Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain-Wide Genome-Wide Association Study for Alzheimer's Disease via Joint Projection Learning and Sparse Regression Model

Brain-wide and genome-wide association (BW-GWA) study is presented in this paper to identify the associations between the brain imaging phenotypes (i.e., regional volumetric measures) and the genetic variants [i.e., single nucleotide polymorphism (SNP)] in Alzheimer's disease (AD). The main challenges of this study include the data heterogeneity, complex phenotype–genotype associations, high-dimensional data (e.g., thousands of SNPs), and the existence of phenotype outliers. Previous BW-GWA studies, while addressing some of these challenges, did not consider the diagnostic label information in their formulations, thus limiting their clinical applicability. To address these issues, we present a novel joint projection and sparse regression model to discover the associations between the phenotypes and genotypes. Specifically, to alleviate the negative influence of data heterogeneity, we first map the genotypes into an intermediate imaging-phenotype-like space. Then, to better reveal the complex phenotype–genotype associations, we project both the mapped genotypes and the original imaging phenotypes into a diagnostic-label-guided joint feature space, where the intraclass projected points are constrained to be close to each other. In addition, we use $\ell _{2,1}$-norm minimization on both the regression loss function and the transformation coefficient matrices, to reduce the effect of phenotype outliers and also to encourage sparse feature selections of both the genotypes and phenotypes. We evaluate our method using AD neuroimaging initiative dataset, and the results show that our proposed method outperforms several state-of-the-art methods in term of the average root-mean-square error of genome-to-phenotype predictions. Besides, the associated SNPs and brain regions identified in this study have also been shown in the previous AD-related studies, thus verifying the effectiveness and potential of our proposed method in AD pathogenesis study.
Local Adaptive Projection Framework for Feature Selection of Labeled and Unlabeled Data

Most feature selection methods first compute a similarity matrix by assigning a fixed value to pairs of objects in the whole data or to pairs of objects in a class or by computing the similarity between two objects from the original data. The similarity matrix is fixed as a constant in the subsequent feature selection process. However, the similarities computed from the original data may be unreliable, because they are affected by noise features. Moreover, the local structure within classes cannot be recovered if the similarities between the pairs of objects in a class are equal. In this paper, we propose a novel local adaptive projection (LAP) framework. Instead of computing fixed similarities before performing feature selection, LAP simultaneously learns an adaptive similarity matrix <inline-formula> <tex-math notation="LaTeX">$\mathbf{S}$ </tex-math></inline-formula> and a projection matrix <inline-formula> <tex-math notation="LaTeX">$\mathbf{W}$ </tex-math></inline-formula> with an iterative method. In each iteration, <inline-formula> <tex-math notation="LaTeX">$\mathbf{S}$ </tex-math></inline-formula> is computed from the projected distance with the learned <inline-formula> <tex-math notation="LaTeX">$\mathbf{W}$ </tex-math></inline-formula> and W is computed with the learned <inline-formula> <tex-math notation="LaTeX">$\mathbf{S}$ </tex-math></inline-formula>. Therefore, LAP can learn better projection matrix <inline-formula> <tex-math notation="LaTeX">$\mathbf{W}$ </tex-math></inline-formula> by weakening the effect of noise features with the adaptive similarity matrix. A supervised feature selection with LAP (SLAP) method and an unsupervised feature selection with LAP (ULAP) method are proposed. Experimental results on eight data sets show the superiority of SLAP compared with seven supervised feature selection methods and the superiority of ULAP compared with five unsupervised feature selection methods.
Low-Rank Preserving Projection Via Graph Regularized Reconstruction

