gebhart/patrepeval huggingface dataset:
Guideline for Care of Patients With the Diagnoses of Craniosynostosis (2015)

This guideline for care of children with craniosynostosis was developed by a national working group with representatives of 11 matrix societies of specialties and the national patients' society. All medical aspects of care for nonsyndromic and syndromic craniosynostosis are included, as well as the social and psychologic impact for the patient and their parents. Managerial aspects are incorporated as well, such as organizing a timely referral to the craniofacial center, requirements for a dedicated craniofacial center, and centralization of this specialized care. The conclusions and recommendations within this document are founded on the available literature, with a grading of the level of evidence, thereby highlighting the areas of care that are in need of high-quality research. The development of this guideline was made possible by an educational grant of the Dutch Order of Medical Specialists. The development of this guideline was supported by an educational grant of the Dutch Order of Medical Specialists.
Imitation in infancy: the wealth of the stimulus (2010)

Imitation requires the imitator to solve the correspondence problem--to translate visual information from modelled action into matching motor output. It has been widely accepted for some 30 years that the correspondence problem is solved by a specialized, innate cognitive mechanism. This is the conclusion of a poverty of the stimulus argument, realized in the active intermodal matching model of imitation, which assumes that human neonates can imitate a range of body movements. An alternative, wealth of the stimulus argument, embodied in the associative sequence learning model of imitation, proposes that the correspondence problem is solved by sensorimotor learning, and that the experience necessary for this kind of learning is provided by the sociocultural environment during human development. In a detailed and wide-ranging review of research on imitation and imitation-relevant behaviour in infancy and beyond, we find substantially more evidence in favour of the wealth argument than of the poverty argument.
Induced Chirality in PNA-PNA Duplexes (1995)

Complementary peptide nucleic acids (PNA) form Watson-Crick base-paired helical duplexes. The preferred helicity of such a duplex is determined by a chiral amino acid attached to the C-terminus. We here show that the induced helicity, as measured by circular dichroism (CD), is drastically dependent on the nucleobase sequence proximal to the chiral center. Chemically linked PNA tetramer duplexes of all 16 combinations of the two bases proximal to a carboxy terminal lysine residue were studied by CD. We conclude that the base next to the chiral center must be either a guanine or a cytosine for efficient stabilization of one helical sense. In case of cytosine, the subsequent base should preferably be a purine. We also show that the side chain properties of the C-terminal amino acid influence the resulting sense of helicity. The propagation length of induced chirality in PNA duplexes is found to be around 10 base pairs. Theoretical calculations of the circular dichroism for B-DNA, using the quantum mechanical matrix method of Schellman, give spectra in reasonable agreement with those found experimentally for PNA duplexes. The rate of helix conversion of the duplexes shows first-order kinetics with a rate constant in the range of minutes. Shorter duplexes are found to have lower activation energy and larger negative activation entropy for helix conversion, in agreement with a conversion mechanism in which a perfect helix is switched to the opposite handedness.
A new approach to analyze cell surface protein complexes reveals specific heterodimeric metabotropic glutamate receptors (2010)

G-protein-coupled receptors (GPCRs) can form heteromeric complexes. Herein, we describe a new approach to test the heteromerization of 2 receptors, or 2 receptor subunits, and to study the stoichiometry of the resulting complexes. As a proof-of-concept study, we investigated whether metabotropic glutamate receptors (mGluRs), in addition to being well-known homodimers, can form heteromers. To that aim, we combine the benefits of time-resolved fluorescence resonance energy transfer (trFRET) with the specific, cell-surface labeling of SNAP- and CLIP-tagged rat mGluR subunits, expressed in a mammalian cell line. First, we show that mGlu2 and mGlu4 subunits (but not mGlu2 and mGlu1) can heteromerize. Moreover, our trFRET data are consistent with mGluR subunits forming strict homodimeric receptors on single expression, and a combination of strict heterodimeric and strict homodimeric receptors on coexpression. Second, a comprehensive analysis reveals that from the 21 possible pairs of 2 mGluR subunits out of 7 subtypes (mGlu1 to 8, but not 6), only 11 are able to form heterodimers. These findings were further validated by biochemical and functional complementation studies. In addition to describing a new method to analyze cell-surface receptor complexes, our data reveal a new level of complexity within the mGluR family.
Altered surface membrane glycoproteins in Vinca alkaloid-resistant human leukemic lymphoblasts. (1979)

