gebhart/patrepeval huggingface dataset:
Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds (2006)

Screening of a phage library for peptides that bind to clotted plasma in the presence of liquid plasma yielded two cyclic decapeptides, CGLIIQKNEC (CLT1) and CNAGESSKNC (CLT2). When injected intravenously into mice bearing various types of tumors, fluorescein-conjugated CLT peptides accumulated in a fibrillar meshwork in the extracellular compartment of the tumors, but were not detectable in other tissues of the tumor-bearing mice. The tumor homing of both peptides was strongly reduced after coinjection with unlabeled CLT2, indicating that the two peptides recognize the same binding site. The CLT peptide fluorescence colocalized with staining for fibrin(ogen) present in the extravascular compartment of tumors, but not in other tissues. The CLT peptides did not home to tumors grown in fibrinogen-null mice or in mice that lack plasma fibronectin. The CLT peptides also accumulated at the sites of injury in arteries, skeletal muscle, and skin. We conclude that the CLT peptides recognize fibrin-fibronectin complexes formed by clotting of plasma proteins that have leaked into the extravascular space in tumors and other lesions. These peptides may be useful in targeting diagnostic and therapeutic materials into tumors and injured tissues.
Type 1 Diabetes (1999)

Abstract Type 1 (insulin-dependent) diabetes occurs worldwide and can appear at any age. The genetic susceptibility is strongly associated with HLA-DQ and DR on chromosome 6, but genetic factors on other chromosomes such as the insulin gene on chromosome 11 and the cytotoxic T-lymphocyte antigen gene on chromosome 2 may modulate disease risk. Numerous studies further support the view that environmental factors are important. Gestational infections may contribute to initiation, whereas later infections may accelerate islet β-cell autoimmunity. The pathogenesis is strongly related to autoimmunity against the islet β cells. Markers of autoimmunity include autoantibodies against glutamic acid decarboxylase, insulin, and islet cell antigen-2, a tyrosine phosphatase-like protein. Molecular techniques are used to establish reproducible and precise autoantibody assays, which have been subject to worldwide standardization. The diagnostic sensitivity (40–80%) and specificity (99%) of all three autoantibodies for type 1 diabetes are high, and double or triple positivity among first-degree relatives predicts disease. Combined genetic and antibody testing improved prediction in the general population despite the transient nature of these autoantibodies. Classification of diabetes has also been improved by autoantibody testing and may be used in type 2 diabetes to predict secondary failure and insulin requirement. Islet autoantibodies do not seem to be related to late complications but rather to metabolic control, perhaps because the presence of islet cell autoantibodies marks different residual β-cell function. Combined genetic and autoantibody screening permit rational approaches to identify subjects for secondary and tertiary intervention trials.
A case for shared instruction cache on chip multiprocessors running OLTP (2003)

Due to their large code footprint, OLTP workloads suffer from significant I-cache miss rates on contemporary microprocessors. This paper analyzes the I-stream behavior of an OLTP workload, called the Oracle Database Benchmark (ODB), on Chip-Multiprocessors (CMP). Our results show that, although, the overall code footprint of ODB is large, multiple ODB threads running concurrently on multiple processors tend to access common code segments frequently, thus exhibiting significant constructive sharing. In fact, in a CMP system, an I-cache shared between multiple processors incurs similar miss rate as a dedicated I-cache per processor where the per processor I-cache has the same capacity as the shared I-cache. Based on these observations, this paper makes the case for a shared I-cache organization in a CMP, instead of the traditional approach of using a dedicated I-cache per processor.Furthermore, this paper shows that OLTP code stream exhibits good spatial locality. Adding a simple dedicated Line Buffer per processor can exploit this spatial locality effectively, to reduce latency and bandwidth requirements on the shared cache. The proposed shared I-cache organization results in an improvement of at least 5X in miss rate over a dedicated cache organization, for the same total capacity.
Adding Amino Acids with Novel Reactivity to the Genetic Code of Saccharomyces Cerevisiae (2003)

Using a novel genetic selection, we have identified a series of mutants of the E. coli tyrosyl-tRNA synthetase that selectively charge an amber suppressor tRNA with p-(propargyloxy)phenylalanine and p-azidophenylalanine in yeast. These evolved tRNA-synthetase pairs can be used to site-specifically label proteins with functional groups orthogonal to normal biological chemistries. As an example, we have shown that proteins containing these amino acids can be efficiently bioconjugated with small organic molecules by a [3 + 2] cycloaddition reaction that is mild enough for the manipulation of biological samples.
Multipotent stem cells from adult olfactory mucosa (2005)

