gebhart/patrepeval huggingface dataset:
Expression of cell cycle regulatory proteins in chronic lymphocytic leukemias. Comparison with non-Hodgkin's lymphomas and non-neoplastic lymphoid tissue. (1995)

The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peripheral blood lymphocytes (PBL) from 25 cases of chronic lymphocytic leukemias (CLL) in order to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison, we also studied the expression of these proteins in: 23 samples of non-Hodgkin's lymphoma (NHL) tissue of different histological types, 10 samples of non-neoplastic lymphoid tissue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated PBL (PHA-PBL) from three healthy donors. Samples were lysed and proteins were resolved on polyacrylamide gel followed by Western blot. The expression of cdk4 and cyclin E, both known to act in early cell cycle stage, was approximately on the same level in all groups of lymphoid pathology examined. In particular, we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk4 positive, ie they expressed these markers over twice the level of non-stimulated healthy PBL. The cdk1 expression was above the level seen in NS-PBL in 14 (56%) cases, but the average expression was significantly lower than in the other tissues examined, including low-grade lymphomas. Cdk2 expression was comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL and in NLT. Cyclins A and B, normally observed in advanced cell cycle phases, were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some cases, indicate that the CLL cells are not quiescent, but are blocked in an early stage of the G1 cell cycle phase, and/or that the expression of these proteins is pathologically deregulated.
HUMAN IMMUNITY TO THE MENINGOCOCCUS (1969)

Results of the present study suggest that natural immunity to meningococcal disease is initiated, reinforced, and broadened by intermittent carriage of different strains of meningococci throughout life. In young adults, carriage of meningococci in the nasopharynx is an efficient process of immune sensitization. 92% of carriers of serogroup B, C, or Bo meningococci were found to develop increased titers of serum bactericidal activity to their own meningococcal isolate, and 87% developed bactericidal activity to heterologous strains of pathogenic meningococci. The rise in bactericidal titer occurred within 2 wk of onset of the carrier state, and was accompanied by an increase in titer of specific IgG, IgM, and IgA antibodies to meningococci. In early childhood, when few children have antibodies to pathogenic meningococci, active immunization seems to occur as a result of carriage of atypical, nonpathogenic strains. Immunity to systemic meningococcal infection among infants in the neonatal period is associated with the passive transfer of IgG antibodies from mother to fetus. The antigenic determinants which initiate the immune response to meningococci include the group-specific C polysaccharide, cross-reactive antigens, and type-specific antigens.
Photoaptamer arrays applied to multiplexed proteomic analysis (2004)

Multiplexed photoaptamer-based arrays that allow for the simultaneous measurement of multiple proteins of interest in serum samples are described. Since photoaptamers covalently bind to their target analytes before fluorescent signal detection, the arrays can be vigorously washed to remove background proteins, providing the potential for superior signal-to-noise ratios and lower limits of quantification in biological matrices. Data are presented here for a 17-plex photoaptamer array exhibiting limits of detection below 10 fM for several analytes including interleukin-16, vascular endothelial growth factor, and endostatin and able to measure proteins in 10% serum samples. The assays are simple, scalable, and reproducible. Affinity of the capture reagent is shown to be directly correlated to the limit of detection for the analyte on the array.
Subunit vaccines based on intimin and Efa-1 polypeptides induce humoral immunity in cattle but do not protect against intestinal colonisation by enterohaemorrhagic Escherichia coli O157:H7 or O26:H- (2007)

