Entanglement and Squeezing of the Optical Field Modes in High Harmonic Generation.

Squeezed optical fields are a powerful resource for a variety of investigations in basic research and technology. However, the generation of intense squeezed light is challenging. Here, we show that intense squeezed light can be produced using strongly laser driven atoms and the so far unrelated process of high harmonic generation. We demonstrate that when the intensity of the driving field significantly depletes the ground state of the atoms, leading to dipole moment correlations, the quantum state of the driving field and the generated high harmonics are entangled and squeezed. Furthermore, we analyze how the resulting quadrature squeezing of the fundamental laser mode after the interaction can be controlled. The findings open the way for the generation of high intensity squeezed light states for a wide range of applications.

Seeing beyond skin deep: High-resolution ultrasound in dermatology-A comprehensive review and future prospects.

High-resolution ultrasound (HRUS), operating at frequencies of 20-25 MHz, is a non-invasive imaging tool that offers dermatologists the ability to visualize structures beneath the skin surface. The objective of this review is to present a comprehensive overview of HRUS applications, emphasising its utility in diagnosing, characterising and managing various dermatological conditions. We undertook a comprehensive literature review on the dermatological application of HRUS across Medline, Embase and Cochrane Library databases, while also incorporating our own clinical experience of over 16 years with the tool. In normal skin, the epidermis and dermis are hyperechoic, and the subcutaneous layer is hypoechoic. Basal cell carcinomas appear hypoechoic with irregular margins, while the presence of hyperechoic inclusion bodies suggests aggressive pathology. Squamous cell carcinomas pose challenges due to acoustic shadow artefacts from the thickened stratum corneum. Melanomas are homogenous hypoechoic lesions, with HRUS used to accurately predict Breslow thickness. HRUS provides dermatologists with a valuable adjunct to traditional clinical examination. Future advancement in image resolution and the standardisation of diagnostic parameters may further expand its utility.

An inverse agonist of orphan receptor GPR61 acts by a G protein-competitive allosteric mechanism.

GPR61 is an orphan GPCR related to biogenic amine receptors. Its association with phenotypes relating to appetite makes it of interest as a druggable target to treat disorders of metabolism and body weight, such as obesity and cachexia. To date, the lack of structural information or a known biological ligand or tool compound has hindered comprehensive efforts to study GPR61 structure and function. Here, we report a structural characterization of GPR61, in both its active-like complex with heterotrimeric G protein and in its inactive state. Moreover, we report the discovery of a potent and selective small-molecule inverse agonist against GPR61 and structural elucidation of its allosteric binding site and mode of action. These findings offer mechanistic insights into an orphan GPCR while providing both a structural framework and tool compound to support further studies of GPR61 function and modulation.

A covalent BTK ternary complex compatible with targeted protein degradation.

Targeted protein degradation using heterobifunctional chimeras holds the potential to expand target space and grow the druggable proteome. Most acutely, this provides an opportunity to target proteins that lack enzymatic activity or have otherwise proven intractable to small molecule inhibition. Limiting this potential, however, is the remaining need to develop a ligand for the target of interest. While a number of challenging proteins have been successfully targeted by covalent ligands, unless this modification affects form or function, it may lack the ability to drive a biological response. Bridging covalent ligand discovery with chimeric degrader design has emerged as a potential mechanism to advance both fields. In this work, we employ a set of biochemical and cellular tools to deconvolute the role of covalent modification in targeted protein degradation using Bruton's tyrosine kinase. Our results reveal that covalent target modification is fundamentally compatible with the protein degrader mechanism of action.

Clinical Outcomes After Bilateral Implantation of a Diffractive Trifocal Intraocular Lens: A Worldwide Pooled Analysis of Prospective Clinical Investigations.

