bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible immunoglobulin-E-dependent sugammadex-induced anaphylaxis caused by an epitope other than γ-cyclodextrin: a case report
Authors: Horiuchi Tatsuo , Takazawa Tomonori , Sakamoto Shinya , Orihara Masaki , Yokohama Akihiko , Uchiyama Mutsumi , Saito Shigeru
Published: June 2021

Background

Sugammadex is a synthetic γ-cyclodextrin derivative designed to selectively bind to steroidal neuromuscular blocking agents and reverse their effects. Although many cases of sugammadex-induced anaphylaxis have been reported, few studies have investigated the underlying mechanism.

Case presentation

A 55-year-old Japanese man underwent a laryngectomy under general anesthesia. One month before laryngectomy, he had undergone laryngoscopy under general anesthesia and received sugammadex administration without causing hypersensitivity. He had no history of allergies. The operation was finished without complications. Shortly after sugammadex administration, his blood pressure dropped to approximately 70 mmHg, and his heart rate increased to 110 beats/minute with systemic erythema. Suspecting anaphylaxis, he was treated with the intravenous injection of phenylephrine, d-chlorpheniramine, and hydrocortisone. After these treatments, his cardiovascular condition stabilized. Eight months after the event, skin prick tests and intradermal tests with all agents used during general anesthesia were performed. Intradermal tests showed positive results only for sugammadex. Subsequently, basophil activation tests with CD203c were performed using sugammadex, γ-cyclodextrin, and positive controls (anti-immunoglobulin-E and formyl-methionyl-leucyl-phenylalanine). In addition to both controls, sugammadex, but not γ-cyclodextrin, induced significant upregulation of CD203c expression. We performed additional basophil activation tests with wortmannin, an inhibitor of phosphoinositide 3-kinase, to investigate the mechanism underlying sugammadex-induced basophil activation. The inhibitory effect of wortmannin on basophil activation due to sugammadex was similar to that of anti-immunoglobulin-E, suggesting an immunoglobulin-E-dependent mechanism. Although the patient showed no hypersensitivity after the first exposure of sugammadex, anaphylaxis appeared after the second administration. Because most cases of sugammadex-induced anaphylaxis reportedly appeared after first administration, this seems to be a rare case.

Conclusions

In the present case, sugammadex-induced anaphylaxis might have occurred through an immunoglobulin-E-dependent mechanism and not involve γ-cyclodextrin as an epitope. Physicians should pay attention to the occurrence of sugammadex-induced anaphylaxis even when the patient has a history of safe administration of sugammadex.
Correction to: Evolutionary divergence in tail regeneration between Xenopus laevis and Xenopus tropicalis
Authors: Wang Shouhong , Shi Yun-Bo
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
Weighted Cheeger constant and first eigenvalue lower bound estimates on smooth metric measure spaces
Authors: Abolarinwa Abimbola , Ali Akram , Alkhadi Ali
Published: June 2021

We establish new eigenvalue inequalities in terms of the weighted Cheeger constant for drifting p-Laplacian on smooth metric measure spaces with or without boundary. The weighted Cheeger constant is bounded from below by a geometric constant involving the divergence of suitable vector fields. On the other hand, we establish a weighted form of Escobar–Lichnerowicz–Reilly lower bound estimates on the first nonzero eigenvalue of the drifting bi-Laplacian on weighted manifolds. As an application, we prove buckling eigenvalue lower bound estimates, first, on the weighted geodesic balls and then on submanifolds having bounded weighted mean curvature.
The impact of the COVID-19 pandemic on healthcare-associated infections in intensive care unit patients: a retrospective cohort study
Authors: Baccolini V. , Migliara G. , Isonne C. , Dorelli B. , Barone L. C. , Giannini D. , Marotta D. , Marte M. , Mazzalai E. , Alessandri F. , Pugliese F. , Ceccarelli G. , De Vito C. , Marzuillo C. , De Giusti M. , Villari P.
Published: June 2021

Background

During the intensive care units’ (ICUs) reorganization that was forced by the COVID-19 emergency, attention to traditional infection control measures may have been reduced. Nevertheless, evidence on the effect of the COVID-19 pandemic on healthcare-associated infections (HAIs) is still limited and mixed. In this study, we estimated the pandemic impact on HAI incidence and investigated the HAI type occurring in COVID-19 patients.

Methods

Patients admitted to the main ICU of the Umberto I teaching hospital of Rome from March 1st and April 4th 2020 were compared with patients hospitalized in 2019. We assessed the association of risk factors and time-to-first event through multivariable Fine and Grey’s regression models, that consider the competitive risk of death on the development of HAI (Model 1) or device related-HAI (dr-HAI, Model 2) and provide estimates of the sub-distribution hazard ratio (SHR) and its associated confidence interval (CI). A subgroup analysis was performed on the 2020 cohort.

Results

Data from 104 patients were retrieved. Overall, 59 HAIs were recorded, 32 of which occurred in the COVID-19 group. Patients admitted in 2020 were found to be positively associated with both HAI and dr-HAI onset (SHR: 2.66, 95% CI 1.31–5.38, and SHR: 10.0, 95% CI 1.84–54.41, respectively). Despite being not confirmed at the multivariable analysis, a greater proportion of dr-HAIs seemed to occur in COVID-19 patients, especially ventilator-associated pneumonia, and catheter-related urinary tract infections.

