Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotypic and Biochemical Analyses of BACE1- and BACE2-deficient Mice*

β-Secretase (BACE1) is the rate-limiting protease for the generation of the amyloid β-peptide (Aβ) in Alzheimer disease. Mice in which the bace1 gene is inactivated are reported to be healthy. However, the presence of a homologous gene encoding BACE2 raises the possibility of compensatory mechanisms. Therefore, we have generated bace1, bace2, and double knockout mice. We report here that BACE1 mice display a complex phenotype. A variable but significant number of BACE1 offspring died in the first weeks after birth. The surviving mice remained smaller than their littermate controls and presented a hyperactive behavior. Electrophysiologically, subtle alterations in the steady-state inactivation of voltage-gated sodium channels in BACE1-deficient neurons were observed. In contrast, bace2 knockout mice displayed an overall healthy phenotype. However, a combined deficiency of BACE2 and BACE1 enhanced the bace1–/– lethality phenotype. At the biochemical level, we have confirmed that BACE1 deficiency results in an almost complete block of Aβ generation in neurons, but not in glia. As glia are 10 times more abundant in brain compared with neurons, our data indicate that BACE2 could indeed contribute to Aβ generation in the brains of Alzheimer disease and, in particular, Down syndrome patients. In conclusion, our data challenge the general idea of BACE1 as a safe drug target and call for some caution when claiming that no major side effects should be expected from blocking BACE1 activity.
Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women.

Although cancer of the vagina is rare and occurs principally in women over age 50 in the form of epidermoid carcinoma 8 girls (15-22) between 1966 and 1969 with adenocarcinoma of the vagina (clear-cell or endometrial) were seen at 2 Boston hospitals. The 4 controls (female) for each case were born within 5 days of the patient and on the same type of service (ward or private). The association between treatment of the mothers (7 or 8) with estrogen diethylstilbestrol during the pregnancies and the development of adenocarcinoma of the vagina in the girls is highly significant (p less than 0.00001). All 7 mothers began therapy in the first trimester and received either a constant dose administered to term or a continually increasing dose given almost to term. Other factors with lower levels of significance are maternal bleeding in the study pregnancy (p less than 0.05) and any prior pregnancy loss (p less than 0.01). Non-significant factors include maternal age at time of birth smoking in parents intrauterine x-ray exposure and breast feeding.
Phase I study of temsirolimus in pediatric patients with recurrent/refractory solid tumors.

PURPOSE To determine dose-limiting toxicities, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of weekly intravenous temsirolimus, a mammalian target of rapamycin (mTOR) signaling pathway inhibitor, in pediatric patients with recurrent or refractory solid tumors. PATIENTS AND METHODS Cohorts of three to six patients 1 to 21 years of age with recurrent or refractory solid tumors were treated with a 1-hour intravenous infusion of temsirolimus weekly for 3 weeks per course at one of four dose levels: 10, 25, 75, or 150 mg/m(2). During the first two courses, pharmacokinetic and pharmacodynamic evaluations (phosphorylation of S6, AKT, and 4EBP1 in peripheral-blood mononuclear cells) were performed. RESULTS Dose-limiting toxicity (grade 3 anorexia) occurred in one of 18 evaluable patients at the 150 mg/m(2) level, which was determined to be tolerable, and an MTD was not identified. In 13 patients evaluable for response after two courses of therapy, one had complete response (CR; neuroblastoma) and five had stable disease (SD). Four patients (three SDs + one CR) remained on treatment for more than 4 months. The sum of temsirolimus and sirolimus areas under the concentration-time curve was comparable to values in adults. AKT and 4EBP1 phosphorylation were inhibited at all dose levels, particularly after two courses. CONCLUSION Weekly intravenous temsirolimus is well tolerated in children with recurrent solid tumors, demonstrates antitumor activity, has pharmacokinetics similar to those in adults, and inhibits the mTOR signaling pathway in peripheral-blood mononuclear cells. Further studies are needed to define the optimal dose for use in combination with other antineoplastic agents in pediatric patients.
Evolving relations between the practices of nurses and patients and a new patient portal

