Miracle-dz/UniFAR-FTUs huggingface dataset:
Profiling proteins related to amyloid deposited brain of Tg2576 mice

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder that is characterized by the extracellular deposition of β‐amyloid and intracellular hyperphosphorylation of tau in the cortex and hippocampus of the brain. These characterizations are caused by abnormal expression, modification and deposition of certain proteins. Post‐translational modifications of proteins including oxidation and nitration might be involved in the pathogenesis of AD. In this study, AD‐related proteins were identified in the cortex of Tg2576 mice used as a model for studying AD. Tg2576 mice express high levels of the Swedish mutated form of human β‐amyloid precursor protein (APP) and generated high levels of β‐amyloid in the brains. Using Western blotting and two‐dimensional electrophoresis, proteins with differences in expression, oxidation and nitration in the cortex of Tg2576 mice brains were compared to littermate mice brains used as a control. The proteins with different expression levels were identified using matrix‐assisted laser desorption/ionization‐time of flight and liquid chromatography‐tandem mass spectrometry analyses. As a result, 12 proteins were identified among 37 different proteins using the PDQuest program. Furthermore, two proteins, laminin receptor and α‐enolase, were more susceptible to oxidative modification in the brains of Tg2576 mice compared to those of littermates. Similarly, α‐enolase, calpain 12, and Atp5b were more modified by nitration in brains of Tg2576 mice than those of littermates. Taken together, these proteins and their modifications may play an important role in the plaque deposition of Tg2576 mice brains.
A Comparison of Intrathecal Morphine-6-Glucuronide and Intrathecal Morphine Sulfate as Analgesics for Total Hip Replacement

Postoperative analgesia was assessed after intrathecal administration of morphine-6-glucuronide (M6G) 100 micro g and 125 micro g in 75 patients undergoing total hip replacement. Analgesia was excellent and was similar to that obtained after intrathecal administration of morphine sulfate 500 micro g. Visual analog pain scores recorded postoperatively were low (median = 0) and were similar in all three groups. However, at 6 and 10 h after operation significantly more patients in the M6G 125 group recorded pain as 0 compared with patients in the morphine group (P < 0.04, P < 0.01) and significantly more patients in the M6G 100 group recorded pain as 0 at 24 h after operation compared with patients in the morphine group (P < 0.04). Postoperative meperidine consumption using a patient-controlled system was also similar in each of the three treatment groups. Nausea and emesis occurred frequently in all groups; morphine (nausea 88%, vomiting 76%), M6G 100 micro g (nausea 76%, vomiting 64%), and M6G 125 micro g (nausea 88%, vomiting 60%). Respiratory depression occurred in two and three patients, respectively, in the M6G 100-micro g and 125-micro g groups but did not occur in any patient who received morphine sulfate. The lack of statistical significance in the difference in incidence of respiratory depression between the groups may represent a type II error. However, the risk of late respiratory depression developing after administration of any intrathecal opioid necessitates careful postoperative observation of patients. As M6G is a potent intrathecal analgesic further investigation of this drug using small doses may be useful. (Anesth Analg 1996;83:1055-9)
Transoesophageal echocardiographic evaluation of central venous catheter positioning using Peres’ formula or a radiological landmark-based approach: a prospective randomized single-centre study†

