Miracle-dz/UniFAR-FTUs huggingface dataset:
GRouNdGAN: GRN-guided simulation of single-cell RNA-seq data using causal generative adversarial networks

We introduce GRouNdGAN, a gene regulatory network (GRN)-guided causal implicit generative model for simulating single-cell RNA-seq data, in-silico perturbation experiments, and benchmarking GRN inference methods. Through the imposition of a user-defined GRN in its architecture, GRouNdGAN simulates steady-state and transient-state single-cell datasets where genes are causally expressed under the control of their regulating transcription factors (TFs). Training on three experimental datasets, we show that our model captures non-linear TF-gene dependences and preserves gene identities, cell trajectories, pseudo-time ordering, and technical and biological noise, with no user manipulation and only implicit parameterization. Despite imposing rigid causality constraints, it outperforms state-of-the-art simulators in generating realistic cells. GRouNdGAN learns meaningful causal regulatory dynamics, allowing sampling from both observational and interventional distributions. This enables it to synthesize cells under conditions that do not occur in the dataset at inference time, allowing to perform in-silico TF knockout experiments. Our results show that in-silico knockout of cell type-specific TFs significantly reduces cells of that type being generated. Interactions imposed through the GRN are emphasized in the simulated datasets, resulting in GRN inference algorithms assigning them much higher scores than interactions not imposed but of equal importance in the experimental training dataset. Benchmarking various GRN inference algorithms reveals that GRouNdGAN effectively bridges the existing gap between simulated and biological data benchmarks of GRN inference algorithms, providing gold standard ground truth GRNs and realistic cells corresponding to the biological system of interest. Our results show that GRouNdGAN is a stable, realistic, and effective simulator with various applications in single-cell RNA-seq analysis.
Advances in the Treatment of Small-Cell Lung Cancer

Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastatic dissemination and responsiveness to initial therapy. The incidence of SCLC has been declining over the past decade, mainly due to a decreased incidence in men. Positron-emission tomographic (PET) scans appear to improve the accuracy of staging and treatment planning in patients with SCLC. Limited-stage (LS) SCLC is a potentially curable disease, with long-term survival of (cid:1) 20% when treated with platinum-based chemotherapy plus concurrent thoracic radiation. Hyperfractionated thoracic radiation and prophylactic cranial irradiation (PCI) may signiﬁcantly improve overall survival in selected patients with LS-SCLC. For patients with extensive-stage (ES) SCLC, survival can be increased with combination chemotherapy, but the disease remains incurable, and long-term survival is rare. The use of PCI has recently been reported to further improve overall survival in ES-SCLC. Several newer cytotoxic agents, such as amrubicin, have promising activity in early clinical trials. Although many potential molecular targets have been identiﬁed in preclinical studies of SCLC, molecularly targeted therapy has yet to demonstrate any substantial activity in clinical trials. Nonetheless, future advances in this disease will undoubtedly depend on improvements in our understanding of the molecular mechanisms that drive the proliferation and survival of SCLC cells.
Enhancer plasticity in endometrial tumorigenesis demarcates non-coding driver mutations and alterations in 3D genome organization to stimulate oncogene expression

The incidence and mortality of Endometrial Cancer (EC) is on the rise. 85% of ECs depend on Estrogen Receptor alpha (ERα) for proliferation, but little is known about its transcriptional regulation in these tumors. We generated epigenomics and Hi-C data streams in healthy and tumor endometrial tissues, identifying robust ERα reprogramming and profound alterations in 3D genome organization that lead to a gain of tumor-specific enhancer activity during EC development. Integration with WGS data from metastatic samples revealed a striking enrichment of non-coding somatic mutations at tumor-enriched ERα sites. Through machine learning-based predictions and interaction proteomics analyses, we identified an enhancer mutation which alters 3D genome organization, impairing recruitment of the transcriptional repressor EHMT2/G9a/KMT1C, thereby alleviating transcriptional repression of ESR1 in EC. In summary, we identified a complex genomic-epigenomic interplay in EC development and progression, altering 3D genome organization to enhance expression of the critical driver ERα.
Essential Thrombocythemia/Polycythemia Vera and Pregnancy: The Need for an Observational Study in Europe

