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PurposeIn today’s turbulent environment, it is important that companies effectively leverage resources available both in-house and in their interorganizational ties. The purpose of this study is to focus on technology as a key resource and aims to analyse contextual factors of the relationship between the technological heterogeneity of suppliers and the buyer firm’s short- and long-term performance in a dynamic approach.Design/methodology/approachThis paper applies a mixed-method approach. The theoretical model has been developed based on extant literature, validated by a workshop with practitioners, and tested using structural equation modelling on a sample of 157 companies.FindingsSuppliers’ technological heterogeneity has a significant positive effect on both the buyer’s actual business performance and its research and development capability. Business performance captures the short term, while the long-term performance implications of heterogeneity are understood as a precondition for future, technology-based competitiveness. The results show that both short- and long-term consequences are mediated by the buyer’s supply chain management efforts (SCMEs), while the relationship between technological heterogeneity and these efforts is moderated by the buyer’s networking capability (NC).Research limitations/implicationsThis study provides the first evidence of potential long-term positive performance consequences of technologically heterogeneous suppliers. Additionally, it develops new insights into how the internal abilities of the focal firm might facilitate or hinder the positive implications of such heterogeneity. Specifically, the role of the buyer’s SCMEs and its NC is analysed. Industry-specific analyses offer new opportunities for future scholarship and future studies could extend research with other contextual factors.Practical implicationsManagers at different levels of the buyer firm should be aware of the organizational capabilities through which they can leverage the potential embedded in technologically heterogeneous suppliers. The results contribute to this understanding, which is especially important when a change in the environment (and the consequent changes in the level of technological heterogeneity) is constant.Originality/valueThis paper reflects on an important critique of the extant literature by applying a dynamic approach. Dynamization is twofold. Firstly, this study does not limit empirical analysis to short-term performance consequences. Secondly, this study discusses contextual factors that capture some aspects of the buyer’s ability to dynamically adapt to the changing environment. SCMEs align the supply chain of the buyer along customer requirements that change over time, while the NC is responsible for the ongoing reconfiguration of the supplier’s base.

Using situation-specific and dyadic data, we analyse how trust in inter-organisational relationships evolve over time. Based on a multidisciplinary approach, we define four trust-related concepts, which include both behavioural and perceptual aspects of this multifaceted phenomenon. We also develop the hypothesis that the behavioural consistency of the trustee affects the level of his/her trustworthiness as perceived by the trustor. To test this hypothesis, the paper specifies a finite Dynamic Trust Game that, in a unique way, models longer-term relationships characterised by interdependent actions between partners. In contrast to the simple Repeated Games modelling discrete exchange episodes, this game corresponds to the requirements of the interaction approach of the relationship management, since the iterations of the game are interrelated and embedded in previous ones. Timely development of the behavioural variables in the game reflects an inverse U-shape with an increasing willingness to cooperate until round 8, with a maximum cooperation level of 80% on average. Behaviour seems to affect the perceived level of trustworthiness. However, we need additional experimental data on inconsistent behaviours to get a clear understanding of this effect.

Logisztikai Évkönyv 2023. ISSN 1218-3849

Large Language Models (LLMs) have revolutionized Artificial Intelligence (AI) services due to their exceptional proficiency in understanding and generating human-like text. LLM chatbots, in particular, have seen widespread adoption, transforming human-machine interactions. However, these LLM chatbots are susceptible to "jailbreak" attacks, where malicious users manipulate prompts to elicit inappropriate or sensitive responses, contravening service policies. Despite existing attempts to mitigate such threats, our research reveals a substantial gap in our understanding of these vulnerabilities, largely due to the undisclosed defensive measures implemented by LLM service providers. In this paper, we present Jailbreaker, a comprehensive framework that offers an in-depth understanding of jailbreak attacks and countermeasures. Our work makes a dual contribution. First, we propose an innovative methodology inspired by time-based SQL injection techniques to reverse-engineer the defensive strategies of prominent LLM chatbots, such as ChatGPT, Bard, and Bing Chat. This time-sensitive approach uncovers intricate details about these services' defenses, facilitating a proof-of-concept attack that successfully bypasses their mechanisms. Second, we introduce an automatic generation method for jailbreak prompts. Leveraging a fine-tuned LLM, we validate the potential of automated jailbreak generation across various commercial LLM chatbots. Our method achieves a promising average success rate of 21.58%, significantly outperforming the effectiveness of existing techniques. We have responsibly disclosed our findings to the concerned service providers, underscoring the urgent need for more robust defenses. Jailbreaker thus marks a significant step towards understanding and mitigating jailbreak threats in the realm of LLM chatbots.

To support software developers in understanding and maintaining programs, various automatic code summarization techniques have been proposed to generate a concise natural language comment for a given code snippet. Recently, the emergence of large language models (LLMs) has led to a great boost in the performance of natural language processing tasks. Among them, ChatGPT is the most popular one which has attracted wide attention from the software engineering community. However, it still remains unclear how ChatGPT performs in (automatic) code summarization. Therefore, in this paper, we focus on evaluating ChatGPT on a widely-used Python dataset called CSN-Python and comparing it with several state-of-the-art (SOTA) code summarization models. Specifically, we first explore an appropriate prompt to guide ChatGPT to generate in-distribution comments. Then, we use such a prompt to ask ChatGPT to generate comments for all code snippets in the CSN-Python test set. We adopt three widely-used metrics (including BLEU, METEOR, and ROUGE-L) to measure the quality of the comments generated by ChatGPT and SOTA models (including NCS, CodeBERT, and CodeT5). The experimental results show that in terms of BLEU and ROUGE-L, ChatGPT's code summarization performance is significantly worse than all three SOTA models. We also present some cases and discuss the advantages and disadvantages of ChatGPT in code summarization. Based on the findings, we outline several open challenges and opportunities in ChatGPT-based code summarization.