Enterohaemorrhagic Escherichia coli (EHEC) infections in humans are an important public health concern and are commonly acquired via contact with ruminant faeces. Cattle are a key control point however cross-protective vaccines for the control of EHEC in the bovine reservoir do not yet exist. The EHEC serogroups that are predominantly associated with human infection in Europe and North America are O157 and O26. Intimin and EHEC factor for adherence (Efa-1) play important roles in intestinal colonisation of cattle by EHEC and are thus attractive candidates for the development of subunit vaccines. Immunisation of calves with the cell-binding domain of intimin subtypes beta or gamma via the intramuscular route induced antigen-specific serum IgG1 and, in some cases salivary IgA responses, but did not reduce the magnitude or duration of faecal excretion of EHEC O26:H- (Int(280)-beta) or EHEC O157:H7 (Int(280)-gamma) upon subsequent experimental challenge. Similarly, immunisation of calves via the intramuscular route with the truncated Efa-1 protein (Efa-1') from EHEC O157:H7 or a mixture of the amino-terminal and central thirds of the full-length protein (Efa-1-N and M) did not protect against intestinal colonisation by EHEC O157:H7 (Efa-1') or EHEC O26:H- (Efa-1-N and M) despite the induction of humoral immunity. A portion of the serum IgG1 elicited by the truncated recombinant antigens in calves was confirmed to recognise native protein exposed on the bacterial surface. Calves immunised with a mixture of Int(280)-gamma and Efa-1' or an EHEC O157:H7 bacterin via the intramuscular route then boosted via the intranasal route with the same antigens using cholera toxin B subunit as an adjuvant were also not protected against intestinal colonisation by EHEC O157:H7. These studies highlight the need for further studies to develop and test novel vaccines or treatments for control of this important foodborne pathogen.
Phase‐Transfer Catalysis (2000)

Abstract The article contains sections titled: 1. Introduction 2. Mechanism and Optimization Ramifications 3. Catalysts 4. Industrial Aspects 5. Uses 5.1. Nucleophilic Displacement 5.2. Dehydrohalogenation 5.3. Oxidation ‐ Reduction
Self-activated emission in ZnS and ZnSe (1984)

In an earlier investigation by the authors concerned with the production of semiconducting dice of ZnS, it was shown that all their samples were contaminated with trace concentrations of copper, and the lowest resistivity ( approximately 102 ohm cm) could be obtained by heating the crystalline material in molten zinc containing 1% Ga and 1/2% Al. The broadband photoluminescence of all the samples used in these conductivity studies has now been measured, and identified as a self-activated emission. At low copper concentrations the emission shifts to higher photon energies on cooling to 80K, but with copper concentrations exceeding 0.85 ppm the emission shifts to lower energies on cooling. A model is suggested to explain this effect. It involves recombination from distant donors to complex centres consisting of (GZn+-AlZn3+) A-centres associated with CuZn+ copper green centres at low copper concentrations, and with (CuZn+-CuI+) copper blue centres at higher concentrations. The model can also explain why heating in Ga+Al is particularly effective in reducing the resistivity. Similar effects occur in ZnSe, where the model can explain why excitonic emission is observed in dice heated in zinc containing 1% gallium.
Navigation Pattern Discovery from Internet Data (1999)

Electronic commerce sites need to learn as much as possible about their customers and those browsing their virtual premises, in order to maximize their marketing effort. The discovery of marketing related navigation patterns requires the development of data mining algorithms capable of discovering sequential access patterns from web logs. This paper introduces a new algorithm called MiDAS that extends traditional sequence discovery with a wide range of web-specific features. Domain knowledge is described as flexible navigation templates that can specify navigational behavior, as network structures for the capture of web site topologies, in addition to concept hierarchies and syntactic constraints. Unlike existing approaches, field dependency has been implemented, which allows the detection of sequences across monitored attributes, such as URLs and http referrers. Three different types of contained-in relationships are supported, which express different types of browsing behavior. The carried out experimental evaluation have shown promising results in terms of functionality as well as scalability. 1
Differentiation-dependent expression of I and sialyl I antigens in the developing lung of human embryos and in lung cancers. (1990)

