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Majority customers of cosmetics are female. Would this imply a high proportion of inventors of cosmetics technology is female? Would the inventor's gender be related to the characteristics and quality of corresponding patent? This study tries to identify manifestation of gender equity in cosmetics technology in terms of patent application and grant, technical characteristics, and its performance. We apply topic modeling, zero-inflated Poisson regression, and survival analysis to patents related to cosmetics that were applied to the United States Patent and Trademark Office from 1970 to 2016. The results show that women's participation in cosmetic inventions is becoming active and has experienced many changes in technical characteristics, but in terms of performance, it is still sluggish. This study is expected to contribute to deepening our understanding about gender issues in technology development.

One of the recent developments in safety systems is an external airbag installed on the front bumper of a vehicle and autonomous emergency braking system. In this paper, we propose a framework for a cost-benefit analysis of the external airbag and autonomous emergency braking system in order to validate its commercialization. Road traffic crash data obtained from the National Automotive Sampling System/Crashworthiness Data System (NASS/CDS) was used, and three different crash types related to frontal damage in vehicles were extracted to estimate the safety performance of an external airbag. An ordinal logistic regression model was applied to estimate the safety performance in terms of the reduced maximum abbreviated injury scale (MAIS) based on a reduction in the total delta-v following the installation of an external airbag. Given the estimated safety performance of the external airbag, a cost-benefit analysis is conducted. According to the results, the external airbag system saves 46% of occupants with MAIS 3+ injuries and prevents 40% of fatalities. Moreover, the benefit/cost ratios of the external airbag system range from 0.496 to 0.509 depending on the scenario. Lastly, sensitivity analyses were performed with important parameters, including the initial and maximum market penetration ratio and the price of the system. This study aims to evaluate the technology of safety devices by analyzing the effectiveness of a new safety device using real-world vehicle accident data. We also statistically estimated its effectiveness and analyzed its societal value. We expect that our comprehensive findings will be helpful in evaluating the effectiveness of safety devices.

Abstract Although psychometric features have been considered for alternative credit scoring, they have not yet been applied to peer-to-peer (P2P) lending because such information is not available on platforms. This study proposed an alternative credit scoring model for P2P lending by extracting typical personality types inferred from the borrowers’ job category. We projected a virtual space of borrowers by using the affinity matrix based on the Myers–Briggs type indicator (MBTI) that fits each job category. Applying the distance in this space to Lending Club data, we used locally weighted logistic regression to vary the coefficients of the variables, which affect loan repayments, with each MBTI type for predicting the default probability. We found that each MBTI type’s credit scoring model has different significant variables. This study provides insights into breakthroughs in developing alternative credit scoring for P2P lending.

[This corrects the article DOI: 10.1371/journal.pone.0220782.].

In the rapidly changing high-tech industry, firms that produce multi-generational products struggle to consistently introduce new products that are superior in innovativeness. However, developing innovative products in a short time sequence period is likely to cause quality problems. Therefore, considering time and resource constraints, two kinds of strategies are commonly employed: sequential innovation strategy, sequentially introducing a new generation of technology product at every launch interval, ensuring timely innovativeness but with relatively uncertain quality, or quality strategy, intermittently introducing a new generation of products, together with a derivative model between generations to enhance the quality. In this study, we propose a framework for a cost-benefit analysis that compares these two strategies by considering competition between firms within a generation as well as that within a firm across multiple generations (i.e., cannibalization) throughout the launch cycle of high-tech products. We apply our proposed framework to the smartphone market and conduct a sensitivity analysis. The results are expected to contribute to strategic decision-making related to the introduction of multi-generational technology products.