Abstract Starting with an established line of human leukemic lymphoblasts (CCRF-CEM), we have developed sublines with varying degrees of resistance to vinblastine by growth in the presence of sublethal concentrations of drug. The resistance of these sublines to vinblastine ranges from 10.6-fold to more than 2000-fold when compared with the sensitive parent cells. These vinblastine-resistant cells tend to form large aggregates in stationary suspension culture, suggesting the possibility of an alteration in the cell surface membrane. The surface glycoproteins of sensitive and vinblastine-resistant CCRF-CEM cells were examined by the galactose oxidase (with or without neuraminidase)-[ 3 H]borohydride procedure. It was found that a glycoprotein with a molecular weight of 170,000 to 190,000 is present on the surface of the drug-resistant cells. This prominent glycoprotein appears to be related to the degree of resistance in that it increases in amount with increased resistance to vinblastine. This relationship obtains with cells up to 269 times more resistant to this drug than is the sensitive parent line. Further increases in the degrees of resistance apparently do not lead to greater amounts of this glycoprotein, suggesting that the changes in the cell surface seen with resistance are not absolute or are not all detectable by the surface-labeling method used in this study. Finally, cells selected for high resistance to 1-β-d-arabinofuranosylcytosine have a cell surface glycoprotein pattern similar to that of the sensitive parent line, indicating that the altered glycoprotein profile shown here is not a characteristic of resistance in general but is rather associated with resistance to such Vinca alkaloids as vinblastine.
Optimization and Mechanistic Analysis of Oligonucleotide Cleavage from Palladium-Labile Solid-Phase Synthesis Supports1 (1998)

Pd(0)-labile solid-phase synthesis supports have been used to produce oligonucleotides containing 3‘-alkyl carboxylic acid and 3‘-hydroxy termini in quantitative yields. Optimization of the cleavage reaction conditions using tetrabutylammonium formate buffer resulted in quantitative yields of oligonucleotides using 4 molar equiv of Pd2(dba)3·CHCl3 in 1 h at 55 °C. A proton source facilitates cleavage of the oligonucleotide from the supports. Trace amounts of water, acting as a nucleophile on the η3-complex, presumably preventing back biting by the initially released oligonucleotide, are required to obtain reproducibly high yields of cleaved oligonucleotides during a 1 h reaction. The previously observed lability of β-cyanoethyl groups to the Pd(0) conditions has been examined using a mononucleotide substrate. Cleavage of the β-cyanoethyl group was shown to proceed to the exclusion of other alkyl groups. A mechanism involving initial insertion by Pd(0) into the carbon−oxygen bond of the β-cyanoethyl group is suggested to account for the cleavage of this group.
Prevalence of tardive dyskinesia. (1979)

Forty-four epidemiologic studies on tardive dyskinesia were evaluated as to whether they provided information on diagnostic criteria, objective scale and assessment, interobserver reliability, period of observation, and specific interhospital coordination. Studies which met these standards were reviewed for data on class of neuroleptic therapy, dose, duration, continuity of treatment, extrapyramidal toxicity, spontaneous dyskinesias, other drugs and treatment modalities, age and sex. A higher prevalence of tardive dyskinesia has been consistently noted in the elderly and in females. No other predisposing factors for tardive dyskinesia have been conclusively demonstrated thus far. Prevalence of tardive dyskinesia is estimated at 24-56% in chronic neuroleptic users.
CCured (2002)

