Miracle-dz/UniFAR-FTUs huggingface dataset:
DETERMINATION OF THE WATER PERMEABILITY (Lp) OF MOUSE OOCYTES AT −25°C AND ITS ACTIVATION ENERGY AT SUBZERO TEMPERATURES✰, ,+

Typically, sub zero permeability measurements are experimentally difficult and infrequently reported. Here we report an approach we have applied to mouse oocytes. Interrupted cooling involves rapidly cooling oocytes (50°C/min) to an intermediate temperature above the intracellular nucleation zone, holding them for up to 40 minutes while they dehydrate, and then rapidly cooling them to −70 °C or below. If the intermediate holding temperature and holding time are well chosen, high post thaw survival of the oocytes is possible because the freezable water is removed during the hold. The length of time required for the exit of the freezable water allows the water permeability at that temperature to be determined. These experiments used 1.5 molar ethylene glycol in PBS and included a transient hold of 2 minutes for equilibration at −10°C, just below the extracellar ice formation temperature. We obtain an Lp = 1.8 × 10−3 μm min−1 atm−1 at −25 °C based on a hold time of 30 minutes yielding 80% survival and the premise that most of the freezable water is removed during the 30 min hold. If we assume that the water permeability is a continuous function of temperature and that its Ea changes at 0°C, we obtain a subzero Ea of 21 kcal/mol; higher than the suprazero value of 14 kcal/mol. A number of assumptions are required for these water loss calculations and the resulting value of Lp can vary by up to a factor of 2, depending on the choices make.
Cannabinoid-1 (CB1) receptors in the mouse ventral pallidum are targeted to axonal profiles expressing functionally opposed opioid peptides and contacting NAPE-PLD terminals

The ventral pallidum (VP) is a major recipient of inhibitory projections from nucleus accumbens (Acb) neurons that differentially express the reward (enkephalin) and aversion (dynorphin) associated opioid peptides. The cannabinoid-1 receptor (CB1R) is present in Acb neurons expressing each of these peptides, but its location in the VP is not known. To address this question, we used electron microscopic dual immunolabeling of the CB1R and either dynorphin 1-8 (Dyn) or Met5-enkephalin (ME) in the VP of C57BL/6J mice, a species in which CB1R gene deletion produces a reward deficit. We also used similar methods to determine the relationship between the CB1R and N-acylphosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D (NAPE-PLD), an anandamide-synthesizing enzyme located presynaptically in other limbic brain regions. CB1R-immunogold was principally localized to cytoplasmic endomembranes and synaptic or extrasynaptic plasma membranes of axonal profiles, but was also affiliated with postsynaptic membrane specializations in dendrites. The axonal profiles included many single CB1R-labeled axon terminals as well as terminals containing CB1R-immunogold and either Dyn or ME immunoreactivity. Dually labeled terminals comprised 26% of all Dynand 17% of all ME-labeled axon terminals. Both single and dual labeled terminals formed mainly inhibitory-type synapses, but almost 16% of these terminals formed excitatory synapses. Approximately 60% of the CB1R-labeled axonal profiles opposed or converged with axon terminals containing NAPEPLD immunoreactivity. We conclude that CB1Rs in the mouse VP have subcellular distributions consistent with on demand activation by endocannabinoids that can regulate the release of functionally opposed opioid peptides and also modulate inhibitory and excitatory transmission.
A Pre-operative Risk Model for Post-operative Pneumonia following Coronary Artery Bypass Grafting

