Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Cholinergic Drugs and Cognitive Training on Dementia: 2-Year Follow-Up

Several studies have shown that pharmacological and cognitive treatments for Alzheimers’s disease improve cognitive function for short periods, but fewer studies have evaluated the efficacy of those treatments for longer (2-year) periods. An initial sample of 68 subjects with mild Alzheimer’s disease underwent clinical and cognitive evaluation. After evaluation, subjects were assigned to four different groups and participated in a 2-year follow-up study. Group 1 (n = 14) received combined drug and cognitive stimulation, group 2 (n = 20) received only drug treatment, group 3 (n = 14) received only cognitive stimulation, and group 4 (n = 30) received no treatment at all. Results confirmed previous investigation, cognitive and combined stimulation improved patients’ performance throughout the 1st year; however, all groups deteriorated gradually throughout the 2nd year of treatment. According to this evidence, it can be concluded that we cannot stop cognitive deterioration after 2 years of treatment, although deterioration is greater and its progress faster in patients not receiving any treatment at all.
A Functional and Neuropathological Testing Paradigm Reveals New Disability-Based Parameters and Histological Features for P0180–190-Induced Experimental Autoimmune Neuritis in C57BL/6 Mice

We assessed novel disability-based parameters and neuropathological features of the P0180–190 peptide-induced model of experimental autoimmune neuritis (EAN) in C57BL/6 mice. We show that functional assessments such as running capacity provide a more sensitive method for detecting alterations in disease severity than a classical clinical scoring paradigm. We performed detailed ultrastructural analysis and show for the first time that tomaculous neuropathy is a neuropathological feature of this disease model. In addition, we demonstrate that ultrastructural assessments of myelin pathology are sufficiently sensitive to detect significant differences in both mean G-ratio and mean axon diameter between mice with EAN induced with different doses of pertussis toxin. In summary, we have established a comprehensive assessment paradigm for discriminating variations in disease severity and the extent of myelin pathology in this model. Our findings indicate that this model is a powerful tool to study the pathogenesis of human peripheral demyelinating neuropathies and that this assessment paradigm could be used to determine the efficacy of potential therapies that aim to promote myelin repair and protect against nerve damage in autoimmune neuritides.
Clustered Importance Sampling for Fast Reflectance Rendering

In realistic image synthesis, a major challenge is how to account for largescale, complex lighting environments in an ecient and robust way. This thesis presents a simple and ecient method for bidirectional importance sampling from large-scale illumination sources.The method is based on a clustered representation of the potential light source samples. Combined with an ecient BRDF sampling strategy, an importance function can rapidly be constructed and used to select the lighting samples that will contribute the most in the rendering equation. Most existing methods similar to the one presented in this thesis are restricted to environment lighting only; in contrast, the proposed algorithm can also be used in local lighting scenarios where the illumination exists on an unstructured point set, which may not have the same natural parameterization as an environment map.
Detecting Pedestrian Abnormal Behavior Based on Fuzzy Associative Memory

Visual analysis of human motion in video sequences has attracted more and more attention to computer visions in recent years. In order to indicate the pedestrian movement in Intelligent Security Monitoring System, an articulated model of human is presented. According to the contour angle movement of bodypsilas major organs, a fuzzy function is designed. Fuzzy Associative Memory (FAM) is proposed to infer abnormal behavior of the walker. The overall degree of the anomaly is resulted from the fuzzy membership of the pedestrian's organ using a three layer FAM. In the realization of the system a combined method of centroid and fuzzy discriminant is presented. Fuzzy discriminant can detect irregularities and implements initiative analysis of body's behaviors in visual surveillance. Therefore, we can recognize some abnormal behaviors and then alarm. The results show that the new algorithm has better performance.
Steelmaking-continuous casting scheduling problem with interval type 2 fuzzy random due dates

In this paper we propose a steelmaking-continuous casting scheduling (SCCS) model, where due dates are interval type 2 fuzzy random variables. Our proposed model is based on just-in-time (JIT) idea. We assign satisfaction level to charge's completion time according to interval type 2 membership functions. Support position of membership functions depend upon the expected due dates, which are exponentially distributed random variables. In this scheduling model, limit for total waiting time between processing and waiting time before casting stage are considered as interval type 2 fuzzy sets. The interval type 2 fuzzy random optimization problem is converted to a crisp and nonlinear optimization problem by using the symmetric approach. Finally an example is presented to show the application of proposed model.
Cloning, nucleotide sequence, and characterization of mtr, the structural gene for a tryptophan-specific permease of Escherichia coli K-12

