The current research was an investigation of the effects of prior, domain-relevant knowledge on self-derivation of new, integrated knowledge. Adults were presented with novel "stem" facts and tested ...for self-derivation of new knowledge through integration of the facts in memory. To examine the effects of prior knowledge on memory integration, we tested participants under three within-subject conditions, in which in advance of stem encoding, they were provided with either: (1) no domain relevant information (No Knowledge control), (2) generally relevant information about the domain (General), or (3) generally relevant information about the domain along with a stem fact that was directly necessary for self-derivation (General + Stem). Prior exposure to both General and General + Stem knowledge facilitated memory for the novel, explicitly-taught stem facts. Moreover, for both prior knowledge conditions, the amount of domain-relevant knowledge retained in memory was associated with trial-by-trial self-derivation success. Importantly, the type of prior knowledge modulated memory integration in different ways. Whereas General + Stem knowledge enhanced selective retrieval and integration of the stem facts, General knowledge supported learning of the individual stem facts, but not their integration with one another. Together, the findings indicate how malleable, domain-specific experience shapes encoding, integration, and flexible extension of new, related information.
Hypothalamic Hormones and Cancer Schally, Andrew V.; Comaru-Schally, Ana Maria; Nagy, Attila ...
Frontiers in neuroendocrinology,
10/2001, Letnik:
22, Številka:
4
Journal Article
Recenzirano
The use of peptide analogs for the therapy of various cancers is reviewed. Inhibition of the pituitary–gonadal axis forms the basis for oncological applications of luteinizing hormone-releasing ...hormone (LH-RH) agonists and antagonists, but direct effects on tumors may also play a role. Analogs of somatostatin are likewise used for treatment of various tumors. Radiolabeled somatostatin analogs have been successfully applied for the localization of tumors expressing somatostatin receptors. Studies on the role of tumoral LH-RH, growth hormone-releasing hormone (GH-RH), and bombesin/GRP and their receptors in the proliferation of various tumors are summarized, but the complete elucidation of all the mechanisms involved will require much additional work. Human tumors producing hypothalamic hormones are also discussed. Treatment of many cancers remains a major challenge, but new therapeutic modalities are being developed based on antagonists of GH-RH and bombesin, which inhibit growth factors or their receptors. Other approaches consist of the use of cytotoxic analogs of LH-RH, bombesin, and somatostatin, which can be targeted to receptors for these peptides in various cancers and their metastases. These new classes of peptide analogs should lead to a more effective treatment for various cancers.
Background
Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1‐INH), leading to overproduction of bradykinin. The current functional diagnostic assays ...employ inhibition of activated C1s; however, an alternative, more physiologic method is desirable.
Methods
ELISAs were developed using biotinylated activated factor XII (factor XIIa) or biotinylated kallikrein bound to avidin‐coated plates. Incubation with plasma was followed by detection of bound C1‐INH.
Results
After standard curves were developed for quantification of C1‐INH, serial dilutions of normal plasma were employed to validate the ability to detect known concentration of C1‐INH in the plasma as a percent of normal. Hereditary angioedema (HAE) types I and II were then tested. The level of functional C1‐INH in all HAE types I and II plasma tested was less than 40% of our normal control. This was evident regardless of whether we measured factor XIIa–C1‐INH or kallikrein–C1‐INH complexes, and the two assays were in close agreement. By contrast, testing the same samples utilizing the commercial method (complex ELISA, Quidel Corp.) revealed the levels of C1‐INH between 0 and 57% of normal (mean, 38%), and 42 samples were considered equivocal (four controls and 38 patients).
Conclusions
Diagnosis of HAE types I and II can be ascertained by inhibition of enzymes of the bradykinin‐forming cascade, namely factor XIIa and kallikrein. Either method yields functional C1‐INH levels in patients with HAE (types I and II) that are clearly abnormal with less variance or uncertainty than the commercial method.