The paper offers preliminary reflections on a patient portal that is part of a glocal digital infrastructure – an EHR - currently being implemented at 18 hospitals in two of the five Danish regions covering more than half of the population. We focus on the evolving relations between the technology and the practices of nurses and patients in a rehabilitation program after a blood cloth, with a specific interest in how the rehabilitation infrastructure promotes clinical governance and patient empowerment. Our analytical lens is that of patient empowerment, understood broadly as the patient’s capacity for and experience of self-care within the infrastructure. This, we contend, may be seen as a specific and increasingly important aspect of clinical governance.
Menopause and breast cancer risk.

Age at menopause and type of menopause from hospital records of breast cancer patients were compared with similar information reported by a national probability sample of women. The national sample comprised 3581 women who responded to the 1960-1962 National Health Examination Survey. The cancer series consisted of 3887 patients selected from those reported to the Connecticut Cancer Registry between 1950 and 1959. No substantial bias was identified when the validity of the comparison and the effect of the relatively large number of breast cancer patients whose menopause histories were deficient were evaluated. Overall, surgically induced menopause was associated with a reduction in breast cancer risk to about 60% of that experienced by women having natural menopause induced before age 35, but induction up to age 50 was protective. There was little effect in the 10 years following the surgical procedure, but substantial reduction occurred in all subsequent periods. Among women with menopause induced before age 35, breast cancer risk stayed as low as 1/3 that expected 30 and more years later. Relative risk of breast cancer increased with age at natural menopause. Women with natural menopause at age 55 or older had twice the breast cancer risk experienced by those whose menopause occurred before age 45. The relative risk of breast cancer associated with late natural menopause was greatest after age 70.
Comparing Object Play in Captive and Wild Dolphins

Examining the role of play as related to individual and group social development is important to understanding a species. The purpose of our study was to examine whether there is a difference in the frequency of object play exhibited by dolphins from two groups – one captive and one wild. Data were collected with underwater video, with resulting videos event sampled for bouts of play involving various objects used by dolphins. From 159 hr of video data, roughly 102 min featured object play: 75 min of dolphins from RIMS and 26 min for dolphins near Bimini. A total of 304 bouts of object play were documented from or between dolphins at RIMS, while 73 bouts were
Sexual behavior and responsiveness to sexual stimuli following laboratory‐induced sexual arousal

Sexual excitement can be seen as an action disposition. In this study sexual arousal was expected to generate sexual action and to increase interest and responsiveness to sexual stimuli. In two experiments, male and female participants were exposed to a neutral or a sexual film. We measured genital and subjective responses to the film, and sexual behavior following the laboratory visit. In Experiment 2, film exposure was followed by a task in which participants rated the sexual arousability of neutral and sexual pictures. Rating time of the sexual pictures served as an index for sexual interest. Responsiveness to the sexual pictures was measured by modulation of spinal tendinous (T) reflexes. Sexual activity, but not sexual desire, was higher for participants in the sexual film condition than for participants in the neutral condition. Sexual interest and responsiveness to still pictures were not higher for participants in the sexual film condition than for those in the neutral film condition. In addition, men who saw the neutral film showed a greater responsiveness to still pictures than men who saw the sexual film. The results support the view of sexual arousal as an emotional state generating action tendencies and actual sexual behavior.
Effects of Salt and Water Stresses on Germination and Seedling Growth of Artemisia vulgaris L

ABSTRACT: Salinity and drought stresses are common environmental factors which reduce germination and growth of plants. This experiment was conducted to study the effects of salinity and drought stress on seed germination and seedling growth of mugwort (Artemisia vulgaris L.). The salinity and drought treatments were applied by NaCl and PEG-6000, respectively. Different concentration of NaCl (0 to 100 mM) and PEG-6000 (0 to -0.25 Mpa) were used for seed treatment. The purpose of the present research was to survey the influence of salt and water stresses on seed germination, seedling growth, fresh and dry weight in mugwort.
Apoptosis and the expression of Bcl-2 and Bax in patients with endometrioid, clear cell, and serous carcinomas of the uterine endometrium.