BackgroundCD161 has been linked to the appearance and development of various cancers.MethodsThe mutation map and the variation of CNVs and SNVs of CD161 were displayed according to cBioportal and GSCALite. We also evaluated the pathway enrichment and drug sensitivity of CD161 according to GSCALite. We performed a single-cell sequencing analysis of cancer cells and T cells in melanoma. The cell communication patterns related to CD161 were further explored. Multiplex immunofluorescence staining of tissue microarrays was used to detect the association between CD161 expression and macrophages and T cells.ResultsA high CD161 level was related to neoantigens expression, pathway enrichment, and drug sensitivity. In addition, single-cell sequencing analysis showed that CD161 was mainly expressed in T cells, M1 and M2 Macrophages, neoplastic, microglial cells, neurons, and cancer cells in many tumor types. Further study on pseudotime trajectories and functional annotation of CD161 proved the critical role of CD161 in tumor progression and T cell immunity in melanoma. Multiplex immunofluorescence revealed that CD161 is closely correlated with the immune infiltration of T cells and macrophages in multiple cancers. In addition, high CD161 expression predicted a favorable immunotherapy response.ConclusionCD161 is involved in the immune infiltration of T cells and macrophages and might be a promising target for tumor immunotherapy.

Background The expression of long non-coding RNAs (lncRNAs) can function as diagnostic and therapeutic biomarkers of tumours, this research explored the effects of programmed cell death ligand-1(PD-L1) related lncRNAs on glioma. Methods Downloading gene expression profiles and clinicopathological information of glioma from TCGA and CGGA databases, 6 PD-L1-related lncRNAs were screened out through correlation analysis, Cox and LASSO regression analysis. The risk score model was established based on 6 PD-L1-related lncRNAs. Using GSVA and GSEA analyses to investigate the biological function. LINC01271 was selected as the target, and bioinformatics analysis and cell experiments in vitro were adopted to verify its effects on glioma. Results Risk scores based on 6 PD-L1-related lncRNAs (AL355974.3, LINC01271, AC011899.3, MIR4500HG, LINC02594, AL357055.3) can predict the prognosis of glioma(LGG and GBM). The high-risk score group has more typical malignant features in the immune-inflammatory microenvironment and is prone to be sensitive to anti-PD-1 treatment. The nomogram combining these lncRNAs and clinical parameters has good forecasting efficiency. LINC01271 expression can be used as a risk stratification index of glioma. Experiments in vitro confirmed its positive regulatory effect on the proliferation and migration of glioma cells. Conclusions This study demonstrates the predictive value of the risk score model based on 6 PD-L1-related lncRNAs for glioma characteristics, prognosis and immunotherapy responsiveness. LncRNA LINC01271 can independently be used as a new target for prognosis evaluation and therapy of glioma.

Alternatively activated macrophages (M2 polarization) play an important role in asthma. Short-chain fatty acids (SCFAs) possessed immune-regulatory functions, but their effects on M2 polarization of alveolar macrophages and its underlying mechanisms are still unclear. In our study, murine alveolar macrophage MH-S cell line and human monocyte-derived macrophages were used to polarize to M2 subset with interleukin-4 (IL-4) treatment. The underlying mechanisms involved were investigated using molecule inhibitors/agonists. In vivo, female C57BL/6 mice were divided into five groups: CON group, ovalbumin (OVA) asthma group, OVA+Acetate group, OVA+Butyrate group, and OVA+Propionate group. Mice were fed with or without SCFAs (Acetate, Butyrate, Propionate) in drinking water for 20 days before developing OVA-induced asthma model. In MH-S, SCFAs inhibited IL-4-incuced protein or mRNA expressions of M2-associated genes in a dose-dependent manner. G-protein-coupled receptor 43 (GPR43) agonist 4-CMTB and histone deacetylase (HDAC) inhibitor (trichostatin A, TSA), but not GPR41 agonist AR420626 could inhibit the protein or mRNA expressions M2-associated genes. 4-CMTB, but not TSA, had no synergistic role in the inhibitory effect of SCFAs on M2 polarization. In vivo study indicated Butyrate and Propionate, but not Acetate, attenuated OVA-induced M2 polarization in the lung and airway inflammation. We also found the inhibitory effect of SCFAs on M2 polarization in human-derived macrophages. Therefore, SCFAs inhibited M2 polarization in MH-S likely through GPR43 activation and/or HDAC inhibition. Butyrate and Propionate but not Acetate could inhibit M2 polarization and airway inflammation in asthma model. SCFAs also abrogated M2 polarization in human-derived macrophages., SCFAs inhibited M2 polarization in MH-S likely through GPR43 activation and HDAC inhibition. Butyrate and Propionate but not Acetate could inhibit M2 polarization and airway inflammation in asthma model. SCFAs also abrogated M2 polarization in human-derived macrophages., Graphical Abstract Graphical Abstract

