Analyzing the representations of the Lorentz group, we give a systematic count and construction of all the possible Lagrangians describing an antisymmetric rank two tensor field. The count yields two scalars: the gauge invariant Kalb-Ramond model, equivalent to the sigma model and familiar from super gravity and string theory, and the conformally invariant Avdeev-Chizhov model, which describes self-dual tensors. The count also includes a third invariant, a pseudoscalar, which is an antisymmetrized form of the Avdeev-Chizhov Lagrangian, first noticed in the $SU(2/1)$ superalgebraic model of the weak interactions. This model is also conformally invariant, and naturally implements the Landau $CP$ symmetry. Then, by extending the Duffin-Kemmer-Petiau 10 component formalism, we recover the model Lagrangians as first order systems. To complete the analysis we classify all local Lorentz invariant potentials (mass terms and quartic couplings) for charged antisymmetric tensor fields coupled to a Yang-Mills field.

Using a theorem of Jackiw and Pi expressing the delicate balance of the spin and the orbital momentum, we systematically classify the flat-space massless Lagrangian quantum field theories that are invariant under the global conformal group SO(D,2). We recover in a uniform way the facts that scalars and spinors are invariant in any dimension, and that gauge p-tensors are invariant only in 2 p + 2 dimensions. This case includes the Maxwell theory in 4 dimensions and the Kalb-Ramond 2-forms theory in 6 dimensions. We then construct two new classes of Lagrangians extending the Avdeev-Chizhov self-dual tensor model to higher dimensions, one class using a symmetric metric and the other a skew metric in internal space. Finally, we prove in the same uniform way that both classes are conformal invariant in any even dimension. In 4 dimensions, these self-dual tensors naturally couple to the chiral Fermions of the standard model.

Taken as a classification paradigm completing the standard model, a new compact form of the SU(2/1) supergroup explains many mysterious properties of the weak interactions: the maximal breaking of parity, the fractional charges of the quarks, the cancellation of the quantum field theory anomalies, and ties together the existence of the right neutrinos and of the heavier Fermions. This compact supergroup is constructed by exponentiating the matrices representing the leptons and the quarks which form a semi-direct sum of Kac modules of the real superalgebra su(2/1,R) such that the overall trace of the U(1) weak-hypercharge Y vanishes. Remarkably, all the elements of this supergroup have Berezinian 1 and determinant 1. In practice, Tr(Y)=0 simply means that the electric charge of the hydrogen atom is zero.

Next-generation sequencing (NGS) has revolutionized genomic research by enabling high-throughput, cost-effective genome and transcriptome sequencing accelerating personalized medicine for complex diseases, including cancer. Whole genome/transcriptome sequencing (WGS/WTS) provides comprehensive insights, while targeted sequencing is more cost-effective and sensitive. In comparison to short-read sequencing, which still dominates the field due to high speed and cost-effectiveness, long-read sequencing can overcome alignment limitations and better discriminate similar sequences from alternative transcripts or repetitive regions. Hybrid sequencing combines the best strengths of different technologies for a more comprehensive view of genomic/transcriptomic variations. Understanding each technology’s strengths and limitations is critical for translating cutting-edge technologies into clinical applications. In this study, we sequenced DNA and RNA libraries of reference samples using various targeted DNA and RNA panels and the whole transcriptome on both short-read and long-read platforms. This study design enables a comprehensive analysis of sequencing technologies, targeting protocols, and library preparation methods. Our expanded profiling landscape establishes a reference point for assessing current sequencing technologies, facilitating informed decision-making in genomic research and precision medicine.

The advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery. We report key genetic pathways, including changes in erythrocyte regulation, stress induction, and immune changes affected by spaceflight. We also present the first m6A methylation profiles for a human space mission, suggesting a significant spike in m6A levels immediately post-flight. These data and results represent the first longitudinal long-read RNA profiles and RNA modification maps for each gene for astronauts, improving our understanding of the human transcriptome's dynamic response to spaceflight. Here the authors explore the role of chemical modifications within RNA molecules in spaceflight response, observing increased m6A mRNA modifications immediately post-spaceflight in gene markers associated with stress response.

