gebhart/patrepeval huggingface dataset:
Using reconciliation to share files between occasionally connected computers (2002)

Future large distributed systems will be made by interconnecting highly autonomous subsystems, rather than by building ever more elaborate complexes which attempt to provide a single system image transparent to the user. The work described here explores the implications of this in the context of file sharing using occasional reconciliation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hair breakage index: an alternative tool for damage assessment of human hair. (2011)

Improper hair care, mechanical abrasion, sun damage and chemical treatment changes the physical and morphological characteristics of hair. Several methods involving microscopic techniques, protein loss and assessment of tensile properties of the hair are generally used to evaluate the extent of damage caused. These are also used to determine the protective effect of hair care products. In the present investigation, the hair breakage index (HBI) was used as an alternative tool to determine the change in the properties of hair on weathering. HBI is a measure of the diameter of hair in a given cross sectional area of a marked region of hair on the scalp. The hair diameter changes as we progress towards the tip of the hair due to breakage. The ratio of the diameter of hair bundle in the distal region to the diameter of hair bundle in the proximal region from the scalp is used as an indicator of hair breakage. Higher HBI value is an indicator of hair damage.A study was conducted for duration of 16 weeks to assess the effect of weathering due to grooming practices on HBI values. The HBI and break stress for a group of 30 subjects were measured at baseline and at the end of 16 weeks (NU). Since Coconut oil (CNO) is known to have a positive benefit on tensile properties of hair, another matched group of 30 subjects who oiled their hair daily with CNO was used as a positive control (CNO). The HBI and break stress for this group were also measured at the baseline and after 16 weeks. It was observed that the HBI significantly increased in the NU group versus the CNO user group. The break stress also significantly decreased in the NU group suggesting its correlation with the HBI data. This study demonstrates the usefulness of HBI as a simple and effective tool for determining hair damage and its protection by different hair care products.
Tissue Distribution of RNAs for Cystatins, Histatins, Statherin, and Proline-rich Salivary Proteins in Humans and Macaques (1989)

The tissue distribution of the mRNAs for a number of salivary proteins [proline-rich proteins (PRPs), statherin, cystatins, and the histatins] has been examined in humans and macaques in order to investigate their possible functions and tissue-specific regulation. We have shown that PRP RNAs (0.8-1.5 kb) are expressed in human and rhesus parotid and submandibular glands, and in the human bronchus. The genes for the acidic and basic PRPs are differentially regulated in these tissues. RNAs for acidic PRPs are predominantly expressed in the submandibular gland, for basic PRPs in the respiratory tract, and for both acidic and basic PRPs in the parotid gland. Protein studies of secretions from these tissues confirm the RNA results. Statherin RNA (0.65 kb) was detected in human and rhesus parotid and submandibular glands and the human bronchus, as well as in rhesus lacrimal glands. Statherin was found by tissue immunoperoxidase staining in the serous cells of respiratory tract submucosal glands, which is the same location for the synthesis of PRPs. Several cystatin RNAs (0.8-1.3 kb) were differentially expressed in human parotid glands, submandibular glands, and the bronchus, and in lacrimal glands from both rhesus and cynomolgus macaques. RNAs (0.6 kb) for the histatins were found only in parotid and submandibular glands. Thus, it appears that PRPs, statherin, and cystatins may play a broader role in the physiology of biological fluids and secretions than previously suspected, since they are found in secretions other than saliva. However, the functions of the histatins are restricted to saliva. These studies also pose some interesting questions regarding the differential expression of these genes in a variety of secretory tissues.
Combined inhibition of the phosphatidylinositol 3-kinase/Akt and Ras/mitogen-activated protein kinase pathways results in synergistic effects in glioblastoma cells (2006)

