Miracle-dz/UniFAR-FTUs huggingface dataset:
Physicochemical stability of cimetidine amorphous forms estimated by isothermal microcalorimetry

The effect of humidity on the physicochemical properties of amorphous forms of cimetidine was investigated using differential scanning calorimetry, isothermal microcalorimetry, and x-ray diffraction analysis. Amorphous forms were obtained by the melting (amorphous form M [AM]) and the cotton candy (amorphous form C [AC]) methods. Thermal behaviors of AM and AC with or without seed crystals were measured using an isothermal microcalorimeter under various conditions of relative humidity (RH) and temperature, respectively. The crystallization kinetics of amorphous solids was analyzed based on 10 kinds of solid-state reaction models. AM transformed into form A at 11% RH, 50°C but transformed into a mixture of form A and monohydrate at 51% and 75% RH at 25°C. The mean crystallization times (MCTs) of the heat flow curve of AM and AC at 11% RH, 50°C were 47.82 and 32.00 hours, respectively, but at 11% RH, 25°C both were more than 4320 hours. In contrast, AC transformed into form A under all storage conditions. The MCTs of AC at 51% and 75% RH were 29.61 and 11.81 hours, respectively; whereas the MCTs of AM were 46.79 and 15.52 hours, respectively. The crystallization of amorphous solids followed the three-dimensional growth of nuclei (Avrami equation) with an induction period (IP). The IP for AM at 11% RH, 50°C was more than 2 times that for AC, but the difference in the crystal growth rate constant (CR) between AC and AM was within 10%. The IP for AM at 75% RH, 25°C was reduced to only 10% of the IP at 51% RH with increasing humidity, but the CR did not change significantly. In contrast, the IP for AC was slightly reduced at 75% RH compared with 51% RH, but the CR was about 5 times greater. At 75% RH, 25°C, the IP and CR of AM were about one-fourth the values of AC. This result suggests that the crystallization process consists of an initial stage during which the nuclei are formed and a final stage of growth.
In Vitro Organogenesis of Liver Tissue a

The high metabolic rate of hepatocytes severely limits the mass of cells which can be transplanted without a vascular supply. We are developing an alternative approach in which vascularized tissue is grown ex vivo for anastamosis into the portal vein. Here, we discuss the key design issues for in vitro organogenesis of vascularized hepatic tissue, describe a fabrication approach for making complex degradable polymer scaffolds to organize cells in three dimensions on the scale of hundreds of microns, and demonstrate the feasibility of using these scaffolds for in vitro tissue organization in mixed-cell cultures.
A three dimensional free body analysis describing variation in the musculoskeletal configuration of the cynodont lower jaw

The evolution of the middle ear from the cynodont craniomandibular bones is one of the key mammalian innovations, and the mechanics underlying this anatomical transformation represents an intriguing paradox. Because the jaw joint of nonmammalian cynodonts was functionally coupled to the inner ear, auditory performance would favor low joint reaction forces. However, this could not be achieved at the expense of feeding performance, favoring high bite forces. The balance of these two seemingly incompatible performance criteria in the context of the morphological diversity of the cynodont lower jaw is poorly understood. Here we derive a series of equations using three dimensional free body analysis that describe the relationship between the orientation and position of the jaw elevator muscles, the position of the jaw articulation relative to the bite point, the joint reaction forces and the bite force in the lower jaw of the nonmammalian cynodont Probainognathus. These equations permit the effects of variation in each variable to be tested independently, yielding three terms that act to limit joint reaction forces without substantially impacting bite force: the reorientation of the resultant muscle force more vertically, shifting the position of the bite point medial to the jaw articulation, and elevating the jaw articulation above the level with the tooth row only when the muscles are oriented principally in the anterior direction. The predictions from our equations provide insights for functional interpretations of patterns of morphological diversity in the cynodont fossil record. They also illustrate that the musculoskeletal configuration of the cynodont lower jaw can be evolutionarily labile without negatively impacting the dual performance criteria of the auditory and feeding system.
Randomized Reliability Study Evaluating Constant-load and Graded-exercise Treadmill Test for Intermittent Claudication