Preserving global and local structures during projection learning is very important for feature extraction. Although various methods have been proposed for this goal, they commonly introduce an extra graph regularization term and the corresponding regularization parameter that needs to be tuned. However, tuning the parameter manually not only is time-consuming, but also is difficult to find the optimal value to obtain a satisfactory performance. This greatly limits their applications. Besides, projections learned by many methods do not have good interpretability and their performances are commonly sensitive to the value of the selected feature dimension. To solve the above problems, a novel method named low-rank preserving projection via graph regularized reconstruction (LRPP_GRR) is proposed. In particular, LRPP_GRR imposes the graph constraint on the reconstruction error of data instead of introducing the extra regularization term to capture the local structure of data, which can greatly reduce the complexity of the model. Meanwhile, a low-rank reconstruction term is exploited to preserve the global structure of data. To improve the interpretability of the learned projection, a sparse term with ${l_{2,1}}$ norm is imposed on the projection. Furthermore, we introduce an orthogonal reconstruction constraint to make the learned projection hold main energy of data, which enables LRPP_GRR to be more flexible in the selection of feature dimension. Extensive experimental results show the proposed method can obtain competitive performance with other state-of-the-art methods.
The CHILDES Project: Tools for Analyzing Talk (third edition): Volume I: Transcription format and programs, Volume II: The database

Thirteen invited papers from a two-day discussion session held in September 1999 are collected in this issue of Philosophical Transactions of The Royal Society. All the papers have been revised and edited, and the discussion following the presentation of each paper has been transcribed and appended. In addition, the editors have contributed a paper-length introduction. The contents are as follows:
Translation elongation and mRNA stability are coupled through the ribosomal A-site

Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in eukaryotic cells. Previous work by us and others has shown that codon identity exerts a powerful influence on mRNA stability. In Saccharomyces cerevisiae, studies using a handful of reporter mRNAs show that optimal codons increase translation elongation rate, which in turn increase mRNA stability. However, a direct link between elongation rate and mRNA stability has not been established across the entire yeast transcriptome. In addition, there is evidence from work in higher eukaryotes that amino acid identity influences mRNA stability, raising the question as to whether the impact of translation elongation on mRNA decay is at the level of tRNA decoding, amino acid incorporation, or some combination of each. To address these questions, we performed ribosome profiling of wildtype yeast. In good agreement with other studies, our data showed faster codon-specific elongation over optimal codons and faster transcript-level elongation correlating with transcript optimality. At both the codon-level and transcript-level, faster elongation correlated with increased mRNA stability. These findings were reinforced by showing increased translation efficiency and kinetics for a panel of 11 HIS3 reporter mRNAs of increasing codon optimality. While we did observe that elongation measured by ribosome profiling is composed of both amino acid identity and synonymous codon effects, further analyses of these data establish that A-site tRNA decoding rather than other steps of translation elongation is driving mRNA decay in yeast.
The Multiplanetary Future of Plant Synthetic Biology

The interest in human space journeys to distant planets and moons has been re-ignited in recent times and there are ongoing plans for sending the first manned missions to Mars in the near future. In addition to generating oxygen, fixing carbon, and recycling waste and water, plants could play a critical role in producing food and biomass feedstock for the microbial manufacture of materials, chemicals, and medicines in long-term interplanetary outposts. However, because life on Earth evolved under the conditions of the terrestrial biosphere, plants will not perform optimally in different planetary habitats. The construction or transportation of plant growth facilities and the availability of resources, such as sunlight and liquid water, may also be limiting factors, and would thus impose additional challenges to efficient farming in an extraterrestrial destination. Using the framework of the forthcoming human missions to Mars, here we discuss a series of bioengineering endeavors that will enable us to take full advantage of plants in the context of a Martian greenhouse. We also propose a roadmap for research on adapting life to Mars and outline our opinion that synthetic biology efforts towards this goal will contribute to solving some of the main agricultural and industrial challenges here on Earth.
Giant Self-Kerr Nonlinearity in the Metal Nanoparticles-Graphene Nanodisks-Quantum Dots Hybrid Systems Under Low-Intensity Light Irradiance

