gebhart/patrepeval huggingface dataset:
Identification of a novel transforming growth factor-beta (TGF-beta 5) mRNA in Xenopus laevis. (1990)

A novel transforming growth factor-beta (TGF-beta) mRNA of about 3.0 kilobases, which encodes a putative protein of 382 amino acids, has been identified in amphibians by cDNA cloning. This mRNA, which we designate as TGF-beta 5, is developmentally regulated and highly expressed beginning at early neurula (stage 14) and in many adult tissues in Xenopus laevis. Following the first methionine, the putative precursor protein has a hydrophobic region, approximately 22 amino acids long, which probably represents a signal sequence, similar to that found in TGF-beta s 1-3. The precursor also has potential sites for glycosylation, integrin binding (RGD), and a tetrabasic amino acid (RKKR) site for potential cleavage of the precursor peptide to a biologically active protein. The putative mature protein consists of 112 amino acids with 9 cysteines and has 76, 66, 69, and 72% identity to TGF-beta s 1-4, respectively.
Expression of PTEN and FHIT is involved in regulating the balance between apoptosis and proliferation in lung carcinomas. (2007)

PTEN and FHIT may contribute to regulation of the balance between apoptosis and proliferation in physiological events in normal lung and during development of lung carcinoma. Down-regulated PTEN appears closely linked to frequent lymphoangiogenic invasion and low FHIT expression, and could provide a molecular basis for differences in genetic sensitivity between men and women to lung carcinogens. PTEN could be a good prognostic factor for lung carcinomas, regardless of the histological types.
TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome–positive leukemia cells (2003)

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) have been implicated in antitumor immunity and therapy. In the present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)-positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the possible contribution of these molecules to immunotherapy against Ph1-positive leukemias. TRAIL, but not FasL, effectively induced apoptotic cell death in most of 5 chronic myelogenous leukemia-derived and 7 acute leukemia-derived Ph1-positive cell lines. The sensitivity to TRAIL was correlated with cell-surface expression of death-inducing receptors DR4 and/or DR5. The TRAIL-induced cell death was caspase-dependent and enhanced by nuclear factor kappa B inhibitors. Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5 expression. Fas-associated death domain protein (FADD) and caspase-8, components of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas-associating protein with death domain-like interleukin-1-converting enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL. Notably, TRAIL could induce cell death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL-specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma, Basel, Switzerland). These results suggested the potential utility of recombinant TRAIL as a novel therapeutic agent and the possible contribution of endogenously expressed TRAIL to immunotherapy against Ph1-positive leukemias.
Facile Approach to 2-Acetamido-2-deoxy-β-d-Glucopyranosides via a Furanosyl Oxazoline (2005)

A concise and convenient route that may be easily scaled is reported for the preparation of unprotected beta-glucopyranosides of N-acetyl-D-glucosamine. Reaction of a wide variety of alcohols with a reactive, readily prepared furanosyl oxazoline under acidic conditions affords the corresponding beta-D-glucopyranosides in good to high yields. Primary alcohols gave only beta-D-glucopyranosides. A mechanism is proposed for this transformation. [reaction: see text]
-Lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli (2003)

Two-component signal transduction systems contribute to beta-lactam resistance in E. coli. Multidrug exporters play roles in two-component signal transduction system-mediated beta-lactam resistance.
[Treatment of lung cancer--state of the art in 2000]. (2000)