Background. The lower superior vena cava (SVC), near its junction with the right atrium (RA), is considered the ideal location for the central venous catheter tip to ensure proper function and prevent injuries. We determined catheter insertion depth with a new formula using the sternoclavicular joint and the carina as radiological landmarks, with a 1.5 cm safety margin. The accuracy of tip positioning with the radiological landmark-based technique (R) and Peres’ formula (P) was compared using transoesophageal echocardiography. Methods. Real-time ultrasound-guided central venous catheter insertion was done through the right internal jugular or subclavian vein. Patients were randomly assigned to either the P group (n=93) or the R group (n=95). Optimal catheter tip position was considered to be within 2 cm above and 1 cm below the RA–SVC junction. Catheter tip position, abutment, angle to the vascular wall, and flow stream were evaluated on a bicaval view. Results. The distance from the skin insertion point to the RA–SVC junction and determined depth of catheter insertion were more strongly correlated in the R group [17.4 (1.2) and 16.7 (1.5) cm; r=0.821, P<0.001] than in the P group [17.3 (1.2) and 16.4 (1.1) cm; r=0.517, P<0.001], with z=3.96 (P<0.001). More tips were correctly positioned in the R group than in the P group (74 vs 93%, P=0.001). Abutment, tip angle to the lateral wall >40°, and disrupted flow stream were comparable. Conclusions. Catheter tip position was more accurate with a radiological landmark-based technique than with Peres’ formula. Clinical trial registration. Clinical Trial Registry of Korea: https://cris.nih. go.kr/cris/index.jsp KCT0001937.
Quantifying the Effects of Expert Selection and Elicitation Design on Experts’ Confidence in Their Judgments About Future Energy Technologies

Expert elicitations are now frequently used to characterize uncertain future technology outcomes. However, their usefulness is limited, in part because: estimates across studies are not easily comparable; choices in survey design and expert selection may bias results; and overconfidence is a persistent problem. We provide quantitative evidence of how these choices affect experts’ estimates. We standardize data from 16 elicitations, involving 169 experts, on the 2030 costs of five energy technologies: nuclear, biofuels, bioelectricity, solar, and carbon capture. We estimate determinants of experts’ confidence using survey design, expert characteristics, and public R&D investment levels on which the elicited values are conditional. Our central finding is that when experts respond to elicitations in person (vs. online or mail) they ascribe lower confidence (larger uncertainty) to their estimates, but more optimistic assessments of best‐case (10th percentile) outcomes. The effects of expert affiliation and country of residence vary by technology, but in general: academics and public‐sector experts express lower confidence than private‐sector experts; and E.U. experts are more confident than U.S. experts. Finally, extending previous technology‐specific work, higher R&D spending increases experts’ uncertainty rather than resolves it. We discuss ways in which these findings should be seriously considered in interpreting the results of existing elicitations and in designing new ones.
Interactions and Reactions of Ferritin with DNA*

Ferritin, normally considered a cytoplasmic iron-storage protein, is also found in the nuclei of some cells. There is no current agreement about its function(s) in this environment. Proposals include DNA protection, provision of iron to nuclear enzymes, and regulation of transcription initiation, but evidence for these functions is scanty. We have shown previously that H-ferritin subunits can be cross-linked to chromosomal DNA in vivo (Thompson, K. J., Fried, M. G., Ye, Z., Boyer, P., and Connor, J. R. (2002) J. Cell Sci. 115, 2165–2177). Here we describe systematic analyses of DNA binding and the covalent stability of DNA in the presence of ferritins from several different sources. Our data show that the H-subunit of human ferritin binds DNA, whereas neither the L-subunit nor the ferroxidase-deficient 222-mutant of the H-subunit has detectable binding activity. DNA binding is without significant preference for base composition, sequence, or the nature of DNA ends. H- and L-ferritins and ferritins of mixed subunit composition stimulate the conversion of superhelical plasmid DNA to the relaxed form. The sensitivity of this conversion to glycerol suggests that DNA is nicked by a free radical mechanism. The rate of nicking correlates with the iron content of the ferritin and is strongly inhibited by chelators. Ferritin-dependent nicking is characterized by a kinetic lag that is not seen in control reactions containing free iron species. These results suggest that the release of iron from ferritin is an important part of the nicking mechanism. The potential role of ferritin as a protector of the genome is discussed in the context of these results.
Lower brain-derived neurotrophic factor in patients with prader-willi syndrome compared to obese and lean control subjects.