Purpose: To investigate visual and safety outcomes of AcrySof® IQ PanOptix® (model TFNT00), a trifocal, presbyopia-correcting intraocular lens (IOL), in patients of different ethnicities across multiple countries, based on a pooled analysis of six prospective multicenter studies. Patients and Methods: This pooled analysis included adult patients from six prospective clinical studies performed across 56 centers worldwide. After cataract removal by phacoemulsification, all patients were implanted with TFNT00; follow-up duration varied from 3 to 12 months according to the studies' design. Binocular defocus curve; absolute manifest refraction spherical equivalent (MRSE); and binocular photopic uncorrected and corrected visual acuities at distance (UCDVA, BCDVA; 4-5 m), intermediate (UCIVA, DCIVA; 60-66 cm), and near (UCNVA, DCNVA; 40 cm) were measured. Results: The study included 557 patients, 547 of whom were implanted bilaterally with the TFNT00 IOL (n = 1094 eyes). Binocular visual data at 1 month and 3-6 months after implantation were available for up to 546 and 542 bilaterally implanted patients, respectively. A continuous range of 0.1 logarithm of the minimum angle of resolution (logMAR) or better vision from distance (0.00 diopter [D], 4-5 m) to near (-3.00 D; optically equivalent to 33 cm) was observed 3-6 months after TFNT00 implantation. At 3-6 months, 88.2% of first eyes achieved an MRSE ≤0.50 D and 88.7% of second eyes achieved an MRSE ≤0.50 D. Overall, 99.3%, 92.3%, and 94.6% of patients bilaterally implanted with TFNT00 achieved binocular photopic BCDVA, DCIVA, and DCNVA of 0.14 logMAR or better, respectively. Ocular adverse device effects and secondary surgical interventions (SSIs) were infrequent. Conclusion: This global pooled analysis showed that TFNT00 provided a continuous range of 0.1 logMAR (~20/25 Snellen) or better vision from distance to 33 cm, with a low incidence of ocular adverse device effects and SSIs.

Dr Google - assessing the reliability and readability of information on general surgical procedures found via search engines.

BACKGROUND: The most common general surgical emergency operations are laparoscopic appendicectomy, laparoscopic cholecystectomy, hernia repair, hemorrhoidectomy and colectomy. Patients commonly perform an internet search for more information prior to undergoing surgery, which can lead to an inappropriate understanding of their procedure. The aim is to assess the quality of information available on three of the most used search engines. METHODS: A search was conducted on Google.com, Bing.com and Yahoo.com using the terms related to laparoscopic appendicectomy, laparoscopic cholecystectomy, hemorrhoidectomy, hernia repair and colectomy. First 20 results from each search engine were collected for evaluation. Results were excluded if they were sponsored, duplicates, academic publications, advertisements, forums, audiovisual tools, social media or any non-English information. Included results were assessed for reliability using DISCERN and JAMA benchmark score. Readability was assessed using Flesch Reading Ease (FRE) Score and Simple Measure of Gobbledygook (SMOG). RESULTS: Hundred and ninety-seven websites were analysed, 44.7% were published by institutions, 34.5% by health websites and 20.8% by independent surgeons. Mean DISCERN scores for Institutions was 54.6 ± 11.3, independent surgeons 45.9 ± 11.4 and health websites 58.7 ± 10.3. Mean JAMA score for Institutions was 1.0 ± 1.0, independent surgeons 0.1 ± 0.4 and health websites 1.7 ± 1.1. FRE scores for institutions was 51.6 ± 10.3, independent surgeons 40.9 ± 10.2, and health websites 45.7 ± 12.3. SMOG scores were 9.8 ± 1.5 for institutions, 11.4 ± 1.6 for independent surgeons and 10.6 ± 1.7 for health websites. CONCLUSION: Health information on common general surgical procedures found on search engines are generally fair to good quality but still above the suggested reading level of the population. Information on surgical procedures should be written at recommended reading level of 13-14 years old.

Ultrafast Imaging of Molecular Chirality with Photoelectron Vortices.

Ultrafast imaging of molecular chirality is a key step toward the dream of imaging and interpreting electronic dynamics in complex and biologically relevant molecules. Here, we propose a new ultrafast chiral phenomenon exploiting recent advances in electron optics allowing access to the orbital angular momentum of free electrons. We show that strong-field ionization of a chiral target with a few-cycle linearly polarized 800 nm laser pulse yields photoelectron vortices, whose chirality reveals that of the target, and we discuss the mechanism underlying this phenomenon. Our Letter opens new perspectives in recollision-based chiral imaging.

