bluuebunny/crossref_metadata_2025_split huggingface dataset:
Additive Insert Molding (AIM) – A Practical Paradigm for Mass Customization of Multi-Material/Functional Parts
Authors: O'Quinn Ryan , Pradeep Sai Aditya , Pilla Srikanth , Farahani Saeed 
Published: September 2023

Abstract
Additive and traditional manufacturing are often regarded as separate schools of thought in end-part production, each with its own advantages and shortcomings. However, several attempts have been made to combine these two approaches in a complementary manner to improve upon their respective downfalls. Motivated by this approach, this work introduces a new integration concept that combines the best-in-class plastic manufacturing process, injection molding (IM), with additive manufacturing (AM) through a hybrid manufacturing process, which is here called Additive Insert Molding (AIM). AIM is the process of additively manufacturing inserts, placing the inserts into a specialized tool for a subsequent injection molding process, and finally ejecting a single hybrid part out of the tool. By this integration, the customizability and geometric freedom of AM are combined with the reliability and high production rate of the IM process. This integration also facilitates the incorporation of multi-material and part consolidation design approaches, hence hypothesizing AIM as a promising route for cost-efficiently mass-customizing multi-material/functional parts. Besides the introduction of the AIM concept, its main benefits and application criteria are herein discussed. Three proof-of-concept case studies are then presented evaluating the feasibility of using AIM for mass personalization, tool/process simplification, and tailored reinforcement. The results of each case study are analyzed to identify the potential benefits and challenges of using AIM in real-world applications. Finally, the important remarks and future research directions are extracted and discussed at the end of this paper.
Vision-Enabled Robot-Mill Collaboration for Hybrid Manufacturing
Authors: Goodwin Jesse , Saldaña Christopher 
Published: September 2023

Abstract
Recently, convergent manufacturing, or the combination of multiple processes into a single system, has gained attention for potential uses in hybrid additive-subtractive manufacturing. Here, a robot-CNC machine combination is explored as a convergent solution to hybrid manufacturing. Usually, hybrid manufacturing is performed either using a sequential process where parts are moved from additive to subtractive cells or using a process where all operations occur in a single machine. A less explored solution to the hybrid machining problem is to use a combination of two machines operating on the same workpiece to complete the process, allowing for interleaved or simultaneous hybrid processing. In this work, a flexible system is presented where a 6-axis robotic arm for deposition is combined with a 3-axis CNC mill for hybrid manufacturing. With this system, the robot can be moved to and away from the CNC as needed for a flexible manufacturing framework. With the added flexibility of the system, comes the problem of robot localization. Vision based robot localization methods were implemented to address this problem, and studies were conducted to determine the effects of disturbances encountered in a manufacturing environment on the localization performance. Results show that the proposed vision system can locate the robot within .5 mm and .25 deg, causing minimal disruption to the machining process.
Mixing of Spherical Solid and Nanoporous Copper Powders As Low-Reflectance Feedstock for Laser Powder Bed Fusion
Authors: Kublik Natalya , Niauzorau Stanislau , Azeredo Bruno 
Published: September 2023

Abstract
Micro- and nanoporous materials have gathered attention from the scientific community due to their size dependent properties, including but not limited to high specific surface area, surface diffusivity, bulk diffusivity and permeability, catalytic activity, and distinct optical properties. In this work, spherical nanoporous copper (np-Cu) powders, due to their nanosized porosity and low Cu2O content, show hemispherical total reflectance of 20% which is significantly lower than its bulk counterpart value for solid or molten copper of approximately 97% at wavelengths of most commercial Laser Powder Bed Fusion (L-PBF) commercial machines. The low-reflectance of np-Cu powders has the potential to be used in L-PBF to improve laser absorption, volumetric energy efficiency, and throughput of this additive manufacturing process. In fact, a prepared mixture of solid Cu powders containing only 5 wt.% of np-Cu powders reflects 34.8 % less than pure copper powders as shown in this paper. Np-Cu powders are fabricated via chemical dealloying of gas atomized CuAl alloy in a robust and scalable approach, and then mixed with pure copper powders to prepare hybrid feedstocks. Under this framework, the crucial role of deglomeration strategies to achieve homogeneity and flowability of np-Cu/Cu hybrid mixtures are evaluated via particle imaging to determine agglomerate size and composition with an eye at obtaining a high-quality print in L-PBF. In np-Cu powders fabrication, washing them in low-surface tension fluids upholds the highest degree of deglomeration in their fabrication process, and for hybrid feedstocks preparation, pre-mixing Cu and CuAl prior to dealloying yields the best homogeneity results with smallest size of agglomerates and good flowability.
Full Stack Virtual Commissioning: Requirements Framework to Bridge Gaps in Current Virtual Commissioning Process
Authors: Sim Jonathan B. , Shah Kavan N. , Saez Miguel , Abell Jeffrey , Zhou Yanli , Faris John , Tilbury Dawn M. , Barton Kira 
Published: September 2023

