bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward 3D dose verification of an electronic brachytherapy source with a plastic scintillation detector
Authors: Georgi Peter , Kertzscher Gustavo , Nyvang Lars , Šolc Jaroslav , Schneider Thorsten , Tanderup Kari , Johansen Jacob Graversen
Published: February 2022

Background

Electronic brachytherapy (eBT) is considered a safe treatment with good outcomes. However, eBT lacks standardized and independent dose verification, which could impede future use.

Purpose

To validate the 3D dose‐to‐water distribution of an electronic brachytherapy (eBT) source using a small‐volume plastic scintillation detector (PSD).

Methods

The relative dose distribution of a Papillon 50 (P50) (Ariane Medical Systems, UK) eBT source was measured in water with a PSD consisting of a cylindrical scintillating BCF‐12 fiber (length: 0.5 mm, Ø: 1 mm) coupled to a photodetector via an optical fiber. The measurements were performed with the PSD mounted on a motorized stage in a water phantom (MP3) (PTW, Germany). This allowed the sensitive volume of the PSD to be moved to predetermined positions relative to the P50 applicator, which pointed vertically downward while just breaching the water surface. The percentage depth‐dose (PDD) was measured from 0 to 50 mm source‐to‐detector distance (SDD) in 1–3 mm steps. Dose profiles were measured along two perpendicular axes at five different SDDs with step sizes down to 0.5 mm. Characterization of the PSD consisted of determining the energy correction through Monte Carlo (MC) simulation and by measuring the stability and dose rate linearity using a well‐type ionization chamber as a reference. The measured PDD and profiles were validated with corresponding MC simulations.

Results

The measured and simulated PDD curves agreed within 2% (except at 0 mm and 43 mm depth) after the PSD measurements were corrected for energy dependency. The absorbed dose decreased by a factor of 2 at 7 mm depth and by a factor of 10 at 26 mm depth. The measured dose profiles showed dose gradients at the profile edges of more than 50%/mm at 5 mm depth and 15%/mm at 50 mm depth. The measured profile widths increased 0.66 mm per 1 mm depth, while the simulated profile widths increased 0.74 mm per 1 mm depth. An azimuthal dependency of > 10% was observed in the dose at 10 mm distance from the beam center. The total uncertainty of the measured relative dose is < 2.5% with a positional uncertainty of 0.4 mm. The measurements for a full 3D dose characterization (PDD and profiles) can be carried out within 8 h, the limiting factor being cooling of the P50.

Conclusion

The PSD and MP3 water phantoms provided a method to independently verify the relative 3D dose distribution in water of an eBT source.
Bonded cumomer analysis of tumor metabolism based on 13C magnetic resonance spectroscopy
Authors: Shestov Alexander A. , Nath Kavindra , Nelson David S. , Wasik Mariusz A. , Glickson Jerry D.
Published: February 2022

Bonded cumomers are sets of isotopomers of 13C‐labeled metabolites containing a particular sequence of contiguously or singly labeled carbon atoms. Only these isotopomers contribute to multiplet structure in the 13C NMR spectrum. We discuss the application of this technique to the study of quantitative tumor metabolism, bioenergetics, and the Warburg effect. The advantages and sensitivity of bonded cumomer analysis over positional enrichment analysis are discussed. When sensitivity requirements are met, bonded cumomer analysis enables the extraction of fluxes through specific metabolic pathways with higher precision. In conjunction with isotopomer control analysis, we evaluate the sensitivity of experimentally measurable metabolite multiplets to determine the robustness of flux analysis in 13C spectra of tumors. This review examines the role of glycolytic and tricarboxylic acid cycle metabolism with special emphasis on flux through the pentose phosphate pathway (PPP). The impact of reversibility of the nonoxidative branch of the PPP with various 13C glucose tracers on fine‐structure multiplets is analyzed.
3D thermoelastic solids under non‐linear interface thermal and orthotropic frictional contact conditions
Authors: Ubero‐Martínez Iván , Rodríguez‐Tembleque Luis , Cifuentes‐Rodríguez Jaime , Vallepuga‐Espinosa José
Published: February 2022

This article presents a robust and efficient methodology to study three‐dimensional thermoelastic contact problems under orthotropic friction conditions, including the effects of non‐linear thermal contact conductance and convective boundary conditions at the interstitial contact zone. The proposed methodology considers the boundary element method to compute the thermomechanical influence coefficients and an augmented Lagrangian formulation to ensure the fulfillment of all these thermomechanical contact conditions. The resulting non‐linear equation set have been solved by an efficient proposed iterative Uzawa scheme. The proposed formulation has been validated by comparison with some available results in the literature and later on, it is considered to study how the thermoelastic contact variables are affected by both: the non‐linear interface thermal and the orthotropic friction conditions in different engineering problems such as a brake disc‐pad contact system.
Obesity and breast cancer: Preventive and therapeutic possibilities for bariatric surgery
Authors: Crafts Trevor D. , Tonneson Jennifer E. , Wolfe Bruce M. , Stroud Andrea M.
Published: February 2022

