Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential effect of nerve growth factor on dopaminergic neurotoxin‐induced apoptosis

Both rotenone and manganese are possible neurotoxins for a wide variety of cell and neuronal types including dopaminergic neurons and induce apoptosis in various cells. Neurotrophic factors have the potential for therapeutic development when used to prevent Parkinson's disease. In this paper, we focused on the differences between rotenone and manganese as toxins, and characterized the influence of neurotrophic factors on toxin‐induced apoptosis in PC12 cells. There were distinct differences in intracellular mechanisms between rotenone‐ and manganese‐induced apoptosis such as the production of reactive oxygen species, the response to antioxidants, and the activation of the c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (MAPK). Nerve growth factor (NGF) almost completely prevented rotenone‐induced but not manganese‐induced caspase activation and DNA fragmentation. The differential effect of NGF was found to be mainly due to the down‐regulation of the Trk tyrosine kinase receptor by manganese but not by rotenone. Prevention of rotenone‐induced apoptosis by NGF was attenuated by the phosphatidylinositol 3‐kinase (PI 3‐kinase) inhibitor, LY294002, but not MAPK kinase (MEK) inhibitors, PD98059 or U0126. These results demonstrate that the potential neurotoxins for dopaminergic cells exert their toxic effect by activation of different signaling pathways of apoptosis and that NGF prevents rotenone‐induced apoptosis through the activation of the PI 3‐kinase pathway not MAPK pathway.
Selection of candidates for islet xenotransplantation

Progress in human islet transplantation has established beta cell replacement therapy as a treatment option for type I diabetes. However, if islet transplantation is to be widely applied, the current supply of human pancreases will not meet the demand and alternative sources will need to be developed. The two most promising alternative sources are stem cells and porcine islets. Stem cells, whether embryonic or adult, have tremendous potential, however formidable obstacles remain with stem cells including; the long-term survival of these cells, their unknown malignant potential, the ability of these cells to synthesize sufficient insulin, and whether they will have similar metabolic regulatory function to normal islets [1]. Porcine islets have a number of potential advantages, including that swine are easily bred; swine have large litters and grow and mature rapidly, are ethically acceptable and the fact that porcine insulin has been used clinically for more than 50 yr [2]. There remain two main concerns that may limit the use of pig tissues as a xenogeneic source of a transplant. First, humans express high titers of antibodies against Galactose-a1,3-Galactose and other residues that is present on most pig cells, which may result in a hyperacute rejection. Secondly, porcine cells contain endogenous retroviruses. These viruses have the potential to infect the human host, particularly with administration of large inoculums under the blanket of immunosuppression [2].
Neuronavigated rTMS in a patient with chronic tinnitus. Effects of 4 weeks treatment

&NA; Clinical, neurophysiological and neuroimaging data suggest that chronic tinnitus resembles neuropsychiatric syndromes characterised by focal brain activation. Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an efficient method in treating brain hyperexcitability disorders. In one patient suffering from chronic tinnitus, [18F]deoxyglucose PET revealed increased metabolic activity in a circumscript area of the left primary auditory cortex (PAC). The effect of MRI and PET guided neuronavigated IHz rTMS of this area was evaluated in a single‐blind, sham‐controlled, cross‐over manner, followed by a 4‐week open treatment. Following active stimulation there was a remarkable effect, enduring several weeks, on tinnitus sensation, which was paralleled by altered cortical excitability. These findings suggest that neuronavigated rTMS of increased PAC activity might offer a new option for treating auditory phantom perceptions like chronic tinnitus. NeuroReport 14:977–980 © 2003 Lippincott Williams & Wilkins.
Do customer profitability analyses pay? A survey of large Norwegian companies

The purpose of this paper is to study the relationships between the extents of use of customer profitability analyses (CPA) and business performance. In addition to CPA as an overall construct, five methods are included: 1) CPA of individual customers; 2) customer segments; 3) assessments of customer lifetime value; 4) valuations of customers; 5) customers as investments. A total of 437 large Norwegian companies were invited to answer a questionnaire, of which 171 participated giving a response rate of 39%. CPA (overall construct) is positively linked to business performance. CPA of individual customers is the only method that significantly drives business performance. Thus, conducting detailed customer profitability analyses to establish reliable customer profitability accounts appears to be worth the effort. The respondents perceive the three forward-looking methods, i.e., (3), (4) and (5) as variations of one approach. Analogous studies are highly recommended. Cost estimation methods could also be addressed.
An analysis of influence factors for academic performance about personality traits and thinking styles of students: Use a C programming language course in college as an example

