gebhart/patrepeval huggingface dataset:
Sensitive detection of chromosome copy number aberrations in prostate cancer by fluorescence in situ hybridization. (1994)

The pattern of chromosomal aberrations and their significance in prostate cancer are poorly understood. We studied 23 prostate cancer and 10 benign prostatic hyperplasia (BPH) specimens by fluorescence in situ hybridization (FISH) using pericentromeric repeat-specific probes for 10 different chromosomes. The aims of the study were: 1) to compare the sensitivity of FISH and DNA flow cytometry in aneuploidy detection, 2) to determine which chromosome copy number changes are most common, and 3) which probe combinations would be most effective in aneuploidy diagnosis. Disaggregated tumor cells from formalin-fixed, paraffin-embedded tissues were pretreated with our newly developed method based on hot glycerol solution to improve probe penetration. All BPH specimens were diploid by DNA flow cytometry and showed no numerical chromosome aberrations by FISH. In prostate cancer, flow cytometry showed abnormal DNA content in 35% of cases, whereas 74% were abnormal by FISH. Aberrant copy number of chromosomes 8 (48% of cases), X (43% of cases), and 7 (39% of cases) were most common. Ninety-four percent of all aneuploid cases would have been detected with these three probes alone. Simple chromosome losses were uncommon but in DNA tetraploid tumors relative losses (trisomy or disomy) of several chromosomes were often found, suggesting progression of prostate cancer through tetraploidization followed by losses of selected chromosomes. In conclusion, our results indicate that FISH using three selected chromosome-specific probes is two to three times more sensitive than flow cytometric DNA content analysis in aneuploidy detection.
Linearization of a Naturally Occurring Circular Protein Maintains Structure but Eliminates Hemolytic Activity, (2003)

Cyclotides are a recently discovered family of disulfide rich proteins from plants that contain a circular protein backbone. They are exceptionally stable, as exemplified by their use in native medicine of the prototypic cyclotide kalata B1. The peptide retains uterotonic activity after the plant from which it is derived is boiled to make a medicinal tea. The circular backbone is thought to be in part responsible for the stability of the cyclotides, and to investigate its role in determining structure and biological activity, an acyclic derivative, des-(24-28)-kalata B1, was chemically synthesized and purified. This derivative has five residues removed from the 29-amino acid circular backbone of kalata B1 in a loop region corresponding to a processing site in the biosynthetic precursor protein. Two-dimensional NMR spectra of the peptide were recorded, assigned, and used to identify a series of distance, angle, and hydrogen bonding restraints. These were in turn used to determine a representative family of solution structures. Of particular interest was a determination of the structural similarities and differences between des-(24-28)-kalata B1 and native kalata B1. Although the overall three-dimensional fold remains very similar to that of the native circular protein, removal of residues 24-28 of kalata B1 causes disruption of some structural features that are important to the overall stability. Furthermore, loss of hemolytic activity is associated with backbone truncation and linearization.
Ig Heavy Chain Gene Rearrangements in T-Cell Acute Lymphoblastic Leukemia Exhibit Predominant Dh6-19 and Dh7-27 Gene Usage, Can Result in Complete V-D-J Rearrangements, and Are Rare in T-Cell Receptor β Lineage (1999)

Rearranged IGH genes were detected by Southern blotting in 22% of 118 cases of T-cell acute lymphoblastic leukemia (ALL) and involved monoallelic and biallelic rearrangements in 69% (18/26) and 31% (8/26) of these cases, respectively. IGH gene rearrangements were found in 19% (13/69) of CD3− T-ALL and in 50% of TCRγδ+ T-ALL (12/24), whereas only a single TCRβ+ T-ALL (1/25) displayed a monoallelicIGH gene rearrangement. The association with the T-cell receptor (TCR) phenotype was further supported by the striking relationship between IGH and TCR delta (TCRD) gene rearrangements, ie, 32% of T-ALL (23/72) with monoallelic or biallelicTCRD gene rearrangements had IGH gene rearrangements, whereas only 1 of 26 T-ALL with biallelic TCRD gene deletions contained a monoallelic IGH gene rearrangement. Heteroduplex polymerase chain reaction (PCR) analysis with Vh and Dh family-specific primers in combination with a Jhconsensus primer showed a total of 39 clonal products, representing 7 (18%) Vh-(Dh-)Jh joinings and 32 (82%) Dh-Jh rearrangements. Whereas the usage of Vh gene segments was seemingly random, preferential usage of Dh6-19 (45%) and Dh7-27 (21%) gene segments was observed. Although the Jh4 and Jh6 gene segments were used most frequently (33% and 21%, respectively), a significant proportion of joinings (28%) used the most upstream Jh1 and Jh2 gene segments, which are rarely used in precursor-B-ALL and normal B cells (1% to 4%). In conclusion, the high frequency of incomplete Dh-Jh rearrangements, the frequent usage of the more downstream Dh6-19 and Dh7-27 gene segments, and the most upstream Jh1 and Jh2 gene segments suggests a predominance of immature IGH rearrangements in immature (non-TCRβ+) T-ALL as a result of continuing V(D)J recombinase activity. More mature β-lineage T-ALL with biallelic TCRD gene deletions apparently have switched off their recombination machinery and are less prone to cross-lineageIGH gene rearrangements. The combined results indicate thatIGH gene rearrangements in T-ALL are postoncogenic processes, which are absent in T-ALL with deleted TCRD genes and completed TCR alpha (TCRA) gene rearrangements.
Resilient overlay networks (2001)