The aim of this randomized study was to compare the reliability of the treadmill test at constant-load (C-test, 3 km/hr; fixed grade of 12%) recommended in Germany with that of the graded-exercise test (G-test, 3 km/hr; increase in grade of 3.5% every 3 minutes) propagated in the United States. In 50 patients with an absolute claudication distance (ACD) in the C-test of between 50 and 400 m, the two treadmill tests were carried out in randomized order on one and the same day, and repeated on 3 days within 1 week. For the initial claudication distance (ICD), the intraclass correlation was 0.88 in the C-test and 0.87 in the G-test. For the ACD the coefficients were identical at 0.91. The within-subject variation (CVwithin) in the C-test and G-test was 25% and 27% for the ICD and for the ACD 24% and 21%, respectively. The between-subject variation was very similar with 72% and 73% (ICD) and with 78% and 68% (ACD). However, in ACDs below 100 m and between 100 to 150 m, the C-test showed significantly smaller coefficients of variation than the G-test: 13% vs 81% and 14% vs 50%, respectively. In conclusion, the results showed that both C-test and G-test are equally well reproducible.
Identification of the 183RWTNNFREY191Region as a Critical Segment of Matrix Metalloproteinase 1 for the Expression of Collagenolytic Activity*

Matrix metalloproteinase 1 (MMP-1) cleaves types I, II, and III collagen triple helices into ¾ and ¼ fragments. To understand the structural elements responsible for this activity, various lengths of MMP-1 segments have been introduced into MMP-3 (stromelysin 1) starting from the C-terminal end. MMP-3/MMP-1 chimeras and variants were overexpressed in Escherichia coli, folded from inclusion bodies, and isolated as zymogens. After activation, recombinant chimeras were tested for their ability to digest triple helical type I collagen at 25 °C. The results indicate that the nine residues 183RWTNNFREY191 located between the fifth β-strand and the second α-helix in the catalytic domain of MMP-1 are critical for the expression of collagenolytic activity. Mutation of Tyr191 of MMP-1 to Thr, the corresponding residue in MMP-3, reduced collagenolytic activity about 5-fold. Replacement of the nine residues with those of the MMP-3 sequence further decreased the activity 2-fold. Those variants exhibited significant changes in substrate specificity and activity against gelatin and synthetic substrates, further supporting the notion that this region plays a critical role in the expression of collagenolytic activity. However, introduction of this sequence into MMP-3 or a chimera consisting of the catalytic domain of MMP-3 with the hinge region and the C-terminal hemopexin domain of MMP-1 did not express any collagenolytic activity. It is therefore concluded that RWTNNFREY, together with the C-terminal hemopexin domain, is essential for collagenolytic activity but that additional structural elements in the catalytic domain are also required. These elements probably act in a concerted manner to cleave the collagen triple helix.
Targeting immune checkpoints in lymphoma

Purpose of reviewThe purpose of this article is to discus. s the tumor microenvironment in lymphoma, and to review potential immune targets that are now becoming relevant because of clinical responses seen with the use of immune checkpoint inhibitors. Recent findingsRecent data have shown that cells within the immune microenvironment in lymphoma express programmed death ligand-1 (PD-L1) and many of the intratumoral T cells with an exhausted immune phenotype express programmed cell death-1 (PD-1). This provides a novel opportunity to inhibit the immune checkpoints and initial clinical trials utilizing antibodies that block the interaction between PD-1 and PD-L1 have demonstrated significant clinical responses in various lymphomas, including Hodgkin lymphoma. SummaryThe use of immune checkpoint inhibitors, including nivolumab and pembrolizumab, in relapsed and refractory patients with lymphoma is proving highly successful. Patients with Hodgkin lymphoma, in particular, have a very high response rate to PD-1 blockade and responses in these patients appear durable.
Recovery from prior stimulation: masking of speech by interrupted noise for younger and older adults with normal hearing.

