gebhart/patrepeval huggingface dataset:
Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. (1987)

The human bladder carcinoma cell line 5637 produces hematopoietic growth factors [granulocyte and granulocyte/macrophage colony-stimulating factors (G-CSF and GM-CSF)] and hemopoietin 1, which synergizes with CSFs to stimulate colony formation by primitive hematopoietic stem cells in 5-fluorouracil-treated mouse bone marrow. Molecular and functional properties of hemopoietin 1 identified it as identical to interleukin 1 alpha (IL-1 alpha). When bone marrow cells from 5-fluorouracil-treated mice were cultured in suspension for 7 days with recombinant human IL-1 alpha and/or G-CSF, it was found that the two factors synergized to enhance recovery of myelopoietic cells and colony-forming cells of both high and low proliferative potential. G-CSF alone did not sustain these populations, but the combination had greater-than-additive stimulating capacity. In vivo, 5-fluorouracil (150 mg/kg) produced profound myelosuppression and delayed neutrophil regeneration for up to 2 weeks in C3H/HeJ mice. Daily administration of recombinant human G-CSF or recombinant human IL-1 alpha accelerated recovery of stem cells, progenitor cells, and blood neutrophils by up to 4 days in 5-fluorouracil-treated C3H/HeJ and B6D2F1 mice. The combination of IL-1 alpha and G-CSF acted synergistically, reducing neutropenia and accelerating recovery of normal neutrophil numbers by up to 7 days. This was accompanied by accelerated regeneration of spleen colony-forming units and erythroid, myeloid, and megakaryocytic progenitor cells in marrow and spleen, with enhanced erythroid and granulocytic differentiation. These results indicate the possible therapeutic potential of combination therapy with IL-1 and hematopoietic growth factors such as G-CSF in the treatment of chemotherapy- or radiation-induced myelosuppression.
Video-based facial discomfort analysis for infants (2014)

Prematurely born infants receive special care in the Neonatal Intensive Care Unit (NICU), where various physiological parameters, such as heart rate, oxygen saturation and temperature are continuously monitored. However, there is no system for monitoring and interpreting their facial expressions, the most prominent discomfort indicator. In this paper, we present an experimental video monitoring system for automatic discomfort detection in infants’ faces based on the analysis of their facial expressions. The proposed system uses an Active Appearance Model (AAM) to robustly track both the global motion of the newborn’s face, as well as its inner features. The system detects discomfort by employing the AAM representations of the face on a frame-by-frame basis, using a Support Vector Machine (SVM) classifier. Three contributions increase the performance of the system. First, we extract several histogram-based texture descriptors to improve the AAM appearance representations. Second, we fuse the outputs of various individual SVM classifiers, which are trained on features with complementary qualities. Third, we improve the temporal behavior and stability of the discomfort detection by applying an averaging filter to the classification outputs. Additionally, for a higher robustness, we explore the effect of applying different image pre-processing algorithms for correcting illumination conditions and for image enhancement to evaluate possible detection improvements. The proposed system is evaluated in 15 videos of 8 infants, yielding a 0.98 AUC performance. As a bonus, the system offers monitoring of the infant’s expressions when it is left unattended and it additionally provides objective judgment of discomfort.
Experimental Improvements in the Use of Silastic Cuff for Peripheral Nerve Repair (1968)

F OR nearly 90 years experimental and clinical evidence has favored structural support about a nerve repair 7,~7 with a material that permitted direct and reproducible maximal axonal spanning without axonal disorganization or connective tissue build-up. Only during the past year has such a material become available. 4 This material, Silastic, formed into thin, elastic tubes was tested in chimpanzees against thicker tubes of the same material, wraps of millipore, collagen, or silicone, and against standard epineural suturing without wrapping. The results have been promising? However, ill-fitting tubes, regardless of the material, can strangulate a nerve anastomosis if too tight or fail to support it if too loose. 13 Therefore, establishing the best cuff dimensions, including such specifications as the proper ratio between the cross-section area of the nerve and the tube, became an important prerequisite to clinical trials. This report describes refinements in the technical details of nerve repair utilizing a Silastic cuff.
Microstructure, growth, resistivity, and stresses in thin tungsten films deposited by rf sputtering (1973)