The management of pregnant patients with essential thrombocythemia (ET) and polycythemia vera (PV) may be problematic. In the literature there are (cid:1) 300 cases of pregnancies reported in ET and less than 50 pregnancies reported in PV. To reduce the effect of reporting bias, we selected articles with either > 10 pregnancies or at least six patients, and here report on the outcome of 195 pregnancies in ET and 36 pregnancies in PV patients. The live birth rate was (cid:1) 60% in ET and 58% in PV. Spontaneous abortion during the ﬁrst trimester was the most frequent fetal complication, occurring in 31% of ET pregnancies and in 22% of PV pregnancies, respectively. Major maternal complications were more frequent in PV compared with ET (44.4 versus 7.7%). Treatment with low-dose aspirin during pregnancy in ET seemed to reduce complications and also seemed beneﬁcial during pregnancy in PV. In high-risk pregnancies, the additional use of low molecular weight heparin and/or interferon a should be considered. This article also describes a registry for an observational study concerning pregnancy in chronic Philadelphia chromo-some-negative myeloproliferative disorders within the European LeukemiaNet. A potential management algorithm for pregnancies in ET or PV is also provided.
Solid solutions of lithium niobate and lithium tantalate: crystal growth and the ferroelectric transition

Abstract Specific heat capacity measurements by differential scanning calorimetry (DSC) of single crystals of solid solutions of LiNbO3 and LiTaO3 are reported and compared with corresponding ab initio calculations, with the aim to investigate the variation of the ferroelectric Curie temperature as a function of composition. For this purpose, single crystals of these solid solutions were grown with Czochralski pulling along the c-axis. Elemental composition of Nb and Ta was investigated using XRF analysis, and small samples with homogeneous and well known composition were used for the DSC measurements. We observed that the ferroelectric Curie temperature decreases linearly with increasing Ta concentration in the LiNb Ta O3 solid solution crystals. Furthermore, the ferroelectric transition width of a mixed crystal appears to be smaller, as compared to pure LiTaO3.
An M/M/2 Queueing System with Heterogeneous Servers Including One Vacationing Server

Abtsrcat This paper analyzes an M/M/2 queueing system with het- erogeneous servers, one of which is always available but the other goes on vacation in the absence of customers waiting for service. The system is analyzed in the steady state using matrix geometric method. Busy period of the system is analyzed and mean waiting time in the stationary regime com- puted. Conditional stochastic decomposition of stationary queue length is obtained. An illustrative example is also provided.
Myeloid Leukemias and Lung Involvement

Myeloid leukemias are clonal malignancies characterized by the presence of increased numbers of immature myeloid cells in the marrow and peripheral blood. Pulmonary involvement by myeloid leukemia is relatively uncommon and seen mainly in patients with severe disease. The most common form of pulmonary involvement consists of leukemic inﬁltration along the lymphatics in the peribronchovascular, septal, and pleural interstitial tissue. Less common manifestations include myeloid sarcoma, leukostasis, leukemic cell lysis pneumopathy, and hyperleukocytic reaction. The radiological manifestations of pulmonary leukemic cell inﬁltration and leukostasis consist mainly of bilateral thickening of the peribronchovascular interstitium and interlobular septa, a pattern that resembles that of interstitial pulmonary edema. The radiological manifestations of leukemic cell lysis pneumopathy and hyperleukocytic reaction consist of symmetric bilateral areas of consolidation. This manuscript reviews the histological and radiological intra-thoracic manifestations of myelogenous leukemias.
Stress mapping of a strain superlattice using scanning moiré fringe imaging