In a previous study [Dubno et al, J. Acoust. Soc. Am. 111, 2897-2907 (2002)], older subjects benefitted less than younger subjects from momentary improvements in signal-to-noise ratio when listening to speech in interrupted maskers. It has been hypothesized that the benefit derived from interrupted maskers may be related to recovery from forward masking, i.e., the recovery of a response to a suprathreshold signal from prior stimulation by a masker. The effect of interrupted maskers on speech recognition may be well suited to test hypotheses regarding recovery from prior stimulation, given that both involve the perception of signals following a masker. Here, younger and older adults with normal but not identical audiograms listened to nonsense syllables at moderate and high levels in a speech-shaped noise that was modulated by a 2-, 10-, 25-, or 50-Hz square wave. An additional low-level noise was always present that was shaped to produce equivalent masked thresholds for all subjects. To assess recovery from forward masking, forward-masked thresholds were measured at 0.5 and 4.0 kHz as a function of the delay between the speech-shaped masker and the signal. Speech recognition in interrupted noise was poorer for older than younger subjects. Small but consistent age-related differences were observed in the decrease in score with interrupted noise relative to the score without interrupted noise. Forward-masked thresholds of older subjects were higher than those of younger subjects, but there were no age-related differences in the amount of forward masking or in simultaneous masking. Negative correlations were observed between speech-recognition scores in interrupted noise and forward-masked thresholds. That is, the benefit derived from momentary improvements in speech audibility in an interrupted noise decreased as forward-masked thresholds increased. Stronger correlations with forward masking were observed for the higher frequency signal, for higher noise interruption rates, and when the signal-to-noise ratio was poor. Comparisons of speech-recognition scores at moderate and high levels for younger and older subjects were not consistent with the hypothesis of an age-related difference in the contribution of low-spontaneous-rate fibers to speech recognition in interrupted noise.
The tracking approach for small target with complex background based on spectral features

Hyperspectral data provide abundant information about materials of targets. The characteristics of different materials can be reflected by the different spectral absorption features of different materials, referred to as spectral features in this paper. Therefore, with the inherent differences of the absorption features of different materials, a tracking approach based on spectral features achieves the precise target detection and has the anti-jamming capability so that the small target under complex environment can be tracked effectively. Firstly, the stable spectral features are extracted from hyperspectral data and then the histogram extension of feature space dimension is performed, by which a parameterized model of stable spectral features of targets is established. Working with the parameterized model, a nonparametric kernel density estimator is proposed to track the target. Experimental results prove that the proposed approach can improve the tracking accuracy and anti-jamming capability, by which the small target with complex background can be tracked effectively.
Socially Assistive Robot HealthBot: Design, Implementation, and Field Trials

Socially assistive robotics is an important emerging research area. Socially assistive robotics is challenging as it is required to move robots out of laboratories and industrial settings to interact with ordinary human beings as peers, which requires social skills. The design process usually requires multidisciplinary research teams, which may comprise subject matter experts from various domains such as robotics, systems integration, medicine, psychology, gerontology, social and cognitive sciences, and neuroscience, among many others. Unlike most other robotic applications, socially assistive robotics faces some unique software and systems integration challenges. In this paper, the HealthBot robot architecture, which was designed to overcome these challenges, is presented. The presented architecture was implemented and used in several field trials. The details of the field trials are presented, and lessons learned are discussed with field trial results.
Semi-supervised discriminant analysis based on sparse-coding theory