Academic performance is one of the indicators to evaluate the achievement of college students, which plays an important role in individual development. However, it is worth mentioning that personality traits and thinking styles have an influence on academic performance. To further study the correlation among personality traits, thinking styles and academic performance, we carry out a series of experiments using certain C programming language course in certain college as an example. Firstly, we eliminate the overlap of personality traits and thinking styles by principal component analysis (PCA). Then, three groups of regression analysis on C programming language course grade are performed, i.e., the personality traits with course grades, the thinking styles with course grades, the principal components of the personality traits and thinking styles with course grades. Finally, the experimental results show that Agreeableness has a positive influence on C programming language grades, while Local has a negative influence on C programming language grades. Meanwhile, the personality traits and thinking styles and C course grades are generally not related and the irrelevance is not caused of the multiple collinearity between personality traits and thinking styles.
Model of incentive system for employees: A case of a manufacturing company in Croatia

Background: One of the main determinants of a company’s business performance is the complete mobility and orientation of its employees towards realising the goals of the company. No single aspect of the company has such a powerful, and simultaneously, invisible influence on the behaviour and feelings of its employees as the organisational climate. Organisational learning creates a climate that encourages employees to learn and to develop their potential.Objectives: The aim of this study is to investigate the incentives and the factors of an organisational climate required to develop a model of an incentive system to motivate employees to work better.Method: A quantitative research methodology was used and data was collected by using a closed-ended type of questionnaire. Data was analysed using descriptive and inferential statistics.Results: The results show that the employees would prefer more incentives, and the factors of a positive organisational climate were far lower than expected by its employees and even lower than what they considered to be essential in order to perform their jobs effectively and to contribute to achieving company objectives.Conclusion: Incentive systems are crucial to employees and the organisational climate and employee satisfaction should be constantly monitored and empowered through an integrated model of incentive system.
IGFBP7 Binds to the IGF-1 Receptor and Blocks Its Activation by Insulin-Like Growth Factors

By inactivating the insulin-like growth factor receptor, IGFBP7 suppresses growth and promotes cell death. Deadly Receptor Blockade When bound to insulin-like growth factor 1 or 2 (IGF-1/2), the IGF-1 receptor (IGF1R) promotes protein synthesis, cell growth, and survival. One mechanism by which the family of IGF-binding proteins (IGFBPs) interferes with IGF1R activation is by binding to IGF-1/2. Evdokimova et al. showed that, unlike other IGFBPs, IGFBP7 attenuated activation of IGF1R in various cell lines by interacting with the extracellular domain of IGF1R and preventing IGF-1/2 from binding to the receptor. IGFBP7 increased the abundance of IGF1R in various normal and cancer cells and xenograft tumors. However, in cultured cells, IGFBP7 treatment resulted in the retention of IGF1R at the cell surface in an inactive form and in apoptosis. Thus, IGFBP7 could be used to trigger cell death in tumors that depend on IGF-1/2 for growth or survival. Insulin-like growth factor–binding protein 7 (IGFBP7) is a secreted factor that suppresses growth, and the abundance of IGFBP7 inversely correlates with tumor progression. Here, we showed that pretreatment of normal and breast cancer cells with IGFBP7 interfered with the activation and internalization of insulin-like growth factor 1 receptor (IGF1R) in response to insulin-like growth factors 1 and 2 (IGF-1/2), resulting in the accumulation of inactive IGF1R on the cell surface and blockade of downstream phosphatidylinositol 3-kinase (PI3K)–AKT signaling. Binding of IGFBP7 and IGF-1 to IGF1R was mutually exclusive, and the N-terminal 97 amino acids of IGFBP7 were important for binding to the extracellular portion of IGF1R and for preventing its activation. Prolonged exposure to IGFBP7 resulted in activation of the translational repressor 4E-binding protein 1 (4E-BP1) and enhanced sensitivity to apoptosis in IGF1R-positive cells. These results support a model whereby IGFBP7 binds to unoccupied IGF1R and suppresses downstream signaling, thereby inhibiting protein synthesis, cell growth, and survival.
Is inactivation of O6-methylguanine DNA methyltransferase still a favorable prognostic factor of patients with diffuse large B-cell lymphoma in the era of R-CHOP chemotherapy?

The prognostic significance of O6-methylguanine DNA methyltransferase (MGMT) inactivation was evaluated in patients with diffuse large B-cell lymphoma (DLBCL) who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in addition to rituximab. In this retrospective study, we used the methylation-specific polymerase chain reaction to investigate MGMT promoter methylation status and immunohistochemistry to evaluate MGMT expression in patients with DLBCL who received rituximab plus CHOP (R-CHOP) chemotherapy. No difference in patient characteristics, disease characteristics, response, or survival in patients with DLBCL who received front-line R-CHOP chemotherapy was observed according to MGMT methylation status and MGMT expression. On multivariate analysis, Grade 3–4 mucositis in the MGMT methylated group was significantly higher than that in the MGMT unmethylated group (hazard ratio (HR) 2.40, 95% CIs: 1.26–7.26, p = 0.014). This study demonstrated that inactivation of MGMT does not appear to play an important role in patients with DLBCL who received R-CHOP chemotherapy either with regard to the response rate or overall survival. Additionally, Grade 3–4 mucositis was found to be significantly related with inactivation of MGMT by a multivariate analysis.
To whom does the driver's seat belong in the future?: a case of negotiation between gender studies and automotive engineering

