gebhart/patrepeval huggingface dataset:
Optimizing PCP therapy. (1997)

Research results to determine the best prophylactic regimen for Pneumocystis carinii pneumonia (PCP) are reported. Overall results from these studies indicate patients who are eligible for PCP prophylaxis should be advised to take double-strength trimethoprim/sulfamethoxazole (TMP/SMX) on a daily basis, a dosage found more effective than thrice-weekly. To handle problems with side effects, one study demonstrated the success of using a 6-day dose escalation method that allowed 80 percent of the participants to complete treatment for 6 months. Patients remaining intolerant to TMP/SMX have the options of using atovaquone (not yet FDA-approved for PCP prophylaxis) or aerosolized pentamidine (not approved for treatment of PCP), which have been shown to be safe and effective in PCP prophylaxis. Due to recent FDA reforms, the use of off-label drugs may increase, but patients and physicians are cautioned that problems with insurance reimbursement may develop.
Diabetic retinopathy is associated with an increased incidence of cardiovascular events in Type 2 diabetic patients (2008)

Diabetic retinopathy (especially in its more advanced stages) is associated with an increased CVD incidence independent of other known cardiovascular risk factors.
SV40‐transformed human fibroblasts: Evidence for cellular aging in precrisis cells (1985)

Pre-crisis SV40-transformed human diploid fibroblast (HDF) cultures have a finite proliferative lifespan, but they do not enter a viable senescent state at end of lifespan. Little is known about either the mechanism for this finite lifespan in SV40-transformed HDF or its relationship to finite lifespan in normal HDF. Recently we proposed that in normal HDF the phenomena of finite lifespan and arrest in a viable senescent state depend on two separate processes: 1) an age-related decrease in the ability of the cells to recognize or respond to serum and/or other mitogens such that the cells become functionally mitogen-deprived at the end of lifespan; and 2) the ability of the cells to enter a viable, G1-arrested state whenever they experience mitogen deprivation. In this paper, data are presented that suggest that pre-crisis SV40-transformed HDF retain the first process described above, but lack the second process. It is shown that SV40-transformed HDF have a progressively decreasing ability to respond to serum as they age, but they continue to traverse the cell cycle at the end of lifespan. Concomitantly, the rate of cell death increases steadily toward the end of lifespan, thereby causing the total population to cease growing and ultimately to decline. Previous studies have shown that when SV40-transformed HDF are environmentally serum deprived, they likewise exhibit continued cell cycle traverse coupled with increased cell death. Thus, these results support the hypothesis that pre-crisis SV40-transformed HDF still undergo the same aging process as do normal HDF, but they end their lifespan in crisis rather than in the normal G1-arrested senescent state because they have lost their ability to enter a viable, G1-arrested state in response to mitogen deprivation.
Interference with viral infection by defective RNA replicase (1987)

RNA-dependent RNA and DNA polymerases have a conserved segment, Tyr-X-Asp-Asp (G. Karmer and P. Argos, Nucleic Acids Res. 12:7269-7282, 1984). To investigate the function of this segment, we changed the Gly residue at position 357 in the conserved sequence Tyr-356-Gly-357-Asp-358-Asp-359 of the replicase of RNA coliphage Q beta to Ala, Ser, Pro, Met, or Val and examined the replicase activity in vivo. Cells carrying the variant plasmids lost the replicase activity and severely inhibited the proliferation of phage Q beta (group III) and related phage SP (group IV) by suppressing phage RNA synthesis. In contrast, substitution of the Gly residue at 390 showed only a slight inhibitory effect, although replicase activity was also lost. These results suggest that the cells harboring an altered replicase at the conserved segment can interfere specifically with the wild-type phage and different but related phage infections.
Integrated resource management for cluster-based Internet services (2002)