Conclusions

We observed an increase in the incidence of patients with HAIs, especially dr-HAIs, mainly sustained by COVID-19 patients. A greater susceptibility of these patients to device-related infections was hypothesized, but further studies are needed.
Surfactant protein D: a useful marker for differentiation of drug-induced pneumonia and bacterial pneumonia
Authors: Waseda Yuko , Yasui Masahide , Kurokawa Kousuke , Chikazawa Ryo , Takeda Toshihiro , Mitsui Miho , Sonoda Tomoaki , Yamaguchi Makiko , Watanabe Satoshi , Takato Hazuki , Ichikawa Yukari , Umeda Yukihiro , Anzai Masaki , Ueda Hiroshi , Kasahara Kazuo , Ishizuka Tamotsu
Published: June 2021

Background

Drug-induced pneumonia (d-pneumonia) and bacterial pneumonia (b-pneumonia) are often difficult to differentiate; therefore, this study examined the possibility of differentiating them using serum biomarkers.

Methods

The study included 22 and 16 patients diagnosed with b- and d-pneumonia, respectively, at our institution or affiliated institutions. For d-pneumonia, the causative drug was minocycline hydrochloride in four patients, gefitinib in two patients, nivolumab in two patients, pembrolizumab in two patients, sulfasalazine in two patients, loxoprofen in one patient, Bouiougitou in one patient, edoxaban tosilate hydrate in one patient, and abemaciclib in one patient. White blood cell (WBC), C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, and SP-A levels were measured in each patient and compared between the groups.

Results

Significant differences were noted in the WBC and SP-D levels between the two groups (P < 0.05, P < 0.001), but not in the CRP, KL-6, or SP-A levels.

Conclusion

The study results suggest that SP-D is a useful marker for differentiating b-pneumonia and d-pneumonia.
Outcomes of COVID-19 in Patients With Cancer: Report From the National COVID Cohort Collaborative (N3C)
Authors: Sharafeldin Noha , Bates Benjamin , Song Qianqian , Madhira Vithal , Yan Yao , Dong Sharlene , Lee Eileen , Kuhrt Nathaniel , Shao Yu Raymond , Liu Feifan , Bergquist Timothy , Guinney Justin , Su Jing , Topaloglu Umit
Published: June 2021

PURPOSE

Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The NCATS’ National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cancer cohort within N3C and identify risk factors for all-cause mortality from COVID-19.

METHODS

We used 4,382,085 patients from 50 US medical centers to construct a cohort of patients with cancer. We restricted analyses to adults ≥ 18 years old with a COVID-19–positive or COVID-19–negative diagnosis between January 1, 2020, and March 25, 2021. We followed N3C selection of an index encounter per patient for analyses. All analyses were performed in the N3C Data Enclave Palantir platform.

RESULTS

A total of 398,579 adult patients with cancer were identified from the N3C cohort; 63,413 (15.9%) were COVID-19–positive. Most common represented cancers were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and GI cancers (10%). COVID-19 positivity was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.20; 95% CI, 1.15 to 1.24). Among COVID-19–positive patients, age ≥ 65 years, male gender, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥ 4, hematologic malignancy, multitumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. Patients who received recent immunotherapies or targeted therapies did not have higher risk of overall mortality.

CONCLUSION

Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.
Black holes thermodynamics from a dual Kaniadakis entropy
Authors: Abreu Everton M. C. , Ananias Neto Jorge
Published: June 2021

Kaniadakis entropy, an important extension of the Boltzmann-Gibbs entropy, was proposed some years ago. Inspired by a dual Renyi entropy, in this paper we have suggested a dual Kaniadakis entropy and we applied this approach to analyze the thermodynamics of black holes. We have obtained an equipartition theorem and, after that, we derived the temperature and the heat capacity. The values ofκand massMwill show if the black hole can be thermally stable or not.
Prediction of Type 1 Diabetes at Birth: Cord Blood Metabolites vs Genetic Risk Score in the Norwegian Mother, Father, and Child Cohort
Authors: Tapia German , Suvitaival Tommi , Ahonen Linda , Lund-Blix Nicolai A , Njølstad Pål R , Joner Geir , Skrivarhaug Torild , Legido-Quigley Cristina , Størdal Ketil , Stene Lars C
Published: June 2021

Background and aim

Genetic markers are established as predictive of type 1 diabetes, but unknown early life environment is believed to be involved. Umbilical cord blood may reflect perinatal metabolism and exposures. We studied whether selected polar metabolites in cord blood contribute to prediction of type 1 diabetes.

Methods

Using a targeted UHPLC-QQQ-MS platform, we quantified 27 low-molecular-weight metabolites (including amino acids, small organic acids, and bile acids) in 166 children, who later developed type 1 diabetes, and 177 random control children in the Norwegian Mother, Father, and Child cohort. We analyzed the data using logistic regression (estimating odds ratios per SD [adjusted odds ratio (aOR)]), area under the receiver operating characteristic curve (AUC), and k-means clustering. Metabolites were compared to a genetic risk score based on 51 established non-HLA single-nucleotide polymorphisms, and a 4-category HLA risk group.