The localization of two carbohydrate antigens, I and sialyl I antigens, in the lungs of developing human embryos was investigated using specific monoclonal antibodies and compared with the distribution patterns of the known embryonic antigen, stage-specific embryonic antigen-1 (Lex hapten). When the future bronchi were actively developing from the bronchial buds in the lungs of 50- to 53-day-old embryos, the immature bronchial bud cells were I-, Lex+, while the fully differentiated epithelial cells of the larger bronchus were I+, Lex-. When the bronchiolar bud cells matured into bronchiolar epithelial cells in the lung of a 12-week-old embryo, the immature bronchiolar bud cells were I-,Lex+, while the fully differentiated epithelial cells of the bronchioles were I+,Lex-. Sialylated forms of the antigens finally appeared in the lungs of 18-week-old embryos, when the terminal bud cells actively proliferated and underwent the differentiation process into epithelial cells of alveoli and alveolar ducts. The immature terminal bud cells at this stage were I-, sialyl I-, Lex+, sialyl Lex-i+, while the fully differentiated alveolar epithelial cells were I+, sialyl I+, Lex-, sialyl Lex-i-. After 8 months, the flattened mature alveolar epithelial cells were strongly positive for both I and sialyl I antigens, the strong expression of which continued after birth and even into the adult stage. These distribution patterns indicate that the I and sialyl I antigens are specific markers for the differentiated type cells in each stage of development, while Lex and related embryonic antigens were specific to the immature bud cells in every stage. The above-described differentiation-dependent expression patterns of these antigens seem to be reflected in the distribution of these antigens in human lung cancers, i.e., I and sialyl I antigens were expressed in lung cancer cells more weakly than in normal lung cells, while the Lex and sialyl Lex-i were expressed in cancer cells much more strongly than in normal lung cells. This was further reflected in the serum levels of these antigens in the patients with respiratory disorders. The distribution pattern of the serum levels of these antigens in patients with lung cancers showed sialyl Lex-i greater than sialyl I, indicating that these serum antigens originated from the lung cancer lesion where sialyl Lex-i is much more dominant than sialyl I antigen.(ABSTRACT TRUNCATED AT 400 WORDS)
B-102 Results from a First-In-Human study with BNZ-1, a novel, selective inhibitor of IL-2, IL-9, and IL-15 at the common gamma-chain receptor, in clinical development for the treatment of HAM/TSP and T-cell malignancies (2018)

Aberrant signaling of IL-2, IL-9, and IL-15, members of the γγγc cytokine family, is involved in multiple human diseases (eg, T-cell malignancies, GvHD, HAM/TSP) that are not effectively or safely treated by the currently available anti-cytokine approaches. BNZ-1 is a selective inhibitor of IL-2, IL-9 and IL-15 signaling through γγc, without altering IL-4, -7, or -21. In this open-label, single-dose study (NCT03046459), 18 healthy adults (n = 3/dose) received a single IV dose of 0.2, 0.4, 0.8, 1.6, 3.2 or 6.4 mg/kg and were monitored for 30 days. BNZ-1 was well-tolerated with a good safety profile (no serious/severe AEs, no DLTs, and no clinically-significant changes on labs, vital signs or ECGs). BNZ-1 exposure was dose proportional with an elimination t1/2 of ∼5 days, supporting weekly or every other week dosing. PD activity was characterized by flow cytometry of Tregs (IL-2), NK cells (IL-15) and CD8+ central memory T-cells (Tcm; IL-2 &amp; IL-15) in PBMCs from days 4, 15 and 31. Tregs were decreased by 50%–60% after doses of 0.4–1.6 mg/kg on day 4 and by 80%–93% at 3.2 and 6.4 mg/kg on day 15. On day 4 NK cells decreased by 20%, 40% and 60% at 0.2, 0.4 and 0.8 mg/kg, respectively, and plateaued at 70%–80% decreases at doses a1.6 mg/kg. Tcm were decreased at day 4 for the top 3 doses that continued to decline to day 15 when all doses, except 0.2 mg/kg, showed a mean decrease ranging from 10% to 81% that trended with dose. Tregs, NK cells, and Tcm returned to/toward baseline by day 31. CD4+ and CD8+ T-cells, B-cells, and monocytes were unchanged at all time points. These clinical data suggest that BNZ-1 is a highly-active, selective immunomodulator that safely decreases Tregs, NKs and Tcm, while sparing the major leukocyte populations.
Utility of impedance plethysmography in the diagnosis of recurrent deep-vein thrombosis (1988)

