Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroimmunoprotective effects of estrogen and derivatives in experimental autoimmune encephalomyelitis: Therapeutic implications for multiple sclerosis

The extensive literature and the work from our laboratory illustrate the large number of complex processes affected by estrogen that might contribute to the striking ability of 17β‐estradiol (E2) and its derivatives to inhibit clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in mice. These effects require sustained exposure to relatively low doses of exogenous hormone and offer better protection when initiated prior to induction of EAE. However, oral ethinyl estradiol (EE) and fluasterone, which lacks estrogenic side effects, could partially reverse clinical EAE when given after the onset of disease. The three main areas discussed in this review include E2‐mediated inhibition of encephalitogenic T cells, inhibition of cell migration into central nervous system tissue, and neuroprotective effects that promote axon and myelin survival. E2 effects on EAE were mediated through Esr1 (α receptor for E2) but not Esr2 (β receptor for E2), as were its antiinflammatory and neuroprotective effects. A novel finding is that E2 up‐regulated the expression of Foxp3 and CTLA‐4 that contribute to the activity of CD4+CD25+ Treg cells. The protective effects of E2 in EAE suggest its use as therapy for MS, although the risk of cardiovascular disease may complicate treatment in postmenopausal women. This risk could be minimized by using subpregnancy levels of exogenous E2 that produced synergistic effects when used in combination another immunoregulatory therapy. Alternatively, one might envision using EE or fluasterone metabolites alone or in combination therapies in both male and female MS patients. © 2004 Wiley‐Liss, Inc.
Segmentation of Graphical Objects as Maximally Stable Salient Regions

Symbol segmentation is the key to affect the performance of symbol recognition in natural scenes. As experimentally confirmed, MSER is effective in segmenting text but not applicable to segmentation of graphical objects like traffic signs. We propose a color space graphical object segmentation method. It extracts stable region of interest by applying different color similarity threshold to evaluate the stability of proximity among pixels. Experimental results show that it outperforms MSER in segmenting graphical object.
Can a Mobile Phone in a Pocket Reliably Recognize Ambient Sounds?

We investigate how different locations inside clothing influence the ability of a system to recognize activity relevant sounds. Specifically, we consider the recognition of sounds from 9 household and office appliances recorded using an iPhone placed in 2 trouser pockets, 2 jacket pockets, a belt holster and the users’ hand. The aim is not to demonstrate good recognition rates on the above sounds (which has been done many times before) but to compare recognition rates from the individual locations and to understand how to best train the system to be location invariant.
Handbook of Early Childhood Intervention: Guiding Principles for a Theory of Early Intervention: A Developmental–Psychoanalytic Perspective

This chapter presents some guiding principles for a theory of early intervention that result from a developmental psychoanalytic systems perspective. Psychoanalytic thinking has provided important incentives for such a perspective, but recent research has taken this thinking in surprising directions. Our goal is to articulate basic principles, relate them to traditional concerns of psychoanalysis, and update them with current perspectives from the developmental sciences. A number of dialectical themes pervade our principles. First among these is the interplay of biology and culture. Development includes aspects of both domains, and it includes their dynamic influences on each other. All principles of intervention include this interplay. A second theme is the interplay of affiliation and control. Attachment research has emphasized the dimension of affiliation in the developing individual but, equally important, is the dimension of control or the child's developing sense of boundaries. From early infancy on the interventionist must consider both dimensions. A third can be thought of as the interplay of science and mystery in our work. We gain knowledge from our science, but the gain is always to some extent uncertain and singular because we as observers participate in creating that knowledge. Because of our transactions, there is always a zone of mystery. We attempt to minimize uncertainty in our knowledge by using multiple windows of observation and by applying differing methods and points of view.
Initiation of Germination and Inactivation of Bacillus pumilus Spores by Hydrostatic Pressure