The growth process and the microstructure of very thin W films (80–500 Å) deposited by rf sputtering on SiO2 and Si substrates have been observed by transmission electron microscopy (TEM). The resistivity and stress in these films have been related to the film microstructure, composition, and to the deposition conditions (substrate bias and rf deposition power). Thin W films deposited on silicon dioxide substrates under zero or positive bias have been found to grow in two distinct growth stages. Stage I corresponds to the formation of a thin continuous film (80–100 Å thick) of β-W. The β-W phase has the A-15 crystal structure and has been identified as a faulted W3W compound. A small grain size (50–100 Å) is characteristic of the β-W film. Stage II corresponds to the transformation of the β-W film into a pure α-W film with the bcc crystal structure. This thermally activated phase transformation takes place in the temperature range 100–200 °C. It is characterized by the growth of α-W nuclei until complete coalescence of the α-W islands; the resulting α-W film consists of large grains (1500–2500 Å) which are free of dislocations. The end of stage II occurs for a critical film thickness tc beyond which the film is a continuous α-W film. The value of tc is controlled by the rf deposition power and the substrate temperature. On the other hand, films deposited on negatively biased substrates do not contain the β-W phase. These films consist of large α-W grains (1500–2000 Å) with a high dislocation density. The resistivity of thin W films deposited under zero or positive bias is controlled by the amount of β-W present in the film. The pure β-W films have a high resistivity (100–300 μΩ cm); after the complete transformation β-W→α-W the large resistivity (30–40 μΩ cm) of these films is attributed to scattering by impurities. In particular, the lower resistivity of W films deposited under negative bias is related to their lower oxygen content. The sign and magnitude of the stress in these films are also controlled by the film microstructure, It is found that the stress in the films containing the β-W phase is always tensile with a σ of (6–12) × 109 dyn/cm2. The films consisting of α-W are always compressively stressed in the range (2–12) × 109 dyn/cm2.
Role of bile in regulation of gut motility (1995)

Bile empties into the duodenum not only after a meal but also in the interdigestive state. In man, interdigestive biliary emptying is related to fasting motor activity, the migrating motor complex (MMC), in the stomach and small bowel and generally occurs during phase 2 preceding a gastroduodenal phase 3 activity (activity front). It seems that the main regulatory peptide to initiate phase 3 is motilin. During a period with 13 phase 3 activities of MMC, 18 episodes of gall-bladder emptying and 19 motilin peaks were observed. Such a peak of plasma motilin usually took place 25 +/- 11 min after onset of biliary emptying. In conclusion, data indicate that motilin is released to the circulation by the biliary output and induces phase 3 of MMC. The induced phase 3 propels bile acids along the gut to promote their absorption in the distal intestine. The choleretic action of recycling of bile acids may cause subsequent episodes of biliary emptying with motilin release by the action of the enterohepatic circulation of bile acids. In such a manner the MMC may be withheld as a recycling motility pattern.
New developments in chemotherapy for advanced non-small cell lung cancer (2006)

Management of non-small cell lung cancer has improved considerably in the past decade. The overall benefit of chemotherapy over supportive care has been shown, platinum-based doublets have been established, nonplatinum regimens have been developed, chemotherapy has been used more broadly in subgroups of patients who have been previously neglected, and a shorter chemotherapy duration has been shown to be equally effective. After hitting a plateau in the benefit of chemotherapy, new drugs with novel action mechanisms such as the ones described here offer hope to improve therapy for this disease.
Macrophage-derived Chemokine Is a Functional Ligand for the CC Chemokine Receptor 4 (1998)