Accurate adjustment of the stress/strain field can significantly affect the physical properties of a strain compensation superlattice structure in quantum cascade lasers. Therefore, precise evaluation of the stress/strain is of significant importance at the nanoscale. In this investigation, nanometer-scale scanning moire fringes (SMFs) with two directions in an In0.6Ga0. 4As/In0.56Al0. 44As superlattice structure are obtained simultaneously by precisely adjusting the formation parameters of SMF using scanning transmission electron microscopy (STEM). Starting from the principle of STEM imaging, the fundamental formation principle and forming condition of STEM moire are systematically studied. The 2D strain/stress distributions parallel and vertical to the growth direction are measured simultaneously, indicating that the maximum absolute value of strain/stress is close to the interface, with the peak stress at the gigapascal level, whereas the minimum absolute value of strain/stress is near the middle of each layer. The calculated resultant force indicates that each In0.56Al0. 44As layer provides effective strain compensation for the adjacent In0.6Ga0. 4As layers. The active region is properly strain-balanced to provide a nearly net-zero strain within a single period, reducing the possibility of forming dislocations.Accurate adjustment of the stress/strain field can significantly affect the physical properties of a strain compensation superlattice structure in quantum cascade lasers. Therefore, precise evaluation of the stress/strain is of significant importance at the nanoscale. In this investigation, nanometer-scale scanning moire fringes (SMFs) with two directions in an In0.6Ga0. 4As/In0.56Al0. 44As superlattice structure are obtained simultaneously by precisely adjusting the formation parameters of SMF using scanning transmission electron microscopy (STEM). Starting from the principle of STEM imaging, the fundamental formation principle and forming condition of STEM moire are systematically studied. The 2D strain/stress distributions parallel and vertical to the growth direction are measured simultaneously, indicating that the maximum absolute value of strain/stress is close to the interface, with the peak stress at the gigapascal level, whereas the minimum absolute value of strain/stress is near the middle of each.
Content and Theme in Attitude Ascriptions

This chapter addresses a less-commonly discussed substitution failure in attitude ascriptions: a “that”-clause and its corresponding proposition description cannot in general be interchanged in the scope of psych-verbs, despite the standard view that the two forms refer to the same proposition. For example, “Holmes suspects that Moriarty has returned” and “Holmes suspects the proposition that Moriarty has returned” mean something quite different. The chapter accounts for these data in the framework of neo-Davidsonian semantics, arguing that substitution does not simply change the syntactic category of the attitude verb from clausal to transitive or vice versa, but also triggers the side-effect of changing thematic relations: when the transitive verb is used, it is the theme of the attitude-state or event that is identified, but when the clausal verb is used, it is the content of the state that is identified.
in Respiratory and Critical Care Medicine

The lungs and interlobar fissures, and the inner surfaces of the chest wall and diaphragm, are lined by delicate mesothelial-lined serous membranes— the visceral and parietal pleurae. The pleurae con tribute to the transmission of forces from the chest wall to the lung, may help maintain the shape of the lung, and are also responsible for the formation and subsequent turnover of the pleural fluid. This fluid provides a lubricating film that minimizes friction between the lung and apposed surfaces during respi ration.
From triangle to hyperbola

86.51 From triangle to hyperbola It is reasonably well-known that if equilateral triangles are constructed externally on the sides of any triangle, then the three lines which join the vertices of the original triangle to the opposite external vertices are concurrent. This property can be generalised, as follows:ABC is any triangle. Isosceles triangles BA'C, CB"A, AC'B, all with the same base angles, are constructed externally on the sides. Then AA', BB", CC are concurrent.
An Update on the von Willebrand Factor Collagen Binding Assay: 21 Years of Age and Beyond Adolescence but Not Yet a Mature Adult

