Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemical and physical guidance of fish spermatozoa into the egg through the micropyle

Abstract Eggs of teleost fish, unlike those of many other animals, allow sperm entry only at a single site, a narrow canal in the egg's chorion called the micropyle. In some fish (e.g., flounder, herring, and Alaska pollock), the micropyle is a narrow channel in the chorion, with or without a shallow depression around the outer opening of micropyle. In some other fish (e.g., salmon, pufferfish, cod, and medaka), the micropyle is like a funnel with a conical opening. Eggs of all the above fish have a glycoprotein tightly bound to the chorion surface around the micropyle. This glycoprotein directs spermatozoa into the micropylar canal in a Ca2+-dependent manner. This substance, called the micropylar sperm attractant or MISA, increases fertilization efficiency and is essential in herring. In flounder, salmon, and perhaps medaka, fertilization is possible without MISA, but its absence makes fertilization inefficient because most spermatozoa swim over the micropyle without entering it. The mechanism underlying sperm-MISA interactions is yet to be determined, but at least in herring the involvement of Ca2+ and K+ channel proteins, as well as CatSper and adenylyl cyclase, is very likely. In some other fish (e.g., zebrafish, loach, and goldfish), the chorion around the micropyle is deeply indented (e.g., zebrafish and loach) or it has radially or spirally arranged grooves around the outer opening of the micropyle (e.g., goldfish). MISA is absent from the eggs of these fish and sperm entry into micropylar canal seems to be purely physical. Summary Sentence In fish, sperm entry into the egg through the micropyle is guided either chemically or physically depending on the species
The Oncogenic Small Tumor Antigen of Merkel Cell Polyomavirus Is an Iron-Sulfur Cluster Protein That Enhances Viral DNA Replication

ABSTRACT Merkel cell polyomavirus (MCPyV) plays an important role in Merkel cell carcinoma (MCC). MCPyV small T (sT) antigen has emerged as the key oncogenic driver in MCC carcinogenesis. It has also been shown to promote MCPyV LT-mediated replication by stabilizing LT. The importance of MCPyV sT led us to investigate sT functions and to identify potential ways to target this protein. We discovered that MCPyV sT purified from bacteria contains iron-sulfur (Fe/S) clusters. Electron paramagnetic resonance analysis showed that MCPyV sT coordinates a [2Fe-2S] and a [4Fe-4S] cluster. We also observed phenotypic conservation of Fe/S coordination in the sTs of other polyomaviruses. Since Fe/S clusters are critical cofactors in many nucleic acid processing enzymes involved in DNA unwinding and polymerization, our results suggested the hypothesis that MCPyV sT might be directly involved in viral replication. Indeed, we demonstrated that MCPyV sT enhances LT-mediated replication in a manner that is independent of its previously reported ability to stabilize LT. MCPyV sT translocates to nuclear foci containing actively replicating viral DNA, supporting a direct role for sT in promoting viral replication. Mutations of Fe/S cluster-coordinating cysteines in MCPyV sT abolish its ability to stimulate viral replication. Moreover, treatment with cidofovir, a potent antiviral agent, robustly inhibits the sT-mediated enhancement of MCPyV replication but has little effect on the basal viral replication driven by LT alone. This finding further indicates that MCPyV sT plays a direct role in stimulating viral DNA replication and introduces cidofovir as a possible drug for controlling MCPyV infection. IMPORTANCE MCPyV is associated with a highly aggressive form of skin cancer in humans. Epidemiological surveys for MCPyV seropositivity and sequencing analyses of healthy human skin suggest that MCPyV may represent a common component of the human skin microbial flora. However, much of the biology of the virus and its oncogenic ability remain to be investigated. In this report, we identify MCPyV sT as a novel Fe/S cluster protein and show that conserved cysteine clusters are important for sT's ability to enhance viral replication. Moreover, we show that sT sensitizes MCPyV replication to cidofovir inhibition. The discovery of Fe/S clusters in MCPyV sT opens new avenues to the study of the structure and functionality of this protein. Moreover, this study supports the notion that sT is a potential drug target for dampening MCPyV infection.
$H^2$--Convergence of least-squares kernel collocation methods

The strong-form asymmetric kernel-based collocation method, commonly referred to as the Kansa method, is easy to implement and hence is widely used for solving engineering problems and partial differential equations despite the lack of theoretical support. The simple least-squares (LS) formulation, on the other hand, makes the study of its solvability and convergence rather nontrivial. In this paper, we focus on general second order linear elliptic differential equations in $\Omega \subset R^d$ under Dirichlet boundary conditions. With kernels that reproduce $H^m(\Omega)$ and some smoothness assumptions on the solution, we provide denseness conditions for a constrained least-squares method and a class of weighted least-squares algorithms to be convergent. Theoretically, we identify some $H^2(\Omega)$ convergent LS formulations that have an optimal error behavior like $h^{m-2}$. We also demonstrate the effects of various collocation settings on the respective convergence rates, as well as how these formulations perform with high order kernels and when coupled with the stable evaluation technique for the Gaussian kernel.
The complete chloroplast genome of a medicinal plant Epimedium koreanum Nakai (Berberidaceae)

