Multiplexing the Identification of Microorganisms via Tandem Mass Tag Labeling Augmented by Interference Removal through a Novel Modification of the Expectation Maximization Algorithm.

Having fast, accurate, and broad spectrum methods for the identification of microorganisms is of paramount importance to public health, research, and safety. Bottom-up mass spectrometer-based proteomics has emerged as an effective tool for the accurate identification of microorganisms from microbial isolates. However, one major hurdle that limits the deployment of this tool for routine clinical diagnosis, and other areas of research such as culturomics, is the instrument time required for the mass spectrometer to analyze a single sample, which can take ∼1 h per sample, when using mass spectrometers that are presently used in most institutes.

Systematic Assessment of Deep Learning-Based Predictors of Fragmentation Intensity Profiles.

In recent years, several deep learning-based methods have been proposed for predicting peptide fragment intensities. This study aims to provide a comprehensive assessment of six such methods, namely Prosit, DeepMass:Prism, pDeep3, AlphaPeptDeep, Prosit Transformer, and the method proposed by Guan et al. To this end, we evaluated the accuracy of the predicted intensity profiles for close to 1.

MiCId GUI: The Graphical User Interface for MiCId, a Fast Microorganism Classification and Identification Workflow with Accurate Statistics and High Recall.

Although many user-friendly workflows exist for identifications of peptides and proteins in mass-spectrometry-based proteomics, there is a need of easy to use, fast, and accurate workflows for identifications of microorganisms, antimicrobial resistant proteins, and biomass estimation. Identification of microorganisms is a computationally demanding task that requires querying thousands of MS/MS spectra in a database containing thousands to tens of thousands of microorganisms. Existing software can't handle such a task in a time efficient manner, taking hours to process a single MS/MS experiment.

Protection of high-frequency low-intensity pulsed electric fields and brain-derived neurotrophic factor for SH-SY5Y cells against hydrogen peroxide-induced cell damage.

Neurodegenerative diseases (NDDs) pose a significant global health threat. In particular, Alzheimer disease, the most common type causing dementia, remains an incurable disease. Alzheimer disease is thought to be associated with an imbalance of reactive oxygen species (ROS) in neurons, and scientists considered ROS modulation as a promising strategy for novel remedies.

Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells.

To reduce side effects and enhance treatment efficacy, study on combination therapy for pancreatic cancer, a deadly cancer, has gained much attraction in recent years. In this study, we propose a novel triple treatment combining propolis and two physical stimuli-thermal cycling-hyperthermia (TC-HT) and low-intensity ultrasound (US). The study found that, after the triple treatment, the cell viability of a human cancer cell line PANC-1 decreased to a level 80% less than the control, without affecting the normal pancreatic cells.

Thermal cycling-hyperthermia ameliorates Aβ-induced cognitive impairment in C57BL/6 mice.

Despite continuation of some controversies, Alzheimer's disease (AD), the most common cause of dementia nowadays, has been widely believed to derive mainly from excessive β-amyloid (Aβ) aggregation, that would increase reactive oxygen species (ROS) and induce neuroinflammation, leading to neuron loss and cognitive impairment. Existing drugs on Aβ have been ineffective or offer only temporary relief at best, due to blood-brain barrier or severe side effects. The study employed thermal cycling-hyperthermia (TC-HT) to ease the Aβ-induced cognitive impairments and compared its effect with continuous hyperthermia (HT) in vivo.

A Simple Method for Robust and Accurate Intrinsic Subtyping of Breast Cancer.

Motivation: The PAM50 signature/method is widely used for intrinsic subtyping of breast cancer samples. However, depending on the number and composition of the samples included in a cohort, the method may assign different subtypes to the same sample. This lack of robustness is mainly due to the fact that PAM50 subtracts a reference profile, which is computed using all samples in the cohort, from each sample before classification.

An 8-Gene Signature for Classifying Major Subtypes of Non-Small-Cell Lung Cancer.

Motivation: The precise diagnosis of the major subtypes, lung adenocarcinoma and lung squamous cell carcinoma, of non-small-cell lung cancer is of practical importance as some treatments are subtype-specific. However, in some cases diagnosis via the commonly-used method, that is staining the specimen using immunohistochemical markers, may be challenging. Hence, having a computational method that complements the diagnosis is desirable.

Identification of Antibiotic Resistance Proteins via MiCId's Augmented Workflow. A Mass Spectrometry-Based Proteomics Approach.