The effect of hydrostatic pressures as high as 1,700 atm at 25 C on the heat and radiation resistance of Bacillus pumilus spores was studied. Phosphate-buffered spores were more sensitive to compression than spores suspended in distilled water. Measurements of the turbidity of suspensions, the viability, refractility, stainability, dry weight, and respiratory activity of spores, and calcium and dipicolinic acid release were made for different pressures and times. Initiation of germination occurred at pressures exceeding 500 atm and was the prerequisite for inactivation by compression. The rate of initiation increased with increasing pressure at constant temperature. This result is interpreted as a net decrease in the volume of the system during initiation as a result of increased solvation of the spore components.
Weissenbacher‐Zweymuller Syndrome; Long‐term Follow‐up of Growth and Psychomotor Development

A child with the distinguishing characteristics of Weissenbacher‐Zweymuller syndrome (WZS), a rare syndrome characterized by multiple skeletal and radiological abnormalities, dwarfism and developmental delays, was followed from birth to eight years. Follow‐up showed that the radiographic anomalies eventually disappeared, and that height, motor, cognitive and language development returned to normal by eight years of age. The child's normal development at school age supports the theory that WZS is a dysmaturational, rather than dysplastic, syndrome. Diagnosis of the syndrome at birth is essential to ensure proper management of the child and counselling for the parents.
Do we need a stressor to be stressed? Insights from cardiac regulation1

In consideration of existing contradictory findings, the aim of the present study was to overcome the limitations of traditional cardiac reactivity studies. First, we examined the cardiac activation that takes place in response to ruminating about stress, independently of the presence of a real stressor, and second, we focused on the underlying physiological components of cardiac regulation during rumination, that is, the sympathetic and parasympathetic components. In 60 participants (27 men and 33 women; mean age = 33.4 ± 9.5 years), we recorded cardiac impedance and heart rate during baseline, an Anger Recall Interview, a reading task, and two recovery periods. Rumination was experimentally manipulated by the use of a distracter. Nondistracted participants showed higher sympathetic activity as suggested by shorter pre-ejection period, higher low-frequency heart rate variability (LF-HRV), higher ratio of LF to high frequency HRV (HF-HRV), and diminished parasympathetic activity (lower HF-HRV). The results underscore the association of rumination with a series of well-known risk factors for health.
Heuristic Strategies for Persuader Selection in Contagions on Complex Networks

Individual decision to accept a new idea or product is often driven by both self-adoption and others’ persuasion, which has been simulated using a double threshold model [Huang et al., Scientific Reports 6, 23766 (2016)]. We extend the study to consider the case with limited persuasion. That is, a set of individuals is chosen from the population to be equipped with persuasion capabilities, who may succeed in persuading their friends to take the new entity when certain conditions are satisfied. Network node centrality is adopted to characterize each node’s influence, based on which three heuristic strategies are applied to pick out persuaders. We compare these strategies for persuader selection on both homogeneous and heterogeneous networks. Two regimes of the underline networks are identified in which the system exhibits distinct behaviors: when networks are sufficiently sparse, selecting persuader nodes in descending order of node centrality achieves the best performance; when networks are sufficiently dense, however, selecting nodes with medium centralities to serve as the persuaders performs the best. Under respective optimal strategies for different types of networks, we further probe which centrality measure is most suitable for persuader selection. It turns out that for the first regime, degree centrality offers the best measure for picking out persuaders from homogeneous networks; while in heterogeneous networks, betweenness centrality takes its place. In the second regime, there is no significant difference caused by centrality measures in persuader selection for homogeneous network; while for heterogeneous networks, closeness centrality offers the best measure.
Alcohol drinking patterns and blood pressure.