Multipotent stem cells are thought to be responsible for the generation of new neurons in the adult brain. Neurogenesis also occurs in an accessible part of the nervous system, the olfactory mucosa. We show here that cells from human olfactory mucosa generate neurospheres that are multipotent in vitro and when transplanted into the chicken embryo. Cloned neurosphere cells show this multipotency. Multipotency was evident without prior culture in vitro: cells dissociated from adult rat olfactory mucosa generate leukocytes when transplanted into bone marrow-irradiated hosts, and cells dissociated from adult mouse olfactory epithelium generated numerous cell types when transplanted into the chicken embryo. It is unlikely that these results can be attributed to hematopoietic precursor contamination or cell fusion. These results demonstrate the existence of a multipotent stem-like cell in the olfactory mucosa useful for autologous transplantation therapies and for cellular studies of disease.
Quantification of Tissue Inhibitor of Metalloproteinases 2 in Plasma from Healthy Donors and Cancer Patients (2005)

Tissue inhibitor of metalloproteinases (TIMP)-2 is a highly conserved molecule, which binds both active and latent matrix metalloproteinase (MMP)-2. TIMP-2 is also involved in the activation of MMP-2 on the cell surface. A quantitative enzyme-linked immunosorbent assay (ELISA) was established and optimized for measurement of TIMP-2 in plasma. The capturing antibody in the ELISA was a monoclonal, while the detecting antibody was a chicken polyclonal antibody recognizing the native form of human TIMP-2. The levels of TIMP-2 were measured in ethylenediaminetetraacetic acid (EDTA) and citrate plasma from healthy donors. The median values were determined as 163 ng/ml (n = 186) with a range of 109-253 ng/ml for EDTA plasma and 139 ng/ml (n = 77) with a range of 95-223 ng/ml for citrate plasma. The TIMP-2 concentration in citrate plasma from 15 patients with advanced, stage IV breast cancer had a median value of 160 ng/ml, only slightly higher but statistically distinguishable from the level found in citrate plasma from the healthy donors. In addition, the TIMP-2 concentration in EDTA plasma from colorectal cancer patients revealed a significantly higher level in plasma from patients with Dukes stage A (P = 0.01) compared with patients with more advanced Dukes stages.
CCI-779 Inhibits Rhabdomyosarcoma Xenograft Growth by an Antiangiogenic Mechanism Linked to the Targeting of mTOR/Hif-1α/VEGF Signaling (2006)

Angiogenesis is one of the critical steps in tumor growth and metastasis. The goal of this study was to evaluate whether the antitumor activity of CCI-779 is related to antiangiogenic effects in vivo in tumors of mice bearing human rhabdomyosarcoma (RMS) xenografts. We now demonstrate that CCI-779 rapidly inhibits mTOR activity, as indicated by S6 reduction and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation in two xenograft models of RMS within 24 hours of treatment. Treatment with a single 20-mg/kg dose of CCI-779 suppressed S6 phosphorylation for more than 72 hours and 4E-BP1 phosphorylation for more than 96 hours. Based on these data, an intermittent treatment schedule (every 3 days for 30 days) was chosen and displayed a significant suppression of both tumor growth and mTOR signaling. Western blot analysis and immunohistochemical studies demonstrated that the antitumor activity of CCI-779 was associated with antiangiogenesis, as indicated by impaired levels of hypoxia-inducible factor-1alpha (Hif-1alpha) and vascular endothelial growth factor (VEGF) protein expression and by decreased microvessel density in Rh30 and RD xenografts. Together, these data suggest that CCI-779 inhibits human RMS xenograft growth by an antiangiogenic mechanism associated with the targeting of mTOR/Hif-1alpha/VEGF signaling.
Systematic Polar Coding (2011)

Polar codes were originally introduced as a class of non-systematic linear block codes. This paper gives encoding and decoding methods for systematic polar coding that preserve the low-complexity nature of non-systematic polar coding while guaranteeing the same frame error rate. Simulation results are given to show that systematic polar coding offers significant advantages in terms of bit error rate performance.
Diet and Rheumatoid Arthritis in Women (1996)