Small-cell lung cancer (SCLC) is, in general, sensitive to anti-cancer chemotherapy and radiotherapy. Standard therapies for extensive SCLC are combination chemotherapies with cyclophosphamide, adriamycin and vincristine (CAV), with cisplatin and etoposide (PE), as well as an alternating CAV/PE program. On the other hand, the standard therapy for limited SCLC is chemoradiotherapy, especially PE and concurrent accelerated hyperfractionated radiotherapy. Based on the therapy, the current state of treatment of small cell lung disease is a median survival time of 10 months and a 3-year survival in 10% of patients with extensive disease, and a median survival time of 30 months and a 3-year survival in 30% of patients with limited disease. Promising trials under investigation including those for dose-intensive chemotherapy, multimodality treatment and combination chemotherapy adopting new drugs are introduced. The standard therapy for inoperable stage III non-small cell lung cancer is a multimodality therapy employing chemotherapy and radiotherapy. However, neither the timing of the radiotherapy nor the optimal combination of anti-cancer agents has yet been established. Nowadays, the combination of cisplatin-based chemotherapy and radiotherapy is expected to bring a median survival time of 15 months and a 3-year survival in 25% of patients. For stage IV non-small cell lung cancer, chemotherapy prolongs survival time by a modest but statistically significant amount of time. For the treatment of inoperable lung cancer, the survival benefit from the use of newly developed drugs with or without platinum is under investigation.
Human immunodeficiency virus type 2 (HIV-2) vector-mediated in vivo gene transfer into adult rabbit retina (2002)

Purpose. To evaluate the potential usefulness of HIV-2 viral vector in in vivo retinal gene therapy. Methods. An HIV-2 virus based viral vector was constructed and administered subretinally and intravitreally into rabbit eyes. After viral vector administration, the eyes were closely monitored for any adverse effects by slit lamp, indirect ophthalmoscopy, and fundus photography. Eyes were enucleated at specified times after injection, and reporter gene expression was identified within cell types and graded by the pattern and distribution of staining cells using fluorescent microscopy. Results. The HIV-2 viral vector demonstrated efficient gene transfer into many types of retinal cells without apparent cytotoxicity. Notably with subretinal injection, the HIV-2 vector resulted in higher efficiency of transduction of photoreceptor cells than of the other cell types (p &lt; 0.05). With the intravitreal administration of HIV-2 viral vectors, cellular transduction and transgene expression in the ganglion cell layer was the dominant finding. Conclusions. HIV-2 viral vector may be a useful gene delivery vehicle for retinal photoreceptor cells and ganglion cells. It deserves further exploration to investigate its potential merit in long term gene therapy protocols and in other animal species.
Effects of Massed versus Distributed Practice on Gross and Fine Motor Proficiency of Educable Mentally Handicapped Adolescents (1991)

Gross and fine motor proficiency were studied in a sample of 52 educable mentally handicapped students ( M = 15.8 yr.), half of whom were assigned to 15 30-sec. trials, a relatively massed practice schedule with 5 sec. between trials, and half to a distributed practice schedule with 30-sec. rests. 5 trials were given 24 hr. later. All subjects performed the stabilometer balance task to measure gross motor proficiency and a 45-rpm pursuit rotor task to measure fine motor proficiency. No significant differences with regard to the practice schedule used early in learning were found, however, boys scored significantly higher on the pursuit rotor than girls.
The geminivirus nuclear shuttle protein is a virulence factor that suppresses transmembrane receptor kinase activity (2004)

Despite the large number of leucine-rich-repeat (LRR) receptor-like-kinases (RLKs) in plants and their conceptual relevance in signaling events, functional information is restricted to a few family members. Here we describe the characterization of new LRR-RLK family members as virulence targets of the geminivirus nuclear shuttle protein (NSP). NSP interacts specifically with three LRR-RLKs, NIK1, NIK2, and NIK3, through an 80-amino acid region that encompasses the kinase active site and A-loop. We demonstrate that these NSP-interacting kinases (NIKs) are membrane-localized proteins with biochemical properties of signaling receptors. They behave as authentic kinase proteins that undergo autophosphorylation and can also phosphorylate exogenous substrates. Autophosphorylation occurs via an intermolecular event and oligomerization precedes the activation of the kinase. Binding of NSP to NIK inhibits its kinase activity in vitro, suggesting that NIK is involved in antiviral defense response. In support of this, infectivity assays showed a positive correlation between infection rate and loss of NIK1 and NIK3 function. Our data are consistent with a model in which NSP acts as a virulence factor to suppress NIK-mediated antiviral responses.
Acetogenins as Selective Inhibitors of the Human Ovarian 1A9 Tumor Cell Line (2003)