Gliomas, originating from the glial cells, are the most lethal type of primary tumors in the central nervous system. Standard treatments like surgery have not significantly improved the prognosis of glioblastoma patients. Recently, immune therapy has become a novel and effective option. As a conserved group of transcriptional regulators, the Sry-type HMG box (SOX) family has been proved to have a correlation with numerous diseases. Based on the large-scale machine learning, we found that the SOX family, with significant immune characteristics and genomic profiles, can be divided into two distinct clusters in gliomas, among which SOX10 was identified as an excellent immune regulator of macrophage in gliomas. The high expression of SOX10 is related to a shorter OS in LGG, HGG, and pan-cancer groups but benefited from the immunotherapy. It turned out in single-cell sequencing that SOX10 is high in neurons, M1 macrophages, and neural stem cells. Also, macrophages are found to be elevated in the SOX10 high-expression group. SOX10 has a positive correlation with macrophage cytokine production and negative regulation of macrophages’ chemotaxis and migration. In conclusion, our study demonstrates the outstanding cluster ability of the SOX family, indicating that SOX10 is an immune regulator of macrophage in gliomas, which can be an effective target for glioma immunotherapy.

Choroid plexus epithelial cells can secrete cerebrospinal fluid into the ventricles, serving as the major structural basis of the selective barrier between the neurological system and blood in the brain. In fact, choroid plexus epithelial cells release the majority of cerebrospinal fluid, which is connected with particular ion channels in choroid plexus epithelial cells. Choroid plexus epithelial cells also produce and secrete a number of essential growth factors and peptides that help the injured cerebrovascular system heal. The pathophysiology of major neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, as well as minor brain damage diseases like hydrocephalus and stroke is still unknown. Few studies have previously connected choroid plexus epithelial cells to the etiology of these serious brain disorders. Therefore, in the hopes of discovering novel treatment options for linked conditions, this review extensively analyzes the association between choroid plexus epithelial cells and the etiology of neurological diseases such as Alzheimer's disease and hydrocephalus. Finally, we review CPE based immunotherapy, choroid plexus cauterization, choroid plexus transplantation, and gene therapy.

Hydrocephalus is mainly characterized by excessive production or impaired absorption of cerebrospinal fluid that causes ventricular dilation and intracranial hypertension. Astrocytes are the key response cells to inflammation in the central nervous system. In hydrocephalus, astrocytes are activated and show dual characteristics depending on the period of development of the disease. They can suppress the disease in the early stage and may aggravate it in the late stage. More evidence suggests that therapeutics targeting astrocytes may be promising for hydrocephalus. In this review, based on previous studies, we summarize different forms of hydrocephalus-induced astrocyte reactivity and the corresponding function of these responses in hydrocephalus. We also discuss the therapeutic effects of astrocyte regulation on hydrocephalus in experimental studies.

Linear scleroderma is the most common type of localized scleroderma in children. Lesions rarely involve areas other than the skin, and nervous system involvement is even rare. We reported a case of a 6-year-old girl who was admitted to the hospital with recurrent seizures for 4 weeks. Before that, she had left frontal plaques for more than 1 year. Radiological imaging of the brain showed multiple abnormal lesions and skin biopsy of the plaques indicated scleroderma. After drug therapy, the girl had no recurrence of epilepsy, and no obvious abnormalities were found in the reexamination of neuroimaging. We performed further radiological examination on this patient and reviewed the literatures for this rare case.

Hydrocephalus is a cerebrospinal fluid physiological disorder that causes ventricular dilation with normal or high intracranial pressure. The current regular treatment for hydrocephalus is cerebrospinal fluid shunting, which is frequently related to failure and complications. Meanwhile, considering that the current nonsurgical treatments of hydrocephalus can only relieve the symptoms but cannot eliminate this complication caused by primary brain injuries, the exploration of more effective therapies has become the focus for many researchers. In this article, the current research status and progress of nonsurgical treatment in animal models of hydrocephalus are reviewed to provide new orientations for animal research and clinical practice., Inflammation, fibrosis, iron overload, etc., play an important role in the development of hydrocephalus. By targeting these mechanisms, researchers have discovered a series of drugs that have therapeutic effects on hydrocephalus.

Traditional glioblastoma (GBM) cell lines do not maintain the heterogeneity of the original tumor, cell interactions, and therapy response, thus limiting their investigation in GBM theranostics. Herein, a kind of GBM tumor-targeting nanoparticles (NPs) TCFNP@iRGD are designed and constructed, which are generated by photoacoustic (PA) contrast agent 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene) malononitrile (TCF)-OH through facile nanoprecipitation and decorated with an active targeting ligand iRGD. Their potential in GBM detection via PA imaging on glioma patient-derived cells intracranial xenograft models is evaluated for the first time. Excellent tumor-specific PA mapping performance of GBM is realized by TCFNP@iRGD, demonstrating its promising potential in the clinical diagnosis of GBM.

Aging has a significant role in the proliferation and development of cancers. This study explored the expression profiles, prognostic value, and potential roles of aging-related genes in gliomas. We designed risk score and cluster models based on aging-related genes and glioma cases using LASSO Cox regression analysis, consensus clustering analysis and univariate cox regression analyses. High risk score was related to malignant clinical features and poor prognosis based on 10 datasets, 2953 cases altogether. Genetic alterations analysis revealed that high risk scores were associated with genomic aberrations of aging-related oncogenes. GSVA analysis exhibited the potential function of the aging-related genes. More immune cell infiltration was found in high-risk group cases, and glioma patients in high-risk group may be more responsive to immunotherapy. Knock-down of CTSC, an aging-related gene, can inhibit cell cycle progression, colony formation, cell proliferation and increase cell senescence in glioma cell lines in vitro. Indeed, high expression of CTSC was associated with poor prognosis in glioma cases. In conclusion, this study revealed that aging-related genes have prognostic potential for glioma patients and further identified potential mechanisms for aging-related genes in tumorigenesis and progression in gliomas.