We consider the problem of semi-supervised graph-based learning. Since in semi-supervised settings, the labeled information is limited, we first propose lα-norm-based label propagation (α-SLP) model to estimate the soft labels by using small set of labeled and large amount of unlabeled training data, and thereby enrich the supervised information. Based on the a-SLP results, we conduct semi-supervised discriminant analysis and present graph-based embedding (SGE) approach by incorporating the estimated soft labels with the local geometric information of both the within-class and between-class training data. Within-class affinity matrices and between-class weight matrix are introduced to preserve the propagated label information and local geometric information of data. This gets rid of the problem that merely concerning about the soft labels may lead to errors. By minimizing the locality-preserved within-class distances and maximizing the weighted between-class separability, subspaces that characterize the intrinsic data structure can be well captured. Experiments in face recognition verify the validity and effectiveness of the proposed methods.
Complementation of murine cells for human immunodeficiency virus envelope/CD4-mediated fusion in human/murine heterokaryons

Murine cell lines expressing human CD4 are resistant to the fusogenic effect of the human immunodeficiency virus (HIV) envelope. Consequently, they cannot be infected by HIV or form syncytia with HIV envelope-expressing cells. Murine cells could either lack human-specific cofactors necessary for the CD4/envelope-mediated membrane fusion or express inhibitors of this process. To address this question, we have tested the ability of heterokaryons made from CD4-expressing murine cells and human cells to undergo HIV envelope-mediated fusion. We have devised a rapid and specific assay based on the induction of lacZ expression, in which membrane fusion events with HIV-infected cells can be detected by a simple histochemical technique. CD4-positive murine/human heterokaryons, but not murine/simian heterokaryons, were found able to fuse with HIV envelope-expressing cells. In these experiments, the fusion resistant phenotype of murine-CD4 cells could be complemented by human cellular factors.
Assessment of domain boundary predictions and the prediction of intramolecular contacts in CASP8

This article details the assessment process and evaluation results for two categories in the 8th Critical Assessment of Protein Structure Prediction experiment (CASP8). The domain prediction category was evaluated with a range of scores including the Normalized Domain Overlap score and a domain boundary distance measure. Residue‐residue contact predictions were evaluated with standard CASP measures, prediction accuracy, and Xd. In the domain boundary prediction category, prediction methods still make reliable predictions for targets that have structural templates, but continue to struggle to make good predictions for the few ab initio targets in CASP. There was little indication of improvement in the domain prediction category. The contact prediction category demonstrated that there was renewed interest among predictors and despite the small sample size the results suggested that there had been an increase in prediction accuracy. In contrast to CASP7 contact specialists predicted contacts more accurately than the majority of tertiary structure predictors. Despite this small success, the lack of free modeling targets makes it unlikely that either category will be included in their present form in CASP9. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Two distinct mechanisms regulate the levels of a cellular tumor antigen, p53

The steady-state levels of p53 protein and p53 mRNA in transformed and nontransformed cells were examined to elucidate the mechanisms controlling expression of p53. mRNA levels were determined by Northern blot hybridization analysis, employing a p53-specific cDNA clone (M. Oren and A.J. Levine, Proc. Natl. Acad. Sci. U.S.A. 80:56-59, 1983), and protein levels were determined by the Western blotting technique. Analysis of p53 mRNA revealed a single polyadenylated mRNA species migrating at ca. 18S. Levels of p53 mRNA in simian virus 40-transformed cell line (SVT2) and in an homologous nontransformed cell line (3T3) were equivalent, although the steady-state levels of p53 protein were 25- to 100-fold higher in the SVT2 cells than in the 3T3 cells. A study with a non-virus-transformed cell system revealed a different result. Embryonal carcinoma cells (F9) were found to have nearly 20-fold higher levels of p53 mRNA in comparison with differentiated benign progeny cells. In this system the difference in p53 mRNA levels corresponded to the difference in p53 protein levels. Pulse-chase experiments were performed to study the half-life of p53 protein in these four types of cells. The turnover of p53 protein occurred with biphasic kinetics. In addition, it was found that protein synthesis inhibitors placed in the medium during the chase period prevented the turnover of p53 protein in transformed cells, but not in nontransformed (3T3) cells. These results provide evidence that the regulation of p53 expression in cells can occur at the level of p53 mRNA abundancy or p53 protein stability depending upon the experimental system under study, and that a regulated degradation process controls the turnover of p53 protein.
Documenting Teacher Candidates' Professional Growth through Performance Evaluation.