Background—Post-operative pneumonia is the most prevalent of all hospital-acquired infections following isolated coronary artery bypass grafting (CAB). Accurate prediction of a patient’s risk of this morbid complication is hindered by its low relative incidence. In an effort to support clinical decision-making and quality improvement, we developed a pre-operative prediction model for post-operative pneumonia following CAB. Methods—We undertook an observational study of 16,084 patients undergoing CAB between Q3 2011 – Q2 2014 across 33 institutions participating in the Michigan Society of Thoracic and Cardiovascular Surgeons – Quality Collaborative. Variables related to patient demographics, medical history, admission status, comorbid disease, cardiac anatomy and the institution performing the procedure were investigated. Logistic regression via forwards stepwise selection (p < 0.05 threshold) was utilized to develop a risk prediction model for estimating the occurrence of pneumonia. Traditional methods were employed to assess the model’s performance. Direct Correspondence to: Donald S. Likosky, Ph.D., Associate Professor, Section Head, Section of Health Services Research and Quality, Department of Cardiac Surgery (5346 CVC), University of Michigan Medical School, Ann Arbor, MI 48109-5864, likosky@umich.edu, 734-232-4216 (P), 734-763-7353 (F). Presented at the 62nd Annual Meeting of the Southern Thoracic Surgical Association, Lake Buena Vista, FL, November 4–7, 2015. HHS Public Access Author manuscript Ann Thorac Surg. Author manuscript; available in PMC 2016 October 01. Published in final edited form as: Ann Thorac Surg. 2016 October ; 102(4): 1213–1219. doi:10.1016/j.athoracsur. 2016.03. 074. A uhor M anscript
CROSS DOMAIN INFERENCE AND PROBLEM EMBEDDING

Metallized level is covered with a relatively thick non-conformal oxide layer, such as sputtered quartz (SiO2). This layer is, in turn, covered with a relatively thin oxide blanket resistant to RIE, such as aluminum oxide (Al2O3) or Yttrium Oxide (Y2O3). A mask, with exposed via opening, is formed in a conventional manner on the aluminum oxide surface and the aluminum oxide in the open areas is removed, for example Al2O3 is etched with BCl3 and O2 gases or wet etch with H3PO4. An RIE process is used to form vias.
Copula Models for Multi-type Life History Processes

This thesis considers statistical issues in the analysis of data in the studies of chronic diseases which involve modeling dependencies between life history processes using copula functions. Many disease processes feature recurrent events which represent events arising from an underlying chronic condition; these are often modeled as point processes. In addition, however, there often exists a random variable which is realized upon the occurrence of each event, which is called a mark of the point process. When considered together, such processes are called marked point processes. A novel copula model for the marked point process is described here which uses copula functions to govern the association between marks and event times. Specifically, a copula function is used to link each mark with the next event time following the realization of that mark to reflect the pattern in the data wherein larger marks are often followed by longer time to the next event. The extent of organ damage in an individual can often be characterized by ordered states, and interest frequently lies in modeling the rates at which individuals progress through these states. Risk factors can be studied and the effect of therapeutic interventions can be assessed based on relevant multistate models. When chronic diseases affect multiple organ systems, joint modeling of progression in several organ systems is also important. In contrast to common intensity-based or frailty-based approaches to modelling, this thesis considers a copula-based framework for modeling and analysis. Through decomposition of the density and by use of conditional independence assumptions, an appealing joint model is obtained by assuming that the joint survival function of absorption transition times is governed by a multivariate copula function. Different approaches to estimation and inference are discussed and compared including composite likelihood and two-stage estimation methods. Special attention is paid to the case of interval-censored data arising from intermittent assessment. Attention is also directed to use of copula models for more general scenarios with a focus on semiparametric two-stage estimation procedures. In this approach nonparametric or semiparametric estimates of the marginal survivor functions are obtained in the first stage and estimates of the association parameters are obtained in the second stage. Bivariate failure time models are considered for data under right-censoring and current status observation schemes, and right-censored multistate models. A new expression for the asymptotic variance of the second-stage estimator for the association parameter along with a way of estimating this for finite samples are presented under these models and observation schemes.
Nonequilibrium statistical thermodynamics of multicomponent interfaces

