On the role of stability in animal morphology and neural control

Mechanical stability is vital for the fitness and survival of animals and is a crucial aspect of robot design and control. Stability depends on multiple factors, including the body\u27s intrinsic mechanical response and feedback control. But feedback control is more fragile than the body\u27s innate mechanical response or open-loop control strategies because of sensory noise and time-delays in feedback. This thesis examines the overarching hypothesis that stability demands have played a crucial role in how animal form and function arise through natural selection and motor learning. In two examples, finger contact and overall body stability, we investigated the relationship between morphology, open-loop control, and stability. By studying the stability of the internal degrees of freedom of a finger when pushing on a hard surface, we find that stability limits the force that we can produce and is a dominant aspect of the neural control of the finger\u27s muscles. In our study on whole body lateral stability during locomotion in terrestrial animals, we find that the overall body aspect ratio has evolved to ensure passive lateral stability on the uneven terrain of natural environments. Precisely gripping an object with the fingertips is a hallmark of human hand dexterity. In Chapter 2, we show how human fingers are intrinsically prone to a buckling-type postural instability and how humans use careful neural orchestration of our muscles so that the elastic response of our muscles can suppress the intrinsic instability. In Chapter 3, we extend these findings further to examine the nature of neuromuscular variability and how the nervous system deals with the need for muscle-induced stability. We find that there is structure to neuromuscular variability so that most of the variability lies within the subspace that does not affect stability. Inspired by the open-loop stable control of our index fingers, in Chapter 4, we derive open-loop stability conditions for a general mechanical linkage with arbitrary joint torques subjected to holonomic constraints. The solution that we derive is physically realizable as cable-driven active mechanical linkages. With a user-prescribed cable layout, we pose the problem of actuating the system to maintain stability while subject to goals like energy minimization as a convex optimization problem. We are thus able to use efficient optimization methods available for convex problems and demonstrate numerical solutions in examples inspired by the finger. Chapter 5 presents a general formulation of the stability criteria for active mechanical linkages subject to Pfaffian holonomic and non-holonomic constraints. Active mechanical linkages subject to multiple constraints represent the mechanics of systems spanning many domains and length scales, such as limbs and digits in animals and robots, and elastic networks like actin meshes in microscopic systems. We show that a constrained mechanical linkage with regular stiffness and damping, and circulation-free feedback, can only destabilize by static buckling when subject to holonomic constraints. In contrast, the same mechanical linkage, subject to a non-holonomic constraint, such as a skate contact, can exhibit either static buckling or flutter instability. Chapter 6 moves away from neural control and studies the shape of animal bodies and their relationship to stability in locomotion. We investigate why small land animals tend to have a crouched or sprawled posture, whereas larger animals are generally more upright. We propose a new hypothesis that the scaling of body aspect ratio with size is driven by the scale-dependent unevenness of natural terrain. We show that the scaling law arising from the need for stability on rough natural terrain correctly predicts the frontal aspect ratio scaling law across 335 terrestrial vertebrates and invertebrates, spanning eight orders of magnitude in mass so that smaller animals have a wider aspect ratio. We also carry out statistical analyses that consider the phylogenetic relationship among the species in our dataset to show that the scaling is not due to gradual changes of the traits over time. Thus, stability demands on natural terrain may have driven the macroevolution of body aspect ratio across terrestrial animals. Interrogating unstable and marginally stable behaviors has helped us identify the morphological and control features that allow animals to perform robustly in noisy environments where perfect sensory feedback cannot be assumed. Although the thesis identifies the `what\u27 and `why,\u27 further studies are needed to understand `how\u27 mechanics and development intertwine to give rise to control and form in growing and adapting biological organisms

Apelin Regulation of K-Cl Cotransport in Vascular Smooth Muscle Cells.