Some researchers have hypothesized that omega-3 fatty acids, found primarily in fish oils, may protect against the development of rheumatoid arthritis. We conducted a population-based case-control study in women, comparing 324 incident rheumatoid arthritis cases with 1,245 controls. We used a food frequency questionnaire to ascertain diet during a 1-year period 5 years before a reference date (first physician visit for joint-symptoms). Consumption of broiled or baked fish, but not of other types of fish, was associated with a decreased risk of rheumatoid arthritis. The adjusted odds ratios (OR) for 1- < 2 servings and > or = 2 servings of broiled or baked fish per week, compared with < 1 serving, were 0.78 [95% confidence interval (CI) = 0.53-1.14] and 0.57 (95% CI = 0.35-0.93). Other analyses showed associations with protein as a percentage of calories (adjusted OR for the top quartile as compared with the bottom quartile = 0.65; 95% CI = 0.46-0.94) and total calories (adjusted OR for the top quartile = 1.62; 95% CI = 1.15-2.28). The associations with broiled or baked fish, protein, and calories became stronger when we restricted our analysis to cases positive for rheumatoid factor. These results support the hypothesis that omega-3 fatty acids may help prevent rheumatoid arthritis.
TRP trapped in fly signaling web (1998)

In the Drosophila eye, photoactivation of rhodopsin leads to the opening of the light-sensitive cation influx channels TRP and TRPL. This response is extremely rapid and results in depolarization of the photoreceptor cells followed by Ca(2+)-mediated feedback regulation of the visual signaling cascade. The mechanisms that facilitate the rapid kinetics of activation and feedback regulation are poorly understood. However, the recent discovery that most of the proteins that function in fly phototransduction associate into a supramolecular complex permits a re-evaluation of the mechanisms underlying the activation and regulation of the cascade. The central player in the signaling complex is INAD, a protein with five protein-interaction motifs known as PDZ domains. The INAD complex does not appear to be a particle, but a massive signaling web composed of an INAD polymer with which some of the target proteins associate through complex multivalent interactions.
Recognition of c9orf72 Mutant RNA by Single-Stranded Silencing RNAs (2016)

Mutations within the chromosome 9 open reading frame 72 (c9orf72) gene are associated with both familial amyotrophic lateral sclerosis and frontotemporal dementia. The mutation leads to an expanded GGGGCC hexanucleotide repeat within the first intron of c9orf72 and an expanded CCCCGG repeat within a corresponding antisense transcript. Both the mutant intronic and antisense RNAs have been implicated in disease. We have previously reported that duplex RNAs complementary to the repeats can recognize disease-causing RNA and block detection of nuclear foci formed by the mutant transcripts. Here, we test the hypothesis that inhibition can also be achieved by single-stranded silencing RNAs (ss-siRNAs). ss-siRNAs are single-stranded antisense oligonucleotides (ASOs) that function through RNAi interference (RNAi) to silence gene expression. ss-siRNAs can block the expanded repeats within both intronic RNA and the antisense transcripts. Inhibition is more potent than by analogous duplex RNAs. Our data suggest that the potent effects on foci are caused by a combination of mechanisms including RNAi and direct binding of the ss-siRNA to the target transcripts. These findings reinforce the suggestion that ss-siRNAs combine the favorable properties of duplex RNA and single-stranded ASOs.
Plasma Cortisol and Growth Hormone Responses to Intravenous Catheterization (1975)

Plasma cortisol and growth hormone (HGH) responses to venous catheterization were studied in 29 volunteer subjects. Repeat characterizations were performed in 18 individuals. Mean plasma cortisol levels were significantly elevated during the first hour of the initial catheterization experience. Morning and afternoon levels of cortisol were not distinguishable during the first catheterization, but PM levels were significantly lower than AM levels during the second catheterization experience. Growth hormone responses were much more variable than cortisol and were distributed logarithmically. Growth hormone responses tended to parallel cortisol responses during the first catheterization experience. Individuals who listed more symptoms in response to venipuncture and catheterization after finishing their first catheterization had significantly higher cortisol and growth hormone levels during this experience. These data suggest a definite endocrine adaptation to catheterization by the second or third hour of the experience.
An alternative to holograms for the portrayal of human teeth (1993)

Currently holograms are being developed to portray casts of human teeth, known as study models, for dental purposes such as orthodontic requirements for the assessment of atheistic unacceptabilities. The paper describes a technique using light striping and artificial vision to create 3-D representations which can be portrayed and manipulated on a computer screen.
Das erste Oxogermanat mit „Stuffed Pyrgoms”: CsNa3Li8{Li[GeO4]}4 (1995)