Macrophage-derived chemokine (MDC) is a recently identified member of the CC chemokine family. MDC is not closely related to other chemokines, sharing most similarity with thymus- and activation-regulated chemokine (TARC), which contains 37% identical amino acids. Both chemokines are highly expressed in the thymus, with little expression seen in other tissues. In addition, the genes for MDC and TARC are encoded by human chromosome 16. To explore this relationship in greater detail, we have more precisely localized the MDC gene to chromosome 16q13, the same position reported for the TARC gene. We have also examined the interaction of MDC with CC chemokine receptor 4 (CCR4), recently shown to be a receptor for TARC. Using a fusion protein of MDC with secreted alkaline phosphatase, we observed high affinity binding of MDC-secreted alkaline phosphatase to CCR4-transfected L1.2 cells (Kd = 0.18 nM). MDC and TARC competed for binding to CCR4, while no binding competition was observed for six other chemokines (MCP-1, MCP-3, MCP-4, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta). MDC was tested for calcium mobilization in L1.2 cells tranfected with seven different CC chemokine receptors. MDC induced a calcium flux in CCR4-transfected cells, but other receptors did not respond to MDC. TARC, which also induced calcium mobilization in CCR4 transfectants, was unable to desensitize the response to MDC. In contrast, MDC fully desensitized a subsequent response to TARC. Both MDC and TARC functioned as chemoattractants for CCR4 transfectants, confirming that MDC is also a functional ligand for CCR4. Since MDC and TARC are both expressed in the thymus, one role for these chemokines may be to attract CCR4-bearing thymocytes in the process of T cell education and differentiation.
Src Family Kinases: Potential Targets for the Treatment of Human Cancer and Leukemia (2003)

The inherited or acquired deregulation of protein kinase activity has been implicated in the pathogenesis of many human diseases, including cancer. Therefore, the inhibition of kinases has been proposed to be a promising strategy in the context of anti-cancer treatment. Many other kinases have been selected as drug discovery targets based on the prevalence of mutations, over-expression and unscheduled activation in human cancer. Of the various protein kinases chosen, Src family kinases are amongst the most extensively studied kinase oncogenes in academia and industry. This review focuses on our current understanding of the deregulation and role of Src family kinases in human cancer and leukemia. Recent data implicate the action of c-Src in cancer metastasis, mediated by up-regulation of various protease systems (calpain, uPA) as well as disruption of E-cadherin signalling. Moreover, novel roles of various Src family members in the development of human leukemia have been found. New insights into downstream signalling mechanisms, including the activation of STAT3, PDK1 and Akt, further corroborate the importance of Src family kinases in tumorigenesis and chemoresistance. Despite our rather clear understanding of Src family kinases as pro-oncogenes no Src family kinase inhibitor has entered a clinical trial so far. This review will discuss prerequisites to be fulfilled for clinically targeting c-Src and its homologues using small molecule drugs.
Adsorption, Diffusion, and Self‐Assembly of an Engineered Gold‐Binding Peptide on Au(111) Investigated by Atomic Force Microscopy (2009)

Go for the gold! The structural evolution of peptide binding and assembly on a Au(111) surface is dynamic and involves surface diffusion and multiple stages of molecular thin-film topology development (see schematic depiction and corresponding AFM images). The new fundamental observations may form the basis of peptide-based novel hybrid molecular technologies of the future.
Mode of Inheritance of Decreased C3b Receptors on Erythrocytes of Patients with Systemic Lupus Erythematosus (1982)

The erythrocytes of patients with systemic lupus erythematosus have been shown to have a decreased number of receptors for the major cleavage fragment of the third component of complement (C3b). We studied the basis for this decreased number of C3b receptors by measuring the uptake of anti-C3b-receptor antibody on cells from 113 normal subjects, 38 patients with systemic lupus erythematosus, 14 of their spouses, and 47 of their relatives. The normal subjects had 5014 +/- (mean +/- S.E.M.) receptor sites per cell, but the patients and their relatives had significantly fewer sites--2809 +/- 241 and 3167 +/- 196, respectively (P less than 0.0005). The number of sites in the patients' spouses did not differ from normal (P greater than 0.3). Three phenotypes, indicated by the numbers of receptors, occurred in the normal population; a high phenotype (HH, with 5500 to 8500 sites per cell), an intermediate phenotype (HL, with 3000 to 5499), and a low phenotype (LL, less than 3000). These three phenotypes were present in 34, 54, and 12 percent, respectively, of the normal subjects; in contrast, 5, 42, and 53 per cent of patients had these respective phenotypes. Pedigree analyses indicated that these phenotypes were inherited in an autosomal codominant manner. We conclude that the decreased number of C3b receptors in lupus is inherited, not acquired.
The Mouse Clock Mutation Behaves as an Antimorph and Maps Within the W19H Deletion, Distal of Kit (1997)