A tanulmány célja annak vizsgálata, hogy miként hat a beszállítók és a megrendelő vállalat technológiai heterogenitása az utóbbi teljesítményére. E kérdés elemzése különösen fontos napjainkban, amikor gyors, gyakran radikális, a cégek versenyképességét növekvő mértékben befolyásoló technológiai innovációkra kerül sor. A hatást a szerzők két dimenzióban tanulmányozzák: egyrészt rövid távon az üzleti teljesítmény jól ismert mutatóival, másrészt hosszú távon a dinamikus képesség koncepciója alapján. Korábbi munkák a diverz üzleti kapcsolatok teljesítménykövetkezményeit tekintve ellentmondásos eredményekről számolnak be, ezért a szerzők az azokat befolyásoló tényezőket is górcső alá veszik. Elméleti modelljüket a strukturális egyenlőségek módszerével, magyarországi vállalati mintán tesztelik, bevonva a vizsgálatba a megrendelő vállalatok ellátásilánc-menedzsmentje által tett fejlesztési erőfeszítések mediáló, illetve hálózati képességük moderáló hatását is. Eredményeik szerint a beszállítók technológiai heterogenitása indirekt módon befolyásolja a központi cég rövid távú üzleti teljesítményét és K+F-képességét a megrendelő vállalat ellátásiláncmenedzsment-fejlesztési erőfeszítésein keresztül. A moderáló hatás elemzése egyértelműen igazolta, hogy a megrendelő fejlett hálózati képessége feltétele a heterogén beszállítói portfólió biztosította pozitív teljesítményhatásnak.

Idiopathic normal pressure hydrocephalus (iNPH) is a rare neurological disorder with no clear prevalence factors and is a significant danger to the elderly. The intracranial glymphatic system is the internal environment that maintains brain survival and metabolism, and thus fluid exchange changes in the glymphatic system under various pathological conditions can provide important insights into the pathogenesis and differential diagnosis of many neurodegenerative diseases such as iNPH. iNPH can be diagnosed using a combination of clinical symptoms, imaging findings and history, and cerebrospinal fluid biomarkers due to the glymphatic system disorder. However, only few researchers have linked the two. Shunt surgery can improve the glymphatic system disorders in iNPH patients, and the surgical approach is determined using a combination of clinical diagnosis and trials. Therefore, we have composed this review to provide a future opportunity for elucidating the pathogenesis of iNPH based on the glymphatic system, and link the glymphatic system to the diagnosis and treatment of iNPH. The review will provide new insights into the medical research of iNPH.

Purpose This paper aims to trace the performance consequences of within-lead firm reconfigurations of global value chains with respect to business performance and upgrading. Design/methodology/approach The study is based on two detailed company case studies which are analysed in an organizational design approach. Findings Lead firms systematically separate and internalize high value-added activities in otherwise low value-added processes leading to constant reconfigurations and reorganizations of the production processes in global value chains. The study finds that similar reconfigurations may trigger different changes and changes and performance consequences may differ considerably according to the level of analysis. The two cases help to understand the specific roles of the outsourcing and offshoring decisions in shaping actual global value chain structures. Originality/value The consequences of within-lead firm reconfigurations are rarely analysed in the literature.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder without a recognized cause. Aquaporins (AQPs) are transmembrane channels that carry water through cell membranes and are critical for cerebrospinal fluid circulation and cerebral water balance. The function of AQPs in developing and maintaining hydrocephalus should be studied in greater detail as a possible diagnostic and therapeutic tool. Recent research indicates that patients with iNPH exhibited high levels of aquaporin 1 and low levels of aquaporin 4 expression, suggesting that these AQPs are essential in iNPH pathogenesis. To determine the source of iNPH and diagnose and treat it, it is necessary to examine and appreciate their function in the genesis and maintenance of hydrocephalus. The expression, function, and regulation of AQPs in iNPH are reviewed in this article, in order to provide fresh targets and suggestions for future research.

Objectives: Surgical treatment is the preferred treatment for pediatric hydrocephalus. The analysis of the outcome of pediatric hydrocephalus surgery and its complications is limited by the lack of available data. Our goal was to better understand the effectiveness of surgery and to explore better surgical treatment methods and management of complications.Methods: 163 patients with pediatric hydrocephalus were included. A retrospective chart review was performed on all patients. Data collected included surgical techniques, number of surgical treatments, complications, and basic demographics.Results: There were 163 patients in this group including 103 males and 60 females. Among the patients, 106 (106/163, 65.0%) patients received ventricular peritoneal shunt (VP), 7 (7/163, 4.3%) patients received ventricle-right atrium shunt (VA) and 50 (50/163, 30.7%) patients received endoscopic third ventriculostomy (ETV). Among the patients who received VP, 74 (74/163, 45.4%) patients were cured and 32 (32/163, 19.6%) patients underwent surgery again. Among the patients who received VA, 38 (38/163, 23.3%) patients were cured and 12 (12/163, 7.4%) patients underwent surgery again. Among the patients who received ETV, 3 (3/163, 1.8%) patients were cured and 4 (4/163, 2.5%) patients underwent surgery again. The most common complication is shunt-related peritonitis or abdominal abscess, abdominal end obstruction (17/163，10.4%).Conclusion: A single surgery can cure most patients, and sometimes more than one surgery is required. For pediatric hydrocephalus, ETV is more efficient and has fewer surgical complications. However, the management of unrelieved symptoms and related complications after ETV surgery and bypass surgery should still be taken seriously.