This article provides an experience report on an interdisciplinary cooperation between two gender researchers and two automotive engineers at a German technical university. It focuses on the negotiation processes around a joint research proposal, dealing with the question of how to create concepts for a trustworthy human-machine interaction in automated driving systems that satisfy the requirements of different user groups. These systems aim to offer the choice of automobility to groups of users who have so far had rather limited access, or have had reasons to refuse usage. Discussions in the interdisciplinary team are still ongoing. Their substantial shifts and their expected methodological and epistemological effects are analyzed from a feminist science and technology studies (STS) perspective. The general objective of this paper is to provide insights about the contributions and challenges of integrating approaches from gender studies into the field of automotive engineering in order to support interdisciplinary dialogues that foster a socially fair and inclusive digital transformation.
A Pancreaticoduodenectomy Risk Model Derived From 8575 Cases From a National Single-Race Population (Japanese) Using a Web-Based Data Entry System: The 30-Day and In-hospital Mortality Rates for Pancreaticoduodenectomy

Objective:To create a mortality risk model after pancreaticoduodenectomy (PD) using a Web-based national database system. Background:PD is a major gastroenterological surgery with relatively high mortality. Many studies have reported factors to analyze short-term outcomes. Subjects and Methods:After initiation of National Clinical Database, approximately 1.2 million surgical cases from more than 3500 Japanese hospitals were collected through a Web-based data entry system. After data cleanup, 8575 PD patients (mean age, 68.2 years) recorded in 2011 from 1167 hospitals were analyzed using variables and definitions almost identical to those of American College of Surgeons–National Surgical Quality Improvement Program. Results:The 30-day postoperative and in-hospital mortality rates were 1.2% and 2.8% (103 and 239 patients), respectively. Thirteen significant risk factors for in-hospital mortality were identified: age, respiratory distress, activities of daily living within 30 days before surgery, angina, weight loss of more than 10%, American Society of Anesthesiologists class of greater than 3, Brinkman index of more than 400, body mass index of more than 25 kg/m2, white blood cell count of more than 11,000 cells per microliter, platelet count of less than 120,000 per microliter, prothrombin time/international normalized ratio of more than 1.1, activated partial thromboplastin time of more than 40 seconds, and serum creatinine levels of more than 3.0 mg/dL. Five variables, including male sex, emergency surgery, chronic obstructive pulmonary disease, bleeding disorders, and serum urea nitrogen levels of less than 8.0 mg/dL, were independent variables in the 30-day mortality group. The overall PD complication rate was 40.0%. Grade B and C pancreatic fistulas in the International Study Group on Pancreatic Fistula occurred in 13.2% cases. The 30-day and in-hospital mortality rates for pancreatic cancer were significantly lower than those for nonpancreatic cancer. Conclusions:We conducted the reported risk stratification study for PD using a nationwide surgical database. PD outcomes in the national population were satisfactory, and the risk model could help improve surgical practice quality.
A newly developed uroplakin II antibody with increased sensitivity in urothelial carcinoma of the bladder.

CONTEXT Uroplakin II is a 15-kDa protein component of the urothelial plaques that enhance the permeability barrier and strength of the urothelium. Studies have shown uroplakin II messenger RNA to be expressed in bladder cancer tissues and peripheral blood of patients with urothelial carcinoma. Little is known about the protein expression of uroplakin II in urothelial carcinoma, possibly because of the absence of a commercially available uroplakin II antibody. Pathologists have used the uroplakin III antibody (AU1) to identify tumors of urothelial origin; however, the use of AU1 is limited because of its poor sensitivity. OBJECTIVES To evaluate a newly developed mouse monoclonal uroplakin II antibody (BC21) in urothelial carcinoma and to compare it with previously developed mouse monoclonal uroplakin III (BC17 and AU1). DESIGN Uroplakin II and III antibodies were optimized for staining using a horseradish peroxidase-polymer detection system and were visualized with 3,3'-diaminobenzidine. RESULTS BC21, BC17, and AU1 demonstrated sensitivities in urothelial carcinoma of the bladder of 79% (44 of 56), 55% (31 of 56) (P = .002), and 34% (19 of 56) (P < .001), respectively. Subsequently, the increased staining sensitivity and intensity of BC21, compared with BC17, was validated in a larger study (134 of 174; 77% and 94 of 174; 54%, respectively) (P < .001). BC21 was found to be highly specific when evaluated in various normal and neoplastic tissues, including prostatic and renal carcinomas. CONCLUSIONS The mouse monoclonal uroplakin II antibody (BC21) demonstrated superior sensitivity and specificity in urothelial carcinoma, compared with uroplakin III (BC17 and AU1), suggesting its advantages in the differential diagnosis of urothelial carcinoma and in the detection of tumors of unknown origin.
Resurrection of a clinical antibody: Template proteogenomic de novo proteomic sequencing and reverse engineering of an anti‐lymphotoxin‐α antibody