Breast cancer is the most common and second deadliest malignancy in women. With rising obesity rates and building evidence for a strong association with obesity, the incidence of breast cancer can be expected to increase. Weight loss reduces breast cancer risk, the mechanisms of which are still poorly understood. As an effective therapy for obesity, bariatric surgery may be a powerful tool in breast cancer prevention and treatment. This review details the potential physiologic mechanisms that may underlie this association, as well as recently published studies that reinforce the link between bariatric surgery and a reduction in incident breast cancer. The use of bariatric surgery as an adjunct therapy in endometrial cancer also raises the potential for similar use in select breast cancer patients. Despite the expanding potential applications of bariatric surgery in this field, publications to date have been strictly observational, highlighting a need for future clinical trials.
Identification of Forsythia suspensa (Thunb.) Vahl in different harvest periods using intelligent sensory technologies, HPLC characteristic fingerprint coupled with chemometrics
Authors: Pan Meng Hua , Su Ya Fei , Liu Xue Jing , Xiang Si Qi , Ding Yan Xia , Li Qin
Published: February 2022

Introduction

Forsythia suspensa (Thunb.) Vahl (FS), the fruit of Oleaceae plants, as a large part of traditional Chinese medicine, is classified as “Qingqiao (Q)” and “Laoqiao (L)” based on the harvest time. Because the maturation of FS is a gradual process, its accurate identification based on different maturity levels is an important issue.

Objectives

We suggest colorimetric, electronic tongue, and high‐performance liquid chromatography (HPLC) characteristic fingerprints to discriminate FS in different harvest periods.

Material and methods

First, FS fruits from different harvest times were collected, and then, their colour parameters, E‐tongue sensory properties, HPLC characteristic fingerprints, and contents of nominal ingredients were determined. Finally, multivariate statistical analyses, including three‐dimensional scatter plots, hierarchical cluster, principal component, linear discriminant, similarity, and partial least squares discriminant analyses were performed.

Results

The results demonstrated that the three experimental techniques could effectively discriminate FS based on different harvest times with 100% accuracy. Under the qualitative conditions, nine common peaks were identified in the HPLC fingerprints of 60 samples, among which, six peaks [variable importance in projection (VIP) > 1] could be used as index peaks for qualitative identification. In fact, the contents of quality marker components, including forsythin, phillygenin, rutin and forsythoside A, were significant different (P < 0.001) at different harvest times. Interestingly, the quality markers not only accurately reflected the maturity of FS but also showed close correlations with the colour parameters and sensory E‐tongue responses.

Conclusion

In our present investigation, bionic technologies, including a colorimeter, E‐tongue analysis, and HPLC characteristic fingerprints, combined with chemometrics, were employed to develop a novel and accurate method for discriminating FS based on different harvest times.
Validation of the multidimensional impact of Cancer Risk Assessment Questionnaire to assess impact of waiting for genome sequencing results
Authors: Best Megan , Napier Christine , Schlub Timothy , Bartley Nicci , Biesecker Barbara , Ballinger Mandy , Butow Phyllis
Published: February 2022

Objective

To determine whether the existing Multidimensional Impact of Cancer Risk Assessment (MICRA) scale, which assesses impact of receiving genetic test results on individuals being assessed for cancer risk, can be successfully adapted to cancer patients experiencing prolonged waiting for results of germline genome sequencing (GS).

Methods

Patients previously diagnosed with likely hereditary cancer (n = 250) who were waiting for germline GS results completed questionnaires 3 months after baseline. We adapted the MICRA to measure anxiety associated with waiting for results, and assessed factor structure, internal consistency, test–retest reliability and construct validation.

Results

Factor analysis revealed four factors: distress, positive experience, family support and uncertainty. Internal consistency for each sub‐scale was high with the values of Cronbach's alpha for the distress, positive experiences, family support and uncertainty sub‐scales 0.92, 0.88, 0.92 and 0.87, respectively. Test–retest reliability was poor, with intra‐class correlations of 0.53, 0.13, 0.33 and 0.52 for the four factors, respectively. Construct validation showed large correlations between the MICRA distress and uncertainty sub‐scale scores and the Impact of Events score intrusion (0.42 and 0.62, respectively) and IES avoidant thinking sub‐scales (0.40 and 0.58, respectively) but not the Hospital Anxiety and Depression Scale sub‐scales.

Conclusions

The adapted MICRA identified test‐related anxiety and uncertainty in a population of cancer patients waiting for germline GS results. Results suggest that the distress and uncertainty sub‐scales of the adapted measure are most useful in this context.
Analgesic and antiinflammatory effects of Nigella orientalis L. seeds fixed oil: Pharmacological potentials and molecular mechanisms
Authors: Ait Eldjoudi Djedjiga , Ruiz‐Fernandez Clara , González‐Rodriguez María , Ait Atmane Sihem , Cordero‐Barreal Alfonso , Farrag Yousof , Pino Jesus , Sineiro Jorge , Lago Francisca , Conde‐Aranda Javier , Khettal Bachra , Gualillo Oreste
Published: February 2022

