gebhart/patrepeval huggingface dataset:
The Adjusting-Paced Serial Addition Test (Adjusting-PSAT): thresholds for speed of information processing as a function of stimulus modality and problem complexity (2003)

A modified computer version of the PASAT (Adjusting-PSAT; Tombaugh, 1999) is described that measures speed of information processing and working memory by means of a temporal threshold rather than number of correct responses. This is accomplished by making the duration of the interval between numbers depend on the correctness of responding—a correct response decreases the interval between digits and an incorrect response increases the interval. Modality of presentation (visual and auditory) was factorially combined with problem difficulty (answers between 2–10 or 2–18). Performance of 60 healthy student volunteers on the Adjusting-PSAT was compared to that obtained on several traditional neuropsychological measures (Digit Span, Trail Making Test, and Symbol Digit Modality Test) and on a test of basic addition skills. The visual version of the test produced a lower threshold than did the auditory version, but problem difficulty did not produce a significant effect. Of the neuropsychological tests, Trails-B (TMT-B) was most highly correlated with thresholds. However, regression analyses revealed that math ability accounted for more variance than did TMT-B. The clinical implications of these finding are discussed.
Immunohistochemical identification of proliferating cells in organ culture using bromodeoxyuridine and a monoclonal antibody. (1986)

The ability to measure cell proliferation is important in the study of cancer biology. The usual technique for quantitating proliferating cells in tissue explant and organ culture by detection of [3H]-thymidine incorporation into DNA by autoradiography is tedious and time-consuming. We have developed a technique for identification and quantitation of bromodeoxyuridine (an analogue of thymidine) in cultured tissue explants. Fetal mouse colon explants were exposed in vitro to bromodeoxyuridine (BUdR) or [3H]-thymidine for 3 to 72 hr and then for various periods to unlabeled thymidine. The tissues were stained with a monoclonal anti-bromodeoxyuridine antibody and in parallel [3H]-thymidine incorporation was detected by autoradiography. Incorporation of BUdR was measured by quantitating the amount of pigment deposited over nuclei after immunohistochemical staining, using an optical data digitizer. It was found that both techniques identified proliferating cells. Dividing cells were present both in crypts and in the surrounding stroma in Day 14 fetal mouse colon cultures. The immunohistochemical technique was more rapid and less cumbersome than autoradiography.
Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). (1992)

Pharyngeal collapse in obstructive sleep apnea patients is likely a product of a sleep-related decrement in pharyngeal dilator muscle activity superimposed upon abnormal airway anatomy. We postulate that during wakefulness, increased pharyngeal dilator muscle activity in apnea patients compensates for diminished airway size thus maintaining patency. We studied the waking genioglossus (GG) electromyogram (EMG) activity in 11 OSA patients and 14 age-matched controls to determine if GG activity is higher in the awake state in apnea patients than controls. To make this determination, we developed a reproducible methodology whereby true maximal GG EMG could be defined and thus basal activity quantitated as a percentage of this maximal value. Therefore, direct comparisons of basal activity between individuals was possible. We observed apnea patients to have significantly greater basal genioglossal activity compared to controls (40.6 +/- 5.6% vs. 12.7 +/- 1.7% of maximum). This difference persisted when size-matched subsets were compared. This augmented GG activity in apnea patients could be reduced with positive airway pressure. We speculate that this neuromuscular compensation present during wakefulness in apnea patients may be lost during sleep leading to airway collapse.
pH-Dependent Association of Factor VIII Chains: Enhancement of Affinity at Physiological pH by Cu2+. (2005)

Abstract Factor VIII circulates as a heterodimer composed of a heavy chain (HC) and light chain (LC). The structural integrity of the heterodimer is crucial for factor VIII function. In this study we found that the reconstitution of factor VIII from isolated HC and LC was pH-dependent. In the presence of Ca2+, up to 80% of native factor VIII activity was recovered over a wide range of pH values. The affinity of HC and LC was maximal at pH 6.5-6.75 (Kd ~ 4 nM), whereas a Kd of ~20 nM was observed at physiological pH (7.25) (Figure). The effect of Cu2+ (0.5 μM total Cu2+) on maximal activity regenerated was negligible at pH 6.25–8.0. However, this level of Cu2+ increased the inter-chain affinity by ~5 fold at pH 7.25 (Figure). This effect resulted from an ~1.5-fold increased association rate constant (kon) and an ~3-fold reduced dissociation rate constant (koff). Addition of Cu2+ to a mixture of HC and LC at equilibrium resulted in an increase in cofactor activity that followed a single exponential, suggesting that association was defined by a simple reaction model. High affinity (Kd = 5.3 fM) of the factor VIII chains for Cu2+, as estimated by increases in cofactor activity, suggested a rapid association rate for the metal ion. Together, these results suggest that the protonation state of specific residues, His in particular, modulate inter-chain affinity. Furthermore, copper ion contributes to the maintenance of the heterodimer at physiologic pH by a mechanism consistent with bridging the two chains. Figure Figure
A discriminatively trained, multiscale, deformable part model (2008)