Abstract Epimedium koreanum is a perennial medicinal plant distributed in Eastern Asia. The complete chloroplast genome sequences of E. koreanum was obtained by de novo assembly using whole genome next-generation sequences. The chloroplast genome of E. koreanum was 157 218 bp in length and separated into four distinct regions such as large single copy region (89 600 bp), small single copy region (17 222 bp) and a pair of inverted repeat regions (25 198 bp). The genome contained a total of 112 genes including 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Phylogenetic analysis with the reported chloroplast genomes revealed that E. koreanum is most closely related to Berberis bealei, a traditional medicinal plant in the Berberidaceae family.
Imaging of piezoelectric activity in laser-ablated c-axis-oriented LiNbO_3/ZnO thin film multilayer on glass using atomic force microscopy

A LiNbO_3/ZnO multilayer with a preferred c -axis orientation normal to the plane of the substrate was grown on glass and SiO_2/Si substrates by laser ablation. The piezoelectric activity in as-deposited films was demonstrated using a novel approach to the atomic force microscope. In the presence of an in-plane, low-frequency (0.1–5 Hz) alternating current electric field, we monitored and imaged the induced piezoelectric response normal to the film plane between two electrodes.
Characterization of Ageing- and Diet-Related Swine Models of Sarcopenia and Sarcopenic Obesity

Sarcopenia and sarcopenic obesity are currently considered major global threats for health and well-being. However, there is a lack of adequate preclinical models for their study. The present trial evaluated the suitability of aged swine by determining changes in adiposity, fatty acids composition, antioxidant status and lipid peroxidation, development of metabolic disturbances and structural changes in tissues and organs. Iberian sows with clinical evidence of aging-related sarcopenia were fed a standard diet fulfilling their maintenance requirements or an obesogenic diet for 100 days. Aging and sarcopenia were related to increased lipid accumulation and cellular dysfunction at both adipose tissue and non-adipose ectopic tissues (liver and pancreas). Obesity concomitant to sarcopenia aggravates the condition by increasing visceral adiposity and causing dyslipidemia, insulin resistance and lipotoxicity in non-adipose tissues. These results support that the Iberian swine model represents certain features of sarcopenia and sarcopenic obesity in humans, paving the way for future research on physiopathology of these conditions and possible therapeutic targets.
The complete mitochondrial genome of the Dipodomys ordii (Ord's kangaroo rat)

Abstract Ord's kangaroo rat is a kangaroo rat native to western North America. In this study, we first reported the complete mitochondrial genome of Dipodomys ordii that the first has the complete mitochondrial genome in the genus of Heteromyidae. The mitogenome is a circular molecule of 16 257 bp in length, containing 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs and a putative displacement loop region. All protein-coding genes started with a traditional ATN codon and terminated with the mitochondria stop codon (TAA/TAG/AGA) or a single T base. The gene order and composition of mitogenome was similar to that of most other Sciurognathi species and its GC content was 36.73%. Thirteen protein-coding genes of D. ordii together with eight other closely species were used to construct the species phylogenetic tree for verification of the accuracy of new determined mitogenome sequences.
Synthetic generation of solar states for smart grid: A multiple segment Markov chain approach

The use of photovoltaic (PV) sources is becoming very popular in smart grid for their ecological benefits, with higher scalability and utilization for local generation and delivery. PV can also potentially avoid the energy losses that are normally associated with long-range grid distribution. The increased penetration of solar panels, however, has introduced a need for solar energy models that are capable of producing realistic synthetic data with small error margins. Such models, for instance, can be used to design the appropriate size of energy storage devices or to determine the maximum charging rate of a PV-powered electric vehicle (EV) charging station. In this regard, this paper proposes a stochastic model for solar generation using a Markov chain approach. Based on real data, it is first shown that the solar states are inter-dependent, and thus suitable for modeling using a Markov model. Then, the probabilities of transition between states are shown to be heterogeneous over different time segments. A model is proposed that captures the intertemporal dependency of solar irradiance through segmentation of the Markov chain across different times of the day. In the studied model, different state transition matrices are constructed for different time segments, which the proposed algorithm then uses to generate the solar states for different times of the day. Numerical examples are provided to show the effectiveness of the proposed synthetic generator.
Fully Automatic Cephalometric Evaluation using Random Forest Regression-Voting

