gebhart/patrepeval huggingface dataset:
Parathyroid Hormone-Related Protein for the Treatment of Postmenopausal Osteoporosis: Defining the Maximal Tolerable Dose (2010)

In doses as high as 750 microg/d, in contrast to PTH, intermittently administered PTHrP appears to act as a pure skeletal anabolic agent. Surprisingly, PTHrP in the high doses studied activates 1,25 dihydroxyvitamin D production. Dosing information obtained herein can be used to design a longer term head-to-head comparative efficacy trial of PTHrP vs. PTH.
VL2 (2009)

To be agile and cost effective, data centers should allow dynamic resource allocation across large server pools. In particular, the data center network should enable any server to be assigned to any service. To meet these goals, we present VL2, a practical network architecture that scales to support huge data centers with uniform high capacity between servers, performance isolation between services, and Ethernet layer-2 semantics. VL2 uses (1) flat addressing to allow service instances to be placed anywhere in the network, (2) Valiant Load Balancing to spread traffic uniformly across network paths, and (3) end-system based address resolution to scale to large server pools, without introducing complexity to the network control plane. VL2's design is driven by detailed measurements of traffic and fault data from a large operational cloud service provider. VL2's implementation leverages proven network technologies, already available at low cost in high-speed hardware implementations, to build a scalable and reliable network architecture. As a result, VL2 networks can be deployed today, and we have built a working prototype. We evaluate the merits of the VL2 design using measurement, analysis, and experiments. Our VL2 prototype shuffles 2.7 TB of data among 75 servers in 395 seconds - sustaining a rate that is 94% of the maximum possible.
Rapid Colorectal Adenoma Formation Initiated by Conditional Targeting of the Apc Gene (1997)

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.
Isolation and characterisation of milk growth factor, a transforming‐growth‐factor‐β2‐related polypeptide, from bovine milk (1991)

A strategy was developed for the purification of a biologically active polypeptide growth and migration factor from skimmed bovine milk. This 25-kDa dimeric molecule, termed milk growth factor (MGF), was isolated by a method consisting of a combination of strong cation-exchange chromatography, low-pressure hydrophobic-interaction chromatography, hydrophobic-interaction HPLC and size-exclusion HPLC steps, which separated the protein according to its properties of charge, hydrophobicity and size, respectively. On average, a total purification of 10(6)-10(7)-fold and a yield of approximately 115 +/- 78 ng/MGF/milk was obtained using the method described. All purification steps were performed with novel combinations of ethanol and volatile acidic salt (ammonium acetate) solutions in order to retain biological activity of the protein. These conditions, together with the easy removal of salt by lyophilization, facilitated the detection of biological activity in fractions collected at each step of the purification by means of a sensitive in vitro fibroblast-migration assay in which the half-maximal activity was obtained at a concentration of approximately 17 +/- 4 pg/ml (i.e. approximately 1 pM) of the pure protein. Biological activity of the dimeric protein was unaffected by heat treatment or exposure to acid (pH 2.0), but was lost upon reduction to its monomeric form. Amino acid composition and sequence analyses demonstrate that MGF is related to transforming growth factor type beta 2.
Diffusion Magnetic Resonance Imaging: an Early Surrogate Marker of Therapeutic Efficacy in Brain Tumors (2000)

These results suggest that diffusion MRI will provide an early surrogate marker for quantification of treatment response in patients with brain tumors.
Expression of Class A Scavenger Receptor Is Enhanced by High Glucose in Vitro and under Diabetic Conditions in Vivo (2004)