Entanglement of orbital angular momentum in non-sequential double ionization.

Entanglement has a capacity to enhance imaging procedures, but this remains unexplored for attosecond imaging. Here, we elucidate that possibility, addressing orbital angular momentum (OAM) entanglement in ultrafast processes. In the correlated process non-sequential double ionization (NSDI) we demonstrate robust photoelectron entanglement. In contrast to commonly considered continuous variables, the discrete OAM allows for a simpler interpretation, computation, and measurement of entanglement. The logarithmic negativity reveals that the entanglement is robust to incoherence and an entanglement witness minimizes the number of measurements to detect the entanglement, both quantities are related to OAM coherence terms. We quantify the entanglement for a range of targets and field parameters to find the most entangled photoelectron pairs. This methodology provides a general way to use OAM to quantify and measure entanglement, well-suited to attosecond processes, and can be exploited to enhance imaging capabilities through correlated measurements, or for generation of OAM-entangled electrons.

Biometric assessment of pseudophakic subjects during objective accommodative stimulation: a prospective observational study.

CLINICAL RELEVANCE: Ultrasound biomicroscopy is an objective method for assessing changes in anterior segment biometry. There is a paucity of data on the reliability of this method. A reliable method for assessing anterior segment changes during physiologically driven accommodation can be a useful tool for clinicians, researchers, and industry. BACKGROUND: To assess the test-retest reliability of ultrasound biomicroscopy for measurements of change in anterior chamber depth during a distance to near fixation task in pseudophakic subjects. METHODS: Subjects were adults with monofocal intraocular lenses implanted in both eyes who completed a 6-month post-operative period and had monocular uncorrected distance visual acuity of 6/15 (0.4 logMAR) or better. The change in anterior chamber depth during a distance to near fixation task was measured with a 35-MHz VuMAX HD ultrasound biomicroscopy device (Sonomed Escalon, New Hyde Park, NY) during two separate visits. An asymmetrical vergence paradigm allowed evaluation of anterior segment biometry at 22-µm axial resolution in one eye, while the fellow eye fixated on the target. To assess the test-retest reliability, 2-sided 95% CI from a paired t test was calculated for the difference in anterior chamber depth change from distance to near between visits. RESULTS: The mean (standard deviation) near-focused anterior chamber depth measured by ultrasound biomicroscopy was 4.331 (0.237) and 4.333 (0.241) mm at visits 1 and 2, respectively. In response to a change in fixation from distance (4 m) to near (40 cm), the mean anterior chamber depth change was -0.012 (0.038) and 0.003 (0.039) mm at visits 1 and 2, respectively. Analysis of the difference in the change in anterior chamber depth between visits was -0.015 mm (95% CI, -0.035 to 0.003). CONCLUSION: Ultrasound biomicroscopy is a repeatable, objective method for assessing change in anterior segment biometry during physiological changes in fixation from distance to near.

Conservation laws for electron vortices in strong-field ionisation.

ABSTRACT: We investigate twisted electrons with a well-defined orbital angular momentum, which have been ionised via a strong laser field. By formulating a new variant of the well-known strong field approximation, we are able to derive conservation laws for the angular momenta of twisted electrons in the cases of linear and circularly polarised fields. In the case of linear fields, we demonstrate that the orbital angular momentum of the twisted electron is determined by the magnetic quantum number of the initial bound state. The condition for the circular field can be related to the famous ATI peaks, and provides a new interpretation for this fundamental feature of photoelectron spectra. We find the length of the circular pulse to be a vital factor in this selection rule and, employing an effective frequency, we show that the photoelectron OAM emission spectra are sensitive to the parity of the number of laser cycles. This work provides the basic theoretical framework with which to understand the OAM of a photoelectron undergoing strong field ionisation.

Dialogue on analytical and ab initio methods in attoscience.