Several bioactive acetogenins were selective against 1A9 (ovarian cancer) cell replication but did not show a corresponding hyperactivity against other cell lines. The most active compound (26, molvizarin) was a selective inhibitor of 1A9 cell replication with a potency (ED(50) = 5 pg/mL) of over 1 million times more than that for other cell lines.
Fluoroscopic tracking of multiple implanted fiducial markers using multiple object tracking (2007)

When treating mobile tumors using techniques such as beam gating or beam tracking, precise localization of tumor position is required, which is often realized by fluoroscopically tracking implanted fiducial markers. Multiple markers placed inside or near a tumor are often preferred to a single marker for the sake of accuracy. In this work, we propose a marker tracking system that can track multiple markers simultaneously, without confusing them, and that is also robust enough to continue tracking even when the markers are moving behind bony anatomy. The integrated radiotherapy imaging system (IRIS), developed at the Massachusetts General Hospital (MGH), was used to take fluoroscopy videos for marker tracking. The tracking system integrates marker detection with a multiple object tracking process, inspired by the multiple hypothesis marker tracking (MHT) process. It also utilizes breathing pattern information to help tracking. Four criteria are used to identify tracking failure, and when tracking failure occurs, the system can immediately inform the user. (In the clinical environment, the system would immediately disable the treatment beam.) In this paper, two liver patients with implanted fiducial markers were studied, and the studies were performed retrospectively to assess the effectiveness of the new tracking system. For both patients, LAT and AP fluoroscopic videos were studied. In order to better test the proposed tracking system, artificial markers were added around the real markers to disturb the tracking of the real markers. The performance of the proposed system was compared to that of a conventional tracking system (one that did not use multiple object tracking). The performance of the new system was also investigated with and without consideration of the breathing pattern information. We found that the conventional tracking system can easily miss tracking markers in the presence of artificial markers, and it cannot detect the tracking failures. On the other hand, our proposed system can track markers well and can also successfully detect tracking failures. Failure rate was calculated on a per-frame-per-marker basis for the proposed tracking system. When the system considered breathing pattern information, it had a 0% failure rate 75% of the time and 0.4% failure rate 25% of the time. However, when the system did not consider breathing patterns, it had a much higher failure rate, in the range of 1.2%-12%. Both examples of the proposed system yielded low e(95) (the maximum marker tracking error at 95% confidence level)-less than 1.5 mm.
Reactivation of latent HIV-1 in central memory CD4+T cells through TLR-1/2 stimulation (2013)

Our findings suggest that the signaling through TLR-1/2 pathway via Pam3CSK4 or other reagents should be explored as an anti-latency strategy either alone or in combination with other anti-latency drugs.
Expression of C4.4A is a Potential Independent Prognostic Factor for Patients with Gastric Cancer (2014)

C4.4A, a metastasis-associated gene, encodes a glycolipid-anchored membrane protein which is overexpressed in several human malignancies. However, there are few data available on C4.4A expression and its relationship with progression in gastric cancer. Our study was designed to explore the expression of C4.4A in gastric cancer and to correlate it with clinical outcome. C4.4A expression was studied by quantitative real-time RT-PCR and immunohistochemistry for assessment of correlations with clinicopathological factors. C4.4A mRNA expression was significantly up-regulated in gastric cancer as compared with noncancerous tissue (p<0.05)., being observed in 107 (88.4%) of the 121 gastric cancer cases by immunohistochemistry. We found that the expression of C4.4A mRNA was correlated with size of the tumor, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Moreover, patients with overexpression of C4.4A has a significantly worse survival (p<0.05). Further multivariable analysis indicated that the expression of C4.4A was an independent prognostic indicator for gastric cancer (p<0.05). In conclusion, overexpression of C4.4A correlates with metastatic potential of gastric cancer and C4.4A could be a novel independent prognostic marker for predicting outcome.
The effect of sodium hyaluronate on the corneal epithelium. An ultrastructural study. (1988)