In the early stage of atherosclerosis, macrophages take up chemically modified low density lipoproteins (LDL) through the scavenger receptors, leading to foam cell formation in atherosclerotic lesions. To get insight into a role of the scavenger receptors in diabetes-enhanced atherosclerotic complications, the effects on class A scavenger receptor (SR-A) of high glucose exposure in vitro as well as the diabetic conditions in vivo were determined in the present study. The in vitro experiments demonstrated that high glucose exposure to human monocyte-derived macrophages led to an increased SR-A expression with a concomitant increase in the endocytic uptake of acetylated LDL and oxidized LDL. The endocytic process was significantly suppressed by an anti-SR-A neutralizing antibody. Stability analyses revealed a significant increased stability of SR-A at a mRNA level but not a protein level, indicating that high glucose-induced up-regulation of SR-A is due largely to increased stability of SR-A mRNA. High glucose-enhanced SR-A expression was prevented by protein kinase C and NAD(P)H oxidase inhibitors as well as antioxidants. High glucose-enhanced production of intracellular peroxides was visualized in these cells, which was attenuated by an antioxidant. The in vivo experiments demonstrated that peritoneal macrophages from streptozotocin-induced diabetic mice increased SR-A expression when compared with those from nondiabetic mice. Endocytic degradation of acetylated LDL and oxidized LDL were also increased with these macrophages but not with the corresponding macrophages from diabetic SR-A knock-out mice. These in vitro and in vivo results probably suggest that reactive oxygen species generated from a protein kinase C-dependent NAD(P)H oxidase pathway plays a role in the high glucose-induced up-regulation of SR-A, leading to the increased endocytic degradation of modified LDL for foam cell formation. This could be one mechanism for an increased rate of atherosclerosis in patients with diabetes.
Optimized three‐dimensional fast‐spin‐echo MRI (2014)

Spin-echo-based acquisitions are the workhorse of clinical MRI because they provide a variety of useful image contrasts and are resistant to image artifacts from radio-frequency or static field inhomogeneity. Three-dimensional (3D) acquisitions provide datasets that can be retrospectively reformatted for viewing in freely selectable orientations, and are thus advantageous for evaluating the complex anatomy associated with many clinical applications of MRI. Historically, however, 3D spin-echo-based acquisitions have not played a significant role in clinical MRI due to unacceptably long acquisition times or image artifacts associated with details of the acquisition method. Recently, optimized forms of 3D fast/turbo spin-echo imaging have become available from several MR-equipment manufacturers (for example, CUBE [GE], SPACE [Siemens], and VISTA [Philips]). Through specific design strategies and optimization, including short non-spatially selective radio-frequency pulses to significantly shorten the echo spacing and variable flip angles for the refocusing radio-frequency pulses to suppress blurring or considerably lengthen the useable duration of the spin-echo train, these techniques permit single-slab 3D imaging of sizeable volumes in clinically acceptable acquisition times. These optimized fast/turbo spin-echo pulse sequences provide a robust and flexible approach for 3D spin-echo-based imaging with a broad range of clinical applications.
Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial. (1998)

The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow-up evaluation.
Induction in Humans of CD8+ and CD4+ T Cell and Antibody Responses by Sequential Immunization with Malaria DNA and Recombinant Protein (2004)

Vaccine-induced protection against diseases like malaria, AIDS, and cancer may require induction of Ag-specific CD8(+) and CD4(+) T cell and Ab responses in the same individual. In humans, a recombinant Plasmodium falciparum circumsporozoite protein (PfCSP) candidate vaccine, RTS,S/adjuvant system number 2A (AS02A), induces T cells and Abs, but no measurable CD8(+) T cells by CTL or short-term (ex vivo) IFN-gamma ELISPOT assays, and partial short-term protection. P. falciparum DNA vaccines elicit CD8(+) T cells by these assays, but no protection. We report that sequential immunization with a PfCSP DNA vaccine and RTS,S/AS02A induced PfCSP-specific Abs and Th1 CD4(+) T cells, and CD8(+) cytotoxic and Tc1 T cells. Depending upon the immunization regime, CD4(+) T cells were involved in both the induction and production phases of PfCSP-specific IFN-gamma responses, whereas, CD8(+) T cells were involved only in the production phase. IFN-gamma mRNA up-regulation was detected in both CD45RA(-) (CD45RO(+)) and CD45RA(+)CD4(+) and CD8(+) T cell populations after stimulation with PfCSP peptides. This finding suggests CD45RA(+) cells function as effector T cells. The induction in humans of the three primary Ag-specific adaptive immune responses establishes a strategy for developing immunization regimens against diseases in desperate need of vaccines.
Interaction of Transforming Growth Factor-β Receptor I with Farnesyl-protein Transferase-α in Yeast and Mammalian Cells (1996)

