Miracle-dz/UniFAR-FTUs huggingface dataset:
The Use of Neurocomputational Models as Alternatives to Animal Models in the Development of Electrical Brain Stimulation Treatments

Recent publications call for more animal models to be used and more experiments to be performed, in order to better understand the mechanisms of neurodegenerative disorders, to improve human health, and to develop new brain stimulation treatments. In response to these calls, some limitations of the current animal models are examined by using Deep Brain Stimulation (DBS) in Parkinson's disease as an illustrative example. Without focusing on the arguments for or against animal experimentation, or on the history of DBS, the present paper argues that given recent technological and theoretical advances, the time has come to consider bioinspired computational modelling as a valid alternative to animal models, in order to design the next generation of human brain stimulation treatments. However, before computational neuroscience is fully integrated in the translational process and used as a substitute for animal models, several obstacles need to be overcome. These obstacles are examined in the context of institutional, financial, technological and behavioural lock-in. Recommendations include encouraging agreement to change long-term habitual practices, explaining what alternative models can achieve, considering economic stakes, simplifying administrative and regulatory constraints, and carefully examining possible conflicts of interest.
Supercritical Fluids : Nanotechnology and Select Emerging Applications

REPORT DOCUMENTATION PAGE OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES COVERED (From To) 09-06-2004 Technical Paper 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER
The pharmacological pathways of GnRH mediating the inhibition of mammary tumours: implications in humans and domestic animals.

The Gonadotropin-Releasing Hormone (GnRH) exists in two isoforms, GnRH-I and GnRH-II, in most vertebrates, including humans. Both of these isoforms and their respective receptors have been found in many healthy and pathologic extra nervous system tissues, such as cells found in cancers of the reproductive systems and, in particular, in breast cancer. GnRH analogues are used as therapeutic agents in the case of sex-hormone-dependent tumours. Besides acting as suppressors of steroidogenesis, GnRH analogues seem to interfere with mitogenic signal transduction pathways, thus behaving as negative regulators of tumour growth and progression. GnRH analogues counteract the proliferating effects of both epidermal growth factor (EGF) and insulin like growth factor (IGF-I); additionally, it affects the mitogen-activated protein kinase (MAPK) cascade and modulates the activity of the urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitory (PAI) system, which is involved in the process of metastasis. In addition, GnRH analogues decrease the expression of many growth factors involved in the development of human uterine myomas (as well as endometriotic tissue), such as the vascular endothelial growth factor (VEGF), which is deeply implied in the angiogenesis of many benign and malignant tumours, including breast cancer. Angiogenesis is one of the primary processes leading to the progression and metastasis of breast cancer cells, and a key therapeutic goal in the fight against tumours is the blocking of new vessel sprouts. Given these premises, this review provides an update on the background of anti-neoplastic properties of GnRH analogues.
Influence of timing and magnitude of arterial wave reflection on left ventricular relaxation.

The influence of timing and magnitude of arterial wave reflection (WR) on afterload-dependent relaxation was evaluated in patients with a variety of heart diseases (group 1, age < 30 yr; group 2, age > 40 yr) and in dogs. While both femoral arteries were compressed (FC), WR returned just after the dicrotic notch (early diastole) in group 1 but before the dicrotic notch (late systole) in group 2. The time constant of the left ventricular pressure decay (tau) was shortened during FC in group 1, whereas it was prolonged in group 2. In dogs, a constriction of the thoracic aorta induced a late systolic augmentation of WR with a prolongation of tau (cf. group 2), whereas constriction of the lower abdominal aorta induced an early diastolic augmentation of WR with a shortening of tau (cf. group 1). With aortic constriction, coronary flow increased, and there was a close correlation between the peak change in backward aortic pressure and that in coronary flow regardless of the timing of WR. Thus the time at which WR returns during the cardiac cycle may have an important effect on left ventricular relaxation and coronary flow.
Saccade Adaptation and Visual Uncertainty

Visual uncertainty may affect saccade adaptation in two complementary ways. First, an ideal adaptor should take into account the reliability of visual information for determining the amount of correction, predicting that increasing visual uncertainty should decrease adaptation rates. We tested this by comparing observers' direction discrimination and adaptation rates in an intra-saccadic-step paradigm. Second, clearly visible target steps may generate a slower adaptation rate since the error can be attributed to an external cause, instead of an internal change in the visuo-motor mapping that needs to be compensated. We tested this prediction by measuring saccade adaptation to different step sizes. Most remarkably, we found little correlation between estimates of visual uncertainty and adaptation rates and no slower adaptation rates with more visible step sizes. Additionally, we show that for low contrast targets backward steps are perceived as stationary after the saccade, but that adaptation rates are independent of contrast. We suggest that the saccadic system uses different position signals for adapting dysmetric saccades and for generating a trans-saccadic stable visual percept, explaining that saccade adaptation is found to be independent of visual uncertainty.
Accommodation: Preventing Injury in Transplantation and Disease1