OBJECTIVES Clear cell and serous carcinoma of the uterus are rare types of endometrial carcinomas. This study was designed to investigate the differential occurrence of apoptosis, Bcl-2, and Bax in endometrioid, clear cell, and serous carcinomas. METHODS In a total of 28 endometrial carcinomas as well as 4 samples of normal postmenopausal endometria, apoptotic changes were examined using molecular biochemical techniques. The expression of Bcl-2 and Bax proteins was also investigated by immunohistochemical staining with appropriate antibodies. RESULTS Labeling of DNA in situ indicated that apoptotic cells were sporadically seen in postmenopausal endometrium (5.2 +/- 2.1, n = 4). In contrast, cells undergoing apoptosis apparently were detected in endometrioid carcinoma (29.3 +/- 3.7, n = 20), and their numbers increased intensely in clear cell (49.5 +/- 5.6, n = 5) and serous carcinomas (50.8 +/- 6.0, n = 3). Autoradiographic analysis revealed that high-molecular-weight DNA was predominant in postmenopausal endometrium. However, a DNA ladder was identified in 7 of 10 carcinomas. Although Bcl-2 was immunonegative or faintly immunopositive in all cases, many cases of endometrioid carcinoma (43.6 +/- 4.1%, n = 20) were immunopositive for Bax, unlike postmenopausal endometrium (17.6 +/- 6.7%, n = 4). Moreover, the number of cells expressing Bax increased in clear cell (60.4 +/- 6.5%, n = 5) and serous carcinomas (66.8 +/- 7.6%, n = 3) compared with that in endometrioid carcinoma. CONCLUSIONS These results indicate that apoptosis occurs in a specific population of cells in different histologic components of endometrial carcinomas. The expression of Bax, but not of Bcl-2, might suggest histologic differentiation in endometrial carcinomas.
Factors in decision making following genetic counseling for pre‐natal diagnosis of de novo chromosomal rearrangements

A retrospective survey of genetic counselors was conducted in order to identify practice patterns and factors that influence a patient's decision making when a de novo translocation is diagnosed pre‐natally. Different variables that influence patients' decisions about pregnancy management were assessed and compared. Specifically, the type of rearrangement and/or knowledge of the breakpoints, risks provided for abnormal outcome, anxiety, fetal ultrasound findings and personal reasons for parental decisions were evaluated. Our findings suggest that patient anxiety level significantly predicts pregnancy management decisions. This information may be of benefit in identifying potential areas of education for genetic counselors as well as other health care providers.
Off-state self-heating, micro-hot-spots, and stress-induced device considerations in scaled technologies

In this paper we show that devices in scaled technologies could undergo self-heating (SH) even in the off-state when subjected to stress conditions that would in turn adversely impact product life-time. We present a detailed methodology in analyzing the impact of off-state SH, thus preventing unintentional overstressing during product stress-screening. We propose an analytical model for modeling this effect, verifying it against detailed TCAD simulations and actual hardware (HW) data from 14nm SOI FinFET technology. We show that the amount of off-state SH depends on the actual device size and the circuit layout. Additional temperature rise (deltaT) can increase ~2.7x for 2-finger vs. 40-finger FETs. We demonstrate the SH impact on off-state hot-carrier-injection (HCI) induced degradation based on HW data. Finally, we analyze its impact on backend electromigration (EM) showing that median-time-to-fail (MTTF) can be reduced as much as 80% in large multi-finger (MF) FETs when off-state SH is taken into account.
Dental caries prevalence in children and adolescents with cystic fibrosis: a qualitative systematic review and recommendations for future research.