Two theories describing antisymmetric tensor fields in 4 dimensions are well known: the gauge invariant Kalb-Ramond model which generalizes the Maxwell Lagrangian and the Avdeev-Chizhov model which describes self-dual 2-tensors. Using a theorem of Jackiw and Pi, we study p-forms in D dimensions and prove that the Kalb-Ramond model is conformal invariant only when the rank p of the gauge tensor is equal to its canonical dimension (D-2)/2 and that the Avdeev-Chizhov model and its new CP generalization inspired by the SU(2/1) superalgebraic chiral structure of the electroweak interactions are both conformal invariant in any even dimension.

Certified RNA reference materials are indispensable for assessing the reliability of RNA sequencing to detect intrinsically small biological differences in clinical settings, such as molecular subtyping of diseases. As part of the Quartet Project for quality control and data integration of multi-omics profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets between two samples, providing cross-platform and cross-laboratory ‘ground truth’. Investigation of the intrinsically subtle biological differences among the Quartet samples enables sensitive assessment of cross-batch integration of transcriptomic measurements at the ratio level. The Quartet RNA reference materials, combined with the ratio-based reference datasets, can serve as unique resources for assessing and improving the quality of transcriptomic data in clinical and biological settings.

We construct a new class of finite dimensional indecomposable representations of simple superalgebras which may explain, in a natural way, the existence of the heavier elementary particles. In type I Lie superalgebras sl(m/n) and osp(2/2n), one of the Dynkin weights labeling the finite dimensional irreducible representations is continuous. Taking the derivative, we show how to construct indecomposable representations recursively embedding N copies of the original irreducible representation, coupled by generalized Cabibbo angles, as observed among the three generations of leptons and quarks of the standard model. The construction is then generalized in the appendix to quasi-reductive Lie superalgebras.

All finite dimensional irreducible representations of the simple Lie-Kac super algebra SU(2/1) are explicitly constructed in the Chevalley basis as complex matrices. For typical representations, the distinguished Dynkin label is not quantized. We then construct the generic atypical indecomposable quivers classified by Marcu, Su and Germoni and typical indecomposable N-generations block triangular extensions for any irreducible module and any integer N. In addition to the quadratic and cubic super-Casimir operators C_2 and C_3, the supercenter of the enveloping algebra contains a chiral ghost super-Casimir operator T of mixed order (2,4)in the odd generators, proportional to the superidentity grading operator χ, and satisfying T = χ C_2 and we define a new factorizable chiral-Casimir T^-=C_2(1-χ)/2=(UV+WX)(VU+XW) where (U,V,W,X) are the odd generators. In most indecomposable cases, the super-Casimirs are non diagonal. We compute their pseudo-eigenvalues.

We establish that for the type I Lie superalgebras $sl(m/n)$ and $osp(2/2n)$, each Kac module admits a 1 parameter family of indecomposable double extensions. The result follows from the explicit evaluation of the $H^1$ Lie superalgebra cohomology valued in the tensor product of the module and its dual.

As an indispensable tool for transcriptome-wide analysis of differential gene expression, RNA sequencing (RNAseq) has demonstrated great potential in clinical applications. However, the lack of multi-group RNA reference materials of biological relevance and the corresponding reference datasets for assessing the reliability of RNAseq hampers its wide clinical applications wherein the underlying biological differences among study groups are often small. As part of the Quartet Project for quality control and data integration of multiomic profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets using multi-batch RNAseq datasets, providing “ground truth” for benchmarking. Moreover, Quartet-sample-based quality metrics were developed for assessing reliability of RNAseq technology in terms of intra-batch proficiency and cross-batch reproducibility. The small intrinsic biological differences among the Quartet samples enable sensitive assessment of performance of transcriptomic measurements. The Quartet RNA reference materials combined with the reference datasets can be served as unique resources for assessing data quality and improving reliability of transcriptomic profiling.