In this paper we propose a scheme that combines type inference and run-time checking to make existing C programs type safe. We describe the CCured type system, which extends that of C by separating pointer types according to their usage. This type system allows both pointers whose usage can be verified statically to be type safe, and pointers whose safety must be checked at run time. We prove a type soundness result and then we present a surprisingly simple type inference algorithm that is able to infer the appropriate pointer kinds for existing C programs.Our experience with the CCured system shows that the inference is very effective for many C programs, as it is able to infer that most or all of the pointers are statically verifiable to be type safe. The remaining pointers are instrumented with efficient run-time checks to ensure that they are used safely. The resulting performance loss due to run-time checks is 0-150%, which is several times better than comparable approaches that use only dynamic checking. Using CCured we have discovered programming bugs in established C programs such as several SPECINT95 benchmarks.
EN LOS ANOS 80 LAS ZONAS MENOS URBANIZADAS DEL PAIS QUEDARON ATRAS (1994)

COMO PARTE DEL SEMINARIO INTERNACIONAL ECONOMIA GLOBAL Y CIUDADES SECUNDARIAS EN MEXICO. CAMBIOS EN LA ESTRUCTURA ECONOMICA Y SOCIAL DEL SISTEMA URBANO, REALIZADO POR EL CENTRO DE INVESTIGACIONES MULTIDISCIPLINARIAS Y EL INSTITUTO DE GEOGRAFIA, EL MAESTRO SALVADOR RIVERA SE REFIRIO A LA INVESTIGACION SOBRE PRODUCTIVIDAD DE LAS CIUDADES MEXICANAS, MIENTRAS QUE LA MAESTRA MARGARITA CAMARENA Y EL DOCTOR LUIS CHIA ABORDARON EL TEMA LAS TENDENCIAS DEL TRANSPORTE Y SU NUEVA ESTRUCTURA.
Patterns of Weight Change Preceding Hospitalization for Heart Failure (2007)

Increases in body weight are associated with hospitalization for heart failure and begin at least 1 week before admission. Daily information about patients' body weight identifies a high-risk period during which interventions to avert decompensated heart failure that necessitates hospitalization may be beneficial.
Histone deacetylases, transcriptional control, and cancer (2000)

A key event in the regulation of eukaryotic gene expression is the posttranslational modification of nucleosomal histones, which converts regions of chromosomes into transcriptionally active or inactive chromatin. The most well studied posttranslational modification of histones is the acetylation of epsilon-amino groups on conserved lysine residues in the histones' amino-terminal tail domains. Significant advances have been made in the past few years toward the identification of histone acetyltransferases and histone deacetylases. Currently, there are over a dozen cloned histone acetyltransferases and at least eight cloned human histone deacetylases. Interestingly, many histone deacetylases can function as transcriptional corepressors and, often, they are present in multi-subunit complexes. More intriguing, at least some histone deacetylases are associated with chromatin-remodeling machines. In addition, several studies have pointed to the possible involvement of histone deacetylases in human cancer. The availability of the cloned histone deacetylase genes has provided swift progress in the understanding of the mechanisms of deacetylases, their role in transcription, and their possible role in health and disease.
KIM185, a monoclonal antibody to CD18 which induces a change in the conformation of CD18 and promotes both LFA‐1‐ and CR3‐dependent adhesion (1993)

Unactivated peripheral blood leukocytes show little tendency to bind to other cells or matrix components, whilst, in the presence of inflammatory mediators, adhesive interactions can rapidly increase. The Leu-CAM (beta 2 integrin) family of adhesion molecules have been shown to mediate a variety of these induced adhesion events. Here we describe a monoclonal antibody against CD18, KIM185, which stimulates JY cell homotypic aggregation by a CD11 a pathway as well as inducing the adherence of neutrophils to protein-coated plastic by a CD11b-dependent mechanism. The antibody recognizes an epitope distinct from the previously described KIM127 antibody and evidence is presented that the binding of KIM185 can cause a change in the conformation of the CD18 molecule.
DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. (1991)

