gebhart/patrepeval huggingface dataset:
Mouse neurexin-1α deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments (2009)

Deletions in the neurexin-1alpha gene were identified in large-scale unbiased screens for copy-number variations in patients with autism or schizophrenia. To explore the underlying biology, we studied the electrophysiological and behavioral phenotype of mice lacking neurexin-1alpha. Hippocampal slice physiology uncovered a defect in excitatory synaptic strength in neurexin-1alpha deficient mice, as revealed by a decrease in miniature excitatory postsynaptic current (EPSC) frequency and in the input-output relation of evoked postsynaptic potentials. This defect was specific for excitatory synaptic transmission, because no change in inhibitory synaptic transmission was observed in the hippocampus. Behavioral studies revealed that, compared with littermate control mice, neurexin-1alpha deficient mice displayed a decrease in prepulse inhibition, an increase in grooming behaviors, an impairment in nest-building activity, and an improvement in motor learning. However, neurexin-1alpha deficient mice did not exhibit any obvious changes in social behaviors or in spatial learning. Together, these data indicate that the neurexin-1alpha deficiency induces a discrete neural phenotype whose extent correlates, at least in part, with impairments observed in human patients.
Signal amplification by rolling circle amplification on DNA microarrays (2001)

While microarrays hold considerable promise in large-scale biology on account of their massively parallel analytical nature, there is a need for compatible signal amplification procedures to increase sensitivity without loss of multiplexing. Rolling circle amplification (RCA) is a molecular amplification method with the unique property of product localization. This report describes the application of RCA signal amplification for multiplexed, direct detection and quantitation of nucleic acid targets on planar glass and gel-coated microarrays. As few as 150 molecules bound to the surface of microarrays can be detected using RCA. Because of the linear kinetics of RCA, nucleic acid target molecules may be measured with a dynamic range of four orders of magnitude. Consequently, RCA is a promising technology for the direct measurement of nucleic acids on microarrays without the need for a potentially biasing preamplification step.
Scale-space theory: a basic tool for analyzing structures at different scales (1994)

An inherent property of objects in the world is that they only exist as meaningful entities over certain ranges of scale. If one aims to describe the structure of unknown real-world signals, then a multi-scale representation of data is of crucial importance. This paper gives a tutorial review of a special type of multi-scale representation—linear scale-space representation—which has been developed by the computer vision community to handle image structures at different scales in a consistent manner. The basic idea is to embed the original signal into a one-parameter family of gradually smoothed signals in which the fine-scale details are successively suppressed. Under rather general conditions on the type of computations that are to be performed at the first stages of visual processing, in what can be termed ‘the visual front-end’, it can be shown that the Gaussian kernel and its derivatives are singled out as the only possible smoothing kernels. The conditions that specify the Gaussian kernel are, basically, linearity and shift invariance, combined with different ways of formalizing the notion that structures at coarse scales should correspond to simplifications of corresponding structures at fine scales-they should not be accidental phenomena created by the smoothing method. Notably, several different ways of choosing scale-space axioms give rise to the same conclusion. The output from the scale-space representation can be used for a variety of early visual tasks; operations such as feature detection, feature classification and shape computation can be expressed directly in terms of (possibly non-linear) combinations of Gaussian derivatives at multiple scales. In this sense the scale-space representation canserve as a basis for early vision. During the last few decades, a number of other approaches to multiscale representations have been developed, which are more or less related to scale-space theory, notably the theories of pyramids, wavelets and multi grid methods.Despite their qualitative differences, the increasing propularity of each of these approaches indicates that the crucial notion of scale is increasingly appreciated by the computer.vision community and by researchers in other related fields. An interesting similarity to biological vision is that the scale-space operators closely resemble receptive field profiles registered in neurophysiological studies of the mam- malian retina and visual cortex.
Assessment of Antiangiogenic Effect Using 99m Tc-EC-Endostatin (2002)

The results indicate that it is feasible to use 99mTc-EC-endostatin to assess efficiency of anti-angiogenesis therapy.
A sequential indexing scheme for flash-based embedded systems (2009)