A bstract A natural generalization of a Lie algebra connection, or Yang-Mills field, to the case of a Lie-Kac superalgebra, for example SU(m/n), just in terms of ordinary complex functions and differentials, is proposed. Using the chirality χ which defines the supertrace of the superalgebra: STr (…) = Tr ( χ… ), we construct a covariant differential: D = χ ( d + A ) + Φ, where A is the standard even Lie-subalgebra connection 1-form and Φ a scalar field valued in the odd module. Despite the fact that Φ is a scalar, Φ anticommutes with ( χA ) because χ anticommutes with the odd generators hidden in Φ. Hence the curvature F = DD is a superalgebra-valued linear map which respects the Bianchi identity and correctly defines a chiral parallel transport compatible with a generic Lie superalgebra structure.

We present recent improvements to Magic-BLAST, an RNA-seq mapper that aligns long as well as short reads to target sequences in a BLAST database. The new features include accessing Sequence Read Archive (SRA) reads from cloud buckets, reporting National Center for Biotechnology Information (NCBI) taxonomy ID's, and reporting unaligned reads in a separate file. A powerful Magic-BLAST feature is that it can access reads from SRA by accession, making pipelines with Magic-BLAST more reusable. NCBI hosts SRA data at cloud providers, supporting large scale hyper-parallel data analyses. Magic-BLAST 1.6.0 downloads SRA data from the cloud. Benefits include uninterrupted downloads, faster download speeds, and huge bandwidth for parallel downloads to multiple running processes or cloud instances. Magic-BLAST provides NCBI taxonomy ID's in the SAM report. Using taxonomy ID's allows unambiguous mapping to taxonomic nodes. This is especially useful for metagenomic projects. Magic-BLAST can report unaligned reads in a separate file in SAM, tabular, or FASTA formats. In this fashion Magic-BLAST can, for example, be used as for contamination screening or for separating virus and host reads from a next-generation sequencing run. This research was supported by the Intramural Research Program of the National Library of Medicine at the NIH.

Background Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. Results All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5–20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. Conclusion This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.

We propose an extension of the Yang-Mills paradigm from Lie algebras to internal chiral superalgebras. We replace the Lie algebra-valued connection one-form A, by a superalgebra-valued polyform A˜ mixing exterior-forms of all degrees and satisfying the chiral self-duality condition A˜=*A˜χ , where χ denotes the superalgebra grading operator. This superconnection contains Yang-Mills vectors valued in the even Lie subalgebra, together with scalars and self-dual tensors valued in the odd module, all coupling only to the charge parity CP-positive Fermions. The Fermion quantum loops then induce the usual Yang-Mills-scalar Lagrangian, the self-dual Avdeev-Chizhov propagator of the tensors, plus a new vector-scalar-tensor vertex and several quartic terms which match the geometric definition of the supercurvature. Applied to the SU(2/1) Lie-Kac simple superalgebra, which naturally classifies all the elementary particles, the resulting quantum field theory is anomaly-free and the interactions are governed by the super-Killing metric and by the structure constants of the superalgebra.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.

Understanding molecular alterations associated with peripheral inflammation is a critical factor in selectively controlling acute and persistent pain. The present report employs in situ hybridization of the 2 opioid precursor mRNAs coupled with quantitative measurements of 2 peptides derived from the prodynorphin and proenkephalin precursor proteins: dynorphin A 1-8 and [Met5]-enkephalin-Arg6-Gly7-Leu8. In dorsal spinal cord ipsilateral to the inflammation, dynorphin A 1-8 was elevated after inflammation, and persisted as long as the inflammation was sustained. Qualitative identification by high performance liquid chromatography and gel permeation chromatography revealed the major immunoreactive species in control and inflamed extracts to be dynorphin A 1-8. In situ hybridization in spinal cord after administration of the inflammatory agent, carrageenan, showed increased expression of prodynorphin (Pdyn) mRNA somatotopically in medial superficial dorsal horn neurons. The fold increase in preproenkephalin mRNA (Penk) was comparatively lower, although the basal expression is substantially higher than Pdyn. While Pdyn is not expressed in the dorsal root ganglion (DRG) in basal conditions, it can be induced by nerve injury, but not by inflammation alone. A bioinformatic meta-analysis of multiple nerve injury datasets confirmed Pdyn upregulation in DRG across different nerve injury models. These data support the idea that activation of endogenous opioids, notably dynorphin, is a dynamic indicator of persistent pain states in spinal cord and of nerve injury in DRG. PERSPECTIVE: This is a systematic, quantitative assessment of dynorphin and enkephalin peptides and mRNA in dorsal spinal cord and DRG neurons in response to peripheral inflammation and axotomy. These studies form the foundational framework for understanding how endogenous spinal opioid peptides are involved in nociceptive circuit modulation.