Hybrid nanocomposites can provide a promising platform for integrated optics. Optical nonlinearity can significantly widen the range of applications of such structures. In the present paper, a theoretical investigation is carried out by solving the density matrix equations derived for a metal nanoparticles-graphene nanodisks-quantum dots hybrid system interacting with weak probe and strong control fields, in the steady state. We derive analytical expressions for linear and third-order nonlinear susceptibilities of the probe field. A giant self-Kerr nonlinear index of refraction is obtained in the optical region with relatively low light intensity. The optical absorption spectrum of the system demonstrates electromagnetically induced transparency and amplification without population inversion in the linear optical response arising from the negative real part of the polarizabilities for the plasmonic components at the energy of the localized surface plasmon resonance of the graphene nanodisks induced by the probe field. We find that the self-Kerr nonlinear optical properties of the system can be controlled by the geometrical features of the system, the size of metal nanoparticles and the strength of the control field. The controllable self-Kerr nonlinearities of hybrid nanocomposites can be employed in many interesting applications of modern integrated optics devices allowing for high nonlinearity with relatively low light intensity.
Combining YESS and TESSYS techniques during percutaneous transforaminal endoscopic discectomy for multilevel lumbar disc herniation

Abstract The authors retrospectively characterized the clinical outcomes of combining the Yeung endoscopic spine system (YESS) and transforaminal endoscopic surgical system (TESSYS) techniques during percutaneous transforaminal endoscopic discectomy (PTED) to treat multilevel lumbar disc herniation. PTED using both YESS and TESSYS was performed on 52 patients with multilevel lumbar disc herniations who had shown no apparent response to previous conservative treatments. Postsurgical follow-ups were conducted at weeks 1, 26, and 48. Patients’ preoperative and postoperative performances were assessed by modified MacNab classification, Japanese Orthopedic Association (JOA) scores, Oswestry disability index (ODI), and visual analog scale (VAS), and compared with 34 and 45 patients who were treated only by YESS and TESSYS, respectively. The postsurgery surgeon-performed assessment showed satisfactory results in 98% of the YESS + TESSYS-treated cases. The average operative time was 116 ± 23 minutes, intraoperative bleeding was 19 ± 12 mL, and bed stay was 3 days. No complications occurred, including infection, nerve injury, or spinal canal hematoma. One week after surgery, the modified MacNab classifications of the patients were excellent in 45, good in 6, fair in 1, and poor in 0 (98% were excellent or good). JOA, ODI, and VAS scores for low back pain significantly improved relative to the preoperative assessment (P < .01) and had remained stable at 26 and 48 weeks. PTED that combined YESS and TESSYS techniques, depending on the predominant type of lumbar disc herniation at individual levels, is safe, minimally invasive, and effective.
Improved Risk-Adjusted Survival for Melanoma Brain Metastases in the Era of Checkpoint Blockade Immunotherapies: Results from a National Cohort

Melanoma patients presenting with brain metastases have been mostly excluded from treatment trials. A large-scale analysis of these patients from a national cohort revealed that after immune checkpoint blockade, median and 4-year overall survival were significantly improved. The successes of checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy trials have generated substantial promise for revolutionizing the management of patients with advanced melanoma. However, because early clinical trials of CBIs and BRAFV600-targeted therapy either excluded or included disproportionately fewer cases of melanoma brain metastases (MBMs), the survival benefit of these novel therapies for MBM remains unknown. We, therefore, evaluated the characteristics, management, and overall survival (OS) of patients who presented with cutaneous MBMs during 2010 to 2015 using the National Cancer Database, which comprises 70% of all newly diagnosed U.S. cancers. OS was analyzed with risk-adjusted proportional hazards and compared by Kaplan–Meier techniques. We found that 2,753 (36%) of patients presenting with stage 4 melanoma had MBMs. Following the 2011 FDA approvals for CBI and BRAFV600-targeted therapy, MBM patients demonstrated a 91% relative increase in 4-year OS to 14.1% from 7.4% preapproval (P < 0.001). Postapproval, the proportion of MBM patients who received CBI rose from 10.5% in 2011 to 34.0% in 2015 (P < 0.001). Initial CBI in MBM patients displayed an improved median and 4-year OS of 12.4 months (compared with 5.2 months; P < 0.001) and 28.1% (compared with 11.1%), respectively. These benefits were pronounced in MBM patients without extracranial metastases, in which CBI demonstrated improved median and 4-year OS of 56.4 months (compared with 7.7 months; P < 0.001) and 51.5% (compared with 16.9%), respectively. Using a large national cohort composed of a “real-life” MBM treatment population, we demonstrated the dramatic OS improvements associated with novel checkpoint blockade immunotherapies. Cancer Immunol Res; 6(9); 1039–45. ©2018 AACR.
Single-shot quantitative phase microscopy based on color-multiplexed Fourier ptychography.