We have previously described the isolation of a cDNA clone, designated NKG2, that was expressed in all natural killer (NK) cells tested but not in T or B cells. In the present communication, the original isolate, when used to probe a cDNA library prepared from a CD3- NK cell clone, was found to crosshybridize with a family of transcripts that fell into four distinct groups designated NKG2-A, -B, -C, and -D. Full-length cDNA sequences were determined for each group, and the DNA and inferred peptide sequences were analyzed. All four transcripts encode type II membrane proteins of 215-233 amino acids. NKG2-A and -B peptides appear to be alternative splicing products of a single gene. NKG2-C is highly homologous with group A, having 94% homology in the external (COOH-terminal) domain and 56% homology throughout the internal and transmembrane regions. NKG2-D is distantly but significantly related (21% amino acid homology) to the first three groups. Therefore, NKG2-A, -C, and -D appear to be encoded by distinct genes within a family of NK cell-specific genes. Peptide sequence homology searches demonstrate that the NKG2 peptides are members of a supergene family that includes several other type II membrane proteins. This family is characterized by the presence of a C-type animal lectin domain, and several of its members have demonstrated transmembrane signaling capability.
General Aspects and Optimization of Enantioselective Biocatalysis in Organic Solvents: The Use of Lipases [New Synthetic Methods (76)] (1989)

Abstract Enantioselective biocatalysis in nonaqueous media is becoming increasingly important in preparative synthetic chemistry. This article discusses (1) the general catalytic properties of enzymes in nonaqueous environments, (2) the basic principles that govern lipase‐catalyzed enantioselective esterification and transesterification reactions in organic media for the preparation of optically active acids and alcohols, (3) the determination of kinetic and thermodynamic parameters, and (4) the quantitative analysis of published data.
Bovine spongiform encephalopathy: epidemiological studies on the origin (1991)

The results of further epidemiological studies of bovine spongiform encephalopathy (BSE) support the previous findings that the onset of exposure of the cattle population to a scrapie-like agent, sufficient to result in clinical disease, occurred in 1981/82. The onset of this exposure was related to the cessation, in all but two rendering plants, of the hydrocarbon solvent extraction of fat from meat and bone meal. A further possible explanation, related to the geographical variation in the reprocessing of greaves to produce meat and bone meal, was identified for the geographical variation in the incidence of BSE.
Waiting times for radiation therapy in Ontario. (2006)

BACKGROUND: The mass media and clinical journals have reported lengthy waiting times after surgery before initiation of radiation therapy (RT) for cancer across Canada. We aimed to describe the length of time between the last date of surgery or biopsy or chemotherapy and first date of RT. METHODS: This is a population-based study measuring waiting times for RT in Ontario among all patients with potentially curable cancer of the cervix, tonsil and larynx and a random sample of women who had had breast cancer resection, whose first date of RT fell between Sept. 1, 2001, and Aug. 31, 2002. Abstraction of original health care records provided each patient's demographics, cancer stage and cancer treatment (last surgery, consultation, simulation, first RT). Last dates of chemotherapy before RT were obtained from abstraction or from Ontario Health Insurance Plan (OHIP) files, and last dates of surgery before RT were compared with dates in the Canadian Institute for Health Information (CIHI) Discharge Abstract Database. RESULTS: Waiting times between the last date of surgery or chemotherapy and the first date of RT varied significantly among the health regions of Ontario. Increasing age, but not the presence of comorbidity, was associated with longer waiting times. Women who did not receive postoperative chemotherapy before RT for breast cancer waited significantly longer than all others. CONCLUSION: Measurement of waiting times for cancer RT must discount time during which adjuvant intravenous chemotherapy is administered after surgery and before RT. There appears to be a formal or informal process by which those at highest risk begin RT most rapidly.
The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models. (2003)