Results

The strongest associations for metabolites were aminoadipic acid (aOR = 1.23; 95% CI, 0.97-1.55), indoxyl sulfate (aOR = 1.15; 95% CI, 0.87-1.51), and tryptophan (aOR = 0.84; 95% CI, 0.65-1.10), with other aORs close to 1.0, and none significantly associated with type 1 diabetes. K-means clustering identified 6 clusters, none of which were associated with type 1 diabetes. Cross-validated AUC showed no predictive value of metabolites (AUC 0.49), whereas the non-HLA genetic risk score AUC was 0.56 and the HLA risk group AUC was 0.78.

Conclusions

In this large study, we found no support of a predictive role of cord blood concentrations of selected bile acids and other small polar metabolites in the development of type 1 diabetes.
Thyroid Hormone Receptor α Regulates Autophagy, Mitochondrial Biogenesis, and Fatty Acid Use in Skeletal Muscle
Authors: Zhou Jin , Gauthier Karine , Ho Jia Pei , Lim Andrea , Zhu Xu-Guang , Han Cho Rong , Sinha Rohit Anthony , Cheng Sheue-Yann , Yen Paul Michael
Published: June 2021

Skeletal muscle (SM) weakness occurs in hypothyroidism and resistance to thyroid hormone α (RTHα) syndrome. However, the cell signaling and molecular mechanism(s) underlying muscle weakness under these conditions is not well understood. We thus examined the role of thyroid hormone receptor α (TRα), the predominant TR isoform in SM, on autophagy, mitochondrial biogenesis, and metabolism to demonstrate the molecular mechanism(s) underlying muscle weakness in these two conditions.

Two genetic mouse models were used in this study: TRα1PV/+ mice, which express the mutant Thra1PV gene ubiquitously, and SM-TRα1L400R/+ mice, which express TRα1L400R in a muscle-specific manner. Gastrocnemius muscle from TRα1PV/+, SM-TRα1L400R/+, and their control mice was harvested for analyses.

We demonstrated that loss of TRα1 signaling in gastrocnemius muscle from both the genetic mouse models led to decreased autophagy as evidenced by accumulation of p62 and decreased expression of lysosomal markers (lysosomal-associated membrane protein [LAMP]-1 and LAMP-2) and lysosomal proteases (cathepsin B and cathepsin D). The expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), mitochondrial transcription factor A (TFAM), and estrogen-related receptor α (ERRα), key factors contributing to mitochondrial biogenesis as well as mitochondrial proteins, were decreased, suggesting that there was reduced mitochondrial biogenesis due to the expression of mutant TRα1. Transcriptomic and metabolomic analyses of SM suggested that lipid catabolism was impaired and was associated with decreased acylcarnitines and tricarboxylic acid cycle intermediates in the SM from the mouse line expressing SM-specific mutant TRα1. Our results provide new insight into TRα1-mediated cell signaling, molecular, and metabolic changes that occur in SM when TR action is impaired.
Hydrostatic mechanical stress regulates growth and maturation of the atrioventricular valve
Authors: Bassen David , Wang Mingkun , Pham Duc , Sun Shuofei , Rao Rashmi , Singh Rishabh , Butcher Jonathan
Published: June 2021

During valvulogenesis, cytoskeletal, secretory and transcriptional events drive endocardial cushion growth and remodeling into thin fibrous leaflets. Genetic disorders play an important role in understanding valve malformations but only account for a minority of clinical cases. Mechanical forces are ever present, but how they coordinate molecular and cellular decisions remains unclear. In this study, we used osmotic pressure to interrogate how compressive and tensile stresses influence valve growth and shape maturation. We found that compressive stress drives a growth phenotype, whereas tensile stress increases compaction. We identified a mechanically activated switch between valve growth and maturation, by which compression induces cushion growth via BMP-pSMAD1/5, while tension induces maturation via pSer-19-mediated MLC2 contractility. The compressive stress acts through BMP signaling to increase cell proliferation and decrease cell contractility, and MEK-ERK is essential for both compressive stress and BMP mediation of compaction. We further showed that the effects of osmotic stress are conserved through the condensation and elongation stages of development. Together, our results demonstrate that compressive/tensile stress regulation of BMP-pSMAD1/5 and MLC2 contractility orchestrates valve growth and remodeling.
Biological scaling analyses are more than statistical line fitting
Authors: Glazier Douglas S.
Published: June 2021

The magnitude of many biological traits relates strongly and regularly to body size. Consequently, a major goal of comparative biology is to understand and apply these ‘size-scaling’ relationships, traditionally quantified by using linear regression analyses based on log-transformed data. However, recently some investigators have questioned this traditional method, arguing that linear or non-linear regression based on untransformed arithmetic data may provide better statistical fits than log-linear analyses. Furthermore, they advocate the replacement of the traditional method by alternative specific methods on a case-by-case basis, based simply on best-fit criteria. Here, I argue that the use of logarithms in scaling analyses presents multiple valuable advantages, both statistical and conceptual. Most importantly, log-transformation allows biologically meaningful, properly scaled (scale-independent) comparisons of organisms of different size, whereas non-scaled (scale-dependent) analyses based on untransformed arithmetic data do not. Additionally, log-based analyses can readily reveal biologically and theoretically relevant discontinuities in scale invariance during developmental or evolutionary increases in body size that are not shown by linear or non-linear arithmetic analyses. In this way, log-transformation advances our understanding of biological scaling conceptually, not just statistically. I hope that my Commentary helps students, non-specialists and other interested readers to understand the general benefits of using log-transformed data in size-scaling analyses, and stimulates advocates of arithmetic analyses to show how they may improve our understanding of scaling conceptually, not just statistically.
Chemical Biology of Double Helical and Non-Double Helical Nucleic Acids: “To B or Not To B, That Is the Question”
Authors: Sugimoto Naoki , Endoh Tamaki , Takahashi Shuntaro , Tateishi-Karimata Hisae
Published: June 2021