The effect of sodium hyaluronate (NaHa) 1% and 0.1% was studied on 14-day chick embryo corneal epithelium by scanning electron microscopy. It was found that NaHa 1% or 0.1% had no toxic effects on the chick corneal epithelium and the normal architecture of the cells and the morphology of the microvilli was well preserved. A combination of NaHa 0.1% and benzalkonium chloride (BAK) 0.01% reduced the toxic effect of BAK on the surface corneal epithelium. NaHa 0.1% provided a better protection of the corneal epithelium against dryness than hydroxyethylcellulose (HEC) 0.1% or phosphate buffer saline (PBS).
Synthesis and antitumor activity of cysteinyl-3,4-dihydroxyphenylalonines and related compounds (1981)

The natural catecholic amino acid 5-S-cysteinyl-3,4-dihydroxyphenylalanine (1) was selectively toxic to a variety of human tumor cell lines in culture and exhibited antitumor activity against L1210 leukemia and B-16 melanoma in mice at doses which were not toxic to the host. Structural analogues of 5-S-cysteinyl-3,4-dihydroxyphenylalanine including several new compounds, were synthesized and tested for growth inhibition of cultured cells of human neuroblastoma YT-nu and Chinese hamster fibroblasts Don-6. Some were also examined for antitumor activity against L1210 and B-16 in vivo. 4-S-Cysteinylcatechols and 2- and 4-S-cyteinylphenols, which cannot be prepared by conventional methods, were synthesized by the reaction of catechols and phenols with cystine and boiling aqueous HBr. 5-S-Cysteinyl- and 2-S-Cysteinyl-3,4-dihyroxyphenylalanine (1 and 2), L-3,4-dihydroxyphenylalanine (L-Dopa), and 2- and 4-S-cysteinylphenol (14 and 15) were toxic to the YT-nu cell line only, while 4-S-cysteinylcatechol (6), 3-S-cysteinyl-5-methylcatechol (8), 5-S-cysteaminyldopamine (9), and 4-methylcatechol were strongly toxic to both cell lines. Compound I (1000 mg/kg), 6 (500 mg/kg), and 8 (400 mg/kg) increased the life span of L1210-bearing mice by 50, 50, and 43%, respectively, and compounds 1 and 8 were marginally effective against B-16 melanoma as well. Compound 9 was too toxic to show any activity. There was a good correlation between the cytotoxicity and the in vivo activity.
A review of the identification and titration of antibodies to herpes simplex viruses type 1 and type 2 in human sera. (1973)

SUMMARY Because of the strong cross-neutralization between herpes simplex viruses types 1 and 2 and because of the high inci dence of antibody to the type 1 virus in the community, the unequivocal identification of type 2 antibody in serum sam ples is sometimes difficult. A variety of serological tech niques have been used for the comparative titration of anti bodies to the type 1and type 2 viruses. The plaque reduction test, the microneutralization test, and the measurement of the kinetics of neutralization all seem to give similar results; the antibody titers can also be measured by the indirect fluorescent antibody technique using the presence of viral antigens in the surface membranes of infected cells and by the passive hemagglutination test using sheep erythrocytes sensitized with either type 1 or type 2 antigens. But with each of these tests difficulty is often encountered in reach ing a decision on whether or not specific type 2 antibody is present. The fluorescent antibody test and the passive he magglutination test have been modified, with some degree of success, for detection of specific type 2 antibodies. The lysis of infected cells by herpes antibody in the presence of complement has also been used in a specific test. The cytolysis is detected by the release of 51Crfrom infected cells that have been appropriately labeled; the sera are rendered specific by prior absorption with nonlabeled cells infected with type 1 virus. The use of this test has indicated that some individuals who already have type 1 antibody do not develop specific type 2 antibody when subsequently in fected with type 2 virus. Studies of the appearance, with increase in age, of anti bodies in the community and of experimental infections of rabbits indicate that sera with dual or intermediate antibody properties are indeed the outcome of infection with both serotypes, although the existence in nature of interme diate serotypes of virus cannot, as yet, be totally excluded. The identification and titration of antibodies to herpes simplex viruses types 1 and 2 when both of these antibodies are present in the same serum have presented some prob lems. The delineation of these antibodies from one another has been difficult because of the strong cross-neutralization between the two viruses. The close relationship is shown in the neutralization kinetics presented in Charts 1 and 2; several workers (10, 19) have been unable to differentiate between the 2 viruses using antisera prepared against type 2.
Blood–Brain Barrier Pathology in Alzheimer's and Parkinson's Disease: Implications for Drug Therapy (2007)

