Unusual kinematics of the Papatea fault (2016 Kaikoura earthquake) suggest anelastic rupture.

A key paradigm in seismology is that earthquakes release elastic strain energy accumulated during an interseismic period on approximately planar faults. Earthquake slip models may be further informed by empirical relations such as slip to length. Here, we use differential lidar to demonstrate that the Papatea fault-a key element within the 2016 Mw 7.8 Kaikoura earthquake rupture-has a distinctly nonplanar geometry, far exceeded typical coseismic slip-to-length ratios, and defied Andersonian mechanics by slipping vertically at steep angles. Additionally, its surface deformation is poorly reproduced by elastic dislocation models, suggesting the Papatea fault did not release stored strain energy as typically assumed, perhaps explaining its seismic quiescence in back-projections. Instead, it slipped in response to neighboring fault movements, creating a localized space problem, accounting for its anelastic deformation field. Thus, modeling complex, multiple-fault earthquakes as slip on planar faults embedded in an elastic medium may not always be appropriate.

[Unusual masquerade of an ocular carcinoma metastasis]. / Untypische Masquerade einer okulären Karzinommetastase.

BACKGROUND: Idiopathic and therapy resistant uveitis especially of unclear origin, is a diagnostic challenge for ophthalmologists. Metastases to the anterior chamber or vitreous body can occasionally mimic the clinical picture of uveitis, a variant on the usual lymphomatous masquerade syndrome. The underlying pathological pathways leading to the metastatic spread of tumor cells within the fluid compartments of the eye remain unclear. CASE REPORT: We present an unusual case of vitreous metastases to the right eye of a patient in whom an underlying primary malignancy was unknown. After recurrent episodes of cortisone-refractive panuveitis with pseudohypopyon, a diagnostic vitreous biopsy was performed. Cytopathological examination of the vitreous sample revealed carcinoma cells with an immune profile suggestive of lung cancer metastasis. Subsequent staging investigations revealed a primary lung adenocarcinoma as well as cerebral, adrenal and osseous metastases. THERAPY: Due to the extent of dissemination of this non-small cell lung cancer (NSCLC), only palliative treatment including external beam irradiation and systemic chemotherapy was possible to reduce pain and to maintain vision as well as an attempt at systemic control of the disease.

Newborn behaviour to locate the breast when skin-to-skin: a possible method for enabling early self-regulation.

AIM: The aim of this study was to provide a more detailed analysis of the infant's behavioural sequence that begins immediately after birth and terminates with grasping the nipple, suckling and then falling asleep. METHOD: Twenty-eight full-term infants were videotaped immediately after birth. A video protocol was developed to examine infant behaviours identified from five random videotapes. RESULTS: When birth crying had stopped, the babies showed a short period of relaxation and then successively became alert. They went through an 'awakening phase', an 'active phase' with movements of limbs, rooting activity and looking at the mother's face, a 'crawling phase' with soliciting sounds, a 'familiarization phase' with licking of the areola, and a 'suckling phase' and last a 'sleeping phase'. Five factors related to the time spent to locate the breast: more number of looks at the breast 10-20 min after birth (p < 0.0001); and exposure to meperidine (p = 0.0006) related to increased time. Early start of crawling (p = 0,0040); increased number of 'soliciting sounds' (p = 0.0022); and performing hand-breast-mouth movements (p = 0.0105) related to shorter time. CONCLUSION: Inborn breastfeeding reflexes were depressed at birth, possibly because of a depressed sensory system. It is hypothesized that when the infant is given the option to peacefully go through the nine behavioural phases birth cry, relaxation, awakening, activity, crawling, resting, familiarization, suckling and sleeping when skin-to-skin with its mother this results in early optimal self-regulation.

Effects of intrapartum oxytocin administration and epidural analgesia on the concentration of plasma oxytocin and prolactin, in response to suckling during the second day postpartum.