Nucleic acids form not only the canonical double helix (duplex) but also the non-canonical (non-double helix) structures such as triplexes, G-quadruplexes, and i-motifs. The formation of these non-canonical structures and their stabilities depend on the microscopic environmental conditions around the nucleic acids. The intracellular environments, where various molecules are densely packed, exhibit molecular crowding. The non-canonical structures are very stable under molecular crowding conditions. The functions and structures of these nucleic acids in cells are optimized to enable them to function well in the crowded environments. We envisaged that molecular crowding in cells may play an important role in the reactions involving functionalized biomolecules and discovered a novel regulatory mechanism underlying the role of the non-canonical structures in gene expression. Based on the results of our work, we have developed novel methods to control the gene expression of non-double helical nucleic acids, leading to new insights into the chemistry of such nucleic acids. Our major achievements are summarized in this review.
Nitrogen-Substitution in the Flapping Wings of Cyclooctatetraene-Fused Molecules
Authors: Suga Kensuke , Yamakado Takuya , Saito Shohei
Published: June 2021

New synthetic protocols for nitrogen-embedded flapping molecules have been developed. Gram-scale synthesis of a key precursor, tetraamine of dibenzo[a,e]cyclooctatetraene has been established for designing flapping quinoxaline and flapping phenazineimide. The impact of the nitrogen substitution on the photophysical properties and the viscosity-probing function has been investigated in comparison with the reported flapping anthraceneimide.
Structure and mechanism of Mycobacterium smegmatis polynucleotide phosphorylase
Authors: Unciuleac Mihaela-Carmen , Ghosh Shreya , de la Cruz M. Jason , Goldgur Yehuda , Shuman Stewart
Published: June 2021

Polynucleotide phosphorylase (PNPase) catalyzes stepwise phosphorolysis of the 3′-terminal phosphodiesters of RNA chains to yield nucleoside diphosphate products. In the reverse reaction, PNPase acts as a polymerase, using NDPs as substrates to add NMPs to the 3′-OH terminus of RNA chains while expelling inorganic phosphate. The apparent essentiality of PNPase for growth of M. tuberculosis militates for mycobacterial PNPase as a potential drug target. A cryo-EM structure of Mycobacterium smegmatis PNPase (MsmPNPase) reveals a characteristic ring-shaped homotrimer in which each protomer consists of two RNase PH-like domains and an intervening α-helical module on the inferior surface of the ring. The carboxy-terminal KH and S1 domains, which impart RNA specificity to MsmPNPase, are on the opposite face of the core ring and are conformationally mobile. Single particle reconstructions of MsmPNPase in the act of poly(A) synthesis highlight a 3′-terminal (rA)4 oligonucleotide and two magnesium ions in the active site and an adenine nucleobase in the central tunnel. We identify amino acids that engage the 3′ segment of the RNA chain (Phe68, Arg105, Arg112, Arg430, Arg431) and the two metal ions (Asp526, Asp532, Gln546, Asp548), and we infer those that bind inorganic phosphate (Thr470, Ser471, His435, Lys534). Alanine mutagenesis pinpointed RNA and phosphate contacts as essential (Arg105, Arg431, Lys534, Thr470 + Ser471), important (Arg112, Arg430), or unimportant (Phe68) for PNPase activity. Severe phosphorolysis and polymerase defects accompanying alanine mutations of the enzymic metal ligands suggest a two-metal mechanism of catalysis by MsmPNPase.
Kinematic Analysis of Dance-Based Exergaming: A Cross-Sectional Study
Authors: Ofori Ernest K. , Subramaniam Savitha , Wang Shuaijie , Bhatt Tanvi
Published: June 2021

Background: Recent studies demonstrate improvements in both postural stability and mobility among aging populations and those with stroke who are exposed to dance-based exergaming (DBExG). However, age-related deficits and aging with cortical pathology may lead to distinct movement
adaptation patterns during DBExG, which could impact therapeutic outcomes.
 Aim: The aim of this study was to examine the movement kinematics (postural stability and mobility) of healthy older adults, older adults with stroke, and young adults for different paces of dance during
DBExG.
 Method: The study included 33 particpants (11 participant from each group of healthy older adults, older adults with chronic stroke, and healthy young adults) who performed the DBExG using slow- (SP), medium- (MP), and fast-paced (FP) songs with movements in the anteroposterior
(AP) and mediolateral (ML) directions. Center of mass (CoM) sway area, excursion (Ex), and peaks as well as hip, knee, and ankle joint excursions were computed.
 Results: Results of the study revealed that CoM sway areas and Exs were greater for healthy young adults than for older
adults with stroke for the SP dance (p < 0.05) and that there were significantly more AP CoM peaks for young adults than for healthy older adults and those with stroke for the FP dance (p < 0.05). Young adults also exhibited greater hip and ankle Exs than older adults with stroke (p
< 0.05) for all song paces. Similarly, knee and ankle Exs were greater for healthy older adults than for older adults with stroke for all song paces (p < 0.05).
 Conclusion: The quantitative evaluation and comparison of the movement patterns presented for the three groups could
provide a foundation for both assessing and designing therapeutic DBExG protocols for these populations.
Association between pesticide exposure and obesity: A cross-sectional study of 20,295 farmers in Thailand
Authors: Noppakun Kajohnsak , Juntarawijit Chudchawal
Published: June 2021