The blood-brain barrier (BBB) is a tightly regulated barrier in the central nervous system. Though the BBB is thought to be intact during neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD), recent evidence argues otherwise. Dysfunction of the BBB may be involved in disease progression, eliciting of peripheral immune response, and, most importantly, altered drug efficacy. In this review, we will give a brief overview of the BBB, its components, and their functions. We will critically evaluate the current literature in AD and PD BBB pathology resulting from insult, neuroinflammation, and neurodegeneration. Specifically, we will discuss alterations in tight junction, transport and endothelial cell surface proteins, and vascular density changes, all of which result in altered permeability. Finally, we will discuss the implications of BBB dysfunction in current and future therapeutics. Developing a better appreciation of BBB dysfunction in AD and PD may not only provide novel strategies in treatment, but will prove an interesting milestone in understanding neurodegenerative disease etiology and progression.
HIV-1 Group M Conserved Elements Vaccine (2007)

Recent HIV vaccine designs have sought to block viral escape pathways by compressing antigenic diversity. In light of HIV's propensity to mutate and thereby to ever ramify viral populations, could it be that providing sufficient protection against global diversity is an insurmountable problem? We propose an alternative HIV-1 vaccine design that deliberately includes viral segments conserved across the entire main group (or M group) of HIV-1 strains and excludes variable segments. We describe a prototype conserved elements (CE) vaccine constituted of 45 viral segments at least eight amino acids long that fulfill stringent conservation criteria.

Our paradigm contends that the best way to cope with HIV-1 diversity may be to avoid it altogether. We argue that a successful vaccine must elicit responses against conserved regions of the viral proteome in which mutations would severely compromise the viability of the virus. Simultaneously, it must not elicit responses against variable, “decoy” elements of the virus, i.e., features that can mutate while retaining function, and that can absorb much of the adaptive host immune response.

Coping with HIV-1′s extensive diversity is a major challenge for vaccine design strategies. Centralized (consensus and ancestral) immunogens [1–3] have in some cases improved the breadth of responses, and recent designs seek to compress the more common variant features among circulating strains into immunogens [4–6]. However, there is a practical limit to antigenic complexity that may prevent inclusion of all escape pathways in realistically sized immunogens. Besides, HIV's propensity to mutate has been shown to provide means for HIV to escape from antiretrovirals and antibody and cytotoxic T lymphocyte (CTL) pressures.

The foregoing considerations led us to propose a vaccine exclusively composed of viral segments strictly conserved in all HIV-1 M group proteins and specifically devoid of mutable segments. The presence of segments that are nearly invariant in all HIV-1 M group proteomes strongly suggests that those CE are both obligatory for viral viability and are the Achilles' heels of the virus. Additionally, considering that variable segments can readily escape CTL pressures and can be highly immunogenic epitopes, we propose that mutable segments may act as immunologic decoys, subverting responses away from conserved elements.