Atherosclerosis and high circulating levels of oxidized low density lipoproteins (oxLDL) are considered among the most important risk factors for the occurrence and development of cardiovascular disease (CVD). During the atherosclerotic lesion repair, phenotypic transition of vascular smooth muscle cells (VSMCs) from contractile to synthetic states plays a central role. In this process, enhanced proliferation/migration of VSMCs, from the tunica media to the intima, is required to sustain blood vessel endothelium integrity, and for inducing vessel wall remodeling in response to injury. At the molecular level, the activity of electroneutral potassium-chloride cotransporters or KCCs, is necessary to: a) allow changes in cell volume (key prerequisites to coordinate cell proliferation/migration) and b) sustain normal cardiovascular function. Stimulation of the adipokine apelin and its receptor APJ (apelin/APJ) signaling pathway has been shown to protect against atherosclerotic lesion formation by lowering blood pressure levels and promoting vasodilation. Upon binding to APJ, apelin promotes nitric oxide (NO)-mediated vasodilation, and cell proliferation via the PI3K/Akt and MAPK pathways. Apelin/APJ exert its action through the same signaling pathways regulating the KCCs. However, the mechanisms of KCC regulation by apelin/APJ remain to be determined. Thus, we hypothesized that KCC expression and activity play an important role during VSMCs\u27 phenotypic transition and could be involved in the apelin/APJ cardioprotective effects. In addition, it is possible that the apelin-mediated effect on KCC activity could also be dependent on factors affecting the transporter, such as, serum, ionic strength, osmolality, cell proliferation and migration. This hypothesis will be tested using rat aortic VSMCs that were immunologically validated by specific markers. KCC activity was measured by atomic absorption spectrophotometry using rubidium as a potassium (K+) congener. KCC expression and transport activity were characterized with respect to the VSMC phenotypes, in the presence or absence of apelin and corresponding inhibitors of the signaling pathways, oxLDL and as a function of the various aforementioned physiological factors. While markers for the contractile VSMC phenotype are well known, they are less defined for the early and late synthetic ones. In the present study, we showed a decrease in expression levels of cytoskeletal proteins like a-actin, desmin and vimentin in late synthetic VSMCs compared to early states suggesting that the latter show similar characteristics to the contractile phenotype. In addition, KCC1 and KCC4 protein expression and overall KCC activity increased in late vs early synthetic VSMCs. The ion binding affinity (Km) for late and early synthetic VSMCs was similar for K+ whereas it decreased for Cl-. Whether the increase in KCC activity in late synthetic VSMCs is due to turnover changes of pre-existing KCCs or enhanced membrane trafficking/insertion of de novo synthesized KCC protein remains to be studied. Using selective inhibitors, we showed that apelin-mediated activation of KCCs occurs through the NO/sGC/PKG pathway in contractile, and by PI3K/Akt and MAPK dependent pathway(s) in synthetic VSMCs. Furthermore, apelin rescued the inhibition of KCC induced by oxLDL in contractile VSMCs. We also showed that the apelin-mediated activation of KCCs is dependent on extracellular sodium, osmolality, presence of serum in the growth media, VSMCs phenotype (contractile vs synthetic), and passage number. Altogether, our results identify apelin/APJ as an important modulator of KCC activity to sustain cell volume regulation and overall vascular function

Miscarriage and early first trimester growth restriction by ultrasound

Background: Concern about the possibility of spontaneous miscarriage is one of the most common reasons women seek evaluation in the emergency department during their first trimester. According to the obstetrics and gynecology literature, it is estimated that 20% to 25% of all clinically recognized pregnancies result in spontaneous miscarriage. The objective of the study is to examine with whether viable early pregnancies that subsequently end in miscarriage exhibit evidence of first-trimester growth restriction. The prospective cohort study design used for this purpose with setting of Antenatal clinic of a teaching hospital. Women attending the clinic between 5 and 10 weeks of gestation took part in the study.Methods: Women with spontaneously conceived intrauterine, viable singleton pregnancies with certain last menstrual period and regular cycles were included. The deviation between the observed and expected crown-rump length (CRL) for gestation was calculated and expressed as a z-score. Pregnancies were followed up until 11-14 weeks, and the deviation between those that remained viable and miscarried subsequently was calculated. Viability at 11-14 weeks was measured.Results: Over 12 months, 320 women met the inclusion criteria. Twenty women were excluded. Of the remaining 300, the pregnancy remained viable in 248 (82.6%) and 52 (17.4%) suffered a miscarriage. At the first transvaginal ultrasound, the z score of the mean measured CRL for pregnancies that remained viable was -0.69 while in pregnancies that subsequently miscarried the z-score was -2.95 and the CRL was significantly smaller (P < 0.048). In the latter group, the initial CRL was below the expected mean for gestational age in all women.Conclusions: CRL was significantly smaller in pregnancies that subsequently ended in miscarriage. This suggests that early first trimester growth restriction is associated with subsequent intrauterine death

