Miracle-dz/UniFAR-FTUs huggingface dataset:
CM Stability and the Generalized Futaki Invariant I

Based on the Cayley, Grothendieck, Knudsen Mumford theory of determinants we extend the CM polarization to the Hilbert scheme. We identify the weight of this refined line bundle with the generalized Futaki invariant of Donaldson. We are able to conclude that CM stability implies K-Stability. An application of the Grothendieck Riemann Roch Theorem shows that this refined sheaf is isomorphic to the CM polarization introduced by Tian in 1994 on any closed, simply connected base .
A Sparse PLS for Variable Selection when Integrating Omics Data

Recent biotechnology advances allow for multiple types of omics data, such as transcriptomic, proteomic or metabolomic data sets to be integrated. The problem of feature selection has been addressed several times in the context of classification, but needs to be handled in a specific manner when integrating data. In this study, we focus on the integration of two-block data that are measured on the same samples. Our goal is to combine integration and simultaneous variable selection of the two data sets in a one-step procedure using a Partial Least Squares regression (PLS) variant to facilitate the biologists' interpretation. A novel computational methodology called ``sparse PLS" is introduced for a predictive analysis to deal with these newly arisen problems. The sparsity of our approach is achieved with a Lasso penalization of the PLS loading vectors when computing the Singular Value Decomposition.Sparse PLS is shown to be effective and biologically meaningful. Comparisons with classical PLS are performed on a simulated data set and on real data sets. On one data set, a thorough biological interpretation of the obtained results is provided. We show that sparse PLS provides a valuable variable selection tool for highly dimensional data sets.
Lack of Type VIII Collagen in Mice Ameliorates Diabetic Nephropathy

OBJECTIVE Key features of diabetic nephropathy include the accumulation of extracellular matrix proteins. In recent studies, increased expression of type VIII collagen in the glomeruli and tubulointerstitium of diabetic kidneys has been noted. The objectives of this study were to assess whether type VIII collagen affects the development of diabetic nephropathy and to determine type VIII collagen–dependent pathways in diabetic nephropathy in the mouse model of streptozotocin (STZ)-induced diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced by STZ injections in collagen VIII–deficient or wild-type mice. Functional and histological analyses were performed 40 days after induction of diabetes. Type VIII collagen expression was assessed by Northern blots, immunohistochemistry, and real-time PCR. Proliferation of primary mesangial cells was measured by thymidine incorporation and direct cell counting. Expression of phosphorylated extracellular signal–regulated kinase (ERK1/2) and p27Kip1 was assessed by Western blots. Finally, Col8a1 was stably overexpressed in mesangial cells. RESULTS Diabetic wild-type mice showed a strong renal induction of type VIII collagen. Diabetic Col8a1−/Col8a2− animals revealed reduced mesangial expansion and cellularity and extracellular matrix expansion compared with the wild type. These were associated with less albuminuria. High-glucose medium as well as various cytokines induced Col8a1 in cultured mesangial cells. Col8a1−/Col8a2− mesangial cells revealed decreased proliferation, less phosphorylation of Erk1/2, and increased p27Kip1 expression. Overexpression of Col8a1 in mesangial cells induced proliferation. CONCLUSIONS Lack of type VIII collagen confers renoprotection in diabetic nephropathy. One possible mechanism is that type VIII collagen permits and/or fosters mesangial cell proliferation in early diabetic nephropathy.
Legume Consumption and All-Cause and Cardiovascular Disease Mortality

Background Legume consumption is suggested to have protective effects against cardiovascular disease (CVD) mortality in the general population, but the results have been equivocal. We conducted a meta-analysis of prospective cohort studies to assess the association between legume consumption and risk of CVD mortality and all-cause mortality. Methods and Results Medline (via Ovid) and EMBASE (via Ovid) databases were searched through April 2017 to identify eligible studies. The two authors independently extracted the data and the adjusted relative risks (RRs) and 95% confidence intervals (CIs) were pooled by using a random-effects model. A total of 6 studies were identified, including the sizes of participants ranging from 23,601 to 59,485 with a sum of 21,8997. Comparing the highest category with the lowest, the pooled RR (95% CI) was 0.96 (0.86–1.06) for CVD mortality and 0.93 (0.87–0.99) for all-cause mortality. Conclusions Results from the current study show that high legume intakes are associated with lower risk of all-cause mortality. In consideration of the small number of studies, the evidence for assessing relationship between legumes intake and risk of all-cause mortality remains inclusive and warrants further study in the future. Further, consuming legumes does not increase the risk of CVD mortality.
SPOCK1 promotes tumor growth and metastasis in human prostate cancer

