gebhart/patrepeval huggingface dataset:
Cytosolic pH regulation in osteoblasts. Regulation of anion exchange by intracellular pH and Ca2+ ions. (1990)

Measurements of cytosolic pH (pHi) 36Cl fluxes and free cytosolic Ca2+ concentration ([Ca2+]i) were performed in the clonal osteosarcoma cell line UMR-106 to characterize the kinetic properties of Cl-/HCO3- (OH-) exchange and its regulation by pHi and [Ca2+]i. Suspending cells in Cl(-)-free medium resulted in rapid cytosolic alkalinization from pHi 7.05 to approximately 7.42. Subsequently, the cytosol acidified to pHi 7.31. Extracellular HCO3- increased the rate and extent of cytosolic alkalinization and prevented the secondary acidification. Suspending alkalinized and Cl(-)-depleted cells in Cl(-)-containing solutions resulted in cytosolic acidification. All these pHi changes were inhibited by 4',4',-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) and H2DIDS, and were not affected by manipulation of the membrane potential. The pattern of extracellular Cl- dependency of the exchange process suggests that Cl- ions interact with a single saturable external site and HCO3- (OH-) complete with Cl- for binding to this site. The dependencies of both net anion exchange and Cl- self-exchange fluxes on pHi did not follow simple saturation kinetics. These findings suggest that the anion exchanger is regulated by intracellular HCO3- (OH-). A rise in [Ca2+]i, whether induced by stimulation of protein kinase C-activated Ca2+ channels, Ca2+ ionophore, or depolarization of the plasma membrane, resulted in cytosolic acidification with subsequent recovery from acidification. The Ca2+-activated acidification required the presence of Cl- in the medium, could be blocked by DIDS, and H2DIDS and was independent of the membrane potential. The subsequent recovery from acidification was absolutely dependent on the initial acidification, required the presence of Na+ in the medium, and was blocked by amiloride. Activation of protein kinase C without a change in [Ca2+]i did not alter pHi. Likewise, in H2DIDS-treated cells and in the absence of Cl-, an increase in [Ca2+]i did not activate the Na+/H+ exchanger in UMR-106 cells. These findings indicate that an increase in [Ca2+]i was sufficient to activate the Cl-/HCO3- exchanger, which results in the acidification of the cytosol. The accumulated H+ in the cytosol activated the Na+/H+ exchanger. Kinetic analysis of the anion exchange showed that at saturating intracellular OH-, a [Ca2+]i increase did not modify the properties of the extracellular site. A rise in [Ca2+]i increased the apparent affinity for intracellular OH- (or HCO3-) of both net anion and Cl- self exchange. These results indicate that [Ca2+]i modifies the interaction of intracellular OH- (or HCO3-) with the proposed regulatory site of the anion exchanger in UMR-106 cells.
Long-Term (15 Years) Results After Radical Prostatectomy For Clinically Localized (Stage T2c Or Lower) Prostate Cancer (1994)

To provide information about long-term outcome after radical prostatectomy for clinically localized prostatic cancer (stage T2c or lower), we undertook a retrospective analysis of 3,170 consecutive patients (mean age 65.3 +/- 6.4 years, range 31 to 81) with a mean followup of 5 years. Complication rates for patients who underwent prostatectomy before 1988 were compared with those who underwent radical prostatectomy more recently. Of the patients 49 (1.5%), 178 (5.6%), 897 (28%) and 2,047 (65%) had clinical stages T1a, T1b, T2a and T2b,c disease, respectively. The Gleason score was 3 or less in 292 patients (9%) and 7 or greater in 782 (25%). Overall, 438 patients (14%) died, 159 (5%) of cancer. The crude 10 and 15-year survival rates for all patients were 75% and 60%, respectively, which is comparable to the expected survival of a control group (67% and 46%). The cause specific survival rates were 90% and 82%, respectively, metastasis-free survival rates 82% and 76%, local recurrence-free survival rates 83% and 75%, overall recurrence-free rates 72% and 61%, and overall recurrence plus prostate specific antigen progression-free (greater than 0.2 ng./ml.) rates 52% and 40%, respectively. Clinical stage did not significantly affect survival but tumor grade was associated: 10 and 15-year cause specific survival rates were 95% and 93%, respectively, for a Gleason score of 3 or less, 90% and 82%, respectively, for a score of 4 to 6, and 82% and 71%, respectively, for a score of 7 or more. Of all patients 26% received adjuvant treatment (hormonal and/or radiation) within 3 months postoperatively because of advanced local pathological stage (pT3 or higher) or margin positive disease. The 30-day mortality rate was 0.3% (0% for 1,728 patients who underwent surgery in 1988 or later). Only 1 patient in the 70 year or older age group died during hospitalization. Complications decreased with time. In a contemporary group the complications were rectal injury in 0.6% of the patients, colostomy in 0.06%, myocardial infarction in 0.4%, deep venous thrombosis in 1.1%, pulmonary embolism in 0.7% and total urinary incontinence (3 or more pads per day) in 0.8%. Recent intraoperative blood loss was a median of 600 ml., and the incidence of recent need for any transfusion was 31% and it is presently less than 5%. In this series patients undergoing radical prostatectomy for clinically localized prostate cancer were usually healthy and, thus, had low co-morbidity. Survival rates at 10 and 15 years compare favorably with those of an age-matched control group.(ABSTRACT TRUNCATED AT 400 WORDS)
Bioconjugated Nanoparticles for DNA Protection from Cleavage (2003)