Intravenous versus oral iron therapy in treatment of postpartum anaemia

Background: Postpartum iron deficiency anaemia (IDA) is common in women. Most women are treated with either oral iron supplementation or blood transfusion. Hence, the aim of our study was to compare the effect of treatment with either oral ferrous sulphate or intravenous ferrous sucrose on postpartum IDA.Methods: 100 postpartum women with proven iron deficiency anaemia with hemoglobin <9gm/dl and serum ferritin <15 µgm/l were included in the study. They were randomized to receive either oral ferrous sulphate 200 mg twice daily for 6 weeks (group 1) or intravenous ferrous sucrose 200 mg, two to three doses given on alternate days (group 2). Total iron deficit was calculated using a standard formula. Target hemoglobin was 11 gm/dl. Results were analysed by the students t-test and chi-square test. Hemoglobin, hematocrit, red cell indices and ferritin were measured on day 2-3, 1-2 weeks and 6 weeks postpartumResults: By 1-2 weeks, hemoglobin level in women treated with intravenous iron had risen from 7.81±0.849 to 9.88±0.760 gm/dl which was more than those treated with oral iron (p<0.01); although by 6 weeks, there was no significant difference between the two groups. Ferritin levels rose rapidly in those treated with intravenous iron and remained significantly higher than in those treated with oral iron (p<0.01).Conclusions: Intravenous iron sucrose increases the hemoglobin level more rapidly than oral ferrous sulphate in women with postpartum IDA. It also replenishes iron stores more rapidly.

Rising concern of nomophobia amongst Indian medical students

Background: Aims and objectives of current study were to assess the pattern of mobile phone usage and prevalence of nomophobia amongst third year medical students in north India. Methods: A cross sectional study was conducted amongst 130 medical students of third year MBBS of Sri Aurobindo institute of medical sciences, Indore. A pre-formed pre-tested questionnaire was used. Data were analyzed statistically by simple proportions.Results: Response rate was 90.76%. Female preponderance (65 females out of 118 respondents) was seen in our study. Most of the students were in the age group of 22-24 years. All of them were having possession of at least one mobile phone with activated internet services in 87% of students. 34% were having two mobile phones, while 4% had more than two mobiles. 61% students had to recharge the internet services once a month, 28% twice a month, while 11% students had to recharge it more than three times a month. 73% of students were nomophobics. 21% of nomophobics experienced rinxiety. 83% of students experienced panic attacks when their mobile phone was misplaced. Headache and lethargy were the commonest side effects that were experienced by 61% of students.Conclusion: Our study gives a brief idea about the woeful outcomes of nomophobia. There is a definite need of further studies in this field.

Clinical profile of tuberculosis with diabetes mellitus

Background: There is now good evidence that people with diabetes mellitus (DM) have 2–3 times the risk of developing active tuberculosis (TB) compared with those who do not have DM. The aim of the study was to analyze typical / atypical presentation of pulmonary tuberculosis with diabetes mellitus.Methods: This study was carried out in the Department of Respiratory Medicine and General Medicine, SAIMS, Indore during the period of July 2012 to June 2014. A prospective study including 100 microscopically proven cases of sputum smear positive pulmonary tuberculosis. Among these, 50 are diabetic patients with sputum positive tuberculosis and 50 are non-diabetic patients with sputum positive tuberculosis.Results: The mean age in diabetic group was 51.92±9.96 years. The mean age in non-diabetic group was 39.58±15.19 years. In the diabetic group, there were 38 (76.00%) male and 12 (24.00%) females, while in the non-diabetic group there were 40 (80.00%) males and 10 (20.00%) females. Fever, cough and weakness were the three most common symptoms seen in patients with tuberculosis in both the groups.Conclusions: There was a preponderance of male in both the groups over the female patients. There is no significant difference in the symptoms in both the groups

The importance of inversion disorder in the visible light induced persistent luminescence in Cr3+^{3+} doped AB2_2O4_4 (A = Zn or Mg and B = Ga or Al)