The perceived dichotomy between analytical and ab initio approaches to theory in attosecond science is often seen as a source of tension and misconceptions. This Topical Review compiles the discussions held during a round-table panel at the 'Quantum Battles in Attoscience' cecam virtual workshop, to explore the sources of tension and attempt to dispel them. We survey the main theoretical tools of attoscience-covering both analytical and numerical methods-and we examine common misconceptions, including the relationship between ab initio approaches and the broader numerical methods, as well as the role of numerical methods in 'analytical' techniques. We also evaluate the relative advantages and disadvantages of analytical as well as numerical and ab initio methods, together with their role in scientific discovery, told through the case studies of two representative attosecond processes: non-sequential double ionisation and resonant high-harmonic generation. We present the discussion in the form of a dialogue between two hypothetical theoreticians, a numericist and an analytician, who introduce and challenge the broader opinions expressed in the attoscience community.

Effectiveness and Safety of the Clareon Monofocal Intraocular Lens: Outcomes from a 12-Month Single-Arm Clinical Study in a Large Sample.

PURPOSE: This study assessed effectiveness and safety of the novel Clareon intraocular lens (IOL; model SY60CL; Alcon Vision LLC). PATIENTS AND METHODS: This was a prospective, single-arm, unmasked clinical trial at 16 investigative clinical sites in the United States. Included were adults ≥22 years who required cataract extraction by phacoemulsification. Following phacoemulsification, 350 subjects received SY60CL IOL unilaterally; 342 completed the study. Monocular best corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA) were evaluated. The primary effectiveness endpoint was the percentage of subjects with CDVA ≤0.3 logMAR at month 12. Safety was assessed by monitoring adverse events (AEs). Visual acuity and safety outcomes were compared with historical safety and performance endpoint (SPE) rates. RESULTS: At 12 months post-implantation, 99.7% of subjects receiving the SY60CL IOL achieved monocular CDVA ≤0.3 logMAR (primary effectiveness endpoint; 1-sided 95% upper confidence limit >SPE rate); 99.7% and 86.8% of subjects achieved monocular CDVA of ≤0.34 (20/40 Snellen or better) and ≤0.04 logMAR (20/20 Snellen or better), respectively. At 12 months, >95% of subjects achieved mean monocular UDVA ≤0.3 logMAR; 97.1% and 57.6% of subjects achieved monocular CDVA of ≤0.34 and ≤0.04 logMAR, respectively. Mean monocular CDVA and UDVA were -0.05 and 0.04 logMAR, respectively. AEs were within SPE limits. The most common nonserious ocular AE was posterior capsule opacification (5.4%). Serious AEs were <1%, and no serious ocular AEs were assessed as related to the device. There were no observations for IOL glistenings at 12 months. CONCLUSION: Results of this study supported effectiveness and safety of the SY60CL IOL. Visual acuity outcomes with the SY60CL IOL exceeded the SPE rates for monocular CDVA and AEs were within the limit of historic SPE rates. (Model number SY60WF is the Clareon lens approved by the FDA.).

Diagnosis of mast cell activation syndrome: a global "consensus-2".

The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of "mast cell activation syndrome" (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a "consensus" (re-termed here as "consensus-1"). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as "consensus-2"), resembling "consensus-1" in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by "consensus-2" criteria has potential to be problematic, but underdiagnosis by "consensus-1" criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.

Visual and Patient-Reported Outcomes of a Diffractive Trifocal Intraocular Lens Compared with Those of a Monofocal Intraocular Lens.