Client request rates for Internet services tend to be bursty and thus it is important to maintain efficient resource utilization under a wide range of load conditions. Network service clients typically seek services interactively and maintaining reasonable response time is often imperative for such services. In addition, providing differentiated service qualities and resource allocation to multiple service classes can also be desirable at times. This paper presents an integrated resource management framework (part of Neptune system ) that provides flexible service quality specification, efficient resource utilization, and service differentiation for cluster-based services. This framework introduces the metric of quality-aware service yield to combine the overall system efficiency and individual service response time in one flexible model. Resources are managed through a two-level request distribution and scheduling scheme. At the cluster level, a fully decentralized request distribution architecture is employed to achieve high scalability and availability. Inside each service node, an adaptive scheduling policy maintains efficient resource utilization under a wide range of load conditions. Our trace-driven evaluations demonstrate the performance, scalability, and service differentiation achieved by the proposed techniques.
Spectra, membrane binding, and potentiometric responses of new charge shift probes (1985)

The properties of a series of new potentiometric membrane probes have been explored. The probes all contain an (aminostyryl)pyridinium chromophore or a more highly conjugated analogue. The spectral properties of the dyes are discussed in terms of the excitation-induced charge shift from the pyridine to the aniline; this charge shift also provides the basis for the voltage dependence of the spectra according to an electrochromic mechanism. The spectral responses to a membrane potential on a hemispherical bilayer have been obtained and, grossly, are quite similar for all probes tested. The more subtle variations from dye to dye can be partially rationalized by consideration of binding parameters, the depth within the membrane, and structural factors. The most potential sensitive dye in this collection has been designated di-4-ANEPPS and has a 6-amino-2-naphthyl group in place of the p-anilino on the parent chromophore. Both the relative fluorescence emission and excitation responses have maxima of 8% per 100 mV, and these two spectra display a striking symmetry.
Role of the cystine-knot motif at the C-terminus of rat mucin protein Muc2 in dimer formation and secretion (2001)

DNA constructs based on the 534-amino-acid C-terminus of rat mucin protein Muc2 (RMC), were transfected into COS cells and the resultant 35S-labelled dimers and monomers were detected by SDS/PAGE of immunoprecipitates. The cystine-knot construct, encoding the C-terminal 115 amino acids, appeared in cell lysates as a 45kDa dimer, but was not secreted. A construct, devoid of the cystine knot, failed to form dimers. Site-specific mutagenesis within the cystine knot was performed on a conserved unpaired cysteine (designated Cys-X), which has been implicated in some cystine-knot-containing growth factors as being important for intermolecular disulphide-bond formation. Dimerization of RMC was effectively abolished. Each cysteine (Cys-1–Cys-6) comprising the three intramolecular disulphide bonds of the cystine knot was then mutated. Dimer formation was impaired in each case, although much less so for the Cys-3 mutant than the others. Abnormal high-molecular-mass, disulphide-dependent aggregates formed with mutations Cys-1, Cys-2, Cys-4 and Cys-5, and were poorly secreted. It is concluded that the intact cystine-knot domain is essential for dimerization of the C-terminal domain of rat Muc2, and that residue Cys-X in the knot plays a key role. The structural integrity of the cystine knot, maintained by intramolecular bonds Cys-1–Cys-4, Cys-2–Cys-5 and Cys-3–Cys-6, also appears to be important for dimerization, probably by allowing correct positioning of the unpaired Cys-X residue for stable intermolecular cystine-bond formation.
Nanoelectromechanical Systems (2000)

Nanoelectromechanical systems are evolving, with new scientific studies and technical applications emerging. Mechanical devices are shrinking in thickness and width to reduce mass, increase resonant frequency, and lower the force constants of these systems. Advances in the field include improvements in fabrication processes and new methods for actuating and detecting motion at the nanoscale. Lithographic approaches are capable of creating freestanding objects in silicon and other materials, with thickness and lateral dimensions down to about 20 nanometers. Similar processes can make channels or pores of comparable dimensions, approaching the molecular scale. This allows access to a new experimental regime and suggests new applications in sensing and molecular interactions.
Immunogenicity of Recombinant Human Adenovirus-Human Immunodeficiency Virus Vaccines in Chimpanzees (1993)