Transforming growth factor beta (TGF-beta) signals through two transmembrane serine/threonine kinases, known as TbetaR-I and TbetaR-II. Several lines of evidence suggest that TbetaR-II acts as a primary receptor, binding TGF-beta and phosphorylating TbetaR-I whose kinase activity then propagates the signal to unknown substrates. We report an interaction between TbetaR-I and the farnesyl-protein transferase-alpha subunit (FT-alpha) both in a yeast two-hybrid system and in mammalian cells. These findings raise the possibility that TGF-beta might regulate cellular functions by altering the ability of FT-alpha to catalyze isoprenylation of targets such as G proteins, lamins, or cytoskeletal components. However, we provide evidence that TGF-beta action does not alter the overall protein isoprenyl transferase activity in Mv1Lu mink lung epithelial cells. In fact, the beta subunits of farnesyl transferase and geranylgeranyl transferase, which are necessary for the activity of FT-alpha, prevent the association of FT-alpha with TbetaR-I. Furthermore, farnesyl transferase activity is shown to be dispensable for TGF-beta signaling of growth inhibitory and transcriptional responses in these cells. These results suggest that the interaction between TbetaR-I and FT-alpha does not affect the known functions of these two proteins.
Delivery of nascent MHC class II-invariant chain complexes to lysosomal compartments and proteolysis of invariant chain by cysteine proteases precedes peptide binding in B-lymphoblastoid cells. (1995)

The intracellular trafficking, proteolysis, and dissociation of invariant chain (li) associated with nascent class II molecules was examined in B-lymphoblastoid cells. Metabolic labeling and Percoll gradient centrifugation was used to assess the kinetics of delivery and processing of class II-li complexes within the endocytic pathway. Catabolism of class II-li complexes rapidly followed their delivery from post-Golgi compartments to dense lysosome-like compartments distinct from early and late endosomes. Direct peptide binding assays revealed that class II molecules associated with even small N-terminal fragments of li failed to bind peptide. Cysteine protease inhibitors alone blocked li proteolysis/dissociation and accumulation of class II-li biosynthetic intermediates within lysosome-containing compartments. Active-site labeling of cysteine proteases in B cells was used to identify cysteine proteases capable of mediating li proteolysis within endosomal compartments. Our results indicate rapid, possibly direct, transport of nascent class II-li complexes from the Golgi/trans-Golgi network to dense lysosomal compartments wherein cysteine protease(s), likely including cathepsin B, mediate complete removal of li. Inhibition of cysteine protease activity results in the accumulation of incompletely processed class II-li complexes, which lack peptide binding ability, within lysosomal compartments.
Two major Smad pathways in TGF‐β superfamily signalling (2002)

Members of the transforming growth factor-beta (TGF-beta) superfamily bind to two different serine/threonine kinase receptors, i.e. type I and type II receptors. Upon ligand binding, type I receptors specifically activate intracellular Smad proteins. R-Smads are direct substrates of type I receptors; Smads 2 and 3 are specifically activated by activin/nodal and TGF-beta type I receptors, whereas Smads 1, 5 and 8 are activated by BMP type I receptors. Nearly 30 proteins have been identified as members of the TGF-beta superfamily in mammals, and can be classified based on whether they activate activin/TGF-beta-specific R-Smads (AR-Smads) or BMP-specific R-Smads (BR-Smads). R-Smads form complexes with Co-Smads and translocate into the nucleus, where they regulate the transcription of target genes. AR-Smads bind to various proteins, including transcription factors and transcriptional co-activators or co-repressors, whereas BR-Smads interact with other proteins less efficiently than AR-Smads. Id proteins are induced by BR-Smads, and play important roles in exhibiting some biological effects of BMPs. Understanding the mechanisms of TGF-beta superfamily signalling is thus important for the development of new ways to treat various clinical diseases in which TGF-beta superfamily signalling is involved.
Treatment of epidemic Kaposi's sarcoma with a combination of interferon-alpha 2b and etoposide. (1988)