PURPOSE: To evaluate the effectiveness and safety of a trifocal intraocular lens (IOL), the TFNT00 (Alcon, Fort Worth, TX), versus a monofocal IOL, the SN60AT (Alcon). DESIGN: Food and Drug Administration-approved, prospective, multicenter, nonrandomized, parallel-group, assessor-masked, confirmatory trial. PARTICIPANTS: Patients enrolled were 22 years of age or older with a diagnosis of bilateral cataract with planned removal by phacoemulsification with a clear corneal incision. METHODS: Consented participants selected their preferred IOL, which was implanted sequentially into each eye of patients meeting eligibility criteria. MAIN OUTCOME MEASURES: The coprimary effectiveness outcomes were mean photopic monocular best-corrected distance visual acuity (BCDVA; 4 m) and distance-corrected near visual acuity (DCNVA; 40 cm) at 6 months after surgery. Secondary effectiveness outcomes included mean monocular distance-corrected intermediate visual acuity (DCIVA; 66 cm) and proportion of participants responding "never" to question 1 of the Intraocular Lens Satisfaction questionnaire (regarding frequency of spectacle use in the past 7 days). Safety outcomes included frequency of "severe" and "most bothersome" visual disturbances. RESULTS: Two hundred forty-three patients underwent cataract surgery with bilateral implantation of the TFNT00 (n = 129) or SN60AT (n = 114) and were followed up for 6 months. Noninferiority of TFNT00 to SN60AT in mean photopic monocular BCDVA (95% upper confidence limit of the difference was <0.1 logarithm of the minimum angle of resolution [logMAR] margin), and superiority in mean photopic monocular DCNVA (difference of 0.42 logMAR; P < 0.001) and DCIVA (difference of 0.26 logMAR; P < 0.001) were demonstrated. The proportion of patients never requiring glasses overall was superior for TFNT00 versus SN60AT (80.5% and 8.2%, respectively). Starbursts, halos, and glare were the most frequently rated severe symptoms with TFNT00; however, less than 5% of patients were very bothered at month 6. CONCLUSIONS: The TFNT00 exhibited superior monocular DCNVA and DCIVA to a spherical monofocal IOL, with comparable monocular BCDVA. Binocular visual acuity was 20/25 or better for distance to near (+0.5 D to -2.5 D), resulting in high levels of spectacle independence. Less than 5% of patients were very bothered by the photic visual disturbances associated with the TFNT00 at 6 months after surgery.

Ten-year safety follow-up and post-explant analysis of an anterior chamber phakic IOL.

PURPOSE: To assess endothelial cell loss (ECL) rate and collect safety data in patients with AcrySof L-series Cachet phakic intraocular lens (pIOL) up to 10 years post-implantation. SETTING: Clinical settings in the United States, European Union, and Canada. DESIGN: Nonrandomized, observational, open-label safety study. METHODS: Central and peripheral endothelial cell density was evaluated and compared with 6-month post-implantation baseline. Nonlinear analysis was performed to identify factors affecting post-explantation ECL. Additional evaluations included uncorrected visual acuity (UCVA), corrected distance visual acuity (CDVA), adverse device effects (ADEs), and serious adverse events (SAEs). RESULTS: The study included 1123 implanted eyes (mean age, 37.5 years). At 10 years, mean central and peripheral ECL was 16% (1.7% annualized). Explantations were performed in 10% of eyes (n = 136/1323). For eyes with pIOL explantation because of ECL (7%), annualized ECL rate post-explantation was numerically lower compared with the overall rate in eyes that underwent explantation for any reason (annualized rate, -1.65% vs -2.03%, respectively; n = 96) and compared with pre-explantation ECL. Mean ± SD CDVA and UCVA were -0.12 ± 0.11 and 0.03 ± 0.22 logarithm of the minimum angle of resolution, respectively. Common ocular ADEs included ECL (10%), pIOL extraction (9%), iris adhesion (7%), and pupillary deformity (2%). Common SAEs included pIOL extraction (11%), ECL (9%), and iris adhesions (8%). CONCLUSIONS: Cachet pIOLs were associated with long-term ECL in some cases. Overall, only 10% of all implanted eyes underwent explantation during 10-year follow-up. In patients requiring explantation because of ECL, the annualized ECL rates decreased post-explantation in some eyes. Continued monitoring of patients regardless of explantation is recommended.

Symphony on strong field approximation.