Abstract
Commissioning forms a crucial part of the initiation of a new manufacturing system. Commissioning activities occur after the design of a new manufacturing system or product line, but before the system is built and deployed into production. Current commissioning practices involve virtual commissioning (VC) tools with limited verification abilities, where virtual models representing a manufacturing system are built and then used in simulation. Software-In-The-Loop (SIL) simulation is applied to virtual models to measure and verify performance metrics that are important to a manufacturer. Due to inaccuracies and gaps in current VC capabilities, physical commissioning is still a common practice for complete verification and validation of a manufacturing system prior to deployment. The need for physical commissioning requires valuable time during the commissioning process. A Full Stack Virtual Commissioning process would eliminate the need for physical commissioning, allowing system integrators to more rapidly commission new manufacturing systems. In this work, we provide an initial Requirements Framework that outlines the critical technological and research gaps that must be addressed in order to achieve a transition toward a Full Stack Virtual Commissioning process. The current state-of-the-art approaches for commissioning are presented, along with an introduction to digital twin technology as an important VC enabler that is being explored within the academic and industrial domains. Lastly we highlight key benefits, important technical gaps, and critical challenges that must be addressed in order to facilitate a transition to Full Stack Virtual Commissioning.
Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis
Authors: Stemkens Ralf , Jager Veronique de , Dawson Rodney , Diacon Andreas H. , Narunsky Kim , Padayachee Sherman D. , Boeree Martin J. , van Beek Stijn W. , Colbers Angela , Coenen Marieke J. H. , Svensson Elin M. , Fuhr Uwe , Phillips Patrick P. J. , te Brake Lindsey H. M. , Aarnoutse Rob E. ,   on behalf of the PanACEA consortium
Published: September 2023

ABSTRACT

Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1–15), followed by RIF40 (days 16–30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%–115%); tolbutamide, 80% (74%–86%); omeprazole, 55% (47%–65%); dextromethorphan, 77% (68%–86%); midazolam, 62% (49%–78%), and 117% (105%–130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number
NCT04525235
.
Biofilm formation stabilizes metabolism in a
Roseobacteraceae
bacterium under temperature increase
Authors: Wang Meng , Lu Jie , Qin Peng , Wang Shuaitao , Ding Wei , Fu Hui-Hui , Zhang Yu-Zhong , Zhang Weipeng 
Published: September 2023

ABSTRACT

Ocean warming profoundly impacts microbes in marine environments; yet, how lifestyle (e.g., free living versus biofilm associated) affects the bacterial response to rising temperature is not clear. Here, we compared transcriptional, enzymatic, and physiological responses of free-living and biofilm-associated
Leisingera aquaemixtae
M597, a member of the
Roseobacteraceae
family isolated from marine biofilms, to the increase in temperature from 25℃ to 31℃. Complete genome sequencing and metagenomics revealed the prevalence of M597 in global ocean biofilms. Transcriptomics suggested a significant effect on the expression of genes related to carbohydrate metabolism, nitrogen and sulfur metabolism, and phosphorus utilization of free-living M597 cells due to temperature increase, but such drastic alterations were not observed in its biofilms. In the free-living state, the transcription of the key enzyme participating in the Embden-Meyerhof-Parnas pathway was significantly increased due to the increase in temperature, accompanied by a substantial decrease in the Entner-Doudoroff pathway, but transcripts of these glycolytic enzymes in biofilm-forming strains were independent of the temperature variation. The correlation between the growth condition and the shift in glycolytic pathways under temperature change was confirmed by enzymatic activity assays. Furthermore, the rising temperature affected the growth rate and the production of intracellular reactive oxygen species when M597 cells were free living rather than in biofilms. Thus, biofilm formation stabilizes metabolism in M597 when grown under high temperature and this homeostasis is probably related to the glycolytic pathways.