The present study uses cell-based screening assays to assess the anticancer effects of targeting phosphatidylinositol 3-kinase-regulated integrin-linked kinase (ILK) in combination with small-molecule inhibitors of Raf-1 or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK). The objective was to determine if synergistic interactions are achievable through the use of agents targeting two key cell signaling pathways involved in regulating glioblastoma cancer. The phosphatidylinositol 3-kinase/protein kinase B (PKB)/Akt and the Ras/MAPK pathway were targeted for their involvement in cell survival and cell proliferation, respectively. The glioblastoma cell lines U87MG, SF-188, and U251MG were transiently transfected with an antisense oligonucleotide targeting ILK (ILKAS) alone or in combination with the Raf-1 inhibitor GW5074 or with the MEK inhibitor U0126. Dose and combination effects were analyzed by the Chou and Talalay median-effect method and indicated that combinations targeting ILK with either Raf-1 or MEK resulted in a synergistic interaction. Glioblastoma cells transfected with ILKAS exhibited reduced levels of ILK and phosphorylated PKB/Akt on Ser473 but not PKB/Akt on Thr308 as shown by immunoblot analysis. These results were confirmed using glioblastoma cells transfected with ILK small interfering RNA, which also suggested enhanced gene silencing when used in combination with U0126. U87MG glioblastoma cells showed a 90% (P < 0.05) reduction in colony formation in soft agar with exposure to ILKAS in combination with GW5074 compared with control colonies. A substantial increase in Annexin V-positive cells as determined by using fluorescence-activated cell sorting methods were seen in combinations that included ILKAS. Combinations targeting ILK and components of the Ras/MAPK pathway result in synergy and could potentially be more effective against glioblastoma cancer than monotherapy.
Criterion-Related Validity of a Simple Muscle Strength Test to Assess Whole Body Muscle Strength in Chinese Children Aged 10 to 12 Years (2018)

Back muscle strength and leg muscle strength can give the highest validity of assessing whole body muscle strength, and also has higher validity in both the urban and rural children. For urban children, but not rural, the knee bent push-up also has a high validity indicator.
Activation of sulfonate ester based matrix metalloproteinase proinhibitors by hydrogen peroxide (2010)

This study details the development of matrix metalloproteinase inhibitor prodrugs (proMMPi) that are activated in the presence of reactive-oxygen species (ROS). Conventional matrix metalloproteinase inhibitors (MMPi) utilize a zinc-binding group (ZBG) that chelates to the catalytic zinc(II) ion of matrix metalloproteinases (MMPs) to inhibit their activity. To create ROS-sensitive prodrugs, sulfonate esters were used as a protecting group for the ZBG to block their metal binding ability. Surprisingly, these sulfonate esters were found to be cleaved by H(2)O(2) only when the ZBG contained an N-oxide donor atom moiety. Sulfonate ester derivatives of full-length MMPi based on these ROS-triggerable systems were synthesized. It was found that proMMPi with sulfonate ester protecting groups showed relatively high rates of cleavage in the presence of H(2)O(2) to release the active MMPi. In vitro MMP inhibition studies confirmed a significant increase in inhibitory activity of proMMPi upon addition of H(2)O(2), demonstrating the use of sulfonate esters to act as cleavable triggers for ROS-activated prodrugs.
Microfluidic vias enable nested bioarrays and autoregulatory devices in Newtonian fluids (2006)

We report on a fundamental technological advance for multilayer polydimethylsiloxane (PDMS) microfluidics. Vertical passages (vias), connecting channels located in different layers, are fabricated monolithically, in parallel, by simple and easy means. The resulting 3D connectivity greatly expands the potential complexity of microfluidic architecture. We apply the vias to printing nested bioarrays and building autoregulatory devices. A current source is demonstrated, while a diode and a rectifier are derived; all are building blocks for analog circuitry in Newtonian fluids. We also describe microfluidic septa and their applications. Vias lay the foundation for a new generation of microfluidic devices.
Variations in Arterial Blood Pressure and Photoplethysmography During Mechanical Ventilation (2006)