NAND Flash has become the most popular stable storage medium for embedded systems. As on-board storage capacity increases, the need for efficient indexing techniques arises. Such techniques are very challenging to design due to a combination of NAND Flash constraints (for example the block-erase-before-page-rewrite constraint and limited number of erase cycles) and embedded system constraints (for example tiny RAM and resource consumption predictability). Previous work adapted traditional indexing methods to cope with Flash constraints by deferring index updates using a log and batching them to decrease the number of rewrite operations in Flash memory. However, these methods were not designed with embedded system constraints in mind and do not address them. In this paper, we propose a new alternative for indexing Flash-resident data that specifically addresses the embedded context. This approach, called PBFilter, organizes the index structure in a purely sequential way. Key lookups are sped up thanks to two principles called Summarization and Partitioning. We instantiate these principles with data structures and algorithms based on Bloom Filters and show the effectiveness of this approach through a comprehensive performance study.
S1‐01‐02: Blood‐brain barrier mechanisms of neurodegeneration in Alzheimer's disease (2015)

Abstract not available.
Discovery and Pharmacological Evaluation of Growth Hormone Secretagogue Receptor Antagonists (2006)

The discovery and pharmacological evaluation of potent, selective, and orally bioavailable growth hormone secretagogue receptor (GHS-R) antagonists are reported. Previously, 2,4-diaminopyrimidine-based GHS-R antagonists reported from our laboratories have been shown to be dihydrofolate reductase (DHFR) inhibitors. By comparing the X-ray crystal structure of DHFR docked with our GHS-R antagonists and GHS-R modeling, we designed and synthesized a series of potent and DHFR selective GHS-R antagonists with good pharmacokinetic (PK) profiles. An amide derivative 13d (Ca2+ flux IC50 = 188 nM, [brain]/[plasma] = 0.97 @ 8 h in rat) showed a 10% decrease in 24 h food intake in rats, and over 5% body weight reduction after 14-day oral treatment in diet-induced obese (DIO) mice. In comparison, a urea derivative 14c (Ca2+ flux IC50 = 7 nM, [brain]/[plasma] = 0.0 in DIO) failed to show significant effect on food intake in the acute feeding DIO model. These observations demonstrated for the first time that peripheral GHS-R blockage with small molecule GHS-R antagonists might not be sufficient for suppressing appetite and inducing body weight reduction.
Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardiac Ca2+-ATPase gene. (1988)

Ca2+-ATPase molecules present in the microsomal fraction from non-muscle cells were examined immunologically. Rabbit whole brain, cerebellum, liver, kidney, and COS-1 cell microsomes all displayed a polypeptide of about 110 kDa which was immunoreactive with a polyclonal antiserum against the cardiac muscle sarcoplasmic reticulum Ca2+-ATPase molecule, but was not immunoreactive with a monoclonal antibody specific for the fast-twitch muscle Ca2+-ATPase. cDNAs encoding the full length of two Ca2+-ATPase molecules were isolated from a human kidney library using a mixture of nucleotide probes derived from both rabbit fast-twitch and cardiac muscle Ca2+-ATPase cDNAs. The human kidney cDNAs, HK1 and HK2, are the products of alternative splicing. HK2 codes for a protein identical to rabbit cardiac muscle Ca2+-ATPase, with the exception of 6 scattered amino acid replacements, whereas HK1 codes for a protein identical to that encoded by HK2, but with the carboxyl-terminal 4 amino acids replaced by an extended sequence of 49 amino acids. cDNAs of the HK1 type are by far the most abundant in the library. The partial structure of a 40-kilobase genomic DNA encoding all but the 5' end of the human cardiac Ca2+-ATPase is described. The exons which give rise to the alternatively spliced products were located by Southern blotting and sequencing, and the alternative splicing patterns were determined.
The essence of the Visitor pattern (2002)