Serial impedance plethysmography has been shown to be a safe and effective alternative to venography in the management of patients with clinically suspected acute venous thrombosis. The rate of normalization of an initial abnormal impedance plethysmogram and, consequently, the usefulness of impedance plethysmography in the management of patients with recurrent symptoms is, however, unknown. In a prospective cohort follow-up study, 161 consecutive patients with proved venous thrombosis and abnormal impedance plethysmograms were studied for one year. After 3, 6, 9, and 12 months, the impedance plethysmograms had normalized in 67%, 85%, 92%, and 95% of the patients, respectively. Thirty-five patients (22%) returned with clinically suspected recurrent thrombosis, of whom 31 had normal impedance plethysmograms prior to their return. In 18 of these patients, repeated tests were normal; these patients did not undergo anticoagulant therapy, and follow-up disclosed no subsequent adverse consequences. In the other 13 patients, the test again became abnormal; 11 patients were shown by venograms to have recurrent deep-vein thrombosis. Consequently, 29 (83%) of the 35 patients in whom the suspicion of recurrent thrombosis arose could have been managed with impedance plethysmography alone without the necessity for venography or anticoagulant therapy. It is concluded that normalization of impedance plethysmography tests occurs in almost all patients within nine months, and that serial impedance plethysmography is useful for patient management in nearly 90% of patients presenting with recurrent symptoms
The combination of living radical polymerization and click chemistry for the synthesis of advanced macromolecular architectures (2011)

Since its introduction, click chemistry has received a considerable amount of interest. In this contribution, the term click chemistry and the reactions that fall under this term are briefly explained. The main focus of this review is on the application of click chemistry in conjunction with living radical polymerization for the synthesis of advanced macromolecular architectures. Therefore the most powerful living radical polymerization (LRP) techniques are discussed and an overview of click chemistry in the different synthetic schemes is given. A large number of examples are shown that include the synthesis of block copolymers, star-shaped polymers, surface modified particles, and polymer-protein conjugates. The enormous potential of LRP/click chemistry is probably best exemplified by the synthesis of different miktoarm star copolymers, to which a separate section is dedicated.
Increased expression of hypoxia inducible factor-1alpha in rat and human prostate cancer. (1998)

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates genes involved in adaptation to hypoxia. Expression of HIF-1alpha was evaluated in rat and human prostate cancer cell lines. Increased expression of HIF-1alpha mRNA in rat prostate cancer cell lines and hypoxia-induced expression of HIF-1alpha protein in human prostate cancer cell lines are associated with increased cell growth rates and metastatic potential. HIF-1alpha mRNA was undetectable in the normal rat ventral prostate by Northern blot hybridization. HIF-1alpha protein expression and HIF-1 DNA binding activity were detected in normoxic PC-3 cells. Human prostate cancer cells plated at low density manifested higher functional HIF-1alpha expression than cells plated at high density independent of O2 tension. HIF-1alpha may become dysregulated in prostate cancer and thus drive the transcription of hypoxia-adaptive genes involved in tumor progression. This is also the first evidence that human cancer cells can express functional HIF-1alpha protein under normoxic conditions.
Ein binaurales Richtungshörsystem für mobile Roboter in echoarmer Umgebung (A Binaural Sound Localization System for Mobile Robots in Low-reflecting Environments) (2003)

Abstract In diesem Beitrag wird ein binaurales Lokalisationsmodell für einen autonomen mobilen Roboter vorgestellt, das sich am menschlichen Hörsystem orientiert. Im Mittelpunkt steht die technische Umsetzung der neuronalen Verarbeitungsmechanismen der Olivenkerne des auditorischen Systems, die ein binaurales Richtungshören ermöglichen. Das System ist in der Lage, im Bereich des Sichtfeldes des Roboters eine Schallquelle in echoarmer, d.h. reflexionsarmer Umgebung anhand von Laufzeitunterschieden und Pegeldifferenzen zu lokalisieren. Die Möglichkeit des Richtungshörens verbessert die Wahrnehmung der unmittelbaren Umgebung des Roboters entscheidend und erlaubt z.B. die Ausrichtung des Roboterkopfes zur Schallquelle.
ANTI-CD4 MONOCLONAL ANTIBODY-INDUCED ALLOGRAFT TOLERANCE IN RATS DESPITE PERSISTENCE OF DONOR-REACTIVE T CELLS1 (1997)