We have developed a novel method to protect DNA from cleavage using bioconjugated nanoparticles. Positively charged amino-modified silica nanoparticles have been directly prepared using water-in-oil microemulsion. Plasmid DNA can be easily enriched onto the positively charged nanoparticle surface, and the DNA strands are well protected from enzymatic cleavage. When incubated with nuclease enzyme for enzymatic cleavage, free plasmid DNA strands are completely cleaved, while those on the nanoparticle surfaces are intact. Our results clearly demonstrate unique properties of nanomaterials when combined with biomolecules. Our simple bionanotechnology will be highly useful in DNA separation, manipulation, and detection, and possibly in genetic engineering and gene therapy, as plasmid DNA can be protected in cellular environments without any change in its property.
Signaling Pathways in T Follicular Helper Cells (2010)

Th cell functional subsets have unique transcriptional programs that form the molecular basis for T cell differentiation and functions. T follicular helper (TFH) cells have emerged as the main providers of T cell help to B cells during the germinal center (GC) reaction, where B cells undergo selection events through competition for Ag and for access to GC T cell-mediated prosurvival and differentiation signals. Because T cell help is one limiting factor for GC B cells, the molecular mechanisms controlling TFH cell abundance and functionality are central to the GC reaction and generation of long-term humoral immunity. Two signaling pathways are absolutely critical for TFH cells: phosphoinositide-3 kinase pathway and the signaling lymphocyte activation molecule-associated protein. In this review, the molecular mechanisms constituting the signaling network in TFH cells will be explored.
Endoscopic topical therapy for the treatment of Helicobacter pylori infection. (1996)

We modified a novel topical therapeutic method for the treatment of Helicobacter pylori infection to increase its effectiveness and tolerability. Sixty-six patients (with nonulcer dyspepsia, inactive ulcer, or active ulcer) were given lansoprazole (30 mg, h.s.) and pronase (18,000 tyrosine units, b.i.d.) orally for 2 days before the topical therapy. One hundred milliliters of 7% sodium bicarbonate solution containing bismuth subnitrate, amoxicillin, metronidazole (at two different regimens), and pronase was instilled into the stomach through an endoscope. A double-lumen tube with a balloon at the tip was inserted into the duodenum along with the endoscope. The balloon was inflated with 25 ml of air and was lodged postbulbarly. The solution was kept in the stomach for 2 h, and the patient's position was changed every 15 min from the sitting to the supine, prone, and right lateral position, each position being maintained twice, to expose the entire gastric mucosa. The solution was aspirated at the end of the procedure. H. pylori infection was cured in 16/22 (72.7%) of patients with nonulcer dyspepsia, in 21/26 (80.7%) of patients with inactive ulcer, and in 1/18 (5.6%) patients with active ulcer. H. pylori eradication was confirmed 4 weeks after the therapeutic procedure by smear, culture, and histology of antral and corpus biopsy specimens. Side effects (loose stools) were observed in two patients only, and one patient had loss of appetite. These effects were transient. This endoscopic topical therapy for H. pylori infection is a safe, effective, and well tolerated procedure. With further modifications of the drug regimens and the method itself, this procedure could be of interest as anti-H. pylori therapy.
Neutron scattering analysis of bacterial lipopolysaccharide phase structure. Changes at high pH. (1987)