von Willebrand disease (VWD) is considered to be the most common inherited bleeding disorder. It is diagnosed after a clinical and physical review, with personal and familial evidence of (primarily mucocutaneous) bleeding, and conﬁrmed by laboratory testing. The latter typically entails initial plasma testing of factor VIII coagulant (FVIII:C), von Willebrand factor (VWF) protein (antigen; VWF:Ag), and VWF function, which has classically been assessed using the ristocetin cofactor (VWF:RCo) assay. More recent attention has focused on another functional VWF assay, the collagen binding (VWF:CB) assay, as a possible replacement for the VWF:RCo assay or as a supplementary test of VWF adhesive ‘‘activity. ’’ Additional laboratory testing can comprise a battery of con-ﬁrmatory and VWD subtype assisting assays, including assessment of VWF:multimers. This review updates our knowledge of VWD diagnostics with a particular emphasis on the VWF:CB assay. There is good evidence now in place that an optimized VWF:CB assay can signiﬁcantly reduce the diagnostic error rate otherwise arising from the use of a test panel restricted to including the VWF:RCo assay as the sole functional VWF assay. Never-theless, the VWF:CB assay should not be used to wholly replace the VWF:RCo assay in phenotypic testing but rather as a supplementary assay. However, with some thought and justiﬁcation, the VWF:CB assay can be used to partly replace the VWF:RCo assay in some ‘‘screening’’ applications and can also be used to abrogate the need to perform routine VWF:multimers in most test cases.
On the Minimum Bisection Problem in Tree-Like and Planar Graphs

Minimum Bisection denotes the NP-hard problem to partition the vertex set of a graph into two classes of equal size while minimizing the number of edges between these classes. This thesis investigates the structure of bounded-degree trees and planar graphs with large minimum bisection width. For tree-like and planar graphs, linear-time algorithms computing bisections within certain bounds are presented. Moreover, the results are generalized to Minimum k-Section.
Screening Tests of Platelet Function: Update on Their Appropriate Uses for Diagnostic Testing

Global tests of platelet function are often used as screening tests during the laboratory investigation of individuals with suspected hemostatic defects. Because global tests of platelet function do not enable speciﬁc diagnosis of platelet disorders, they are normally performed as the ﬁrst part of a two-step strategy that requires further testing with more specialized assays of platelet function to conﬁrm or refute the diagnosis. The most commonly proposed rationale for testing global platelet function as a ﬁrst-line investigation is that normal test results may exclude a diagnosis of platelet function disorder so that further specialized testing can be avoided. For this reason, global platelet function tests are usually initially performed at the same time as global assays of coagulation pathway function (prothrombin time and activated partial thromboplastin time, von Willebrand factor screening tests [VWF:Ag, VWF:RCo, and FVIII:C]) and measurement of platelet number. The most widely performed tests for screening platelet function disorders are currently the template bleeding time and the closure time within the Platelet Function Analyzer. These tests will therefore be considered in detail in this review, and we will discuss the limitations of these methods in screening individuals for platelet disorders.
Hamiltonian renormalization with applications to the quantum quartic oscillator

This paper reviews the main aspects of the renormalization group concept, from its early applications in quantum field theory, to modern asymptotic analysis, and also obtains some new results concerning the quantum quartic oscillator. This problem is approached using the Hamiltonian, or flow renormalization method. After an exposition of several examples, where the Hamiltonian renormalization is applied to exactly solvable models, the flow equations for the quartic oscillator are obtained, and solved numerically, in an approximation suitable to the study of low-lying states. So, one finds that the Hamiltonian renormalization is a valuable tool for the study of the quartic oscillator.
Automatic Generation of Test Cases for Data Flow Test Paths Using K-Means Clustering and Generic Algorithm

Automatic test case generation is one of the major difficulties in software testing that satisfy a given adequacy criterion. This paper presents an evolutionary structural testing approach to automatically generate test cases. The genetic algorithm (GA) is an evolutionary algorithm which is used here for the generation of test cases automatically to cover its def-use associations. The GA conducts its search by constructing new test data from previously generated test data that are evaluated as effective test data. In this paper the proposed algorithm will produces a set of random generated test cases within a domain, these test cases have been divided in different groups (clusters) using K-Mean clustering algorithm. Each cluster find a group of path covered, refined these clustered based on path covered and apply genetic algorithm to produce new test cases in each cluster for increasing the path coverage.
Interfering with Hemostatic System Components: Possible New Approaches to Antiangiogenic Therapy