CONTEXT Brain-derived neurotrophic factor (BDNF) haploinsufficiency is associated with hyperphagia and obesity in both animals and humans. BDNF appears to function downstream of the leptin-melanocortin signaling pathway to control energy balance. The potential role of BDNF in the etiology of the severe hyperphagia associated with PWS has not been previously explored. OBJECTIVE The aim was to compare BDNF concentrations in subjects with PWS and obese controls (OC) and lean controls (LC). DESIGN AND SETTING We conducted a cross-sectional study at an outpatient clinical research center. PARTICIPANTS We studied 13 subjects with PWS [five females and eight males; mean + or - sd: age, 11.0 + or - 4.1 yr; body mass index (BMI)-Z, 2.05 + or - 0.78], 13 OC (eight females, five males; age, 12.3 + or - 2.7 yr; BMI-Z, 2.18 + or - 0.61), and 13 LC (six females, seven males; age, 12.4 + or - 2.6 yr; BMI-Z, -0.57 + or - 0.73). MAIN OUTCOME MEASURE BDNF was measured in serum and plasma by ELISA. Analysis of covariance adjusted for age, sex, and BMI-Z. RESULTS All groups were comparable for age (P = 0.50) and sex distribution (P = 0.49). BMI-Z was comparable between PWS and OC (P = 0.89) and lower in LC (P < 0.001). Adjusted serum BDNF was comparable (P = 0.35) in OC (mean + or - sem: 13.5 + or - 1.2 ng/ml) and LC (19.2 + or - 1.3 ng/ml), but lower in PWS (8.3 + or - 1.2 ng/ml; P = 0.01 vs. OC; P = 0.03 vs. LC). Adjusted plasma BDNF in PWS (217 + or - 130 pg/ml) was lower than OC (422 + or - 126 pg/ml; P = 0.02), but statistically comparable with LC (540 + or - 143 pg/ml; P = 0.10). CONCLUSIONS Lower BDNF in PWS suggests insufficient central BDNF production because BDNF in peripheral circulation is believed to reflect cerebral BDNF output. Decreased BDNF may be a potential cause for the disordered satiety and morbid obesity associated with PWS. Further studies are needed to confirm this preliminary pilot study in a larger cohort of patients with PWS.
Implantation and maintenance of functional human bone marrow in SCID-hu mice.

Human fetal bone fragments implanted in the immunodeficient C.B-17 scid/scid (SCID) mouse were shown to sustain active human hematopoiesis in vivo. Human progenitor cell activity was maintained for as long as 20 weeks after implantation and was associated with multilineage differentiation in the engrafted bone. Thus, the bone implants provided stem cells as well as the microenvironment requisite for their long-term maintenance and multilineage differentiation. Administration of human erythropoietin (Epo) stimulated human erythropoiesis in human bone implants. This animal model may facilitate direct analysis of a wide variety of physiologic and pathologic conditions of human bone marrow (BM) in vivo.
and Minority Communities? Testing O'Connor and Thomas: Does the Use of Eminent Domain Target Poor

In dissenting from the US Supreme Court’s 2005 Kelo decision upholding the use of eminent domain for private-to-private transfers of property, Justices O’Connor and Thomas asserted, based on the history of urban renewal, that eminent domain for private development would disproportionately hurt poor and minority communities. This study uses US census data and a sample of redevelopment project areas using or identifi ed for the use of eminent domain to test the assertions of Justices O’Connor and Thomas. Results reveal that such project areas are, in fact, disproportionately populated by those who are poor, minority and less educated.
Burden of Community-Acquired Pneumonia in North American Adults