Nigella species have been widely used in traditional medicine. The aim of this study was to evaluate the antiinflammatory and analgesic potentials of Nigella orientalis L. seeds fixed oil (NOO). The acetic acid writhing test and the formaldehyde‐induced licking paw were performed to assess the analgesic activity of the oil. The antiinflammatory activity was first evaluated in vitro by the erythrocyte membrane stabilization then in vivo by xylene‐ and carrageenan‐induced ear and paw edema, respectively. To further understand the molecular mechanism of action of the Nigella extract, lipopolysaccharide‐activated RAW 264.7 macrophages were used. Nitric oxide (NO) production was measured by Griess reaction and cell viability by MTT assay. The gene and protein expression of inflammatory mediators were assessed by RT‐PCR and western blot, respectively. NOO exerted a potent analgesic effect in in vivo models of writhing test and induced edema. The analyzed molecular mechanisms revealed a role for NO and prostaglandins as molecules mediating the pharmacological effects of the extract through a mechanism involving nuclear factor‐κB and mitogen‐activated protein kinases. This study demonstrates, for the first time, that the fixed oil of N. orientalis has strong antinociceptive and antiinflammatory properties and might be a promising agent for the treatment of certain inflammation‐related diseases.
A Prospective Diversity of Antibacterial Small Peptidomimetic and Quorum Sensing Mediated Drug: A Review
Authors: Bhukta Swadhapriya , Samal Sangram Keshari , Vasudevan Sahana , Sarveswari Hema Bhagavathi , Shanmugam Karthi , Princy S. Adline , Dandela Rambabu
Published: February 2022

The global threat of antimicrobial resistance demands alternative tackling approaches with a unique mechanism of action. Antimicrobial peptides are currently explored widely as the potential next generation antimicrobials and anti‐infectives. They provide multiple advantages in terms of wide spectrum activity ranging from antimicrobial, anti‐infective to immunomodulatory agents. The most striking feature is the delayed resistance development. Owing to their reduced stability and easy degradation, the current research is focused on the development of small peptidomimetic molecules (SPMs) provides longer half‐life and improved stability. In addition, they are widely explored as quorum sensing inhibitors. These are proven to be effective quorum quenchers against both Gram ‐ positive and Gram – negative bacteria. Specifically these molecules are shown to have potent anti‐biofilm activity. In this regard, this review provides the structural aspects in the development of SPMs as both antibacterial and anti‐quorum drugs for the last five years.
Iodide Salt Mediated Synthesis of β‐Keto Sulfones Using Arylsulfonyl Chlorides as the Sulfur Sources
Authors: Yuan Zhi‐ying , Zhang Shuai , Teng Fan , Jin Xue‐Feng , Sheng Wen‐bing , Gui Qing‐Wen
Published: February 2022

An efficient, green strategy has been developed to synthesize β‐keto sulfones using available and inexpensive sulfonyl chlorides as a sulfur source in reaction with aromatic alkenes in the presence of cheap iodide. It is particularly pointed out that this method involves the construction of C−S bonds and the desired product can be obtained either through the free radical pathway. This agreement involves a green and simple synthesis method, and is functionalized with styrene and the present method is applicable to a wide range of benzenesulfonyl chloride compounds and styrenes with a variety of functional groups.
Synthesis of Pentacyclic Pyran Fused Pyrazolo Benzo[h]quinolines by Multicomponent Reaction and Their Photophysical Studies
Authors: Yadav Rahul , Darakshan  , Bhaumick Prabhas , Choudhury Lokman H. , Parvin Tasneem
Published: February 2022

Herein we report for the first time a one‐pot method for the synthesis of pentacyclic pyran fused pyrazolo benzo[h]quinolines in acetic acid medium from the three‐component reaction of 2‐hydroxy‐1,4‐naphthoquinone, α, β‐unsaturated aldehydes and 5‐aminopyrazoles under the reflux conditions. In this reaction, four new bonds (2 C−C, 1 C−N and 1 C−O) and two new rings (pyridine and pyran) were formed in one‐pot. The novel products contain four bioactive moieties such as pyran, pyridine, pyrazole and α‐naphthol. The salient features of this method are: one‐pot process, short reaction time, easier purification, no need of column chromatography and good yields of the products. All the products were characterized by IR, NMR and HRMS. Most of our synthesized compounds were found highly fluorescent. Therefore, we further studied their photophysical properties by UV‐Visible and Fluorescence spectroscopy. We have calculated their quantum yields which were found in the range 0.243–0.424 in CHCl3 solution (c=10−5 M). Compound 4 e showed the highest quantum yield of 0.424.
In Operando Neutron Scattering Multiple‐Scale Studies of Lithium‐Ion Batteries
Authors: Wang Huibo , Ning De , Wang Litong , Li Heng , Li Qingyuan , Ge Mingzheng , Zou Junyan , Chen Shi , Shao Huaiyu , Lai Yuekun , Zhang Yanyan , Xing Guichuan , Pang Wei Kong , Tang Yuxin
Published: February 2022