Humoral immunity, as a cause of damage to blood vessels, poses a major barrier to successful transplantation of organs. Under some conditions, humoral immunity causes little or no damage to an organ graft. We have referred to this condition, in which a vascularized graft functions in the face of humoral immunity directed against it, as “accommodation. ” In this paper, we review changes in the graft and in the host that may account for accommodation, and we consider that what we call accommodation of organ grafts may occur widely in the context of immune responses, enabling immune responses to target infectious organisms without harming self-tissues.
The development of the acoustico‐vestibular centres in the chick embryo in the absence of the afferent root fibers and of descending fiber tracts

The developmental response of secondary sensory centers to the removal or addition of associated sense organs (eye, ear, nose) has been investigated extensively, especially in Amphibia (see Piatt, '48) I n birds and mammals the same problem has been met with occasionally in connection with a somewhat different experimental procedure ; namely, the production of changes in the peripheral fields which affected primarily the sensory ganglia, and only indirectly the secondary centers in the spinal cord (mainly, limb extirpation experiments). Practically all authors agree that ablation results in a hypoplasia of the associated centers, and that the resulrt of peripheral overloading is a hyperplasia (reviews in Detwiler, '36; Harrison, '35; Piatt, '48). The finer details of these reactions have been studied only in one instance with the help of the silver impregnation method, namely, in the case of eye extirpation in the frog embryo by LarseEl ( '31). This author
Student Views of Effective Online Teaching in Higher Education

This study investigated student views of online instruction in higher education courses. Data were collected from 199 online students using a Web-based instrument. The instrument consisted of items that were expected to be associated with effective online teaching. One overall effective teaching item was regressed onto twenty-five items in order to identify a core group of items that related most strongly with effective teaching. Seven items emerged as the core group: adapting to student needs, using meaningful examples, motivating students to do their best, facilitating the course effectively, delivering a valuable course, communicating effectively, and showing concern for student learning. These seven items explained 86.2% of the variability in effective teaching and provided one definition of effective online teaching. In open-ended comments, the students wrote that effective teachers are visibly and actively involved in the learning, work hard to establish trusting relationships, and provide a structured, yet flexible classroom environment.
[Karyotype of Fasciola sp. obtained from Korean cattle]

As a series of systematic classification for Korean common liver fluke, Fasciola sp. , karyotype was investigated by means of the modified air-drying technique and of the regular Giemsa staining, Also, C-staining method was applied for detailed karyological analysis from the germ cells of the fluke. The following is a brief summary of the leading facts gained through the experiment. Korean Fasciola sp. was classified into three types based on their chromosomal complements; individuals with 20 or 30 chromosomes and with a 20/30 mosaic constitution. Worms having 30 chromosomes represent a triploid form with 3 sets of 10 basic chromosomes, while those with 20 chromosomes were diploid and mosaic individuals were 2n/3n mixoploid. The frequency of the individual type calculated is as follows; 67.45% of 212 flukes examined was of diploid, 10.85%, triploid, and the rest, 21.7%, mixoploid, respectively. In many cases, two or three types were found in the peculiar bovine host while single type inhabitant was about 20% out of 52 cases. The twenty chromosomes consisted of 1 parir of large metacentrics, 4 pairs of medium-sized subtelocentrics, and 5 pairs of small submetacentrics, while constitution of the thirty chromosomes was nearly interpreted as a triploid form with 3 sets of 10 basic chromosomes. The high centromeric indexes of both types are the first pairs among all the examined, and 37.93% was of diploid and 47.93%, triploid, respectively. In mixoploid individuals, constitution of the chromosomes of diploid or triploid cells was the same as that of diploid or triploid individuals. All the chromosomes of the germ cells in both types showed C-band around the centromeic region and especially the chromosomes no's 3, 7, and 8 showed a remarkable C-band distinguished from other chromosomes. The variance for the sizes of the worms and the eggs were not parallel with three different genotypes in Korean common liver fluke.
Short Article: Attentional Orientation Induced by Temporarily Established Self-Referential Cues

Self-referential stimuli such as self-face surpass other-referential stimuli in capture of attention, which has been attributed to attractive perceptual features of self-referential stimuli. We investigated whether temporarily established self-referential stimuli are different from other-referential cues in guiding voluntary visual attention. Temporarily established self-referential or friend-referential shapes served as central cues in Posner's endogenous cueing task. We found that, relative to friend-referential cues, self-referential cues induced smaller cueing effect (i.e., the difference in reaction times to targets at cued and uncued locations) when the interstimulus interval was short but larger cueing effect when the interstimulus interval was long. Our findings suggest that temporarily established self-referential cues are more efficient to capture reflexive attention at the early stage of perceptual processing and to shift voluntary attention at the later stage of perceptual processing.
Use of sertraline, paroxetine and fluvoxamine by nursing women