Abstract To determine the burden of community-acquired pneumonia (CAP) affecting adults in North America, a comprehensive literature review was conducted to examine the incidence, morbidity and mortality, etiology, antibiotic resistance, and economic impact of CAP in this population. In the United States, there were approximately 4.2 million ambulatory care visits for pneumonia in 2006. Pneumonia and influenza continue to be a common cause of death in the United States (ranked eighth) and Canada (ranked seventh). In 2005, there were > 60 000 deaths due to pneumonia in persons aged ≥ 15 years in the United States alone. The hospitalization rate for all infectious diseases increased from 1525 hospitalizations per 100 000 persons in 1998 to 1667 per 100 000 persons in 2005. Admission to an intensive care unit was required in 10% to 20% of patients hospitalized with pneumonia. The mean length of stay for pneumonia was ≥ 5 days and the 30-day rehospitalization rate was as high as 20%. Mortality was highest for CAP patients who were hospitalized; the 30-day mortality rate was as high as 23%. All-cause mortality for CAP patients was as high as 28% within 1 year. Streptococcus pneumoniae continues to be the most frequently identified pathogen associated with CAP, and pneumococcal resistance to antimicrobials may make treatment more difficult. The economic burden associated with CAP remains substantial at > $17 billion annually in the United States. Despite the availability and widespread adherence to recommended treatment guidelines, CAP continues to present a significant burden in adults. Furthermore, given the aging population in North America, clinicians can expect to encounter an increasing number of adult patients with CAP. Given the significance of the disease burden, the potential benefit of pneumococcal vaccination in adults is substantial.
Microbeads: a novel multiparticulate drug delivery technology for increasing the solubility and dissolution of celecoxib

Abstract The purpose of this study was to develop a novel multipaticulate drug delivery technology suitable for the delivery of pre-solubilized celecoxib to the gastrointestinal tract and more specifically to the colon. The solubility of celecoxib in a range of oils, surfactants and co-solvents was evaluated. Celecoxib was solubilized in mixtures of these vehicles to produce liquid formulations. The in vitro dissolution of these liquid formulations was assessed and the data obtained was used to design microbead formulations containing celecoxib dissolved within an emulsion/micellar solution core. Microbead formulations were optimized to increase drug loading, avoid precipitation and to achieve good in vitro dissolution performance. An optimized formulation with a celecoxib loading of 6% w/w was produced and yielded an in vitro dissolution result of 80% over 6 h. The structure of these microbead formulations was characterized using light microscopy to reveal a correlation between droplet size and dissolution performance.
Subjective response to alcohol: a critical review of the literature.

BACKGROUND Subjective response to alcohol (SR), which reflects individual differences in sensitivity to the pharmacological effects of alcohol, may be an important endophenotype in understanding genetic influences on drinking behavior and alcohol use disorders (AUDs). SR predicts alcohol use and problems and has been found to differ by a range of established risk factors for the development of AUDs (e.g., family history of alcoholism). The exact pattern of SR associated with increased risk for alcohol problems, however, remains unclear. The Low Level of Response Model (LLR) suggests that high-risk individuals experience decreased sensitivity to the full range of alcohol effects, while the Differentiator Model (DM) asserts that high risks status is associated with increased sensitivity to alcohol's positive effects but decreased sensitivity to negative effects. AIMS The current paper (1) reviews two prominent models of subjective response, (2) reviews extant laboratory-based research on subjective response, (3) highlights remaining gaps in our understanding and assessment of subjective response, and (4) encourages collaborative efforts to address these methodological and conceptual concerns. METHODS This paper reviews studies which employed placebo-controlled and non-placebo-controlled alcohol challenge paradigms to assess a range of alcohol effects including impairment, stimulation, and sedation. RESULTS The research literature provides at least partial support for both the LLR and DM models. High-risk individuals have been shown to have a reduced response to alcohol with respect to sedative or impairing effects, particularly on the descending limb of the blood alcohol curve (BAC). There is also evidence that ascending limb stimulant effects are more pronounced or operate differently for high-risk individuals. DISCUSSION Despite commendable advances in SR research, important questions remain unanswered. Inconsistent results across studies may be attributable to a combination of an inadequate understanding of the underlying construct and methodological differences across studies (e.g., number and timing of assessments across the BAC, inclusion of a placebo condition). With respect to the underlying construct, existing measures fail to adequately distinguish between cognitive/behavioral impairment and sedation, aspects of which may be perceived positively (e.g., anxiolysis) due to their ability to act as negative reinforcers. CONCLUSIONS Addressing the concerns raised by the current review will be integral to making meaningful scientific progress in the field of subjective response.
Scaling Cu Pillars to 20um Pitch and Below: Critical Role of Surface Finish and Barrier Layers