Real‐time observation of the electrochemical mechanistic behavior at various scales offers new insightful information to improve the performance of lithium‐ion batteries (LIBs). As complementary to the X‐ray‐based techniques and electron microscopy‐based methodologies, neutron scattering provides additional and unique advantages in materials research, owing to the different interactions with atomic nuclei. The non‐Z‐dependent elemental contrast, in addition to the high penetration ability and weak interaction with matters, makes neutron scattering an advanced probing tool for the in operando mechanistic studies of LIBs. The neutron‐based techniques, such as neutron powder diffraction, small‐angle neutron scattering, neutron reflectometry, and neutron imaging, have their distinct functionalities and characteristics regimes. These result in their scopes of application distributed in different battery components and covering the full spectrum of all aspects of LIBs. The review surveys the state‐of‐the‐art developments of real‐time investigation of the dynamic evolutions of electrochemically active compounds at various scales using neutron techniques. The atomic‐scale, the mesoscopic‐scale, and at the macroscopic‐scale within LIBs during electrochemical functioning provide insightful information to battery researchers. The authors envision that this review will popularize the applications of neutron‐based techniques in LIB studies and furnish important inspirations to battery researchers for the rational design of the new generation of LIBs.
Prediction of bug‐fixing time based on distinguishable sequences fusion in open source software
Authors: Du Junwei , Ren Xinshuang , Li Haojie , Jiang Feng , Yu Xu
Published: February 2022

Generally, open source software (OSS) has a longer bug‐fixing time. If the bug‐fixing time can be predicted accurately as early as possible, it will be beneficial to the efficiency of bug fixing. Traditional bug‐fixing time prediction models are usually based on static features of bug report. It is difficult to go into service due to inappropriate feature extraction of data and low prediction accuracy of models. The HMM prediction model can predict the bug‐fixing time accurately according to earlier fixing activities. However, this method of temporal sequence feature selection results in a large number of inconsistent samples, and the HMM prediction model can only capture the adjacent activity behavior information of one sequence, and hence, it will reduce the performance of bug‐fixing time prediction. By incorporating the activity information and time information of bug activity transfer, the proportion of inconsistent samples is reduced significantly. In this paper, a double‐sequence input LSTM model (LSTM‐DA) is designed to capture both sequences interaction features and long‐distance‐dependent features. The results of the experiments show that the proposed model can improve the F‐measure and accuracy indicators by about 10% compared with the HMM model in all dimensions, which demonstrates the effectiveness of our method.
Application of engineered cementitious composites in the plastic hinge of reinforced concrete beams for seismic enhancing
Authors: Zhang Yangxi , Yao Xinyuan , Li Tong , Deng Mingke
Published: February 2022

Shear failure of the potential plastic hinge region of reinforced concrete (RC) beam usually causes irrational failure mechanism and low seismic response of the whole frame structure. In this study, engineered cementitious composite (ECC) was proposed to apply locally in the potential plastic hinge region of RC beams to improve the failure mode and rotation capacity of the members. One RC beam and five ECC‐RC composite beams were manufactured, and tested by lateral cyclic loading. The test variables were the length of ECC strengthening region, stirrup ratio and longitudinal reinforcement ratio. The test results indicated that the plastic hinge region of the RC beam failed in shear with poor plastic deformation and low energy dissipation. For the ECC strengthened beams, flexural behavior dominated the ECC region and shear failure was migrated up into the concrete region or eliminated. The ECC region of the composite beams exhibited great rotation capacity, thus the hysteretic response, plastic deformability and energy dissipation of the ECC strengthened beams were improved significantly. Meanwhile, applying ECC in the plastic hinge effectively enhances the damage tolerance of the beams. Based on the test results, the substituting length of ECC in the potential plastic hinge of the RC beam is recommended to be no less than the beam height. Besides, the strength of ECC strengthened beam can be calculated and checked by the current design codes.
Optimal verification strategies in multi‐firm projects
Authors: Kulkarni Aditya U. , Salado Alejandro , Wernz Christian
Published: February 2022

Verification activities are intended to reduce the costs of system development by identifying design errors before deploying the system. However, subcontractors in multifirm projects are motivated to implement locally cost‐effective verification strategies over verification strategies that benefit the main contractor. Incentivizing verification activities is one mechanism by which the contractor can motivate subcontractors to implement verification strategies desirable to the contractor. Prior work on mathematical models of verification in systems engineering has neither explored optimal verification strategies nor incentives in multi‐firm projects. In this paper, we present a modeling concept for determining optimal verification strategies in multi‐firm projects. Our models are belief‐based, which means that contractors and subcontractors incorporate their at times limited knowledge about true verification state through a probabilistic assessment of possible states. We develop an initial two‐level model, where one contractor directly works with multiple subcontractors at the next lower level. This model is then extended to a general network model with multiple, multilevel contractor‐subcontractor relationship. We derive solution algorithms that characterize the optimal verification strategies and incentives for each of the firms. Our work contributes to the systems engineering literature by laying the foundation for the study of incentives as a mechanism to align verification activities in multi‐firm systems engineering projects.
Biogeography and systematics ofCarexsubgenusUncinia(Cyperaceae): A unique radiation for the genusCarexin the Southern Hemisphere
Authors: García‐Moro Pablo , Otero Ana , Benítez‐Benítez Carmen , Costa Lucas , Martín‐Bravo Santiago , Naczi Robert F.C. , Reznicek Anton A. , Roalson Eric H. , Starr Julian R. , Jiménez‐Mejías Pedro
Published: February 2022