Although CD4-targeted therapy abrogates acute rejection and may induce permanent graft acceptance in rodents, little is known about the mechanisms of long-term graft survival in these models. Recently, we have shown that treatment with a nondepleting anti-CD4 monoclonal antibody (mAb) (RIB-5/2) induces long-term survival of renal, heart, and skin allografts in strong major histocompatibility complex I/II incompatible rat strains. Here, we demonstrate that the development of major histocompatibility complex-specific and tissue-nonspecific tolerance rather than graft adaptation is responsible for long-term anti-CD4 mAb-induced transplant survival. Donor-specific but not third-party heart and pancreatic islet grafts were accepted permanently without adjunctive therapy in long-term kidney allograft recipients, and infusion of naive or alloimmune splenocytes failed to break the tolerant state. Interestingly, alloreactive T cells were not depleted in these long-term survivors, as ex vivo donor-specific mixed lymphocyte reaction was largely unaffected. The reverse transcriptase-polymerase chain reaction analyses of long-term renal allografts before and after donor-specific antigen challenge revealed no changes in CD3 mRNA level, but showed up-regulation of CD25, interleukin (IL) 2, interferon (IFN) gamma, IL-4, and IL-10 mRNA in the early phase, suggesting the presence of alloreactive T cells in tolerant rats. At later time points, the expression of IFN-gamma declined rapidly, whereas IL-4 persisted, resulting in a reversal of IFN-gamma/IL-4 ratio. Our data demonstrate the stability of anti-CD4 mAb-induced tolerance despite persistence of alloreactive T cells, suggesting the role of active tolerance-maintaining mechanisms. The T helper (Th) 1/Th2 shift may be involved in this regulatory process, as anti-CD4 mAb prevents acute graft-deteriorating rejection by effectively blocking Th1 responses, and well-functioning grafts may tolerize themselves by inducing regulatory cells.
Stochastic Sensing on a Modular Chip Containing a Single-Ion Channel (2007)

Engineered protein channels have many potential applications in biosensing at the single-molecule level. A future generation of biosensor could be an array of target-specific ion channels, where each protein pore acts as a sensor element. An important step toward this goal is to create a portable, durable, single-protein channel-integrated chip device. Here we report a versatile, modular chip that contains a single-ion channel for single-molecular biosensing. The core of the device is a long-lived lipid membrane that has been sandwiched between two air-insulated agarose layers which gel in situ. A single-protein pore embedded in the membrane serves as the sensor element. The modular device is highly portable, allowing a single-ion channel to continuously function following detachment of the chip from the instrument and independent transportation of the device. The chip also exhibits high durability, which is evidenced from long-duration continuous observation of single-channel dynamics. Once engineered protein pores are installed, the chip becomes a robust stochastic sensor for real-time targeting such as detection of the second messenger IP3. This pluggable biochip could be incorporated with many applicable devices, such as a microfluidic system, and be made into a microarray for both biomedical detection and membrane protein research.
The solution structure of gomesin, an antimicrobial cysteine‐rich peptide from the spider (2002)

Gomesin is the first peptide isolated from spider exhibiting antimicrobial activities. This highly cationic peptide is composed of 18 amino-acid residues including four cysteines forming two disulfide linkages. The solution structure of gomesin has been determined using proton two-dimensional NMR (2D-NMR) and restrained molecular dynamics calculations. The global fold of gomesin consists in a well-resolved two-stranded antiparallel betasheet connected by a noncanonical betaturn. A comparison between the structures of gomesin and protegrin-1 from porcine and androctonin from scorpion outlines several common features in the distribution of hydrophobic and hydrophilic residues. The N- and C-termini, the betaturn and one face of the betasheet are hydrophilic, but the hydrophobicity of the other face depends on the peptide. The similarities suggest that the molecules interact with membranes in an analogous manner. The importance of the intramolecular disulfide bridges in the biological activity of gomesin is being investigated.
Some observations on limited feedback for multiaccess channels (2009)

Most information-theoretic analyses of communication systems with feedback assume perfect output feedback. For multiaccess channels, this feedback can enable cooperation between users. However, as shown by a simple example, the rate required by the feedback link may exceed the capacity gains in the forward link. It is therefore of interest to look at systems where the feedback is rate-limited. For the compound multiaccess channel zero-rate feedback can tune the communication system to the realized channel, but for discrete memoryless channel the capacity region under zero-rate feedback is the same as that without feedback.