Background: Obesity is a serious condition because it is associated with other chronic diseases which affect the quality of life. In addition to diet and exercise, recent research has found that pesticide exposure might be another important risk factor.  

Methods: The objective of this large cross-sectional study was to determine the association between pesticide exposure and obesity among farmers in Nakhon Sawan and Phitsanulok province, Thailand. Data on pesticide use and obesity prevalence from 20,295 farmers aged 20 years and older was collected using an in-person interview questionnaire. The association was analysed using multivariable logistic regression, adjusted for its potential confounding factors. 

Results: Obesity was found to be associated with pesticide use in the past. The risk of obesity was significantly predicted by types of pesticides, including insecticides (OR = 2.27, 95% CI 1.09-4.74), herbicides (OR = 4.72, 95% CI 1.16-19.29), fungicides (OR = 2.17, 95% CI 1.37-3.44), rodenticides (OR = 2.52, 95% CI 1.59-3.99), and molluscicides (OR = 3.37, 95% CI 2.13-5.31). Among 35 surveyed individual pesticides, 24 were significantly associated with higher obesity prevalence (OR = 1.75, 95% CI 1.00-3.06 to OR = 8.37, 95% CI 3.97-17.64), including herbicide butachlor, 17 insecticides (three carbamate insecticides, five organochlorine insecticides, and nine organophosphate insecticides), and six fungicides. 

Conclusion: This study found obesity in farmers in Nakhon Sawan and Phitsanulok province, Thailand, to be associated with the long-term use of several types of pesticides. The issue should receive more public attention, and pesticide use should be strictly controlled.
Highlights from the 16th International Society for Computational Biology Student Council Symposium 2020
Authors: Cuypers Wim L. , Dönertaş Handan Melike , Grewal Jasleen K. , Fatima Nazeefa , Donnelly Chase , Mer Arvind Singh , Krieger Spencer , Cuypers Bart , Rahman Farzana
Published: June 2021

In this meeting overview, we summarise the scientific program and organisation of the 16th International Society for Computational Biology Student Council Symposium in 2020 (ISCB SCS2020). This symposium was the first virtual edition in an uninterrupted series of symposia that has been going on for 15 years, aiming to unite computational biology students and early career researchers across the globe.
Living It Up at the Hotel California: Employee Mobility Barriers and Collaborativeness in Firms’ Innovation
Authors: Seo Eunkwang , Somaya Deepak
Published: June 2021

Research has long recognized the importance of collaboration for innovation, but relatively little is known about the strategic drivers of collaborative innovation in firms. We posit that robust collaboration within firms can increase the interfirm mobility of inventors and increase spillovers of innovative knowledge to competitors by mobile inventors. Therefore, by mitigating these value capture hazards associated with collaboration, barriers to employee mobility may induce firms to increase collaborativeness in innovation. Additionally, consistent with the mechanism underlying this proposition, we hypothesize that firms whose innovation entails more complex knowledge, which is known to impede interfirm knowledge spillovers, will increase collaboration less when employee mobility increases. We test these hypotheses by leveraging quasi-exogenous changes in two legal mobility barriers for inventors across U.S. states and find that higher-mobility barriers are associated with greater inventor collaboration (as observed in patented innovation), and this effect is weaker for firms possessing more complex knowledge. These findings deepen our understanding of the strategic tradeoffs between value creation and value capture entailed in collaborative innovation within firms and of human capital strategies that help to manage these tradeoffs.
New to entrepreneurship? Part 2: taking your big idea to market
Authors: Ratcliffe Jason
Published: June 2021

Last month's article discussed starting a business idea from scratch by honing one's mindset and developing some big ideas around what product wants to be sold. The second part of this series now considers how a big idea can be turned into a product that people will want to buy and how to market it
Peramalan Banyak Pengunjung Pantai Pandasimo Bantul Menggunakan Regresi Runtun Waktu dan Seasonal Autoregressive Integrated Moving Average Exogenous
Authors: Prakoso Tito Tatag , Zukhronah Etik , Pratiwi Hasih
Published: June 2021