IMPORTANCE
Biofilm formation is one of the most successful strategies employed by microbes against environmental fluctuations. In this study, using a marine Roseobacteraceae bacterium, we studied how biofilm formation affects the response of marine bacteria to the increase in temperature. This study enhances our understanding of the function of bacterial biofilms and the microbe-environment interactions in the framework of global climate change.
IL-9 promotes methicillin-resistant
Staphylococcus aureus
pneumonia by regulating the polarization and phagocytosis of macrophages
Authors: Xu Weihua , Tian Keyin , Hu Shaowen , Chen Mingxiao , Zhang Meng 
Published: September 2023

ABSTRACT

In this study, we examined the effect of
Il9
deletion on macrophages in methicillin-resistant
Staphylococcus aureus
(MRSA) infection. MRSA-infected mice were employed for the
in vivo
experiments, and RAW264.7 cells were stimulated with MRSA for the
in vitro
experiments. Macrophage polarization was determined by flow cytometry and quantitative real-time PCR; macrophage phagocytosis was assessed by flow cytometry and laser scanning confocal microscopy; cell apoptosis was assessed by flow cytometry and western blotting.
Il9
deletion markedly elevated macrophage phagocytosis and M2 macrophages in MRSA infection, which was accompanied by elevated expression of
Il10
and
Arg1
and reduced expression of
Inos
, tumor necrosis factor-α (
Tnfα)
, and
Il6. Il9
deletion also inhibited macrophage apoptosis in MRSA infection, which was manifested by elevated B-cell lymphoma 2 (BCL-2) protein level and reduced protein levels of cleaved cysteine protease 3 (CASPASE-3) and BCL2-Associated X (BAX). Both the
in vivo
and
in vitro
experiments further showed the activation of phosphoinositide 3-kinase (PI3K)/AKT (also known as protein kinase B, PKB) signaling pathway in MRSA infection and that the regulation of
Il9
expression may be dependent on Toll-like receptor (TLR) 2/PI3K pathway. The above results showed that
Il9
deletion exhibited a protective role against MRSA infection by promoting M2 polarization and phagocytosis of macrophages and the regulation of
Il9
partly owing to the activation of TLR2/PI3K pathway, proposing a novel therapeutic strategy for MRSA-infected pneumonia.
Transcriptome screening identifies TIPARP as an antiviral host factor against the Getah virus
Authors: Jiao Houqi , Yan Ziqing , Zhai Xiaofeng , Yang Yichen , Wang Ningning , Li Xiaoling , Jiang Zhiwen , Su Shuo 
Published: September 2023

ABSTRACT
Alphaviruses are emerging and re-emerging viruses that cause severe disease and threaten public health worldwide. To advance the understanding of the underlying mechanisms of alphavirus replication and identify new host restriction factors, we performed RNA-seq and identified antiviral host factors on the Getah virus (GETV), a re-emerging alphavirus. We identified tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase (TIPARP) as a host antiviral factor. TIPARP is downregulated in GETV-infected Vero cells, and its overexpression significantly inhibits GETV replication, while TIPARP deficiency results in significantly increased viral titers. We demonstrated that TIPARP interacts with the viral E2 glycoprotein, inducing k48-linked ubiquitination and subsequent proteasomal degradation. Additionally, we found that TIPARP recruits the E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8) to modify the ubiquitination, leading to the degradation of E2. Lys253 in E2 was identified as the TIPARP-facilitated ubiquitination site. A mutation in Lys253 resulted in the loss of TIPARP’s anti-GETV effect. Our study demonstrated for the first time that host TIPARP is a restricting factor against GETV replication. Investigating the underlying mechanisms and understanding TIPARP for GETV will be essential to fully understanding viral pathogenesis and developing novel broad-spectrum therapeutic strategies against alphavirus infection.