Recombinant human adenovirus (Ad) type 4-, 5-, and 7-vectored vaccines expressing either the HIV env or gag-protease genes were tested for immunogenicity in three chimpanzees. The first phase of the vaccination protocol consisted of a primary and two booster immunizations with Ad-HIVs by the oral route of administration, followed by a single booster immunization with Gag and/or Env subunit vaccines. The second phase of the vaccination protocol consisted of intranasal administration of Ad-HIVs previously administered by the oral route. Following the first phase adenovirus was shed into stools for only 1-7 days and modest type-specific anti-adenovirus neutralizing antibody titers were induced. Strong anti-Env binding antibody responses were detected in all three animals following the second oral booster immunization. One chimpanzee responded with a low-titered type-specific neutralizing antibody response to HIV. Cell-mediated immune responses to Env were not detected after the primary vaccination, but were detected following all booster immunizations. Administration of the Gag subunit vaccine boosted both humoral and cell-mediated immune responses to Gag antigens. In contrast, the Env subunit vaccine boosted cellular but not humoral immune responses. In the second phase of the vaccination protocol, both virus shedding and anti-adenovirus responses were enhanced. All three chimpanzees responded to the intranasal administration of Ad7-HIVs with boosted anti-HIV serum responses, including low-titered type-specific neutralizing antibodies, elicited anti-HIV antibodies at secretory sites, and stimulated cell-mediated immune responses to both Gag and Env antigens.
Differential expression of the complement regulatory proteins in the human eye. (1993)

Identification of MCP, DAF, and CD59 in the human eye provides evidence that a regulatory system exists to protect these cells from destruction by complement-activating events. It remains to be determined if other more specialized functions exist for these proteins, especially in the case of CD59 because of its extensive expression in the retina.
AlGaN-Cladding-Free Nonpolar InGaN/GaN Laser Diodes (2007)

We demonstrate highly manufacturable nonpolar (m-plane) InGaN/GaN laser diodes without any Al-containing waveguide cladding layers. These devices utilize thick InGaN quantum wells to generate transverse optical mode confinement and can be grown and fabricated in a manner analogous to InGaN/GaN light emitting diodes. Pulsed lasing operation was demonstrated, with threshold voltages and current densities of 6.7 V and 3.7 kA/cm2, respectively.
Peptide nucleic acid clamp PCR: A novel K‐ras mutation detection assay for colorectal cancer micrometastases in lymph nodes (2004)

Inaccurate staging of colorectal cancer (CRC) has been attributed to the failure to detect lymph node metastases by conventional pathology. We have previously reported the use of lymphatic mapping to accurately identify those lymph nodes most likely to harbor micrometastatic disease and permit focused pathologic examination. Mutation of K-ras allele at codons 12 or 13 occurs frequently in early stages of CRC development. The purpose of our study was to assess sentinel lymph nodes (SLN) for occult CRC micrometastases using a unique peptide nucleic acid (PNA) clamp PCR assay specific for K-ras mutations. Seventy-two paraffin-embedded primary CRC and paired SLN were evaluated by PNA clamp PCR for K-ras mutations. Thirty primary tumors (42%) were positive for K-ras mutations, and in 5 of these cases the SLN were positive for metastases by Hematoxylin and Eosin staining. PNA clamp PCR identified occult metastases in an additional 6 patients, upstaging 24% of K-ras positive primary CRCs (p = 0.014). No K-ras mutations were detected among the 20 noncancer lymph nodes assessed. This study demonstrates the utility, specificity and sensitivity of PNA clamp PCR assay in identifying occult micrometastases in the SLN of CRC patients by single-base mutation analysis.
ROCK Isoform Regulation of Myosin Phosphatase and Contractility in Vascular Smooth Muscle Cells (2009)

Abnormal vascular smooth muscle cell (VSMC) contraction plays an important role in vascular diseases. The RhoA/ROCK signaling pathway is now well recognized to mediate vascular smooth muscle contraction in response to vasoconstrictors by inhibiting myosin phosphatase (MLCP) activity and increasing myosin light chain phosphorylation. Two ROCK isoforms, ROCK1 and ROCK2, are expressed in many tissues, yet the isoform-specific roles of ROCK1 and ROCK2 in vascular smooth muscle and the mechanism of ROCK-mediated regulation of MLCP are not well understood. In this study, ROCK2, but not ROCK1, bound directly to the myosin binding subunit of MLCP, yet both ROCK isoforms regulated MLCP and myosin light chain phosphorylation. Despite that both ROCK1 and ROCK2 regulated MLCP, the ROCK isoforms had distinct and opposing effects on VSMC morphology and ROCK2, but not ROCK1, had a predominant role in VSMC contractility. These data support that although the ROCK isoforms both regulate MLCP and myosin light chain phosphorylation through different mechanisms, they have distinct roles in VSMC function.
Anti-insulin effects of amylin and calcitonin-gene-related peptide on hepatic glycogen metabolism (1991)