Severe RSV infection is the main cause of hospitalization to children under the age of five. The regulation of miRNAs on the severity of RSV infection is unclear. The aim of the study was to identify the critical differential expression miRNAs (DE miRNAs) that can regulate the pathological response in RSV‐infected airway epithelial cells. In this study, miRNA and mRNA chips of RSV‐infected airway epithelia from Gene Expression Omnibus (GEO) were screened and analysed, separately. DE miRNAs‐targeted genes were performed for further pathway and process enrichment analysis. DE miRNA‐targeted gene functional network was constructed on the basis of miRNA‐mRNA interaction. The screened critical miRNA was also investigated by bioinformatics analysis. Then, RSV‐infected human bronchial epithelial cells (HBECs) were constructed to verify the expression of the DE miRNAs. Finally, specific synthetic DE miRNAs mimics were used to confirm the effect of DE miRNAs on the RSV‐infected HBECs. 45 DE miRNAs were identified from GEO62306 dataset. Our results showed that hsa‐mir‐34b‐5p and hsa‐mir‐34c‐5p decreased significantly in HBECs after RSV infection. Consistent with the biometric analysis, hsa‐mir‐34b/c‐5p is involved in the regulation of mucin expression gene MUC5AC. In RSV‐infected HBECs, the inducement of MUC5AC production by decreased hsa‐mir‐34b/c‐5p was partly mediated through activation of c‐Jun. These findings provide new insights into the mechanism of mucus obstruction after RSV infection and represent valuable targets for RSV infection and airway obstruction treatment.

The article puts the topic of Sales & Operations Planning at the centre of the study. It is a relatively new management solution, which is interesting from a theoretical point of view, but also important for corporate practice. Nevertheless, to the best of the authors’ knowledge, no article on the topic has been published in Hungarian yet. One of the aims of their work, therefore, is to draw attention to this area. The other goal is to present the S&OP practice of domestic companies in the light of a complex maturity model. The chosen model maps S&OP practice of corporations along four main dimensions: the efficiency and effectiveness of the planning process, organizational/human readiness, and IT support. Creating a benchmarking opportunity, the study describes the maturity of the companies in the sample and makes suggestions in respect of further developing related practice and increase maturity. A cikk a Sales & Operations Planning temakoret helyezi a vizsgalat kozeppontjaba. Ez az ellatasi lanc realfolyamatainak taktikai szintű tervezese soran alkalmazott szervezeti egyeztetesi folyamat, melynek celja, hogy dinamikus ujratervezesi ciklusokon keresztul egyensulyt teremtsen a tenyleges kereslet, a rendelkezesre allo erőforrasok es az altaluk biztosithato kinalat kozott ugy, hogy tamogassa az uzleti terv megvalosulasat. Egy viszonylag uj, elmeleti szempontbol erdekes, de a vallalati gyakorlat szamara is fontos kerdeskorről van szo. Ennek ellenere a szerzők legjobb tudomasa szerint meg nem jelent meg magyar nyelven cikk a temakorben. Munkajuk egyik celja ezert az, hogy felhivjak a figyelmet erre a teruletre. A masik cel, hogy egy komplex erettsegi modell tukreben bemutassak a hazai vallalatok S&OP gyakorlatat. A valasztott modell negy fő dimenzio menten terkepezi fel a vallalati gyakorlatot: a tervezesi folyamat hatekonysaga, eredmenyessege, a szervezeti/emberi felkeszultseg es az informatikai tamogatottsag. A tanulmany benchmarking lehetőseget teremtve ismerteti a mintaban szereplő vallalatok gyakorlatanak erettseget es fejlesztesi javaslatokat fogalmaz meg.

Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin β4 (ITGB4) is a structural adhesion molecule that is down-regulated in the airway epithelium of asthma patients. Although a few studies hint toward the role of ITGB4 in asthmatic inflammation pathogenesis, their specific resultant effects remain unexplored. In the present study, we determined the role of ITGB4 of AECs in the regulation of Th2 response and identified the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated lung inflammation and AHR with higher production of CCL17 in house dust mite (HDM)-treated mice. ITGB4 regulated CCL17 production in AECs through EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 both inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated the involvement of ITGB4 deficiency in the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway in AECs.

Deregulation of aerobic glycolysis is a common phenomenon in human cancers, including glioblastoma (GBM). In the present study, we demonstrated that the natural compound xanthohumol has a profound anti-tumor effect on GBM via direct inhibition of glycolysis. Xanthohumol suppressed cell proliferation and colony formation of GBM cells, and significantly impaired glucose metabolism via inhibiting Hexokinase 2 (HK2) expression. We demonstrated that down-regulation of c-Myc was required for xanthohumol-induced decrease of HK2. Xanthohumol destabilization of c-Myc, and promoted FBW7-mediated ubiquitination of c-Myc. Xanthohumol attenuated Akt activity and inhibited the activation of GSK3β, resulted in c-Myc degradation. Overexpression of Myr-Akt1 significantly rescued xanthohumol-mediated c-Myc inhibition and glycolysis suppression. Finally, the xanthohumol-mediated down-regulation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis promoted the destabilization of c-Myc. Finally, the animal results demonstrated that xanthohumol substantially inhibited tumor growth in vivo. Collectively, xanthohumol appears to be a promising new anti-tumor agent with the therapeutic potential for GBM.