Prostate cancer is the most diagnosed noncutaneous cancer and ranks as the second leading cause of cancer-related deaths in American males. Metastasis is the primary cause of prostate cancer mortality. Survival rate is only 28% for metastatic patients, but is nearly 100% for patients with localized prostate cancers. Molecular mechanisms that underlie this malignancy remain obscure, and this study investigated the role of SPARC/osteonectin, cwcv, and kazal-like domain proteoglycan 1 (SPOCK1) in prostate cancer progression. Initially, we found that SPOCK1 expression was significantly higher in prostate cancer tissues relative to noncancerous tissues. In particular, SPOCK1 expression was also markedly high in metastatic tissues compared with nonmetastatic cancerous tissues. SPOCK1 expression knockdown by specific short hairpin RNA in PC3 cells was significantly inhibited, whereas SPOCK1 overexpression in RWPE-1 cells promoted cell viability, colony formation in vitro, and tumor growth in vivo. Moreover, the SPOCK1 knockdown in PC3 cells was associated with cell cycle arrest in G0/G1 phase, while the SPOCK1 overexpression in RWPE-1 cells induced cell cycle arrest in S phase. The SPOCK1 knockdown in PC3 cells even increased cell apoptosis. SPOCK1 modulation was also observed to affect cancerous cell proliferation and apoptotic processes in the mouse model of prostate cancer. Additionally, the SPOCK1 knockdown decreased, whereas the SPOCK1 overexpression increased cell migration and invasion abilities in vitro. Injection of SPOCK1-depleted PC3 cells significantly decreased metastatic nodules in mouse lungs. These findings suggest that SPOCK1 is a critical mediator of tumor growth and metastasis in prostate cancer.
Utility of a Novel Biofeedback Device for Within-Breath Modulation of Heart Rate in Rats: A Quantitative Comparison of Vagus Nerve vs. Right Atrial Pacing

In an emerging bioelectronics era, there is a clinical need for physiological devices incorporating biofeedback that permits natural and demand-dependent control in real time. Here, we describe a novel device termed a central pattern generator (CPG) that uses cutting edge analog circuitry producing temporally controlled, electrical stimulus outputs based on the real time integration of physiological feedback. Motivated by the fact that respiratory sinus arrhythmia (RSA), which is the cyclical changes in heart rate every breath, is an essential component of heart rate variability (HRV) (an indicator of cardiac health), we have explored the versatility and efficiency of the CPG for producing respiratory modulation of heart rate in anesthetized, spontaneously breathing rats. Diaphragmatic electromyographic activity was used as the input to the device and its output connected to either the right cervical vagus nerve or the right atrium for pacing heart rate. We found that the CPG could induce respiratory related heart rate modulation that closely mimicked RSA. Whether connected to the vagus nerve or right atrium, the versatility of the device was demonstrated by permitting: (i) heart rate modulation in any phase of the respiratory cycle, (ii) control of the magnitude of heart rate modulation, and (iii) instant adaptation to changes in respiratory frequency. Vagal nerve pacing was only possible following transection of the nerve limiting its effective use chronically. Pacing via the right atrium permitted better flexibility and control of heart rate above its intrinsic level. This investigation now lays the foundation for future studies using this biofeedback technology permitting closer analysis of both the function and dysfunction of RSA.
Isolation and Identification of Escherichia coli from Buffalo’s Milk using PCR Technique in Nineveh Governorate