BACKGROUND Children and adolescents with cystic fibrosis (CF) are believed to be at low risk for dental caries, but this paradigm has not been critically evaluated. AIMS To conduct a qualitative systematic review of the international literature on dental caries prevalence in children and adolescents with CF and make recommendations on future CF-related oral health research priorities. DESIGN The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was used to identify relevant studies published between 1960 and 2013. RESULTS The search resulted in 696 studies. Fifteen publications were included in the qualitative systematic review. Ten studies concluded that children with CF had significantly lower caries prevalence than control children, three studies reported that children with CF had higher caries prevalence, and two studies found no difference by CF status. Of the seven studies including age-based subgroup analyses, only one study supported the current paradigm. All studies had limitations that may bias study results. CONCLUSIONS While children with CF may be a lower risk for dental caries, adolescents with CF may not be at lower caries than those without CF. Additional research is needed to evaluate a potentially flawed paradigm regarding caries risk in children and adolescents with CF.
Cytotoxic, antibacterial and antioxidant activities of extracts of the bark of Melia azedarach (China Berry)

Nature provides a variety of drugs and medicinal agents derived from plants. This study was conducted to determine antimicrobial, antioxidant and cytotoxic activities of extracts of Melia azedarach bark with methanol/water (9:1 v/v), chloroform, butanol, hexane, water and ethyl acetate. For the determination of the antimicrobial activities, the agar well diffusion method was employed. Cytotoxicity was studied by brine shrimp lethality assay; antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl. The chloroform extract was active against Enterobacter aerogenes and Proteus mirabilis, the ethyl acetate extract had highest antibacterial spectrum against Pseudomonas aeruginosa, the n-hexane extract had highest inhibition against E. aerogenes, the aqueous extract showed highest activities against P. mirabilis, the butanol fraction showed highest activities against E. aerogenes and the methanolic extract was highly active against P. mirabilis.
A comprehensive Study on spectrum sensing and resource allocation for cognitive cellular network

The wireless communication system are facing the spectrum shortage and interference problem for the latest developments in the cellular industry. These problems can be solved by using a new technology known as Cognitive Radio Network (CRN) where dynamic utilization of spectrum takes place. Cognitive Radio is an intelligent transceiver system that continuously monitors its radio environment in search of the unused frequency slots (known as spectrum holes) which can be seen in the environment, analyze and take decisions from threshold. This frequency slots are used up by secondary user in the absence of primary user. In this paper, we have analyzed four different types of spectrum sensing techniques, challenges faced by spectrum sensing method and strategies to solve this problem.
Study on the aging characteristics of transformer oil-paper insulation based on improved time domain dielectric spectroscopy

In order to study the aging characteristics of oil-paper insulation, and thus providing reliable basis for condition assessment of transformer insulation, in this paper, we carried out accelerated thermal aging test in Laboratory environment and researched the polarization/depolarization current of samples by using time domain dielectric spectroscopy. Then, we proposed an algorithm for improving time domain dielectric spectroscopy by wavelet transform theory. The results show that time domain dielectric spectroscopy can reflect the overall polarization processes of oil-paper insulation and as the aging time increases, the peak value of the dielectric spectroscopy increases. The improved wavelet transform algorithm can effectively improve the time domain dielectric spectrum, thus the main polarization processes of oil-paper insulation is clearly shown in the time domain dielectric spectroscopy. Peaks' value and time of improved time domain dielectric spectroscopy correspond to the intensity and responding speed of different polarization processes, and peaks value has a good linear relationship with aging times which can be used to quantitatively assess the aging condition of different part of oil-paper insulation.
Modular antigen-translocation as a novel vaccine strategy for allergen-specific immunotherapy