This paper describes a discriminatively trained, multiscale, deformable part model for object detection. Our system achieves a two-fold improvement in average precision over the best performance in the 2006 PASCAL person detection challenge. It also outperforms the best results in the 2007 challenge in ten out of twenty categories. The system relies heavily on deformable parts. While deformable part models have become quite popular, their value had not been demonstrated on difficult benchmarks such as the PASCAL challenge. Our system also relies heavily on new methods for discriminative training. We combine a margin-sensitive approach for data mining hard negative examples with a formalism we call latent SVM. A latent SVM, like a hidden CRF, leads to a non-convex training problem. However, a latent SVM is semi-convex and the training problem becomes convex once latent information is specified for the positive examples. We believe that our training methods will eventually make possible the effective use of more latent information such as hierarchical (grammar) models and models involving latent three dimensional pose.
Incremental on-line feature space MLLR adaptation for telephony speech recognition (2002)

In this paper, we present a method for incremental on-line adaptation based on feature space Maximum Likelihood Linear Regression (FMLLR) for telephony speech recognition applications. We explain how to incorporate a feature space MLLR transform into a stack decoder and perform on-line adaptation. The issues discussed are as follows: collecting adaptation data on-line and in real time; mapping adaptation data from previous feature space to the present feature space; and smoothing adaptation statistics with initial statistics based on original acoustical model to achieve stability. Testing results on various systems demonstrate that on-line incremental FMLLR adaptation could be an effective and stable method when the adaptation statistics are mapped and smoothed.
Single-Cell RNA-Seq Reveals Dynamic, Random Monoallelic Gene Expression in Mammalian Cells (2014)

Expression from both alleles is generally observed in analyses of diploid cell populations, but studies addressing allelic expression patterns genome-wide in single cells are lacking. Here, we present global analyses of allelic expression across individual cells of mouse preimplantation embryos of mixed background (CAST/EiJ × C57BL/6J). We discovered abundant (12 to 24%) monoallelic expression of autosomal genes and that expression of the two alleles occurs independently. The monoallelic expression appeared random and dynamic because there was considerable variation among closely related embryonic cells. Similar patterns of monoallelic expression were observed in mature cells. Our allelic expression analysis also demonstrates the de novo inactivation of the paternal X chromosome. We conclude that independent and stochastic allelic transcription generates abundant random monoallelic expression in the mammalian cell.
Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models (2011)

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in Hdh(Q111/+) mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool.
Inhibition of Lymphangiogenesis and Angiogenesis in Breast Tumor Xenografts and Lymph Nodes by a Peptide Derived from Transmembrane Protein 45A (2013)

Angiogenesis, the formation of new blood vessels from preexisting blood vessels, is a process that supports tumor growth and metastatic dissemination. Lymphangiogenesis also facilitates metastasis by increasing dissemination through the lymphatic vessels (LVs). Even after treatment with antiangiogenic agents, breast cancer patients are vulnerable to LV-mediated metastasis. We report that a 14-amino acid peptide derived from transmembrane protein 45A shows multimodal inhibition of lymphangiogenesis and angiogenesis in breast cancer. The peptide blocks lymphangiogenic and angiogenic phenotypes of lymphatic and blood endothelial cells induced by tumor-conditioned media prepared from MDA-MB-231 breast cancer cells. The peptide delays growth of MDA-MB-231 tumor xenografts and normalizes tumor-conditioned lymph nodes (LNs). These studies demonstrate the antilymphangiogenic and antiangiogenic potential of the peptide against primary tumors and premetastatic, tumor-conditioned regional LNs. Mechanistically, the peptide blocks vascular endothelial growth factor receptors 2 and 3 (VEGFR2/3) and downstream proteins by binding to neuropilin 1/2 (NRP1/2) and inhibiting VEGFR2/3 and NRP1/2 complex formation in the presence of VEGFA/C.
Tunable Thermoassociation of Binary Guanosine Gels (2008)