Significance Interfaces and their dynamics are critical in many biological, physical, and industrial processes. However, the thermodynamics of interfaces far from equilibrium are subtle and have not been firmly or rigorously established. In analogy with well-known bulk phenomena, we hypothesize a “local” equilibrium for interfaces in multicomponent, multiphase systems and examine the resulting theoretical implications. We then conduct high-precision molecular dynamics simulations to validate the underlying theory, and show that generalized equilibrium thermodynamic equations can be applied to systems far beyond equilibrium. These results lay the groundwork for accurate and thermodynamically consistent modeling of transport at interfaces.
A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice

Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct epitopes within the lateral ridge and C-C′ loop of the EDIII. By creating a subunit-based nanoparticle immunogen with vaccine potential that elicits antibodies with protective activity against POWV infection, our findings enhance our understanding of the molecular determinants of antibody-mediated neutralization of TBFVs.
Parsonage–Turner Syndrome mimicking musculoskeletal shoulder pain: A case report during the SARS-CoV-2 pandemic era

Parsonage–Turner Syndrome or neuralgic amyotrophy is a peripheral neuropathy typically characterized by an abrupt onset of pain, followed by progressive neurological deficits (e.g. weakness, atrophy, occasionally sensory abnormalities) that involve the upper limb, mainly the shoulder, encompassing an extensive spectrum of clinical manifestations, somehow difficult to recognize. This case report describes the proper management of a 35-year-old, bank employee and sports amateur who reported subtle and progressive upper limb disorder with previous history of neck pain. SARS-CoV-2 pandemic era made patient's access to the healthcare system more complicated. Nevertheless, proper management of knowledge, relevant aspects of telerehabilitation-based consultation for musculoskeletal pain, advanced skills, tools and technologies led the physiotherapist to suspect an atypical presentation of Parsonage–Turner Syndrome. Further, neurologist consultation and electromyography suggested signs of denervation in the serratus anterior and supraspinatus muscle. Therefore, an appropriate physiotherapist's screening for referral is conducted to correct diagnosis and thorough treatment.
The transmembrane α‐helix of LptC participates in LPS extraction by the LptB2FGC transporter

Lipopolysaccharide (LPS) is an essential component of the outer membrane of most Gram‐negative bacteria that provides resistance to various toxic compounds and antibiotics. Newly synthesized LPS is extracted from the inner membrane by the ATP‐binding cassette (ABC) transporter LptB2FGC, which places the glycolipid onto a periplasmic protein bridge that connects to the outer membrane. This ABC transporter is structurally unusual in that it associates with an additional protein, LptC. The periplasmic domain of LptC is part of the transporter's bridge while its transmembrane α‐helix intercalates into the LPS‐binding cavity of the core LptB2FG transporter. LptC’s transmembrane helix affects the in vitro ATPase activity of LptB2FG, but its role in LPS transport in cells remains undefined. Here, we describe two roles of LptC’s transmembrane helix in Escherichia coli. We demonstrate that it is required to maintain proper levels of LptC and participates in coupling the activity of the ATPase LptB to that of its transmembrane partners LptF/LptG prior to loading LPS onto the periplasmic bridge. Our data support a model in which the association of LptC’s transmembrane helix with LptFG creates a nonessential step that slows down the LPS transporter.
Seasonal Variation of Temperature in an Atmosphere at Rest

The variation of temperature of an atmosphere at rest with latitude and time is invest 'gated. The heating of an air column which is due to short-wave and long-wave radiation is estimated by simple parameterization. A condition of heat balance is assumed at the earth's surface to evaluate sensible heat flux there. An analysis of the equation shows that the heat capacity and the properties of the long-wave radiation of the atmosphere determine the time lag between variations in t ')u,J . ))'ature and insolation. In the numerical integration, extreme temperatures at middle latitude occurred about one month after the solstices. In the equatorial region, two maxima and two minima appeared in the temperature variation. The lowest temperat,ure in the polar region took place in spring because of the winter polar night. A comparison of the r esults of the integration with the observed variation demonstrates the importance of the meridional transport of energy in the atmosphere and ocean. T his comparison also suggests the importance of the storage of energy in the ocean and land.
Identification of mechanics-responsive osteocyte signature in osteoarthritis subchondral bone