We analyzed ventilation-induced changes in arterial blood pressure and photoplethysmography from waveforms obtained by monitoring 57 patients in the operating room and intensive care unit. Analysis of systolic and pulse pressure variations during positive pressure ventilation, DeltaUp, DeltaDown, and changes in the preejection period on both arterial and photoplethysmographic waveforms were possible in 49 (86%) patients. The pulse pressure variation and preejection period were similar when calculated using both arterial blood pressure and photoplethysmography, whereas the other variables were different. Photoplethysmographic pulse variation >9% identified patients with arterial pulse pressure variation >13% (area under ROC curve = 0.85) or DeltaDown >5 mm Hg (area under ROC curve = 0.85). In hypotensive patients, photoplethysmographic pulse variation >9% remained the best threshold value (pulse pressure variation >13%: area under ROC curve = 0.90; DeltaDown >5 mm Hg: area under ROC curve = 0.93) for predicting fluid responsiveness. In conclusion, this study showed that pulse variations observed in the arterial pressure waveform and photoplethysmogram are similiar in response to positive pressure ventilation. Furthermore, photoplethysmographic pulse variation > 9% identifies patients with ventilation-induced arterial blood pressure variation that is likely to respond to fluid administration.
Tumor Imaging Using 1-(2'-deoxy-2'-18F- Fluoro- -D-Arabinofuranosyl)Thymine and PET (2007)

Tissue retention ratio measurements obtained over 11 min can replace flux measurements in (18)F-FMAU imaging. The SUVmean and the SUVmax in 5-11 min images correlated well with those of images obtained at 50-60 min. The quality of the images and tissue kinetics in 11 min of imaging makes it a desirable and shorter tumor imaging option.
Dramatic Enhancement of Genome Editing by CRISPR/Cas9 Through Improved Guide RNA Design (2015)

Success with genome editing by the RNA-programmed nuclease Cas9 has been limited by the inability to predict effective guide RNAs and DNA target sites. Not all guide RNAs have been successful, and even those that were, varied widely in their efficacy. Here we describe and validate a strategy for Caenorhabditis elegans that reliably achieved a high frequency of genome editing for all targets tested in vivo. The key innovation was to design guide RNAs with a GG motif at the 3' end of their target-specific sequences. All guides designed using this simple principle induced a high frequency of targeted mutagenesis via nonhomologous end joining (NHEJ) and a high frequency of precise DNA integration from exogenous DNA templates via homology-directed repair (HDR). Related guide RNAs having the GG motif shifted by only three nucleotides showed severely reduced or no genome editing. We also combined the 3' GG guide improvement with a co-CRISPR/co-conversion approach. For this co-conversion scheme, animals were only screened for genome editing at designated targets if they exhibited a dominant phenotype caused by Cas9-dependent editing of an unrelated target. Combining the two strategies further enhanced the ease of mutant recovery, thereby providing a powerful means to obtain desired genetic changes in an otherwise unaltered genome.
Mismatch correction catalyzed by cell-free extracts of Saccharomyces cerevisiae. (1986)

Heteroduplex DNA substrates containing a 4- or 7-base-pair insertion/deletion mismatch or each of the eight possible single-base-pair mismatches were constructed. Extracts of mitotic Saccharomyces cerevisiae cells catalyzed the correction of mismatched nucleotides in a reaction that required Mg2+ and had a partial requirement for ATP and the four dNTPs. The insertion/deletion mismatches and the A X C and G X T mismatches were repaired efficiently, while the six other single-base-pair mismatches were repaired poorly or at undetectable rates. Mismatch correction was accompanied by the specific incorporation of less than 20 nucleotides at or near the site of the repaired mismatch.
TheybxIGene ofBacillus subtilis168 Encodes a Class D β-Lactamase of Low Activity (2004)

The ybxI gene of Bacillus subtilis 168 encodes a preprotein of 267 amino acid residues, including a putative signal peptide of 23 residues. The YbxI primary structure exhibits high similarity scores with two members of the superfamily of the serine penicillin-recognizing enzymes: the class D beta-lactamases and the hydrophilic carboxy-terminal domains of the BlaR and MecR penicillin receptors. To determine the function and the activity of this putative penicillin-recognizing enzyme, we have subcloned the ybxI gene in the pET-26b expression vector. Transformation of Escherichia coli BL21(DE3) by the recombinant plasmid pCIP51 resulted in the export of the mature YbxI in the periplasm as a water-soluble protein. The recombinant protein was purified to 95% homogeneity. YbxI interacts with several beta-lactam antibiotics and can hydrolyze some of them. YbxI is not inactivated by clavulanic acid. The YbxI function and its enzymatic activity in B. subtilis remain unknown. The acyl-enzyme obtained after incubation of YbxI with a fluorescent derivative of ampicillin can be detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, confirming that YbxI can be acylated by beta-lactam antibiotics. YbxI does not hydrolyze some of the standard substrates of D-alanyl-D-alanine peptidases, the targets of penicillin. YbxI belongs to the penicillin-recognizing enzyme family but has an activity intermediate between those of a penicillin-binding protein and a beta-lactamase.
A novel taxane active against an orthotopically growing human glioma xenograft (2001)