UBCLINICAL mastitis (SCM) poses a considerable burden and challenge to modern dairy management. The occurence of Escherichia coli ( E. coli ) in numerous categories of food such as meat, egg, and milk also increases a public health concern, particularly through the consumption of unpasteurized dairy products, impacting human health. The primary objective of current study was to detect E. coli from states of sub-clinical mastitis in buffalo. The researchers employed classical methods for isolation and identification. Additionally, they utilized PCR (Polymerase Chain Reaction) techniques to detect specific virulence factors encoding genes, namely Stx1, and Stx2 , which are associated with the pathogenicity of E. coli . Between March and July 2023, a total of fifty milk specimens were taken from buffalo. These specimens were obtained from diverse regions, including Kenitra, Haoy Al-Kanysa, Busyf, Al-Shamseat, Badoush, Kuba, and Tlkeif, all situated in Nineveh province. The findings of the current study indicated the proportion of E. coli detected in the milk was 42% (21 out of 50 specimenss). Additionally, during the molecular monitoring for an exact E. coli gene, it was observed totally isolates (100%) have the uidA gene. One isolate of E. coli possessed the Stx1 gene 1/21 (4.8%). The Stx2 gene was not discovered in E. coli . The results of this research could contribute to addressing a key factor in subclinical mastitis in buffalo, offering potential benefits for the private sector in effectively managing the disease. E. coli isolates carry virulence factors that are responsible for causing food poisoning in humans.
Kinetic signatures of microRNA modes of action Material Supplemental

MicroRNAs (miRNAs) are key regulators of all important biological processes, including development, differentiation, and cancer. Although remarkable progress has been made in deciphering the mechanisms used by miRNAs to regulate translation, many contradictory findings have been published that stimulate active debate in this field. Here we contribute to this discussion in three ways. First, based on a comprehensive analysis of the existing literature, we hypothesize a model in which all proposed mechanisms of microRNA action coexist, and where the apparent mechanism that is detected in a given experiment is determined by the relative values of the intrinsic characteristics of the target mRNAs and associated biological processes. Among several coexisting miRNA mechanisms, the one that will effectively be measurable is that which acts on or changes the sensitive parameters of the translation process. Second, we have created a mathematical model that combines nine known mechanisms of miRNA action and estimated the model parameters from the literature. Third, based on the mathematical modeling, we have developed a computational tool for discriminating among different possible individual mechanisms of miRNA action based on translation kinetics data that can be experimentally measured (kinetic signatures). To confirm the discriminatory power of these kinetic signatures and to test our hypothesis, we have performed several computational experiments with the model in which we simulated the coexistence of several miRNA action mechanisms in the context of variable parameter values of the translation.
Initiation, Establishment, and Maintenance of Heritable MuDR Transposon Silencing in Maize Are Mediated by Distinct Factors

Paramutation and transposon silencing are two epigenetic phenomena that have intrigued and puzzled geneticists for decades. Each involves heritable changes in gene activity without changes in DNA sequence. Here we report the cloning of a gene whose activity is required for the maintenance of both silenced transposons and paramutated color genes in maize. We show that this gene, Mop1 (Mediator of paramutation1) codes for a putative RNA-dependent RNA polymerase, whose activity is required for the production of small RNAs that correspond to the MuDR transposon sequence. We also demonstrate that although Mop1 is required to maintain MuDR methylation and silencing, it is not required for the initiation of heritable silencing. In contrast, we present evidence that a reduction in the transcript level of a maize homolog of the nucleosome assembly protein 1 histone chaperone can reduce the heritability of MuDR silencing. Together, these data suggest that the establishment and maintenance of MuDR silencing have distinct requirements.
Current status of amantadine and rimantadine as anti-influenza-A agents: memorandum from a WHO meeting.

Amantadine (1-adamantanamine hydrochloride), an anti-influenza drug, effectively inhibits the replication of all human subtypes of influenza A virus (H1N1, H2N2 and H3N2) both in laboratory studies and in a variety of clinical situations in young and old persons. So far, it has been used on a relatively limited scale by community and hospital clinicians, partly because of concern over mild side-effects in approximately 6% of persons. The related compound, rimantadine (alpha-methyl-1-adamantane-methylamine hydrochloride), shows comparable antiviral activity with few or no side-effects. Although the mode of antiviral action is considered to be similar, the two drugs differ in their metabolic and pharmacological properties.Both amantadine and rimantadine have therapeutic uses and shorten the duration of influenza-A-induced fever, malaise, and virus shedding. A dosage of 200 mg of either drug for a 3-5-day period is effective but treatment has to commence on the first day of symptoms. Prophylaxis, particularly using rimantadine, could be usefully initiated in elderly and other high-risk individuals living in institutions and in the general community.
Algorithms for Cytoplasm Segmentation of Fluorescence Labelled Cells