To evaluate the effects of amylin and calcitonin-gene-related peptide (CGRP) as anti-insulin agents in hepatic tissue, we have studied whether these two agents counteracted the action of insulin on glycogen metabolism in isolated rat hepatocytes. In this system insulin stimulates [14C]glucose incorporation into glycogen and activates glycogen synthase. Incubation of the cells with insulin in the presence of amylin or CGRP markedly blocked the insulin stimulation of these two parameters, whereas amylin or CGRP acting alone did not induce any effect. We also examined the ability of amylin and CGRP to modify the anti-glucagon effects of insulin. In the presence of 100 nM-amylin or -CGRP, 10 nM-insulin was almost unable to counteract the inactivation of glycogen synthase and the activation of phosphorylase induced by glucagon. In contrast, neither amylin nor CGRP modified the effect of glucagon on these two enzymes. Our results indicate that amylin and CGRP are able to impair the action of insulin on hepatic glycogen metabolism.
Effect of Exogenous Nerve Growth Factor on Neurotoxicity of and Neuronal Gene Delivery by a Herpes Simplex Amplicon Vector in the Rat Brain (1994)

We have previously shown that local destruction of neural tissue by wild-type herpes simplex virus type 1 (HSV-1) is attenuated by intracerebral infusion of nerve growth factor (NGF). To investigate the effect of NGF on the extent of neurolysis and efficacy of neuronal gene transfer mediated by an HSV-1 amplicon vector system in vivo, rats were stereotaxically injected in the striatum with an amplicon preparation, pHSVlac. This amplicon contains the Escherichia coli lacZ gene under the transcriptional control of the HSV-1 immediate early 4/5 promoter and is packaged by an HSV-1 helper virus carrying a deletion in the immediate early 3 gene. Vector injection was followed by continuous intracerebral infusion of NGF-beta (total dose 5 micrograms) or vehicle solution over 7 days. Animals were sacrificed at the end of the 7-day infusion period for histological analysis of the brains. A distinct zone of inflammation and necrosis surrounded the injection site in all vector-inoculated animals. The volume of striatal tissue destruction was significantly smaller in NGF-treated animals (1.27 +/- 0.19 mm3; mean +/- SEM) than in the vehicle-treated controls (2.16 +/- 0.37 mm3; P < 0.05 by t-test). Immunohistochemical staining for HSV and beta-galactosidase (beta-Gal) in vehicle-treated animals revealed that many striatal cells harbored HSV antigens (3,678 +/- 636), but only a small number expressed the reporter gene at 7 days post-injection (294 +/- 60). NGF infusion did not significantly affect the number of HSV-immunoreactive cells (4,224 +/- 618), or the number of cells expressing beta-Gal (330 +/- 72) at this time.(ABSTRACT TRUNCATED AT 250 WORDS)
Preclinical evaluation of adoptive cell therapy for patients with metastatic renal cell carcinoma. (2009)

Interleukin-2 (IL-2) shows encouraging clinical results in metastatic renal cell carcinoma (RCC) patients, but is limited by substantial toxicity. Cell-based therapy holds a promise, but past attempts in RCC were unsuccessful. Advances in tumor-infiltrating lymphocytes (TIL) generation technology and modified clinical protocols recently yielded a 50% response in refractory melanoma patients.RCC-derived TIL and tumor cells were processed by current protocols from tumor specimens in a clean laboratory. The expanded TIL were characterized and tested in functional assays.The TIL cultures were efficiently generated and massively expanded. Virtually all the expanded cells were T-cells, but a considerable variability in the CD4/CD8 ratio and a frequent CD4-CD8-phenotype were observed. The TIL exerted cytotoxic or IFNgamma-release activities against autologous targets in major histocompatibility (MHC) class I-restricted and -independent functional patterns. The functional results were superior to former technologies.Recent developments in TIL generation technology and clinical patient conditioning protocols indicate that the TIL-based approach for RCC could be revisited.
Use of Secreted Alkaline Phosphatase as a Reporter of Gene Expression in Mammalian Cells (2003)