A mouse hybridoma antibody directed against a member of the tumour necrosis factor (TNF)‐superfamily, lymphotoxin‐alpha (LT‐α), was isolated from stored mouse ascites and purified to homogeneity. After more than a decade of storage the genetic material was not available for cloning; however, biochemical assays with the ascites showed this antibody against LT‐α (LT‐3F12) to be a preclinical candidate for the treatment of several inflammatory pathologies. We have successfully rescued the LT‐3F12 antibody by performing MS analysis, primary amino acid sequence determination by template proteogenomics, and synthesis of the corresponding recombinant DNA by reverse engineering. The resurrected antibody was expressed, purified and shown to demonstrate the desired specificity and binding properties in a panel of immuno‐biochemical tests. The work described herein demonstrates the powerful combination of high‐throughput informatic proteomic de novo sequencing with reverse engineering to reestablish monoclonal antibody‐expressing cells from archived protein sample, exemplifying the development of novel therapeutics from cryptic protein sources.
ABT-702 (4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin- 3-yl)pyrido[2,3-d]pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory properties. II. In vivo characterization in the rat.

Adenosine kinase (AK; EC 2.7.1.20) is a key intracellular enzyme regulating intra-and extracellular concentrations of adenosine (ADO), an endogenous neuromodulator, antinociceptive, and anti-inflammatory autocoid. AK inhibition provides a means of potentiating local tissue concentrations of endogenous ADO, and AK inhibitors may have therapeutic potential as analgesic and anti-inflammatory agents. The effects of ABT-702, a novel, potent (IC(50) = 1.7 nM), and selective non-nucleoside AK inhibitor were examined in rat models of nociception and acute inflammation. ABT-702 was orally effective and fully efficacious to suppress nociception in a spectrum of pain models in the rat, including carrageenan-induced thermal hyperalgesia, the formalin test of persistent pain, and models of nerve injury-induced and diabetic neuropathic pain (tactile allodynia after L5/L6 spinal nerve ligation or streptozotocin injection, respectively.) ABT-702 was especially potent at relieving inflammatory thermal hyperalgesia (ED(50) = 5 micromol/kg p.o. ). ABT-702 was also effective in the carrageenan-induced paw edema model of acute inflammation (ED(50) = 70 micromol/kg p.o. ). The antinociceptive and anti-inflammatory effects of ABT-702 were blocked by selective ADO receptor antagonists, consistent with endogenous ADO accumulation and ADO receptor activation as a mechanism of action. The antinociceptive effects of ABT-702 were not blocked by the opioid antagonist naloxone. In addition, ABT-702 showed less potential to develop tolerance to its antinociceptive effects compared with morphine. ABT-702 had no significant effect on rotorod performance or heart rate (at 30-300 micromol/kg p.o.), mean arterial pressure (at 30-100 micromol/kg p.o.), or exploratory locomotor activity (at </=10 micromol/kg p.o.). Thus, ABT-702 is a novel, non-nucleoside AK inhibitor, with a nonopioid, non-nonsteroidal anti-inflammatory drug mechanism of action, which shows antinociceptive and anti-inflammatory activity in vivo.
Measuring unilateral otolith function via the otolith-ocular response and the subjective visual vertical.

In the present study, attention is directed to the unilateral response of the otolith system to static and dynamic tilt, as reflected by subjective estimation of the visual vertical (oculogravic perception). Measurements were performed with a variable radius rotary chair, which permits controlled modulation of the centripetal, or radial, acceleration. By limiting the radius, i.e. eccentric displacement of the head by 3.5 cm during constant-velocity rotation about the earth-vertical axis, adequate unilateral stimulation of the otolith organ--predominantly the utricle--is generated, without involving the semicircular canals. This paradigm has been employed to measure the unilateral utriculo-ocular response. In contrast to the otolith-ocular response (OOR), the subjective visual vertical (SVV) reflects the processing of otolithic information in the higher brain centres (thalamus, vestibular cortex). Exploitation of these two complementary approaches provides useful information for both experimental and clinical scientists. The findings also reveal that centripetal acceleratory stimulation during constant angular velocity with the subject centred on axis is sufficient to localize peripheral otolith dysfunction by means of SVV estimation. This represents a novel test of otolith function that can be easily integrated into routine clinical testing.