Malignant cells characteristically exhibit altered metabolic patterns when compared with normal mammalian cells with increased reliance on anaerobic metabolism of glucose to lactic acid even in the presence of abundant oxygen. The inefficiency of the anaerobic pathway is compensated by increased glucose flux, a phenomenon first noted by Otto Warburg approximately 80 years ago and currently exploited for 2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging in clinical radiology. The latter has demonstrated the glycolytic phenotype is a near-universal phenomenon in human cancers. The potential role of the glycolytic phenotype in facilitating tumor invasion has been investigated through mathematical models of the tumor-host interface. Modified cellular automaton and diffusion reaction models demonstrate protons will diffuse from the tumor into peritumoral normal tissue subjecting nontransformed cells adjacent to the tumor edge to an extracellular pH significantly lower than normal. This leads to normal cell death via p53-dependent apoptosis pathways, as well as degradation of the interstitial matrix, loss of intercellular gap junctions, enhanced angiogenesis, and inhibition of the host immune response to tumor antigens. Transformed cells maintain their proliferative capacity in acidic extracellular pH because of mutations in p53 or some other component in the apoptosis pathways. This allows tumor cells to remain proliferative and migrate into the peritumoral normal tissue producing the invasive phenotype. Mathematical models of invasive cancer based on tumor-induced acidification are consistent with extant data on tumor microenvironment and results from clinical positron emission tomography imaging, including the observed correlation between tumor invasiveness and glucose utilization. Novel treatment approaches focused on perturbation of the tumor microenvironment are predicted from the mathematical models and are supported by recent clinical data demonstrating the benefits of azotemia and metabolic acidosis in survival of patients with metastatic renal cancer. The evolutionary basis for adoption of the glycolytic phenotype during carcinogenesis remains unclear because it appears to confer significant competitive disadvantages on the tumor cells due to of inefficient energy production and expenditure of resources to remove the acid byproducts. We propose that the glycolytic phenotype represents a successful adaptation to environmental selection parameters because it confers the ability to invade. That is, the glycolytic phenotype allows the cell to move from the microenvironment of a premalignant lesion to adjacent normal tissue. There it competes with normal cells that are less fit than the populations within the tumor in a microenvironment of relative substrate abundance. The consequent unrestrained proliferation allows the glycolytic phenotype to emerge simultaneous with the transition from a premalignant lesion to an invasive cancer.
Immunohistochemical localization of beta‐amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy (1992)

Immunohistochemical staining with antibodies directed against four segments of the amyloid precursor protein (APP) was studied by light and electron microscopy in normal and Alzheimer (AD) brain tissue. The segments according to the Kang et al. sequence were: 18-38 (T97); 527-540 (R36); 597-620 (1-24 of beta-amyloid protein [BAP], R17); and 681-695 (R37) (Kang et al. [1987]: Nature 325:733-736). The antibodies recognized full length APP in Western blots of extracts of APP transfected cells. They stained cytoplasmic granules in some pyramidal neurons in normal appearing tissue from control and AD cases. In AD affected tissue, the antibodies to amino terminal sections of APP stained tangled neurons and neuropil threads, and intensely stained dystrophic neurites in senile plaques. By electron microscopy, this staining was localized to abnormal filaments. The antibody to the carboxy terminal segment failed to stain neurofibrillary tangles or neuropil threads; it did stain some neurites with globular swellings. It also stained globular and elongated deposits in senile plaque areas. The antibody against the BAP intensely stained extracellular material in senile plaques and diffuse deposits. By electron microscopy, the antibodies all stained intramicroglial deposits. Some of the extracellular and intracellular BAP-positive deposits were fibrillary. Communication between intramicroglial and extracellular fibrils was detected in plaque areas. These data suggest the following sequence of events. APP is normally concentrated in intraneuronal granules. In AD, it accumulates in damaged neuronal fibers. The amino terminal portion binds to abnormal neurofilaments. Major fragments of APP are phagocytosed and processed by microglia with the BAP portion being preserved. The preserved BAP is then extruded and accumulates in extracellular tissue.