Background The pharmacological treatment of depression in nursing women requires information on the magnitude of medication exposure to the infant that may occur through breast milk. Aims To examine serum concentrations of antidepressants in infants exposed to these medications through breast-feeding. Method Maternal and infant serum concentrations of sertraline, paroxetine and fluvoxamine were determined with high-performance liquid chromatography (limit of detections=1 ng/ml). Results No detectable medication was present in any infant exposed to paroxetine (n=16) or fluvoxamine (n=4). Among infants exposed to sertraline (n=30), detectable medication was present in 24% of serum samples. A significant negative correlation was found between infant age and infant serum concentration. Sertraline was significantly more likely to be detected in an infant if the mother's daily dose was 100 mg or higher. No adverse sequelae occurred in any infant. Conclusions This study shows that paroxetine, fluvoxamine and sertraline produce minimal exposure to infants when taken by nursing mothers.
Proton therapy for cancer treatment

Proton beam therapy is the latest advancement in the treatment of various types of cancer. It is a precise form of radiotherapy. It uses a beam of protons to target the cancer cells and destroys them. It scores high on precision and effectiveness when compared to other conventional cancer treatments like surgery, chemotherapy and xray radiotherapy. Proton beam therapy destroys the cancerous cells without harming the healthy cells. Thus it considerably reduces the side-effects that accompany conventional cancer treatments. Supporters say the technology allows physicians to treat a broad spectrum of cancers with few adverse effects, while more precisely targeting tumor cells with higher doses of radiation. Detractors say proton beam therapy is hugely expensive and has not been shown to be superior to conventional radiation treatment. With proton beam therapy, physicians use a cyclotron to accelerate protons and fire them directly into tumor cells with submillimeter precision. Because healthy tissue is largely spared, oncologists can, in theory, deliver much higher doses of radiation, while improving local control and reducing the risk for recurrence and morbidities.
A conical phased array for reliable and discrete communications

This paper presents a phased array antenna printed on a conical structure. The array is designed to ensure reliable communications using a compact reconfigurable beam forming network embedded in a fuze. Simulations are carried out to assess the performances of such an array (in terms of radiation) and define the best phase weight coefficient for each radiating element of the antenna array. The numerical results demonstrate that the proposed array allows maintaining a significant gain in a given direction (transverse to the fuze axis) while presenting low radiation levels in undesirable and sensitive directions.
Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles.

The murine Mf1 and Mfh1 genes have overlapping patterns of expression in the embryo and encode forkhead/winged helix transcription factors with virtually identical DNA binding domains. Previous studies have shown that Mfh1 null mutants have severe cardiovascular defects, including interruptions and coarctations of the aortic arch and ventricular septal defects (Iida et al., Development 124, 4627-4638, 1997). Here, we show that Mf1(lacZ) homozygous null mutants also have a similar spectrum of cardiovascular abnormalities. Moreover, most embryos doubly heterozygous for Mfh1(tm1) and Mf1(lacZ) die before birth with interruptions and coarctations of the aortic arch, dysgenesis of the aortic and pulmonary valves, ventricular septal defects, and other cardiac anomalies. This nonallelic noncomplementation and the similar patterns of expression of the two genes in the mesenchyme and endothelial cells of the branchial arches, outflow tract, and heart suggest that Mf1 and Mfh1 play interactive roles in the morphogenesis of the cardiovascular system. Implications for the development of human congenital heart defects are discussed.
Chaos, predictability, and idealization in physics

METHODOLOGICAL PRELIMINARIES: THE PHYSICAL WORLD AND ITS DESCRIPTIONS Doing science is more interesting than philosophizing about it, and I am therefore a bit hesitant to start the present contribution with methodological considerations. This appears imperative, however, when speaking of fundamental aspects of predictability, because prediction definitely refers to descriptions of the physical world rather than to the world itself. Predictions about the gross position of the World Trade Center in the next week are easy, predictions about who will be there are more problematic. Examples of this sort force on us the necessity to choose a description, modelization, or idealization of the physical world before we can meaningfully speak of predictability. It is a familiar fact that theories used by physicists are not an exact description of Nature. Not only are different theories more or less accurate in different applications, but the conceptual frameWe discuss the unpredictability of physical systems due to chaos. A meaningful analysis requires the choice of a specific idealization of the system, so that its time evolution is well described by deterministic dynamics. In that case, the existence of a Lyapunov exponent λ>0 (chaos) creates a real wall of unpredictability, which is particularly impressive in the case of weather predictions because it stands just a few weeks away. works of these theories do not fit very well together. (Think of classical and quantum mechanics). There is a naïve temptation to say that we only want to consider the best, most accurate theory. But this attitude cannot be maintained because some very useful concepts make sense only in low-grade approximate theories. For instance we may want to talk about the viscosity of nitroglycerin at room temperature, even though an accurate definition of this concept would lead to serious difficulties, because nitroglycerin is not stable thermodynamically. The same can be said about the density of diamond at normal pressure and temperature. And the concept of a human being is so messy from a physical point of view, with its constant exchange of matter with the outside world, that you don’t even want to think about it. To summarize, we speak of the world in terms of various idealized descriptions, or theories. These theories differ not only in being more or less accurate, but also in proposing concepts that are more or less useful.
Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance).