Clock is a semidominant mutation identified from an N-ethyl-N-nitrosourea mutagenesis screen in mice. Mice carrying the Clock mutation exhibit abnormalities of circadian behavior, including lengthening of endogenous period and loss of rhythmicity. To identify the gene affected by this mutation, we have generated a high-resolution genetic map (> 1800 meioses) of the Clock locus. We report that Clock is 0.7 cM distal of Kit on mouse chromosome 5. Mapping shows that Clock lies within the W19H deletion. Complementation analysis of different Clock and W19H compound genotypes indicates that the Clock mutation behaves as an antimorph. This antimorphic behavior of Clock strongly argues that Clock defines a gene centrally involved in the mammalian circadian system.
Enhancing the Thermoelectric Properties of Germanium Antimony Tellurides by Substitution with Selenium in Compounds GenSb2(Te1–xSex)n+3 (0 ≤ x ≤ 0.5; n ≥ 7) (2014)

Quenched pseudocubic germanium antimony tellurides (GST compounds) exhibit promising thermoelectric properties. These are related to the nanostructures which can be influenced by varying the composition and the thermal treatment. The substitution of Te by Se in bulk samples of GenSb2Ten+3 with high thermoelectric figures of merit (ZT) is possible over a wide compositional range. This results in solid solution series GenSb2(Te1–xSex)n+3 with 0 < x < 0.75 for n ≥ 7. Se substitution reduces the average lateral extension of the defect layers in quenched samples. This is a consequence of the reduced mobility during the quenching process due to the lower cubic to trigonal phase transition temperatures of Se-substituted samples. Most pronounced for n = 7, Se doping increases the transition temperatures between the nanostructured (pseudo)cubic modification of quenched samples and their layered trigonal phase. This increases the temperature ranges in which the materials can be employed without altering their nanostructures and properties. When Se is introduced, the Seebeck coefficient increases and the thermal conductivity decreases. The ZT value of Ge7Sb2Te8Se2, for instance, increases up to 1.2 at 425 °C, which is 6 times higher than that of Ge7Sb2Te10. Similarly, the ZT value of Ge12Sb2(Te1–xSex)15 increases up to a factor of 2 for x = 0.2 at temperatures below 400 °C. The most promising thermoelectric properties (ZT = 1.2 at 425 °C for n = 7 and ZT = 1.1 at 350 °C for n = 12) are observed for x = 0.2 whereas higher Se substitution rates result in a less pronounced effect. The average structures were determined by powder as well as single crystal X-ray diffraction (SCXRD). The real structure of quenched GenSb2(Te1–xSex)n+3 (0 ≤ x ≤ 0.5; n ≥ 7) bulk material was investigated by high-resolution electron microscopy (HRTEM) with respect to the degree of substitution (x) and correlated with the resulting changes of the thermoelectric properties. The decrease of the lateral extension of the defect layers with increasing Se content as found by HRTEM and electron diffraction is confirmed by SCXRD data for Ge∼5Sb2(Te0.13Se0.87)∼8.
CD105 antagonizes the inhibitory signaling of transforming growth factor βl on human vascular endothelial cells (2000)

CD105 (endoglin), a receptor for transforming growth factor beta (TGFbeta), is highly expressed in tissue-cultured, activated endothelial cells in vitro and in tissues undergoing angiogenesis in vivo. The absence of CD105 in knockout mice leads to their death from defective vascular development, but the role of CD105 in the modulation of angiogenesis has not been elucidated. TGFbeta1 is a well-recognized regulator of angiogenesis. Using an antisense approach, we have shown that inhibition of CD105 protein translation in cultured human endothelial cells enhances the ability of TGFbeta1 to suppress growth and migration in these cells. The ability of endothelial cells to form capillary tubes was evaluated by the use of a 3-dimensional collagen matrix system where TGFbeta1 not only reduced the length of capillary-like structures, but also caused massive mortality in CD105-deficient cells compared to control cultures. These results provide direct evidence that CD105 antagonizes the inhibitory effects of TGFbeta1 on human vascular endothelial cells and that normal cellular levels of CD105 are required for the formation of new blood vessels.
Insights on Evolution of Virulence and Resistance from the Complete Genome Analysis of an Early Methicillin-Resistant Staphylococcus aureus Strain and a Biofilm-Producing Methicillin-Resistant Staphylococcus epidermidis Strain (2005)