BACKGROUND: Oxytocin and prolactin stimulate milk ejection and milk production during breastfeeding. The aim of the present study was to make a detailed analysis of maternal release of oxytocin and prolactin in response to breastfeeding during the second day postpartum in mothers who had received oxytocin either intravenously for stimulation of labor or intramuscularly for prevention of postpartum hemorrhage and/or epidural analgesia or those who had received no such treatment in connection with birth. METHODS: In a descriptive comparative study plasma oxytocin and prolactin concentrations were measured in response to suckling during the second day postpartum in women who had received intravenous intrapartum oxytocin (n = 8), intramuscular postpartum oxytocin (n = 13), or epidural analgesia, either with (n = 14) or without (n = 6) intrapartum oxytocin infusion, and women who received none of these interventions (n = 20). Hormone levels were analyzed by enzyme immunoassay. RESULTS: All mothers showed a pulsatile oxytocin pattern during the first 10 minutes of breastfeeding. Women who had received epidural analgesia with oxytocin infusion had the lowest endogenous median oxytocin levels. The more oxytocin infusion the mothers had received during labor, the lower their endogenous oxytocin levels were during a breastfeeding during the second day postpartum. A significant rise of prolactin was observed after 20 minutes in all women, but after 10 minutes in mothers having received oxytocin infusion during labor. In all women, oxytocin variability and the rise of prolactin levels between 0 and 20 minutes correlated significantly with median oxytocin and prolactin levels. CONCLUSION: Oxytocin, released in a pulsatile way, and prolactin were released by breastfeeding during the second day postpartum. Oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Furthermore, oxytocin infusion facilitated the release of prolactin. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively.

Influence of oxytocin or epidural analgesia on personality profile in breastfeeding women: a comparative study.

Women undergo physiological and psychological changes during pregnancy, labor and lactation. The psychological adaptations can be affective, cognitive and behavioral and can be measured by dimensional personality instruments. This study aims to compare (1) the personality profile in mothers after birth with a normative group of non-lactating women and to examine (2) whether the personality profile differs 2 days, 2 months and 6 months after birth between mothers who have been exposed to epidural anesthesia, oxytocin administration or neither. Sixty-nine primiparae were assigned to four groups: mothers having received oxytocin infusion during labor (OT iv group, n = 9), mothers having received epidural analgesia with/without oxytocin infusion (EDA group, n = 23), mothers having received 10 iU oxytocin intramuscularly after birth (OT im group, n = 15) and mothers having received none of these treatments (unmedicated group, n = 22). At 2 days and 2 and 6 months postpartum mothers completed the Karolinska Scales of Personality (KSP). The unmedicated, the OT iv- and OT im groups scored significantly lower on anxiety and aggression related scales and higher on the socialization subscale during the entire observation period when compared with a normative group. These differences were not observed in the EDA group 2 days postpartum. At 2 and 6 months postpartum, the scores of the EDA group had changed significantly and were almost similar to the KSP scores of the other groups. ANCOVA analysis revealed that OT infusion, over and above the effects of EDA, was associated with decreased levels of several anxiety and aggression subscales. We conclude that women who received exogenous oxytocin during labor show similar positive personality traits during breastfeeding such as reduction in anxiety and aggression and increasing socialization, including maternal behavior, that have previously been ascribed to endogenous oxytocin. More importantly, these effects were not seen at 2 days postpartum in women who received epidural anesthesia during labor.

Short- and long-term decrease of blood pressure in women during breastfeeding.

BACKGROUND AND AIMS: The benefits of breastfeeding for infants are well known. Recently data have started to emerge showing that breastfeeding may also induce positive effects in the mother. This study aimed to investigate the pattern of maternal blood pressure before, during, and after a breastfeed 2 days postpartum. Additionally, blood pressure during the following 25-week breastfeeding period was investigated. METHODS: Sixty-six primiparae with normal deliveries were consecutively recruited. Blood pressure was measured at -5, 10, 30, and 60 minutes in connection with a morning breastfeed. Thirty-three women continued to measure blood pressure before and after breastfeeding for 25 weeks. RESULTS: Blood pressure fell significantly in response to breastfeeding 2 days after birth. The fall in systolic and diastolic blood pressure amounted to 8.8 (SD = 11.00) and 7.7 (SD = 9.3) mm Hg, respectively. During the 25-week follow-up period a significant fall of basal blood pressure (systolic, df = 3, F = 7.843, p < 0.001; diastolic, df = 3, F = 5.453, p = 0.002) was observed. The total fall in systolic and diastolic blood pressure amounted to a mean of 15 (SD = 10.4) mm Hg and 10 (SD = 9.7) mm Hg, respectively. In addition, blood pressure fell significantly in response to individual breastfeeding sessions during the entire observation period. CONCLUSIONS: In conclusion, both systolic and diastolic blood pressures fall during a breastfeeding session, and pre-breastfeeding blood pressure decreases during at least the first 6 months of a breastfeeding period in a homelike environment. This study lends further support to the health-promoting effects of breastfeeding.