Mn
54Al
44C
2 ribbon samples have been prepared by melt spinning in a single-phase ɛ hexagonal disordered state and its exothermal transformation at around 500
°C into a tetragonal L1
0 type magnetic ...structure (τ-phase) was followed by DTA, DSC, X-ray diffraction and thermomagnetic measurements. The metastable τ-phase stabilized by carbon addition could be transformed reversibly into the ɛ-phase at around 800
°C, without decomposition into the stable Al
8Mn
5 and β manganese phases. The almost constant Curie temperature obtained for partially transformed two-phase samples indicated a compositionally invariant transformation. By grinding the thin (25
μm) ribbon into sub-millimeter flakes, a bulk anisotropic magnet could be compacted by magnetic field oriented powder technology.
Urinary tract infections are considered among the most common infectious disorders in humans. Various infections may have a role in inducing HAE attacks. Our study intended to evaluate bacteriuria in ...the urinalysis of patients with C1‐INH‐HAE. Urine specimens contributed by 139 patients with C1‐INH‐HAE at the annual control visits were studied retrospectively for microorganisms. We analyzed the presence of bacteriuria in relation to the clinical symptoms. Taking into account three randomly selected urine specimens, we found that the cumulative number of edematous attacks was higher in patients with bacteriuria than in those without (P = 0.019, P = 0.022, P = 0.014). Considering the same patients, attack number was significantly higher (14.51 vs 8.63) in patients with bacteriuria than in those without (P < 0.0001). In patients with bacteriuria, we found a higher incidence of edema formation during the year before evaluation, which may suggest the triggering role of bacteriuria in the occurrence of edematous episodes.
The current research was an investigation of the cognitive correlates of individual differences in participants' capacity to derive new factual knowledge through integration of information acquired ...across separate yet related learning episodes. In a sample of 117 adults (Experiment 1) and 57 children aged 8 to 10 years (Experiment 2), we investigated the respective roles of verbal comprehension, working memory span, and relational reasoning in self-derivation of new knowledge through memory integration. The findings revealed patterns of consistency and inconsistency in the cognitive profiles underlying this form of learning in adults and children. In both adults and children, verbal knowledge and skills accounted for variability in self-derivation. Variance in adults, but not in children, was further explained by working memory. Given that individual differences in self-derivation have implications for real-world academic outcome, we also investigated the association between self-derivation and academic performance. We found that performance on the experimentally based self-derivation paradigm was related to concurrent and longitudinal academic success in both samples. The present research thus builds on the growing body of behavioral and neuroscientific research to advance our understanding of the cognitive factors associated with behaviors that depend on memory integration in both childhood and adulthood and also provides suggestive evidence of critical ways in which the process may differ in children and adults. Together, the findings provide a theoretically plausible and practically significant framework from which to guide future research aimed at enhancing this educationally relevant learning phenomenon.
To build a general knowledge base, it is imperative that individuals acquire, integrate, and further extend knowledge across experiences. For instance, in one episode an individual may learn that ...George Washington was the first president. In a separate episode they may then learn that Washington was the commander of the Continental Army. Integration of the information in memory may then support self-derivation of the new knowledge that the leader of the Continental Army was also the first president. Despite a considerable amount of fMRI research aimed at further elucidating the neuroanatomical regions supporting this ability, a consensus has yet to be reached with regards to the precise neurocognitive processes involved. In the present research, we capitalized on the high temporal resolution of event-related potentials (ERPs) to inform the time course of processes elicited during successful integration and further extension of new factual knowledge. Adults read novel, related stem facts and were tested for self-derivation of novel integration facts while ERPs were recorded. Consistent with current theoretical models, memory integration was first triggered by novelty detection within 400 msec of experience of a second, related stem fact. Two additional temporally staged encoding processes were then observed interpreted to reflect (1) explicit meaning comprehension and (2) representation of the integrated relation in memory. During the test for self-derivation, a single ERP was elicited, which presumably reflected retrieval and/or recombination of previously integrated knowledge. Together, the present research provides important insight into the time course of neurocognitive processing associated with the formation of a knowledge base.