We present a single-shot quantitative phase imaging (QPI) method based on color-multiplexed Fourier ptychographic microscopy (FPM). Three light-emitting diode (LED) elements with respective R/G/B channels in a programmable LED array illuminate the specimen simultaneously, providing triangle oblique illuminations matching the numerical aperture of the objective precisely. A color image sensor records the light transmitted through the specimen, and three monochromatic intensity images at each color channel are then separated and utilized to recover the phase of the specimen. After one-step deconvolution based on the phase contrast transfer function, the obtained initial phase map is further refined by the FPM-based iterative recovery algorithm to overcome pixel-aliasing and improve the phase recovery accuracy. The high-speed, high-throughput QPI capabilities of the proposed approach are demonstrated by imaging HeLa cells mitosis in vitro, achieving a half-pitch resolution of 388 nm across a wide field of view of 1.33 mm2 at camera-limited frame rates (50 fps).
Analysis of gonadotrophin‐releasing hormone‐1 and kisspeptin neuronal systems in the nonphotoregulated seasonally breeding eastern rock elephant‐shrew (Elephantulus myurus)

Of the 18 sub‐Saharan elephant‐shrew species, only eastern rock elephant‐shrews reproduce seasonally throughout their distribution, a process seemingly independent of photoperiod. The present study characterizes gonadal status and location/intensity of gonadotrophin‐releasing hormone‐1 (GnRH‐1) and kisspeptin immunoreactivities in this polyovulating species in the breeding and nonbreeding seasons. GnRH‐1‐immunoreactive (ir) cell bodies are predominantly in the medial septum, diagonal band, and medial preoptic area; processes are generally sparse except in the external median eminence. Kisspeptin‐ir cell bodies are detected only within the arcuate nucleus; the density of processes is generally low, except in the septohypothalamic nucleus, ventromedial bed nucleus of the stria terminalis, arcuate nucleus, and internal and external median eminence. Kisspeptin‐ir processes are negligible at locations containing GnRH‐1‐ir cell bodies. The external median eminence is the only site with conspicuously overlapping distributions of the respective immunoreactivities and, accordingly, a putative site for kisspeptin's regulation of GnRH‐1 release in this species. In the nonbreeding season in males, there is an increase in the rostral population of GnRH‐1‐ir cell bodies and density of GnRH‐1‐ir processes in the median eminence. In both sexes, the breeding season is associated with increased kisspeptin‐ir process density in the rostral periventricular area of the third ventricle and arcuate nucleus; at the latter site, this is positively correlated with gonadal mass. Cross‐species comparisons lead us to hypothesize differential mechanisms within these peptidergic systems: that increased GnRH‐1 immunoreactivity during the nonbreeding season reflects increased accumulation with reduced release; that increased kisspeptin immunoreactivity during the breeding season reflects increased synthesis with increased release.
Oxygen Consumption Rate Analysis of Mitochondrial Dysfunction Caused by Bacillus cereus Cereulide in Caco-2 and HepG2 Cells