Carexsubg.Uncinia(Cyperaceae) constitutes one of six currently recognizedCarexsubgenera. This subgenus is mainly distributed on the American continent and in the Pacific region, and it is the only subgenus almost entirely absent from the Old World and primarily diversified in the Southern Hemisphere. It includes some of the fewCarexspecies with clear epizoochoric traits: the representatives ofC. sect.Unciniapossess utricles with an exserted and hooked rachilla that allows the diaspores to attach to feather or hair. We performed phylogenetic (ITS, ETS‐1f,matK), biogeographic, and ancestral state reconstruction analyses to elucidate the systematic structure, origin and dispersal routes, and major morphological evolutionary patterns of the different lineages within the subgenus. Our phylogenetic reconstructions revealed that the subgenus comprises seven different clades that mostly match previously recognized sections. One of the clades, however, represents a new section described herein asC. sect.Wheelerianae. Unispicate lineages evolved repeatedly from ancestors bearing multispicate inflorescences, while the presence of a rachilla, often pictured as a plesiomorphy inCarex, seems to have developed four independent times in the evolution ofC. subg.Uncinia. The origin of the subgenus dates back to the beginning of the Miocene, probably in North America from where it colonized the Southern Hemisphere. It first dispersed to South America during the Early Miocene. Later, in the Middle Miocene, representatives ofC. sect.Unciniawould reach the Pacific Southwest region (New Zealand, Australasia) from South America in at least two independent dispersal events. The vast majority of the biogeographic events seem to be explained by long‐distance dispersal. The remarkable dispersal ability ofC. sect.Unciniaenabled by the hooked rachilla has allowed it to reach remote archipelagos in the Pacific and Subantarctic regions, probably bird‐mediated.
A critical review of disproportionality in loss and damage from climate change
Authors: Dorkenoo Kelly , Scown Murray , Boyd Emily
Published: February 2022

The notion of disproportionate impacts of climate change on certain groups and regions has long been a part of policy debates and scientific inquiry, and was instrumental to the emergence of the “Loss and Damage” (L&D) policy agenda in international negotiations on climate change. Yet, ‘disproportionality’ remains relatively undefined and implicit in science on loss and damage from climate change. A coherent theoretical basis of disproportionality is needed for advancing science and policy on loss and damage. It is necessary to ask: What is disproportionate, to whom, and in relation to what? We critically examine the uses of disproportionality in loss and damage scholarship by analyzing how disproportionality is treated in the literature conceptually, methodologically, and empirically. We review publications against a set of criteria derived from seminal work on disproportionality in other fields, mainly environmental justice and disaster studies that have analyzed environment–society interactions. We find disproportionality to be dynamic and multidimensional, spanning the themes of risks, impacts, and burdens. Our results show that while the concept is often used in loss and damage scholarship, its use relies on unarticulated notions of justice and often lacks conceptual, methodological and empirical grounding. Disproportionality also appears as a boundary concept, enabling critical and multiscalar explorations of historical processes that shape the uneven impacts of climate change, alongside social justice and normative claims for desired futures. This emerging area of science offers an opportunity to critically re‐evaluate the conceptualization of the relationship between climate‐change‐related impacts, development, and inequality.

This article is categorized under:

Climate, Nature, and Ethics > Climate Change and Global Justice

Climate and Development > Social Justice and the Politics of Development
What makes carbon nanoparticle a potent material for biological application?
Authors: Chatterjee Niranjan , Kumar Piyush , Kumar Krishan , Misra Santosh K.
Published: February 2022

Carbon materials are generally utilized in the form of carbon allotropes and their characteristics are exploited as such or for improving the thermal, electrical, optical, and mechanical properties of other biomaterials. This has now found a broader share in conventional biomaterial space with the generation of nanodiamond, carbon dot, carbon nanoparticles (CNPs), and so forth. With properties of better biocompatibility, intrinsic optical emission, aqueous suspendability, and easier surface conjugation possibilities made CNPs as one of the fore most choice for biological applications especially for use in intracellular spaces. There are various reports available presenting methods of preparing, characterizing, and using CNPs for various biological applications but a collection of information on what makes CNP a suitable biomaterial to achieve those biological activities is yet to be provided in a significant way. Herein, a series of correlations among synthesis, characterization, and mode of utilization of CNP have been incorporated along with the variations in its use as agent for sensing, imaging, and therapy of different diseases or conditions. It is ensembled that how simplified and optimized methods of synthesis is correlated with specific characteristics of CNPs which were found to be suitable in the specific biological applications. These comparisons and correlations among various CNPs, will surely provide a platform to generate new edition of this nanomaterial with improvised applications and newer methods of evaluating structural, physical, and functional properties. This may ensure the eventual use of CNPs for human being for specific need in near future.