Cr$^{3+}$ doped spinel compounds AB$_2$O$_4$ with A=Zn, Mg and B=Ga, Al exhibit a long near infrared persistent luminescence when excited with UV or X-rays. In addition, persistent luminescence of ZnGa$_2$O$_4$ and to a lesser extent MgGa$_2$O$_4$, can also be induced by visible light excitation via $^4$A$_2$ $\rightarrow$ $^4$T$_2$ transition of Cr$^{3+}$, which makes these compounds suitable as biomarkers for in vivo optical imaging of small animals. We correlate this peculiar optical property with the presence of antisite defects, which are present in ZnGa$_2$O$_4$ and MgGa$_2$O$_4$. By using X-ray absorption fine structure (XAFS) spectroscopy, associated with electron paramagnetic resonance (EPR) and optical emission spectroscopy, it is shown that an increase in antisite defects concentration results in a decrease in the Cr-O bond length and the octahedral crystal field energy. A part of the defects are in the close environment of Cr$^{3+}$ ions, as shown by the increasing strain broadening of EPR and XAFS peaks observed upon increasing antisite disorder. It appears that ZnAl$_2$O$_4$, which exhibits the largest crystal field splitting of Cr$^{3+}$ and the smallest antisite disorder, does not show considerable persistent luminescence upon visible light excitation as compared to ZnGa$_2$O$_4$ and MgGa$_2$O$_4$. These results highlight the importance of Cr$^{3+}$ ions with neighboring antisite defects in the mechanism of persistent luminescence exhibited by Cr$^{3+}$ doped AB$_2$O$_4$ spinel compounds.Comment: 10 pages + supplementary (available on request

Scanning electron microscopic comparison of endophallus of Apis cerana and Apis mellifera

During the present investigations, the detailed morphoarchitecture of the male genitalia viz., the endophallus of the drone of A.cerana F. and A.mellifera L. was scanned under the electron microscope. Endophallus of each species was studied for its unique characteristics. Significant interspecific differences were observed in the 2 different species. These differences highlight the reproductive isolation in the genus. These species specific differences in the endophallus are highlighted in the paper

Role of FNAC in the diagnosis of intraosseous jaw lesions

Background: FNAC of intraosseous jaw lesions has not been widely utilized for diagnosis due to rarity and diversity of these lesions, limited experience and lack of well established cytological features. Aim of the study was to determine the role of FNAC in the diagnosis of intraosseous jaw swellings. Material and Methods: 42 patients underwent FNAC over a period of 7 years (2007-2013), of which 37 (88.1%) aspirates were diagnostic. Histopathology correlation was available in 33 cases and diagnostic accuracy of FNAC was calculated. Results: Lesions were categorized into inflammatory 3, cysts/hamartomas 15 and neoplasms 19. Mandibular and maxillary involvement was seen in 21 and 16 patients respectively. Of these, benign cysts and malignant lesions were commonest, accounting for 27% lesions (10 cases) each. One case of cystic ameloblastoma was misdiagnosed as odontogenic cyst on cytology. Overall, sensitivity and specificity of FNAC were 94.7% and 100% respectively with a diagnostic accuracy of 97.3%. Definitive categorization of giant cell lesions, fibro-osseous lesions, odontogenic tumors and cystic lesions was not feasible on FNAC. Conclusions: FNAC is a simple, safe and minimally invasive first line investigation which can render an accurate preoperative diagnosis of intraosseous jaw lesions, especially the malignant ones in the light of clinic-radiological correlation

Antenatal counselling as a tool to increase acceptability of postpartum intrauterine contraceptive device insertion in a tertiary care hospital

Background: Acceptance of postpartum intrauterine device (IUD) insertions in women in Uttar Pradesh is low. In response to the concept that a good postpartum programme should begin prenatally, this study was designed to determine whether the provision of expert contraceptive counselling during the antenatal period would have an impact on its uptake as compared to women who were counselled in post partum period.Methods: Expert contraceptive counselling was given to 264 and154 women during their antenatal visits and postpartum hospitalization, respectively. Acceptors received IUCDs within 48 h of delivery in the case of vaginal delivery or transcesarean insertion in case of abdominal delivery. The acceptance rate of PPIUCD and the percentage of actual insertions were recorded. The causes of refusal were also recorded.Results: Among the 264 couples counselled in antenatal period 116 (43.9%) had PPIUCD insertion. Among the 154 unbooked women who were counselled postpartum only PPIUCD was inserted in 36 (23.4%) women. PPIUCD insertion was significantly high in women receiving expert counselling during antenatal period as compared to the women who were counselled in postnatal period (p< 0.001). Family refusal, No knowledge of PPIUCD and preference for another contraceptive methods were the most common reasons for refusing the use of PPIUCD.Conclusion: Acceptability of PPIUCD insertion was high in women counselled in antenatal period. Hence, it is suggested that counselling for PPIUCD should start in antenatal period