gebhart/patrepeval huggingface dataset:
A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease (2003)

The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels. Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors. Tau protein deposition is also affected by androgen supplementation in animals. We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition, in particular the visual-spatial domain. Thirty-six male patients with a new diagnosis of Alzheimer's disease had their total and bioavailable testosterone levels measured. None of the patients had been on acetylcholinesterase inhibitors. Ten of the 36 patients (28%) were deemed biochemically hypogonadal (total testosterone < 240 ng/dl or 7 nmol/l). Five of the hypogonadal patients were randomized to testosterone and five to placebo. Initial Alzheimer's Disease Assessment Scale cognitive subscale (ADAScog) and Mini Mental Status Examination (MMSE) ranged from 31 to 19 and from 17 to 22, respectively. The clock drawing test (CDT) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities. Normal prostate-specific antigen (PSA) levels were essential before treatment with intramuscular testosterone, 200 mg every 2 weeks. Measurement of testosterone, complete blood count, lipids, PSA and neuropsychological cognitive tests were repeated at 3, 6, 9 and 12 months of treatment. In the testosterone-treated group, levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l (p = 0.11). Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l (p = 0.10). PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml (p = 0.07). ADAScog improved from a mean of 25 to 16.3 (p = 0.02); MMSE improved from a mean of 19.4 to 23.2 (p = 0.02), CDT also improved from 2.2 to 3.2 (p = 0.07). One patient stopped treatment because of hypersexual behavior. The placebo-treated group deteriorated gradually. This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition, including visual-spatial skills in mild to moderate Alzheimer's disease.
Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity (2008)

Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes--proteolysis, lipolysis, ketogenesis, and glycolysis--reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy.
Characterization of a New Primary Human Pancreatic Tumor Line (1986)

A primary human pancreatic tumor line (BxPC-3) has been established from a biopsy specimen of a histologically confirmed adenocarcinoma of the body of the pancreas. Tumorigenicity was proven by xenograft in athymic nude mice. Upon re-establishment of tumor xenografts in tissue culture, the epithelial tumor cells retained their original morphology. Histopathologically, the tumors grown in nude mice exhibited the original characteristics of the primary adenocarcinoma in the patient, producing traceable mucin and displaying moderately well to poorly differentiated adenocarcinomas with occasional lymphocytic infiltrations at the tumor peripheries. Furthermore, the tumor xenografts differentially expressed carcinoembryonic antigen, human pancreas cancer-associated antigen, and human pancreas-specific antigen. Karyotyping and glucose-6-phosphate dehydrogenase isoenzyme characterization revealed that this tumor line was of human origin and devoid of HeLa cell contamination. The BxPC-3 tumor line has been maintained for more than four years in our laboratory and represents a valuable model for primary human pancreatic cancer.
The developmental capacity of nuclei transplanted from keratinized skin cells of adult frogs (1975)

Nuclei from keratinized skin cells of adult Xenopus foot-webs have been transplanted to enucleated eggs of the same species. 2. The cells used to provide donor nuclei were obtained as a monolayer outgrowth from cultured foot-web explants. When explants were cultured without plasma for 3 days, over 99-9% of the outgrowth cells contained keratin as revealed by the binding of monospecific fluorescent antibody prepared against purified Xenopus keratin. Nuclei were transplanted from cells which had been cultured for 31/2 days. 3. None of the first transfer embryos developed as far as tadpoles. Eleven clones of embryos were prepared from the nuclei of partial first-transfer blastulae by use of serial nuclear transplantation. Eight of these clones contained swimming tadpoles with functional muscle and nerve cells, and six clones contained tadpoles with beating hearts, well differentiated eyes, and other organs. 4. To prove that the nuclei of nuclear-transplant tadpoles were derived from the transplanted skin cell nuclei and not from a failure of ultraviolet light to inactivate the recipient egg nucleus, 1-nu skin cell nuclei were transplanted to eggs laid by 2-nu frogs. Several advanced tadpoles from six clones were analysed for nucleolar and chromosome number and found to be 1-nu diploids. 5. The six clones of advanced tadpoles which were proved to carry the donor nuclear marker represent six first-transfer nuclei in a total sample of 129 skin cell nuclei originally transplanted. The probability that all six nuclei were derived from the 0-1% of the donor cell population not proved to contain keratin is less than one in 10(10). 6. We conclude that cell specialization does not involve any loss, irreversible inactivation or permanent change in chromosomal genes required for development.
A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation (2011)

Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks. Substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride. (Funded by Vertex Pharmaceuticals and others; VX08-770-102 ClinicalTrials.gov number, NCT00909532.).
Curriculum Drama: Using Imagination and Inquiry in a Middle School Social Studies Classroom (2017)