Forecasting is a ways to predict what will happen in the future based on the data in the past. Data on the number of visitors in Pandansimo beach are time series data. The pattern of the number of visitors in Pandansimo beach is influenced by holidays, so it looks like having a seasonal pattern. The majority of Indonesian citizens are Muslim who celebrate Eid Al-Fitr in every year. The determination of Eid Al-Fitr does not follow the Gregorian calendar, but based on the Lunar calendar. The variation of the calendar is about the determination of Eid Al-Fitr which usually changed in the Gregorian calendar, because in the Gregorian calendar, Eid Al-Fitr day will advance one month in every three years. Data that contain seasonal and calendar variations can be analyzed using time series regression and Seasonal Autoregressive Integrated Moving Average Exogenous  (SARIMAX) models. The aims of this study are to obtain a better model between time series regression and SARIMAX and to forecast the number of Pandansimo beach visitors using a better model. The result of this study indicates that the time series regression model is a better model. The forecasting from January to December 2018 in succession are 13255, 6674, 8643, 7639, 13255, 8713, 22635, 13255, 13255, 9590, 8549, 13255 visitors.
Keywords: time series regression, seasonal, calendar variations, SARIMAX, forecasting
A Review on Fabrication of Thermoset Prepreg Composites using Out-of-Autoclave Technology
Authors: SHAIK Feroz , RAMAKRISHNA M. , VARMA P. Dhaval
Published: June 2021

Autoclave is the technology that has been extensively used to manufacture high-grade performance composite parts for aerospace applications. This technology has been limited to aerospace industries only, primarily due to its high cost in manufacturing parts. The researchers then considered an alternative approach “Out-of-autoclave” (OOA) process, aiming at cost and time optimization. Non-autoclave methods such as OOA cure processes have been developed lately. The OOA process has a high potential for a drastic cost reduction in the manufacturing of composite aerospace structures. It processes parts that have a quality similar to that of parts cured using the autoclave technology. Specially designed OOA prepregs are available in the market for OOA processing, some of which are certified for aerospace manufacturing. This review paper briefly focuses on OOA prepregs and OOA processes that are used for aerospace components manufacturing. Future areas of development in the aerospace sector based on cost optimization and faster cycle times are also discussed in this paper.
Detection of Faults and Vibration Analysis in Beam Structures - A Review
Authors: KUMAR MADISETTY KIRAN , GARIKAPATI DIWAKAR , PRASANNA JENA SHAKTI
Published: June 2021

This review focuses on vibrating beam structures with different constraints. The review is also aimed to analyse the different fault detection approaches for condition monitoring of cracks in vibrating structures. The advancement in this field with significant and diversified techniques namely analytical, numerical and experimental approaches are elaborated and presented here. The significance of crack location and the severe effects on the responses of the vibrating structure are discussed. The application of piezoelectric material on structures, as well as different fault detection and soft computing techniques are summarized to monitor the conditions of a structure. A concise review study has also been conducted for better improvement in the service period. The integrity of the structure can be improved with the aid of vibration control and Structural Health Monitoring (SHM) approaches.
Quasi-phase-matching stack of 25 GaAs plates with high transmittance for high-power mid-infrared wavelength conversion fabricated by use of room-temperature bonding
Authors: Tanimoto Rika , Takahashi Yuki , Shoji Ichiro
Published: June 2021

A quasi-phase-matching (QPM) stack of 25 GaAs plates with better surface flatness and reduced internal loss has been successfully fabricated using the room-temperature-bonding technique, which is for a high-power and highly efficient wavelength-conversion device in the mid-infrared region. This is accomplished owing to an improved process in which GaAs plates are set on

Y

3

A
l

5

O

12

crystals with the flat surfaces polished to laser grade. The loss coefficient and the loss per interface of the fabricated 2.1 mm long, 25-plate-stacked GaAs QPM device are

2.1

c
m

−
1

and 1.8%, respectively, which are 70% smaller than those of a 0.92 mm long, 11-plate stack fabricated with the previous process.
Hardware-efficient blind frequency offset estimation for digital subcarrier multiplexing signals
Authors: Xiang Meng , Lv Hong , Fu Songnian , Li Jianpin , Xu Ou , Peng Di , Gao Zhensen , Wang Yuncai , Qin Yuwen
Published: June 2021

Since the frequency offset estimation (FOE) must be implemented before the subcarrier de-multiplexing and chromatic dispersion compensation (CDC) for digital subcarrier multiplexing (DSM) signals, traditional FOE algorithms for single carrier transmission is no longer suitable. Here, we propose a hardware-efficient blind FOE solution for the DSM signals by monitoring spectral dips in the frequency domain. With the use of a smoothing filter, the estimation accuracy of FOE can be significantly increased. Moreover, we identify that the proposed FOE method is robust to various transmission impairments, including amplified spontaneous emission (ASE) noise, optical filtering, and fiber nonlinearity. The effective function of the proposed FOE method is numerically and experimentally verified under scenarios of both back-to-back (B2B) and the 2560 km standard single-mode fiber (SSMF) transmission, leading to a FOE error less than 100 MHz with a FFT size of 1024.
Quasi-omnidirectional transmitter for underwater wireless optical communication systems using a prismatic array of three high-power blue LED modules
Authors: Tong Zhijian , Yang Xingqi , Chen Xiao , Zhang Hao , Zhang Yufan , Zou Haiwu , Zhao Lyufang , Xu Jing
Published: June 2021