Dermatological diseases pose a major threat to the global health, affecting almost one-third of the world's population. Various studies have demonstrated that early diagnosis and intervention are often critical to prognosis and outcome. To this end, the past decade has witnessed the rapid evolvement of deep learning based smartphone apps, which allow users to conveniently and timely identify issues that have emerged around their skins. In order to collect sufficient data needed by deep learning and at the same time protect patient privacy, federated learning is often used, where individual clients aggregate a global model while keeping datasets local. However, existing federated learning frameworks are mostly designed to optimize the overall performance, while common dermatological datasets are heavily imbalanced. When applying federated learning to such datasets, significant disparities in diagnosis accuracy may occur. To address such a fairness issue, this paper proposes a fairness-aware federated learning framework for dermatological disease diagnosis. The framework is divided into two stages: In the first in-FL stage, clients with different skin types are trained in a federated learning process to construct a global model for all skin types. An automatic weight aggregator is used in this process to assign higher weights to the client with higher loss, and the intensity of the aggregator is determined by the level of difference between losses. In the latter post-FL stage, each client fine-tune its personalized model based on the global model in the in-FL stage. To achieve better fairness, models from different epochs are selected for each client to keep the accuracy difference of different skin types within 0.05. Experiments indicate that our proposed framework effectively improves both fairness and accuracy compared with the state-of-the-art., Comment: 8 pages, 2 figures

RESTful APIs are arguably the most popular endpoints for accessing Web services. Blackbox testing is one of the emerging techniques for ensuring the reliability of RESTful APIs. The major challenge in testing RESTful APIs is the need for correct sequences of API operation calls for in-depth testing. To build meaningful operation call sequences, researchers have proposed techniques to learn and utilize the API dependencies based on OpenAPI specifications. However, these techniques either lack the overall awareness of how all the APIs are connected or the flexibility of adaptively fixing the learned knowledge. In this paper, we propose Morest, a model-based RESTful API testing technique that builds and maintains a dynamically updating RESTful-service Property Graph (RPG) to model the behaviors of RESTful-services and guide the call sequence generation. We empirically evaluated Morest and the results demonstrate that Morest can successfully request an average of 152.66%-232.45% more API operations, cover 26.16%-103.24% more lines of code, and detect 40.64%-215.94% more bugs than state-of-the-art techniques. In total, we applied Morest to 6 real-world projects and found 44 bugs (13 of them cannot be detected by existing approaches). Specifically, 2 of the confirmed bugs are from Bitbucket, a famous code management service with more than 6 million users.

Robotic Vehicles (RVs) have gained great popularity over the past few years. Meanwhile, they are also demonstrated to be vulnerable to sensor spoofing attacks. Although a wealth of research works have presented various attacks, some key questions remain unanswered: are these existing works complete enough to cover all the sensor spoofing threats? If not, how many attacks are not explored, and how difficult is it to realize them? This paper answers the above questions by comprehensively systematizing the knowledge of sensor spoofing attacks against RVs. Our contributions are threefold. (1) We identify seven common attack paths in an RV system pipeline. We categorize and assess existing spoofing attacks from the perspectives of spoofer property, operation, victim characteristic and attack goal. Based on this systematization, we identify 4 interesting insights about spoofing attack designs. (2) We propose a novel action flow model to systematically describe robotic function executions and unexplored sensor spoofing threats. With this model, we successfully discover 103 spoofing attack vectors, 26 of which have been verified by prior works, while 77 attacks are never considered. (3) We design two novel attack methodologies to verify the feasibility of newly discovered spoofing attack vectors.

The choroid plexus is a tissue located in the lateral ventricles of the brain and is composed mainly of choroid plexus epithelium cells. The main function is currently thought to be the secretion of cerebrospinal fluid and the regulation of its pH, and more functions are gradually being demonstrated. Assistance in the removal of metabolic waste and participation in the apoptotic pathway are also the functions of choroid plexus. Besides, it helps to repair the brain by regulating the secretion of neuropeptides and the delivery of drugs. It is involved in the immune response to assist in the clearance of infections in the central nervous system. It is now believed that the choroid plexus is in an inflammatory state after damage to the brain. This state, along with changes in the cilia, is thought to be an abnormal physiological state of the choroid plexus, which in turn leads to abnormal conditions in cerebrospinal fluid and triggers hydrocephalus. This review describes the pathophysiological mechanism of hydrocephalus following choroid plexus epithelium cell abnormalities based on the normal physiological functions of choroid plexus epithelium cells, and analyzes the attempts and future developments of using choroid plexus epithelium cells as a therapeutic target for hydrocephalus.