The aggregate structure of lipopolysaccharide isolated from an Re strain of Escherichia coli was examined at different pH values using small angle neutron scattering.At pH values of 6 and 7.4, angle-averaged scattering of the sodium salt of this isolate was consistent with randomly coiled tubular micelles approximately 100 A in diameter.At pH 9.1, however, Kratky analysis of the scattering data was distinctly different and consistent with pairing of uniform tubular micelle sections of length 1440 and 110 A in diameter.Contrast variation measurements of the micelles yielded an average micellar weight of the sample at pH 9.1 of approximately 1.1 1 X lo' daltons and suggested that the aggregates were tubular micelles of size and length similar to that derived from the scattering intensity data.Anisotropic scattering patterns of samples under shear indicated a rigidification of the micelles as the pH was increased to 9.1 and the temperature decreased from 25 to 10 "C.The rotational diffusion constants deduced from the observed shear anisotropy indicate that the structure at pH 9.1 must have smallest and largest dimensions which differ by at least an order of magnitude, ruling out spherical or moderately ellipsoidal structures.Analysis of the shear rate needed to induce anisotropic scattering indicated that the stiffness leagth of the micelles at pH 9.1 was approximately 1000 A and decreased at higher and lower pH values.A variety of physical techniques has been used to measure the architecture and conformation of isolated LPS' from smooth and rough strains of enteric bacteria (1-6).While some investigators suggest that under most conditions extracted LPS exists as bilayers (1, 5), others have indicated that, under certain conditions, LPS may form nonlamellar aggregates (2-4,6).Recent studies have suggested that ReLPS may form inverted micellar structures (3, 7), and that LPS from smooth strains (8) as well as rough LPS under conditions of high pH (7) forms tubular micelles.To further characterize
Design and Implementation of a Portable Wireless System for Structural Health Monitoring (2016)

In the health monitoring of large metal structure, the traditional strain measurement systems with wired and bulky instruments face the challenges of harsh environment, changing network topology and limited energy supply. To meet these requirements and improve the efficiency, a portable wireless strain monitoring system combined with wireless sensor network technology and portable design has been developed in this paper. Consisting of handheld coordinator, router and sensor, this novel system takes miniaturization, portability and low-power design as core capabilities in both software and hardware design. With tests in laboratory environment, its time domain response and power consumption have been analyzed to verify its performance and efficiency. Additionally, after calibration on an equal strength cantilever, comparative tests on quayside cranes have been explored to show that this system has an equivalent accuracy compared with the traditional measurement system. However, it improves the work efficiency and can meet the serious challenges within health monitoring of large metal structure.
Geometric decision trees for optical character recognition (extended abstract) (1997)

A fundamental problem in computer vision is identifying which of a given set of geometric models is present in animage. Reconsider anapproach to model recognition basedon computing efficient strategies (decision trees) for 'probing" a scanned image of a typeset document, in order to perform fast and effective optical character recognition (OCR). We consider a "proben to be a simply computed local operator that can be applied to discriminate between two sets of possible models. By carefully constructing effective probes, and assembling them into a geometric decision tree, we have devised, implemented, and compared a variety of methods to perform OCR. In this paper, we present algorithms for probing strategies and decision tree construction, and we report experiment al results on the effectiveness of theae algorithms in identifying English characters and numerals in scanned images of printed pages of text. These algorithms are implemented as part of a system used by a document processing company (Syngen Corp.).
Cyclophosphamide, doxorubicin, and vincristine in etoposide- and cisplatin-resistant small cell lung cancer. (1987)