This essay provides a vivid window into an eighth-grade class engaged in a legislative curriculum drama. Students acted as members of political parties within the Senate and participated in legislative hearings, discussed costs and benefits to legislation, and engaged in debates. Curriculum drama formed a bridge that linked the task of teaching and learning about a defined unit of study to the authentic interests, concerns, and energies of the students
Ischemic Insults Direct Glutamate Receptor Subunit 2-Lacking AMPA Receptors to Synaptic Sites (2006)

Regulated AMPA receptor (AMPAR) trafficking at excitatory synapses is a mechanism critical to activity-dependent alterations in synaptic efficacy. The role of regulated AMPAR trafficking in insult-induced synaptic remodeling and/or cell death is, however, as yet unclear. Here we show that brief oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia, promotes redistribution of AMPARs at synapses of hippocampal neurons, leading to a switch in AMPAR subunit composition. Ischemic insults promote internalization of glutamate receptor subunit 2 (GluR2)-containing AMPARs from synaptic sites via clathrin-dependent endocytosis and facilitate delivery of GluR2-lacking AMPARs to synaptic sites via soluble N-ethylmaleimide-sensitive factor attachment protein receptor-dependent exocytosis, evident at early times after insult. The OGD-induced switch in receptor subunit composition requires PKC activation, dissociation of GluR2 from AMPA receptor-binding protein, and association with protein interacting with C kinase-1. We further show that AMPARs at synapses of insulted neurons exhibit functional properties of GluR2-lacking AMPARs. AMPAR-mediated miniature EPSCs exhibit increased amplitudes and enhanced sensitivity to subunit-specific blockers of GluR2-lacking AMPARs, evident at 24 h after ischemia. The OGD-induced alterations in synaptic AMPA currents require clathrin-mediated receptor endocytosis and PKC activation. Thus, ischemic insults promote targeting of GluR2-lacking AMPARs to synapses of hippocampal neurons, mechanisms that may be relevant to ischemia-induced synaptic remodeling and/or neuronal death.
NY‐ESO‐1 protein expression and humoral immune responses in prostate cancer (2004)

NY-ESO-1 is expressed in a subset of HRPC patients and, together with other C/T antigens, may serve as a target antigen for development of immunotherapy of PC. Spontaneous serological responses against NY-ESO-1 may be associated with poor survival.
Squamous cell carcinoma of the ovary. (1995)

Benign cystic teratoma is a very common ovarian lesion; and it commonly occurs during a woman's reproductive years and most often is benign. In approximately 1% to 2% of cases, however, it can undergo a malignant transformation with a very poor prognosis. This is especially the case when disseminated disease is present. Usually the associated malignancy is squamous cell carcinoma, and radical surgery is recommended. An American Samoan woman was air-evacuated to Tripler Army Medical Center for further evaluation and therapy after having undergone an exploratory laparotomy and right ovarian cystectomy. Her pathology at the time of her initial procedure revealed a mature cystic teratoma with a malignant degenerative component. Her diagnostic evaluation upon arrival was unremarkable except for her physical exam and pelvic CT. She subsequently underwent a radical surgical procedure to include a surgical staging procedure, revealing disseminated squamous cell carcinoma with FIGO stage III disease. Whereas malignant transformation of a benign cystic teratoma is a rare occurrence, a high index of suspicion should be maintained whenever a preoperative diagnosis is encountered; a radical surgical approach with en bloc resection should be employed. Adjuvant therapy with radiation or chemotherapeutic agents in general has not been shown to improve the outcome, especially in disseminated disease.
Carbon—Carbon Bonding Made Easy (2006)

Abstract For Abstract see ChemInform Abstract in Full Text.
Antigenic and Genomic Relatedness among Ehrlichia risticii, Ehrlichia sennetsu, and Ehrlichia canis (1992)

Antigenic and genomic relatedness among Ehrlichia risticii, E. sennetsu, and E. canis was analyzed by enzyme-linked immunosorbent assay, Western blotting (immunoblotting) and DNA-DNA hybridization. E. risticii and E. sennetsu were serologically related, and their Western blot antigen profiles were nearly identical. Two antigens of E. sennetsu corresponding to the 28- and 51-kDa antigens of E. risticii were apparently larger than the E. risticii antigens, and the 55-kDa antigen of E. risticii appeared to be unique to this species. The 110-, 70-, and 44-kDa antigens of these two species were identical, as determined by the use of monospecific antibodies. DNA homology between these two species was high. On the other hand, E. canis was antigenically least reactive with the antisera to E. risticii and E. sennetsu. However, a dog convalescent-stage E. canis antiserum recognized antigens in the other two species which were different from those recognized by their homologous antisera. Similarly, homology between the DNA of E. canis and the DNAs of the other two species was very minimal. These results indicate that E. risticii and E. sennetsu are closely related both at the genomic and antigenic levels and that the relationship of these two species with E. canis is minimal.
Selection of phage‐displayed llama single‐domain antibodies that transmigrate across human blood‐brain barrier endothelium (2001)