Staphylococcus aureus is an opportunistic pathogen and the major causative agent of numerous hospital- and community-acquired infections. Staphylococcus epidermidis has emerged as a causative agent of infections often associated with implanted medical devices. We have sequenced the approximately 2.8-Mb genome of S. aureus COL, an early methicillin-resistant isolate, and the approximately 2.6-Mb genome of S. epidermidis RP62a, a methicillin-resistant biofilm isolate. Comparative analysis of these and other staphylococcal genomes was used to explore the evolution of virulence and resistance between these two species. The S. aureus and S. epidermidis genomes are syntenic throughout their lengths and share a core set of 1,681 open reading frames. Genome islands in nonsyntenic regions are the primary source of variations in pathogenicity and resistance. Gene transfer between staphylococci and low-GC-content gram-positive bacteria appears to have shaped their virulence and resistance profiles. Integrated plasmids in S. epidermidis carry genes encoding resistance to cadmium and species-specific LPXTG surface proteins. A novel genome island encodes multiple phenol-soluble modulins, a potential S. epidermidis virulence factor. S. epidermidis contains the cap operon, encoding the polyglutamate capsule, a major virulence factor in Bacillus anthracis. Additional phenotypic differences are likely the result of single nucleotide polymorphisms, which are most numerous in cell envelope proteins. Overall differences in pathogenicity can be attributed to genome islands in S. aureus which encode enterotoxins, exotoxins, leukocidins, and leukotoxins not found in S. epidermidis.
Nitric Oxide-Releasing Alginates (2018)

Low and high molecular weight alginate biopolymers were chemically modified to store and release potentially therapeutic levels of nitric oxide (NO). Carbodiimide chemistry was first used to modify carboxylic acid functional groups with a series of small molecule alkyl amines. The resulting secondary amines were subsequently converted to N-diazeniumdiolate NO donors via reaction with NO gas under basic conditions. NO donor-modified alginates stored between 0.4-0.6 μmol NO·mg<sup>-1</sup>. In aqueous solution, the NO-release kinetics were diverse (0.3-13 h half-lives), dependent on the precursor amine structure. The liberated NO showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus with pathogen eradication efficiency dependent on both molecular weight and NO-release kinetics. The combination of lower molecular weight (∼5 kDa) alginates with moderate NO-release durations (half-life of ∼4 h) resulted in enhanced killing of both planktonic and biofilm-based bacteria. Toxicity against human respiratory epithelial (A549) cells proved negligible at NO-releasing alginate concentrations required to achieve a 5-log reduction in viability in the biofilm eradication assay.
Progress in the Delivery of Therapeutic Oligonucleotides: Organ/Cellular Distribution and Targeted Delivery of Oligonucleotides In Vivo (2003)

Oligonucleotide (ODN) therapy is a powerful tool for modulation of gene expression in vivo. With advances in ODN chemistry and progress in formulation development, ODNs are becoming widely acceptable drugs. This review summarizes the current status and future trend of the in vivo application of ODN therapeutics, especially antisense ODNs. Here, we review the current understanding of the tissue/organ distribution and cellular uptake of ODN drugs administered parenterally or nonparenterally to intact animals. The problems and advantages inherent in the use of different delivery methods for the treatment of particular diseases are discussed in detail. Emphasis is placed on the most widely studied ODN analogs, the phosphorothioates (PS). Lessons learned from antisense PS studies have broad implications for ODN therapeutics in general.
Natural History of Cervical Intraepithelial Neoplasia (1993)

The literature dealing with the natural history of cervical intraepithelial neoplasia (CIN) since 1950 is reviewed, in particular from the viewpoint of regression, persistence, and progression. When stratified into the various grades of severity, the composite data indicate the approximate likelihood of regression of CIN 1 is 60%, persistence 30%, progression to CIN 3 10%, and progression to invasion 1%. The corresponding approximations for CIN 2 are 40%, 40%, 20%, and 5%, respectively. The likelihood of CIN 3 regressing is 33% and progressing to invasion greater than 12%. It is obvious from the above figures that the probability of an atypical epithelium becoming invasive increases with the severity of the atypia, but does not occur in every case. Even the higher degrees of atypia may regress in a significant proportion of cases. As morphology by itself does not predict which lesion will progress or regress, future efforts should seek factors other than morphological to determine the prognosis in individual patients.