In this study, a quasi-omnidirectional underwater wireless optical communication (UWOC) system is implemented with a prismatic array consisting of three uniformly distributed high-power LED modules as the transmitter. Over a 10-m underwater channel in a 50-m standard swimming pool, a data rate of 22 Mbps is achieved without adopting any digital signal processing algorithm. With zero forcing (ZF) based frequency domain equalization (FDE) and a maximum ratio combining (MRC) algorithm, the maximum net data rates achieved are 69.65 Mbps, 39.8 Mbps and 29.85 Mbps over 10-m, 30-m, and 40-m underwater channels, respectively. In the proposed UWOC system, the receiver could successfully capture optical signals at different directions from the transmitter and the bit error rates (BERs) measured in different directions show small fluctuations. The proposed system could meet the demands of high-speed data transmission among units in a swarm-robot system and last meter user access in an underwater optical cellular network system.
Total internal reflection of the mid-IR near single-cycle light bullet in LiF
Authors: Kompanets Victor , Dormidonov Alexander , Chekalin Sergey
Published: June 2021

Mid-IR light bullets formation and self-reconstruction after total internal reflection in LiF is investigated experimentally and through numerical simulations. The experiment showed that spatial-temporal deformations of the wave packet in inhomogeneous wave on a reflecting interface can be neglected for this process and a near single-cycle light bullet can be formed or recovered after a distance determined by its energy loss for ionization and supercontinuum radiation. The estimation of the reconstruction distance by an empirical formula for self-focusing distance on the base of the peak power and the radius of the LB numerical simulation are in a good agreement with experimental data received.
Microtubule associated protein WAVE DAMPENED2-LIKE (WDL) controls microtubule bundling and the stability of the site of tip-growth in Marchantia polymorpha rhizoids
Authors: Champion Clement , Lamers Jasper , Jones Victor Arnold Shivas , Morieri Giulia , Honkanen Suvi , Dolan Liam
Published: June 2021

Tip-growth is a mode of polarized cell expansion where incorporation of new membrane and wall is stably restricted to a single, small domain of the cell surface resulting in the formation of a tubular projection that extends away from the body of the cell. The organization of the microtubule cytoskeleton is conserved among tip-growing cells of land plants: bundles of microtubules run longitudinally along the non-growing shank and a network of fine microtubules grow into the apical dome where growth occurs. Together, these microtubule networks control the stable positioning of the growth site at the cell surface. This conserved dynamic organization is required for the spatial stability of tip-growth, as demonstrated by the formation of sinuous tip-growing cells upon treatment with microtubule-stabilizing or microtubule-destabilizing drugs. Microtubule associated proteins (MAPs) that either stabilize or destabilize microtubule networks are required for the maintenance of stable tip-growth in root hairs of flowering plants. NIMA RELATED KINASE (NEK) is a MAP that destabilizes microtubule growing ends in the apical dome of tip-growing rhizoid cells in the liverwortMarchantia polymorpha. We hypothesized that both microtubule stabilizing and destabilizing MAPs are required for the maintenance of the stable tip-growth in liverworts. To identify genes encoding microtubule-stabilizing and microtubule-destabilizing activities we generated 120,000 UV-B mutagenized and 336,000 T-DNA transformedMarchantia polymorphaplants and screened for defective rhizoid phenotypes. We identified 119 mutants and retained 30 mutants in which the sinuous rhizoid phenotype was inherited. The 30 mutants were classified into at least 4 linkage groups. Characterisation of two of the linkage groups showed that MAP genes–WAVE DAMPENED2-LIKE(WDL) andNIMA-RELATED KINASE(NEK)–are required to stabilize the site of tip growth in elongating rhizoids. Furthermore, we show that MpWDL is required for the formation of a bundled array of parallel and longitudinally orientated microtubules in the non-growing shank of rhizoids where MpWDL-YFP localizes to microtubule bundles. We propose a model where the opposite functions of MpWDL and MpNEK on microtubule bundling are spatially separated and promote tip-growth spatial stability.
An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens
Authors: Jin Hongli , Jiao Cuicui , Cao Zengguo , Huang Pei , Chi Hang , Bai Yujie , Liu Di , Wang Jianzhong , Feng Na , Li Nan , Zhao Yongkun , Wang Tiecheng , Gao Yuwei , Yang Songtao , Xia Xianzhu , Wang Hualei
Published: June 2021

The global spread of Zika virus (ZIKV), which caused a pandemic associated with Congenital Zika Syndrome and neuropathology in newborns and adults, prompted the pursuit of a safe and effective vaccine. Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were constructed: ZI-D (prM-E), ZI-E (transmembrane domain (TM) of prM-E replaced with RABV G) and ZI-F (signal peptide and TM domain of prM-E replaced with the region of RABV G). When the TM of prM-E was replaced with the region of RABV G (termed ZI-E), it promoted ZIKV E protein localization on the cell membrane and assembly on recombinant viruses. In addition, the change in the signal peptide with RABV G (termed ZI-F) was not conducive to foreign protein expression. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in BALB/c mice. After immunization with ZI-E, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titers of neutralizing antibodies (NAbs) against ZIKV and RABV at week 6 were all greater than the protective titers. Moreover, ZI-E stimulated the proliferation of splenic lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cells (TCMs) among CD4+/CD8+ T cells and stimulated B cell activation and maturation. These results indicate that ZI-E could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into a promising vaccine for protection against both ZIKV and RABV infections.
The interplay of seizures-induced axonal sprouting and transcription-dependent Bdnf repositioning in the model of temporal lobe epilepsy
Authors: Skupien-Jaroszek Anna , Walczak Agnieszka , Czaban Iwona , Pels Katarzyna Karolina , Szczepankiewicz Andrzej Antoni , Krawczyk Katarzyna , Ruszczycki Błażej , Wilczynski Grzegorz Marek , Dzwonek Joanna , Magalska Adriana
Published: June 2021