Delivery to the brain of drugs, peptides, and genes depends on the availability of brain-specific delivery vectors. We used a phage-displayed library of llama single-domain antibodies (sdAbs) to enrich for species that selectively bind to and are internalized by human cerebromicrovascular endothelial cells (HCEC). Two sdAbs (FC5 and FC44) were selected, sequenced, subcloned, and expressed as fusion proteins with c-Myc-His5 tags. Similar to phage-displayed sdAbs, soluble FC5 and FC44 were shown to selectively bind HCEC and to transmigrate across an in vitro human blood-brain barrier (BBB) model. Both FC5 and FC44, in contrast to an unrelated llama sdAb, were also detected in the brain after i.v. injection into mice. These small (approximately 14 kDa) antibodies have characteristics essential for a carrier-vector and can be used to facilitate drug transport across the BBB.
A Short and Efficient Route to Novel Scyphostatin Analogues (2001)

[structure: see text]. Several novel scyphostatin analogues have been prepared in up to 18% yield over five steps from commercially available 4-bromoguaiacol, utilizing an organometallic addition to afford the desired syn-hydroxy-epoxides.
Respiratory Syncytial Virus Infection in Children With Bronchopulmonary Dysplasia (1988)

Little is known about the risk of severe illness from respiratory syncytial virus infection in children with bronchopulmonary dysplasia. A prospective study was done of the natural history of respiratory syncytial virus infection in 30 children less than 2 years of age with bronchopulmonary dysplasia who were in a home oxygen program. Surveillance to identify children with acute respiratory symptoms was done by weekly telephone interview. Symptomatic children were examined, oxygen saturation was determined by oximetry, and nasopharyngeal lavage fluid was collected for virus cultures and rapid respiratory syncytial virus antigen tests. During the 4-month study period (December to April), 27 children had one or more acute respiratory illnesses, and respiratory syncytial virus developed in 16/27 (59%). Passive smoking and greater than or equal to four members in the home increased the risk of symptomatic respiratory syncytial virus (P less than .01 and P less than .03, respectively). Of 16 children, 11 (69%) required hospitalization. Of the 11 hospitalized children with respiratory syncytial virus, nine were either still receiving oxygen at home or required oxygen therapy within the previous 3 months v none of five nonhospitalized children (P less than .005). Five of the hospitalized children were greater than 12 months of age and five had respiratory syncytial virus infection previously that had been confirmed by culture results. Hospitalizations were prolonged and complicated. Seven of 11 children were hospitalized for greater than 1 week; four were admitted to the intensive care unit; four were treated with ribavirin aerosol, and two needed mechanical ventilation. There were no deaths.(ABSTRACT TRUNCATED AT 250 WORDS)
Scalable collection summarization and selection (1999)

Information retrieval o ver the Internet increasingly requires the ltering of thousands of i n f o r mation sources. As the number and variety of sources increases, new ways of automatically summarizing, discovering, and selecting sources relevant t o a u s er's query a re needed. Pharos i s a h i g hly scalable distributed architecture for locating heterogeneous information sources. Its design is hierarchical, thus allowing it to scale well as the numberofinformation sources increases. We demonstrate the feasibility of the Pharos architecture using 2500 Usenet newsgroups as separate collections. Each n e wsgroup is summarized viaautomated Library o f C o ngress classi cation. We s how that using Pharos as an i n termediate retrieval mechanism provides acceptable accuracy of source selection compared to selecting sources using complete classi cation information, while maintaining good scalability. This implies that hierarchical distributed metadata and automated classi cation are potentially useful paradigms to address scalability problems in large-scale distributed information r etrieval applications.
Site-specific incorporation of biophysical probes into proteins. (1994)

Biophysical probes which can detect structural changes in proteins and the interaction of proteins with other macromolecules are important tools in studying protein function. Many difficulties remain, however, in introducing probes into proteins site-specifically. Here we report the successful site-specific incorporation of a spin-labeled, a fluorescent, and a photoactivatible amino acid into a variety of surface and internal sites in bacteriophage T4 lysozyme by using unnatural amino acid mutagenesis. In addition, we report the purification and spectral characterization of T4 lysozyme mutants containing the spin-labeled amino acid and the fluorescent amino acid. The ability to incorporate these probes site-specifically allows for novel studies of protein structure and dynamics. Moreover, this work demonstrates that the Escherichia coli protein biosynthetic machinery can tolerate unnatural amino acids with little resemblance to the natural amino acids.
A role for phospholipase C-gamma-mediated signaling in tumor cell invasion. (1999)