For two chemotherapy regimens to be truly non-cross-resistant, each should be active as first-line therapy and also as second-line therapy. The effectiveness of both cyclophosphamide, doxorubicin, and vincristine (CAV) and etoposide and cisplatin (VPP) in previously untreated patients with small cell lung cancer has been well-documented. Also, VPP has caused tumor regression in up to 50% of patients when used as second-line therapy after CAV. The effectiveness of CAV after progression or relapse after VPP has not been documented. We identified 29 patients who received CAV after their tumors failed to respond or relapsed after VPP or etoposide and carboplatin (VPC). There were 21 male and eight female patients (median age, 57 years; range, 30-79). Thirteen patients were treated following failure to respond to VPP or VPC and 16 at the time of relapse. Eight patients had limited disease and 21 had extensive disease. Metastatic sites included liver (11 patients), bone (ten), lymph nodes (seven), bone marrow (three), brain (four), and contralateral lung (one). There were three complete responses (durations of 16, 22, and 26 weeks) and five partial responses (duration, 8+ to 36 weeks). Three patients had stable disease and 18 patients had disease progression while receiving treatment. The median survival of the entire group was 15 weeks. Responding patients had a median survival of 34 weeks (range, 8+ to 72+) and stable and nonresponding patients had a survival of only 9 weeks (range, 2-38). A granulocyte count nadir less than 500 X 10(9)/L was seen after 7.9% of evaluable treatment cycles and a platelet count nadir less than 50,000 X 10(9)/L occurred after only 5.3% of cycles. Five patients required transfusion for anemia, and two patients required dose reduction of vincristine for peripheral neuropathy. This study demonstrates that CAV has limited activity following failure to respond to VPP.
A Carboxyl-Terminal Propeptide Is Necessary for Proper Sorting of Barley Lectin to Vacuoles of Tobacco (1990)

Sebastian Y. Bednarek, Thea A. Wilkins, James E. Dombrowski, Natasha V. Raikhel, A Carboxyl-Terminal Propeptide Is Necessary for Proper Sorting of Barley Lectin to Vacuoles of Tobacco, The Plant Cell, Vol. 2, No. 12 (Dec., 1990), pp. 1145-1155
The gastrointestinal stem cell (2004)

The longevity of adult stem cells, and their potential for vast tissue regeneration, makes them a focal point of current research and debate, with future aspirations for the use of stem cells in the treatment of a number of human pathological conditions. Due to the rapid rate of cell turnover in the gastrointestinal tract, the stem cells of this tissue are amongst the most assiduous in the body, although they remain unidentified to this day due to their immature, undifferentiated phenotype. However, our knowledge of the mechanisms regulating gastrointestinal stem cell function is evolving, with the identification of putative cellular markers and the elucidation of signalling pathways which regulate cell behaviour in the normal and neoplastic gastrointestinal tract. This review describes the fundamental properties of the gastrointestinal stem cell including: (i) their number, location and origins, (ii) their primary function of deriving gastrointestinal cell lineages and maintaining tissue homeostasis, (iii) the acquisition of gastrointestinal cell lineages from adult stem cells of extraneous tissues and the consequences of this in a therapeutic context, and (iv) the genetic and morphological phenomena surrounding neoplastic transformation in the gastrointestinal tract.
A Probabilistic Approach to the Patient Identification Problem (1981)

Patient identification, viz, the association of a person with a hospital medical record number is the foundation of all hospital information systems. An advanced empirically based algorithm has been utilized at the University of California, San Francisco Hospitals and Clinics for patient identification since 1978. A new algorithm based on a probability model has been designed and tested and found to provide a meaningful enhancement over the previous highly successful system. The algorithm provides the system user with a probability estimate of a match between the information provided by a person presenting to the hospital and records contained in the patient identification system file. This probability based algorithm has the advantage of not only providing weights for matching specific variables in a record, such as last name, first name, date of birth, etc., but has the ability to provide quantitative differentiation within a single variable, such as last name, even when an identical match is found.
Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors (2020)