Abstract A global pandemic of the 2019 coronavirus disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is responsible for over 150,000 deaths worldwide, including >12,000 deaths in New York City (NYC) alone. Given the rapid emergence of this pathogen, little is known about its genetic variation, immune system interactions, population prevalence, and environmental distribution. As a result, there is a pressing clinical and public health need for scalable molecular technologies that can rapidly detect SARS-CoV-2 infection and robustly interrogate strain evolution and host response in patients. To address these challenges, we designed a loop-mediated isothermal amplification (LAMP) assay to identify SARS-CoV-2 infection within 30 minutes of application, including directly from lysed cells. Simultaneously, we developed a large-scale host and viral transcriptomic profiling platform that employs total RNA sequencing (RNA-seq) of nasopharyngeal swab specimens. Applying both technologies to 442 samples, spanning 338 clinical samples tested for SARS-CoV-2, 86 environmental samples from the NYC subway, and 14 controls, we assembled a broad molecular picture of the COVID-19 epidemic in NYC. We found close concordance between viral titers measured with our rapid LAMP assay, RNA-seq, and the state-of-the-art RT-PCR. Full transcriptomic analyses revealed a distinct subset of the Western European clade A2a as the predominant genomic subtype in NYC cases, which was defined by two single nucleotide variants in nsp2 and ORF 3a and a clade-specific, 9-bp in-frame deletion in the virulence factor nsp1. High SARS-CoV2 viral titers were associated with distinct host transcriptional responses, including activation of the ACE2 gene and interferon response genes (e.g., IFIT1). Since ACE inhibitors (ACEIs) can also increase ACE2 expression, outcomes for patients taking ACEIs were examined, and showed a significantly increased risk of intubation and death. Our results demonstrate the utility of two molecular diagnostic platforms in defining the genetic features of an evolving global pandemic and provide insights that can aid future COVID-19 diagnostics, public health monitoring, and therapeutic options.

Curiously, a natural generalization of a connection, or Yang-Mills field, to the case of a Lie super-algebra, for example SU(m/n), just in terms of ordinary complex functions and differentials, is lacking. All previous attempts require super-space coordinates or elements of non commutative geometry. Using the chirality chi of the super-algebra which defines its super-trace: STr(...) = Tr (chi ...), we construct a universal solution to this problem: D = chi (d + A) + Phi, where A is the standard Lie-subalgebra connection 1-form and Phi a scalar field valued in the odd module. Despite the fact that Phi is a scalar, Phi anti-commutes with chi A because chi anti-commutes with the odd generators hidden in Phi. Hence the curvature is a super-algebra valued tensor which respects the Bianchi identity and correctly defines a chiral parallel transport on a generic Lie super-algebra fiber bundle.

At the classical level, the SU(2/1) superalgebra offers a natural description of the elementary particles: leptons and quarks massless states, graded by their chirality, fit the smallest irreducible representations of SU(2/1). Our new proposition is to pair the left/right space-time chirality with the superalgebra chirality and to study the model at the one-loop quantum level. If, despite the fact that they are non-Hermitian, we use the odd matrices of SU(2/1) to minimally couple an oriented complex Higgs scalar field to the chiral Fermions, novel anomalies occur. They affect the scalar propagators and vertices. However, these undesired new terms cancel out, together with the Adler-Bell-Jackiw vector anomalies, because the quarks compensate the leptons. The unexpected and striking consequence is that the scalar propagator must be normalized using the antisymmetric super-Killing metric and the scalar-vector vertex must use the symmetric d_aij structure constants of the superalgebra. Despite this extraordinary structure, the resulting Lagrangian is actually Hermitian.