A prospective clinical trial of concomitant interferon-alpha 2b and etoposide was conducted in 24 previously untreated patients with epidemic Kaposi's sarcoma. Eight of 21 evaluable patients (38%) achieved either a complete response (1 patient) or a partial response (7 patients). None of the responders had a prior history of opportunistic infection. Hematologic toxicity was severe, and 8 patients developed an opportunistic infection. The combination of interferon-alpha 2b and etoposide has modest activity, but no additive or synergistic activity was evident in the dose and schedule utilized in this study. The exact role for interferon-alpha in epidemic Kaposi's sarcoma, both as a single agent and in combinations, remains to be determined.
The effect of geometry on three-dimensional tissue growth (2008)

Tissue formation is determined by uncountable biochemical signals between cells; in addition, physical parameters have been shown to exhibit significant effects on the level of the single cell. Beyond the cell, however, there is still no quantitative understanding of how geometry affects tissue growth, which is of much significance for bone healing and tissue engineering. In this paper, it is shown that the local growth rate of tissue formed by osteoblasts is strongly influenced by the geometrical features of channels in an artificial three-dimensional matrix. Curvature-driven effects and mechanical forces within the tissue may explain the growth patterns as demonstrated by numerical simulation and confocal laser scanning microscopy. This implies that cells within the tissue surface are able to sense and react to radii of curvature much larger than the size of the cells themselves. This has important implications towards the understanding of bone remodelling and defect healing as well as towards scaffold design in bone tissue engineering.
Changes in lipid, peroxide, and anti-oxidant blood levels during piroxicam (Hotemin) treatment. (1993)

The authors examined the lipid-peroxide (malondialdehyde) blood concentration of patients suffering from rheumatoid arthritis of osteoarthrosis. Of the anti-oxidant compounds, they examined the vitamin E concentration of blood plasma and catalase as well as glutathione-peroxidase enzyme activities. They also measured the oxidation capacity of blood plasma. It has been observed that the functional condition of patients in both disease groups improved following a 14-day treatment (20 md/day Hotemin). The degree of lipid-peroxidation (malondialdehyde content) as well as plasma oxidation capacity decreased in patients with osteoarthrosis, while these values did not change in patients suffering from rheumatoid arthritis. When examining the anti-oxidant enzymes in rheumatoid arthritis, a significant change was observed in glutathione-peroxidase activity. On the basis of the results it may be concluded that piroxicam has no direct anti-inflammatory action, but as an anti-oxidant, it exerts an action which is disease specific.
Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote (2004)

The considerable phylogenetic distance between Apicomplexa and other Eukaryotes is reflected by profound divergences between the kinome of malaria parasites and that of yeast or mammalian cells.
Studies toward Lipid A:  Synthesis of Differentially Protected Disaccharide Fragments (1997)

Disaccharides containing two glucosamine units are readily synthesized where the two amine functionalities are orthogonally protected as the tetrachlorophthaloyl and pent-4-enoyl moieties. The 1→6 linked disaccharide has the potential to be developed toward a series of biologically interesting lipid A analogs.
Design, Synthesis, and Biological Investigation of Thailanstatin A and Spliceostatin D Analogues Containing Tetrahydropyran, Tetrahydrooxazine, and Fluorinated Structural Motifs (2021)

Thailanstatin A and spliceostatin D, two naturally occurring molecules endowed with potent antitumor activities by virtue of their ability to bind and inhibit the function of the spliceosome, and their natural siblings and designed analogues, constitute an appealing family of compounds for further evaluation and optimization as potential drug candidates for cancer therapies. In this article, the design, synthesis, and biological investigation of a number of novel thailanstatin A analogues, including some accommodating 1,1-difluorocyclopropyl and tetrahydrooxazine structural motifs within their structures, are described. Important findings from these studies paving the way for further investigations include the identification of several highly potent compounds for advancement as payloads for antibody-drug conjugates (ADCs) as potential targeted cancer therapies and/or small molecule drugs, either alone or in combination with other anticancer agents.
Generation and characterization of embryonic striatal conditionally immortalized ST14A cells (1998)