Abstract Durch Tempern der binären Oxide CsO 0,52 , NaO 0,45 , LiO 0,5 und GeO 2 im mol. Verhältnis 1,24:1,4:6,7:3,9 (Ni‐Bömbchen; 600°C/89 bzw. 65 d) wurden erstmals Einkristalle von CsNa 3 Li 8 {Li[GeO 4 ]} 4 in Form von schwachgelblichen Prismen sowie blaßgelbem Pulver erhalten: Raumgruppe I 4/ m (I. T. Nr. 87) mit a = 1 120,73(5); c = 651,64(5) pm; Z = 2; (Vierkreisdiffraktometerdaten; Mo‐Kα; 5 152 I o ( hkl ); R = 1,7%; R w = 1,6%), Parameter siehe Text. Die Strukturbestimmung belegt die Isotypie mit CsKNaLi 9 {Li[SiO 4 ]} 4 , CsKNa 2 Li 8 {Li[SiO 4 ]} 4 und RbNa 3 Li 8 {Li[SiO 4 ]} 4 . Ferner werden der Madelunganteil der Gitterenergie (MAPLE), Effektive Koordinationszahlen (ECoN), Mittlere Fiktive Ionenradien (MEFIR) und die Ladungsverteilung (CHARDI) berechnet.
Yeast Cystathionine β-Synthase Is a Pyridoxal Phosphate Enzyme but, Unlike the Human Enzyme, Is Not a Heme Protein (2000)

Our studies of cystathionine beta-synthase from Saccharomyces cerevisiae (yeast) are aimed at clarifying the cofactor dependence and catalytic mechanism and obtaining a system for future investigations of the effects of mutations that cause human disease (homocystinuria or coronary heart disease). We report methods that yielded high expression of the yeast gene in Escherichia coli and of purified yeast cystathionine beta-synthase. The absorption and circular dichroism spectra of the homogeneous enzyme were characteristic of a pyridoxal phosphate enzyme and showed the absence of heme, which is found in human and rat cystathionine beta-synthase. The absence of heme in the yeast enzyme facilitates spectroscopic studies to probe the catalytic mechanism. The reaction of the enzyme with L-serine in the absence of L-homocysteine produced the aldimine of aminoacrylate, which absorbed at 460 nm and had a strong negative circular dichroism band at 460 nm. The formation of this intermediate from the product, L-cystathionine, demonstrates the partial reversibility of the reaction. Our results establish the overall catalytic mechanism of yeast cystathionine beta-synthase and provide a useful system for future studies of structure and function. The absence of heme in the functional yeast enzyme suggests that heme does not play an essential catalytic role in the rat and human enzymes. The results are consistent with the absence of heme in the closely related enzymes O-acetylserine sulfhydrylase, threonine deaminase, and tryptophan synthase.
A protein kinase bound to the projection portion of MAP 2 (microtubule-associated protein 2) (1981)

In previous work we have demonstrated that the microtubule-associated protein 2 (MAP 2) molecule consists of two structural parts. One part of the molecule, referred to as the assembly-promoting domain, binds to the microtubule surface and is responsible for promoting microtubule assembly; the other represents a filamentous projection observed on the microtubule surface that may be involved in the interaction of microtubules with other cellular structures. MAP 2 is known to be specifically phosphorylated as the result of a protein kinase activity that is present in microtubule preparations. We have now found that the activity copurifies with the projection portion of MAP 2 itself. Kinase activity coeluted with MAP 2 when microtubule protein was subjected to either gel- filtration chromatography on bio-gel A-15m or ion-exchange chromatography on DEAE- Sephadex. The activity was released from microtubules by mild digestion with chymotrypsin in parallel with the removal by the protease of the MAP 2 projections from the microtubule surface. The association of the activity with the projection was demonstrated directly by gel filtration chromatography of the projections on bio-gel A-15m. Three protein species (M(r) = 39,000, 55,000, and 70,000) cofractionated with MAP 2, and two of these (M(r) = 39,000 and 55,000) may represent the subunits of an associated cyclic AMP- dependent protein kinase. The projection-associated activity was stimulated 10-fold by cyclic AMP and was inhibited more than 95 percent by the cyclic AMP-dependent protein kinase inhibitor from rabbit skeletal muscle. It appeared to represent the only significant activity associated with microtubules, almost no activity being found with tubulin, other MAPs, or the assembly-promoting domain of MAP 2, and was estimated to account for 7-22 percent of the total brain cytosolic protein kinase activity. The location of the kinase on the projection is consistent with a role in regulating the function of the projection, though other roles for the enzyme are also possible.
Immunization with live aroA recombinant Salmonella typhimurium producing invasin inhibits intestinal translocation of Yersinia pseudotuberculosis (1994)