This article is categorized under:

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Diagnostic Tools > Biosensing

Diagnostic Tools > In Vitro Nanoparticle‐Based Sensing

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Silicon‐carbon hybrid [2]‐ladderanes
Authors: Lambert Marcel , Poitiers Nadine E. , Huch Volker , Goforth Andrea , Scheschkewitz David
Published: February 2022

The first silicon‐carbon hybrid ladderanes consisting of trisila and tricarba ladder rails were obtained by the reactions of lithium disilenide R2Si=SiRLi (R=2,4,6‐triisopropylphenyl) with allylchlorosilanes. The steric strain in the 1,2,6‐trisilabicyclo[2.2.0]hexanes imposed by the bulky substituents leads to highly distorted ring systems with extreme puckering and long silicon‐carbon bridgehead bonds. All 1,2,6‐trisilabicyclo[2.2.0]hexanes show strong absorptions in the UV/vis and the rigidity of the [2]‐ladderane framework gives rise to turquoise fluorescence.
Proton lifetime in minimal SUSY SU(5) in light of LHC results
Authors: Babu K. S. , Gogoladze Ilia , Ün Cem Salih
Published: February 2022

Abstract

We examine proton decay mediated by color-triplet Higgsinos in minimal supersymmetric SU(5) grand unified theory in light of the discovery of the Higgs boson and the absence of SUSY signals at the LHC. We pay special attention to various threshold effects arising from Planck-suppressed operators that affect the color-triplet Higgsino mass and also allow for correcting the wrong mass relations for the light fermions. Our analysis allows for a non-universal SUSY spectrum with the third family sfermions having a separate mass compared to the first two families. We identify the allowed parameter space of the model and show that the SUSY scalar masses are constrained by current limits from proton lifetime to be above 5 TeV, while the glunio, Wino and the Higgsinos may be within reach of the LHC. When the SUSY scalar masses are required to be ≤ 30 TeV, so that they are within reach of next generation collider experiments, we find that proton lifetime for the decay p → $$ \overline{\nu} $$

ν
¯

K+ is bounded by τ(p → $$ \overline{\nu} $$

ν
¯

K+) ≤ 1.1 × 1035 yrs.
Disentangling jet modification in jet simulations and in Z+jet data
Authors: Brewer Jasmine , Brodsky Quinn , Rajagopal Krishna
Published: February 2022

Abstract

The selection of jets in heavy-ion collisions based on theirpTafter jet quenching is known to bias towards jets that lost little energy in the quark-gluon plasma. In this work, we study and quantify the impact of this selection bias on jet substructure observables so as to isolate effects caused by the modification of the substructure of jets by quenching. We do so at first in a simplified Monte Carlo study in which it is possible to identify the same jet before and after quenching. We show explicitly that jets selected based on their quenched (i.e. observable)pThave substantially smaller fractional energy loss than those selected based on thepTthat they would have had in the absence of any quenching. This selection bias has a large impact on jet structure and substructure observables. As an example, we consider the angular separation ∆Rof the hardest splitting in each jet, and find that the ∆Rdistribution of the (biased) sample of jets selected based upon their quenchedpTis almost unmodified by quenching. In contrast, quenching causes dramatic modifications to the ∆Rdistribution of a sample of jets selected based upon their unquenchedpT, with a significant enhancement at larger ∆Rcoming from the soft particles originating from the wake of the jet in the quark-gluon plasma. The jets which contribute to this enhancement are those which have lost the most energy and which were, therefore, left out of the sample selected after quenching. In a more realistic study, we then show that the same qualitative effects can all be observed inZ+jet events. Selecting jets in such events based on either the jetpTor theZ-bosonpTprovides an experimentally accessible way to quantify the effects of selection biases in jet observables and separate them from the modification of jet substructure caused by quenching. SelectingZ+jet events based upon the jetpTyields a ∆Rdistribution that appears almost unmodified whereas selectingZ+jet events based upon theZ-bosonpTreveals a significant modification to the ∆R-distribution caused by quenching, once again arising from the wakes of those jets that lose more energy.
Quantum bit threads and holographic entanglement
Authors: Agón Cesar A. , Pedraza Juan F.
Published: February 2022

Abstract

Quantum corrections to holographic entanglement entropy require knowledge of the bulk quantum state. In this paper, we derive a novel dual prescription for the generalized entropy that allows us to interpret the leading quantum corrections in a geometric way with minimal input from the bulk state. The equivalence is proven using tools borrowed from convex optimization. The new prescription does not involve bulk surfaces but instead uses a generalized notion of a flow, which allows for possible sources or sinks in the bulk geometry. In its discrete version, our prescription can alternatively be interpreted in terms of a set of Planck-thickness bit threads, which can be either classical or quantum. This interpretation uncovers an aspect of the generalized entropy that admits a neat information-theoretic description, namely, the fact that the quantum corrections can be cast in terms of entanglement distillation of the bulk state. We also prove some general properties of our prescription, including nesting and a quantum version of the max multiflow theorem. These properties are used to verify that our proposal respects known inequalities that a von Neumann entropy must satisfy, including subadditivity and strong subadditivity, as well as to investigate the fate of the holographic monogamy. Finally, using the Iyer-Wald formalism we show that for cases with a local modular Hamiltonian there is always a canonical solution to the program that exploits the property of bulk locality. Combining with previous results by Swingle and Van Raamsdonk, we show that the con- sistency of this special solution requires the semi-classical Einstein’s equations to hold for any consistent perturbative bulk quantum state.
Late-stage rescue of visually guided behavior in the context of a significantly remodeled retinitis pigmentosa mouse model
Authors: Kajtna Jacqueline , Tsang Stephen H. , Koch Susanne F.
Published: February 2022