For object-oriented programming, the Visitor pattern enables the definition of a new operation on an object structure without changing the classes of the objects. The price has been that the set of classes must be fixed in advance, and they must each have a so-called accept method. In this paper we demonstrate how to program visitors without relying on accept methods and without knowing all classes of the objects in advance. The idea, derived from related work on shape polymorphism in functional programming, is to separate (1) accessing subobjects, and (2) acting on them. In the object-oriented setting, reflection techniques support access to sub-objects, as demonstrated in our Java class, Walkabout. It supports all visitors as subclasses, and they can be programmed without any further use of reflection. Thus a program using the Visitor pattern can now be understood as a specialized version of a program using the Walkabout class.
Unrelated Umbilical Cord Blood Transplantation for an Infant With ??-Thalassemia Major (2004)

Umbilical cord blood transplantation from related and unrelated donors should be considered for patients with beta-thalassemia major who lack traditional bone marrow donors. As most newborns undergo screening for hemoglobinopathies, those with disease could be transplanted early in life before experiencing the morbidity and mortality caused by transfusion therapy, alloimmunization, and iron overload, increasing the likelihood of successful transplantation therapy.
Role of the Chaperone Protein Hsp104 in Propagation of the Yeast Prion-Like Factor [ psi + ] (1995)

The yeast non-Mendelian factor [psi+] has been suggested to be a self-modified protein analogous to mammalian prions. Here it is reported that an intermediate amount of the chaperone protein Hsp104 was required for the propagation of the [psi+] factor. Over-production or inactivation of Hsp104 caused the loss of [psi+]. These results suggest that chaperone proteins play a role in prion-like phenomena, and that a certain level of chaperone expression can cure cells of prions without affecting viability. This may lead to antiprion treatments that involve the alteration of chaperone amounts or activity.
DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. (2001)

Increased levels of DNA fragments have frequently been found in the blood plasma of cancer patients. Published data suggest that only a fraction of the DNA in blood plasma is derived from cancer cells. However, it is not known how much of the circulating DNA is from cancer or from noncancer cells. By quantitative methylation-specific PCR of the promoter region of the CDKN2A tumor suppressor gene, we were able to quantify the fraction of plasma DNA derived from tumor cells. In the plasma samples of 30 unselected cancer patients, we detected quantities of tumor DNA from only 3% to as much as 93% of total circulating DNA. We investigated possible origins of nontumor DNA in the plasma and demonstrate here a contribution of T-cell DNA in a few cases only. To investigate the possibility that plasma DNA originates from apoptotic or necrotic cells, we performed studies with apoptotic (staurosporine) and necrotic (staurosporine plus oligomycin) cells in vitro and with mice after induction of apoptotic (anti-CD95) or necrotic (acetaminophen) liver injury. Increasing amounts of DNA were found to be released in the supernatants of cells and in the blood plasma samples of treated animals. A clear discrimination of apoptotic and necrotic plasma DNA was possible by gel electrophoresis. The same characteristic patterns of DNA fragments could be identified in plasma derived from different cancer patients. The data are consistent with the possibility that apoptotic and necrotic cells are a major source for plasma DNA in cancer patients.
70A: IMPACT OF PEDOT ON PERIPHERAL NERVE REGENERATION AND MUSCLE REINNERVATION (2010)

Baghmanli, Z; Urbanchek, MG; Wei, B; Shim, BS; Martin, D; Cederna, PS Author Information
Acquired genomic copy number aberrations and survival in adult acute myelogenous leukemia (2010)

Genomic aberrations are of predominant importance to the biology and clinical outcome of patients with acute myelogenous leukemia (AML), and conventional karyotype-based risk classifications are routinely used in clinical decision making in AML. One of the known limitations of cytogenetic analysis is the inability to detect genomic abnormalities less than 5 Mb in size, and it is currently unclear whether overcoming this limitation with high-resolution genomic single-nucleotide polymorphism (SNP) array analysis would be clinically relevant. Furthermore, given the heterogeneity of molecular mechanisms/aberrations that underlie the conventional karyotype-based risk classifications, it is likely that further refinements in genomic risk prognostication can be achieved. In this study, we analyzed flow cytometer-sorted, AML blast-derived, and paired, buccal DNA from 114 previously untreated prospectively enrolled AML patients for acquired genomic copy number changes and loss of heterozygosity using Affymetrix SNP 6.0 arrays, and we correlated genomic lesion load and specific chromosomal abnormalities with patient survival. Using multivariate analyses, we found that having ≥ 2 genomic lesions detected through SNP 6.0 array profiling approximately doubles the risk of death when controlling for age- and karyotype-based risk. Finally, we identified an independent negative prognostic impact of p53 mutations, or p53 mutations and 17p-loss of heterozygosity combined on survival in AML.
Adsorption of PEO−PPO−PEO Triblock Copolymers at the Solid/Liquid Interface:  A Surface Plasmon Resonance Study (1997)

Poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide) (PEO−PPO−PEO) triblock copolymers are used in a wide range of industrial applications from detergents to pharmaceutical materials. We have employed surface plasmon resonance (SPR) to monitor the adsorption of these materials, from aqueous solutions to a model hydrophobic surface. The effect of varying the PPO or PEO block size of the copolymer on adsorption has been investigated, and a linear increase in SPR angle shift with increasing PPO or PEO chain length is observed. The SPR angle shifts show a greater increase in SPR angle with increasing PPO block size compared to an equivalent increase in PEO block size. This has been explained by considering the effect each block has on the dielectric properties of the adsorbed polymer at the interface. The presence of micelles in solution and their influence on Pluronic adsorption has also been considered, and adsorption from micellar solutions has been determined to be dependent on the PPO content of the copolymer.
Protein “fingerprinting” in complex mixtures with peptoid microarrays (2005)

We report here that microarrays comprised of several thousand peptoids (oligo-N-substituted glycines) are useful tools for the identification of proteins via a "fingerprinting" approach. By using maltose-binding protein, glutathione S-transferase, and ubiquitin, a specific and highly reproducible pattern of binding was observed when fluorescently labeled protein was hybridized to the array. A similar pattern was obtained when binding of an unlabeled protein to the array was visualized by secondary hybridization of a labeled antibody against that protein, showing that native proteins can be identified without the requirement for prior chemical labeling. This work suggests that small-molecule microarrays might be used for more complex fingerprinting assays of potential diagnostic value.
An Improved Bioluminescence Resonance Energy Transfer Strategy for Imaging Intracellular Events in Single Cells and Living Subjects (2007)

Abstract Bioluminescence resonance energy transfer (BRET) is currently used for monitoring various intracellular events, including protein-protein interactions, in normal and aberrant signal transduction pathways. However, the BRET vectors currently used lack adequate sensitivity for imaging events of interest from both single living cells and small living subjects. Taking advantage of the critical relationship of BRET efficiency and donor quantum efficiency, we report generation of a novel BRET vector by fusing a GFP2 acceptor protein with a novel mutant Renilla luciferase donor selected for higher quantum yield. This new BRET vector shows an overall 5.5-fold improvement in the BRET ratio, thereby greatly enhancing the dynamic range of the BRET signal. This new BRET strategy provides a unique platform to assay protein functions from both single live cells and cells located deep within small living subjects. The imaging utility of the new BRET vector is shown by constructing a sensor using two mammalian target of rapamycin pathway proteins (FKBP12 and FRB) that dimerize only in the presence of rapamycin. This new BRET vector should facilitate high-throughput sensitive BRET assays, including studies in single live cells and small living subjects. Applications will include anticancer therapy screening in cell culture and in small living animals. [Cancer Res 2007;67(15):7175–83]
Detection of mutations in the mitogen-activated protein kinase pathway in human melanoma. (2003)

Activating mutations of the MAPK pathway were present in approximately 60% of samples tested and caused activation of this cellular pathway that appears to be important in the pathogenesis of melanoma.
The relationship of clinical and inflammatory markers to outcome in stable patients with cystic fibrosis (2007)