Newborn skin temperature two days postpartum during breastfeeding related to different labour ward practices.

AIM: To investigate (1) the skin temperature pattern in newborns two days after birth in connection to breastfeeding and to examine (2) if the administration of epidural analgesia (EDA) and oxytocin (OT) infusion during labour influences this parameter at this point of time. METHOD: Forty-seven mother-infant pairs were included in the study: nine mothers had received OT stimulation during labour (OT group), 20 mothers had received an EDA and OT during labour (EDA group), while 18 mothers had received neither EDA nor OT stimulation during labour (control group). A skin temperature electrode was attached between the newborn's shoulder blades. The newborn was placed skin-to-skin on the mother's chest and covered with a blanket. The temperature was recorded immediately after the newborn was put on the mother's chest and at 5, 10, 20 and 30 min. RESULTS: The temperature measured when the newborns were put skin-to-skin on their mothers' chest was significantly higher in the infants of the EDA group (35.07 degrees C) when compared to the control group (34.19 degrees C, p=0.025). Skin temperature increased significantly (p=0.001) during the entire experimental period in the infants belonging to the control group. The same response was observed in infants whose mothers received OT intravenously during labour (p=0.008). No such rise was observed in infants whose mothers were given an EDA during labour. CONCLUSION: The results show that the skin temperature in newborns rises when newborns are put skin-to-skin to breastfeed two days postpartum. This effect on temperature may be hampered by medical interventions during labour such as EDA.

Maternal analgesia during labor disturbs newborn behavior: effects on breastfeeding, temperature, and crying.

BACKGROUND: Newborns not exposed to analgesia, when placed on the mother's chest, exhibit an inborn prefeeding behavior. This study was performed to assess the effects of different types of analgesia during labor on the development of spontaneous breastfeeding movements, crying behavior, and skin temperature during the first hours of life in healthy term newborns. METHODS: Video recordings were made of 28 newborns who had been dried and placed in skin-to-skin contact between their mother's breasts immediately after delivery. The video recordings were analyzed blindly with respect to infant exposure to analgesia. Defined infant behaviors were assessed every 30 seconds. Group 1 mothers (n = 10) had received no analgesia during labor, group 2 mothers (n = 6) had received mepivacaine via pudendal block, and group 3 mothers (n = 12) had received pethidine or bupivacaine or more than one type of analgesia during labor. RESULTS: All infants made finger and hand movements, but the infant's massagelike hand movements were less frequent in infants whose mothers had received labor analgesia. A significantly lower proportion of group 3 infants made hand-to-mouth movements (p < 0.001), and a significantly lower proportion of the infants in groups 2 and 3 touched the nipple with their hands before suckling (p < 0.01), made licking movements (p < 0.01), and sucked the breast (p < 0.01). Nearly one-half of the infants, all in groups 2 or 3, did not breastfeed within the first 2.5 hour of life. The infants whose mothers had received analgesia during labor had higher temperatures (p = 0.03) and they cried more (p = 0.05) than infants whose mothers had not received any analgesia. CONCLUSIONS: The present data indicate that several types of analgesia given to the mother during labor may interfere with the newborn's spontaneous breast-seeking and breastfeeding behaviors and increase the newborn's temperature and crying.

Postpartum maternal oxytocin release by newborns: effects of infant hand massage and sucking.