BACKGROUND Although blood pressure tends to increase with average alcohol consumption, little is known about the effects of drinking patterns on blood pressure. Therefore, the effects of average drinks per day and drinking pattern (defined as the independent and interactive effects of quantity and frequency) on blood pressure were compared. METHODS Data were obtained from a random sample survey of 1,635 household residents in Erie County, New York. Alcohol-blood pressure relationships were examined using multiple regression analyses that controlled for the potentially confounding influence of 13 additional risk factors for elevated blood pressure. RESULTS Consistent with prior research, a positive relationship was found between average drinks per day and diastolic and systolic blood pressure. Analyses examining the effect of drinking pattern indicated that drinking frequency had a positive effect on both diastolic and systolic blood pressure, whereas drinking quantity did not affect either. Furthermore, there was little evidence that the frequency-by-quantity interaction affected blood pressure. CONCLUSIONS Low average alcohol intake and low blood pressure were associated with infrequent drinking, rather than with frequent drinking of small amounts of alcohol. Results suggest that the standard practice of averaging alcohol consumption may obscure important effects of drinking frequency on health.
Results from phase Ib studies of PX-12, a thioredoxin inhibitor in patients with advanced solid malignancies.

2571 Background: PX-12, a small-molecule inhibitor of Thioredoxin-1 (Trx-1) stimulates apoptosis, down-regulates HIF- 1α, VEGF in animal models. High levels of Trx-1 have been linked to chemoresistance in lung cancers. The phase 2 dose of PX-12 was 226 mg/m2 given by 3-h infusion IV x 5 days, q 21d (Ramanathan RK et al. CCR 13; 2109; 2007). Two Phase 1b trials of PX-12 in patients with advanced solid tumors have been completed to determine the safety, tolerability and optimal biologic dose when delivered by prolonged infusion. METHODS PX-12 was administered as a 24-h infusion every q7- 14d starting at 150 mg/m2/day (n=18); or a 72-h infusion q 21d, starting at 300 mg/m2/day (n=14) using a portable delivery pump. RESULTS Both the 24- or 72-h infusion of PX-12 were well tolerated in patients at doses up to 400 mg/m2/day. Common grade 1/2 AE's included fatigue, taste alteration, and odor caused by expired drug metabolite. In the 24 h study the maximal dose evaluated was 450 mg/m2. No DLTs were observed in this study. Since no MTD was reached on 24-h infusion up to 450 mg/m2 dose level, additional higher doses were explored utilizing 72-h infusion. DLT in the 72-h study at the highest dose administered (500 mg/m2/day) included reversible hypoxia with or without pneumonitis. Best response was stable disease in 3 pts (SD): liver cancer and colon cancer (24-h infusion) and rectal cancer (72-h infusion). Pharmacodynamics (PD): PX- 12 lowered circulating Trx-1 levels in patients who had starting Trx-1 levels 3-fold greater than that of the normal population (5.4 ng/mL) including all three SD. Circulating VEGF and FGF-2 levels were also lowered over multiple courses of treatment in these patients. The pharmacokinetics of PX-12 showed a dose dependent increase of Cmax and no accumulation over multiple cycles following a 24 h infusion. CONCLUSIONS Dosing at 400 mg/m2/day appears safe and tolerable as a 24-72-h infusion. Extending the infusion time to 72h appears to decrease the intensity of cough and odor compared to bolus 1-3 h infusion. The PD effect produced by PX-12 was apparent only in those patients with elevated plasma Trx-1 levels. Patients with elevated TRX-1 levels appear to have the best probability of having SD. Supported by ProlX Pharmaceuticals/Oncothyreon through an award from the NCI. [Table: see text].
Visual activity evoked by infrared in humans after dark adaptation

We evaluated the visual response to infrared (IR) in humans after dark adaptation. In seven adult participants, visual perception, visual sensitivity, and the visual response to IR after light adaptation were tested. Over the course of dark adaptation, we found visual perception and sensitivity to our experimental IR stimulus increased, while the relative IR intensity necessary for perception decreased. Visual perception of the IR stimulus was abolished during a transient light exposure; however, when turned back off, perception to the IR stimulus returned for all participants. These novel findings may be relevant for both pre-clinical and clinical visual research.
Altered folate metabolism modifies cell proliferation and progesterone secretion in human placental choriocarcinoma JEG-3 cells