A Resilient Overlay Network (RON) is an architecture that allows distributed Internet applications to detect and recover from path outages and periods of degraded performance within several seconds, improving over today's wide-area routing protocols that take at least several minutes to recover. A RON is an application-layer overlay on top of the existing Internet routing substrate. The RON nodes monitor the functioning and quality of the Internet paths among themselves, and use this information to decide whether to route packets directly over the Internet or by way of other RON nodes, optimizing application-specific routing metrics.Results from two sets of measurements of a working RON deployed at sites scattered across the Internet demonstrate the benefits of our architecture. For instance, over a 64-hour sampling period in March 2001 across a twelve-node RON, there were 32 significant outages, each lasting over thirty minutes, over the 132 measured paths. RON's routing mechanism was able to detect, recover, and route around all of them, in less than twenty seconds on average, showing that its methods for fault detection and recovery work well at discovering alternate paths in the Internet. Furthermore, RON was able to improve the loss rate, latency, or throughput perceived by data transfers; for example, about 5% of the transfers doubled their TCP throughput and 5% of our transfers saw their loss probability reduced by 0.05. We found that forwarding packets via at most one intermediate RON node is sufficient to overcome faults and improve performance in most cases. These improvements, particularly in the area of fault detection and recovery, demonstrate the benefits of moving some of the control over routing into the hands of end-systems.
OPTIMAL WARRANTY PERIOD AND OPTIMAL REPLACEMENT AGE OUT-OF-WARRANTY (2005)

This paper considers a general repairable product sold under a failure-free renewing warranty agreement. In the case of a general repairable model, there can be two types of failure: type Ⅰ failure (a minor failure), which can be rectified by minimal repairs; and type Ⅱ failure (a catastrophic failure), which can be removed only by replacement. After a minimal repair, the product is operational but the failure rate of the product remains unchanged. The aim of this paper is to determine the optimal warranty period and the optimal out-of-warranty replacement age, from the perspective of the seller (manufacturer) and the buyer (consumer), respectively, while minimizing the corresponding cost functions. And we can prove under some mild conditions, the optimal solution that minimizing the cost function is uniquely exists and finite. Finally, a numerical example is presented.
Structure-function studies on a polyreactive (natural) autoantibody. Polyreactivity is dependent on somatically generated sequences in the third complementarity-determining region of the antibody heavy chain. (1994)

SMI is a previously characterized IgM kappa polyreactive (natural) autoantibody. The variable regions of the heavy and light chains of SMI are respectively encoded by a nonmutated VH1 gene, designated 51p1, and a conserved nonmutated V kappa gene, designated Humkv325. These V genes seem to be over-represented in the autoimmune and fetal B cell repertoires, and to be frequently expressed in malignant B cells during certain lymphoid proliferations such as chronic lymphocytic leukemia. Polyreactive natural autoantibodies are thought to rely mainly on the use of such V genes in germ-line configuration. However, this model underestimates the contribution of the somatically generated heavy chain third complementarity-determining region (HCDR3) to autoantibody specificity. We used oligonucleotide site-directed mutagenesis to permute the sequence of the SMI-HCDR3 to generate a family of mutant proteins, each of which differed from the original SMI-IgM kappa by one amino acid residue. This allowed us to examine the relative contribution of selected amino acid residues in this region to the binding affinity of SMI against a panel of self-Ags. We found that a single amino acid substitution within the HCDR3 could dramatically alter the specificity of this autoantibody. Some substitutions abrogated the reactivity with all the tested Ags, whereas others changed the affinity or spectrum of reactivity for certain self-Ags. These results demonstrate that the autoantibody-binding activity of these conserved autoantibody-associated germ-line V genes is dependent upon heavy chain junctional sequences that are generated somatically during Ig gene rearrangement.
Protective immune responses to the E and NS1 proteins of Murray Valley encephalitis virus in hybrids of flavivirus-resistant mice (1996)