Subcontractors depend heavily on their prime contractor and thus find it very risky to enter a new business on their own. This study proposes a framework for these subcontractors to develop blue ocean technologies related to their prime contractor. First, the primary technologies predicted to be promising are extracted from the business reports of the prime contractor. Sub-technologies are then selected through a patent-based search using keywords and International Patent Classification codes of the primary technologies. From them, blue ocean technologies are proposed by optimizing the weighted mean of the min-max normalized market value, degree of competition in the technology market, and subcontractors' potential technological capabilities for each sub-technology. This study shows that subcontractors can enhance their technology competitiveness by finding a low-risk blue ocean technology. Our empirical research on the subcontractors of a semiconductor firm identified technological patent fields for them to pursue. From our framework, subcontractors can identify blue ocean technologies by considering their prime contractor's future industrial areas and technologies of interest as well as their own technological capabilities. Furthermore, the prime contractors can gain the synergy effect of technology expansion through cooperation.

Potential relationship among loan applicants can provide valuable information for evaluating default risk. However, most of the existing credit scoring models either ignore this relationship or consider a simple connection information. This study assesses the applicants’ relation in terms of their distance estimated based on their characteristics. This information is then utilized in a proposed spatial probit model to reflect the different degree of borrowers’ relation on the default prediction of loan applicant. We apply this method to peer-to-peer Lending Club Loan data. Empirical results show that the consideration of information on the spatial autocorrelation among loan applicants can provide high predictive power for defaults.

Solving the supply-demand imbalance is the most crucial issue for stable implementation of a public bike-sharing system. This gap can be reduced by increasing the accuracy of demand prediction by considering spatial and temporal properties of bike demand. However, only a few attempts have been made to account for both features simultaneously. Therefore, we propose a prediction framework based on graph convolutional networks. Our framework reflects not only spatial dependencies among stations, but also various temporal patterns over different periods. Additionally, we consider the influence of global variables, such as weather and weekday/weekend to reflect non-station-level changes. We compare our framework to other baseline models using the data from Seoul's bike-sharing system. Results show that our approach has better performance than existing prediction models.

Governments and also local councils create and enforce their own regional public health care plans for the problem of overweight and obesity in the population. Public sports facilities can help these plans. In this paper, we investigated the contribution of public sports facilities to the reduction of the obesity of local residents. We used the data obtained from the Fifth Korea National Health and Nutrition Examination Surveys; and measured the degree of obesity using body mass index (BMI). We conducted various spatial regression analyses including the global Moran’s I test and local indicators of spatial autocorrelation analysis finding that there exists spatial dependence in the error term of spatial regression model for BMI. However, we also observed that the number of local public sports facilities is not significantly related to local BMI. This result can be caused by the low utilization ratio and an unbalanced spatial distribution of local public sports facilities. Based on our findings, we suggest that local councils need to improve the quality of public sports facilities encouraging the establishment of preferred types of pubic sports facilities.

Accurate demand forecasting for new technology products is a key factor in the success of a business. We propose a way to forecasting a new product's diffusion through technology diffusion and interest diffusion. Technology diffusion and interest diffusion are measured by the volume of patent citations and web search traffic, respectively. We apply the proposed method to forecast the sales of hybrid cars and industrial robots in the US market. The results show that that technology diffusion, as represented by patent citations, can explain long-term sales for hybrid cars and industrial robots. On the other hand, interest diffusion, as represented by web search traffic, can help to improve the predictability of market sales of hybrid cars in the short-term. However, interest diffusion is difficult to explain the sales of industrial robots due to the different market characteristics. Finding indicates our proposed model can relatively well explain the diffusion of consumer goods.

BACKGROUND:Recently, the need for rapid wound-healing has significantly increased because of the increasing number of patients who are diagnosed with diabetes and obesity. These conditions have contributed to a surge in the number of patients with chronic wounds worldwide. Furthermore, many cost-effective wound-healing technologies have been developed in order to keep up with the increased demand. In this paper, we performed a quantitative study of the trends associated with wound-healing technologies using patent data. METHODOLOGY:We analyzed the trends considering four different groups of patent applicants: firms, universities, research institutes, and individuals using a structural topic model. In addition, we analyzed the knowledge flow between patent applicants using citation analysis, and confirmed the role of applicants in the knowledge-flow network using k-means clustering. As a result, the primary wound-healing technology patents applied for by the four groups varied considerably, and we classified the roles of patent applicants were found in the knowledge-flow network. CONCLUSIONS:Our results showed the organizations that are leading each area of wound-healing technology. Furthermore, from the results, we identified specific institutions that are efficient for spreading knowledge related to wound-healing technology based on the patents. This information can contribute to the planning of investment strategies and technology policies related to wound-healing.