The Yersinia pseudotuberculosis inv gene encodes invasin, a 103-kDa outer membrane protein that allows bacteria to enter mammalian cells. The gene was subcloned into the attenuated aroA mutant of Salmonella typhimurium SL3261. Invasin was produced by the recombinant Salmonella strain and increased the ability of microorganisms to translocate from the intestinal lumen to the mesenteric lymph nodes. Specific antibodies for invasin were detected in sera and intestinal secretions of mice following oral immunization with the live Inv+ Salmonella strain. The immunization strongly inhibited intestinal translocation of Y. pseudotuberculosis when this pathogen was inoculated to mice but failed to prevent Yersinia dissemination from the gut lymphoid tissue.
Trimeric G protein-dependent signaling by Frizzled receptors in animal development (2008)

Receptors of the Frizzled family transduce important signals during animal development and are conserved from sponges to humans. Frizzled receptors belong to the superfamily of G protein-coupled receptors (GPCRs), but until recently were considered G protein-independent in their signaling. In the present article we review the extensive knowledge demonstrating the functions of trimeric G proteins in Frizzled signal transduction in vertebrates and lower animals. Other structural and functional similarities of Frizzled receptors and the GPCRs are also discussed.
High-temperature superconductor-shielded high power dielectric dual-mode filter for applications in satellite communications (2002)

We introduce a novel high-temperature superconductor (HTS)-shielded dual-mode resonator based on the degenerated fundamental mode of a dielectric hemisphere. By employing coupling with electric probes and dual-mode splitting with dielectric rods, we have built an HTS-shielded dual-mode two-pole filter at a center frequency of 6.4 GHz with a bandwidth of 0.4% and an insertion loss of 0.02 dB.
Metabotropic glutamate receptor 2/3‐dependent long‐term depression in the nucleus accumbens is blocked in morphine withdrawn mice (2002)

The nucleus accumbens (NAc) plays a crucial role in addiction. We have recently shown that activation of presynaptic metabotropic glutamate 2/3 receptors (mGlu2/3) induces long-term depression (LTD) at glutamatergic synapses in the mouse nucleus accumbens (NAc) through the long lasting inhibition of P/Q-type Ca2+ channels and the cAMP/protein kinase A (PKA) pathway. Because presynaptic mGlu2/3 functions are augmented in the ventral tegmental area of morphine-withdrawn rats, we have evaluated the consequences of opiate treatment on mGlu2/3 LTD at prelimbic NAc glutamatergic synapses. Here we report that mGlu2/3 LTD is abolished after 1 week of withdrawal from chronic morphine treatment; in the morphine-withdrawn group LTD measured 5.99 +/- 4.84% (P < 0.05) compared with 21.13 +/- 5.42% in the sham group. In contrast, chronic morphine treatment did not alter the mechanisms normally underlying mGlu2/3 LTD, such as the cAMP/PKA pathway or P/Q-type Ca2+ channels. This study shows that one long-term consequence of morphine treatment is an alteration of synaptic plasticity at glutamatergic synapses in the NAc. Considering that mGlu2/3 agonists (e.g. LY-354740 used in the present study to induce LTD) reduce behavioural symptoms of morphine withdrawal, these findings could be important in the understanding of the cellular events underlying the dependence-inducing properties of opiates.
Chlorotoxin: Structure, activity, and potential uses in cancer therapy (2015)

Chlorotoxin is a disulfide-rich stable peptide from the venom of the Israeli scorpion Leiurus quinquestriatus, which has potential therapeutic applications in the treatment of cancer. Its ability to preferentially bind to tumor cells has been harnessed to develop an imaging agent to help visualize tumors during surgical resection. In addition, chlorotoxin has attracted interest as a vehicle to deliver anti-cancer drugs specifically to cancer cells. Given its interesting structural and biological properties, chlorotoxin also has the potential to be used in a variety of other biotechnology and biomedical applications. Here, we review the structure, activity and potential applications of chlorotoxin as a drug design scaffold.