Fast and accurate identifications of pathogenic bacteria along with their associated antibiotic resistance proteins are of paramount importance for patient treatments and public health. To meet this goal from the mass spectrometry aspect, we have augmented the previously published croorganism lassification and entification (MiCId) workflow for this capability. To evaluate the performance of this augmented workflow, we have used MS/MS datafiles from samples of 10 antibiotic resistance bacterial strains belonging to three different species: , , and .

Rigorous treatment of pairwise and many-body electrostatic interactions among dielectric spheres at the Debye-Hückel level.

Electrostatic interactions among colloidal particles are often described using the venerable (two-particle) Derjaguin-Landau-Verwey-Overbeek (DLVO) approximation and its various modifications. However, until the recent development of a many-body theory exact at the Debye-Hückel level (Yu in Phys Rev E 102:052404, 2020), it was difficult to assess the errors of such approximations and impossible to assess the role of many-body effects. By applying the exact Debye-Hückel level theory, we quantify the errors inherent to DLVO and the additional errors associated with replacing many-particle interactions by the sum of pairwise interactions (even when the latter are calculated exactly).

Mass Spectrometry Proteotyping-Based Detection and Identification of , , and in Blood.

Bloodstream infections (BSIs), the presence of microorganisms in blood, are potentially serious conditions that can quickly develop into sepsis and life-threatening situations. When assessing proper treatment, rapid diagnosis is the key; besides clinical judgement performed by attending physicians, supporting microbiological tests typically are performed, often requiring microbial isolation and culturing steps, which increases the time required for confirming positive cases of BSI. The additional waiting time forces physicians to prescribe broad-spectrum antibiotics and empirically based treatments, before determining the precise cause of the disease.

Effect of high-frequency low-intensity pulsed electric field on protecting SH-SY5Y cells against hydrogen peroxide and β-amyloid-induced cell injury via ERK pathway.

As the most common type of neurodegenerative diseases (NDDs), Alzheimer's disease (AD) is thought to be caused mainly by the excessive aggregation of β-amyloid protein (Aβ). However, a growing number of studies have found that reactive oxygen species (ROS) play a key role in the onset and progression of AD. The present study aimed to probe the neuroprotective effect of high-frequency low-intensity pulsed electric field (H-LIPEF) for SH-SY5Y cells against hydrogen peroxide (H2O2) and Aβ-induced cytotoxicity.

Novel Insights into Quantitative Proteomics from an Innovative Bottom-Up Simple Light Isotope Metabolic (bSLIM) Labeling Data Processing Strategy.

Simple light isotope metabolic labeling (SLIM labeling) is an innovative method to quantify variations in the proteome based on an original labeling strategy. Heterotrophic cells grown in U-[C] as the sole source of carbon synthesize U-[C]-amino acids, which are incorporated into proteins, giving rise to U-[C]-proteins. This results in a large increase in the intensity of the monoisotope ion of peptides and proteins, thus allowing higher identification scores and protein sequence coverage in mass spectrometry experiments.

Electrostatics of charged dielectric spheres with application to biological systems. III. Rigorous ionic screening at the Debye-Hückel level.

The unequivocal role of electrostatic forces in biological (and colloidal) systems underscores the importance of attaining accurate and rapid calculations of electrostatic forces if one wishes to faithfully simulate the electrostatic aspect of a biological system. This paper makes significant progress toward this aspect as it rigorously incorporates ionic screening at the Debye-Hückel level for an electrolyte system containing dielectric spheres of finite radii. We investigated earlier this system without mobile ions via a surface charge method.

Thermal cycling protects SH-SY5Y cells against hydrogen peroxide and β-amyloid-induced cell injury through stress response mechanisms involving Akt pathway.

Neurodegenerative diseases (NDDs) are becoming a major threat to public health, according to the World Health Organization (WHO). The most common form of NDDs is Alzheimer's disease (AD), boasting 60-70% share. Although some debates still exist, excessive aggregation of β-amyloid protein (Aβ) and neurofibrillary tangles has been deemed one of the major causes for the pathogenesis of AD.

Robust Accurate Identification and Biomass Estimates of Microorganisms via Tandem Mass Spectrometry.

Rapid and accurate identification of microorganisms and estimation of their biomasses are of extreme importance to public health. Mass spectrometry has become an important technique for these purposes. Previously we published a workflow named croorganism lassification and entification (MiCId v.