The mtr gene of Escherichia coli K-12 encodes an L-tryptophan-specific permease. This gene was originally identified through the isolation of mutations in the 69-min region of the chromosome, closely linked to argG. Cells with lesions in mtr display a phenotype of 5-methyltryptophan resistance. The mtr gene was cloned by using the mini-Mu system. The amino acid sequence of Mtr (414 codons), deduced by DNA sequence analysis, was found to be 33% identical to that of another single-component transport protein, the tyrosine-specific permease, TyrP. The hydropathy plots of the two permeases were similar. Possible operator sites for the tyrosine and tryptophan repressors are situated within the region of DNA that is likely to be the mtr promoter.
Pharmacodynamic principles in chemical teratology: dose-effect relationships.

A deterministic approach to the bimolecular and irreversible interaction of chemicals with receptors was used to develop pharmacodynamic relationships which are applicable in teratology. Pharmacokinetic principles governing the rates of absorption, distribution, metabolism and elimination of drugs were incorporated into a general model to yield equations which quantitate the effects of two classes of chemical teratogens. Compounds such as thalidomide and cyclophosphamide, called class I teratogens, have no minimum embryopathic dose, and there is a linear relation with a negative slope between the dose of teratogen and the logarithm of the fraction of unaffected embryos or fetuses. The slope of the graph and the TD5O (dose which produces 50% embryopathy) were related to the teratogen-receptor association rate constant and the integral of drug amount in the receptor compartment over time. Drugs such as hydroxyurea and 5-fluorouracil, called class II teratogens, have dose-effect curves which are related to the same factors at large doses. However, these compounds also have a minimum dose intercept which can be related to a threshold number of drug-receptor interactions which elicits the initial effect. These relationships, in general, characterize drugs which attach irreversibly to cell receptors in the process of producing their pharmacologic or toxic effects.
Effect of tension on flap perfusion: Laboratory and clinical findings

Centuries ago scientific reports were frequently written in the first person. Authors sometimes described their circumstances very clearly, often mentioning the weather and specifically describing the patients about whom they were writing. While our current conventions mandate a more detached tone, precedent clearly exists for writing in a more personal way. Because this article is being written to honor Dr. Thomas K. Hunt on the occasion of his retirement from active practice, and because of the nature of the report itself, I will make occasional use of the first person and the article will read like a cross between science and story. Upon first entering Dr. Hunt’s Wound Healing Laboratory in 1983, I was motivated to ‘‘get to the bottom’’ of wound healing. Michael Banda and David Knighton had performed, under Dr. Hunt’s direction, several experiments showing that isolated cultures of macrophages responded to hypoxic conditions by secreting an angiogenesis factor. As someone with a background in biochemistry and cell biology, I was motivated to look at the biochemical interactions in the healing wound, which I later did. When Dr. Hunt told me that he wanted me to start with tissue oxygen measurements, I objected. After all, what business did someone who had done 3 years of surgical training have making oxygen measurements? Dr. Hunt told me that when he started out doing research, he didn’t know where he was going either. He thought it would be best for me to learn something about oxygen measurements. I did the measurements. Sometime during my first month in research, I met the Swedish surgeon Kent Jonsson who was concluding his tenure in the laboratory. He was finishing a project of measuring oxygen tension in delayed and undelayed random-pattern flaps in dogs. I was skeptical of the oxygen measurements. The platinum electrode used in the measurements would sometimes wander—and this made me suspicious of the data. I spent the first month arguing with Drs. Jonsson and Hunt about what the oxygen data actually meant and whether the data were reliable. By the end of my time with Dr. Hunt, I believed that the most important predictor of surgical wound healing (with the exception of bacteria) was perfusion of the wound. This research was done to investigate the effect of tension on perfusion of random-pattern flaps in the canine model. The findings that I made in dogs were later confirmed in humans.
Living Life With My Child’s Pain: The Parent Pain Acceptance Questionnaire (PPAQ)