BACKGROUND: Newborns placed skin-to-skin with their mothers show an inborn sequence of behavior similar to that seen in other mammals. The purpose of this study was to make a detailed exploration of hand movements and sucking behavior in healthy term newborns who were placed skin-to-skin on their mothers' chests, and to study maternal oxytocin release in relation to these behaviors. METHODS: Ten vaginally delivered infants whose mothers had not been exposed to maternal analgesia were video-recorded from birth until the first breastfeeding. Video protocols were developed based on observations of the videotapes. Each infant's hand, finger, mouth, and tongue movements, positions of the hand and body, and sucking behavior were assessed every 30 seconds. Maternal blood samples were collected every 15 minutes, and oxytocin levels were analyzed by radioimmunoassay. A statistical test for establishing the relationship between maternal oxytocin levels and infants' hand movements or sucking behavior was developed. RESULTS: Infants used their hands to explore and stimulate their mother's breast in preparation for the first breastfeeding. A coordinated pattern of infant hand and sucking movements was also identified. When the infants were sucking, the massagelike hand movements stopped and started again when the infants made a sucking pause. Periods of increased massagelike hand movements or sucking of the mother's breast were followed by an increase in maternal oxytocin levels (p < 0.005). CONCLUSIONS: The findings indicate that the newborns use their hands as well as their mouths to stimulate maternal oxytocin release after birth, which may have significance for uterine contraction, milk ejection, and mother-infant interaction.

Difference in apoptosis induction between surface IgD and IgM.

In the classic 'two-signal' model for B cell activation, signal 1 through the antigen receptor plus signal 2 through lymphokine receptors and CD40 leads to proliferation, but signal 1 alone leads to tolerance or anergy. In a protocol designed to deliver signal 1 in vitro with anti-delta without signal 2, purified small dense B cells from untreated mice exposed to any of three monoclonal anti-delta antibodies or to polyclonal anti-delta in vitro showed modest S phase entry at 50 microg/ml. In contrast, at low doses (0.1-0.5 microg/ml) of anti-delta, there was no cell cycle entry at 64 h, but apoptosis was accelerated at 16 h. Polyclonal anti-mu and three monoclonal anti-mus did not show this early apoptosis induction. Anti-CD40 and IL-4 inhibited apoptosis in B cells treated with 0.5 microg/ml anti-delta and increased S phase entry at 10 microg/ml anti-delta. Low-dose anti-delta (but not anti-mu) induced increased B7-2 and class II MHC expression on a subset of B cells, many of which were in apoptosis. Larger transient increases in c-Myc and Egr-1 expression were seen with low-dose anti-delta than with anti-mu, followed by an abrupt fall below baseline, a sequence previously linked to apoptosis. There was no change in Bcl-2, Bcl-x(L) or Bax. These data suggest a functional difference between delta and mu cross-linking on resting spleen B cells. A BCR stimulus sufficient for early activation events, but insufficient for full G1 entry, may lead to apoptosis.

[A comparative study of cardiac function in transgenic hypertensive rats, in spontaneously hypertensive rats and in normotensive rats]. / Etude comparative de la fonction cardiaque chez le rat transgénique hypertendu, chez le rat spontanément hypertendu et chez le rat normotendu.

Left ventricular hypertrophy (LVH) entails numerous functional and molecular changes that ultimately lead to cardiac insufficiency. The renin-angiotensin system and adrenergic receptor signalling pathway have both been implicated in LVH progression and interactions between these factors may precipitate contractile dysfunction. We therefore investigated cardiac function in hypertensive rats transgenic for the human renin and angiotensinogen genes (TGR) having a genetic activation of the renin-angiotensin system, stroke-prone spontaneously hypertensive rats (SHR) and normotensive controls (CTR) aged 6 weeks. The isolated perfused heart model was used and the effect of isoproterenol (0.1-1000 nmol/L on cardiac function was studied. Cardiac protein and gene expression was studied by Western blot and RNase protection assay. TGR had 75 mmHg higher blood pressure and a 24% higher cardiac/body weight ratio than CTR; blood pressure in SHR was 17 mmHg higher without heart weight difference (p < 0.05). Basal Pmax, +dP/dt and -dP/dt were higher in TGR and SHR compared with CTR hearts. Isoproterenol stimulated these parameters by a maximum factor 6-8 in CTR and SHR but had almost no effect in TGR (p < 0.05). Basal CF per g heart weight was similar in all experimental groups. Isoproterenol produced a significantly smaller vasodilation in TGR compared with CTR or SHR. beta 1 and beta 2 receptor and Gs alpha proteins were similar in TGR, SHR and CTR. Gi alpha was increased in TGR hearts (p < 0.05). Converting enzyme and atrial natriuretic factor mRNA expression was increased (p < 0.01) while beta 1 receptor, adenylyl-cyclase V, SERCA2a and phospholamban mRNA expression was unchanged in TGR compared with CTR. Thus, LVH in TGR is characterised by early adrenergic dysfunction and beta 1 receptor signalling abnormalities indicating progressive functional deterioration. The data may serve as support for an early preventive intervention in angiotensin-II dependent cardiac hypertrophy and may have also implications for patients with genetic alterations of the renin-angiotensin system.