CD73 is essential in promoting tumor growth by prohibiting anti-tumor immunity in many cancer types. While the mechanism remains largely unknown, our paper comprehensively confirmed the onco-immunological characteristics of CD73 in the tumor microenvironment (TME) of pan-cancer. This paper explored the expression pattern, mutational profile, prognostic value, tumor immune infiltration, and response to immunotherapy of CD73 in a continuous cohort of cancers through various computational tools. The co-expression of CD73 on cancer cells, immune cells, and stromal cells in the TME was also detected. Especially, we examined the correlation between CD73 and CD8+ (a marker of T cell), CD68+ (a marker of macrophage), and CD163+ (a marker of M2 macrophage) cells using multiplex immunofluorescence staining of tissue microarrays. CD73 expression is significantly associated with a patient’s prognosis and could be a promising predictor of these cancers. High CD73 levels are strongly linked to immune infiltrations, neoantigens, and immune checkpoint expression in the TME. In particular, enrichment signaling pathway analysis demonstrated that CD73 was obviously related to activation pathways of immune cells, including T cells, macrophages, and cancer-associated fibroblasts (CAFs). Meanwhile, single-cell sequencing algorithms found that CD73 is predominantly co-expressed on cancer cells, CAFs, M2 macrophages, and T cells in several cancers. In addition, we explored the cellular communication among 14 cell types in glioblastoma (GBM) based on CD73 expression. Based on the expression of CD73 as well as macrophage and T cell markers, we predicted the methylation and enrichment pathways of these markers in pan-cancer. Furthermore, a lot of therapeutic molecules sensitive to these markers were predicted. Finally, potential anticancer inhibitors, immunotherapies, and gene therapy responses targeting CD73 were identified from a series of immunotherapy cohorts. CD73 is closely linked to clinical prognosis and immune infiltration in many cancers. Targeting CD73-dependent signaling pathways may be a promising therapeutic strategy for future tumor immunotherapy.

Accurate assessing CO2 exchange of tundra ecosystems is essential for better understanding and prediction of the CO2 responses of tundra ecosystems to climate change. In this study, the effects of warming on growing season CO2 exchange in an alpine tundra ecosystem were examined with closed transparent chamber attached to an infrared gas analyzer. Compared to ambient controls, open-top chambers (OTCs) increased growing season air (15 cm above ground surface) and soil (10 cm in depth) temperature by 1 and 0.2°C, respectively. Compared to the controls, OTCs tended to increase the plant height of Dryas octopetala and Vaccinium uliginosum by 15.1% (but P > 0.05) and 7.5% (P > 0.05), respectively. During the growing season, OTC-warming increased net ecosystem CO2 exchange by 136% and gross ecosystem exchange by 63%, whereas no significant difference in ecosystem respiration was found. Our results suggest that the predicted air warming will increase ecosystem carbon uptake of the Changbai Mountain alpine tundra during growing season. However, there is an uncertainty about the net CO2 exchange of that ecosystem at an annual scale, because, due to the inaccessibility, we did not study the winter respiration. Further studies are, therefore, needed to estimate the annual and long-term trade-off between CO2 uptake and emission in that region.

Distributed denial of service (DDoS) cyber-attack poses a severe threat to the industrial Internet of Things (IIoT) operation due to the security vulnerabilities resulted from increased connectivity and openness, and the large number of deployed low computation power devices. This paper applies Fog computing concept in DDoS mitigation by allocating traffic monitoring and analysis work close to local devices, and, on the other hand, coordinating and consolidating work to cloud central servers so as to achieve fast response while at low false alarm rate. The mitigation scheme consists of real-time traffic filtering via field firewall devices, which are able to reversely filter the signature botnet attack packets; offline specification based traffic analysis via virtualized network functions (VNFs) in the local servers; and centralized coordination via cloud server, which consolidates and correlates the information from the distributed local servers to make a more accurate decision. The proposed scheme is tested in an industrial control system testbed and the experiments evaluate the detection time and rate for two types of DDoS attacks and demonstrate the effectiveness of the scheme.

Container technology can effectively control soil environment and nutrient status to obtain the optimal plant growth condition. Peat, green waste compost (GWC), soil and perlite were used as substr...

The performance of organic polar tunnel junctions under external electrical/mechanical stimuli is crucial for their great promise in developing flexible and high-performance sensor and memristive devices. Here, we prepared a single P(VDF-TrFE) monolayer on an Au(111) atomic-level surface by using a Langmuir–Blodgett (LB) technique. The polarity stability and electronic transport behavior of the monolayer were investigated via piezoresponse force microscopy (PFM) and conductive atomic force microscopy (c-AFM) measurements. We observed a strong polarity asymmetry in the P(VDF-TrFE) monolayer tunnel junction. Electrical bias and mechanical force exerted by the tip both can switch the monolayer from the metastable state (“H–Au” state, down polarity) to the stable state (“F–Au” state, up polarity). Moreover, the conductance of the monolayer tunnel junction can be controlled not only by the electrical bias but also by the tip force. Interestingly, a decrease of conductance from the ON state to OFF state is caus...

Alzheimer’s disease (AD), a common neurodegenerative disease, is the main cause of dementia, with cognitive decline as the core symptom observed during diagnosis. Synaptic loss may be the main cause of early cognitive dysfunction in AD, but the detailed mechanism is still unclear. In this study, we investigated the role of abnormal miR-455–5p/CPEB1 pathway in AD mouse model. We found that miR-455–5p was upregulated, while its downstream target, cytoplasmic polyadenylation element-binding 1 (CPEB1), was downregulated in the hippocampus of APP/PS1 mice at the age of 9 m. Abnormal miR-455–5p/CPEB1 pathway mediated cognitive deficits in APP/PS1 mice through suppressing α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor expressions. And miR-455–5p suppression, CPEB1 overexpression or application of a peptide disrupting the miR-455–5p/CPEB1 interaction in CA1 of APP/PS1 mice rescued AD-like phenotypes in mice, including deficits in synaptic plasticity and memory. In conclusion, our results indicated that miRNA-455–5p/CPEB1 pathway mediated synaptic and memory deficits in Alzheimer’s Disease through targeting on AMPARs, providing a potential therapeutic strategy for AD.