Automatic cell segmentation has various applications in cytometry, and while the nucleus is often very distinct and easy to identify, the cytoplasm provides a lot more challenge. A new combination of image analysis algorithms for segmentation of cells imaged by fluorescence microscopy is presented. The algorithm consists of an image pre‐processing step, a general segmentation and merging step followed by a segmentation quality measurement. The quality measurement consists of a statistical analysis of a number of shape descriptive features. Objects that have features that differ to that of correctly segmented single cells can be further processed by a splitting step. By statistical analysis we therefore get a feedback system for separation of clustered cells. After the segmentation is completed, the quality of the final segmentation is evaluated. By training the algorithm on a representative set of training images, the algorithm is made fully automatic for subsequent images created under similar conditions. Automatic cytoplasm segmentation was tested on CHO‐cells stained with calcein. The fully automatic method showed between 89% and 97% correct segmentation as compared to manual segmentation.
Bayesian Optimization in a Billion Dimensions via Random Embeddings

Bayesian optimization techniques have been successfully applied to robotics, planning, sensor placement, recommendation, advertising, intelligent user interfaces and automatic algorithm configuration. Despite these successes, the approach is restricted to problems of moderate dimension, and several workshops on Bayesian optimization have identified its scaling to high-dimensions as one of the holy grails of the field. In this paper, we introduce a novel random embedding idea to attack this problem. The resulting Random EMbedding Bayesian Optimization (REMBO) algorithm is very simple, has important invariance properties, and applies to domains with both categorical and continuous variables. We present a thorough theoretical analysis of REMBO. Empirical results confirm that REMBO can effectively solve problems with billions of dimensions, provided the intrinsic dimensionality is low. They also show that REMBO achieves state-of-the-art performance in optimizing the 47 discrete parameters of a popular mixed integer linear programming solver.
The Wang-Landau Algorithm for Monte Carlo computation in general state spaces

(Technical Report) Abstract We generalize to general state spaces a Monte Carlo algorithm recently proposed by Wang and Landau (2001). The algorithm can be seen as an adaptive Markov Chain Monte Carlo algorithm where a partition of the state space is chosen and the target density sequentially reweighted is each component of the partition in such a way that at the limit the empirical occupation measure of the components are equal. We develop convergence results for the algorithm. We also show that the algorithm can be used to e ciently self-tune the weights (the so-called pseudo prior) in the simulated tempering. Applied to the reversible jump, the Wang-Landau algorithm can also be used to improve on the between-model acceptance rate of the algorithm. Simulations example are given to illustrate.
ToPoliNano: A CAD Tool for Nano Magnetic Logic

In the post-CMOS scenario, field coupled nanotechnologies represent an innovative and interesting new direction for electronic nanocomputing. Among these technologies, nanomagnet logic (NML) makes it possible to finally embed logic and memory in the same device. To fully analyze the potential of NML circuits, design tools that mimic the CMOS design-flow should be used for circuit design. We present, in this paper, the latest and improved version of Torino Politecnico Nanotechnology (ToPoliNano), our design and simulation framework for field coupled nanotechnologies. ToPoliNano emulates the top-down design process of CMOS technology. Circuits are described with a VHSIC hardware description language netlist and layout is then automatically generated considering in-plane NML (iNML) technology. The resulting circuits can be simulated and performance can be analyzed. In this paper, we describe several enhancements to the tool itself, like a circuit editor for custom design of field coupled nanodevices, improved algorithms for netlist optimization and new algorithms for the place and route of iNML circuits. We have validated and analyzed the tool by using extensive metrics, both by using standard circuits and ISCAS’85 benchmarks. This contribution highlights the improvements of ToPoliNano, which is now a innovative and complete tool for the development of iNML technology.
Regional scale hydrology: II. Application of the VIC-2L model to the Weser River, Germany