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma driven by mutations in <i>KIT</i> or platelet-derived growth factor α (<i>PDGFR</i>α). Although first-line treatment, imatinib, has revolutionized GIST treatment, drug resistance due to acquisition of secondary <i>KIT</i>/<i>PDGFR</i>α mutations develops in a majority of patients. Second- and third-line treatments, sunitinib and regorafenib, lack activity against a plethora of mutations in KIT/PDGFRα in GIST, with median time to disease progression of 4 to 6 months and inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) causing high-grade hypertension. Patients with GIST have an unmet need for a well-tolerated drug that robustly inhibits a range of KIT/PDGFRα mutations. Here, we report the discovery and pharmacological characterization of AZD3229, a potent and selective small-molecule inhibitor of KIT and PDGFRα designed to inhibit a broad range of primary and imatinib-resistant secondary mutations seen in GIST. In engineered and GIST-derived cell lines, AZD3229 is 15 to 60 times more potent than imatinib in inhibiting KIT primary mutations and has low nanomolar activity against a wide spectrum of secondary mutations. AZD3229 causes durable inhibition of KIT signaling in patient-derived xenograft (PDX) models of GIST, leading to tumor regressions at doses that showed no changes in arterial blood pressure (BP) in rat telemetry studies. AZD3229 has a superior potency and selectivity profile to standard of care (SoC) agents-imatinib, sunitinib, and regorafenib, as well as investigational agents, avapritinib (BLU-285) and ripretinib (DCC-2618). AZD3229 has the potential to be a best-in-class inhibitor for clinically relevant KIT/PDGFRα mutations in GIST.
Intergeneric Transfer and Functional Expression of the Tomato Disease Resistance Gene Pto (1995)

Caius M. T. Rommens, John M. Salmeron, Giles E. D. Oldroyd, Brian J. Staskawicz, Intergeneric Transfer and Functional Expression of the Tomato Disease Resistance Gene Pto, The Plant Cell, Vol. 7, No. 10 (Oct., 1995), pp. 1537-1544
A taskonomy of 3D web use (2011)

This paper aims to shed some light on the fundamental tasks users engage in while browsing the 3D Web. Firstly, we will provide an overview and discussion of several field studies that provide insights on how the current version of the Web is used focusing on the tasks that users carry out. Then we will present a comprehensive review of the state of the art of mouse-based 3D interaction techniques for Desktop 3D Virtual Environments (DVEs). Finally, we will introduce a simple taxonomy - a "3D Web Taskonomy" that was designed to assists designers and developers of interactive 3D Web applications to better evaluate their options when choosing and implementing an interaction technique.
Sucrose Release into the Endosperm Cavity of Wheat Grains Apparently Occurs by Facilitated Diffusion across the Nucellar Cell Membranes (1995)

Nutrients required for the growth of the embryo and endosperm of developing wheat (Triticum aestivum L.) grains are released into the endosperm cavity from the maternal tissues across the nucellar cell plasma membranes. We followed the uptake and efflux of sugars into and out of the nucellus by slicing grains longitudinally through the endosperm cavity to expose the nucellar surface to experimental solutions. Sucrose uptake and efflux are passive processes. Neither was sensitive to metabolic inhibitors, pH, or potassium concentration. p-Chloromercuribenzene sulfonate, however, strongly inhibited both uptake and efflux, although not equally. Except for p-chloromercuribenzene sensitivity, these characteristics of efflux and the insensitivity of Suc movement to turgor pressure are similar to those of sucrose release from maize pedicels, but they contrast with legume seed coats. Although the evidence is incomplete, movement appears to be carrier mediated rather than channel mediated. In vitro rates of sucrose efflux were similar to or somewhat less than in vivo rates, suggesting that transport across the nucellar cell membranes could be a factor in the control of assimilate import into the grain.
Progress in Developing PNA as a Gene-Targeted Drug (1997)

Peptide nucleic acid (PNA) is a DNA mimic in which the nucleobases are attached to a pseudopeptide backbone. This achiral, uncharged, and rather flexible peptide backbone permits more stable hybridization to DNA and RNA oligomers with uncompromised or even improved sequence selectivity. Additional advantages of PNA are stability against nucleases and proteases and convenient solid phase synthesis. At the RNA level, PNA can be targeted to mRNA to block protein synthesis in an antisense strategy. PNA can also be targeted to the RNA component of ribonucleoproteins (RNPs) to inhibit their enzymatic activities. At the DNA level, the unique ability of PNA to bind DNA by duplex invasion can be used to arrest transcription within a gene sequence or to provide an artificial open complex to promote transcription. This review focuses on recent progress toward the development of PNA as a sequence-targeted drug.
Characterization of mild coagulation factor VII deficiency: activity and clearance of the Arg315Trp and Arg315Lys variants in the Cys310-Cys329 loop (c170s). (2004)

These findings suggest a dual role of R315 for FVII function and clearance, and indicate that substitutions at this position have appreciable effects on human FVII biology, compatible with residual FVII function and thus with mild FVII deficiency.