Linear scleroderma is the most common type of localized scleroderma in children. Lesions rarely involve areas other than the skin, and nervous system involvement is even rare. We reported a case of a 6-year-old girl who was admitted to the hospital with recurrent seizures for 4 weeks. Before that, she had left frontal plaques for more than 1 year. Radiological imaging of the brain showed multiple abnormal lesions and skin biopsy of the plaques indicated scleroderma. After drug therapy, the girl had no recurrence of epilepsy, and no obvious abnormalities were found in the reexamination of neuroimaging. We performed further radiological examination on this patient and reviewed the literatures for this rare case.

AI has provided us with the ability to automate tasks, extract information from vast amounts of data, and synthesize media that is nearly indistinguishable from the real thing. However, positive tools can also be used for negative purposes. In particular, cyber adversaries can use AI (such as machine learning) to enhance their attacks and expand their campaigns. Although offensive AI has been discussed in the past, there is a need to analyze and understand the threat in the context of organizations. For example, how does an AI-capable adversary impact the cyber kill chain? Does AI benefit the attacker more than the defender? What are the most significant AI threats facing organizations today and what will be their impact on the future? In this survey, we explore the threat of offensive AI on organizations. First, we present the background and discuss how AI changes the adversary's methods, strategies, goals, and overall attack model. Then, through a literature review, we identify 33 offensive AI capabilities which adversaries can use to enhance their attacks. Finally, through a user study spanning industry and academia, we rank the AI threats and provide insights on the adversaries.

Purpose: Persistent negative results (at least 3 times) of reverse transcription–polymerase chain reaction (RT-PCR) from pharyngeal swabs are not rare in coronavirus disease 2019 (COVID-19) patients, but their characteristics have not yet been well studied.Methods: PCR confirmed, serum antibody confirmed with persistent negative PCR results, and clinically diagnosed patients hospitalized in two medical centers during February and March 2020 were included. Differences in clinical, imaging and laboratory characteristics as well as factors affecting their prognosis were analyzed.Results: There were 114 PCR confirmed, 17 serology confirmed and 21 clinically diagnosed patients included. Time from onset of disease to the first PCR and admission were similar among the groups. Compared with PCR-confirmed patients, serology-confirmed patients were older and likely to have hypertension, vomiting, or symptoms of chest pain and dyspnea. Regarding imaging manifestations, serology-confirmed patients were more prone to pleural effusion. In addition, higher levels of C-reactive protein, neutrophil-to-lymphocyte ratio, total bilirubin, D-dimer, fibrinogen, troponin, interleukin-6 and IL-8 were also found. Although with similar mortality, serology confirmed patients were more likely to have disease progression. High levels of D-dimer and IL-6 were possibly the underlying factors leading to their worse prognosis. On the other hand, clinically diagnosed patients were more similar to PCR-confirmed patients.Conclusion: Serology confirmed COVID-19 patients with at least three negative PCR results had different clinical characteristics and were likely to have disease progression, possibly due to more severe hypercoagulation status and cytokine storm.

The pentraxin is a superfamily of proteins with the same domain known as the pentraxin domain at C-terminal. This family has two subgroups, namely; short pentraxins (C-reactive protein and serum amyloid P component) and long pentraxins (neuronal pentraxin 1, neuronal pentraxin 2, neuronal pentraxin receptor, pentraxin 3 and pentraxin 4). Each group shares a similar structure with the pentameric complexes arranged in a discoid shape. Previous studies revealed the functions of different pentraxin family members. Most of them are associated with human innate immunity. Inflammation has commonly been associated with tumor progression, implying that the pentraxin family might also participate in tumor progression. Therefore, we reviewed the basic characteristics and functions of the pentraxin family and their role in tumor progression.

Asthma and bronchiectasis are known to be two distinct diseases with different etiology, pathophysiology, management, and prognosis. However, a high prevalence of bronchiectasis has been reported in patients with severe asthma. Thus, it is of great importance to identify the impact of bronchiectasis on asthmatic patients.Databases including PubMed, Embase, Cochrane, Web of Science were searched comprehensively to identify relevant human clinical studies published until February 2020.Two investigators (Gelei Lan and Guochao Shi) independently obtained the potentially eligible articles based on their titles and abstracts. When opinions differed between the investigators, discussions were made to reach an agreement. The authors of the included studies were contacted for inquiry when necessary.Six observational studies with 1004 patients were included in the meta-analysis. The mean prevalence of bronchiectasis in patients with asthma was 35.2% (ranging from 2.2% to 47%). Asthmatic patients with bronchiectasis were older, had a longer disease duration, exhibited greater severity, and showed more frequent exacerbations and hospitalization, and poorer lung function, compared with the patients without bronchiectasis.Despite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of comorbid bronchiectasis on asthmatic patients. Thus, coexistence of bronchiectasis should be considered a clinical phenotype of asthma, which may have associations with exacerbation and hospitalization.