Abstract Folate is an essential B vitamin required for de novo purine and thymidylate synthesis, and for the remethylation of homocysteine to form methionine. Folate deficiency has been associated with placenta-related pregnancy complications, as have SNP in genes of the folate-dependent enzymes, methionine synthase (MTR) and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1). We aimed to determine the effect of altered folate metabolism on placental cell proliferation, viability and invasive capacity and on progesterone and human chorionic gonadotropin (hCG) secretion. Human placental choriocarcinoma (JEG-3) cells cultured in low folic acid (FA) (2 nm) demonstrated 13 % (P<0·001) and 26 % (P<0·001) lower proliferation, 5·5 % (P=0·025) and 7·5 % (P=0·004) lower invasion capacity, and 5 to 7·5 % (P=0·004–0·025) lower viability compared with control (20 nm) or supplemented (100 nm) cells, respectively. FA concentration had no effect on progesterone or hCG secretion. Small interfering RNA (siRNA) knockdown of MTR gene and protein expression resulted in 17·7 % (P<0·0001) lower proliferation and 61 % (P=0·014) higher progesterone secretion, but had no effect on cell invasion and hCG secretion. siRNA knockdown of MTHFD1 gene expression in the absence of detectable changes in protein expression resulted in 10·3 % (P=0·001) lower cell proliferation, but had no effect on cell invasion and progesterone or hCG secretion. Our data indicate that impaired folate metabolism can result in lower trophoblast proliferation, and could alter viability, invasion capacity and progesterone secretion, which may explain in part the observed associations between folate and placenta-related complications.
Analysis of non-uniform temperature-dependent interconnect performance in high performance ICs

Non-uniform temperature profiles along global interconnect lines in high-performance ICs can significantly impact the performance of these lines. This paper presents a detailed analysis and modeling of the interconnect performance degradation due to non-uniform temperature profiles that exist along their lengths, which in turn arise due to the thermal gradients in the underlying substrate. A non-uniform temperature-dependent distributed RC interconnect delay model is proposed for the first time. The model has been applied to a wide variety of interconnect layouts and temperature distributions to quantify the impact on signal integrity issues including clock skew fluctuations.
Identification, by a monoclonal antibody, of a 53-kD protein associated with a tubulo-vesicular compartment at the cis-side of the Golgi apparatus

Purified Golgi membranes of the human intestinal adenocarcinoma cell line Caco-2 were used as an antigen to produce a monoclonal antibody, G1/93, which specifically labels a tubulovesicular compartment near the cis side of the Golgi apparatus, including the first cis-cisterna itself, as visualized by single and double immunoelectron microscopy with antibodies against galactosyltransferase. The antigen recognized by G1/93 was identified as a protein with a subunit size of 53 kD. Pulse-chase experiments revealed that the 53-kD protein dimerizes immediately after synthesis followed by formation of oligomers of approximately 310 kD, probably homohexamers. The protein has a transmembrane topology with only a short cytoplasmic segment as assessed by protease protection experiments. Glycosidase digestion studies indicated that the protein is probably not glycosylated. The unique subcellular distribution of the G1/93 antigen in close vicinity to the cis-Golgi is in line with the notion that this protein may delineate the biosynthetic transport pathway from the endoplasmic reticulum to the Golgi apparatus. Moreover, G1/93 is a useful marker to identify the cis side of the Golgi apparatus in a variety of human cells.
Increased Susceptibility to Ischemic Brain Injury in Neuroplastin 65-Deficient Mice Likely via Glutamate Excitotoxicity