In the United States, colleges of education are responding to demands for increased accountability. The purpose of this article is to describe one teacher education program’s implementation of a performance evaluation tool during final internship that measures teacher candidates’ development across four domains: Planning and Preparation, Instruction and Management, Assessment, and Personal and Professional Development. Researchers examined data collected via midpoint and final internship evaluations across three program tracks using a measure created by the authors entitled the Profile for Evaluation of Intern (PEI). Although this measure is still in its preliminary phases, data analyses indicated positive, statistically significant differences across three tracks on 16 criteria on the performance evaluation tool and on candidates’ overall ‘grand’ averages at the midpoint evaluation; however, no statistically significant differences remained at the final evaluation point. Benefits and challenges involved in employing a performance evaluation tool in teacher preparation are discussed. Implications for teacher educators, including recommendations for programmatic design and suggestions for how such tools inform program development and the field of teacher education, are discussed.
INSECT RESISTANCE

O. G. A. BERGGREN, of the Gynrecological Departmentof the Radiumhemmet,Stockholm, notes that Sweden is a particularly appropriate country in which to study the social and hygienic factors underlying the incidence of cancer of the uterine cervix;" for in Sweden,since 1928, practically every patient with cancer of the cervix has beentreatedat one of the four "JubileeClinics" by radium implantation. Berggrenhas concentratedhis attention on morbidity-that is, case incidence-especiallyin the years of the five-yearly Swedishcensus. He rather surprisingly omits any referenceto death rates from the disease. In his Table I, he gives caseincidenceratesfrom A. Lindell's' study, on which we" have alreadycommented. There was an increase in the incidence rates of cervical cancer of perhapsone-third between the years 1930 and 1947, and Berggren proposesto find the cause.
Hypodiploidy and 22q11 rearrangements at diagnosis are associated with poor prognosis in patients with multiple myeloma

Our aim was to evaluate the clinical use of cytogenetic analysis as a prognostic factor in the outcome of newly diagnosed multiple myeloma (MM) patients. The present series includes 111 newly diagnosed MM patients treated with one of three standard‐dose regimens or autologous transplantation over an 8‐year time interval. As expected, the presence of an abnormal karyotype (39% of patients) correlated with poor prognosis (progression rate 63% v 47%, P = 0.042), shorter event‐free (EFS, P = 0.014) and overall (OS, P = 0.005) survival. Two distinct cytogenetic abnormalities were the most significant variables that influenced EFS and OS in the univariate analysis. The presence of hypodiploid karyotypes or rearrangements of band 22q11 were associated with higher progression rate (P = 0.001) and shorter EFS (P < 0.024) and OS (P < 0.004). The median EFS and OS for patients with hypodiploidy was 4 and 7 months respectively. Multivariate analysis showed that absence of hypodiploidy was the most favourable prognostic variable for OS (P = 0.022) followed by stage ≤IIA, serum calcium ≤2875 μmol/l, and absence of abnormalities 22q. The data suggest that the presence of hypodiploid karyotypes and rearrangements on 22q11 band show a higher progression rate and shorter survival in MM patients.
Mechanisms of Enhanced Radiation-Induced Degradation Due to Excess Molecular Hydrogen in Bipolar Oxides

Bipolar junction test structures packaged in hermetically sealed packages with excess molecular hydrogen (H2) showed enhanced degradation after radiation exposure. Using chemical kinetics, we propose a model that quantitatively establishes the relationship between excess H2 and radiation-induced interface trap formation. Using environments with different molecular hydrogen concentrations, radiation experiments were performed and the experimental data showed excellent agreement with the proposed model. The results, both experimentally and theoretically, showed increased radiation induced degradation with H2 concentration, and device degradation saturate at both high and low ends of H2 concentrations.