Objective:Parents’ emotional, cognitive, and behavioral responses are highly influential on children’s pain and functional outcomes. One important response to pediatric pain is acceptance: the degree to which an individual participates in routine daily activities in the presence of pain and is willing to let pain be a part of their life without efforts to control or avoid it. However, no tool currently exists to assess parents’ own acceptance of their child’s pain. The aim of this study was to validate the Parent Pain Acceptance Questionnaire (PPAQ). Materials and Methods:The PPAQ was administered to 310 parents of youth with chronic pain in an outpatient pediatric headache program and a day hospital pain rehabilitation program. An exploratory factor analysis revealed 2 factors for the PPAQ: an 11-item Activity Engagement scale and a 4-item Acceptance of Pain-related Thoughts and Feelings scale. Results:The PPAQ total score and subscales demonstrated strong internal consistency. Greater parent pain acceptance was positively associated with child pain acceptance, and was negatively correlated with parent protective behaviors, parent minimizing behaviors, parent and child pain catastrophizing, and child fear of pain. Parent protective behaviors and child pain acceptance both served as mediators of the relationship between parent pain acceptance and child functional disability. Conclusions:The PPAQ is a valid measure of parent pain acceptance and may provide valuable insights into parent responses to child pain and the ways in which parent acceptance influences child outcomes. Clinical implications and suggestions for future research are discussed.
On a characteristic of cortical arousals in individuals with obstructive sleep apnea.

STUDY OBJECTIVE To identify the frequency and duration of those arousals exceeding fifteen seconds in length, in patients with obstructive sleep apnea. METHODS The polysomnographic tracings from fifty consecutive patients with obstructive sleep apnea were carefully analyzed to delineate the duration of each arousal event. These data were then collated to define the frequency of arousals of differing durations, and the impact thereof on the total time spent in an arousal state. RESULTS Respiratory event related prolonged arousals (> or = 15 seconds) were identified in 100% of the patients. These longer arousals accounted for 22% of all arousals, and 37% of all arousal time. The frequency of the arousals decreased with CPAP treatment, as did the time spent in an arousal state. CONCLUSIONS Patients with obstructive sleep apnea experience frequent respiratory event associated cortical arousals, many of which are greater than fifteen seconds in duration. There is the potential for these more prolonged arousals to be scored as epochs of Wake, which may result in their being reported as contributing to Wake After Sleep Onset (WASO) time, rather than as distinct arousals. This may result in an under-appreciation of both the frequency with which these prolonged arousals may occur, and the potential effect these arousals may have on the severity of the sleep fragmentation.
Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein 3 as Diagnostic Markers of Growth Hormone Deficiency in Infancy

Background: The diagnosis of growth hormone deficiency (GHD) in infancy is difficult, and no specific cutoff value during GH provocative testing is recommended in early life. Methods: Serum insulin-like growth factor I (IGF-I) and serum IGF-binding protein 3 (IGFBP-3) levels were evaluated as diagnostic markers of GHD. Measurements of IGF-I and IGFBP-3 during the 1st year of life were analyzed in 11 patients clinically suspected of having GHD (neonatal hypoglycemia, micropenis, or evidence of other pituitary hormone deficiencies), in whom the diagnosis was later verified. A prospective cohort of 51 healthy infants served as controls. Results: The sensitivity of IGF-I as a diagnostic marker of GHD was 90% (10 out of 11 patients) with a cutoff value of –2 standard deviations (SD), and the sensitivity of IGFBP-3 measurements was 81% (9 out of 11 patients) with a cutoff value below –2 SD. One patient had serial measurements before initiation of GH treatment where the IGF-I was fluctuating (3 of 6 slightly above –2 SD), whereas all IGFBP-3 measurements were below –2 SD. Conclusions: The IGF-I had a high sensitivity in detecting infants with GHD. The combination of IGF-I and IGFBP-3 increased the diagnostic sensitivity. We speculate that assessment of IGF-I and IGFBP-3 may add diagnostic value in infants suspected of having GHD and furthermore that values below –2 SD are highly suggestive of GHD.
Insulin-like Growth Factor-1 Induces Adhesion and Migration in Human Multiple Myeloma Cells via Activation of 1-Integrin and Phosphatidylinositol 3-Kinase / AKT Signaling 1