Because of the remarkable developments in robotics in recent years, technological convergence has been active in this area. We focused on finding patterns of convergence within robot technology using network analysis of patents in both the USPTO and KIPO. To identify the variables that affect convergence, we used quadratic assignment procedures (QAP). From our analysis, we observed the patent network ecology related to convergence and found technologies that have great potential to converge with other robotics technologies. The results of our study are expected to contribute to setting up convergence based R&D policies for robotics, which can lead new innovation.

Decapod iridescent virus 1 (DIV1) is a dangerous new virus that causes mortality to shrimp and crayfish. This virus has been reported in China, which is a major exporter of decapods to South Korea and its neighboring countries, Taiwan and Thailand. This virus can be regarded as a pathogen with a high risk of entry into Korea. Therefore, South Korea has been conducting emergency quarantine for DIV1 since 2020, and in this study, an import risk analysis was performed following the World Organization of Animal Health and domestic laws and regulations to present scientific grounds and validity for South Korea's DIV1 emergency quarantine. Import risk analysis was performed by hazard identification, entry assessment, exposure assessment, and consequence assessment. As a result of the import risk analysis, it was confirmed that the current DIV1 quarantine can significantly reduce the import risk. However, it was also established that the management of prawns and polychaetes intended for animal feed or bait and currently not subjected to quarantine is also required. Additionally, two species of crabs that would meet the criteria for a completely susceptible species and two species of crayfish that required surveillance of the import amount or route of exposure were also identified. In conclusion, these uses and susceptible species were designated as quarantine targets for nonhuman consumption requiring risk management and import sanitary conditions to be performed before export and after import. Finally, alternatives to reduce the cost burden of stakeholders following the introduction of the system were also presented. [ABSTRACT FROM AUTHOR]

Infestations of parasites, particularly those caused by copepods and monogeneans, are a major hindrance to aquaculture and have a big negative economic impact. Sebastes schlegelii, a farmed Korean rockfish, is particularly prone to copepods and monogeneans. This study comprehended how parasitic copepods and rockfish from a farm in Tongyeong-si, Gyeongsangnam-do, Korea, are related to the monogenean trematode Microcotyle sebastis. Our research revealed that monogeneans predominated, with a rate of 98.4% and an average infection intensity of 7 per infected fish. With an average infection intensity of 4 per sick fish, the infection rate for parasitic copepods was equally considerable, coming in at 91.7%. The high co-infection rate of both parasite families, at 90.8%, is noteworthy. Furthermore, Lepeophtheirus elegans and Peniculus truncatus, 2 parasitic copepod species, were discovered to have M. sebastis eggs attached to their bodies. This demonstrates a connection between parasitic copepod infestations in farmed Korean rockfish and the monogenean trematode M. sebastis. These discoveries highlight the necessity for creating more potent parasite control methods for the aquaculture sector and shed light on the intricate relationships between various parasite species. [ABSTRACT FROM AUTHOR]

A random effects Weigbull regression model for predicting for efficient human resource management and occupational life expectancy of employees is presented. The proposed model can help to control the brain-drain.

Studies found that the Drosha-DGCR8 complex initiates microRNA maturation by precise cleavage of the stem loops, which are embedded in primary transcripts. A model is proposed for this process that is based upon evidence from both computational and biochemical analyses.

In order to determine the ideal environment for commercialization from the R&D stage, a Structural Equation Model (SEM) forecasting the Technology Commercialization Success Index (TCSI), has been used. The findings are then verified with the American Customer Satisfaction Index (ACSI).