Application of non-invasive low-intensity pulsed electric field with thermal cycling-hyperthermia for synergistically enhanced anticancer effect of chlorogenic acid on PANC-1 cells.

Most existing cancer treatments involve high-cost chemotherapy and radiotherapy, with major side effects, prompting effort to develop alternative treatment modalities. It was reported that the combination of thermal-cycling hyperthermia (TC-HT) and phenolic compound exhibited a moderate cytotoxic effect against human pancreatic cancer PANC-1 cells. In this study, we investigate the efficacy of triple combination in PANC-1 cancer cells by adopting low-intensity pulsed electric field (LIPEF) to couple with TC-HT and CGA (chlorogenic acid).

Electrostatics of charged dielectric spheres with application to biological systems. II. A formalism bypassing Wigner rotation matrices.

Given the crucial role of electrostatic forces in biological systems, accurate and rapid calculations of electrostatic forces are imperative in faithfully simulating biological systems. More than a decade ago, we proposed a surface charge method, applied it to a system of an arbitrary number of charged dielectric spheres, and obtained an exact solution for arbitrary configuration of the spheres. The precision depends only on the number of terms kept in a series expansion, and can therefore be controlled at will.

Exploring induced pluripotency in human fibroblasts via construction, validation, and application of a gene regulatory network.

Reprogramming of somatic cells to induced pluripotent stem cells, by overexpressing certain factors referred to as the reprogramming factors, can revolutionize regenerative medicine. To provide a coherent description of induced pluripotency from the gene regulation perspective, we use 35 microarray datasets to construct a reprogramming gene regulatory network. Comprising 276 nodes and 4471 links, the resulting network is, to the best of our knowledge, the largest gene regulatory network constructed for human fibroblast reprogramming and it is the only one built using a large number of experimental datasets.

Thermal cycling-hyperthermia in combination with polyphenols, epigallocatechin gallate and chlorogenic acid, exerts synergistic anticancer effect against human pancreatic cancer PANC-1 cells.

Hyperthermia (HT) has shown feasibility and potency as an anticancer therapy. Administration of HT in the chemotherapy has previously enhanced the cytotoxicity of drugs against pancreatic cancer. However, the drugs used when conducting these studies are substantially conventional chemotherapeutic agents that may cause unwanted side effects.

RAId: Knowledge-Integrated Proteomics Web Service with Accurate Statistical Significance Assignment.

Mass spectrometry-based proteomics starts with identifications of peptides and proteins, which provide the bases for forming the next-level hypotheses whose "validations" are often employed for forming even higher level hypotheses and so forth. Scientifically meaningful conclusions are thus attainable only if the number of falsely identified peptides/proteins is accurately controlled. For this reason, RAId continued to be developed in the past decade.

The protective effect of non-invasive low intensity pulsed electric field and fucoidan in preventing oxidative stress-induced motor neuron death via ROCK/Akt pathway.

With the expansion of the aged population, it is predicted that neurodegenerative diseases (NDDs) will become a major threat to public health worldwide. However, existing therapies can control the symptoms of the diseases at best, rather than offering a fundamental cure. As for the complex pathogenesis, clinical and preclinical researches have indicated that oxidative stress, a central role in neuronal degeneration, is a possible therapeutic target in the development of novel remedies.

Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells.

Efficiency of reprogramming of human cells into induced pluripotent stem cells (iPSCs) has remained low. We report that individual adult human CD49f long-term hematopoietic stem cells (LT-HSCs) can be reprogrammed into iPSCs at close to 50% efficiency using Sendai virus transduction. This exquisite sensitivity to reprogramming is specific to LT-HSCs, since it progressively decreases in committed progenitors.

Thermal Expansion of Single-Crystal H_{2}O and D_{2}O Ice Ih.

Thermal expansion of H_{2}O and D_{2}O ice Ih with relative resolution of 1 ppb is reported. A large transition in the thermal expansion coefficient at 101 K in H_{2}O moves to 125 K in D_{2}O, revealing one of the largest-known isotope effects. Rotational oscillatory modes that couple poorly to phonons, i.

Robust Hund rule without Coulomb repulsion and exclusion principle in quantum antiferromagnetic chains of composite half spins.

Quantum spin chains with composite spins have been used to approximate conventional chains with higher spins. For instance, a spin 1 (or [Formula: see text]) chain was sometimes approximated by a chain with two (or three) spin [Formula: see text]'s per site. However, little examination has been given as to whether this approximation, effectively assuming the first Hund rule per site, is valid and why.