The lack of an effective animal model has been a major obstacle in attempts to define the role of humoral and cellular immune responses in protection against flavivirus infection. We have used F1 hybrid mice (BALB/c x C3H/RV) that are heterozygous for the flavivirus resistance allele F1vr and show reduced virus replication in the brain after intracerebral inoculation. F1 hybrid mice challenged by intracerebral inoculation with Murray Valley encephalitis (MVE) virus developed encephalitis 2-3 days later than a genetically susceptible strain (BALB/c) but showed a similar mortality rate. This delay in the onset of disease provided more opportunity for virus clearance by primed immune responses. Using F1 hybrid mice we were able to demonstrate protective immunity induced by structural and non-structural proteins of MVE virus by immunization with pure NS1 protein or recombinant vaccinia viruses that expressed various regions of the MVE genome. These constructs included VV-STR (C-prM-E-NS1-NS2A), VV-delta C (prM-E-Ns1-NS2A) and VV-NS1 (NS1-NS2A). VV-delta C vaccinated mice were completely protected (100% survival)from challenge with 1000 infectious units of MVE virus, while mice inoculated with VV-STR, VV-NS1 or pure NS1 were partially protected (40%, 47% and 85% respectively). Analysis of prechallenge sera and in vivo depletion studies revealed that the solid protection induced by VV-delta C was mediated by neutralizing antibody to the E protein and did not require a CD8+ T cell response. The partial protection provided by VV-STR, VV-NS1 and pure NS1 occurred after induction of antibody to NS1. However, depletion of CD8+ cells prior to virus challenge ablated the protection provided by VV-NS1 indicating some requirement for class I restricted cytotoxic T cells.
RTX cytotoxins recognize β 2 integrin receptors through N-linked oligosaccharides (2008)

Bordetella pertussis adenylate cyclase (AC) toxin-hemolysin (Hly) (CyaA, ACT, or AC-Hly) is a cytotoxin of the RTX (repeat in toxin) family. It delivers into target cells an AC domain that catalyzes uncontrolled conversion of ATP to cAMP, a key signaling molecule subverting phagocyte functions. CyaA utilizes a heavily N-glycosylated beta(2) integrin receptor CD11b/CD18 (alpha(M)beta(2), Mac-1, or CR3). We show that deglycosylation of cell surface proteins by glycosidase treatment, or inhibition of protein N-glycosylation by tunicamycin, ablates CyaA binding and penetration of CD11b-expressing cells. Furthermore, binding of CyaA to cells was strongly inhibited in the presence of free saccharides occurring as building units of integrin oligosaccharide complex, whereas saccharides absent from integrin oligosaccharide chains failed to inhibit CyaA binding to CD11b/CD18-expressing cells. CyaA, hence, selectively recognized sugar residues of N-linked oligosaccharides of integrins. Moreover, glycosylation of CD11a/CD18, another receptor of the beta(2) integrin family, was also essential for cytotoxic action of other RTX cytotoxins, the leukotoxin of Aggregatibacter actinomycetemcomitans (LtxA) and the Escherichia coli alpha-Hly (HlyA). These results show that binding and killing of target cells by CyaA, LtxA, and HlyA depends on recognition of N-linked oligosaccharide chains of beta(2) integrin receptors. This sets a new paradigm for action of RTX cytotoxins.
Abdominal Obesity, Independent from Caloric Intake, Accounts for the Development of Intestinal Tumors in Apc1638N/+ Female Mice (2013)