It is well-known that aqueous solutions of individual guanosine compounds can form gels through reversible self-assembly. Typically, gelation is favored at low temperature and acidic pH. We have discovered that binary mixtures of 5'-guanosine monophosphate (GMP) and guanosine (Guo) can form stable gels at neutral pH over a temperature range that can be tuned by varying the relative proportions of the hydrophobic Guo and the hydrophilic GMP in the mixture. Gelation was studied over the temperature range of 5-40 degrees C or 60 degrees C at pH 7.2 using visual detection, circular dichroism (CD) spectroscopy, and CD thermal melt experiments. Solutions with high GMP/Guo ratios behaved similar to solutions of GMP alone while solutions with low GMP/Guo formed firm gels across the entire temperature range. Most interesting were solutions between these two extremes, which were found to exhibit thermoassociative behavior; these solutions are liquid at refrigerator temperature and undergo sharp transitions to a gel only at higher temperatures. Increasing the GMP/Guo ratio and increasing the total concentration of guanosine compounds shifted the onset of gelation to higher temperatures (ranging from 20 to 40 degrees C), narrowed the temperature range of the gel phase, and sharpened the reversible phase transitions. The combination of self-assembly, reversibility, and tunability over biologically relevant temperature ranges and pH offers exciting possibilities for these simple and inexpensive materials in medical, biological, analytical, and nanotechnological applications.
A Variant of Herpes Simplex Virus Type 2 Strain HG52 with a 1.5 kb Deletion in RL between 0 to 0.02 and 0.81 to 0.83 Map Units Is Non-neurovirulent for Mice (1989)

The virulence of a deletion variant of herpes simplex virus type 2 (HSV-2) strain HG52 has been determined by intracranial inoculation of 3-week-old BALB/c mice. The variant JH2604 has a 1.5 kb deletion within each copy of the long repeat region (RL) of the genome between 0 to 0.02 and 0.81 to 0.83 map units. JH2604 is avirulent for mice compared to the parental wild-type virus, and fails to replicate in mouse brain in vivo. Correction of the deletion by marker rescue resulted in the isolation of recombinants which gave LD50 values comparable to those of individual plaque stocks of the parental HG52. Introduction of the deletion into wild-type virus resulted in recombinants which on intracranial inoculation of mice were avirulent. The results imply that sequences within the 3 kb terminal portion of RL are required for virulence of HSV-2 strain HG52.
Modelling of poliovirus (1990)

We have used laboratory-based molecular modelling to identify structural features of antigen chimaeras of poliovirus expressing epitopes from human immunodeficiency virus (HIV-1) that may affect virus viability. Chimaeras were constructed by replacement of antigenic site 1 of VP1 by sequences corresponding to epitopes from HIV-1. Loop volume, estimated by approximating the loop to an ellipsoid was significantly (P less than 0.001) lower in viable (2062.1 A3 +/- 400.2) than in non-viable (3617 A3 +/- 650.7) constructs. Our results suggest that viable virus will only be formed when antigen chimeras modified at antigenic site of VP1 have a loop occupying a similar volume in space to that occupied by the antigenic site 1 loop. In addition, the modified loop must fit with the peptide bond angles and distances at the top of the beta-barrel of VP1.
Mass Spectrometric Detection of an SNP Panel as an Internal Positive Control for Fetal DNA Analysis in Maternal Plasma (2007)

Total 74 41 36 a An SNP locus was considered applicable when maternal buffy coat analysis revealed a homozygous maternal genotype. b An applicable SNP locus was further considered to be informative if CVS tissue analysis revealed that the fetal genotype was heterozygous. c The number of informative fetal SNP loci detectable from maternal plasma by SABER analysis.
Short-term comparative study of the effects of preserved and unpreserved topical levofloxacin on the human ocular surface (2010)

Regarding the short-term effects on the ocular surface of patients with age-related cataracts, no clinically and statistically significant differences were observed between topical levofloxacin preserved with BOB and its unpreserved counterpart.
Molecular Biology of the Natriuretic Peptide System (2007)

Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer this process is available in the click Request Permissions in the middle column of the Web page under Services. Further information about Office. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the EditorialHypertensionin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on March 5,
Corticotropin Releasing Hormone and Proopiomelanocortin Involvement in the Cutaneous Response to Stress (2000)