Insulin-like growth factor-1 (IGF-I) is a growth and survival factor in human multiple myeloma (MM) cells. Here we examine the effect of IGF-I on MM cell adhesion and migration, and define the role of 1 integrin in these processes. IGF-I increases adhesion of MM.1S and OPM6 MM cells to fibronectin (FN) in a timeand dose-dependent manner, as a consequence of IGF-IR activation. Conversely, blocking anti1 integrin monoclonal antibody, RGD peptide, and cytochalasin D inhibit IGF-I-induced cell adhesion to FN. IGF-I rapidly and transiently induces association of IGF-IR and 1 integrin, with phosphorylation of IGF-IR, IRS-1, and p85. IGF-I also triggers phosphorylation of AKT and ERK significantly. Both IGF-IR and 1 integrin colocalize to lipid rafts on the plasma membrane after IGF-I stimulation. In addition, IGF-I triggers polymerization of F-actin, induces phosphorylation of p125 and paxillin, and enhances 1 integrin interaction with these focal adhesion proteins. Importantly, using pharmacological inhibitors of phosphatidylinositol 3 kinase (PI3-K) (LY294002 and wortmannin) and extracellular signalregulated kinase (PD98059), we demonstrate that IGF-I-induced MM cell adhesion to FN is achieved only when PI3-K/AKT is activated. IGF-I induces a 1.7–2.2 (MM.1S) and 2–2.5-fold (OPM6) increase in migration, whereas blocking anti-IGF-I and anti1 integrin monoclonal antibodies, PI3-K inhibitors, as well as cytochalasin D abrogate IGF-I-induced MM cell transmigration. Finally, IGF-I induces adhesion of CD138 patient MM cells. Therefore, these studies suggest a role for IGF-I in trafficking and localization of MM cells in the bone marrow microenvironment. Moreover, they define the functional association of IGF-IR and 1 integrin in mediating MM cell homing, providing the preclinical rationale for novel treatment strategies targeting IGF-I/IGF-IR in MM.
Mitigation of Reverse Short-Channel Effect With Multilayer TiN/Ti/TiN Metal Gates in Gate Last PMOSFETs

This letter investigates the mitigation of reverse short-channel effect (RSCE) using multilayer atomic layer deposition (ALD) TiN/PVD Ti/CVD TiN metal gates (MG) for the p-channel metal-oxide-semiconductor field-effect transistors fabricated the by gate-last process. It is found that work function (WF) of multilayer ALD titanium nitride/physical vapor deposition titanium/chemical vapor deposition titanium nitride (ALD TiN/PVD Ti/CVD TiN) MG in devices of short channels is larger than in devices of long channels. This mainly results from different ALD TiN crystal orientations for devices with different gate lengths, that is, TiN(100) for devices with short gate length, whereas TiN(111) for devices with long gate length. The WF of ALD TiN(100) is larger than TiN(111). Meanwhile, because of the property of PVD sputtering, the Ti layer is thinner in devices of short channels than in devices of long channels. Our results on MOSCAP show that the flat-band voltage (Vfb) for TiN MG with a Ti layer is reduced by 0.2 V. Taking all the aforementioned into account, Vth roll-up is suppressed as the gate length shrinks, leading to the mitigation of RSCE.
Simultaneous Mutation of Methylated Lysine Residues in Histone H3 Causes Enhanced Gene Silencing, Cell Cycle Defects, and Cell Lethality in Saccharomyces cerevisiae