To determine whether visceral fat (VF), independent of other confounders, is causally linked to intestinal tumorigenesis, we surgically removed visceral fat in Apc(1638/N+) mice. At 15 weeks of age, male and female Apc(1638/N+) mice were randomized to one of three groups: ad libitum, visceral fat removal (VF-) and ad libitum fed, or caloric restriction, and were studied for effects on tumorigenesis and survival. As compared with ad libitum, VF- and caloric restriction reduced macroadenomas to a similar extent (P < 0.05), but only caloric restriction significantly improved survival (P < 0.05). Given that a significant group × gender interaction was observed, we next examined males and females separately. In females, macroadenomas were markedly attenuated by VF- (1.33 ± 0.23 mean ± SE; P < 0.05), but not by caloric restriction (2.35 ± 0.25; P = 0.71), as compared with ad libitum (2.50 ± 0.34). In males, however, caloric restriction (1.71 ± 0.26; P < 0.01), but not VF- (2.94 ± 0.42; P = 0.29), reduced macroadenomas, as compared with ad libitum males (3.47 ± 0.30). In females, both VF- (P = 0.05) and caloric restriction (P < 0.01) improved survival, but not in male mice (P = 0.15). The benefits observed with caloric restriction were consistent with favorable metabolic adaptations, but protection conferred in VF- females was despite lower adiponectin levels (P < 0.05), and failure to reduce body mass, total adiposity, glucose, insulin, leptin, and chemokine (C-X-C motif) ligand 1 (CXCL-1) levels. In conclusion, these data provide the first causal evidence linking visceral fat to intestinal cancer risk, and suggest that factors, other than known metabolic mediators, may impact tumor development. Furthermore, these data emphasize that strategies designed to deplete visceral fat stores in humans should be considered in the prevention of intestinal cancer. Cancer Prev Res; 6(3); 177-87. ©2012 AACR.
The relationship between thermal stability and pH optimum studied with wild‐type and mutant Trichoderma reesei cellobiohydrolase Cel7A (2003)

The major cellulase secreted by the filamentous fungus Trichoderma reesei is cellobiohydrolase Cel7A. Its three-dimensional structure has been solved and various mutant enzymes produced. In order to study the potential use of T. reesei Cel7A in the alkaline pH range, the thermal stability of Cel7A was studied as a function of pH with the wild-type and two mutant enzymes using different spectroscopic methods. Tryptophan fluorescence and CD measurements of the wild-type enzyme show an optimal thermostability between pH 3.5-5.6 (Tm, 62 +/- 2 degrees C), at which the highest enzymatic activity is also observed, and a gradual decrease in the stability at more alkaline pH values. A soluble substrate, cellotetraose, was shown to stabilize the protein fold both at optimal and alkaline pH. In addition, unfolding of the Cel7A enzyme and the release of the substrate seem to coincide at both acidic and alkaline pH, demonstrated by a change in the fluorescence emission maximum. CD measurements were used to show that the five point mutations (E223S/A224H/L225V/T226A/D262G) that together result in a more alkaline pH optimum [Becker, D., Braet, C., Brumer, H., III, Claeyssens, M., Divne, C., Fagerström, R.B., Harris, M., Jones, T.A., Kleywegt, G.J., Koivula, A., et al. (2001) Biochem. J.356, 19-30], destabilize the protein fold both at acidic and alkaline pH when compared with the wild-type enzyme. In addition, an interesting time-dependent fluorescence change, which was not observed by CD, was detected for the pH mutant. Our data show that in order to engineer more alkaline pH cellulases, a combination of mutations should be found, which both shift the pH optimum and at the same time improve the thermal stability at alkaline pH range.
<title>In-situ optimization of an i-line optical projection lens</title> (1995)

An in-situ process has been developed to optimize lens element alignment on a wafer stepper. This technique evaluates and analyzed the optical wavefront using the photoresist line and space profile. The advantage of this technique is that the photoresist sensitivity to the optical wavefront of the lens is automatically considered in the optimization process. The technique uses theoretical prediction and empirical critical dimension (CD) data to adjust the projection lens for optimum performance on the stepper. Successful implementation in production has been achieved. While the procedure has been developed on a high efficiency 1X projection lens, it can also be implemented on a reduction lens.
Automated refinement and inference of analytical models for metabolic networks (2011)