The skin is a known target organ for the proopiomelanocortin (POMC)-derived neuropeptides alpha-melanocyte stimulating hormone (alpha-MSH), beta-endorphin, and ACTH and also a source of these peptides. Skin expression levels of the POMC gene and POMC/corticotropin releasing hormone (CRH) peptides are not static but are determined by such factors as the physiological changes associated with hair cycle (highest in anagen phase), ultraviolet radiation (UVR) exposure, immune cytokine release, or the presence of cutaneous pathology. Among the cytokines, the proinflammatory interleukin-1 produces important upregulation of cutaneous levels of POMC mRNA, POMC peptides, and MSH receptors; UVR also stimulates expression of all the components of the CRH/POMC system including expression of the corresponding receptors. Molecular characterization of the cutaneous POMC gene shows mRNA forms similar to those found in the pituitary, which are expressed together with shorter variants. The receptors for POMC peptides expressed in the skin are functional and include MC1, MC5 and mu-opiate, although most predominant are those of the MC1 class recognizing MSH and ACTH. Receptors for CRH are also present in the skin. Because expression of, for example, the MC1 receptor is stimulated in a similar dose-dependent manner by UVR, cytokines, MSH peptides or melanin precursors, actions of the ligand peptides represent a stochastic (predictable) nonspecific response to environmental/endogenous stresses. The powerful effects of POMC peptides and probably CRH on the skin pigmentary, immune, and adnexal systems are consistent with stress-neutralizing activity addressed at maintaining skin integrity to restrict disruptions of internal homeostasis. Hence, cutaneous expression of the CRH/POMC system is highly organized, encoding mediators and receptors similar to the hypothalamic-pituitary-adrenal (HPA) axis. This CRH/POMC skin system appears to generate a function analogous to the HPA axis, that in the skin is expressed as a highly localized response which neutralizes noxious stimuli and attendant immune reactions.
Infrared spectroscopy and microscopy in cancer research and diagnosis. (2012)

Since the middle of 20(th) century infrared (IR) spectroscopy coupled to microscopy (IR microspectroscopy) has been recognized as a non destructive, label free, highly sensitive and specific analytical method with many potential useful applications in different fields of biomedical research and in particular cancer research and diagnosis. Although many technological improvements have been made to facilitate biomedical applications of this powerful analytical technique, it has not yet properly come into the scientific background of many potential end users. Therefore, to achieve those fundamental objectives an interdisciplinary approach is needed with basic scientists, spectroscopists, biologists and clinicians who must effectively communicate and understand each other's requirements and challenges. In this review we aim at illustrating some principles of Fourier transform (FT) Infrared (IR) vibrational spectroscopy and microscopy (microFT-IR) as a useful method to interrogate molecules in specimen by mid-IR radiation. Penetrating into basics of molecular vibrations might help us to understand whether, when and how complementary information obtained by microFT-IR could become useful in our research and/or diagnostic activities. MicroFT-IR techniques allowing to acquire information about the molecular composition and structure of a sample within a micrometric scale in a matter of seconds will be illustrated as well as some limitations will be discussed. How biochemical, structural, and dynamical information about the systems can be obtained by bench top microFT-IR instrumentation will be also presented together with some methods to treat and interpret IR spectral data and applicative examples. The mid-IR absorbance spectrum is one of the most information-rich and concise way to represent the whole "… omics" of a cell and, as such, fits all the characteristics for the development of a clinically useful biomarker.
Simultaneous multi-cancer detection and tissue of origin (TOO) localization using targeted bisulfite sequencing of plasma cell-free DNA (cfDNA). (2019)

44 Background: A noninvasive cfDNA blood test detecting multiple cancers at earlier stages could decrease cancer mortality. In earlier discovery work, whole-genome bisulfite sequencing outperformed whole-genome and targeted sequencing approaches for multi-cancer detection across stages at high specificity. Here, multi-cancer detection and TOO localization using bisulfite sequencing of plasma cfDNA to identify methylomic signatures was evaluated in preparation for clinical validation, utility, and implementation studies. Methods: 2301 analyzable participants (1422 cancer [ &gt; 20 tumor types, all stages], 879 non-cancer) were included in this prespecified substudy from the Circulating Cell-free Genome Atlas (CCGA) (NCT02889978) study - a prospective, multi-center, observational, case-control study with longitudinal follow-up. Plasma cfDNA was subjected to a targeted methylation sequencing assay using high-efficiency methylation chemistry to enrich for methylation targets, and a machine learning classifier determined cancer status and tissue of origin (TOO). Observed methylation fragments characteristic of cancer and TOO were combined across targeted regions and assigned a relative probability of cancer and of a specific TOO. Results: Performance is reported at 99% specificity (ie, a combined false positive rate across all cancer types of 1%), a level required for population-level screening. Across cancer types, sensitivity ranged from 59 to 86%. Combined cancer detection (sensitivity [95% CI]) was 34% (27-43%) in stage I (n = 151), 77% (70-83%) in stage II (n = 171), 84% (79-89%) in stage III (n = 204), and 92% (88-95%) in stage IV (n = 281). TOO was provided for 94% of all cancers detected; of these, TOO was correct in &gt; 90% of cases. Conclusions: Detection of multiple deadly cancers across stages using methylation signatures in plasma cfDNA was achieved with a single, fixed, low false positive rate, and simultaneously provided accurate TOO localization. This targeted methylation assay is undergoing validation in preparation for prospective clinical investigation as a cancer detection diagnostic. Clinical trial information: NCT02889978.