Autoantibodies against the beta- and muscarinic receptors in cardiomyopathy.

The sera of patients with idiopathic dilated cardiomyopathy and the Chagas' disease contain agonist-like autoantibodies directed against the beta 1-adrenoceptor and/or the muscarinic M2-receptor. The anti-beta 1-adrenoceptor antibodies could be directed against amino acid sequences of the first or second extracellular loop. In patients with dilated cardiomyopathy the first as well as the second extracellular loop was identified as an antibody epitope. In Chagas' disease the anti-beta 1-adrenoceptor antibody recognizes only 1 epitope on the second extracellular loop. The anti-beta 1-adrenoceptor antibodies acting like the beta-adrenergic agonist isoprenaline and exert a positive chronotropic effect in cultured rat cardiomyocytes. In contrast to isoprenaline the antibody caused no downregulation of the beta-adrenergic signal transduction cascade within 6 hours. The anti-M2 receptor antibodies recognize in both diseases an epitope on the second extracellular loop. The anti-M2-receptor antibody exert a negative chronotropic response in cultured cardiomyocytes. This antibody induced no downregulation of the muscarinic M2-receptor. The negative chronotropic effect was unabated for 6 hours. Based on these findings it is believed that the agonist-like autoantibodies that act against the beta 1-adrenoceptor and the muscarinic M2-receptor may play a role in the pathogenesis of dilated cardiomyopathy and Chagas' disease.

Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) frequently is a progressive disease without causative therapy options. Following the hypothesis that in certain patients autoantibodies against cardiac structures may induce, maintain, or promote the progression of the disease, we investigated whether the elimination of these autoantibodies through immunoadsorption would improve cardiac function. METHODS AND RESULTS: This prospective case-control study included 34 patients with IDC. Each patient presented with moderate to severe heart failure and evidence of autoantibodies directed against beta(1)-adrenoceptors (beta(1)-AABs). Seventeen patients received standard medical therapy (control group), whereas 17 were also treated with immunoadsorption (treatment group) to eliminate beta(1)-AABs. A 1-year follow-up included echocardiographic assessment of left ventricular ejection fraction and internal diameters, beta(1)-AAB levels, and clinical status every 3 months. Within 1 year, the mean+/-SD left ventricular ejection fraction rose from 22.3+/-3.3% to 37.9+/-7.9% (P=0.0001) in the treatment group, with a relative increase of 69.9%. However, in the control group, no overall increase was seen (from 23.8+/-3.0% to 25.2+/-5.9%, P=0. 3154). Left ventricular diameter in diastole decreased by 14.5% from 74.5+/-7.1 to 63.7+/-6.0 mm in the treatment group (P=0.0001) and by 3.8% (P=0.2342) in the control group. In the treatment group, the NYHA functional rating improved after immunoadsorption (P=0.0001). beta(1)-AABs did not increase anew. CONCLUSIONS: In IDC, the use of immunoadsorption is superior to the use of standard medical therapy. It significantly improves cardiac performance and clinical status.

Is it necessary to suture all lacerations after a vaginal delivery?

BACKGROUND: Midwives tend to leave minor perineal lacerations to heal spontaneously, and clinical experience and studies show that women can suffer from their stitched lacerations. The study purpose was to determine any differences in the healing process and experience of minor perineal lacerations when they were sutured or not sutured. METHODS: Eighty term pregnant primiparas with minor perineal lacerations of grades I-II were randomized after childbirth. The experimental group was nonsutured and the control group was sutured. A follow-up examination was performed at 2 to 3 days, 8 weeks, and 6 months after the delivery. Participants were asked about the type of discomfort, and the effect of the laceration on breastfeeding and sexual intercourse. RESULTS: No significant differences were found in the healing process. The type of pain differed between the groups, but the amount of discomfort was the same. The sutured group had to visit the midwife more often because of discomfort from the stitches. Sixteen percent of the women in the sutured group, but none in the nonsutured group (p = 0.0385), considered that the laceration had had a negative influence on breastfeeding. CONCLUSIONS: Minor perineal lacerations can be left to heal spontaneously. The benefits for the woman include the possibility of having a choice, avoiding the discomfort of anesthesia and suturing, providing positive affects on breastfeeding.

Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor.

Immune mechanisms and the renin-angiotensin system are implicated in preeclampsia. We investigated 25 preeclamptic patients and compared them with 12 normotensive pregnant women and 10 pregnant patients with essential hypertension. Antibodies were detected by the chronotropic responses to AT1 receptor-mediated stimulation of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists. Immunoglobulin from all preeclamptic patients stimulated the AT1 receptor, whereas immunoglobulin from controls had no effect. The increased autoimmune activity decreased after delivery. Affinity-column purification and anti-human IgG and IgM antibody exposure implicated an IgG antibody directed at the AT1 receptor. Peptides corresponding to sites on the AT1 receptor's second extracellular loop abolished the stimulatory effect. Western blotting with purified patient IgG and a commercially obtained AT1 receptor antibody produced bands of identical molecular weight. Furthermore, confocal microscopy of vascular smooth muscle cells showed colocalization of purified patient IgG and AT1 receptor antibody. The protein kinase C (PKC) inhibitor calphostin C prevented the stimulatory effect. Our results suggest that preeclamptic patients develop stimulatory autoantibodies against the second extracellular AT1 receptor loop. The effect appears to be PKC-mediated. These novel autoantibodies may participate in the angiotensin II-induced vascular lesions in these patients.

A case of bullous frostbite following recreational snowmobiling.

Frostbite is the occurrence of localized tissue freezing and injury. It results following cold exposure of sufficient magnitude or duration to cause acute tissue damage. Although there are several conditions that predispose to frostbite, all are at risk if subject to sufficient cold exposure. We discuss a case of frostbite presenting with bullae localized to the neck resulting from extreme cold encountered while snowmobiling at night in Minnesota, an entity known by some local practitioners as "polaris vulgaris."

Agonist-like beta-adrenoceptor antibodies in heart failure.

Anti-beta1-adrenoceptor antibodies may play a harmful role, and the elimination of these antibodies could have beneficial effects for some patients with dilated cardiomyopathy. In vitro experiments showed that the antibody was able to influence the function of cultured cardiomyocytes. In these experiments, the antibody prevented the down-regulation of the beta-adrenoceptor-mediated chronotropic response. This lack of desensitization, which resulted in permanent stimulation, could also influence the Ca2+ homeostasis of cardiomyocytes. However, in longer-term (72 hours)-treated cells, the antibodies were able to decrease subtype-specific expression of the beta1 adrenoceptor. In animal experiments, it was shown that long-term immunization with a peptide corresponding to the second extracellular loop of the beta1 adrenoceptor induced a failing heart similar to that in dilated cardiomyopathy. In humans, we observed a remarkable correlation between disappearance of the antibodies and improvement of heart function. Furthermore, in anti-beta1-adrenoceptor-positive patients with dilated cardiomyopathy treated with the immunoadsorption technique, removal of the antibodies also led to improvement of cardiac function and quality of life. This finding indicates that autoimmune processes may be involved in some patients with dilated cardiomyopathy.

Peptide design by artificial neural networks and computer-based evolutionary search.

A technique for systematic peptide variation by a combination of rational and evolutionary approaches is presented. The design scheme consists of five consecutive steps: (i) identification of a "seed peptide" with a desired activity, (ii) generation of variants selected from a physicochemical space around the seed peptide, (iii) synthesis and testing of this biased library, (iv) modeling of a quantitative sequence-activity relationship by an artificial neural network, and (v) de novo design by a computer-based evolutionary search in sequence space using the trained neural network as the fitness function. This strategy was successfully applied to the identification of novel peptides that fully prevent the positive chronotropic effect of anti-beta1-adrenoreceptor autoantibodies from the serum of patients with dilated cardiomyopathy. The seed peptide, comprising 10 residues, was derived by epitope mapping from an extracellular loop of human beta1-adrenoreceptor. A set of 90 peptides was synthesized and tested to provide training data for neural network development. De novo design revealed peptides with desired activities that do not match the seed peptide sequence. These results demonstrate that computer-based evolutionary searches can generate novel peptides with substantial biological activity.