Patients with progressive neurodegenerative disorder retinitis pigmentosa (RP) are diagnosed in the midst of ongoing retinal degeneration and remodeling. Here, we used a Pde6b-deficient RP gene therapy mouse model to test whether treatment at late disease stages can halt photoreceptor degeneration and degradative remodeling, while sustaining constructive remodeling and restoring function. We demonstrated that when fewer than 13% of rods remain, our genetic rescue halts photoreceptor degeneration, electroretinography (ERG) functional decline and inner retinal remodeling. In addition, in a water maze test, the performance of mice treated at 16 weeks of age or earlier was indistinguishable from wild type. In contrast, no efficacy was apparent in mice treated at 24 weeks of age, suggesting the photoreceptors had reached a point of no return. Further, remodeling in the retinal pigment epithelium (RPE) and retinal vasculature was not halted at 16 or 24 weeks of age, although there appeared to be some slowing of blood vessel degradation. These data suggest a novel working model in which restoration of clinically significant visual function requires only modest threshold numbers of resilient photoreceptors, halting of destructive remodeling and sustained constructive remodeling. These novel findings define the potential and limitations of RP treatment and suggest possible nonphotoreceptor targets for gene therapy optimization.
Sterbefälle mit unbekannter oder ungenau bezeichneter Todesursache – attestierte Todesarten und durchgeführte Obduktionen
Authors: Krause Maike , Graw M. , Gleich S.
Published: February 2022

Hintergrund

Eine unzureichende Qualität von Leichenschau und ausgefertigten Todesbescheinigungen (TB) ist in der Literatur seit langem Gegenstand kontroverser Diskussionen. Häufig zu bemängeln sind fehlerhafte oder unplausible Kausalketten und eine fälschlicherweise attestierte natürliche Todesart.

Ziel der Arbeit

Es soll untersucht werden, welche Todesart bei einer unbekannten oder ungenau bezeichneten Todesursache durch den Leichenschauer attestiert wurde, und wie häufig bei diesen Fällen eine Obduktion am Institut für Rechtsmedizin (IRM) durchgeführt wurde.

Methode

Es wurden vertraulicher und nicht vertraulicher Teil aller TB des 2. Quartals 2013 der Stadt München standardisiert erfasst und statistisch ausgewertet.

Ergebnisse

Im Studienzeitraum wurden insgesamt 3228 TB erfasst. Es wurde bei 900 Fällen (27,9 %) unter Ia bzw. bei 462 Fällen (14,3 %) unter Ic eine unbekannte oder ungenau bezeichnete Todesursache attestiert. Trotz unbekannter Todesursache wurde gleichzeitig bei 4,0 % der Fälle eine natürliche Todesart bescheinigt. Eine Obduktion wurde bei Sterbefällen mit unbekannter Todesursache um ein Vielfaches häufiger (Ia: 52,0 % und Ic: 52,1 %) als bei Fällen mit ungenau bezeichneter Todesursache durchgeführt (Ia: 5,2 % und Ic: 7,5 %).

Diskussion

Bei den meisten Fällen haben die Leichenschauer die korrekte Todesart bei einer unbekannten Todesursache attestiert (96,0 %), jedoch bei 4,0 % auch fälschlicherweise gleichzeitig eine natürliche Todesart. Dies hat weitreichende, insbesondere strafprozessuale Konsequenzen, da bei Angabe einer natürlichen Todesart keine Benachrichtigung der Ermittlungsbehörden mit dem Ziel der Klärung der Todesumstände erfolgt. An dieser Stelle besteht das Risiko einer „Erfassungslücke“ nicht natürlicher Todesfälle.
The integrated nuclear medicine and radiology residency program in the Netherlands: strengths and potential areas for improvement according to nuclear medicine physicians and radiologists
Authors: Velleman Ton , Kwee Thomas C. , Dierckx Rudi A. J. O. , Ongena Yfke P. , Noordzij Walter
Published: February 2022

Purpose

To evaluate the Dutch integrated nuclear medicine and radiology residency program from the perspective of nuclear medicine physicians and radiologists.

Methods

A survey was distributed among nuclear medicine physicians and radiologists in hospitals that participate in the Dutch integrated nuclear medicine and radiology training program.

Results

A total of 139 completed questionnaires were included. Nuclear medicine physicians (n = 36) assigned a mean score of 5.7 ± 2.0, and radiologists (n = 103) assigned a mean score of 6.5 ± 2.8 (on a 1–10 scale) to the success of the integrated training program in their hospital. On multiple regression, female gender of the survey participant (B = 2.22, P = 0.034), musculoskeletal radiology as subspecialty of the survey participant (B = 3.36, P = 0.032), and the survey participant’s expectancy of resident’s ability to handle workload after completion of residency were significantly associated with perceived success of the integrated training program (B = 1.16, P = 0.023). Perceived strengths of the integrated training program included broadening of expertise, a better preparation of future imaging specialists for hybrid imaging, increased efficiency in training residents, and increased efficiency in multidisciplinary meetings. Perceived weaknesses of the integrated training program included reduced exposure to nuclear medicine, less time for research and innovation, and concerns about its international recognition.