The Brain-Derived Neurotrophic Factor is one of the most important trophic proteins in the brain. The role of this growth factor in neuronal plasticity, in health and disease, has been extensively studied. However, mechanisms of epigenetic regulation of Bdnf gene expression in epilepsy are still elusive. In our previous work, using a rat model of neuronal activation upon kainate-induced seizures, we observed a repositioning of Bdnf alleles from the nuclear periphery towards the nuclear center. This change of Bdnf intranuclear position was associated with transcriptional gene activity. In the present study, using the same neuronal activation model, we analyzed the relation between the percentage of the Bdnf allele at the nuclear periphery and clinical and morphological traits of epilepsy. We observed that the decrease of the percentage of the Bdnf allele at the nuclear periphery correlates with stronger mossy fiber sprouting—an aberrant form of excitatory circuits formation. Moreover, using in vitro hippocampal cultures we showed that Bdnf repositioning is a consequence of transcriptional activity. Inhibition of RNA polymerase II activity in primary cultured neurons with Actinomycin D completely blocked Bdnf gene transcription and repositioning occurring after neuronal excitation. Interestingly, we observed that histone deacetylases inhibition with Trichostatin A induced a slight increase of Bdnf gene transcription and its repositioning even in the absence of neuronal excitation. Presented results provide novel insight into the role of BDNF in epileptogenesis. Moreover, they strengthen the statement that this particular gene is a good candidate to search for a new generation of antiepileptic therapies.
Effect of transportation and social isolation on facial expressions of healthy horses
Authors: Lundblad Johan , Rashid Maheen , Rhodin Marie , Haubro Andersen Pia
Published: June 2021

Horses have the ability to generate a remarkable repertoire of facial expressions, some of which have been linked to the affective component of pain. This study describes the facial expressions in healthy horses free of pain before and during transportation and social isolation, which are putatively stressful but ordinary management procedures. Transportation was performed in 28 horses by subjecting them to short-term road transport in a horse trailer. A subgroup (n = 10) of these horses was also subjected to short-term social isolation. During all procedures, a body-mounted, remote-controlled heart rate monitor provided continuous heart rate measurements. The horses’ heads were video-recorded during the interventions. An exhaustive dataset was generated from the selected video clips of all possible facial action units and action descriptors, time of emergency, duration, and frequency according to the Equine Facial Action Coding System (EquiFACS). Heart rate increased during both interventions (p<0.01), confirming that they caused disruption in sympato-vagal balance. Using the current method for ascribing certain action units (AUs) to specific emotional states in humans and a novel data-driven co-occurrence method, the following facial traits were observed during both interventions: eye white increase (p<0.001), nostril dilator (p<0.001), upper eyelid raiser (p<0.001), inner brow raiser (p = 0.042), tongue show (p<0.001). Increases in ‘ear flicker’ (p<0.001) and blink frequency (p<0.001) were also seen. These facial actions were used to train a machine-learning classifier to discriminate between the high-arousal interventions and calm horses, which achieved at most 79% accuracy. Most facial features identified correspond well with previous findings on behaviors of stressed horses, for example flared nostrils, repetitive mouth behaviors, increased eye white, tongue show, and ear movements. Several features identified in this study of pain-free horses, such as dilated nostrils, eye white increase, and inner brow raiser, are used as indicators of pain in some face-based pain assessment tools. In order to increase performance parameters in pain assessment tools, the relations between facial expressions of stress and pain should be studied further.
Seroprevalence and associated risk factors of Toxoplasma gondii infection among pregnant mother in Makassar, Indonesia
Authors: Polanunu Nurul Fadilah Ali , Wahyuni Sitti , Hamid Firdaus
Published: June 2021

The protozoan parasite, Toxoplasma gondii is estimated to infect one-third of the world’s population. Infection in pregnant women can cause severe conditions for their babies. Until now, there is no data regarding Toxoplasma infection from Makassar pregnant mothers. This study aims to obtain information on Toxoplasma specific antibodies and to measure the risk factor associate with parasite infection. This cross-sectional study conducted in 9 of 47 primary health centres (Puskesmas) in Makassar. Blood samples and questionnaires were collected from 184 pregnant women aged 15–42 years old from September to October 2020. ELISA technique was used to examine the IgG and IgM antibodies. Univariable and multivariable analyses were carried out to measure factors that independently associate with Toxoplasma antibody positivity. Our result showed the range of Toxoplasma IgM and IgG are 0.06–1.01 and 0.09–3.01, respectively. While no one of our participants has an acute Toxoplasma gondii infection (IgM positive), we found 32,6% pregnant mothers are exposed to parasite (positive IgG). Contact with cats [OR(95%CI): 10.45(3.77–28.99)], consume chicken satay [OR(95%CI): 9.72(3.71–25.48)] and consume un-boiled water/ filtered water [OR(95%CI): 5.98(1.77–20.23)] are independently associate with positive Toxoplasma IgG antibody. Based on the result, we conclude that pregnant women in Makassar are exposed to T. gondii and the oocyst and tissue cyst of parasite contaminates food and water in Makassar.