Inhibition of angiogenesis has progressed from a theoretical and esoteric discipline scrutinized in but a few laboratories far removed from the clinic, to mainstream experimental clinical cancer therapeutics. Dramatic progress in this ﬁeld represents a triumph of the concept of translational biomedical research. Growth of knowledge in this discipline has brought to light a bewildering yet tantalizing array of interacting enzymatic algorithms that participate in the highly orchestrated process of new blood vessel formation critical for tumor growth and dissemination. It is clear that pathways of blood coagulation (in broad context) and angiogenesis are inextricably linked. The facts that much is already known about many components of these pathways and that stalling of tumor growth has already been demonstrated for several interventions aimed at participants in these reactions send a clear signal that more effective and less toxic cancer therapy may be at hand in the near future. There is no lack of candidate targets for intervention brought to light by preclinical scientists. Numerous well-characterized investigational agents are on hand for testing. The challenge is clearly in the hands of the clinical investigators to proceed with human intervention studies while armed with knowledge of opportunities and pitfalls that should guide insightful clinical trial design. A particularly compelling feature of this treatment paradigm is that it is not aimed directly at distruction of tumor through inhibition of the DNA replication machinery of the cell. Rather it is aimed at restoring the normal state by modulating the dysregulated interaction of tumor cells with their environment that is characteristic of cancer.
Dynamics and excitation in a low mass-damping cylinder in cross-flow with side-by-side interference

Experiments have been conducted with a low mass-damping circular cylinder, elastically supported in a cross-flow, in the vicinity of a second stationary cylinder. The dynamic response, including amplitudes and frequencies of oscillation, together with the fluid excitation, were measured covering a large parametric space, consisting of variations in the gap distance between the cylinders as well as in the reduced velocity and Reynolds number. The flow dynamics in the near wake was also measured using planar particle image velocimetry. The results show how there is a strong wake interaction between the cylinders that greatly modifies the vortex-induced vibrations (VIV) of the elastically mounted cylinder when the centre-to-centre distance between the models is initially set to values smaller than $3.5D$ , where $D$ is the external diameter. The wake interference leads to responding amplitudes that are reduced if compared to those of isolated cylinders undergoing VIV, while responding frequencies are increased. The transverse force coefficients observed in the lock-in region increase and the upper branch shifts to smaller reduced velocities. The phase between motion and excitation is also shifted and values measured in the lower branch of the response tend to be smaller than those typical of isolated cylinders. At the smallest separation distances investigated, the wakes of the cylinders are synchronised in an out-of-phase mode of shedding, characterised by a biased flow towards the oscillating cylinder.
Anatomic Factors in Recurrent Pregnancy Loss

Anatomic uterine defects are present in 15% of women evaluated for three or more consecutive spontaneous abortions. These anatomic abnormalities can be classiﬁed as congenital or acquired. In addition to pregnancy loss, uterine malformations appear to predispose women to other reproductive difﬁculties including infertility, preterm labor, and abnormal presentation. These poor reproductive outcomes resulting from uterine septum, intrauterine adhesions, polyps, and ﬁbroids are amenable to surgical correction. Therefore, it is essential to make an accurate diagnosis to offer an adequate treatment. In this article, we review the common congenital and acquired uterine anomalies associated with recurrent pregnancy losses, and discuss contemporary diagnosis and treatment options.
An Approach to the Evaluation of Peripheral Neuropathies

The clinical evaluation of peripheral neuropathies can be challenging. This article presents an approach based on a structured assessment that asks a series of yes or no questions during the history and examination that leads to localization and characterization of the neuropathy. The ﬁnal assessment includes further characterization by electrodiag-nostic evaluation. At this point, a reasonable differential diagnosis can be generated and appropriate laboratory tests ordered.
New perturbation bounds and condition numbers for the hyperbolic QR factorization

Abstract Using the modified matrix-vector equation approach, the technique of Lyapunov majorant function and the Banach fixed point theorem, we obtain some new rigorous perturbation bounds for R factor of the hyperbolic QR factorization under normwise perturbation. These bounds are always tighter than the one given in the literature. Moreover, the optimal first-order perturbation bounds and the normwise condition numbers for the hyperbolic QR factorization are also presented.