Investors are paying increasing attention to cost to benefits analysis (CBA) of developing new technologies. This paper shows the usefulness of a multigeneration technology diffusion model in developing a more accurate CBA assessment for information technology.

We performed femtosecond two-color experiments (four-wave mixing and pump probe) using two independently tunable, partially synchronized femtosecond lasers. Despite the fact that the jitter is of the order of 5-10 ps, the time resolution is limited only by the pulse width when a homemade sample-and-hold switch is used.

Background: Data on the association between coronavirus disease 2019 (COVID-19) and thyroid have been reported, including overt thyrotoxicosis and suppression of thyroid function. We aimed to evaluate the thyroid hormone profile and its association with the prognosis of COVID-19 in Korean patients. Methods: The clinical data of 119 patients with COVID-19, admitted in the Myongji Hospital, Goyang, South Korea, were retrospectively evaluated. The thyroid hormone profiles were analyzed and compared based on disease severity (non-severe disease vs. severe to critical disease). Clinical outcomes were analyzed according to the tertiles of thyroid hormones. Results: Of the 119 patients, 76 (63.9%) were euthyroid, and none presented with overt thyroid dysfunction. Non-thyroidal illness syndrome was the most common manifestation (18.5%), followed by subclinical thyrotoxicosis (14.3%) among patients with thyroid dysfunction. Thyroid stimulating hormone (TSH) and triiodothyronine (T3) levels were significantly lower in patients with severe to critical disease than in those with non-severe disease (P<0.05). Patients in the lowest T3 tertile (<0.77 ng/mL) had higher rates of mechanical ventilation, intensive care unit admission, and death than those in the middle and highest (>1.00 ng/mL) T3 tertiles (P<0.05). COVID-19 patients in the lowest T3 tertile were independently associated with mortality (hazard ratio, 5.27; 95% confidence interval, 1.09 to 25.32; P=0.038) compared with those in the highest T3 tertile. Conclusion: Thyroid dysfunction is common in COVID-19 patients. Changes in serum TSH and T3 levels may be important markers of disease severity in COVID-19. Decreased T3 levels may have a prognostic significance in COVID-19 related outcome. [ABSTRACT FROM AUTHOR]

Background: Whether hyperthyroidism is an independent risk factor for cardiovascular events remains controversial. We aimed to evaluate the association of overt and subclinical hyperthyroidism with the risk of ischemic heart disease (IHD), stroke, heart failure, and cardiovascular mortality. Methods: Studies regarding the association between hyperthyroidism and cardiovascular events were searched on PubMed and Embase databases. The cardiovascular disease (CVD) risk was classified as high and low, based on pre-existing diseases, including history of coronary, cerebral, or peripheral artery disease; heart failure; atrial fibrillation; diabetes mellitus; or chronic kidney disease. Results: Thirty-seven cohort studies were included in this meta-analysis. The pooled hazard ratio for subjects with overt hyperthyroidism compared with the control group was 1.11 (95% confidence interval [CI], 1.03 to 1.19) for IHD, 1.35 (95% CI, 1.03 to 1.75) for stroke, and 1.20 (95% CI, 1.00 to 1.46) for cardiovascular mortality. For subjects with subclinical hyperthyroidism, the pooled hazard ratio was 1.24 (95% CI, 1.07 to 1.45) for IHD, when compared with the control group. Subgroup analysis by CVD risk showed that the risk of stroke in overt hyperthyroidism was increased in the low CVD risk group; however, these association was not observed in the high CVD risk group. Similarly, the risk of IHD in subjects with subclinical hyperthyroidism was significantly increased in the low CVD risk group. Conclusion: Overt hyperthyroidism is associated with increased risk of IHD, stroke, and cardiovascular mortality, and subclinical hyperthyroidism is associated with increased risk of IHD. These associations were particularly observed in the low risk CVD group without underlying CVD. [ABSTRACT FROM AUTHOR]