IMPORTANCE
Alphaviruses threaten public health continuously, and Getah virus (GETV) is a re-emerging alphavirus that can potentially infect humans. Approved antiviral drugs and vaccines against alphaviruses are few available, but several host antiviral factors have been reported. Here, we used GETV as a model of alphaviruses to screen for additional host factors. Tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase was identified to inhibit GETV replication by inducing ubiquitination of the glycoprotein E2, causing its degradation by recruiting the E3 ubiquitin ligase membrane-associated RING-CH8 (MARCH8). Using GETV as a model virus, focusing on the relationship between viral structural proteins and host factors to screen antiviral host factors provides new insights for antiviral studies on alphaviruses.
Inhalation of vaccines and antiviral drugs to fight respiratory virus infections: reasons to prioritize the pulmonary route of administration
Authors: Heida Rick , Frijlink Henderik W. , Hinrichs Wouter L. J. 
Published: September 2023

ABSTRACT
Many of the current pandemic threats are caused by viruses that infect the respiratory tract. Remarkably though, the majority of vaccines and antiviral drugs are administered via alternative routes. In this perspective, we argue that the pulmonary route of administration deserves more attention in the search for novel therapeutic strategies against respiratory virus infections. Firstly, vaccines administered at the viral portal of entry can induce a broader immune response, employing the mucosal arm of the immune system; secondly, direct administration of antiviral drugs at the target site leads to superior bioavailability, enabling lower dosing and reducing the chance of side effects. We further elaborate on why the pulmonary route may induce a superior effect compared to the intranasal route of administration and provide reasons why dry powder formulations for inhalation have significant advantages over standard liquid formulations.
The VBNC state: a fundamental survival strategy of
Acinetobacter baumannii
Authors: König Patricia , Wilhelm Alexander , Schaudinn Christoph , Poehlein Anja , Daniel Rolf , Widera Marek , Averhoff Beate , Müller Volker 
Published: September 2023

ABSTRACT

The viable but non-culturable (VBNC) state is a persistence strategy adopted by bacteria to withstand long-lasting periods of unfavorable conditions. VBNC cells evade classical detection methods and are therefore easily transmitted in the hospital causing relapsing infections. The opportunistic human pathogen
Acinetobacter baumannii
has become a major threat in health care institutions and the food industry due to multiple antibiotic resistances and its ability to quickly adapt to very different ecological niches. Here, we report an additional, novel survival strategy of
A. baumannii
. Upon prolonged incubation in high-salt media, cells became unculturable. However, LIVE/DEAD staining followed by flow cytometry, respiratory activity assays, and resuscitation experiments revealed that these cells were viable but non-culturable. VBNC cells underwent large morphological changes. Entry into the VBNC state was also induced by pH and temperature stress, as well as by desiccation and anaerobiosis. The VBNC state was found in several strains of
A. baumannii
. Genome-wide expression profiling revealed a plethora of genes differentially regulated upon entry into the VBNC state. In summary, this study presents unequivocal evidence for a dormancy state in
A. baumannii
that has important consequences for detection of this pathogen and recurrent outbreaks.

IMPORTANCE

Currently, the viable but non-culturable (VBNC) state is an underappreciated niche for pathogenic bacteria which provides a continuous source for recurrent infections and transmission. We propose the VBNC state to be a global persistence mechanism used by various
A. baumannii
strains to cope with many stresses it is confronted with in the clinical environment and in the host. This requires a novel strategy to detect viable cells of this pathogen that is not only based on plating assays.
Immunosuppressive CD29+Treg accumulation in the liver in mice on checkpoint inhibitor therapy
Authors: Green Benjamin L , Myojin Yuta , Ma Chi , Ruf Benjamin , Ma Lichun , Zhang Qianfei , Rosato Umberto , Qi Jonathan , Revsine Mahler , Wabitsch Simon , Bauer Kylynda , Benmebarek Mohamed-Reda , McCallen Justin , Nur Amran , Wang Xin , Sehra Vivek , Gupta Revant , Claassen Manfred , Wang Xin Wei , Korangy Firouzeh , Greten Tim F 
Published: September 2023