The invasive and metastatic transformation of cancers often results in death. However, the mechanisms that promote this transformation remain unclear. Two closely related receptors, the epidermal growth factor receptor (EGFR) and ErbB2, are overexpressed in a significant percentage of breast and prostate carcinomas, among others, with this up-regulated signaling correlating with tumor progression. Previous studies in our laboratory have demonstrated that an EGFR-phospholipase C (PLC)gamma-mediated motility-associated signaling pathway is rate-limiting for tumor cell invasion in vitro and in vivo in one model of prostate carcinoma. Therefore, we investigated whether this PLCgamma signaling pathway also was rate-limiting for invasion in other tumor cell lines and types and whether this EGFR activity is subsumed by the closely related ErbB2. We determined the effects of PLCgamma signal abrogation by pharmacological (U73122) and molecular (expression of the dominant-negative PLCz) means on the in vitro invasiveness of tumor cells. Inhibition of PLCgamma signaling concomitantly decreased invasiveness of de novo-occurring transgenic adenocarcinoma mouse prostate (TRAMP) lines and the human breast cancer cell lines MDA-468 and MDA-231; these lines present up-regulated EGFR signaling. Because the prostate and breast cancer lines usually present autocrine stimulatory loops involving EGFR, we also examined transgenic adenocarcinoma mouse prostate C1 and MDA-468 treated with the EGFR-specific kinase inhibitor PD153035 to determine whether invasiveness is dependent on EGFR signaling. PD153035 reduced invasiveness to levels similar to those seen with U73122, suggesting that the autocrine EGFR stimulatory loop is functioning to promote invasiveness. To determine whether this signaling pathway also promotes invasiveness of ErbB2-overexpressing tumors, we examined the human breast carcinoma line MDA-361; again, U73122 inhibition of PLCgamma decreased invasiveness. In all situations, the inhibition of PLCgamma signaling did not decrease mitogenic signaling. Thus, the motility-associated PLCgamma signaling pathway is a generalizable rate-limiting step for tumor cell progression.
A Conserved Phenylalanine as a Relay between the α5 Helix and the GDP Binding Region of Heterotrimeric Gi Protein α Subunit (2014)

G protein activation by G protein-coupled receptors is one of the critical steps for many cellular signal transduction pathways. Previously, we and other groups reported that the α5 helix in the G protein α subunit plays a major role during this activation process. However, the precise signaling pathway between the α5 helix and the guanosine diphosphate (GDP) binding pocket remains elusive. Here, using structural, biochemical, and computational techniques, we probed different residues around the α5 helix for their role in signaling. Our data showed that perturbing the Phe-336 residue disturbs hydrophobic interactions with the β2-β3 strands and α1 helix, leading to high basal nucleotide exchange. However, mutations in β strands β5 and β6 do not perturb G protein activation. We have highlighted critical residues that leverage Phe-336 as a relay. Conformational changes are transmitted starting from Phe-336 via β2-β3/α1 to Switch I and the phosphate binding loop, decreasing the stability of the GDP binding pocket and triggering nucleotide release. When the α1 and α5 helices were cross-linked, inhibiting the receptor-mediated displacement of the C-terminal α5 helix, mutation of Phe-336 still leads to high basal exchange rates. This suggests that unlike receptor-mediated activation, helix 5 rotation and translocation are not necessary for GDP release from the α subunit. Rather, destabilization of the backdoor region of the Gα subunit is sufficient for triggering the activation process.
Human Immunodeficiency Virus Type 1 Subtype E Envelope Recombinant Peptides Containing Naturally Immunogenic Epitopes (2000)

A series of recombinant peptides of the human immunodeficiency virus type 1 (HIV-1) subtype E envelope were used to address the question of whether immunogenic epitopes similar to those described for the subtype B envelope are also present in structurally analogous regions of another HIV-1 subtype with divergent sequences. Five recombinant peptides, covering the V2 and V3 domains of gp120, the cysteine-loop region of gp41, a gp41 region involved in oligomerization, and the cytoplasmic tail of gp41, were found to react with >50% of the serum samples analyzed. All but the V2 region in the HIV-1 subtype B envelope have been reported to contain continuous epitopes that are highly immunogenic during natural infection. This finding suggests that, despite the sequence divergence between subtype E and B envelopes, most of the continuous epitopes that are highly immunogenic during natural infection are located at structurally analogous regions of the envelope.
Vagus nerve stimulation in the treatment of morbid obesity (2002)

Despite these alarming facts, treatmentoptions for obesity remain limited. It isestimated that 50-60% of the population ofthe USA are obese or overweight. Of thesepatients, 5-6% are considered morbidly obesebecause they are approximately 100 pounds(about 45 kg) above their ideal body weight.