Streptozotocin (STZ) is widely used to induce diabetic rodent models. It is specifically toxic to pancreatic beta cells and causes severe destruction and dysfunction. We investigated the effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on an STZ-induced diabetic mouse model. PLAG attenuated the glucose increase and maintained serum insulin at levels similar to those seen with control mice. In pancreatic beta cell line INS-1, STZ-induced cell apoptosis and intracellular reactive oxygen species (ROS) generation were significantly reduced to nearly normal levels after PLAG treatment. Glucose transporter 2 (GLUT2) localization analyses and glucose uptake assays showed that PLAG accelerated GLUT2 internalization, which ameliorated excessive entry of glucose, as well as STZ. STZ-induced cytotoxic effects were significantly reduced in PLAG-treated groups. The biological activity of PLAG was further confirmed in GLUT2-silenced cells, and the specificity of PLAG was verified using its derivative 1-palmitoyl-2-linoleoyl-3-hydroxyl-rac-glycerol (PLH). Our results suggest that PLAG may be a useful agent for protecting beta cells in the setting of excessive glucose influx. [ABSTRACT FROM AUTHOR]

Consider a graph G of order n and maximum degree ∆. Let f:V(G)→{0,1,…,⌈Δ/2⌉+1} be a function that labels the vertices of G. Let B0 = {v ∈ V (G) : f(v) = 0}. The function f is a strong Roman dominating function for G if every v ∈ B0 has a neighbor w such that f(w)≥1+⌈½|N(w)∩B0|⌉. In this paper, we study the bounds on strong Roman domination numbers of the Cartesian product Pm □Pk of paths Pm and paths Pk. We compute the exact values for the strong Roman domination number of the Cartesian product P2 □Pk and P3 □Pk. We also show that the strong Roman domination number of the Cartesian product P4 □Pk is between ⌈1/3(8k-⌊k/8⌋+1⌋ and ⌈8k/3⌋+ k ≥ 8, and that both bounds are sharp bounds. [ABSTRACT FROM AUTHOR]

Several new varieties of airbags are under consideration for development. However, their commercialization decision must be backed by a positive Cost-Benefit Analysis (CBA) outcome. In this study, we propose a CBA framework for the frontal center curtain airbag, a newly designed safety system intended to reduce the injury risk of rear-seat passengers. The proposed CBA covers not only economic benefits of the producer but also the effectiveness in sustainable reduction of the fatal and injury rate. In this context, with accumulated field data on road traffic accidents, a forecasting method reflecting the reduced casualties and the market share of vehicle sales associated with frontal center curtain airbag is utilized. Our results suggest that the use of frontal center curtain airbags helps to reduce the number of casualties with a Maximum Abbreviated Injury Scale (MAIS) of 3 or above by 87.4%. Furthermore, both the initial market penetration rate and price of the frontal center curtain airbag significantly influence its socioeconomic benefits. By evaluating the effectiveness of the frontal center curtain airbag, our study can contribute to the decision making for its commercialization. [ABSTRACT FROM AUTHOR]

Financial technology has become an important part of the banking industry in recent times. This study attempts to propose a framework to identify emerging areas and trends using financial business method patents. Based on the abstracts of financial business method patents registered at the United States Patent and Trademark Office, this study first applies latent Dirichlet allocation to identify emerging topics. The probability of the annual occurrence of each topic is adjusted through the exponentially weighted moving average to reflect the importance of the recent probability of topics. Each topic is classified as “hot” or “cold” depending on whether the exponentially weighted moving average of the probabilities exceeds the threshold. We applied survival analysis to the time gap of recurrently becoming hot from a cold status with the associated factor of financial business method patents. The findings suggest that the topic with the short granted period and high forward citation is likely to become hot. In addition, the topic that is aged and specific in narrow areas is likely to continuously change into the hot or cold status. The approach proposed in this study contributes toward understanding topic emergence in the financial area and pursuing sustainable development. [ABSTRACT FROM AUTHOR]