ObjectiveLiver metastases are often resistant to immune checkpoint inhibitor therapy (ICI) and portend a worse prognosis compared with metastases to other locations. Regulatory T cells (Tregs) are one of several immunosuppressive cells implicated in ICI resistance of liver tumours, but the role played by Tregs residing within the liver surrounding a tumour is unknown.DesignFlow cytometry and single-cell RNA sequencing were used to characterise hepatic Tregs before and after ICI therapy.ResultsWe found that the murine liver houses a Treg population that, unlike those found in other organs, is both highly proliferative and apoptotic at baseline. On administration of αPD-1, αPD-L1 or αCTLA4, the liver Treg population doubled regardless of the presence of an intrahepatic tumour. Remarkably, this change was not due to the preferential expansion of the subpopulation of Tregs that express PD-1. Instead, a subpopulation of CD29+(Itgb1, integrin β1) Tregs, that were highly proliferative at baseline, doubled its size in response to αPD-1. Partial and full depletion of Tregs identified CD29+Tregs as the prominent niche-filling subpopulation in the liver, and CD29+Tregs demonstrated enhanced suppressionin vitrowhen derived from the liver but not the spleen. We identified IL2 as a critical modulator of both CD29+and CD29−hepatic Tregs, but expansion of the liver Treg population with αPD-1 driven by CD29+Tregs was in part IL2-independent.ConclusionWe propose that CD29+Tregs constitute a unique subpopulation of hepatic Tregs that are primed to respond to ICI agents and mediate resistance.
Toward extracting $$\gamma $$ from $$B\rightarrow DK$$ without binning
Authors: Backus Jeffrey V. , Freytsis Marat , Grossman Yuval , Schacht Stefan , Zupan Jure 
Published: September 2023

Abstract$$B^\pm \rightarrow DK^\pm $$

B
±

→
D

K
±

transitions are known to provide theoretically clean information about the CKM angle $$\gamma $$
γ
, with the most precise available methods exploiting the cascade decay of the neutral D into CP self-conjugate states. Such analyses currently require binning in the D decay Dalitz plot, while a recently proposed method replaces this binning with the truncation of a Fourier series expansion. In this paper, we present a proof of principle of a novel alternative to these two methods, in which no approximations at the level of the data representation are required. In particular, our new strategy makes no assumptions about the amplitude and strong phase variation over the Dalitz plot. This comes at the cost of a degree of ambiguity in the choice of test statistic quantifying the compatibility of the data with a given value of $$\gamma $$
γ
, with improved choices of test statistic yielding higher sensitivity. While our current proof-of-principle implementation does not demonstrate optimal sensitivity to $$\gamma $$
γ
, its conceptually novel approach opens the door to new strategies for $$\gamma $$
γ
extraction. More studies are required to see if these can be competitive with the existing methods.
A Simple and Cost-effective Approach to Make a Modified Suture Anchor in Orthopaedics
Authors: KAMATH B. N. Jagannath , NAYAK U. Keerthan Ranga , KAMATH K. Ramachandra , JAYASHEELAN Nikil 
Published: September 2023

The purpose of this study is to describe a technique of using an affordable suture anchor for various soft tissue repairs of both upper and lower limb surgeries in our series of patients. Eighteen patients with minimum 1-year follow-up after various upper limb surgeries using modified suture anchor were assessed both clinically and radiographically. In all 18 cases, the purpose of the suture anchor was served in terms of attachment of ligament or the tendon. There was no incidence of breakage of suture material or loosening of the implant seen during the insertion. There were no complications related to the implant noted. This novel technique turns a simple screw and suture material into an efficient suture anchor while saving time, being quick, easy, affordable and repeatable. Level of Evidence: Level V (Therapeutic)