Decreased survival in patients with cystic fibrosis has been related to FEV1, BMI, and infection with Burkholderia cepacia complex (BCC). We have assessed the relationship of blood, sputum, and urine inflammatory markers to lung function, BMI, colonization with B cenocepacia (Bc), and patient survival. Thirty-nine stable cystic fibrosis (CF) patients (10 with Bc) were enrolled in a study to determine the effect of alpha-1-antitrypsin on airways inflammation. Pre-treatment measurements were used in this study. Demographics, sputum microbiology, heart rate, oxygen saturation, lung function were recorded. Blood samples were obtained for white blood count (WBC), C-Reactive Protein (CRP), and plasma neutrophil elastase/AAT complexes (pNEC). Neutrophil elastase (NE), neutrophil elastase/AAT complexes (sNEC), interleukin-8 (IL-8), TNF-receptor 1 (sTNFr), and myeloperoxidase (MPO) were measured in sputum and urinary desmosine concentration determined. Patients with Bc had significantly higher levels of pNEC, 332 +/- 91.4 ng/ml (mean +/- SEM) versus 106 +/- 18.2 ng/ml (P = 0.0005) and sNEC, 369 +/- 76.6 ng/ml versus 197 +/- 36.0 ng/ml compared to those who were not. Five deaths were reported at the end of 1 year, (four with Bc) (P = 0.011). Patients who subsequently died had significantly lower lung function FEV1, 1.2 +/- 0.2 L versus 2.0 +/- 0.1 L (P = 0.03) and FVC, 2 +/- 0.3 L versus 3.1 +/- 0.2 L (P = 0.01), compared to those that survived. There was significantly higher NE activity, 3.6 +/- 1.6 U/ml versus 1.5 +/- 0.6 U/ml (P = 0.03), pNEC, 274 +/- 99 ng/ml versus 142 +/- 30 ng/ml (P = 0.05), MPO, 163 +/- 62 mcg/ml versus 54 +/- 6.9 mcg/ml (P = 0.03), and urinary desmosines 108 +/- 19.9 pM/mg creatinine versus 51.1 +/- 3.3 pM/mg creatinine (P = 0.001), in those patients who subsequently died compared to those that survived. These data suggest there is increased neutrophil degranulation in patients infected with Bc and these patients have a poor outcome.
Transoral-transpharyngeal approach to the anterior craniocervical junction (1988)

The anterior transoral-transpharyngeal operation to correct ventral irreducible compression of the cervicomedullary junction was utilized in 72 individuals. The patients' ages ranged from 6 to 82 years, and 29 were children. The pathology encountered was primary basilar invagination, rheumatoid irreducible cranial settling, secondary basilar invagination due to migration of odontoid fracture fragments, dystopic os odontoideum, granulation masses, clivus chordoma, osteoblastoma, and chondroma of the atlas. Fifteen patients had associated Chiari malformation with basilar invagination. Fifty-two patients required subsequent atlantoaxial or occipitocervical fusion. Neurological improvement was the rule. There were two deaths within 30 days of surgery: one from myocardial infarction 4 weeks after surgery and one from Gram-negative septicemia of urinary tract origin. There was one pharyngeal wound infection. The ventral transoral approach provides a safe, rapid, and effective means for decompression of the abnormal craniovertebral junction.
Modeling clip: some more results (1990)

The modedling clip of the PHIGS ISO Standard is mathematically analysed. The most important result of this analysis is the fact that the projective image of a modding clip body (that is a not necessarily bounded convex body in space) is simply the union of two convex bodies. Furthermore, it will also be proved that in some cases one of these two bodies is empty. This fact makes the implementation of the modelling clip fairly straightforward and makes it also possible to use all already existing results on clipping against general convex bodies without change.
Polyketide Chain Length Control by Chain Length Factor (2003)

Bacterial aromatic polyketides are pharmacologically important natural products. A critical parameter that dictates product structure is the carbon chain length of the polyketide backbone. Systematic manipulation of polyketide chain length represents a major unmet challenge in natural product biosynthesis. Polyketide chain elongation is catalyzed by a heterodimeric ketosynthase. In contrast to homodimeric ketosynthases found in fatty acid synthases, the active site cysteine is absent from the one subunit of this heterodimer. The precise role of this catalytically silent subunit has been debated over the past decade. We demonstrate here that this subunit is the primary determinant of polyketide chain length, thereby validating its designation as chain length factor. Using structure-based mutagenesis, we identified key residues in the chain length factor that could be manipulated to convert an octaketide synthase into a decaketide synthase and vice versa. These results should lead to novel strategies for the engineered biosynthesis of hitherto unidentified polyketide scaffolds.