. Currently, a combination of cytology and cystoscopy is the routinely used methodology for diagnosis, prognosis and disease surveillance. However, both the poor sensitivity of cytology tests as well as the high invasiveness and big variation in tumour stage and grade interpretation using cystoscopy, emphasizes the urgent need for improvements in BC clinical guidance. Liquid biopsy represents a new non-invasive approach that has been extensively studied over the last decade and holds great promise. Even though its clinical use is still compromised, multiple studies have recently focused on the potential application of biomarkers in liquid biopsies for BC, including circulating tumour cells and DNA, RNAs, proteins and peptides, metabolites and extracellular vesicles. In this review, we summarize the present knowledge on the different types of biomarkers, their potential use in liquid biopsy and clinical applications in BC.
Strong Chromatic Index of Graphs With Maximum Degree Four

A strong edge-coloring of a graph $G$ is a coloring of the edges such that every color class induces a matching in $G$. The strong chromatic index of a graph is the minimum number of colors needed in a strong edge-coloring of the graph. In 1985, Erdős and Nešetřil conjectured that every graph with maximum degree $\Delta$ has a strong edge-coloring using at most $\frac{5}{4}\Delta^2$ colors if $\Delta$ is even, and at most $\frac{5}{4}\Delta^2 - \frac{1}{2}\Delta + \frac{1}{4}$ if $\Delta$ is odd. Despite recent progress for large $\Delta$ by using an iterative probabilistic argument, the only nontrivial case of the conjecture that has been verified is when $\Delta = 3$, leaving the need for new approaches to verify the conjecture for any $\Delta\ge 4$. In this paper, we apply some ideas used in previous results to an upper bound of 21 for graphs with maximum degree 4, which improves a previous bound due to Cranston in 2006 and moves closer to the conjectured upper bound of 20.
Associations Among Suicidal Ideation, White Matter Integrity and Cognitive Deficit in First-Episode Schizophrenia

Objective: The study was aimed to investigate the possible associations among suicidal ideation, brain white matter (WM) integrity and cognitive deficit in first-episode schizophrenia (FES) using diffusion tensor imaging. Methods: The sample contained 18 FES patients with suicidal ideation (SI+), 45 FES patients without suicidal ideation (SI–) and 44 healthy controls. The Calgary Depression Scale for Schizophrenia was used to measure the suicidal ideation and depression symptoms. The whole brain WM integrity and three domains of cognitive function: working memory, verbal comprehension as well as processing speed were compared between the three groups. Results: Compared with SI–, SI+ showed preserved WM integrity as indicated by significantly higher factional anisotropy (FA) or lower mean diffusivity (MD) in multiple WM tracts, and higher FA coupled with lower MD in bilateral posterior corona radiata. Compared with SI−, SI+ were more depressed and had less cognitive deficit in working memory and verbal comprehension. The fiber tracts in bilateral posterior corona radiata connect to the precuneus as shown by probabilistic tractography, and their WM integrity disruptions were found to be positively associated with the cognitive deficits in the FES patients. Discussion: Preserved WM integrity may be a risk factor for suicidal ideation in FES patients. One possible explanation is that it contributes to preserved cognitive function, especially in working memory and verbal comprehension, which may be associated with greater insight and could lead to increased depression and suicidal ideation. The posterior corona radiata and the precuneus may be linked to the related biological processes.
Phylogeographic patterns in the Philippine archipelago influence symbiont diversity in the bobtail squid–Vibrio mutualism

Abstract Marine microbes encounter a myriad of biotic and abiotic factors that can impact fitness by limiting their range and capacity to move between habitats. This is especially true for environmentally transmitted bacteria that cycle between their hosts and the surrounding habitat. As geologic history, biogeography, and other factors such as water temperature, salinity, and physical barriers can inhibit bacterial movement to novel environments, we chose to examine the genetic architecture of Euprymna albatrossae (Mollusca: Cephalopoda) and their Vibrio fischeri symbionts in the Philippine archipelago using a combined phylogeographic approach. Eleven separate sites in the Philippine islands were examined using haplotype estimates that were examined via nested clade analysis to determine the relationship between E. albatrossae and V. fischeri populations and their geographic location. Identical analyses of molecular variance (AMOVA) were used to estimate variation within and between populations for host and symbiont genetic data. Host animals demonstrated a significant amount of variation within island groups, while symbiont variation was found within individual populations. Nested clade phylogenetic analysis revealed that hosts and symbionts may have colonized this area at different times, with a sudden change in habitat. Additionally, host data indicate restricted gene flow, whereas symbionts show range expansion, followed by periodic restriction to genetic flow. These differences between host and symbiont networks indicate that factors “outside the squid” influence distribution of Philippine V. fischeri. Our results shed light on how geography and changing environmental factors can impact marine symbiotic associations at both local and global scales.
Lignans from Tujia Ethnomedicine Heilaohu: Chemical Characterization and Evaluation of Their Cytotoxicity and Antioxidant Activities