Cephalometric analysis is commonly used as a standard tool for orthodontic diagnosis and treatment planning. The identification of cephalometric landmarks on images of the skull allows the quantification and classification of anatomical abnormalities. In clinical practice, the landmarks are placed manually which is time-consuming and subjective. This work investigates the application of Random Forest regression-voting to fully automatically detect cephalometric landmarks, and to use the identified positions for automatic cephalometric evaluation. Validation experiments on two sets of 150 images show that we achieve an average mean error of 1.6mm - 1.7mm and a successful detection rate of 75% - 85% for a 2mm precision range, and that the accuracy of our automatic cephalometric evaluation is 77% - 79%. This work shows great promise for application to computer-assisted cephalometric treatment and surgery planning.
Differences in white matter structure and cortical thickness between patients with traumatic and idiopathic chronic neck pain: Associations with cognition and pain modulation?

Brain alterations are hypothesized to be present in patients with chronic whiplash‐associated disorders (CWAD). The aim of this case–control study was to examine alterations in cortical thickness and white matter (WM) structure, and the presence of brain microhemorrhages in a patient group encountering chronic neck pain of traumatic origin (i.e., CWAD) when compared with a patient group characterized by nontraumatic chronic neck pain [i.e., chronic idiopathic neck pain (CINP)], and healthy controls. Furthermore, we aimed to investigate associations between brain structure on one hand and cognitive performance and central sensitization (CS) on the other hand. T1‐weighted, diffusion‐weighted and T2*‐weighted magnetic resonance images of the brain were acquired in 105 women (31 controls, 37 CINP, 37 CWAD) to investigate regional cortical thickness, WM structure, and microhemorrhages, respectively. Next, cognitive performance, and CS encompassing distant hyperalgesia and conditioned pain modulation (CPM) efficacy were examined. Cortical thinning in the left precuneus was revealed in CWAD compared with CINP patients. Also, decreased fractional anisotropy, together with increased values of mean diffusivity and radial diffusivity could be observed in the left cingulum hippocampus and tapetum in CWAD compared with CINP, and in the left tapetum in CWAD patients compared with controls. Moreover, the extent of WM structural deficits in the left tapetum coincided with decreased CPM efficacy in the CWAD group. This yields evidence for associations between decreased endogenous pain inhibition, and the degree of regional WM deficits in CWAD. Our results emphasize the role of structural brain alterations in women with CWAD compared with CINP.
Metagenomic Analysis of the Microbiota from the Crop of an Invasive Snail Reveals a Rich Reservoir of Novel Genes

The shortage of petroleum reserves and the increase in CO2 emissions have raised global concerns and highlighted the importance of adopting sustainable energy sources. Second-generation ethanol made from lignocellulosic materials is considered to be one of the most promising fuels for vehicles. The giant snail Achatina fulica is an agricultural pest whose biotechnological potential has been largely untested. Here, the composition of the microbial population within the crop of this invasive land snail, as well as key genes involved in various biochemical pathways, have been explored for the first time. In a high-throughput approach, 318 Mbp of 454-Titanium shotgun metagenomic sequencing data were obtained. The predominant bacterial phylum found was Proteobacteria, followed by Bacteroidetes and Firmicutes. Viruses, Fungi, and Archaea were present to lesser extents. The functional analysis reveals a variety of microbial genes that could assist the host in the degradation of recalcitrant lignocellulose, detoxification of xenobiotics, and synthesis of essential amino acids and vitamins, contributing to the adaptability and wide-ranging diet of this snail. More than 2,700 genes encoding glycoside hydrolase (GH) domains and carbohydrate-binding modules were detected. When we compared GH profiles, we found an abundance of sequences coding for oligosaccharide-degrading enzymes (36%), very similar to those from wallabies and giant pandas, as well as many novel cellulase and hemicellulase coding sequences, which points to this model as a remarkable potential source of enzymes for the biofuel industry. Furthermore, this work is a major step toward the understanding of the unique genetic profile of the land snail holobiont.
Internet banking in Pakistan: an extended technology acceptance perspective

The growing attractiveness of internet banking is contributing well in the success and growth process of banking sector around the world (Xu et al., 2009). This study examines the integrative framework of internet banking (IB) in Pakistan using technology acceptance model (TAM) with the integration of several risk dimensions and initial trust model. The techniques of both exploratory and confirmatory factor analyses are employed to assess the reliability and validity of the measurement model. The structural equation modelling method was also applied to investigate the hypothetical framework with the help of literature's recommended goodness-of-fit measurements. The findings of the study found significant contribution of personal propensity to trust, structural assurance, and familiarity with bank in influencing initial trust of people to accept IB. The findings are beneficial for banks that are pursuing IB in formulating strategies of enhancing user's acceptance of internet banking in Pakistan.
Multi‐Variate Gaussian‐Based Inverse Kinematics