PURPOSE To evaluate the efficacy of maintenance sunitinib after chemotherapy for small-cell lung cancer (SCLC). PATIENTS AND METHODS The Cancer and Leukemia Group B 30504 trial was a randomized, placebo-controlled, phase II study that enrolled patients before chemotherapy (cisplatin 80 mg/m(2) or carboplatin area under the curve of 5 on day 1 plus etoposide 100 mg/m(2) per day on days 1 to 3 every 21 days for four to six cycles). Patients without progression were randomly assigned 1:1 to placebo or sunitinib 37.5 mg per day until progression. Cross-over after progression was allowed. The primary end point was progression-free survival (PFS) from random assignment for maintenance placebo versus sunitinib using a one-sided log-rank test with α = . 15; 80 randomly assigned patients provided 89% power to detect a hazard ratio (HR) of 1.67. RESULTS One hundred forty-four patients were enrolled; 138 patients received chemotherapy. Ninety-five patients were randomly assigned; 10 patients did not receive maintenance therapy (five on each arm). Eighty-five patients received maintenance therapy (placebo, n = 41; sunitinib, n = 44). Grade 3 adverse events with more than 5% incidence were fatigue (19%), decreased neutrophils (14%), decreased leukocytes (7%), and decreased platelets (7%) for sunitinib and fatigue (10%) for placebo; grade 4 adverse events were GI hemorrhage (n = 1) and pancreatitis, hypocalcemia, and elevated lipase (n = 1; all in same patient) for sunitinib and thrombocytopenia (n = 1) and hypernatremia (n = 1) for placebo. Median PFS on maintenance was 2.1 months for placebo and 3.7 months for sunitinib (HR, 1.62; 70% CI, 1.27 to 2.08; 95% CI, 1.02 to 2.60; one-sided P = .02). Median overall survival from random assignment was 6.9 months for placebo and 9.0 months for sunitinib (HR, 1.28; 95% CI, 0.79 to 2.10; one-sided P = .16). Three sunitinib and no placebo patients achieved complete response during maintenance. Ten (77%) of 13 patients evaluable after cross-over had stable disease on sunitinib (6 to 27 weeks). CONCLUSION Maintenance sunitinib was safe and improved PFS in extensive-stage SCLC.
The Implications of Acute Rejection for Allograft Survival in Contemporary U.S. Kidney Transplantation

Background We examined the frequency and clinical impact of acute rejection (AR) in contemporary U.S. kidney transplantation. Methods Data for Medicare-insured kidney transplant recipients in 2000 to 2007 (n=48,179) were drawn from the United States Renal Data System. AR events were ascertained from Organ Procurement and Transplantation Network reports. AR was subclassified as antibody (Ab)-treated AR or other management (non–Ab-treated AR). Associations of AR with subsequent all-cause graft loss were estimated with time-varying Cox regression. Covariates included recipient, donor, and transplant factors in the United Network for Organ Sharing Kidney Allocation Review Committee survival model. Results The frequencies of non–Ab-treated AR per 100 graft-years at risk among standard criteria donor recipients over the first 6, 12, 24, and 36 months after transplantation were 9.93, 8.43, 5.71, and 4.70, respectively. Non–Ab-treated AR was consistently more than twice as common as Ab-treated AR by risk period and donor type. Development of Ab-treated AR predicted a greater risk of graft loss than non–Ab-treated AR. The relative risk for graft loss from Ab-treated AR continuously increased with later timing of AR after transplantation, whereas risk associated with non–Ab-treated AR peaked for events reported in months 13 to 24 after kidney transplantation. Regardless of the diagnosis time, the relative risk of graft loss was higher in the first 89 days after a given AR report compared with 90 days and beyond. Conclusions AR events recognized later after transplantation have more serious graft loss implications, especially within the first 89 days after AR reporting. This observation may reflect reduced intensity of monitoring, delays in diagnosis, or clinicopathologic features of late AR.