The study provides evidence of an additional pharmacologic advantage of BAY 59-8862, i.e., the ability to affect the growth of intracranial tumors, probably due to the lack of recognition by the P-glycoprotein-mediated transport systems. The favorable behavior of BAY 59-8862 supports the potential interest in the analog for clinical studies in patients with brain tumors or metastases.
Herceptin-Geldanamycin Immunoconjugates (2004)

The efficacy of monoclonal antibodies (mAbs) as single agents in targeted cancer therapy has proven to be limited. Arming mAbs with a potent toxic drug could enhance their activity. Here we report that conjugating geldanamycin (GA) to the anti-HER2 mAb Herceptin improved the activity of Herceptin. The IC(50)s of the immunoconjugate H-GA were 10-200-fold lower than that of Herceptin in antiproliferative assays, depending on the cell line. The H-GA mode of action involved HER2 degradation, which was partially lactacystin sensitive and thus proteasome dependent. The linkage between GA and Herceptin remained stable in the circulation, as suggested by the pharmacokinetics of Herceptin and conjugated GA, which were almost identical and significantly different from that of free GA. Tumor uptake of Herceptin and H-GA were similar (52 +/- 7 and 43 +/- 7% of the initial injected dose per gram tissue, respectively; P = 0.077), indicating no apparent damage attributable to conjugation. Therapy experiments in xenograft-bearing mice consisted of weekly i.p. doses, 4 mg/kg for 4 months. H-GA showed a greater antitumor effect than Herceptin because it induced tumor regression in 69% of the recipients compared with 7% by Herceptin alone. Median survival time was 145 days as opposed to 78 days, and 31% of the recipients remained tumor free 2 months after therapy was terminated versus 0% in the Herceptin group. Enhancement of Herceptin activity could be of significant clinical value. In addition, the chemical linkage and the considerations in therapeutic regimen described here could be applied to other immunoconjugates for targeted therapy of a broad spectrum of cancers.
Tumor regression in monoclonal antibody-treated patients correlates with the presence of anti-idiotype-reactive T lymphocytes. (1995)

Treatment of cancer patients with unconjugated mAbs directed against tumor-associated antigens is considered passive immunotherapy due to the main suggested effector mechanisms: antibody-dependent cellular cytotoxicity, complement-dependent cytolysis, and apoptosis. The therapeutic antibody (ab1) may, however, also give rise to an idiotypic network response, i.e., an immunizing effect. Induced anti-idiotypic antibodies (ab2) mimicking the epitope that ab1 recognizes might subsequently induce an anti-anti-idiotypic humoral (ab3) and T-cell (T3) response recognizing the nominal tumor-associated antigen. Twenty-four patients with metastatic colorectal carcinoma were treated with MAb17-1A against the tumor associated antigen GA733-2 and were analyzed for the induction of T3 cells. Five of the patients responded to mAb therapy with tumor regression. These five patients all had T cells specifically recognizing human ab2 (DNA synthesis) after treatment, while all nonresponding patients lacked such T cells. Four of the five patients with ab2-reactive T cells also showed induction of T cells recognizing GA733-2. The association between T3 cells and tumor regression was highly significant (P = 0.0005). Thus, induction of T3 cells might be an important secondary antitumor effector function of therapy with unconjugated mAbs. Antibody therapy may therefore also be considered active specific immunotherapy.
Identification of CD4 and transferrin receptor antibodies by CXCR4 antibody‐guided Pathfinder selection (2003)