Abstract This paper describes the application of a grid network version of the twolayer Variable Infiltration Capacity (VIC-2L) macroscale hydrological model. The VIC-2L model is implemented on a rotated grid, which is compatible with the weather forecast and climate model REMO (Regional Model), a joint project of the German Weather Service (DWD), GKSS Research Centre and the Max-Planck-Institute for Meteorology, Hamburg. Observed surface meteorological data in the Weser River basin are used to force the model off-line on a daily time step. After a 22-month calibration period, simulated and measured streamflow data are compared for a 12-year period. The resulting predictions compare well with observations at daily, monthly and annual time scales. A sensitivity analysis is presented.
Spatially Distinct Binding of Cdc42 to PAK1 and N-WASP in Breast Carcinoma Cells

ABSTRACT While a significant amount is known about the biochemical signaling pathways of the Rho family GTPase Cdc42, a better understanding of how these signaling networks are coordinated in cells is required. In particular, the predominant subcellular sites where GTP-bound Cdc42 binds to its effectors, such as p21-activated kinase 1 (PAK1) and N-WASP, a homolog of the Wiskott-Aldritch syndrome protein, are still undetermined. Recent fluorescence resonance energy transfer (FRET) imaging experiments using activity biosensors show inconsistencies between the site of local activity of PAK1 or N-WASP and the formation of specific membrane protrusion structures in the cell periphery. The data presented here demonstrate the localization of interactions by using multiphoton time-domain fluorescence lifetime imaging microscopy (FLIM). Our data here establish that activated Cdc42 interacts with PAK1 in a nucleotide-dependent manner in the cell periphery, leading to Thr-423 phosphorylation of PAK1, particularly along the lengths of cell protrusion structures. In contrast, the majority of GFP-N-WASP undergoing FRET with Cy3-Cdc42 is localized within a transferrin receptor- and Rab11-positive endosomal compartment in breast carcinoma cells. These data reveal for the first time distinct spatial association patterns between Cdc42 and its key effector proteins controlling cytoskeletal remodeling.
Cetuximab-Based Immunotherapy and Radioimmunotherapy of Head and Neck Squamous Cell Carcinoma

Purpose: To show the relationship between antibody delivery and therapeutic efficacy in head and neck cancers, in this study we evaluated the pharmacokinetics and pharmacodynamics of epidermal growth factor receptor (EGFR)–targeted immunotherapy and radioimmunotherapy by quantitative positron emission tomography (PET) imaging. Experimental Design: EGFR expression on UM-SCC-22B and SCC1 human head and neck squamous cell cancer (HNSCC) cells were determined by flow cytometry and immunostaining. Tumor delivery and distribution of cetuximab in tumor-bearing nude mice were evaluated with small animal PET using 64Cu-DOTA-cetuximab. The in vitro toxicity of cetuximab to HNSCC cells was evaluated by MTT assay. The tumor-bearing mice were then treated with four doses of cetuximab at 10 mg/kg per dose, and tumor growth was evaluated by caliper measurement. FDG PET was done after the third dose of antibody administration to evaluate tumor response. Apoptosis and tumor cell proliferation after cetuximab treatment were analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Ki-67 staining. Radioimmunotherapy was done with 90Y-DOTA-cetuximab. Results: EGFR expression on UM-SCC-22B cells is lower than that on SCC1 cells. However, the UM-SCC-22B tumors showed much higher 64Cu-DOTA-cetuximab accumulation than the SCC1 tumors. Cetuximab-induced apoptosis in SCC1 tumors and tumor growth was significantly inhibited, whereas an agonistic effect of cetuximab on UM-SCC-22B tumor growth was observed. After cetuximab treatment, the SCC1 tumors showed decreased FDG uptake, and the UM-SCC-22B tumors had increased FDG uptake. UM-SCC-22B tumors are more responsive to 90Y-DOTA-cetuximab treatment than SCC1 tumors, partially due to the high tumor accumulation of the injected antibody. Conclusion: Cetuximab has an agonistic effect on the growth of UM-SCC-22B tumors, indicating that tumor response to cetuximab treatment is not necessarily related to EGFR expression and antibody delivery efficiency, as determined by PET imaging. Although PET imaging with antibodies as tracers has limited function in patient screening, it can provide guidance for targeted therapy using antibodies as delivery vehicles. Clin Cancer Res; 16(7); 2095–105. ©2010 AACR.