The emetic syndrome of Bacillus cereus is a food intoxication caused by cereulide (CER) and manifested by emesis, nausea and in most severe cases with liver failure. While acute effects have been studied in the aftermath of food intoxication, an exposure to low doses of cereulide might cause unnoticed damages to the intestines and liver. The toxicity which relies on the mitochondrial dysfunction was assessed on Caco-2 and HepG2 cells after exposure of one, three and ten days to a range of low doses of cereulide. Oxygen consumption rate analyses were used to study the impact of low doses of CER on the bioenergetics functions of undifferentiated Caco-2 and HepG2 cells using Seahorse XF extracellular flux analyzer. Both Caco-2 and HepG2 cells experienced measurable mitochondrial impairment after prolonged exposure of 10 days to 0.25 nM of cereulide. Observed mitochondrial dysfunction was greatly reflected in reduction of maximal cell respiration. At 0.50 nM CER, mitochondrial respiration was almost completely shut down, especially in HepG2 cells. These results corresponded with a severe reduction in the amount of cells and an altered morphology, observed by microscopic examination of the cells. Accurate and robust quantification of basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration allowed better understanding of the effects of cereulide in underlying respiratory malfunctions in low-dose exposure.
SEGF: A Novel Method for Gene Fusion Detection from Single-End Next-Generation Sequencing Data

With the development and application of next-generation sequencing (NGS) and target capture technology, the demand for an effective analysis method to accurately detect gene fusion from high-throughput data is growing. Hence, we developed a novel fusion gene analyzing method called single-end gene fusion (SEGF) by starting with single-end DNA-seq data. This approach takes raw sequencing data as input, and integrates the commonly used alignment approach basic local alignment search tool (BLAST) and short oligonucleotide analysis package (SOAP) with stringent passing filters to achieve successful fusion gene detection. To evaluate SEGF, we compared it with four other fusion gene discovery analysis methods by analyzing sequencing results of 23 standard DNA samples and DNA extracted from 286 lung cancer formalin fixed paraffin embedded (FFPE) samples. The results generated by SEGF indicated that it not only detected the fusion genes from standard samples and clinical samples, but also had the highest accuracy and sensitivity among the five compared methods. In addition, SEGF was capable of detecting complex gene fusion types from single-end NGS sequencing data compared with other methods. By using SEGF to acquire gene fusion information at DNA level, more useful information can be retrieved from the DNA panel or other DNA sequencing methods without generating RNA sequencing information to benefit clinical diagnosis or medication instruction. It was a timely and cost-effective measure with regard to research or diagnosis. Considering all the above, SEGF is a straightforward method without manipulating complicated arguments, providing a useful approach for the precise detection of gene fusion variation.
Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis

Peptidoglycan synthesis is an important target for antibiotics and relies on intermediates derived from central metabolism. As a result, alterations of metabolism may affect antibiotic sensitivity. An aspB mutant is auxotrophic for aspartate (Asp) and asparagine (Asn) and lyses when grown in Difco sporulation medium (DSM), but not in LB medium. Genetic and physiological studies, supported by amino acid analysis, reveal that cell lysis in DSM results from Asp limitation due to a relatively low Asp and high glutamate (Glu) concentrations, with Glu functioning as a competitive inhibitor of Asp uptake by the major Glu/Asp transporter GltT. Lysis can be specifically suppressed by supplementation with 2,6‐diaminopimelate (DAP), which is imported by two different cystine uptake systems. These studies suggest that aspartate limitation depletes the peptidoglycan precursor meso‐2,6‐diaminopimelate (mDAP), inhibits peptidoglycan synthesis, upregulates the cell envelope stress response mediated by σM and eventually leads to cell lysis. Aspartate limitation sensitizes cells to antibiotics targeting late steps of PG synthesis, but not steps prior to the addition of mDAP into the pentapeptide sidechain. This work highlights the ability of perturbations of central metabolism to sensitize cells to peptidoglycan synthesis inhibitors.