Conclusion

This study provided insights into the experiences of nuclear medicine physicians and radiologists with the Dutch integrated nuclear medicine and radiology residency program, which may be helpful to improve the program and similar residency programs in other countries.
Plasma biomarkers for Alzheimer’s Disease in relation to neuropathology and cognitive change
Authors: Smirnov Denis S. , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik , Simrén Joel , Lantero-Rodriguez Juan , Karikari Thomas K. , Hiniker Annie , Rissman Robert A. , Salmon David P. , Galasko Douglas
Published: February 2022

Plasma biomarkers related to amyloid, tau, and neurodegeneration (ATN) show great promise for identifying these pathological features of Alzheimer’s Disease (AD) as shown by recent clinical studies and selected autopsy studies. We have evaluated ATN plasma biomarkers in a series of 312 well-characterized longitudinally followed research subjects with plasma available within 5 years or less before autopsy and examined these biomarkers in relation to a spectrum of AD and related pathologies. Plasma Aβ42, Aβ40, total Tau, P-tau181, P-tau231 and neurofilament light (NfL) were measured using Single molecule array (Simoa) assays. Neuropathological findings were assessed using standard research protocols. Comparing plasma biomarkers with pathology diagnoses and ratings, we found that P-tau181 (AUC = 0.856) and P-tau231 (AUC = 0.773) showed the strongest overall sensitivity and specificity for AD neuropathological change (ADNC). Plasma P-tau231 showed increases at earlier ADNC stages than other biomarkers. Plasma Aβ42/40 was decreased in relation to amyloid and AD pathology, with modest diagnostic accuracy (AUC = 0.601). NfL was increased in non-AD cases and in a subset of those with ADNC. Plasma biomarkers did not show changes in Lewy body disease (LBD), hippocampal sclerosis of aging (HS) or limbic-predominant age-related TDP-43 encephalopathy (LATE) unless ADNC was present. Higher levels of P-tau181, 231 and NfL predicted faster cognitive decline, as early as 10 years prior to autopsy, even among people with normal cognition or mild cognitive impairment. These results support plasma P-tau181 and 231 as diagnostic biomarkers related to ADNC that also can help to predict future cognitive decline, even in predementia stages. Although NfL was not consistently increased in plasma in AD and shows increases in several neurological disorders, it had utility to predict cognitive decline. Plasma Aβ42/40 as measured in this study was a relatively weak predictor of amyloid pathology, and different assay methods may be needed to improve on this. Additional plasma biomarkers are needed to detect the presence and impact of LBD and LATE pathology.
Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation
Authors: Wilson Miranda L. , Thysell Jarl A. , Baumann Kristen K. , Quaranta Danny V. , Liang W. Sandy , Erickson Michelle A.
Published: February 2022

Purpose

Anesthetics are required for procedures that deliver drugs/biologics, infectious/inflammatory agents, and toxicants directly to the lungs. However, the possible confounding effects of anesthesia on lung inflammation and injury are underreported. Here, we evaluated the effects of two commonly used anesthetic regimens on lung inflammatory responses to ozone in mice.

Methods

We tested the effects of brief isoflurane (Iso) or ketamine/xylazine/atipamezole (K/X/A) anesthesia prior to ozone exposure (4 h, 3 ppm) on lung inflammatory responses in mice. Anesthesia regimens modeled those used for non-surgical intratracheal instillations and were administered 1–2 h or 24 h prior to initiating ozone exposure.

Results

We found that Iso given 1–2 h prior to ozone inhibited inflammatory responses in the lung, and this effect was absent when Iso was given 23–24 h prior to ozone. In contrast, K/X/A given 1–2 h prior to ozone increased lung and systemic inflammation.

Conclusion

Our results highlight the need to comprehensively evaluate anesthesia as an experimental variable in the assessment of lung inflammation in response to ozone and other inflammatory stimuli.
Cold for centuries: a brief history of cryotherapies to improve health, injury and post-exercise recovery
Authors: Allan Robert , Malone James , Alexander Jill , Vorajee Salahuddin , Ihsan Mohammed , Gregson Warren , Kwiecien Susan , Mawhinney Chris
Published: February 2022

For centuries, cold temperatures have been used by humans for therapeutic, health and sporting recovery purposes. This application of cold for therapeutic purposes is regularly referred to as cryotherapy. Cryotherapies including ice, cold-water and cold air have been popularised by an ability to remove heat, reduce core and tissue temperatures, and alter blood flow in humans. The resulting downstream effects upon human physiologies providing benefits that include a reduced perception of pain, or analgesia, and an improved sensation of well-being. Ultimately, such benefits have been translated into therapies that may assist in improving post-exercise recovery, with further investigations assessing the role that cryotherapies can play in attenuating the ensuing post-exercise inflammatory response. Whilst considerable progress has been made in our understanding of the mechanistic changes associated with adopting cryotherapies, research focus tends to look towards the future rather than to the past. It has been suggested that this might be due to the notion of progress being defined as change over time from lower to higher states of knowledge. However, a historical perspective, studying a subject in light of its earliest phase and subsequent evolution, could help sharpen one’s vision of the present; helping to generate new research questions as well as look at old questions in new ways. Therefore, the aim of this brief historical perspective is to highlight the origins of the many arms of this popular recovery and treatment technique, whilst further assessing the changing face of cryotherapy. We conclude by discussing what lies ahead in the future for cold-application techniques.