Various types of government credit guarantee programs exist for small- and medium-sized enterprises (SMEs). The SMEs guaranteed by these programs can resolve their financial difficulties by obtaining loans from banks or being included in a pool for the issuance of primary collateralized bond obligations. However, the loan default rate for these supported firms is high owing to their moral hazard, which can be associated with unethical behavior in the accounting process. Since the stakeholders of credit guarantee programs initiated by the government include not only lenders and borrowers, but also taxpayers, the default risk of moral hazard must be minimized. Thus, an additional evaluation step is required to deal with accounting ethics, which has not thus far been considered in the literature. In this study, we propose an accounting ethics-based credit scoring model as a complementary approach, which can be used to select suitable borrowers. The proposed model is expected to reduce the default rate resulting from the moral hazard associated with unethical accounting behaviors in the supported firms. [ABSTRACT FROM AUTHOR]

Credit scoring models are usually formulated by fitting the probability of loan default as a function of individual evaluation attributes. Typically, these attributes are measured using a Likert-type scale, but are treated as interval scale explanatory variables to predict loan defaults. Existing models also do not distinguish between types of default, although they vary: default by an insolvent company and default by an insolvent debtor. This practice can bias the results. In this paper, we applied Quantification Method II, a categorical version of canonical correlation analysis, to determine the relationship between two sets of categorical variables: a set of default types and a set of evaluation attributes. We distinguished between two types of loan default patterns based on quantification scores. In the first set of quantification scores, we found knowledge management, new technology development, and venture registration as important predictors of default from non-default status. Based on the second quantification score, we found that the technology and profitability factors influence loan defaults due to an insolvent company. Finally, we proposed a credit-risk rating model based on the quantification score. [ABSTRACT FROM AUTHOR]

While patents do have many advantages, their disadvantages include requiring disclosure of technical information and imposing the burden of patenting and litigation costs. In this study, we investigate the relationship between a firm's negative perception on patents, technology management strategies, and subsequent performance. For this purpose, we use a categorical canonical correlation analysis of the top 200, large, R&D-intensive firms in Korea. We find that negative perceptions such as burdensome transaction costs, non-patenting culture, and uncertainty of the outcome of patent litigation are associated with firms' technology management strategies, such as purchase of licenses, and subsequent performance, such as an increase in the number of inventions from the cross-fertilization of different technologies. The results of this study are expected to contribute to a better understanding of firms' negative attitudes toward the effects of patents, their subsequent technology management strategies, and resulting performance. [ABSTRACT FROM AUTHOR]

A 74-year-old man presented with recurrent vomiting and aspiration pneumonia in the left lower lobe. He entered the intensive care unit to manage the pneumonia and septic shock. Although a percutaneous endoscopic gastrostomy tube was implanted for recurrent vomiting, vomiting and aspiration recurred frequently during admission. Subsequently, he complained of neck pain when in an upright position. A videofluoroscopic swallowing study showed compression of the esophagus by cervical osteophytes and tracheal aspiration caused by an abnormality at the laryngeal inlet. Cervical spine X-rays and computed tomography showed anterior cervical osteophytes at the C3-6 levels. Surgical decompression was scheduled, but was cancelled due to his frailty. Unfortunately, further recurrent vomiting and aspiration resulted in respiratory arrest leading to hypoxic brain damage and death. Physicians should consider cervical spine disease, such as diffuse skeletal hyperostosis as an uncommon cause of recurrent aspiration pneumonia. [ABSTRACT FROM AUTHOR]

Makers of heavy-duty diesel engines (HDDEs) need to reduce their inventory of old-generation products in preparation for the demand for next-generation products that satisfy new emission regulations. In this paper, a new demand forecasting model is proposed to reflect special conditions raised by the technological generational shift owing to new emission regulation enforcement. In addition, sensitivity analyses are conducted to better accommodate uncertainty involved at the time of prediction. Our proposed model can help support manufacturers' production and sales management for a series of products in response to new emission regulations. [ABSTRACT FROM AUTHOR]