The reverse engineering of metabolic networks from experimental data is traditionally a labor-intensive task requiring a priori systems knowledge. Using a proven model as a test system, we demonstrate an automated method to simplify this process by modifying an existing or related model--suggesting nonlinear terms and structural modifications--or even constructing a new model that agrees with the system's time series observations. In certain cases, this method can identify the full dynamical model from scratch without prior knowledge or structural assumptions. The algorithm selects between multiple candidate models by designing experiments to make their predictions disagree. We performed computational experiments to analyze a nonlinear seven-dimensional model of yeast glycolytic oscillations. This approach corrected mistakes reliably in both approximated and overspecified models. The method performed well to high levels of noise for most states, could identify the correct model de novo, and make better predictions than ordinary parametric regression and neural network models. We identified an invariant quantity in the model, which accurately derived kinetics and the numerical sensitivity coefficients of the system. Finally, we compared the system to dynamic flux estimation and discussed the scaling and application of this methodology to automated experiment design and control in biological systems in real time.
Topical Pazopanib Blocks VEGF-Induced Vascular Leakage and Neovascularization in the Mouse Retina but Is Ineffective in the Rabbit (2012)

Administration of pazopanib topically or systemically suppressed retinal vascular leakage in mice, but not rabbits. These data suggest differences in the blood-retinal barrier (BRB) of mice and rabbits and indicate that penetration through the outer BRB may be needed for topically administered drugs to exert effects in the retina.
Limited-Sample NMR Using Solenoidal Microcoils, Perfluorocarbon Plugs, and Capillary Spinning (1998)

This study demonstrates three improvements to mass-limited NMR using solenoidal microcoils as detectors: (1) sample confinement using liquid perfluorocarbon plugs to increase the observe factor, (2) design and incorporation of a capillary spinner to improve spectral line widths, and (3) facile sample changing via the use of a capillary insert. The probe is constructed to spin a fused silica capillary of 530 microns i.d., 700 microns o.d. inside a solenoidal coil wound around a 0.8 mm i.d., 1 mm o.d. glass capillary. The smaller capillary contains the sample, and capillaries with different samples can be exchanged easily. In high-resolution limited sample microcoil NMR studies published thus far, the length of the sample plug has been 7-10 times the length of the solenoid to avoid line broadening from volume magnetic susceptibility (chi v) mismatches at both ends of the sample. This arrangement is not efficient since it places most of the sample volume outside of the coil observe volume. It is shown here that the observe factor cannot exceed 23% if the sample plug is bracketed by air, without substantial line broadening occurring. However, if the sample is bracketed by two liquid perfluorocarbon plugs, the observe factor can be increased to 70% while maintaining high spectral resolution. This is equivalent to improving the limit of detection by a factor of 3, or reducing the total data acquisition time for a given signal-to-noise by a factor of 9. It is also shown that, for the 440-nL sample plug used in this study (bracketed by the perflurocarbon plugs), sample spinning can improve the spectral resolution from 1.5 (nonspinning) to 0.6 Hz (spinning). This corresponds to a further improvement in the limit of detection of 2.5, or just over a factor of 6 decrease in data acquisition time.
News Briefs (1992)

IBM Announces Multimedia Authoring Tool. IBM announces LinkWay Live!™, a new member of the Linkway™ family. LinkWay Live! is an inexpensive, DOS‐based authoring and presentation tool that allows teachers, students, professional authors, and others to use full‐motion video, sound, animation, and high‐resolution graphics to create multimedia applications.
A novel enzyme, citryl‐CoA synthetase, catalysing the first step of the citrate cleavage reaction in Hydrogenobacter thermophilus TK‐6 (2004)

We attempted to purify ATP citrate lyase (ACL) from Hydrogenobacter thermophilus by following the citrate-, ATP- and CoA-dependent formation of an acyl-CoA species that was detected as hydroxamate. However, citryl-CoA rather than acetyl-CoA was found, indicating that the purified enzyme was a novel citryl-CoA synthetase (CCS) rather than ACL. Because the reaction catalysed by CCS corresponds to the first half of that mediated by ACL, CCS may be responsible for citrate cleavage in H. thermophilus. Thus, a novel citrate cleavage pathway, which does not involve ACL, appears to exist in this organism. Citryl-CoA synthetase is composed of two different polypeptides: a large beta subunit of 46 kDa and a small alpha subunit of 36 kDa. The corresponding genes were cloned and sequenced. The deduced amino acid sequences of the two subunits of CCS display significant similarity to those of succinyl-CoA synthetase (SCS) in the database. As a comparison, SCS was also purified from H. thermophilus and the corresponding genes were cloned and sequenced. Citryl-CoA synthetase and SCS were homologous, but showed different substrate specificity. The deduced amino acid sequences of the CCS subunits show similarity to part of the ACL sequence. The evolutionary relationship between CCS, SCS and ACL is discussed.