Purpose of review The purpose of the present review is to describe recent approaches aimed at improving the treatment of allergic diseases through allergen-specific immunotherapy (SIT). Special emphasis will be given to the approach based on specific targeting of the major histocompatibility complex (MHC) class-II antigen-presentation pathway. Recent findings It is well recognized that IgE-mediated allergic diseases including rhinitis, atopic eczema and allergic asthma are increasing worldwide to a pandemic dimension. The only curative treatment remains allergen-SIT, which, however, requires a long treatment time of 3–5 years with up to 80 injections to confer protection. Recent findings strongly indicate that the treatment time and the number of injections could be drastically reduced by turning immunotherapy to a true vaccination. Direct injection of allergen extracts into the inguinal lymph nodes and targeting the MHC class-II antigen-presentation pathway by recombinant modular antigen-translocating vaccines have the potential to cure allergic diseases in a very short time. Summary The mechanisms of allergic inflammation can be divided into four distinct stages: T cell activation, organ-selective homing, survival/reactivation and effector functions. On the basis of this new knowledge several novel concepts aimed at treating allergic diseases have been developed. The area of allergen-SIT is experiencing exciting developments. Reciprocal regulation of effector and regulatory T cell subsets is being more and more used to develop novel strategies for immunomodulation.
Anatomical and Pathological Considerations in Percutaneous Vertebroplasty and Kyphoplasty: A Reappraisal of the Vertebral Venous System

Objectives. To focus attention of the clinician on the anatomy and (patho)physiology of the vertebral venous system, so as to offer a tool to better understand and anticipate (potential) complications that are related to the application of percutaneous vertebroplasty and kyphoplasty. Background. Percutaneous vertebroplasty and kyphoplasty are newly developed, minimally invasive techniques for the relief of pain and for the strengthening of bone in vertebral body lesions. With the clinical implementation of these techniques, a number of serious neurologic and cardiopulmonary complications have been reported in the international medical literature. Most complications appear to be related to the extrusion of bone cement into the vertebral venous system. Methods. The literature about complications of percutaneous vertebroplasty and kyphoplasty is reviewed, and the anatomic and (patho)physiologic characteristics of the vertebral venous system are reported. Based on what is currently known from the anatomy and physiology of the vertebral venous system, the procedures of percutaneous vertebroplasty and kyphoplasty are analyzed, and suggestions are made to improve the safety of these techniques. Conclusions. Thorough knowledge of the anatomic and (patho)physiologic characteristics of the vertebral venous system is mandatory for all physicians that participate in percutaneous vertebroplasty and kyphoplasty. To reduce the risk of cement extrusion into the vertebral venous system during injection, vertebral venous pressure should be increased during surgery. This can be achieved by operating the patient in the prone position and by raising intrathoracic venous pressure with the aid of the anesthesiologist during intravertebral instrumentation and cement injection. Intensive theoretical and practical training, critical patient selection, and careful monitoring of the procedures, also taking into account patient positioning and intrathoracic and intra-abdominal pressures, will help to facilitate low morbidity outcomes inthese very promising minimally invasive techniques.
System-on-Chip (SOC) design for CNC system

In the paper, a new complete design and implementation of a System on Chip solution for CNC system is presented, using FPGA technology. It integrates a general-purpose processor, a Motion-Control core, an Axis-Control core, a PLC core, a Wishbone compliant bus and a standard external communication interface on a single FPGA. The proposed CNC system based on SOC has the advantages of high speed and robust. They demonstrate a promising alternative to developing CNC systems.
Trust Based Security Enhancement Mechanism For Neighbor Discovery Protocol In IPV 6

In recent days Internet Protocol Version 6 is being developed to extend the properties of IPv4. However, several transition issues and attacks could have potentially severe security implication if not properly addressed. The newly addressed features of IPv6 introduce many newer protocol attacks. To avoid all attacks and attack features in IPv6 it has been used Neighbor Discovery Protocol (NDP) to discover other nodes on the link. Neighbor discovery includes both router discover and redirect mechanisms. Commonly router discovery is used to discover the presence of router and their corresponding parameters on an attached link. An original router discovery mechanism does not offer any security mechanisms that are venerable to many kinds of security exploitations. In this paper we investigate various kinds of existing router discovery method’s weakness. So our proposed system is used to improve existing router discovery mechanism and introduce a new security mechanism for router discovery process. In this paper we propose a new trust based neighbor discovery protocol. Our simulation result shows that our proposed system provides decreased bandwidth, reduces transmission delay and traffic overhead.