Neural progenitor cells have been isolated from the embryonic central nervous system (CNS) of several mammalian species. These exhibit properties of immature cells, including expression of the intermediate filament protein Nestin, the ability to self renew, and to give rise to terminally differentiated cell types. In this study we describe some of the properties of ST14A cells, which were established via retroviral transduction of the temperature-sensitive mutant of the SV40 Large T Antigen into primary cells derived from the embryonic day 14 (E14) rat Striatum primordia. At 33 degrees C, ST14A cells proliferate and express Nestin, whereas at the nonpermissive temperature, cell growth becomes restricted in coincidence with the disappearance of the immortalizing oncoprotein. We also describe the ability of ST14A cells to differentiate and express MAP2. Furthermore, we analyzed the expression of specific growth factors and growth factor receptors in the ST14A cells, and found that nerve growth factor (NGF) and Trk receptors are most commonly expressed.
Effects of some novel inhibitors of C17,20-lyase and 5alpha-reductase in vitro and in vivo and their potential role in the treatment of prostate cancer. (1998)

The effects of some novel steroidal compounds were evaluated against both human C17,20-lyase and 5alpha-reductase in vitro and also against androgen synthesis in normal male rats. L-2, L-36, L-37, and I-41 showed potent inhibition of human testicular C17,20-lyase, with IC50s of 43, 39, 42, and 58 nM, respectively. In contrast, ketoconazole, a competitive inhibitor of C17,20-lyase, had an IC50 of 76 n.M. L-36 also showed potent inhibitory activity against 5a-reductase in human prostatic microsomes, with an IC50 of approximately 31 nM. The inhibitory activities of L-2 and 1-41 on 5alpha-reductase were moderate, with IC50s of 75 and 151 nM, respectively, whereas L-37 showed little inhibitory activity against this enzyme. In comparison, finasteride, a potent inhibitor of 5alpha-reductase, had an IC50 of 33 nM. When normal male rats were treated with these novel compounds (50 or 100 mg/kg/day) for 14 consecutive days, the wet weight of the prostate was significantly reduced by L-36, L-37, and I-41, compared to the control group. Testosterone levels in rat serum were also reduced by L-36 (55%), L-37 (86%), and I-41 (53%). The concentrations of testosterone in rat testes were reduced by these novel compounds by 13-74%. The compounds also reduced the concentration of testosterone in rat prostates by 35-75%. Similarly, dihydrotestosterone (DHT) concentration in rat serum was reduced 30-89% by these compounds, compared to the control group. Prostatic DHT levels were also lower in rats treated with L-36 (48%), L-37 (54%), or I-41 (26%). In contrast, L-2 enhanced serum testosterone and prostatic DHT concentrations by >50%. These findings suggest that the dual activities of several of these novel inhibitors of C17,20-lyase and 5alpha-reductase accounts for the diminished levels of circulating androgens in vivo.
Automatic allocation of arrays to memories in FPGA processors with multiple memory banks (2003)

FPGA-based processors, like many conventional DSP systems, often associate small high performance memories with each processing chip. These memories may be on-board embedded SRAMs or discrete parts. In the process of mapping a computation onto an FPGA processor, it is necessary to map the applications' data to memories. In this work, we present an algorithm that has been implemented in our NAPA C compiler to assign data automatically to memories to produce minimum overall execution time of the loops in the program. With the addition of this algorithm to our compiler, the programmer need not explicitly annotate array declarations with location information. Rather, the compiler analyzes the usage patterns of variables and selects the optimal location for each variable. The algorithm uses a search technique known as implicit enumeration to reduce the otherwise exponential search space. In practice, the use of this memory allocation compiler phase in our SUIF-based NAPA C compiler has negligible effect on compiler run time.