High-performance computing has been aggressively driving pitch and performance requirements for off-chip interconnections over the last several decades, pushing solder-based interconnections to their limits. The most leading-edge Cu pillar technology faces many fundamental challenges in scaling to pitches below 30um, in particular with stress management and increased risks of Au embrittlement as solder volume is reduced All-intermetallic interconnections formed by solid-liquid interdiffusion (SLID) bonding have been concurrently explored to extend solders to finer pitches and improve their performance, but face their own set of manufacturability and reliability challenges that have, so far, limited their use to 3D-ICs. This research comprehensively addresses these challenges with innovative interconnection designs and advances in surface finish metallurgies, which allow for precisely controlled and unique interfacial reactions. A two-fold approach is pursued to: 1) extend scalability of conventional Cu pillars by replacing standard ENEPIG with ultra-thin electroless Pd autocatalytic Au (EPAG) surface finish, and, for further pitch scaling and enhanced electrical and thermal performances, 2) enable void-free, manufacturable all-intermetallic joints solely composed of the metastable Cu6Sn5 phase by introduction of diffusion barrier layers. This paper presents the design, demonstration and characterization of such high-performance solder-based interconnections at 20um pitch, highlighting the strategic role of surface finish and diffusion barrier layers for potential further pitch scaling.
Pervasive developmental disorder and parental adaptation: previewing and reviewing atypical development with parents in child psychiatric consultation.

Parenting young children with pervasive developmental disorder engenders unique sustained stresses, which have been termed "burden of care. " One specific source of stress for parents is the children's uneven developmental progress, in which delays and accelerations of adaptive functioning may exist side by side. This paper proposes a clinical method that may be incorporated into periodic child psychiatric consultations with parents of young children who have high-functioning autism or Asperger's disorder. Using a semistructured technique, the clinician reviews with the parents the details of the child's recent developmental course and attempts to identify emergent skills that may serve to preview upcoming developmental issues and gains. This method is aimed at enhancing parental abilities to track and anticipate developmental progress and the resultant shifts in the parent-child relationship, in order to reduce one source of sustained parental stress. Case illustrations of children ages 2-8 years old are discussed in light of recent literature on adaptive issues in families of individuals with a chronic medical or psychiatric condition and, specifically, families of children with pervasive developmental disorder.
Developmental decrease in ethanol inhibition of N-methyl-D-aspartate receptors in rat neocortical neurons: relation to the actions of ifenprodil.

Inhibition of N-methyl-D-aspartate (NMDA) receptor function by ethanol (EtOH) and interactions between EtOH and the noncompetitive NMDA receptor antagonist ifenprodil were examined in neocortical neurons from rat and human embryonic kidney (HEK) 293 cells expressing recombinant NMDA receptors. Ethanol inhibited receptor function at concentrations in the 10 to 100 mM range in cortical neurons. EtOH inhibition of NMDA receptor function decreased as a function of time in culture over a 4-wk period. No difference in EtOH inhibition of AMPA/kainate receptor function was observed in neurons from 2- to 4-wk-old cultures. The time course of decreased EtOH inhibition paralleled a developmental decrease in inhibition by the noncompetitive NMDA receptor antagonist ifenprodil in these cortical neurons. Inhibition by EtOH was decreased in magnitude in the presence of 10 microM ifenprodil in 2- to 3-wk-old cortical neurons, but not in 1-wk-old neurons. Ifenprodil inhibited the function of recombinant NMDA receptors expressed in HEK 293 cells. Consistent with earlier reports, ifenprodil selectively inhibited responses mediated by recombinant receptors containing the NMDAR2B subunit at concentrations up to 10 microM. EtOH also inhibited the function of recombinant NMDA receptors expressed in HEK 293 cells. The potency of EtOH for inhibiting responses differed slightly among receptors containing different R2 subunits, especially at low EtOH concentrations. Finally, ifenprodil did not alter the effect of EtOH on recombinant R2A or 2B-containing NMDA receptors. (ABSTRACT TRUNCATED AT 250 WORDS)