Aims Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA. Methods Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature. Results A group of 77 persistent genes that are highly relevant to extracellular matrix (ECM) biology and bone remodelling signalling were identified in OA subchondral lesions. A loading responsive gene set, including 446 principal genes, was highly enriched in OA medial tibial plateaus compared to lateral tibial plateaus. Of this gene set, a total of 223 genes were identified as the main contributors that were strongly associated with osteocyte functions and signalling pathways, such as ECM modelling, axon guidance, Hippo, Wnt, and transforming growth factor beta (TGF-β) signalling pathways. We limited the loading-responsive genes obtained via the osteocyte transcriptome signature to identify a subgroup of genes that are highly relevant to osteocytes, as the mechanics-responsive osteocyte signature in OA. Based on WGCNA, we found that this signature was highly co-expressed and identified three clusters, including early, late, and persistently responsive genes. Conclusion In this study, we identified the mechanics-responsive osteocyte signature in OA-lesioned subchondral bone. Cite this article: Bone Joint Res 2022;11(6):362–370.
Contextual cues are not unique for motor learning: Task-dependant switching of feedback controllers

The separation of distinct motor memories by contextual cues is a well known and well studied phenomenon of feedforward human motor control. However, there is no clear evidence of such context-induced separation in feedback control. Here we test both experimentally and computationally if context-dependent switching of feedback controllers is possible in the human motor system. Specifically, we probe visuomotor feedback responses of our human participants in two different tasks—stop and hit—and under two different schedules. The first, blocked schedule, is used to measure the behaviour of stop and hit controllers in isolation, showing that it can only be described by two independent controllers with two different sets of control gains. The second, mixed schedule, is then used to compare how such behaviour evolves when participants regularly switch from one task to the other. Our results support our hypothesis that there is contextual switching of feedback controllers, further extending the accumulating evidence of shared features between feedforward and feedback control.
CRISPR/Cas9-mediated targeted mutagenesis of GmTCP19L increasing susceptibility to Phytophthora sojae in soybean

The TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factors is one of the superfamilies of plant-specific transcription factors involved in plant growth, development, and biotic and abiotic stress. However, there is no report on the research of the TCP transcription factors in soybean response to Phytophthora sojae. In this study, Agrobacterium-mediated transformation was used to introduce the CRISPR/Cas9 expression vector into soybean cultivar “Williams 82” and generated targeted mutants of GmTCP19L gene, which was previously related to involve in soybean responses to P. sojae. We obtained the tcp19l mutants with 2-bp deletion at GmTCP19L coding region, and the frameshift mutations produced premature translation termination codons and truncated GmTCP19L proteins, increasing susceptibility to P. sojae in the T2-generation. These results suggest that GmTCP19L encodes a TCP transcription factor that affects plant defense in soybean. The new soybean germplasm with homozygous tcp19l mutations but the BAR and Cas9 sequences were undetectable using strip and PCR methods, respectively, suggesting directions for the breeding or genetic engineering of disease-resistant soybean plants.
Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson’s disease