To generate human antibodies against CXCR4, a seven-transmembrane chemokine receptor and a principal coreceptor for HIV-1, several rounds of Pathfinder and Step-back selection from a large phage display antibody library were performed on Jurkat cells. A mAb against CXCR4 or biotinyated phage antibodies were used as guide molecules. Over 100 pan-Jurkat-cell-positive antibodies were characterized, but none were CXCR4 specific. However, several antibodies against CD4 and the transferrin receptor were identified. Our results indicate that, although Pathfinder and Step-back selection can be used to select phage antibodies on whole cells, the successful selection of certain targets is still complex and limited. The reason is probably, in part, due to the inaccessibility of the targeted extracellular structures and the range of the horseradish peroxidase-labeled guide molecule. Refinements of these techniques are required to improve target specificity and selectivity.
The Effect of Factor Xa/Phospholipid Infusion on the Acute Phase Response in Baboons (1997)

Disseminated intravascular coagulation (DIC) is a frequent complication of septicemia or tissue injury and may be accompanied by elevations of interleukin-6, a mediator of the acute phase response. It is not known whether thrombin or fibrin deposition may directly induce an acute phase response. To study this, we employed a baboon model of in vivo thrombin generation, induced by the administration of purified bovine Factor Xa and phospholipid vesicles. Two Xa/phospholipid dosages were used, a low dosage (2 animals) leading to a rapid 49% decrease in fibrinogen and a high dosage (two injections at 5h interval; 3 animals) leading to complete fibrinogen depletion. Thereafter, fibrinogen levels increased in both treatment groups, reached a maximum of 2.52 +/- 0.23 g/l (mean +/- SE, n = 5; p < 0.01 with respect to basal levels) at day 2, and returned to normal by day seven. In five control (injection of 0.15% NaCl) baboons no significant changes of fibrinogen were observed (maximal values: 1.88 +/- 0.12 g/l). Serum concentrations of C-reactive protein, an acute phase protein, increased from 3.7 +/- 0.4 mg/l to a maximum of 33.0 +/- 7.3 at day one, which was five-fold higher (p < 0.01) than in control animals at day one (6.2 +/- 0.5 mg/l). Transient increases were observed within 6h for interleukin-6 from basal values of 6.2 +/- 1.7 ng/l to peak plasma levels of 42.9 +/- 21.4 ng/l, a value three-fold higher (p = 0.07) than in control animals (14.8 +/- 4.0 ng/l). The preliminary results of this observational study suggest that factor Xa/phospholipid infusion is followed by an acute phase response, leading after one day to significant increases of fibrinogen and of C-reactive protein.
Distinct modes of floor plate induction in the chick embryo (2003)

To begin to reconcile models of floor plate formation in the vertebrate neural tube, we have performed experiments aimed at understanding the development of the early floor plate in the chick embryo. Using real-time analyses of cell behaviour, we provide evidence that the principal contributor to the early neural midline, the future anterior floor plate, exists as a separate population of floor plate precursor cells in the epiblast of the gastrula stage embryo, and does not share a lineage with axial mesoderm. Analysis of the tissue interactions associated with differentiation of these cells to a floor plate fate reveals a role for the nascent prechordal mesoderm, indicating that more than one inductive event is associated with floor plate formation along the length of the neuraxis. We show that Nr1, a chick nodal homologue, is expressed in the nascent prechordal mesoderm and we provide evidence that Nodal signalling can cooperate with Shh to induce the epiblast precursors to a floor-plate fate. These results indicate that a shared lineage with axial mesoderm cells is not a pre-requisite for floor plate differentiation and suggest parallels between the development of the floor plate in amniote and anamniote embryos.
Adiponectin is synthesized and secreted by human and murine cardiomyocytes (2005)

Adiponectin is thought to play a decisive role in the relationships among obesity, insulin resistance and cardiovascular risk. This study investigated whether cardiomyocytes synthesize and secrete adiponectin, and the effects of this hormone on cardiac cells. RT-PCR showed that mouse, rat and human cardiomyocytes produced mRNA for adiponectin and adiponectin receptors 1 and 2. Immunohistochemistry confirmed the presence of adiponectin in the cytoplasm of cultured cardiomyocytes, and radioimmunoassay showed that these cells secreted adiponectin into the culture medium. Exogenous adiponectin enhanced glucose and fatty acid uptake and induced AMPK phosphorylation in cultured cardiomyocytes. Our results demonstrate that adiponectin is synthesized and secreted by isolated murine and human cardiomyocytes, and suggest that the local production of this hormone by cardiomyocytes could be involved in the regulation of cardiac metabolism and function.