Cell adhesion molecules (CAMs) are involved in synaptic plasticity and neuronal survival in the adult brain. Neuroplastin 65 (Np65), one member of the immunoglobulin superfamily of CAMs, is brain-specific and highly expressed in rodent forebrain. The roles of Np65 in synaptic plasticity have been confirmed, however, whether Np65 affects neuronal survival remains unknown. To address this gap, we generated, to our knowledge, the first Np65 knockout (KO) mice. By occluding middle cerebral artery to perform ischemic stroke model, we showed that Np65 KO mice exhibited more severe neurological deficits and larger infarction volume measured by TTC staining and more apoptotic cells confirmed by TUNEL staining compared to wild type (WT) mice. Besides, western blot analysis showed that the vesicular glutamate transporter-1(VGluT1), and N-Methyl D-Aspartate receptors, including NR1, NR2A, and NR2B were significantly increased in Np65 KO mice compared with WT mice. In contrast, vesicular gamma amino butyric acid transporter (VGAT) levels were unchanged in two genotypes after stroke. Additionally, phosphorylated-extracellular signal-regulated kinase 1/2 levels were significantly increased in Np65 KO mice compared with WT mice after stroke. Together, these results suggest that Np65 KO mice may be more susceptible to ischemic events in the brain.
Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A‐induced bronchoconstriction in asthma patients

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK1/NK2 receptor antagonist, DNK333, on NKA‐induced bronchoconstriction in asthma. A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled, crossover trial. Increasing concentrations of NKA (3.3×10−9 to 1.0×10−6 mol·mL−1) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo. It was observed that DNK333 did not affect baseline lung function but did protect against NKA‐induced bronchoconstriction in those patients. The mean log10 provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was −5.6 log10 mol·mL−1 at 1 h after DNK333 treatment and −6.8 log10 mol·mL−1 after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment. The results shown in this report indicate that DNK333 blocks neurokinin A‐induced bronchoconstriction in patients with asthma.
Post sign-off leakage power optimization

With the scaling down of the CMOS technologies, leakage power is becoming an increasingly important issue in IC design. There is a trade-off between subthreshold leakage power consumption and clock frequency in the circuit; i.e., for higher performance, leakage power consumption must be sacrificed and vice versa. Meanwhile, timing analysis during synthesis and physical design is pessimistic, which means there are some slacks available to be traded for leakage power minimization. This power minimization can be done after the sign-off which is more accurate and realistic than if it is done before the sign-off. The available slack can be traded for leakage power minimization by footprint-based cell swapping and threshold voltage assignment. In this paper, we introduce our post sign-off leakage power optimization problem as a nonlinear mathematical program and solve it by using conjugate gradient (CG) method. We set up a novel transformation technique to manipulate the constraints of the optimization problem to be solved by CG. We show that by doing this optimization we can reduce the leakage power consumption by 34% on average in comparison with no power optimization after sign-off. All experiments are done on the real industrial designs.
Translation as Weighted Deduction

We present a unified view of many translation algorithms that synthesizes work on deductive parsing, semiring parsing, and efficient approximate search algorithms. This gives rise to clean analyses and compact descriptions that can serve as the basis for modular implementations. We illustrate this with several examples, showing how to build search spaces for several disparate phrase-based search strategies, integrate non-local features, and devise novel models. Although the framework is drawn from parsing and applied to translation, it is applicable to many dynamic programming problems arising in natural language processing and other areas.
Gang Crime and the Media in Late Nineteenth-Century London

ABSTRACT This article will offer a fresh perspective on media attitudes towards working-class youth in late Victorian London by looking in detail at a case study of violent youth crime. It offers an analysis of gang crime in the late nineteenth-century capital and explores the use of class and stereotyping in the reporting of working-class youth. It considers the extent to which the problems of violent youth gangs were manipulated by the press to portray the capital as a ‘city out of control’. Finally, it will argue that these contemporary representations of youth helped create a fear that exaggerated the threat posed by gangs.
On the Expected Performance of Systems with Complex Interactions Among Components

A class of combinatorial optimization models is presented for studying certain systems that arise in biology, physics, business, and elsewhere. These systems consist of a finite number of parts. For each part, it is necessary to choose one of several interchangeable components so as to maximize a performance measure of the resulting system that depends on how the chosen parts interact with each other. Probabilistic analysis and computer simulations provide insight into some factors that affect the expected performance of such systems. These models provide the ability to control the interactions among the components and to study the effect of replacing a single component in the system.