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic risk factors for Parkinson’s disease (PD). Increased LRRK2 kinase activity is thought to impair lysosomal function and may contribute to the pathogenesis of PD. Thus, inhibition of LRRK2 is a potential disease-modifying therapeutic strategy for PD. DNL201 is an investigational, first-in-class, CNS-penetrant, selective, ATP-competitive, small-molecule LRRK2 kinase inhibitor. In preclinical models, DNL201 inhibited LRRK2 kinase activity as evidenced by reduced phosphorylation of both LRRK2 at serine-935 (pS935) and Rab10 at threonine-73 (pT73), a direct substrate of LRRK2. Inhibition of LRRK2 by DNL201 demonstrated improved lysosomal function in cellular models of disease, including primary mouse astrocytes and fibroblasts from patients with Gaucher disease. Chronic administration of DNL201 to cynomolgus macaques at pharmacologically relevant doses was not associated with adverse findings. In phase 1 and phase 1b clinical trials in 122 healthy volunteers and in 28 patients with PD, respectively, DNL201 at single and multiple doses inhibited LRRK2 and was well tolerated at doses demonstrating LRRK2 pathway engagement and alteration of downstream lysosomal biomarkers. Robust cerebrospinal fluid penetration of DNL201 was observed in both healthy volunteers and patients with PD. These data support the hypothesis that LRRK2 inhibition has the potential to correct lysosomal dysfunction in patients with PD at doses that are generally safe and well tolerated, warranting further clinical development of LRRK2 inhibitors as a therapeutic modality for PD. Description The LRRK2 inhibitor DNL201 has a safety, tolerability, and pharmacodynamic profile that supports further testing as a therapy for Parkinson’s disease. A big step forward for Parkinson’s disease Inhibition of LRRK2 has emerged as a promising disease-modifying therapeutic target for Parkinson’s disease. Jennings et al. now report evidence that DNL201, a first-in-class CNS-penetrant LRRK2 kinase inhibitor, reduces LRRK2 activity and restores lysosomal function in cellular and animal models. In healthy volunteers and patients with Parkinson’s disease, DNL201 inhibited LRRK2 kinase activity and demonstrated an impact on lysosomal function at doses that were safe and generally well tolerated. As discussed in a related Focus, these findings provide support for advancing the investigation of LRRK2 inhibitors to late-stage clinical studies in patients with Parkinson’s disease.
The prevalence and distribution of human papillomavirus in 4267 Turkish women with or without cervical lesions: A hospital‐based study

In the present study, it was aimed to screen the genotypes of human papillomavirus (HPV) retrospectively in women with gynecological symptoms who were admitted to a tertiary care university hospital in Ankara, Turkey. A total of 4267 cervical swab samples of women aged 18–79 years were sent to Medical Virology Laboratory from January 2017 to November 2020. Nucleic acid extraction and amplification of samples were done by an automated system. The test can detect 14 high‐risk HPV (HR‐HPV) types in a single analysis that performs a real‐time polymerase chain reaction, by providing individual results on the highest‐risk genotypes HPV 16 and HPV 18 and pooled results on other high‐risk genotypes (OHR‐HPV) (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). HPV DNA positivity was detected in 14.2% (605/4267) of the samples. HPV type 16 and type 18 were detected in 2.4% and 0.7% of the samples, respectively. OHR‐HPV types were found in 8.8% of the samples. Of the 1.9% and 0.4% samples had mixed types with type 16+ OHR‐HPV and type 18+ OHR‐HPV, respectively. The results of this study presented the rates of HR‐HPV genotypes of a university hospital in Ankara, over a 4‐year period. It was observed that the positivity rate of type 18 is decreasing and some OHR‐HPV types are increasing. HPV vaccination is not in the national immunization program in Turkey yet, however, HPV vaccines are available and the vaccination rates for women are increasing.
On the complexity of polynomial factorization over P-adic fields

Let p be a rational prime and Z( x ) be a monic irreducible polynomial in Z p [ x ]. Based on the work of Ore on Newton polygons (Ore, 1928) and MacLane's characterization of polynomial valuations (MacLane, 1936), Montes described an algorithm for the decomposition of the ideal [Special characters omitted. ] over an algebraic number field (Montes, 1999). We give a simplified version of the Montes algorithm with a full MAPLE implementation which tests the irreducibility of Z( x ) over Q p . We derive an estimate of the complexity of this simplified algorithm in the worst case, when Z( x ) is irreducible over Q p . We show that in this case the algorithm terminates in at most[Special characters omitted. ] bit operations. Lastly, we compare the "one-element" and "two-element" variations of the Zassenhaus "Round Four" algorithm with the Montes algorithm