This paper has been prepared by the Symphony collaboration (University of Warsaw, Uniwersytet Jagiellonski, DESY/CNR and ICFO) on the occasion of the 25th anniversary of the 'simple man's models' which underlie most of the phenomena that occur when intense ultrashort laser pulses interact with matter. The phenomena in question include high-harmonic generation (HHG), above-threshold ionization (ATI), and non-sequential multielectron ionization (NSMI). 'Simple man's models' provide both an intuitive basis for understanding the numerical solutions of the time-dependent Schrödinger equation and the motivation for the powerful analytic approximations generally known as the strong field approximation (SFA). In this paper we first review the SFA in the form developed by us in the last 25 years. In this approach the SFA is a method to solve the TDSE, in which the non-perturbative interactions are described by including continuum-continuum interactions in a systematic perturbation-like theory. In this review we focus on recent applications of the SFA to HHG, ATI and NSMI from multi-electron atoms and from multi-atom molecules. The main novel part of the presented theory concerns generalizations of the SFA to: (i) time-dependent treatment of two-electron atoms, allowing for studies of an interplay between electron impact ionization and resonant excitation with subsequent ionization; (ii) time-dependent treatment in the single active electron approximation of 'large' molecules and targets which are themselves undergoing dynamics during the HHG or ATI processes. In particular, we formulate the general expressions for the case of arbitrary molecules, combining input from quantum chemistry and quantum dynamics. We formulate also theory of time-dependent separable molecular potentials to model analytically the dynamics of realistic electronic wave packets for molecules in strong laser fields. We dedicate this work to the memory of Bertrand Carré, who passed away in March 2018 at the age of 60.

MICRAT: a novel algorithm for inferring gene regulatory networks using time series gene expression data.

BACKGROUND: Reconstruction of gene regulatory networks (GRNs), also known as reverse engineering of GRNs, aims to infer the potential regulation relationships between genes. With the development of biotechnology, such as gene chip microarray and RNA-sequencing, the high-throughput data generated provide us with more opportunities to infer the gene-gene interaction relationships using gene expression data and hence understand the underlying mechanism of biological processes. Gene regulatory networks are known to exhibit a multiplicity of interaction mechanisms which include functional and non-functional, and linear and non-linear relationships. Meanwhile, the regulatory interactions between genes and gene products are not spontaneous since various processes involved in producing fully functional and measurable concentrations of transcriptional factors/proteins lead to a delay in gene regulation. Many different approaches for reconstructing GRNs have been proposed, but the existing GRN inference approaches such as probabilistic Boolean networks and dynamic Bayesian networks have various limitations and relatively low accuracy. Inferring GRNs from time series microarray data or RNA-sequencing data remains a very challenging inverse problem due to its nonlinearity, high dimensionality, sparse and noisy data, and significant computational cost, which motivates us to develop more effective inference methods. RESULTS: We developed a novel algorithm, MICRAT (Maximal Information coefficient with Conditional Relative Average entropy and Time-series mutual information), for inferring GRNs from time series gene expression data. Maximal information coefficient (MIC) is an effective measure of dependence for two-variable relationships. It captures a wide range of associations, both functional and non-functional, and thus has good performance on measuring the dependence between two genes. Our approach mainly includes two procedures. Firstly, it employs maximal information coefficient for constructing an undirected graph to represent the underlying relationships between genes. Secondly, it directs the edges in the undirected graph for inferring regulators and their targets. In this procedure, the conditional relative average entropies of each pair of nodes (or genes) are employed to indicate the directions of edges. Since the time delay might exist in the expression of regulators and target genes, time series mutual information is combined to cooperatively direct the edges for inferring the potential regulators and their targets. We evaluated the performance of MICRAT by applying it to synthetic datasets as well as real gene expression data and compare with other GRN inference methods. We inferred five 10-gene and five 100-gene networks from the DREAM4 challenge that were generated using the gene expression simulator GeneNetWeaver (GNW). MICRAT was also used to reconstruct GRNs on real gene expression data including part of the DNA-damaged response pathway (SOS DNA repair network) and experimental dataset in E. Coli. The results showed that MICRAT significantly improved the inference accuracy, compared to other inference methods, such as TDBN, etc. CONCLUSION: In this work, a novel algorithm, MICRAT, for inferring GRNs from time series gene expression data was proposed by taking into account dependence and time delay of expressions of a regulator and its target genes. This approach employed maximal information coefficients for reconstructing an undirected graph to represent the underlying relationships between genes. The edges were directed by combining conditional relative average entropy with time course mutual information of pairs of genes. The proposed algorithm was evaluated on the benchmark GRNs provided by the DREAM4 challenge and part of the real SOS DNA repair network in E. Coli. The experimental study showed that our approach was comparable to other methods on 10-gene datasets and outperformed other methods on 100-gene datasets in GRN inference from time series datasets.