ABSTRACT The methylation of specific lysine residues in histone H3 is integral to transcription regulation; however, little is known about how combinations of methylated lysine residues act in concert to regulate genome-wide transcription. We have systematically mutated methylated histone lysine residues in yeast and found that the triple mutation of H3K4, H3K36, and H3K79 to arginine (H3 K4,36,79R) is lethal. The histone H3 K4,36,79R mutant causes a mitotic cell cycle delay and a progressive transcription defect that initiates in telomere regions and then spreads into the chromosome. This effect is mediated by the silent information regulator (SIR) silencing complex, as we observe increased binding of the SIR complex to genomic regions adjacent to yeast telomeres in the H3 K4,36,79R mutant and deletion of SIR2, SIR3, or SIR4 rescues the lethal phenotype. Curiously, a yeast strain in which the histone methyltransferase genes are simultaneously deleted is viable. Indeed, deletion of the histone methyltransferase genes can suppress the H3 K4,36,79R lethal phenotype. These and other data suggest that the cause of lethality may in part be due to the association of histone methyltransferase enzymes with a histone substrate that cannot be methylated.
Early Carotid Atherosclerosis in Overweight Non-diabetic Individuals is Associated with Subclinical Chronic Inflammation Independent of Underlying Insulin Resistance

Overweight in children and young adults is an increasing problem in Western industrialized countries with potential impact on cardiovascular morbidity. Whether early arterial wall thickening in these subjects mainly results from the often associated insulin resistance syndrome or from increased subclinical chronic inflammation probably triggered by adipose tissue is still under discussion. We therefore determined insulin sensitivity index (ISI) by performing an euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate 1 mU/kg/min) and high-sensitivity C-reactive protein (hsCRP) levels in relation to the intima-media thickness (IMT) at the common carotid artery (high resolution ultrasound; 13 MHz) in 81 young (age 33 +/- 1 years), moderately overweight subjects. To reduce the number of confounding variables, subjects with disturbances in glucose metabolism (75 g oral glucose tolerance test) and hypertension were excluded. As expected, higher BMI was positively correlated with increased IMT (r = 0.358; p = 0.001). After multiple regression analysis, hsCRP levels independently correlated to IMT (r = 0.251; p = 0.03), even after adjusting for age, sex, BMI, ISI, LDL cholesterol and smoking as cofactors. However, taking all above listed factors into account, glucose-clamp assessed insulin sensitivity was not correlated with IMT. Thus, overweight might trigger inflammatory mechanisms leading to vascular wall hypertrophy independent of the insulin resistance syndrome already early in life.
DIVE: Fluid Display for 3D CG Manipulation with Visual Continuity

In this paper, we propose "DIVE", an intuitive 3D CG manipulation system with fluid display. DIVE displays 3D CG objects on the surface of a tank that is filled with opaque liquid. DIVE's user inserts his/her arm into the fluid display, and manipulates the CG objects by the hand under the liquid surface. DIVE also displays a CG hand (virtual hand) on the surface instead of the unseen hand under the surface. The virtual hand seems to be joined to the user's real arm above the surface. Its appearance and motion are synchronized with that of the unseen hand. Using DIVE, we can feel as if we are manipulating 3D CG objects with our own hand. Experimental results showed that the prototype could provide acceptable accuracy and stability in a part of the fluid display.
The Florida “truth” anti-tobacco media evaluation: design, first year results, and implications for planning future state media evaluations

OBJECTIVES To outline the design and present selected findings from the evaluation of a state counter-advertising, anti-tobacco media campaign. The appropriateness of the design for states developing media evaluations is discussed. DESIGN Four cross sectional, telephone surveys of the 12–17 year old population were used to track and monitor advertising and campaign awareness, confirmed awareness, and receptivity. The Florida baseline and one year surveys were used with two parallel national surveys in a quasi-experimental design to assess attitude and smoking related behaviour change attributable to the campaign. MEASURES Awareness was measured by self report, confirmed awareness by unaided description, and receptivity by self reports of how well advertisements were liked, talked to friends about, and made one think about whether or not to smoke. Eleven attitude and three smoking behaviour items for Florida (treatment) and a national (control) population were compared at baseline and after 12 months. RESULTS Significant increases in ad specific awareness, confirmed, receptivity, and campaign awareness, and confirmed awareness were reached by the sixth week. They continued to rise through the first year. No attitude and only minor behaviour differences were noted between the treatment and comparison populations at baseline. By the end of the first year, Florida youth had stronger anti-tobacco attitudes and better behaviour patterns than the comparison population. CONCLUSIONS The industry manipulation strategy used in the Florida campaign resulted in high rates of recall, significant changes in attitudes/beliefs, and reduced rates of smoking behaviour among youth.