Inverse kinematics (IK) equations are usually solved through approximated linearizations or heuristics. These methods lead to character animations that are unnatural looking or unstable because they do not consider both the motion coherence and limits of human joints. In this paper, we present a method based on the formulation of multi‐variate Gaussian distribution models (MGDMs), which precisely specify the soft joint constraints of a kinematic skeleton. Each distribution model is described by a covariance matrix and a mean vector representing both the joint limits and the coherence of motion of different limbs. The MGDMs are automatically learned from the motion capture data in a fast and unsupervised process. When the character is animated or posed, a Gaussian process synthesizes a new MGDM for each different vector of target positions, and the corresponding objective function is solved with Jacobian‐based IK. This makes our method practical to use and easy to insert into pre‐existing animation pipelines. Compared with previous works, our method is more stable and more precise, while also satisfying the anatomical constraints of human limbs. Our method leads to natural and realistic results without sacrificing real‐time performance.
Finding latent performance bugs in systems implementations

Robust distributed systems commonly employ high-level recovery mechanisms enabling the system to recover from a wide variety of problematic environmental conditions such as node failures, packet drops and link disconnections. Unfortunately, these recovery mechanisms also effectively mask additional serious design and implementation errors, disguising them as latent performance bugs that severely degrade end-to-end system performance. These bugs typically go unnoticed due to the challenge of distinguishing between a bug and an intermittent environmental condition that must be tolerated by the system. We present techniques that can automatically pinpoint latent performance bugs in systems implementations, in the spirit of recent advances in model checking by systematic state space exploration. The techniques proceed by automating the process of conducting random simulations, identifying performance anomalies, and analyzing anomalous executions to pinpoint the circumstances leading to performance degradation. By focusing our implementation on the MACE toolkit, MACEPC can be used to test our implementations directly, without modification. We have applied MACEPC to five thoroughly tested and trusted distributed systems implementations. MACEPC was able to find significant, previously unknown, long-standing performance bugs in each of the systems, and led to fixes that significantly improved the end-to-end performance of the systems.
Influence Of The Filament Winding ProcessVariables On The Mechanical Behavior Of AComposite Pressure Vessel

A numerical analysis of a composite internally pressurized cylindrical vessel with spherical domes is presented. The structure is considered a filament winding process vessel in which a continuous strand of fiber is wound over a rotating male mandrel. During the winding process a variable thickness is created in the dome region which considerably alters its mechanical performance. Additionally, the fiber path depends on the surface where the fibers are wound; as a result the winding angle varies in the dome with regards to its longitudinal direction. The vessel is modeled as a non-structural internal liner reinforced with an orthotropic composite: carbon fiber reinforced plastic. Stress was calculated by applying the first-order shear deformation theory, and the Tsai-Wu failure criterion was considered as the limit state function of the laminate. The structure’s optimum design is performed taking into account the main process variables, the winding angle and layer thickness. A finite element analysis was performed considering the winding angles as well as the thickness change through the dome, in order to study the effects of the winding process variables on the mechanical behavior of the composite vessel. A convergence study was carried out in order to verify the finite element analysis. It considered several shell element types. In order to model the structure, quadrilateral stress/displacement shell elements with 8-nodes (6-degrees of freedom each), quadratic interpolation and reduced integration were used.
CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss

Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration–approved drugs to prevent or treat it. We screened 4,385 small molecules in a cochlear cell line and identified 10 compounds that protected against cisplatin toxicity in mouse cochlear explants. Among them, kenpaullone, an inhibitor of multiple kinases, including cyclin-dependent kinase 2 (CDK2), protected zebrafish lateral-line neuromasts from cisplatin toxicity and, when delivered locally, protected adult mice and rats against cisplatin- and noise-induced hearing loss. CDK2-deficient mice displayed enhanced resistance to cisplatin toxicity in cochlear explants and to cisplatin- and noise-induced hearing loss in vivo. Mechanistically, we showed that kenpaullone directly inhibits CDK2 kinase activity and reduces cisplatin-induced mitochondrial production of reactive oxygen species, thereby enhancing cell survival. Our experiments have revealed the proapoptotic function of CDK2 in postmitotic cochlear cells and have identified promising therapeutics for preventing hearing loss.
Generative Recurrent Networks for De Novo Drug Design

Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short‐term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine‐tuned the RNN′s predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN‐LSTM system for high‐impact use cases, such as low‐data drug discovery, fragment based molecular design, and hit‐to‐lead optimization for diverse drug targets.