Heilaohu, the roots of Kadsura coccinea, has a long history of use in Tujia ethnomedicine for the treatment of rheumatoid arthritis and gastroenteric disorders, and a lot of work has been done in order to know the material basis of its pharmacological activities. The chemical investigation led to the isolation and characterization of three new (1–3) and twenty known (4–23) lignans. Three new heilaohulignans A-C (1–3) and seventeen known (4–20) lignans possessed dibenzocyclooctadiene skeletons. Similarly, one was a diarylbutane (21) and two were spirobenzofuranoid dibenzocyclooctadiene (22–23) lignans. Among the known compounds, 4–5, 7, 13–15 and 17–22 were isolated from this species for the first time. The structures were established, using IR, UV, MS and NMR data. The absolute configurations of the new compounds were determined by circular dichroism (CD) spectra. The isolated lignans were further evaluated for their cytotoxicity and antioxidant activities. Compound 3 demonstrated strong cytotoxic activity with an IC50 value of 9.92 µM, compounds 9 and 13 revealed weak cytotoxicity with IC50 values of 21.72 µM and 18.72 µM, respectively in the HepG-2 human liver cancer cell line. Compound 3 also showed weak cytotoxicity against the BGC-823 human gastric cancer cell line and the HCT-116 human colon cancer cell line with IC50 values of 16.75 µM and 16.59 µM, respectively. A chemiluminescence assay for antioxidant status of isolated compounds implied compounds 11 and 20, which showed weak activity with IC50 values of 25.56 µM and 21.20 µM, respectively.
Physics-Based Semantic Reasoning for Function Model Decomposition

In graph-based function models, the function verb and flow noun types are usually controlled by vocabularies of standard classes. The grammar is also controlled at different levels of formalism and contribute to reasoning. However, the text written in plain English for the names of the functions and flows is not used for formal reasoning to help with modeling or exploring the design space. This paper presents a formalism for semantic and physics-based reasoning on function model graphs, esp. to automatically decompose black box models and to generate design alternatives using those plain-English texts. A previously established formal language, which ensures that function models are consistent with physics laws, is used as a baseline. Semantic reasoning is added to use the unstructured information of the flow phrases to infer possible means of decomposing the model into a topology connecting appropriate subfunctions and to generate multiple alternative decompositions. A data structure of flow nouns, flow attributes, qualitative value scales, and qualitative physics laws is used as the data representation. An eight-step algorithm manipulates this data for reasoning. The paper shows two validation case studies to demonstrate the workings of the language.
Algorithm/Architecture Co-Design for Near-Memory Processing

With mainstream technologies to couple logic tightly with memory on the horizon, near-memory processing has re-emerged as a promising approach to improving performance and energy for data-centric computing. DRAM, however, is primarily designed for density and low cost, with a rigid internal organization that favors coarse-grain streaming rather than byte-level random access. This paper makes the case that treating DRAM as a block-oriented streaming device yields significant efficiency and performance benefits, which motivate for algorithm/architecture co-design to favor streaming access patterns, even at the price of a higher order algorithmic complexity. We present the Mondrian Data Engine that drastically improves the runtime and energy efficiency of basic in-memory analytic operators, despite doing more work as compared to traditional CPU-optimized algorithms, which heavily rely on random accesses and deep cache hierarchies
Regional Differences and Similarities in the Brain Transcriptome for Mice Selected for Ethanol Preference From HS-CC Founders

The high genetic complexity found in heterogeneous stock (HS-CC) mice, together with selective breeding, can be used to detect new pathways and mechanisms associated with ethanol preference and excessive ethanol consumption. We predicted that these pathways would provide new targets for therapeutic manipulation. Previously (Colville et al., 2017), we observed that preference selection strongly affected the accumbens shell (SH) genes associated with synaptic function and in particular genes associated with synaptic tethering. Here we expand our analyses to include substantially larger sample sizes and samples from two additional components of the “addiction circuit,” the central nucleus of the amygdala (CeA) and the prelimbic cortex (PL). At the level of differential expression (DE), the majority of affected genes are region-specific; only in the CeA did the DE genes show a significant enrichment in GO annotation categories, e.g., neuron part. In all three brain regions the differentially variable genes were significantly enriched in a single network module characterized by genes associated with cell-to-cell signaling. The data point to glutamate plasticity as being a key feature of selection for ethanol preference. In this context the expression of Dlg2 which encodes for PSD-93 appears to have a key role. It was also observed that the expression of the clustered protocadherins was strongly associated with preference selection.
Long‐term analysis of transorally resected p16 + Oropharynx cancer: Outcomes and prognostic factors

We observed high survival in a previous report of a p16‐positive, oropharyngeal carcinoma (OPC) cohort treated primarily with transoral laser microsurgery (TLM) ± adjuvant therapy and followed for ≥ 12 months. To address long‐term outcomes of primary transoral surgery for this unique disease, we present an updated analysis of our cohort with extended follow‐up.
Comparing line and AST granularity level for program repair using PyGGI

PyGGI is a lightweight Python framework that can be used to implement generic Genetic Improvement algorithms at the API level. The original version of PyGGI only provided lexical modifications, i.e., modifications of the source code at the physical line granularity level. This paper introduces new extensions to PyGGI that enables syntactic modifications for Python code, i.e., modifications that operates at the AST granularity level. Taking advantage of the new extensions, we also present a case study that compares the lexical and syntactic search granularity level for automated program repair, using ten seeded faults in a real world open source Python project. The results show that search landscapes at the AST granularity level are more effective (i.e. eventually more likely to produce plausible patches) due to the smaller sizes of ingredient spaces (i.e., the space from which we search for the material to build a patch), but may require longer time for search because the larger number of syntactically intact candidates leads to more fitness evaluations.