The cDNA encoding secreted alkaline phosphatase (SEAP; ) is a powerful tool for investigating the function of known or presumed enhancer/promoter elements in transfected cells. As a reporter of gene expression, SEAP differs from intracellular reporters such as chloramphenicol acetyltransferase (CAT) and firefly luciferase in that SEAP is secreted from transfected cells. SEAP can thus be assayed using a small portion of the culture medium. The SEAP gene encodes a truncated form of human placental alkaline phosphatase (PLAP), an enzyme which normally resides on the cell surface. The SEAP gene lacks sequences encoding the membrane anchoring domain, thereby allowing the expressed protein to be efficiently secreted from cells. Levels of SEAP activity detected in the culture media are directly proportional to changes in intracellular concentrations of SEAP mRNA and protein (). SEAP has the unusual properties of being extremely heat-stable and resistant to the phosphatase inhibitor L-homoarginine. Therefore, endogenous alkaline phosphatase activity can be eliminated by treatment of samples at 65°C and incubation with this inhibitor. The secreted nature of SEAP provides several advantages for the use of this enzyme as a genetic reporter: 1. Preparation of cell lysates is not required. 2. The kinetics of gene expression can be easily studied using the same cultures by repeated collection of the medium. 3. Transfected cells are not disturbed for measurement of SEAP activity, and remain intact for further investigations such as RNA and protein analysis. 4. Background from endogenous alkaline phosphatase activity in the culture media is almost absent. 5. Sample collection and assay can be automated using 96-well microtiter plates.
The Metabolic Response of Articular Cartilage to Abnormal Mechanical Loading Induced by Medial or Lateral Meniscectomy (1993)

The effects of medial versus lateral meniscectomy on articular cartilage (AC) of adult sheep was investigated. In vitro incorporation of 35S into proteoglycans (PGs) and their release into media was used to assess cartilage metabolism. Lateral meniscectomy produced higher loss of PGs from AC and lower 35S-PG biosynthesis than for AC from medial meniscectomized joints. These findings were consistent with the proposed role of the lateral meniscus in joint mechanics.
Local Structural Preferences in the .alpha.-Lactalbumin Molten Globule (1995)

Molten globules have been proposed to be general intermediates in protein folding. Despite numerous studies, a detailed description of the structure of a molten globule remains elusive. Recently, we showed that the molten globule formed by the helical domain of alpha-lactalbumin (alpha-LA) has a native-like backbone topology. Here we probe local structural preferences in the helical domain of the alpha-LA molten globule by analyzing a set of native and nonnative single disulfide bond variants using a combination of circular dichroism spectroscopy and determination of the equilibrium constant for disulfide bond formation. We find that the region surrounding the 28-111 disulfide bond has a high preference to adopt a native-like structure. Formation of other native or nonnative disulfide bonds is significantly less favorable. Our results suggest that molten globules contain regions with varying degrees of specificity for native-like structure and that the core region surrounding the 28-111 disulfide bond plays an important role in alpha-LA folding by stabilizing the molten globule intermediate.
Fast bilateral filtering for the display of high-dynamic-range images (2002)

We present a new technique for the display of high-dynamic-range images, which reduces the contrast while preserving detail. It is based on a two-scale decomposition of the image into a base layer, encoding large-scale variations, and a detail layer. Only the base layer has its contrast reduced, thereby preserving detail. The base layer is obtained using an edge-preserving filter called the bilateral filter. This is a non-linear filter, where the weight of each pixel is computed using a Gaussian in the spatial domain multiplied by an influence function in the intensity domain that decreases the weight of pixels with large intensity differences. We express bilateral filtering in the framework of robust statistics and show how it relates to anisotropic diffusion. We then accelerate bilateral filtering by using a piecewise-linear approximation in the intensity domain and appropriate subsampling. This results in a speed-up of two orders of magnitude. The method is fast and requires no parameter setting.
The PedsQL™: Measurement Model for the Pediatric Quality of Life Inventory (1999)

The results support the PedsQL as a reliable and valid measure of HRQOL. The PedsQL core and modular design makes it flexible enough to be used in a variety of research and clinical applications for pediatric chronic health conditions.