The present research investigated the retention of new factual knowledge derived through integration of information acquired across temporally distributed learning episodes. Young adults were exposed ...to novel facts as they read long lists of seemingly unrelated information, one sentence at a time. They then were presented open-ended questions, the answers to which could be self-derived through integration of pairs of facts from the list. Experiment
1
was the first test of self-derivation of new factual knowledge through integration in adults using open-ended testing (as opposed to forced-choice testing). Participants successfully self-derived integrated knowledge under these more challenging conditions. Experiment
2
was a test for long-term retention of newly self-derived information. Newly derived knowledge remained accessible after a 1-week delay. Striking individual differences were also observed, which were related to whether individuals spontaneously identified the relational structure of the learning task. Insight into the relation between explicit task knowledge and strategic processing was also revealed through examination of response speed at the time of test. Specifically, knowledge of the task structure was associated with response latencies on unsuccessful (but not successful) trials, such that participants who were aware of the opportunity to integrate spent longer when they were subsequently unsuccessful, presumably reflecting directed search strategies and heightened perseverance when those processes failed. Together, the present findings provide direct evidence for the role of memory integration in the long-term accumulation of a semantic knowledge base and have theoretical implications for our understanding of this fundamental form of learning.
Ghrelin synergizes with growth hormone-releasing hormone (GHRH) to potentiate growth hormone (GH) response through a mechanism not yet fully characterized. This study was conducted to analyze the ...role of GHRH as a potential ligand of the ghrelin receptor, GHS-R1a. The results show that hGHRH(1-29)NH₂ (GHRH) induces a dose-dependent calcium mobilization in HEK 293 cells stably transfected with GHS-R1a an effect not observed in wild-type HEK 293 cells. This calcium rise is also observed using the GHRH receptor agonists JI-34 and JI-36. Radioligand binding and cross-linking studies revealed that calcium response to GHRH is mediated by the ghrelin receptor GHS-R1a. GHRH activates the signaling route of inositol phosphate and potentiates the maximal response to ghrelin measured in inositol phosphate turnover. The presence of GHRH increases the binding capacity of ¹²⁵I-ghrelin in a dose dependent-fashion showing a positive binding cooperativity. In addition, confocal microscopy in CHO cells transfected with GHS-R1a tagged with enhanced green fluorescent protein shows that GHRH activates the GHS-R1a endocytosis. Furthermore, the selective GHRH-R antagonists, JV-1-42 and JMR-132, act also as antagonists of the ghrelin receptor GHS-R1a. Our findings suggest that GHRH interacts with ghrelin receptor GHS-R1a, and, in consequence, modifies the ghrelin-associated intracellular signaling pathway. This interaction may represent a form of regulation, which could play a putative role in the physiology of GH regulation and appetite control.
The room-temperature magnetoresistance (MR) characteristics of nanocrystalline (nc) Ni metal with various grain sizes (between 30 and 100 nm) are investigated in this work for the first time. The ...nc-Ni foils were produced by electrodeposition and the results are compared with data measured on coarse-grained (bulk) pure Ni metal samples prepared by cold-rolling and annealing. The MR(
H
) curves measured in magnetic fields up to
H
= 9 kOe are analyzed in detail to determine the anisotropic magnetoresistance (AMR) ratio. The magnitude of the AMR ratio was found to be around 2.5% for bulk Ni and in the range from about 2 to 2.5% for the nc-Ni samples, the latter data not exhibiting a systematic dependence on the grain size. On the other hand, the field-induced resistivity anisotropy splitting ∆ρ
AMR
in the magnetically saturated state of the nc-Ni series was found to be proportional to the zero-field resistivity of the same samples with different grain sizes. The slope of this proportionality relation provided an AMR ratio of 2.4% for all nc-Ni samples, matching well the value for the bulk Ni samples. Thus, the AMR ratio for polycrystalline Ni metal seems to be fairly independent of the microstructural features. This also means that the AMR ratio is an inherent characteristic of the Ni metal matrix and it remains the same even if the matrix resistivity changes (e.g., by introducing grain boundaries) without noticeably modifying the electronic density of states at least in the vicinity of the Fermi level.
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