One of the main missions of Microfinance Institutions is to improve the status of under-privileged people. However, MFI's mission drift or enhancement can occur under adverse economic condition. In this paper, we investigate the direction of changes in supporting women borrowers who make up the majority of the poor by using the lending patterns of Latin American and Caribbean MFIs during the recent global financial crisis. P control chart is applied to detect assignable changes in the lending rate to woman over different MFIs. In order to identify related characteristics to the outlying MFIs identified from the P control chart, we perform logistic regression analysis. Our study results can contribute to understand MFI's mission change in terms of supporting women borrowers and identify the related characteristics of MFIs. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced mucositis can limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In this study, we investigated the therapeutic effect of PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride) in 5-fluorouracil (5-FU)-induced oral mucositis animal models. Hamsters were administered 5-FU (80 mg/kg) intraperitoneally on days 0, 6, and 9. The animals’ cheek pouches were then scratched equally with the tip of an 18-gage needle on days 1, 2, and 7. PLAG was administered daily at 250 mg/kg/day. PLAG administration significantly reduced 5-FU/scratching-induced mucositis. Dramatic reversal of weight loss in PLAG-treated hamsters with mucositis was observed. Histochemical staining data also revealed newly differentiated epidermis and blood vessels in the cheek pouches of PLAG-treated hamsters, indicative of recovery. Whole blood analyses indicated that PLAG prevents 5-FU-induced excessive neutrophil transmigration to the infection site and eventually stabilizes the number of circulating neutrophils. In a mouse mucositis model, mice with 5-FU-induced disease treated with PLAG exhibited resistance to body-weight loss compared with mice that received 5-FU or 5-FU/scratching alone. PLAG also dramatically reversed mucositis-associated weight loss and inhibited mucositis-induced inflammatory responses in the tongue and serum. These data suggest that PLAG enhances recovery from 5-FU-induced oral mucositis and may therefore be a useful therapeutic agent for treating side effects of chemotherapy, such as mucositis and cachexia. [ABSTRACT FROM AUTHOR]

The adenovirus (Ad) early region 4 (E4)-ORF3 protein regulates diverse cellular processes to optimize the host environment for the establishment of Ad replication. E4-ORF3 self-assembles into multimers to form a nuclear scaffold in infected cells and creates distinct binding interfaces for different cellular target proteins. Previous studies have shown that the Ad5 E4-ORF3 protein induces sumoylation of multiple cellular proteins and subsequent proteasomal degradation of some of them, but the detailed mechanism of E4-ORF3 function remained unknown. Here, we investigate the role of E4-ORF3 in the sumoylation process by using transcription intermediary factor (TIF)-1γ as a substrate. Remarkably, we discovered that purified E4-ORF3 protein stimulates TIF-1γ sumoylation in vitro, demonstrating that E4-ORF3 acts as a small ubiquitin-like modifier (SUMO) E3 ligase. Furthermore, E4-ORF3 significantly increases poly-SUMO3 chain formation in vitro in the absence of substrate, showing that E4-ORF3 has SUMO E4 elongase activity. An E4-ORF3 mutant, which is defective in protein multimerization, exhibited severely decreased activity, demonstrating that E4-ORF3 self-assembly is required for these activities. Using a SUMO3 mutant, K11R, we found that E4-ORF3 facilitates the initial acceptor SUMO3 conjugation to TIF-1γ as well as poly-SUMO chain elongation. The E4-ORF3 protein displays no SUMO-targeted ubiquitin ligase activity in our assay system. These studies reveal the mechanism by which E4-ORF3 targets specific cellular proteins for sumoylation and proteasomal degradation and provide significant insight into how a small viral protein can play a role as a SUMO E3 ligase and E4-like SUMO elongase to impact a variety of cellular responses. [ABSTRACT FROM AUTHOR]